WorldWideScience

Sample records for based microfluidic devices

  1. Fabrication of paper based microfluidic devices

    CSIR Research Space (South Africa)

    Govindasamy, K

    2012-07-01

    Full Text Available This paper describes an inexpensive method of fabricating paper based microfluidic devices, a new point of care technology. The method uses a solid ink printer, chromatography paper and a heating source. The printer deposits wax onto the surface...

  2. Paper based microfluidic devices for environmental diagnostics

    CSIR Research Space (South Africa)

    Govindasamy, K

    2012-09-01

    Full Text Available such as elevated temperatures and mechanical stresses. Paper based microfluidic chips are patterned with micron sized hydrophobic barriers which penetrate the paper?s cross section. These barriers guide the capillary movement of fluids through the cellulose...

  3. A microfluidic device based on an evaporation-driven micropump

    NARCIS (Netherlands)

    Nie, C.; Frijns, A.J.H.; Mandamparambil, R.; Toonder, J.M.J. den

    2015-01-01

    In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface

  4. Fully enclosed microfluidic paper-based analytical devices.

    Science.gov (United States)

    Schilling, Kevin M; Lepore, Anna L; Kurian, Jason A; Martinez, Andres W

    2012-02-07

    This article introduces fully enclosed microfluidic paper-based analytical devices (microPADs) fabricated by printing toner on the top and bottom of the devices using a laser printer. Enclosing paper-based microfluidic channels protects the channels from contamination, contains and protects reagents stored on the device, contains fluids within the channels so that microPADs can be handled and operated more easily, and reduces evaporation of solutions from the channels. These benefits extend the capabilities of microPADs for applications as low-cost point-of-care diagnostic devices. © 2012 American Chemical Society

  5. Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

    Science.gov (United States)

    Alapan, Yunus; Hasan, Muhammad Noman; Shen, Richang; Gurkan, Umut A

    2015-05-01

    Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.

  6. Isotachophoretic preconcenetration on paper-based microfluidic devices.

    Science.gov (United States)

    Moghadam, Babak Y; Connelly, Kelly T; Posner, Jonathan D

    2014-06-17

    Paper substrates have been widely used to construct point-of-care lateral flow immunoassay (LFIA) diagnostic devices. Paper based microfluidic devices are robust and relatively simple to operate, compared to channel microfluidic devices, which is perhaps their greatest advantage and the reason they have reached a high level of commercial success. However, paper devices may not be well suited for integrated sample preparation, such as sample extraction and preconcentration, which is required in complex samples with low analyte concentrations. In this study, we investigate integration of isotachophoresis (ITP), an electrokinetic preconcentration and extraction technique, onto nitrocellulose-based paper microfluidic devices with the goal to improve the limit of detection of LFIA. ITP has been largely used in traditional capillary based microfluidic devices as a pretreatment method to preconcentrate and separate a variety of ionic compounds. Our findings show that ITP on nitrocellulose is capable of up to a 900 fold increase in initial sample concentration and up to 60% extraction from 100 μL samples and more than 80% extraction from smaller sample volumes. Paper based ITP is challenged by Joule heating and evaporation because it is open to the environment. We achieved high preconcentration by mitigating evaporation induced dispersion using novel cross-shaped device structures that keep the paper hydrated. We show that ITP on the nitrocellulose membrane can be powered and run several times by a small button battery suggesting that it could be integrated to a portable point-of-care diagnostic device. These results highlight the potential of ITP to increase the sensitivity of paper based LFIA under conditions where small analyte concentrations are present in complex biological samples.

  7. Paper-based inkjet-printed microfluidic analytical devices.

    Science.gov (United States)

    Yamada, Kentaro; Henares, Terence G; Suzuki, Koji; Citterio, Daniel

    2015-04-27

    Rapid, precise, and reproducible deposition of a broad variety of functional materials, including analytical assay reagents and biomolecules, has made inkjet printing an effective tool for the fabrication of microanalytical devices. A ubiquitous office device as simple as a standard desktop printer with its multiple ink cartridges can be used for this purpose. This Review discusses the combination of inkjet printing technology with paper as a printing substrate for the fabrication of microfluidic paper-based analytical devices (μPADs), which have developed into a fast-growing new field in analytical chemistry. After introducing the fundamentals of μPADs and inkjet printing, it touches on topics such as the microfluidic patterning of paper, tailored arrangement of materials, and functionalities achievable exclusively by the inkjet deposition of analytical assay components, before concluding with an outlook on future perspectives. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A microfluidic device based on an evaporation-driven micropump.

    Science.gov (United States)

    Nie, Chuan; Frijns, Arjan J H; Mandamparambil, Rajesh; den Toonder, Jaap M J

    2015-04-01

    In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface between the device and the skin, is used to collect the fluid (e.g., sweat) and enter this into the microfluidic device. A controllable evaporation driven pump is used to drive a continuous fluid flow through a microfluidic channel and over a sensing area. The key element of the pump is a micro-porous membrane mounted at the channel outlet, such that a pore array with a regular hexagonal arrangement is realized through which the fluid evaporates, which drives the flow within the channel. The system is completely fabricated on flexible polyethylene terephthalate (PET) foils, which can be the backbone material for flexible electronics applications, such that it is compatible with volume production approaches like Roll-to-Roll technology. The evaporation rate can be controlled by varying the outlet geometry and the temperature. The generated flows are analyzed experimentally using Particle Tracking Velocimetry (PTV). Typical results show that with 1 to 61 pores (diameter = 250 μm, pitch = 500 μm) flow rates of 7.3 × 10(-3) to 1.2 × 10(-1) μL/min are achieved. When the surface temperature is increased by 9.4°C, the flow rate is increased by 130 %. The results are theoretically analyzed using an evaporation model that includes an evaporation correction factor. The theoretical and experimental results are in good agreement.

  9. [Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

    Science.gov (United States)

    Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

    2010-06-01

    With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

  10. 3D Printed Paper-Based Microfluidic Analytical Devices

    Directory of Open Access Journals (Sweden)

    Yong He

    2016-06-01

    Full Text Available As a pump-free and lightweight analytical tool, paper-based microfluidic analytical devices (μPADs attract more and more interest. If the flow speed of μPAD can be programmed, the analytical sequences could be designed and they will be more popular. This reports presents a novel μPAD, driven by the capillary force of cellulose powder, printed by a desktop three-dimensional (3D printer, which has some promising features, such as easy fabrication and programmable flow speed. First, a suitable size-scale substrate with open microchannels on its surface is printed. Next, the surface of the substrate is covered with a thin layer of polydimethylsiloxane (PDMS to seal the micro gap caused by 3D printing. Then, the microchannels are filled with a mixture of cellulose powder and deionized water in an appropriate proportion. After drying in an oven at 60 °C for 30 min, it is ready for use. As the different channel depths can be easily printed, which can be used to achieve the programmable capillary flow speed of cellulose powder in the microchannels. A series of microfluidic analytical experiments, including quantitative analysis of nitrite ion and fabrication of T-sensor were used to demonstrate its capability. As the desktop 3D printer (D3DP is very cheap and accessible, this device can be rapidly printed at the test field with a low cost and has a promising potential in the point-of-care (POC system or as a lightweight platform for analytical chemistry.

  11. Commercialization of microfluidic devices.

    Science.gov (United States)

    Volpatti, Lisa R; Yetisen, Ali K

    2014-07-01

    Microfluidic devices offer automation and high-throughput screening, and operate at low volumes of consumables. Although microfluidics has the potential to reduce turnaround times and costs for analytical devices, particularly in medical, veterinary, and environmental sciences, this enabling technology has had limited diffusion into consumer products. This article analyzes the microfluidics market, identifies issues, and highlights successful commercialization strategies. Addressing niche markets and establishing compatibility with existing workflows will accelerate market penetration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Fabrication of polyimide based microfluidic channels for biosensor devices

    DEFF Research Database (Denmark)

    Zulfiqar, Azeem; Pfreundt, Andrea; Svendsen, Winnie Edith

    2015-01-01

    The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabr......The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use...... for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel...

  13. Low-cost rapid prototyping of flexible plastic paper based microfluidic devices

    KAUST Repository

    Fan, Yiqiang

    2013-04-01

    This research presents a novel rapid prototyping method for paper-based flexible microfluidic devices. The microchannels were fabricated using laser ablation on a piece of plastic paper (permanent paper), the dimensions of the microchannels was carefully studied for various laser powers and scanning speeds. After laser ablation of the microchannels on the plastic paper, a transparent poly (methyl methacrylate)(PMMA) film was thermally bonded to the plastic paper to enclose the channels. After connection of tubing, the device was ready to use. An example microfluidic device (droplet generator) was also fabricated using this technique. Due to the flexibility of the fabricated device, this technique can be used to fabricate 3D microfluidic devices. The fabrication process was simple and rapid without any requirement of cleanroom facilities. © 2013 IEEE.

  14. 1000-fold sample focusing on paper-based microfluidic devices.

    Science.gov (United States)

    Rosenfeld, Tally; Bercovici, Moran

    2014-12-07

    We present an experimental and analytical study of a novel paper-based analytical device (μPAD) for isotachophoretic sample focusing. Guided by a simple heat transfer model, we further developed wax printing fabrication to enable the creation of shallow channels, which are critical in providing sufficient dissipation of Joule heat, and thus enable the use of high electric fields and short analysis time. This results in a device that is self-contained on a simple piece of filter paper and does not require any specialized enclosures or cooling devices to combat evaporation at high temperatures. Furthermore, we provide an analytical model for isotachophoretic sample accumulation in porous media, introduce a simple figure of merit for evaluating and comparing the efficiency of such devices, and present experimental validation in both paper and glass channels. Using this device we demonstrate the processing of 30 μL of sample achieving 1000-fold increase in peak concentration in 6 min. We believe that this method and device can serve as a guide to the design of low-cost, rapid and highly sensitive paper-based diagnostic platforms.

  15. Error analysis for pesticide detection performed on paper-based microfluidic chip devices

    Science.gov (United States)

    Yang, Ning; Shen, Kai; Guo, Jianjiang; Tao, Xinyi; Xu, Peifeng; Mao, Hanping

    2017-07-01

    Paper chip is an efficient and inexpensive device for pesticide residues detection. However, the reasons of detection error are not clear, which is the main problem to hinder the development of pesticide residues detection. This paper focuses on error analysis for pesticide detection performed on paper-based microfluidic chip devices, which test every possible factor to build the mathematical models for detection error. In the result, double-channel structure is selected as the optimal chip structure to reduce detection error effectively. The wavelength of 599.753 nm is chosen since it is the most sensitive detection wavelength to the variation of pesticide concentration. At last, the mathematical models of detection error for detection temperature and prepared time are concluded. This research lays a theory foundation on accurate pesticide residues detection based on paper-based microfluidic chip devices.

  16. Microfluidic Cell Culture Device

    Science.gov (United States)

    Takayama, Shuichi (Inventor); Cabrera, Lourdes Marcella (Inventor); Heo, Yun Seok (Inventor); Smith, Gary Daniel (Inventor)

    2014-01-01

    Microfluidic devices for cell culturing and methods for using the same are disclosed. One device includes a substrate and membrane. The substrate includes a reservoir in fluid communication with a passage. A bio-compatible fluid may be added to the reservoir and passage. The reservoir is configured to receive and retain at least a portion of a cell mass. The membrane acts as a barrier to evaporation of the bio-compatible fluid from the passage. A cover fluid may be added to cover the bio-compatible fluid to prevent evaporation of the bio-compatible fluid.

  17. Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones.

    Science.gov (United States)

    Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

    2016-03-21

    Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field.

  18. Novel Developments of Mobile Sensing Based on the Integration of Microfluidic Devices and Smartphone

    Science.gov (United States)

    Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

    2016-01-01

    Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS2) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS2 offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS2 in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS2 enables applications to remote infield testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS2 by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field. PMID:26899264

  19. Determination of Escherichia coli in urine using a low-cost foil-based microfluidic device.

    Science.gov (United States)

    Mašková, Tereza; Hárendarčíková, Lenka; Petr, Jan

    2017-08-01

    We developed a simple low-cost cultivation-based microfluidic device from office-laminator foil and Parafilm for the determination of specific microorganisms in water samples. The main goal was to obtain a device that would be portable and cheap compared to common laboratory techniques testing microorganisms. This device needs only 10µL of a sample and can be easily used in terrain by a non-specialist. Moreover, we dealt with some technical aspects of the device fabrication such as low-cost lamination techniques and the use of different cultivation media. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Mkit: A Cell Migration Assay Based on Microfluidic Device and Smartphone

    OpenAIRE

    Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

    2017-01-01

    Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS2-based cell functi...

  1. Particle-Based Microfluidic Device for Providing High Magnetic Field Gradients

    Science.gov (United States)

    Lin, Adam Y. (Inventor); Wong, Tak S. (Inventor)

    2013-01-01

    A microfluidic device for manipulating particles in a fluid has a device body that defines a main channel therein, in which the main channel has an inlet and an outlet. The device body further defines a particulate diverting channel therein, the particulate diverting channel being in fluid connection with the main channel between the inlet and the outlet of the main channel and having a particulate outlet. The microfluidic device also has a plurality of microparticles arranged proximate or in the main channel between the inlet of the main channel and the fluid connection of the particulate diverting channel to the main channel. The plurality of microparticles each comprises a material in a composition thereof having a magnetic susceptibility suitable to cause concentration of magnetic field lines of an applied magnetic field while in operation. A microfluidic particle-manipulation system has a microfluidic particle-manipulation device and a magnet disposed proximate the microfluidic particle-manipulation device.

  2. Methods of making microfluidic devices

    KAUST Repository

    Buttner, Ulrich

    2017-06-01

    Microfluidics has advanced in terms of designs and structures, however, fabrication methods are either time consuming or expensive to produce, in terms of the facilities and equipment needed. A fast and economically viable method is provided to allow, for example, research groups to have access to microfluidic fabrication. Unlike most fabrication methods, a method is provided to fabricate a microfluidic device in one step. In an embodiment, a resolution of 50 micrometers was achieved by using maskless high-resolution digital light projection (MDLP). Bonding and channel fabrication of complex or simple structures can be rapidly incorporated to fabricate the microfluidic devices.

  3. Bioprocess microfluidics: applying microfluidic devices for bioprocessing.

    Science.gov (United States)

    Marques, Marco Pc; Szita, Nicolas

    2017-11-01

    Scale-down approaches have long been applied in bioprocessing to resolve scale-up problems. Miniaturized bioreactors have thrived as a tool to obtain process relevant data during early-stage process development. Microfluidic devices are an attractive alternative in bioprocessing development due to the high degree of control over process variables afforded by the laminar flow, and the possibility to reduce time and cost factors. Data quality obtained with these devices is high when integrated with sensing technology and is invaluable for scale-translation and to assess the economical viability of bioprocesses. Microfluidic devices as upstream process development tools have been developed in the area of small molecules, therapeutic proteins, and cellular therapies. More recently, they have also been applied to mimic downstream unit operations.

  4. Microfluidic devices for cellomics: a review

    NARCIS (Netherlands)

    Andersson, Helene; van den Berg, Albert

    2003-01-01

    A review of microfluidic devices for cellomics is presented. After a brief description of the historical background of Lab-on-Chip (LOC) devices, different areas are reviewed. Devices for cell sampling are presented, followed by cell trapping and cell sorting devices based upon mechanical and

  5. Magnetic-adhesive based valves for microfluidic devices used in low-resource settings.

    Science.gov (United States)

    Harper, Jason C; Andrews, Jenna M; Ben, Candice; Hunt, Andrew C; Murton, Jaclyn K; Carson, Bryan D; Bachand, George D; Lovchik, Julie A; Arndt, William D; Finley, Melissa R; Edwards, Thayne L

    2016-10-18

    Since the introduction of micro total analytical systems (μTASs), significant advances have been made toward development of lab-on-a-chip platforms capable of performing complex biological assays that can revolutionize public health, among other applications. However, use of these platforms in low-resource environments (e.g. developing countries) has yet to be realized as the majority of technologies used to control microfluidic flow rely on off-device hardware with non-negligible size, cost, power requirements and skill/training to operate. In this paper we describe a magnetic-adhesive based valve that is simple to construct and operate, and can be used to control fluid flow and store reagents within a microfluidic device. The design consists of a port connecting two chambers on different planes in the device that is closed by a neodymium disk magnet seated on a thin ring of adhesive. Bringing an external magnet into contact with the outer surface of the device unseats and displaces the valve magnet from the adhesive ring, exposing the port. Using this configuration, we demonstrate on-device reagent storage and on-demand transport and reaction of contents between chambers. This design requires no power or external instrumentation to operate, is extremely low cost ($0.20 materials cost per valve), can be used by individuals with no technical training, and requires only a hand-held magnet to actuate. Additionally, valve actuation does not compromise the integrity of the completely sealed microfluidic device, increasing safety for the operator when toxic or harmful substances are contained within. This valve concept has the potential to simplify design of μTASs, facilitating development of lab-on-a-chip systems that may be practical for use in point-of-care and low-resource settings.

  6. Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices.

    Science.gov (United States)

    Wan, Yuan; Tan, Jifu; Asghar, Waseem; Kim, Young-tae; Liu, Yaling; Iqbal, Samir M

    2011-12-01

    The isolation and detection of rare circulating tumor cells (CTCs) has been one of the focuses of intense research recently. In a microfluidic device, a number of factors can influence the enrichment capability of surface-bound probe molecules. This article analyzes the important factor of flow velocity in a microfluidic channel. The competition of surface-grafted anti-EGFR aptamers to bind the overexpressed EGFR on cell membranes against the drag force from the fluid flow is an important efficiency determining factor. The flow rate variations are applied both in experiments and in simulation models to study their effects on CTC capture efficiency. A mixture of mononuclear cells and human Glioblastoma cells is used to isolate cancer cells from the cellular flow. The results show interdependence between the adhesion probability, isolation efficiency, and flow rate. This work can help in designing flow-through lab-on-chip devices that use surface-bound probe affinities against overexpressed biomarkers for cell isolation. This work demonstrates that microfluidic based approaches have strong potential applications in CTC detection and isolation. © 2011 American Chemical Society

  7. Microfluidic Devices for Blood Fractionation

    Directory of Open Access Journals (Sweden)

    Chwee Teck Lim

    2011-07-01

    Full Text Available Blood, a complex biological fluid, comprises 45% cellular components suspended in protein rich plasma. These different hematologic components perform distinct functions in vivo and thus the ability to efficiently fractionate blood into its individual components has innumerable applications in both clinical diagnosis and biological research. Yet, processing blood is not trivial. In the past decade, a flurry of new microfluidic based technologies has emerged to address this compelling problem. Microfluidics is an attractive solution for this application leveraging its numerous advantages to process clinical blood samples. This paper reviews the various microfluidic approaches realized to successfully fractionate one or more blood components. Techniques to separate plasma from hematologic cellular components as well as isolating blood cells of interest including certain rare cells are discussed. Comparisons based on common separation metrics including efficiency (sensitivity, purity (selectivity, and throughput will be presented. Finally, we will provide insights into the challenges associated with blood-based separation systems towards realizing true point-of-care (POC devices and provide future perspectives.

  8. Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

    Science.gov (United States)

    Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

    2015-05-01

    In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work.

  9. Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

    International Nuclear Information System (INIS)

    Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

    2015-01-01

    In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work. (note)

  10. Novel and facile viscometer using a paper-based microfluidic device

    Science.gov (United States)

    Kang, Hyunwoong; Jang, Ilhoon; Song, Simon

    2017-11-01

    In clinical applications, it is important to rapidly estimate the blood viscosity of a patient with a high accuracy and a small sample consumption. Unfortunately, ordinary mechanical viscometers require long analysis time, large volume of sample and skilled person. To address this issue, silicon-based viscometers have been developed, but they are still far from prevail usage in clinical environments due to complexity in process and analysis. Recently, a paper-based microfluidic device is emerged as a new platform for a facile point-of-care diagnostic device due to low cost, disposability and ease of use. Thus, we propose a novel and facile method of measuring a viscosity with a paper-based microfluidic devices and a smartphone. This viscometer utilizes mixing characteristics of two fluid flows in a T-shape channel: one for reference and the other for test fluid. The mixing strongly depends on viscosity difference between the two fluids. Also, the fluids are dyed for colorimetric analysis with a smartphone. We found that the accuracy of viscometer is about 3 percent when it was tested for various glycerin aqueous solutions. More detailed information will be discussed in the presentation. This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

  11. A review on wax printed microfluidic paper-based devices for international health.

    Science.gov (United States)

    Altundemir, S; Uguz, A K; Ulgen, K

    2017-07-01

    Paper-based microfluidics has attracted attention for the last ten years due to its advantages such as low sample volume requirement, ease of use, portability, high sensitivity, and no necessity to well-equipped laboratory equipment and well-trained manpower. These characteristics have made paper platforms a promising alternative for a variety of applications such as clinical diagnosis and quantitative analysis of chemical and biological substances. Among the wide range of fabrication methods for microfluidic paper-based analytical devices ( μ PADs), the wax printing method is suitable for high throughput production and requires only a commercial printer and a heating source to fabricate complex two or three-dimensional structures for multipurpose systems. μ PADs can be used by anyone for in situ diagnosis and analysis; therefore, wax printed μ PADs are promising especially in resource limited environments where people cannot get sensitive and fast diagnosis of their serious health problems and where food, water, and related products are not able to be screened for toxic elements. This review paper is focused on the applications of paper-based microfluidic devices fabricated by the wax printing technique and used for international health. Besides presenting the current limitations and advantages, the future directions of this technology including the commercial aspects are discussed. As a conclusion, the wax printing technology continues to overcome the current limitations and to be one of the promising fabrication techniques. In the near future, with the increase of the current interest of the industrial companies on the paper-based technology, the wax-printed paper-based platforms are expected to take place especially in the healthcare industry.

  12. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2015-06-01

    Full Text Available A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT, gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS microfluidic channels. DNA aptamer, or “artificial antibody”, was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the “aptamer beacon”, highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  13. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

    Science.gov (United States)

    Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

    2015-06-11

    A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  14. Paper-based microfluidic devices for electrochemical immunofiltration analysis of human chorionic gonadotropin.

    Science.gov (United States)

    Cao, Liangli; Fang, Cheng; Zeng, Ruosheng; Zhao, Xiongjie; Jiang, Yuren; Chen, Zhencheng

    2017-06-15

    An electrochemical immunofiltration analysis was introduced into microfluidic paper-based analytical devices (μPADs) for the first time, which was based on photolithography and screen-printing technology. The hydrophilic test zones of the aldehyde-functionalized screen-printed electrodes (SPEs) were biofunctionalized with capture antibodies (Ab 1 ). A sensitive immune detection method was developed by using primary signal antibody functionalized gold nanoparticles (GNPs/Ab 2 ) and alkaline phosphatase conjugated secondary antibody (ALP-IgG). Differential pulse voltammetry (DPV) was performed to detect the electrochemical response. The microfluidic paper-based electrochemical immunosensor (μ-PEI) was optimized and characterized for the detection of human chorionic gonadotropin (HCG), a model analyte, in a linear range from 1.0mIUmL -1 to 100.0 IU mL -1 with a detection limit of 0.36mIUmL -1 . Additionally, the proposed μ-PEI was used to test HCG in real human serum and obtained satisfactory results. The disposable, efficient, sensitive and low-cost μ-PEI has exhibited great potential for the development of point-of-care testing (POCT) devices that can be applicated in healthcare monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Polymer-Based Microfluidic Devices for Pharmacy, Biology and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Kerstin Ramser

    2012-07-01

    Full Text Available This paper reviews microfluidic technologies with emphasis on applications in the fields of pharmacy, biology, and tissue engineering. Design and fabrication of microfluidic systems are discussed with respect to specific biological concerns, such as biocompatibility and cell viability. Recent applications and developments on genetic analysis, cell culture, cell manipulation, biosensors, pathogen detection systems, diagnostic devices, high-throughput screening and biomaterial synthesis for tissue engineering are presented. The pros and cons of materials like polydimethylsiloxane (PDMS, polymethylmethacrylate (PMMA, polystyrene (PS, polycarbonate (PC, cyclic olefin copolymer (COC, glass, and silicon are discussed in terms of biocompatibility and fabrication aspects. Microfluidic devices are widely used in life sciences. Here, commercialization and research trends of microfluidics as new, easy to use, and cost-effective measurement tools at the cell/tissue level are critically reviewed.

  16. A portable microfluidic fluorescence spectrometer device for γ-H2AX-based biological dosimetry

    International Nuclear Information System (INIS)

    Pope, I.A.; Barber, P.R.; Horn, S.; Ainsbury, E.; Rothkamm, K.; Vojnovic, B.

    2011-01-01

    Following a radiological incident the rapid identification of those individuals exposed to critically high radiation doses is important for initial triage and medical treatment. It has been previously demonstrated that scoring of radiation-induced foci of the phosphorylated histone γ-H2AX, which form at the sites of DNA double-strand breaks, may be used to determine radiation exposure levels from blood samples. Although faster than the 'gold standard' dicentric assay, foci scoring is still impractical in a field situation where large numbers of people may need to be screened. To deal with such a situation, an inexpensive portable device with high throughput capacity is desirable. Here we describe a portable microfluidic fluorescence spectrometer device which passes a suspension of γ-H2AX immunofluorescence-stained lymphocytes through a focused 488 nm laser beam in a microfluidic chamber and records emission spectra over the range 495-725 nm. The recorded emission spectra are spectrally unmixed into their constituent parts from which radiation exposure levels are determined. Proof of principle is demonstrated using cultured lymphoblastoid cells, exposed to X-ray doses between 0 and 8 Gy. With the current prototype setup it takes approximately 6 min to acquire and analyse 10,000 spectra. Further effort is required to fully develop this approach into a portable triage tool that could be used to help classify people into appropriate treatment categories based on radiation exposure levels.

  17. Development of a Mechatronic Syringe Pump to Control Fluid Flow in a Microfluidic Device Based on Polyimide Film

    Science.gov (United States)

    Sek Tee, Kian; Sharil Saripan, Muhammad; Yap, Hiung Yin; Fhong Soon, Chin

    2017-08-01

    With the advancement in microfluidic technology, fluid flow control for syringe pump is always essential. In this paper, a mechatronic syringe pump will be developed and customized to control the fluid flow in a poly-dimethylsiloxane (PDMS) microfluidic device based on a polyimide laminating film. The syringe pump is designed to drive fluid with flow rates of 100 and 1000 μl/min which intended to drive continuous fluid in a polyimide based microfluidic device. The electronic system consists of an Arduino microcontroller board and a uni-polar stepper motor. In the system, the uni-polar stepper motor was coupled to a linear slider attached to the plunger of a syringe pump. As the motor rotates, the plunger pumps the liquid out of the syringe. The accuracy of the fluid flow rate was determined by adjusting the number of micro-step/revolution to drive the stepper motor to infuse fluid into the microfluidic device. With the precise control of the electronic system, the syringe pump could accurately inject fluid volume at 100 and 1000 μl/min into a microfluidic device.

  18. A laser microwelding method for assembly of polymer based microfluidic devices

    Science.gov (United States)

    Jiang, Xin; Chandrasekar, Soni; Wang, Changhai

    2015-03-01

    This paper presents the development of a laser microwelding method for assembly and packaging of polymer based microfluidic devices. In this approach a diode laser was used to weld two poly(methyl methacrylate) (PMMA) substrates together at the interface using a thin film metal spot based intermediate layer design as a localized absorber. A broad laser beam with a top-hat profile was used to carry out the laser microwelding work. The effects of laser power and processing time on the resultant heated affected zone (HAZ) and the melted zone were investigated. For large area welding, a 2×2 array of thin film metal spots were used to investigate the effect of separation between the spots on the resultant interfacial bond between the two polymer substrates. For comparison, a large area titanium film with a comparable size to that of the 2×2 array was also studied. The results show that the discrete film pattern based design is better than a single large area film in order to reduce the effect of substrate distortion resulting from the higher temperature rise associated with the latter. The tensile strength of the laser welded joints was determined to be about 6 MPa for a sample produced using the 2×2 array of circular titanium spot pattern design. The laser microwelding method has been demonstrated successfully in leak-free encapsulation of a microfluidic channel.

  19. Mkit: A cell migration assay based on microfluidic device and smartphone.

    Science.gov (United States)

    Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

    2018-01-15

    Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS 2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS 2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS 2 -based cell functional assay for testing cell migration (the M kit ). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the M kit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the M kit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the M kit . In addition to research applications, we demonstrated the effective use of the M kit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed M kit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Microfluidic device for drug delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  1. Metering the capillary-driven flow of fluids in paper-based microfluidic devices.

    Science.gov (United States)

    Noh, Hyeran; Phillips, Scott T

    2010-05-15

    This article describes an exceedingly simple and low-cost method for metering the capillary-driven flow rate of fluids within three-dimensional (3D) microfluidic, paper-based analytical devices (microPADs). Initial prototypes of 3D microPADs control the spatial distribution of fluids within a device, but they provide little control over how quickly (or slowly) fluids move within the device. The methods described in this article provide control over when and how quickly a fluid is distributed into detection zones. These methods are inexpensive (the metering regions are composed of paraffin wax), the devices are easy to fabricate, and they are capable of controlling the flow of fluids to detection zones with precise time delays (e.g., +/-6% of the total wicking time). We anticipate that this type of precise control over fluid distribution rates will be useful particularly for point-of-care assays that require multiple steps (where each step requires that the reagents interact for a defined period of time) or for simultaneously displaying the results of multiple different assays on a single device.

  2. 3D printed Lego®-like modular microfluidic devices based on capillary driving.

    Science.gov (United States)

    Nie, Jing; Gao, Qing; Qiu, Jing-Jiang; Sun, Miao; Liu, An; Shao, Lei; Fu, Jian-Zhong; Zhao, Peng; He, Yong

    2018-03-12

    The field of how to rapidly assemble microfluidics with modular components continuously attracts researchers' attention, however, extra efforts must be devoted to solving the problems of leaking and aligning between individual modules. This paper presents a novel type of modular microfluidic device, driven by capillary force. There is no necessity for a strict seal or special alignment, and its open structures make it easy to integrate various stents and reactants. The key rationale for this method is to print different functional modules with a low-cost three-dimensional (3D) printer, then fill the channels with capillary materials and assemble them with plugs like Lego ® bricks. This rapidly reconstructed modular microfluidic device consists of a variety of common functional modules and other personalized modules, each module having a unified standard interface for easy assembly. As it can be printed by a desktop 3D printer, the manufacturing process is simple and efficient, with controllable regulation of the flow channel scale. Through diverse combinations of different modules, a variety of different functions can be achieved, without duplicating the manufacturing process. A single module can also be taken out for testing and analysis. What's more, combined with basic circuit components, it can serve as a low-cost Lego ® -like modular microfluidic circuits. As a proof of concept, the modular microfluidic device has been successfully demonstrated and used for stent degradation and cell cultures, revealing the potential use of this method in both chemical and biological research.

  3. Acid-base titrations using microfluidic paper-based analytical devices.

    Science.gov (United States)

    Karita, Shingo; Kaneta, Takashi

    2014-12-16

    Rapid and simple acid-base titration was accomplished using a novel microfluidic paper-based analytical device (μPAD). The μPAD was fabricated by wax printing and consisted of ten reservoirs for reaction and detection. The reaction reservoirs contained various amounts of a primary standard substance, potassium hydrogen phthalate (KHPth), whereas a constant amount of phenolphthalein was added to all the detection reservoirs. A sample solution containing NaOH was dropped onto the center of the μPAD and was allowed to spread to the reaction reservoirs where the KHPth neutralized it. When the amount of NaOH exceeded that of the KHPth in the reaction reservoirs, unneutralized hydroxide ion penetrated the detection reservoirs, resulting in a color reaction from the phenolphthalein. Therefore, the number of the detection reservoirs with no color change determined the concentration of the NaOH in the sample solution. The titration was completed within 1 min by visually determining the end point, which required neither instrumentation nor software. The volumes of the KHPth and phenolphthalein solutions added to the corresponding reservoirs were optimized to obtain reproducible and accurate results for the concentration of NaOH. The μPADs determined the concentration of NaOH at orders of magnitude ranging from 0.01 to 1 M. An acid sample, HCl, was also determined using Na2CO3 as a primary standard substance instead of KHPth. Furthermore, the μPAD was applicable to the titrations of nitric acid, sulfuric acid, acetic acid, and ammonia solutions. The μPADs were stable for more than 1 month when stored in darkness at room temperature, although this was reduced to only 5 days under daylight conditions. The analysis of acidic hot spring water was also demonstrated in the field using the μPAD, and the results agreed well with those obtained by classic acid-base titration.

  4. Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices by Rational Device Design.

    Science.gov (United States)

    Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Milan, Luis Aparecido; Stockton, Amanda M; Carrilho, Emanuel

    2017-05-02

    Paper-based devices are a portable, user-friendly, and affordable technology that is one of the best analytical tools for inexpensive diagnostic devices. Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) are an evolution of single layer devices and they permit effective sample dispersion, individual layer treatment, and multiplex analytical assays. Here, we present the rational design of a wax-printed 3D-μPAD that enables more homogeneous permeation of fluids along the cellulose matrix than other existing designs in the literature. Moreover, we show the importance of the rational design of channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) reactions. We present an alternative method for layer stacking using a magnetic apparatus, which facilitates fluidic dispersion and improves the reproducibility of tests performed on 3D-μPADs. We also provide the optimized designs for printing, facilitating further studies using 3D-μPADs.

  5. A Simple Paper-Based Microfluidic Device for the Determination of the Total Amino Acid Content in a Tea Leaf Extract

    Science.gov (United States)

    Cai, Longfei; Wu, Yunying; Xu, Chunxiu; Chen, Zefeng

    2013-01-01

    An experiment was developed to demonstrate a microfluidic device in the analytical chemistry (instrumental analysis) laboratory. Students made the paper-based microfluidic device with a wax pen and a piece of filter paper and used it to determine the total quantity of amino acids in a green tea leaf

  6. Fabrication of PDMS-Based Microfluidic Devices: Application for Synthesis of Magnetic Nanoparticles

    Science.gov (United States)

    Thu, Vu Thi; Mai, An Ngoc; Le The Tam; Van Trung, Hoang; Thu, Phung Thi; Tien, Bui Quang; Thuat, Nguyen Tran; Lam, Tran Dai

    2016-05-01

    In this work, we have developed a convenient approach to synthesize magnetic nanoparticles with relatively high magnetization and controllable sizes. This was realized by combining the traditional co-precipitation method and microfluidic techniques inside microfluidic devices. The device was first designed, and then fabricated using simplified soft-lithography techniques. The device was utilized to synthesize magnetite nanoparticles. The synthesized nanomaterials were thoroughly characterized using field emission scanning electron microscopy and a vibrating sample magnetometer. The results demonstrated that the as-prepared device can be utilized as a simple and effective tool to synthesize magnetic nanoparticles with the sizes less than 10 nm and magnetization more than 50 emu/g. The development of these devices opens new strategies to synthesize nanomaterials with more precise dimensions at narrow size-distribution and with controllable behaviors.

  7. Blood coagulation screening using a paper-based microfluidic lateral flow device.

    Science.gov (United States)

    Li, H; Han, D; Pauletti, G M; Steckl, A J

    2014-10-21

    A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition.

  8. A microfluidic paper-based analytical device for rapid quantification of particulate chromium

    International Nuclear Information System (INIS)

    Rattanarat, Poomrat; Dungchai, Wijitar; Cate, David M.; Siangproh, Weena; Volckens, John; Chailapakul, Orawon; Henry, Charles S.

    2013-01-01

    Graphical abstract: -- Highlights: •Cr detection using a paper-based analytical device. •Analysis of total Cr levels in particulate matter was achieved. •Method for on-paper oxidation of Cr to Cr(VI) using Ce(IV) was established. -- Abstract: Occupational exposure to Cr is concerning because of its myriad of health effects. Assessing chromium exposure is also cost and resource intensive because the analysis typically uses sophisticated instrumental techniques like inductively coupled plasma-mass spectrometry (ICP-MS). Here, we report a novel, simple, inexpensive microfluidic paper-based analytical device (μPAD) for measuring total Cr in airborne particulate matter. In the μPAD, tetravalent cerium (Ce(IV)) was used in a pretreatment zone to oxidize all soluble Cr to Cr(VI). After elution to the detection zone, Cr(VI) reacts with 1,5-diphenylcarbazide (1,5-DPC) forming 1,5-diphenylcarbazone (DPCO) and Cr(III). The resulting Cr(III) forms a distinct purple colored complex with the DPCO. As proof-of-principle, particulate matter (PM) collected on a sample filter was analyzed with the μPAD to quantify the mass of total Cr. A log-linear working range (0.23–3.75 μg; r 2 = 0.998) between Cr and color intensity was obtained with a detection limit of 0.12 μg. For validation, a certified reference containing multiple competing metals was analyzed. Quantitative agreement was obtained between known Cr levels in the sample and the Cr measured using the μPAD

  9. Detection of distributed static and dynamic loads with electrolyte-enabled distributed transducers in a polymer-based microfluidic device

    International Nuclear Information System (INIS)

    Gu, Wenting; Cheng, Peng; Ghosh, Arindam; Beskok, Ali; Hao, Zhili; Liao, Yuxi; Liao, Boxiong

    2013-01-01

    This paper reports on the use of electrolyte-enabled distributed transducers in a polymer-based microfluidic device for the detection of distributed static and dynamic loads. The core of the device is a polymer rectangular microstructure integrated with electrolyte-enabled distributed transducers. Distributed loads acting on the polymer microstructure are converted to different deflections along the microstructure length, which are further translated to electrical resistance changes by electrolyte-enabled distributed transducers. Owing to the great simplicity of the device configuration, a standard polymer-based fabrication process is employed to fabricate this device. With custom-built electronic circuits and custom LabVIEW programs, fabricated devices filled with two different electrolytes, 0.1 M NaCl electrolyte and 1-ethyl-3-methylimidazolium dicyanamide electrolyte, are characterized, demonstrating the capability of detecting distributed static and dynamic loads with a single device. As a result, the polymer-based microfluidic device presented in this paper is promising for offering the capability of detecting distributed static and dynamic loads in biomedical/surgical, manufacturing and robotics applications. (paper)

  10. Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

    Science.gov (United States)

    Lim, Wei Yin; Goh, Boon Tong; Khor, Sook Mei

    2017-08-15

    Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Geometrical Alignment of Multiple Fabrication Steps for Rapid Prototyping of Microfluidic Paper-Based Analytical Devices.

    Science.gov (United States)

    Rahbar, Mohammad; Nesterenko, Pavel N; Paull, Brett; Macka, Mirek

    2017-11-21

    Three main fabrication steps for microfluidic paper-based analytical devices (μPADs) were fully integrated with accurate geometrical alignment between the individual steps in a simple and rapid manner. A wax printer for creating hydrophobic barriers was integrated with an inexpensive (ca. $300) electronic craft plotter/cutter for paper cutting, followed by colorimetric reagent deposition using technical pens. The principal shortcoming in the lack of accurate and precise alignment of the features created by these three individual fabrication steps was addressed in this work by developing appropriate alignment procedures during the multistep fabrication process. The wax printing step was geometrically aligned with the following cutting and plotting (deposition) steps in a highly accurate and precise manner using optical scanning function of the plotter/cutter based on registration marks printed on the paper using the wax printer and scanned by the plotter/cutter. The accuracy and precision of alignment in a two-dimensional plane were quantified by cutting and plotting cross-shaped features and measuring their center coordinates relative to wax printed reference lines. The average accuracy along the X- and Y-axis was 0.12 and 0.16 mm for cutting and 0.19 and 0.17 mm for plotting, respectively. The potential of this approach was demonstrated by fabricating μPADs for instrument-free determination of cobalt in waters using distance-based readout, with excellent precision (%RSD = 5.7) and detection limit (LOD) of 2.5 ng and 0.5 mg/L (mass and concentration LODs, respectively).

  12. Isolation of Circulating Plasma Cells in Multiple Myeloma Using CD138 Antibody-Based Capture in a Microfluidic Device

    Science.gov (United States)

    Qasaimeh, Mohammad A.; Wu, Yichao C.; Bose, Suman; Menachery, Anoop; Talluri, Srikanth; Gonzalez, Gabriel; Fulciniti, Mariateresa; Karp, Jeffrey M.; Prabhala, Rao H.; Karnik, Rohit

    2017-04-01

    The necessity for bone marrow aspiration and the lack of highly sensitive assays to detect residual disease present challenges for effective management of multiple myeloma (MM), a plasma cell cancer. We show that a microfluidic cell capture based on CD138 antigen, which is highly expressed on plasma cells, permits quantitation of rare circulating plasma cells (CPCs) in blood and subsequent fluorescence-based assays. The microfluidic device is based on a herringbone channel design, and exhibits an estimated cell capture efficiency of ~40-70%, permitting detection of numbers in blood samples of MM patients in remission (20-24 CD138+ cells/mL), and yet higher numbers in MM patients exhibiting disease (45-184 CD138+ cells/mL). Analysis of CPCs isolated using the device was consistent with serum immunoglobulin assays that are commonly used in MM diagnostics. These results indicate the potential of CD138-based microfluidic CPC capture as a useful ‘liquid biopsy’ that may complement or partially replace bone marrow aspiration.

  13. Microfluidic ion-sensing devices.

    Science.gov (United States)

    Johnson, R Daniel; Gavalas, Vasilis G; Daunert, Sylvia; Bachas, Leonidas G

    2008-04-14

    Quantitative determinations of ions in a variety of media have been performed traditionally via one of three approaches: optical instrumental methods (e.g., atomic absorption, and inductively-coupled plasma-optical emission or mass spectrometry), "wet" methods, or ion-selective sensors. Each of the approaches, though, possesses limitations including: power/reagent consumption and lack of portability for instrumental techniques; laborious sample-treatment steps for wet methods; and lack of selectivity and sensitivity with sensors when employed with complex samples. Microfluidic device have emerged as a solution to some of these challenges associated with ion analysis. Such systems can integrate multiple sample handling, calibration, and detection steps ("lab-on-a-chip" concept) into a footprint amenable to portability, while requiring small amounts of sample and power. Furthermore, devices can be constructed for multi-analyte detection, either through multiple parallel fluidic architectures or by using arrays of detection elements. This paper reviews recent progress in the development of total-analysis systems for ionic species. Fabrication techniques and various fluid-handling operations are discussed briefly, followed by a number of more mature strategies for microfluidic ion analysis. A variety of approaches expected to comprise the next generation of devices are also presented.

  14. Integrated lenses in polystyrene microfluidic devices

    KAUST Repository

    Fan, Yiqiang

    2013-04-01

    This paper reports a new method for integrating microlenses into microfluidic devices for improved observation. Two demonstration microfluidic devices were provided which were fabricated using this new technique. The integrated microlenses were fabricated using a free-surface thermo-compression molding method on a polystyrene (PS) sheet which was then bonded on top of microfluidic channels as a cover plate, with the convex microlenses providing a magnified image of the channel for the easier observation of the flow in the microchannels. This approach for fabricating the integrated microlens in microfluidic devices is rapid, low cost and without the requirement of cleanroom facilities. © 2013 IEEE.

  15. Design of a microfluidic paper-based device for analysis of biomarkers from urine samples on diapers.

    Science.gov (United States)

    Couto, Adriana; Tao Dong

    2017-07-01

    Among all infections, urinary tract infections (UTI) are one of the most common. Nowadays the procedures to analyze urine and consequently detect UTI are often painful and time-consuming. Recent studies about microfluidic paper-based devices have developed the interest of researchers due their outstanding characteristics. In this paper is presented a novel design for a microfluidic paper-based device for screening and analysis of multiple biomarkers from urine samples on diapers. The device consists on a set of eight layers. It was designed based on the previous attempts to improve and overcome some problems detected as the continuous entrance of fluids, the possibility of contamination and the invalidity of results due to communication between different reagent pads. One approach was create a "self-locking" mechanism that closes the sample inlet in approximately four minutes solving the first two problems. Furthermore, is important that comfort is guaranteed, hence a device with a total thickness of 5,3 mm is presented. This device can keep the results for eight hours and can be used as a low-cost and more effective alternative than conventional methods being a strategy with potential for the diagnostic and analysis of biological samples in the future improving healthcare.

  16. Microfluidic Devices for Blood Fractionation

    OpenAIRE

    Hou, Han Wei; Bhagat, Ali Asgar S.; Lee, Wong Cheng J.; Huang, Sha; Han, Jongyoon; Lim, Chwee Teck

    2011-01-01

    Blood, a complex biological fluid, comprises 45% cellular components suspended in protein rich plasma. These different hematologic components perform distinct functions in vivo and thus the ability to efficiently fractionate blood into its individual components has innumerable applications in both clinical diagnosis and biological research. Yet, processing blood is not trivial. In the past decade, a flurry of new microfluidic based technologies has emerged to address this compelling problem. ...

  17. Pressure driven digital logic in PDMS based microfluidic devices fabricated by multilayer soft lithography.

    Science.gov (United States)

    Devaraju, Naga Sai Gopi K; Unger, Marc A

    2012-11-21

    Advances in microfluidics now allow an unprecedented level of parallelization and integration of biochemical reactions. However, one challenge still faced by the field has been the complexity and cost of the control hardware: one external pressure signal has been required for each independently actuated set of valves on chip. Using a simple post-modification to the multilayer soft lithography fabrication process, we present a new implementation of digital fluidic logic fully analogous to electronic logic with significant performance advances over the previous implementations. We demonstrate a novel normally closed static gain valve capable of modulating pressure signals in a fashion analogous to an electronic transistor. We utilize these valves to build complex fluidic logic circuits capable of arbitrary control of flows by processing binary input signals (pressure (1) and atmosphere (0)). We demonstrate logic gates and devices including NOT, NAND and NOR gates, bi-stable flip-flops, gated flip-flops (latches), oscillators, self-driven peristaltic pumps, delay flip-flops, and a 12-bit shift register built using static gain valves. This fluidic logic shows cascade-ability, feedback, programmability, bi-stability, and autonomous control capability. This implementation of fluidic logic yields significantly smaller devices, higher clock rates, simple designs, easy fabrication, and integration into MSL microfluidics.

  18. Microfluidic toner-based analytical devices: disposable, lightweight, and portable platforms for point-of-care diagnostics with colorimetric detection.

    Science.gov (United States)

    Oliveira, Karoliny Almeida; de Souza, Fabrício Ribeiro; de Oliveira, Cristina Rodrigues; da Silveira, Lucimeire Antonelli; Coltro, Wendell Karlos Tomazelli

    2015-01-01

    This chapter describes the development of microfluidic toner-based analytical devices (μTADs) to perform clinical diagnostics using a scanner or cell-phone camera. μTADs have been produced in a platform composed of polyester and toner by the direct-printing technology (DPT) in a matter of minutes. This technology offers simplicity and versatility, and it does not require any sophisticated instrumentation. Toner-based devices integrate the current generation of disposable analytical devices along paper-based chips. The cost of one μTAD has been estimated to be lower than $0.10. In addition, these platforms are lightweight and portable thus enabling their use for point-of-care applications. In the last 5 years, great efforts have been dedicated to spread out the use of μTADs in bioassays. The current chapter reports the fabrication of printed microplates and integrated microfluidic toner-based devices for dengue diagnostics and rapid colorimetric assays with clinically relevant analytes including cholesterol, triglycerides, total proteins, and glucose. The use of μTADs associated with cell-phone camera may contribute to the health care, in special, to people housed in developing regions or with limited access to clinics and hospitals.

  19. Development of a microfluidic paper-based analytical device for the determination of salivary aldehydes.

    Science.gov (United States)

    Ramdzan, Adlin N; Almeida, M Inês G S; McCullough, Michael J; Kolev, Spas D

    2016-05-05

    A low cost, disposable and easy to use microfluidic paper-based analytical device (μPAD) was developed for simple and non-invasive determination of total aldehydes in saliva with a potential to be used in epidemiological studies to assess oral cancer risk. The μPAD is based on the colour reaction between aldehydes (e.g. acetaldehyde, formaldehyde), 3-methyl-2-benzothiazolinone hydrazone (MBTH) and iron(III) to form an intense blue coloured formazan dye. The newly developed μPAD has a 3D design with two overlapping paper layers. The first layer comprises 15 circular detection zones (8 mm in diameter), each impregnated with 8 μL of MBTH, while the second layer contains 15 reagent zones (4 mm in diameter). Two μL of iron(III) chloride are added to each one of the second layer zones after the addition of sample to the detection zones in the first layer. All hydrophilic zones of the μPAD are defined by wax printing using a commercial wax printer. Due to the 2-step nature of the analytical reaction, the two paper layers are separated by a cellulose acetate interleaving sheet to allow for the reaction between the aldehydes in the saliva sample with MBTH to proceed first with the formation of an azine, followed by a blue coloured reaction between the azine and the oxidized by iron(III) form of MBTH, produced after the removal of the interleaving sheet. After obtaining a high resolution image of the detection side zone of the device using a flatbed scanner, the intensity of the blue colour within each detection zone is measured with Image J software. Under optimal conditions, the μPAD is characterised by a working range of 20.4-114.0 μM, limit of detection of 6.1 μM, and repeatability, expressed as RSD, of less than 12.7% (n = 5). There is no statistically significant difference at the 95% confidence level between the results obtained by the μPAD and the reference method (Student's t-test: 0.090 < 0.38). The optimized μPAD is stable for more than 41 days

  20. Chemometrics-assisted microfluidic paper-based analytical device for the determination of uric acid by silver nanoparticle plasmon resonance.

    Science.gov (United States)

    Hamedpour, Vahid; Postma, Geert J; van den Heuvel, Edwin; Jansen, Jeroen J; Suzuki, Koji; Citterio, Daniel

    2018-03-01

    This manuscript reports on the application of chemometric methods for the development of an optimized microfluidic paper-based analytical device (μPAD). As an example, we applied chemometric methods for both device optimization and data processing of results of a colorimetric uric acid assay. Box-Behnken designs (BBD) were utilized for the optimization of the device geometry and the amount of thermal inkjet-deposited assay reagents, which affect the assay performance. Measurement outliers were detected in real time by partial least squares discriminant analysis (PLS-DA) of scanned images. The colorimetric assay mechanism is based on the on-device formation of silver nanoparticles (AgNPs) through the interaction of uric acid, ammonia, and poly(vinyl alcohol) with silver ions under mild basic conditions. The yellow color originating from visible light absorption by localized surface plasmon resonance of AgNPs can be detected by the naked eye or, more quantitatively, with a simple flat-bed scanner. Under optimized conditions, the linearity of the calibration curve ranges from 0.1-5 × 10 -3 mol L -1 of uric acid with a limit of detection of 33.9 × 10 -6 mol L -1 and a relative standard of deviation 4.5% (n = 3 for determination of 5.0 × 10 -3 mol L -1 uric acid). Graphical abstract A chemometrics-assisted microfluidic paper-based analytical device was developed as a low-cost and rapid platform for the determination of uric acid (UA). The detection method is based on the chemical interaction of UA, ammonia, and polyvinyl alcohol under mild basic condition with silver ions inducing formation of yellow silver nanoparticles (AgNPs).

  1. Microfluidic Devices in Advanced Caenorhabditis elegans Research

    Directory of Open Access Journals (Sweden)

    Muniesh Muthaiyan Shanmugam

    2016-08-01

    Full Text Available The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

  2. Image analysis for a microfluidic paper-based analytical device using the CIE L*a*b* color system.

    Science.gov (United States)

    Komatsu, Takeshi; Mohammadi, Saeed; Busa, Lori Shayne Alamo; Maeki, Masatoshi; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

    2016-11-28

    The combination of a microfluidic paper-based analytical device (μPAD) and digital image analysis is widely used for quantitative analysis with μPADs because of its easy and simple operation. Herein, we have demonstrated a quantitative analysis based on multiple color changes on a μPAD. The CIE L*a*b* color system was employed to analyse the digital images obtained with the μPAD. We made pH measurements using a universal pH-indicator showing multiple color changes for various pH values of aqueous test solutions. The detectable pH range of this method was wider than the typical grayscale-based image analysis, and we succeeded in the measurements for a wide pH range of 2-9.

  3. Beyond PDMS: off-stoichiometry thiol-ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices.

    Science.gov (United States)

    Carlborg, Carl Fredrik; Haraldsson, Tommy; Öberg, Kim; Malkoch, Michael; van der Wijngaart, Wouter

    2011-09-21

    In this article we introduce a novel polymer platform based on off-stoichiometry thiol-enes (OSTEs), aiming to bridge the gap between research prototyping and commercial production of microfluidic devices. The polymers are based on the versatile UV-curable thiol-ene chemistry but takes advantage of off-stoichiometry ratios to enable important features for a prototyping system, such as one-step surface modifications, tuneable mechanical properties and leakage free sealing through direct UV-bonding. The platform exhibits many similarities with PDMS, such as rapid prototyping and uncomplicated processing but can at the same time mirror the mechanical and chemical properties of both PDMS as well as commercial grade thermoplastics. The OSTE-prepolymer can be cast using standard SU-8 on silicon masters and a table-top UV-lamp, the surface modifications are precisely grafted using a stencil mask and the bonding requires only a single UV-exposure. To illustrate the potential of the material we demonstrate key concepts important in microfluidic chip fabrication such as patterned surface modifications for hydrophobic stops, pneumatic valves using UV-lamination of stiff and rubbery materials as well as micromachining of chip-to-world connectors in the OSTE-materials. This journal is © The Royal Society of Chemistry 2011

  4. Dry Film Photoresist-based Electrochemical Microfluidic Biosensor Platform: Device Fabrication, On-chip Assay Preparation, and System Operation.

    Science.gov (United States)

    Bruch, Richard; Kling, André; Urban, Gerald A; Dincer, Can

    2017-09-19

    In recent years, biomarker diagnostics became an indispensable tool for the diagnosis of human disease, especially for the point-of-care diagnostics. An easy-to-use and low-cost sensor platform is highly desired to measure various types of analytes (e.g., biomarkers, hormones, and drugs) quantitatively and specifically. For this reason, dry film photoresist technology - enabling cheap, facile, and high-throughput fabrication - was used to manufacture the microfluidic biosensor presented here. Depending on the bioassay used afterwards, the versatile platform is capable of detecting various types of biomolecules. For the fabrication of the device, platinum electrodes are structured on a flexible polyimide (PI) foil in the only clean-room process step. The PI foil serves as a substrate for the electrodes, which are insulated with an epoxy-based photoresist. The microfluidic channel is subsequently generated by the development and lamination of dry film photoresist (DFR) foils onto the PI wafer. By using a hydrophobic stopping barrier in the channel, the channel is separated into two specific areas: an immobilization section for the enzyme-linked assay and an electrochemical measurement cell for the amperometric signal readout. The on-chip bioassay immobilization is performed by the adsorption of the biomolecules to the channel surface. The glucose oxidase enzyme is used as a transducer for electrochemical signal generation. In the presence of the substrate, glucose, hydrogen peroxide is produced, which is detected at the platinum working electrode. The stop-flow technique is applied to obtain signal amplification along with rapid detection. Different biomolecules can quantitatively be measured by means of the introduced microfluidic system, giving an indication of different types of diseases, or, in regard to therapeutic drug monitoring, facilitating a personalized therapy.

  5. Porous Microfluidic Devices - Fabrication adn Applications

    NARCIS (Netherlands)

    de Jong, J.; Geerken, M.J.; Lammertink, Rob G.H.; Wessling, Matthias

    2007-01-01

    The major part of microfluidic devices nowadays consists of a dense material that defines the fluidic structure. A generic fabrication method enabling the production of completely porous micro devices with user-defined channel networks is developed. The channel walls can be used as a (selective)

  6. Three-dimensional ordered titanium dioxide-zirconium dioxide film-based microfluidic device for efficient on-chip phosphopeptide enrichment.

    Science.gov (United States)

    Zhao, De; He, Zhongyuan; Wang, Gang; Wang, Hongzhi; Zhang, Qinghong; Li, Yaogang

    2016-09-15

    Microfluidic technology plays a significant role in separating biomolecules, because of its miniaturization, integration, and automation. Introducing micro/nanostructured functional materials can improve the properties of microfluidic devices, and extend their application. Inverse opal has a three-dimensional ordered net-like structure. It possesses a large surface area and exhibits good mass transport, making it a good candidate for bio-separation. This study exploits inverse opal titanium dioxide-zirconium dioxide films for on-chip phosphopeptide enrichment. Titanium dioxide-zirconium dioxide inverse opal film-based microfluidic devices were constructed from templates of 270-, 340-, and 370-nm-diameter poly(methylmethacrylate) spheres. The phosphopeptide enrichments of these devices were determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The device constructed from the 270-nm-diameter sphere template exhibited good comprehensive phosphopeptide enrichment, and was the best among these three devices. Because the size of opal template used in construction was the smallest, the inverse opal film therefore had the smallest pore sizes and the largest surface area. Enrichment by this device was also better than those of similar devices based on nanoparticle films and single component films. The titanium dioxide-zirconium dioxide inverse opal film-based device provides a promising approach for the efficient separation of various biomolecules. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 3D Printed Multi-layer Microfluidic Devices

    Science.gov (United States)

    Bishop, Nathan; Shirk, Kathryn

    Microfluidic devices are increasingly important to the field of bioanalysis for their ability to quickly process a sample in the microliter and picoliter scale. It has been shown that single-layered microfluidic devices can be produced quickly and inexpensively using a 3D printer, PDMS, and shrinking material. This research will expand these methods to create multi-layered microfluidic devices. This research will focus on two main obstacles when creating multi-layer microfluidic devices: layer alignment, and surface roughness. The development of multilayer microfluidic devices allows for more compact microfluidic chip design. This research was funded by the Shippensburg University Undergraduate Research Grant Program.

  8. Fluid control in microfluidic devices using a fluid conveyance extension and an absorbent microfluidic flow modulator.

    Science.gov (United States)

    Yuen, Po Ki

    2013-05-07

    This article presents a simple method for controlling fluid in microfluidic devices without the need for valves or pumps. A fluid conveyance extension is fluidly coupled to the enclosed outlet chamber of a microfluidic device. After a fluid is introduced into the microfluidic device and saturates the fluid conveyance extension, a fluid flow in the microfluidic device is generated by contacting an absorbent microfluidic flow modulator with the fluid conveyance extension to absorb the fluid from the fluid conveyance extension through capillary action. Since the fluid in the microfluidic device is fluidly coupled with the fluid conveyance extension and the fluid conveyance extension is fluidly coupled with the absorbent microfluidic flow modulator, the absorption rate of the absorbent microfluidic flow modulator, which is the rate at which the absorbent microfluidic flow modulator absorbs fluid, matches the fluid flow rate in the microfluidic device. Thus, the fluid flow rate in the microfluidic device is set by the absorption rate of the absorbent microfluidic flow modulator. Sheath flow and fluid switching applications are demonstrated using this simple fluid control method without the need for valves or pumps. Also, the ability to control the fluid flow rate in the microfluidic device is demonstrated using absorbent microfluidic flow modulators with various absorbent characteristics and dimensions.

  9. Rapid, low-cost prototyping of centrifugal microfluidic devices for effective implementation of various microfluidic components

    Directory of Open Access Journals (Sweden)

    Smith, Suzanne

    2015-05-01

    Full Text Available A centrifugal microfluidic platform to develop various microfluidic operations – the first of its kind in South Africa – is presented. Rapid and low-cost prototyping of centrifugal microfluidic disc devices, as well as a set-up to test the devices using centrifugal forces, is described. Preliminary results show that various microfluidic operations such as fluidic valving, transportation, and microfluidic droplet generation can be achieved. This work provides a complete centrifugal microfluidic platform and the building blocks on which to develop a variety of microfluidic applications and potential products rapidly and at a low cost.

  10. Microfluidic devices for biological applications

    CSIR Research Space (South Africa)

    Potgieter, S

    2010-01-01

    Full Text Available Microfluidics is a multi-disciplinary field that deals with the behaviour, control and manipulation of fluids constrained to sub-millilitre volumes. It is proving to be a useful tool for biological studies, affording advantages such as reduced cost...

  11. AlScN thin film based surface acoustic wave devices with enhanced microfluidic performance

    International Nuclear Information System (INIS)

    Wang, W B; Xuan, W P; Chen, J K; Wang, X Z; Luo, J K; Fu, Y Q; Chen, J J; Duan, P F; Mayrhofer, P; Bittner, A; Schmid, U

    2016-01-01

    This paper reports the characterization of scandium aluminum nitride (Al 1−xS c xN , x   =  27%) films and discusses surface acoustic wave (SAW) devices based on them. Both AlScN and AlN films were deposited on silicon by sputtering and possessed columnar microstructures with (0 0 0 2) crystal orientation. The AlScN/Si SAW devices showed improved electromechanical coupling coefficients ( K 2 , ∼2%) compared with pure AlN films (<0.5%). The performance of the two types of devices was also investigated and compared, using acoustofluidics as an example. The AlScN/Si SAW devices achieved much lower threshold powers for the acoustic streaming and pumping of liquid droplets, and the acoustic streaming and pumping velocities were 2  ×  and 3  ×  those of the AlN/Si SAW devices, respectively. Mechanical characterization showed that the Young’s modulus and hardness of the AlN film decreased significantly when Sc was doped, and this was responsible for the decreased acoustic velocity and resonant frequency, and the increased temperature coefficient of frequency, of the AlScN SAW devices. (paper)

  12. Rapid photochemical surface patterning of proteins in thiol-ene based microfluidic devices

    DEFF Research Database (Denmark)

    Lafleur, Josiane P.; Kwapiszewski, Radoslaw; Jensen, Thomas Glasdam

    2012-01-01

    ” and “ene” monomers present in the microfluidic chip bulk material provides a simple and efficient way of tuning the chip’s surface chemistry. Here, thiol-ene chips displaying an excess of functional thiol groups at their surfaces are functionalized with biotin and streptavidin in a controlled fashion using...

  13. Tabu Search-based Synthesis of Digital Microfluidic Biochips with Dynamically Reconfigurable Non-rectangular Devices

    DEFF Research Database (Denmark)

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2010-01-01

    rectangular. In this paper, we present a Tabu Search metaheuristic for the synthesis of digital microfluidic biochips, which, starting from a biochemical application and a given biochip architecture, determines the allocation, resource binding, scheduling and placement of the operations in the application...

  14. Micro-Fluidic Device for Drug Delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  15. AlScN thin film based surface acoustic wave devices with enhanced microfluidic performance

    OpenAIRE

    Wang, Wenbo; Fu, Yong Qing; Chen, Jinju; Xuan, Weipeng; Chen, Jinkai; Mayrhofer, Paul; Duan, Pengfei; Bittner, Elmar; Luo, Jikui

    2016-01-01

    This paper reports the characterization of scandium aluminum nitride (Al1−x Sc x N, x  =  27%) films and discusses surface acoustic wave (SAW) devices based on them. Both AlScN and AlN films were deposited on silicon by sputtering and possessed columnar microstructures with (0 0 0 2) crystal orientation. The AlScN/Si SAW devices showed improved electromechanical coupling coefficients (K 2, ~2%) compared with pure AlN films (

  16. Microfluidic chip-capillary electrophoresis devices

    CERN Document Server

    Fung, Ying Sing; Du, Fuying; Guo, Wenpeng; Ma, Tongmei; Nie, Zhou; Sun, Hui; Wu, Ruige; Zhao, Wenfeng

    2015-01-01

    Capillary electrophoresis (CE) and microfluidic chip (MC) devices are relatively mature technologies, but this book demonstrates how they can be integrated into a single, revolutionary device that can provide on-site analysis of samples when laboratory services are unavailable. By introducing the combination of CE and MC technology, Microfluidic Chip-Capillary Electrophoresis Devices broadens the scope of chemical analysis, particularly in the biomedical, food, and environmental sciences. The book gives an overview of the development of MC and CE technology as well as technology that now allows for the fabrication of MC-CE devices. It describes the operating principles that make integration possible and illustrates some achievements already made by the application of MC-CE devices in hospitals, clinics, food safety, and environmental research. The authors envision further applications for private and public use once the proof-of-concept stage has been passed and obstacles to increased commercialization are ad...

  17. Microfluidic paper-based analytical devices for colorimetric detection of urinary tract infection biomarkers on adult diapers.

    Science.gov (United States)

    Chaohao Chen; Tao Dong

    2015-08-01

    Urinary tract infections (UTI) are common infection diseases in elderly patients. The conventional method of detecting UTI involves the collection of significant urine samples from the elderly patients. However, this is a very difficult and time-consuming procedure. This paper addresses the development of a microfluidic paper-based analytical device (μPAD) to detect UTI from urine collected from adult diapers. The design and fabrication for the μPAD is shown. The fabrication process involves melting solid wax on top of filter paper using a hot plate, followed by pattern transfer using a mold with rubbed wax. To demonstrate the feasibility of the proposed method, the μPAD with deposited nitrite reagent had detected different concentrations of nitrite solutions from 0.5 ppm to 100 ppm spiked in urine samples. A calibration curve was obtained by plotting the gray scale intensity values against the various nitrite concentrations. The results showed that the proposed paper-based device holds great potential as low-cost, disposable solution to sensitively detect UTI markers in urine sampled from diapers.

  18. Reaction and separation opportunities with microfluidic devices

    NARCIS (Netherlands)

    Kolfschoten, R.C.

    2011-01-01

    Microfluidic devices make precisely controlled processing of substances possible on a microliter level. The advantage is that, due to the small sizes, the driving forces for mass and heat transfer are high. The surface to volume ratios are also high, which can benefit many surface oriented

  19. Probing cell mechanical properties with microfluidic devices

    Science.gov (United States)

    Rowat, Amy

    2012-02-01

    Exploiting flow on the micron-scale is emerging as a method to probe cell mechanical properties with 10-1000x advances in throughput over existing technologies. The mechanical properties of cells and the cell nucleus are implicated in a wide range of biological contexts: for example, the ability of white blood cells to deform is central to immune response; and malignant cells show decreased stiffness compared to benign cells. We recently developed a microfluidic device to probe cell and nucleus mechanical properties: cells are forced to deform through a narrow constrictions in response to an applied pressure; flowing cells through a series of constrictions enables us to probe the ability of hundreds of cells to deform and relax during flow. By tuning the constriction width so it is narrower than the width of the cell nucleus, we can specifically probe the effects of nuclear physical properties on whole cell deformability. We show that the nucleus is the rate-limiting step in cell passage: inducing a change in its shape to a multilobed structure results in cells that transit more quickly; increased levels of lamin A, a nuclear protein that is key for nuclear shape and mechanical stability, impairs the passage of cells through constrictions. We are currently developing a new class of microfluidic devices to simultaneously probe the deformability of hundreds of cell samples in parallel. Using the same soft lithography techniques, membranes are fabricated to have well-defined pore distribution, width, length, and tortuosity. We design the membranes to interface with a multiwell plate, enabling simultaneous measurement of hundreds of different samples. Given the wide spectrum of diseases where altered cell and nucleus mechanical properties are implicated, such a platform has great potential, for example, to screen cells based on their mechanical phenotype against a library of drugs.

  20. Capillary-driven microfluidic paper-based analytical devices for lab on a chip screening of explosive residues in soil.

    Science.gov (United States)

    Ueland, Maiken; Blanes, Lucas; Taudte, Regina V; Stuart, Barbara H; Cole, Nerida; Willis, Peter; Roux, Claude; Doble, Philip

    2016-03-04

    A novel microfluidic paper-based analytical device (μPAD) was designed to filter, extract, and pre-concentrate explosives from soil for direct analysis by a lab on a chip (LOC) device. The explosives were extracted via immersion of wax-printed μPADs directly into methanol soil suspensions for 10min, whereby dissolved explosives travelled upwards into the μPAD circular sampling reservoir. A chad was punched from the sampling reservoir and inserted into a LOC well containing the separation buffer for direct analysis, avoiding any further extraction step. Eight target explosives were separated and identified by fluorescence quenching. The minimum detectable amounts for all eight explosives were between 1.4 and 5.6ng with recoveries ranging from 53-82% from the paper chad, and 12-40% from soil. This method provides a robust and simple extraction method for rapid identification of explosives in complex soil samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A novel screen-printed microfluidic paper-based electrochemical device for detection of glucose and uric acid in urine.

    Science.gov (United States)

    Yao, Yong; Zhang, Chunsun

    2016-10-01

    A novel screen-printed microfluidic paper-based analytical device with all-carbon electrode-enabled electrochemical assay (SP-ACE-EC-μPAD) has been developed. The fabrication of these devices involved wax screen-printing, which was simple, low-cost and energy-efficient. The working, counter and reference electrodes were screen-printed using carbon ink on the patterned paper devices. Different wax screen-printing processes were examined and optimized, which led to an improved method with a shorter heating time (~5 s) and a lower heating temperature (75 °C). Different printing screens were examined, with a 300-mesh polyester screen yielding the highest quality wax screen-prints. The carbon electrodes were screen-printed on the μPADs and then examined using cyclic voltammetry. The analytical performance of the SP-ACE-EC-μPADs for the detection of glucose and uric acid in standard solutions was investigated. The results were reproducible, with a linear relationship [R(2) = 0.9987 (glucose) or 0.9997 (uric acid)] within the concentration range of interest, and with detection limits as low as 0.35 mM (glucose) and 0.08 mM (uric acid). To determine the clinical utility of the μPADs, chronoamperometry was used to analyze glucose and uric acid in real urine samples using the standard addition method. Our devices were able to detect the analytes of interest in complex real-world biological samples, and have the potential for use in a wide variety of applications.

  2. Perfusion-based microfluidic device for three-dimensional dynamic primary human hepatocyte cell culture in the absence of biological or synthetic matrices or coagulants.

    Science.gov (United States)

    Goral, Vasiliy N; Hsieh, Yi-Cheng; Petzold, Odessa N; Clark, Jeffery S; Yuen, Po Ki; Faris, Ronald A

    2010-12-21

    We describe a perfusion-based microfluidic device for three-dimensional (3D) dynamic primary human hepatocyte cell culture. The microfluidic device was used to promote and maintain 3D tissue-like cellular morphology and cell-specific functionality of primary human hepatocytes by restoring membrane polarity and hepatocyte transport function in vitro without the addition of biological or synthetic matrices or coagulants. A unique feature of our dynamic cell culture device is the creation of a microenvironment, without the addition of biological or synthetic matrices or coagulants, that promotes the 3D organization of hepatocytes into cord-like structures that exhibit functional membrane polarity as evidenced by the expression of gap junctions and the formation of an extended, functionally active, bile canalicular network.

  3. Rapid and low-cost fabrication of polystyrene-based molds for PDMS microfluidic devices using a CO2 laser

    KAUST Repository

    Li, Huawei

    2011-11-01

    In this article, we described a rapid and low-cost method to fabricate polystyrene molds for PDMS microfluidic devices using a CO2 laser system. It takes only several minutes to fabricate the polystyrene mold with bump pattern on top of it using a CO2 laser system. The bump pattern can be easily transferred to PDMS and fabricate microchannles as deep as 3μm on PDMS. © (2012) Trans Tech Publications, Switzerland.

  4. Optimization of monolithic columns for microfluidic devices

    Science.gov (United States)

    Pagaduan, Jayson V.; Yang, Weichun; Woolley, Adam T.

    2011-06-01

    Monolithic columns offer advantages as solid-phase extractors because they offer high surface area that can be tailored to a specific function, fast mass transport, and ease of fabrication. Porous glycidyl methacrylate-ethylene glycol dimethacrylate monoliths were polymerized in-situ in microfluidic devices, without pre-treatment of the poly(methyl methacrylate) channel surface. Cyclohexanol, 1-dodecanol and Tween 20 were used to control the pore size of the monoliths. The epoxy groups on the monolith surface can be utilized to immobilize target-specific probes such as antibodies, aptamers, or DNA for biomarker detection. Microfluidic devices integrated with solid-phase extractors should be useful for point-of-care diagnostics in detecting specific biomarkers from complex biological fluids.

  5. Nanoplasmonic and Microfluidic Devices for Biological Sensing

    KAUST Repository

    Perozziello, G.

    2017-02-16

    In this chapter we report about recent advances on the development and application of 2D and 3D plasmonic nanostructures used for sensing of biological samples by Raman spectroscopy at unprecedented resolution of analysis. Besides, we explain how the integration of these nanodevices in a microfluidic apparatus can simplify the analysis of biological samples. In the first part we introduce and motivate the convenience of using nanoplasmonic enhancers and Raman spectroscopy for biological sensing, describing the phenomena and the current approaches to fabricate nanoplasmonic structures. In the second part, we explain how specific multi-element devices produce the optimal enhancement of the Raman scattering. We report cases where biological sensing of DNA was performed at few molecules level with nanometer spatial resolutions. Finally, we show an example of microfluidic device integrating plasmonic nanodevices to sort and drive biological samples, like living cells, towards the optical probe in order to obtain optimal conditions of analysis.

  6. Fluid control structures in microfluidic devices

    Science.gov (United States)

    Mathies, Richard A.; Grover, William H.; Skelley, Alison; Lagally, Eric; Liu, Chung N.

    2017-05-09

    Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

  7. MEMS monocrystalline-silicon based thermal devices for chemical and microfluidic applications

    OpenAIRE

    Mihailovic, M.

    2011-01-01

    This thesis explores the employment of monocrystalline silicon in microsystems as an active material for different thermal functions, such as heat generation and heat transfer by conduction. In chapter 1 applications that need thermal micro devices, micro heaters and micro heat exchangers, are briefly introduced. The shortcomings of commonly used materials are listed, and monocrystalline silicon is identified as an appropriate choice for several thermal micro devices. Chapter 2 briefly presen...

  8. Optical Detection and Magnetic Manipulation of Drops in Microfluidic Devices

    Science.gov (United States)

    Kerbage, Charles

    2005-03-01

    We demonstrate an integrated magneto-optic microfluidic device for drop detection and sorting. Optical detection of water drops formed in a continuous oil phase flow is performed using optical fibers which are integrated into the channels of the PDMS (Polydimethylsiloxane) based microfluidic device. The size and the velocity of the drops can be determined by measuring the transmission intensity as a function of time. We also show that such a device can be used to detect fluorescent materials introduced in the drop itself. Moreover, introducing nano-scale magnetic particles into the water drops allows for drop sorting by means of a magnetic field gradient. This magnetic field is generated through thin film permalloy integrated into the device itself and tuned by an external coil. We show that the sorting depends on the magnetic field gradient, material composite and volume fraction of the magnetic material in the drops.

  9. MEMS monocrystalline-silicon based thermal devices for chemical and microfluidic applications

    NARCIS (Netherlands)

    Mihailovic, M.

    2011-01-01

    This thesis explores the employment of monocrystalline silicon in microsystems as an active material for different thermal functions, such as heat generation and heat transfer by conduction. In chapter 1 applications that need thermal micro devices, micro heaters and micro heat exchangers, are

  10. Paper-Based Microfluidic Device with a Gold Nanosensor to Detect Arsenic Contamination of Groundwater in Bangladesh

    Directory of Open Access Journals (Sweden)

    Mosfera A. Chowdury

    2017-03-01

    Full Text Available In this paper, we present a microfluidic paper-based analytical device (μPAD with a gold nanosensor functionalized with α-lipoic acid and thioguanine (Au–TA–TG to detect whether the arsenic level of groundwater from hand tubewells in Bangladesh is above or below the World Health Organization (WHO guideline level of 10 μg/L. We analyzed the naturally occurring metals present in Bangladesh groundwater and assessed the interference with the gold nanosensor. A method was developed to prevent interference from alkaline metals found in Bangladesh groundwater (Ca, Mg, K and Na by increasing the pH level on the μPADs to 12.1. Most of the heavy metals present in the groundwater (Ni, Mn, Cd, Pb, and Fe II did not interfere with the μPAD arsenic tests; however, Fe III was found to interfere, which was also prevented by increasing the pH level on the μPADs to 12.1. The μPAD arsenic tests were tested with 24 groundwater samples collected from hand tubewells in three different districts in Bangladesh: Shirajganj, Manikganj, and Munshiganj, and the predictions for whether the arsenic levels were above or below the WHO guideline level agreed with the results obtained from laboratory testing. The μPAD arsenic test is the first paper-based test validated using Bangladesh groundwater samples and capable of detecting whether the arsenic level in groundwater is above or below the WHO guideline level of 10 μg/L, which is a step towards enabling the villagers who collect and consume the groundwater to test their own sources and make decisions about where to obtain the safest water.

  11. One-step fabrication of 3D silver paste electrodes into microfluidic devices for enhanced droplet-based cell sorting

    Directory of Open Access Journals (Sweden)

    Lang Rao

    2015-05-01

    Full Text Available 3D microelectrodes are one-step fabricated into a microfluidic droplet separator by filling conductive silver paste into PDMS microchambers. The advantages of 3D silver paste electrodes in promoting droplet sorting accuracy are systematically demonstrated by theoretical calculation, numerical simulation and experimental validation. The employment of 3D electrodes also helps to decrease the droplet sorting voltage, guaranteeing that cells encapsulated in droplets undergo chip-based sorting processes are at better metabolic status for further potential cellular assays. At last, target droplet containing single cell are selectively sorted out from others by an appropriate electric pulse. This method provides a simple and inexpensive alternative to fabricate 3D electrodes, and it is expected our 3D electrode-integrated microfluidic droplet separator platform can be widely used in single cell operation and analysis.

  12. Synthesis of bioactive microcapsules using a microfluidic device.

    Science.gov (United States)

    Kim, Byeong Il; Jeong, Soon Woo; Lee, Kyoung G; Park, Tae Jung; Park, Jung Youn; Song, Jae Jun; Lee, Seok Jae; Lee, Chang-Soo

    2012-01-01

    Bioactive microcapsules containing Bacillus thuringiensis (BT) spores were generated by a combination of a hydro gel, microfluidic device and chemical polymerization method. As a proof-of-principle, we used BT spores displaying enhanced green fluorescent protein (EGFP) on the spore surface to spatially direct the EGFP-presenting spores within microcapsules. BT spore-encapsulated microdroplets of uniform size and shape are prepared through a flow-focusing method in a microfluidic device and converted into microcapsules through hydrogel polymerization. The size of microdroplets can be controlled by changing both the dispersion and continuous flow rate. Poly(N-isoproplyacrylamide) (PNIPAM), known as a hydrogel material, was employed as a biocompatible material for the encapsulation of BT spores and long-term storage and outstanding stability. Due to these unique properties of PNIPAM, the nutrients from Luria-Bertani complex medium diffused into the microcapsules and the microencapsulated spores germinated into vegetative cells under adequate environmental conditions. These results suggest that there is no limitation of transferring low-molecular-weight-substrates through the PNIPAM structures, and the viability of microencapsulated spores was confirmed by the culture of vegetative cells after the germinations. This microfluidic-based microencapsulation methodology provides a unique way of synthesizing bioactive microcapsules in a one-step process. This microfluidic-based strategy would be potentially suitable to produce microcapsules of various microbial spores for on-site biosensor analysis.

  13. Optimized fabrication protocols of microfluidic devices for X-ray analysis

    KAUST Repository

    Catalano, Rossella

    2014-07-01

    Microfluidics combined with X-ray scattering techniques allows probing conformational changes or assembly processes of biological materials. Our aim was to develop a highly X-ray transparent microfluidic cell for detecting small variations of X-ray scattering involved in such processes. We describe the fabrication of a polyimide microfluidic device based on a simple, reliable and inexpensive lamination process. The implemented microstructured features result in windows with optimized X-ray transmission. The microfluidic device was characterized by X-ray microbeam scattering at the ID13 beamline of the European Synchrotron Radiation Facility. © 2014 Elsevier B.V. All rights reserved.

  14. Fabrication of Microstructures Embedding Controllable Particles inside Dielectrophoretic Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Tao Yue

    2013-02-01

    Full Text Available This paper presents a method of particle manipulation by dielectrophoresis (DEP and immobilization using photo-crosslinkable resin inside microfluidic devices. High speed particle manipulation, including patterning and concentration control by DEP was demonstrated. Immovable and movable microstructures embedding particles were fabricated on-chip. Several microelectrodes were fabricated using Indium Tin Oxides (ITO and Cr/Au. The two kinds of DEP responses of yeast cells (W303 and other particles were experimentally confirmed. Based on negative DEP phenomenon, cell traps generated by microelectrodes were demonstrated. Position control, transportation and patterning of cells were performed with cell traps. The on-chip fabrication of arbitrary shapes of microstructures based on Poly(ethylene glycol diacrylate (PEGDA was reported. With cell patterning by DEP and immobilization using on-chip fabrication, microstructures embedding line patterned cells were fabricated inside microfluidic channels. A novel microfluidic device was designed to separate patterning and fabrication areas and movable microstructures embedding concentration controllable particles were fabricated inside this device.

  15. Microwave dielectric heating of drops in microfluidic devices.

    Science.gov (United States)

    Issadore, David; Humphry, Katherine J; Brown, Keith A; Sandberg, Lori; Weitz, David A; Westervelt, Robert M

    2009-06-21

    We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picolitre-scale drop of water, enabling very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature change of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperature changes as large as 30 degrees C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature and can benefit from this new technique.

  16. An easy-to-use microfluidic interconnection system to create quick and reversibly interfaced simple microfluidic devices

    DEFF Research Database (Denmark)

    Pfreundt, Andrea; Andersen, Karsten Brandt; Dimaki, Maria

    2015-01-01

    The presented microfluidic interconnection system provides an alternative for the individual interfacing of simple microfluidic devices fabricated in polymers such as polymethylmethacrylate, polycarbonate and cyclic olefin polymer. A modification of the device inlet enables the direct attachment...

  17. Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

    KAUST Repository

    Li, Erqiang

    2013-12-16

    Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology. Polydimethylsiloxane soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. Here, we report the design and fabrication of simple and inexpensive microfluidic devices based on microscope glass slides and pulled glass capillaries, for generating monodisperse multiple emulsions. The advantages of our method lie in a simple manufacturing procedure, inexpensive processing equipment and flexibility in the surface modification of the designed microfluidic devices. Different types of devices have been designed and tested and the experimental results demonstrated their robustness for preparing monodisperse single, double, triple and multi-component emulsions. © 2014 IOP Publishing Ltd.

  18. Characterization of Fluid Flow in Paper-Based Microfluidic Systems

    Science.gov (United States)

    Walji, Noosheen; MacDonald, Brendan

    2014-11-01

    Paper-based microfluidic devices have been presented as a viable low-cost alternative with the versatility to accommodate many applications in disease diagnosis and environmental monitoring. Current microfluidic designs focus on the use of silicone and PDMS structures, and several models have been developed to describe these systems; however, the design process for paper-based devices is hindered by a lack of prediction capability. In this work we simplify the complex underlying physics of the capillary-driven flow mechanism in a porous medium and generate a practical numerical model capable of predicting the flow behaviour. We present our key insights regarding the properties that dictate the behaviour of fluid wicking in paper-based microfluidic devices. We compare the results from our model to experiments and discuss the application of our model to design of paper-based microfluidic devices for arsenic detection in drinking water in Bangladesh.

  19. Electrostatic charging and control of droplets in microfluidic devices.

    Science.gov (United States)

    Zhou, Hongbo; Yao, Shuhuai

    2013-03-07

    Precharged droplets can facilitate manipulation and control of low-volume liquids in droplet-based microfluidics. In this paper, we demonstrate non-contact electrostatic charging of droplets by polarizing a neutral droplet and splitting it into two oppositely charged daughter droplets in a T-junction microchannel. We performed numerical simulation to analyze the non-contact charging process and proposed a new design with a notch at the T-junction in aid of droplet splitting for more efficient charging. We experimentally characterized the induced charge in droplets in microfabricated devices. The experimental results agreed well with the simulation. Finally, we demonstrated highly effective droplet manipulation in a path selection unit appending to the droplet charging. We expect our work could enable precision manipulation of droplets for more complex liquid handling in microfluidics and promote electric-force based manipulation in 'lab-on-a-chip' systems.

  20. Microfluidic devices for forensic DNA analysis: A review

    NARCIS (Netherlands)

    Bruijns, Brigitte Bibiche; van Asten, A.; Tiggelaar, Roald M.; Gardeniers, Johannes G.E.

    2016-01-01

    Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for

  1. Synthesis of Bioactive Microcapsules Using a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Chang-Soo Lee

    2012-07-01

    Full Text Available Bioactive microcapsules containing Bacillus thuringiensis (BT spores were generated by a combination of a hydro gel, microfluidic device and chemical polymerization method. As a proof-of-principle, we used BT spores displaying enhanced green fluorescent protein (EGFP on the spore surface to spatially direct the EGFP-presenting spores within microcapsules. BT spore-encapsulated microdroplets of uniform size and shape are prepared through a flow-focusing method in a microfluidic device and converted into microcapsules through hydrogel polymerization. The size of microdroplets can be controlled by changing both the dispersion and continuous flow rate. Poly(N-isoproplyacrylamide (PNIPAM, known as a hydrogel material, was employed as a biocompatible material for the encapsulation of BT spores and long-term storage and outstanding stability. Due to these unique properties of PNIPAM, the nutrients from Luria-Bertani complex medium diffused into the microcapsules and the microencapsulated spores germinated into vegetative cells under adequate environmental conditions. These results suggest that there is no limitation of transferring low-molecular-weight-substrates through the PNIPAM structures, and the viability of microencapsulated spores was confirmed by the culture of vegetative cells after the germinations. This microfluidic-based microencapsulation methodology provides a unique way of synthesizing bioactive microcapsules in a one-step process. This microfluidic-based strategy would be potentially suitable to produce microcapsules of various microbial spores for on-site biosensor analysis.

  2. Fabrication of gravity-driven microfluidic device

    Science.gov (United States)

    Yamada, H.; Yoshida, Y.; Terada, N.; Hagihara, S.; Komatsu, T.; Terasawa, A.

    2008-12-01

    We have studied the micro total analysis system as a blood test. A microfluidic device with a three-pronged microchannel and artificial capillary vessels was fabricated. The microchannel is to transport blood, focus blood cells, and line them up. The vessels are to observe red blood cell deformation. An excimer laser was used to form grooves and so on. Numbers of thermosetting resin film and fluororesin were piled up on a cover glass. A laser fabricated part of the channel at the each film every lamination, and then a three-dimensional structure microchannel was fabricated. The channel sizes have widths of 50-150 μm and depths of 45 μm. Through holes used as artificial capillary vessels are made in the fluororesin having a minimum diameter of 5 μm and a length of 100 μm. As blood and a physiological saline are injected into the microchannel, the device stands upward facing the channel, and blood cells go into the vessels by the force of gravity and sheath flow of the saline. By gravity various groove patterns were made changing the width and length for measurement of blood focusing. Moreover, the red blood cell deformation was observed in the vessels with a microscope.

  3. Microfluidic Devices for Studying Biomolecular Interactions

    Science.gov (United States)

    Wilson, Wilbur W.; Garcia, Carlos d.; Henry, Charles S.

    2006-01-01

    Microfluidic devices for monitoring biomolecular interactions have been invented. These devices are basically highly miniaturized liquid-chromatography columns. They are intended to be prototypes of miniature analytical devices of the laboratory on a chip type that could be fabricated rapidly and inexpensively and that, because of their small sizes, would yield analytical results from very small amounts of expensive analytes (typically, proteins). Other advantages to be gained by this scaling down of liquid-chromatography columns may include increases in resolution and speed, decreases in the consumption of reagents, and the possibility of performing multiple simultaneous and highly integrated analyses by use of multiple devices of this type, each possibly containing multiple parallel analytical microchannels. The principle of operation is the same as that of a macroscopic liquid-chromatography column: The column is a channel packed with particles, upon which are immobilized molecules of the protein of interest (or one of the proteins of interest if there are more than one). Starting at a known time, a solution or suspension containing molecules of the protein or other substance of interest is pumped into the channel at its inlet. The liquid emerging from the outlet of the channel is monitored to detect the molecules of the dissolved or suspended substance(s). The time that it takes these molecules to flow from the inlet to the outlet is a measure of the degree of interaction between the immobilized and the dissolved or suspended molecules. Depending on the precise natures of the molecules, this measure can be used for diverse purposes: examples include screening for solution conditions that favor crystallization of proteins, screening for interactions between drugs and proteins, and determining the functions of biomolecules.

  4. Integration of Capacitive Micromachined Ultrasound Transducers to Microfluidic Devices

    KAUST Repository

    Viržonis, Darius

    2013-10-22

    The design and manufacturing flexibility of capacitive micromachined ultrasound transducers (CMUT) makes them attractive option for integration with microfluidic devices both for sensing and fluid manipulation. CMUT concept is introduced here by presentin

  5. Ionic current devices-Recent progress in the merging of electronic, microfluidic, and biomimetic structures.

    Science.gov (United States)

    Koo, Hyung-Jun; Velev, Orlin D

    2013-05-09

    We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks-an intrinsic component of the ionic devices-could play the role of wires and circuits in conventional electronics.

  6. A microfluidic dialysis device for complex biological mixture SERS analysis

    KAUST Repository

    Perozziello, Gerardo

    2015-08-01

    In this paper, we present a microfluidic device fabricated with a simple and inexpensive process allowing rapid filtering of peptides from a complex mixture. The polymer microfluidic device can be used for sample preparation in biological applications. The device is fabricated by micromilling and solvent assisted bonding, in which a microdialysis membrane (cut-off of 12-14 kDa) is sandwiched in between an upper and a bottom microfluidic chamber. An external frame connects the microfluidic device to external tubes, microvalves and syringe pumps. Bonding strength and interface sealing are pneumatically tested. Microfluidic protocols are also described by using the presented device to filter a sample composed of specific peptides (MW 1553.73 Da, at a concentration of 1.0 ng/μl) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancer, and albumin (MW 66.5 kDa, at a concentration of 35 μg/μl), the most represented protein in human plasma. The filtered samples coming out from the microfluidic device were subsequently deposited on a SERS (surface enhanced Raman scattering) substrate for further analysis by Raman spectroscopy. By using this approach, we were able to sort the small peptides from the bigger and highly concentrated protein albumin and to detect them by using a label-free technique at a resolution down to 1.0 ng/μl.

  7. Use of Vacuum Bagging for Fabricating Thermoplastic Microfluidic Devices

    Science.gov (United States)

    Cassano, Christopher L.; Simon, Andrew J.; Liu, Wei; Fredrickson, Carl; Fan, Z. Hugh

    2014-01-01

    In this work we present a novel thermal bonding method for thermoplastic microfluidic devices. This simple method employs a modified vacuum bagging technique, a concept borrowed from the aerospace industry, to produce conventional thick substrate microfluidic devices, as well as multi-layer film devices. The bonds produced using this method are superior to those obtained using conventional thermal bonding methods, including thermal lamination, and are capable of sustaining burst pressures in excess of 550 kPa. To illustrate the utility of this method, thick substrate devices were produced, as well as a six-layer film device that incorporated several complex features. PMID:25329244

  8. Droplet Microfluidics for Chip-Based Diagnostics

    Directory of Open Access Journals (Sweden)

    Karan V. I. S. Kaler

    2014-12-01

    Full Text Available Droplet microfluidics (DMF is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays.

  9. Microfluidic Paper-based Analytical Device for the Determination of Hexavalent Chromium by Photolithographic Fabrication Using a Photomask Printed with 3D Printer.

    Science.gov (United States)

    Asano, Hitoshi; Shiraishi, Yukihide

    2018-01-01

    This article describes a simple and inexpensive microfluidic paper-based analytical device (μPAD) for the determination of hexavalent chromium (Cr VI ) in water samples. The μPADs were fabricated on paper by photolithography using a photomask printed with a 3D printer and functionalized with reagents for a colorimetric assay. In the μPAD, Cr VI reacts with 1,5-diphenylcarbazide to form a violet-colored complex. Images of μPADs were captured with a digital camera; then the red, green, and blue color intensity of each detection zone were measured using images processing software. The green intensity analysis was the best sensitive among the RGB color. A linear working range (40 - 400 ppm; R 2 = 0.981) between the Cr VI and green intensity was obtained with a detection limit of 30 ppm. All of the recoveries were between 94 and 109% in recovery studies on water samples, and good results were obtained.

  10. Advances in the Analysis of Water and Wastewater Samples Using Various Sensing Protocols and Microfluidic Devices Based on PAD and μTAS Systems.

    Science.gov (United States)

    Piaskowski, Krzysztof; Świderska-Dąbrowska, Renata; Kaleniecka, Aleksandra; Zarzycki, Paweł K

    2017-07-01

    The main goal of this review is to summarize practical approaches concerning the application of microfluidic systems for the analysis of various biomarkers and pollutants, as well as microbes, in water and wastewater matrixes. This problem involves multidisciplinary expertise combining research knowledge from various areas, including wet chemistry, biochemistry, physical chemistry, molecular biology, genetics, signal processing, microelectronics material science, and separation science. It has been documented that fairly primitive but fast and inexpensive screening methods involving paper-based analytical devices (PADs) and micro total analytical systems (μTAS) can be considered as serious alternatives to their more advanced counterparts such as GC, HPLC, and capillary electrophoresis coupled to various sophisticated detectors (e.g., multiwavelength spectrophotometers such as UV-Vis/DAD and mass spectrometers). The main advantage of PAD- and μTAS-driven technology is that such sensing devices may work under on-site and real-time conditions and measure a number of physical parameters and chemical factors simultaneously. Moreover, hybrid miniaturized analytical systems may combine sensing and data acquisition modules with common mobile phones and electronic devices working with global positioning systems and communicating through the Internet.

  11. Microfluidic mixing devices for fast optical analysis of liquids

    International Nuclear Information System (INIS)

    Buchegger, W.

    2012-01-01

    For the temporal investigation of chemical reactions a proper mixing of reagents is a prime requirement. Compared to macroscale devices, mixing in microscale underlies a series of new physical effects. The challenge in the design of micromixers is to bring these effects to a beneficial result. The main theme of this thesis is the design of unique microfluidic chips for the investigation of liquids by different analysis techniques. Unique design ideas are evaluated by numerical simulation tools before the realization of the device. Characterization measurements precede experiments with biological samples validating the functional principle and the performance of the proposed microfluidic systems. A continuous flow device, utilizing molecular diffusion for mixing of two liquids, is presented. A multilaminar flow approach is followed to reduce the diffusion length and hence, the mixing time. The combination of multiple fluid layers with an optimized inlet geometry enables the formation of highly uniform fluid layers over the main part of the channel. Thereby, mixing times in the low millisecond range are possible. The micromixer is characterized by a coloration experiment and confocal laser-scanning microscopy supported by software evaluation. Using different materials for fabrication allows the utilization of different optical and spectral analysis techniques. The mixing channel with a height of 8 μm allows the investigation of aqueous solutions by time resolved infrared spectroscopy, despite the high absorption characteristics of water in the infrared region. Design variations with different channel heights allow to optimize the signal intensity for certain applications so that the device is also applicable for Raman spectroscopic measurements. To highlight the feasibility of using the device as fast bioreactor, an enzymatic reaction is investigated by fluorescence microscopy. The microfluidic flow regime allows the generation of highly monodisperse fluidic

  12. Split and flow: reconfigurable capillary connection for digital microfluidic devices.

    Science.gov (United States)

    Lapierre, Florian; Harnois, Maxime; Coffinier, Yannick; Boukherroub, Rabah; Thomy, Vincent

    2014-09-21

    Supplying liquid to droplet-based microfluidic microsystems remains a delicate task facing the problems of coupling continuous to digital or macro- to microfluidic systems. Here, we take advantage of superhydrophobic microgrids to address this problem. Insertion of a capillary tube inside a microgrid aperture leads to a simple and reconfigurable droplet generation setup.

  13. Direct digital manufacturing of autonomous centrifugal microfluidic device

    Science.gov (United States)

    Ukita, Yoshiaki; Takamura, Yuzuru; Utsumi, Yuichi

    2016-06-01

    This paper presents strategies that attempt to solve two key problems facing the commercialization of microfluidics: cost reduction in microfluidic chip manufacturing and microfluidic device driver development. To reduce the cost of microfluidic chip manufacturing, we propose to use of three-dimensional (3D) printers for direct digital manufacturing (DDM). An evaluation of 3D micro-scale structure printing using several 3D printers is reported, and some of the technical issues to be addressed in the future are suggested. To evaluate micro-scale printing, three types of 3D printers, with the ability to print structures on the scale of several hundred meters, were selected by first screening six 3D printers. Line and space patterns with line widths of 100-500 µm and an aspect ratio of one were printed and evaluated. The estimated critical dimension was around 200 µm. The manufacturing of a monolithic microfluidic chip with embedded channels was also demonstrated. Monolithic microfluidic chips with embedded microchannels having 500 × 500 and 250 × 250 µm2 cross sections and 2-20 mm lengths were printed, and the fidelity of the channel shape, residual supporting material, and flow of liquid water were evaluated. The liquid flow evaluation showed that liquid water could flow through all of the microchannels with the 500 × 500 µm2 cross section, whereas this was not possible through some of the channels with the 250 × 250 µm2 cross section because of the residual resin or supporting material. To reduce the device-driver cost, we propose to use of the centrifugal microfluidic concept. An autonomous microfluidic device that could implement sequential flow control under a steadily rotating condition was printed. Four-step flow injection under a steadily rotating condition at 1500 rpm was successfully demonstrated without any external triggering such as changing the rotational speed.

  14. Enhanced physicochemical properties of polydimethylsiloxane based microfluidic devices and thin films by incorporating synthetic micro-diamond.

    Science.gov (United States)

    Waheed, Sidra; Cabot, Joan M; Macdonald, Niall P; Kalsoom, Umme; Farajikhah, Syamak; Innis, Peter C; Nesterenko, Pavel N; Lewis, Trevor W; Breadmore, Michael C; Paull, Brett

    2017-11-08

    Synthetic micro-diamond-polydimethylsiloxane (PDMS) composite microfluidic chips and thin films were produced using indirect 3D printing and spin coating fabrication techniques. Microfluidic chips containing up to 60 wt% micro-diamond were successfully cast and bonded. Physicochemical properties, including the dispersion pattern, hydrophobicity, chemical structure, elasticity and thermal characteristics of both chip and films were investigated. Scanning electron microscopy indicated that the micro-diamond particles were embedded and interconnected within the bulk material of the cast microfluidic chip, whereas in the case of thin films their increased presence at the polymer surface resulted in a reduced hydrophobicity of the composite. The elastic modulus increased from 1.28 for a PDMS control, to 4.42 MPa for the 60 wt% composite, along with a three-fold increase in thermal conductivity, from 0.15 to 0.45 W m -1 K -1 . Within the fluidic chips, micro-diamond incorporation enhanced heat dissipation by efficient transfer of heat from within the channels to the surrounding substrate. At a flow rate of 1000 μL/min, the gradient achieved for the 60 wt% composite chip equalled a 9.8 °C drop across a 3 cm long channel, more than twice that observed with the PDMS control chip.

  15. Recent microfluidic devices for studying gamete and embryo biomechanics.

    Science.gov (United States)

    Lai, David; Takayama, Shuichi; Smith, Gary D

    2015-06-25

    The technical challenges of biomechanic research such as single cell analysis at a high monetary cost, labor, and time for just a small number of measurements is a good match to the strengths of microfluidic devices. New scientific discoveries in the fertilization and embryo development process, of which biomechanics is a major subset of interest, is crucial to fuel the continual improvement of clinical practice in assisted reproduction. The following review will highlight some recent microfluidic devices tailored for gamete and embryo biomechanics where biomimicry arises as a major theme of microfluidic device design and function, and the application of fundamental biomechanic principles are used to improve outcomes of cryopreservation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A microfluidic device for efficient chemical testing using Caenorhabditis elegans.

    Science.gov (United States)

    Song, Pengfei; Zhang, Weize; Sobolevski, Alexandre; Bernard, Kristine; Hekimi, Siegfried; Liu, Xinyu

    2015-04-01

    The nematode worm Caenorhabditis elegans has been employed as a popular model organism in many fields of biological research. In this paper, we present a microfluidic device for facilitating chemical testing using C. elegans. For testing chemicals on chip, the device houses single nematodes in microfluidic chambers and precisely adjusts the chamber's chemical environment during experiments. Eight nematodes can be readily loaded into the chambers through separate loading channels in a quick and gentle manner. In addition, a custom-made software with a graphic user interface is also created for quantitative analysis of locomotion parameters (swimming frequency and bend amplitude) of the nematodes in response to chemical stimuli, thus greatly enhancing the efficiency of data collection. We perform proof-of-concept experiments using two chemicals, zinc ion (Zn(2+)) and glucose, to demonstrate the effectiveness of the microfluidic device.

  17. Using Adhesive Patterning to Construct 3D Paper Microfluidic Devices.

    Science.gov (United States)

    Kalish, Brent; Tsutsui, Hideaki

    2016-04-01

    We demonstrate the use of patterned aerosol adhesives to construct both planar and nonplanar 3D paper microfluidic devices. By spraying an aerosol adhesive through a metal stencil, the overall amount of adhesive used in assembling paper microfluidic devices can be significantly reduced. We show on a simple 4-layer planar paper microfluidic device that the optimal adhesive application technique and device construction style depends heavily on desired performance characteristics. By moderately increasing the overall area of a device, it is possible to dramatically decrease the wicking time and increase device success rates while also reducing the amount of adhesive required to keep the device together. Such adhesive application also causes the adhesive to form semi-permanent bonds instead of permanent bonds between paper layers, enabling single-use devices to be non-destructively disassembled after use. Nonplanar 3D origami devices also benefit from the semi-permanent bonds during folding, as it reduces the likelihood that unrelated faces may accidently stick together. Like planar devices, nonplanar structures see reduced wicking times with patterned adhesive application vs uniformly applied adhesive.

  18. Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection

    Directory of Open Access Journals (Sweden)

    André Darveau

    2007-09-01

    Full Text Available The desideratum to develop a fully integrated Lab-on-a-chip device capable ofrapid specimen detection for high throughput in-situ biomedical diagnoses and Point-of-Care testing applications has called for the integration of some of the novel technologiessuch as the microfluidics, microphotonics, immunoproteomics and Micro ElectroMechanical Systems (MEMS. In the present work, a silicon based microfluidic device hasbeen developed for carrying out fluorescence based immunoassay. By hybrid attachment ofthe microfluidic device with a Spectrometer-on-chip, the feasibility of synthesizing anintegrated Lab-on-a-chip type device for fluorescence based biosensing has beendemonstrated. Biodetection using the microfluidic device has been carried out usingantigen sheep IgG and Alexafluor-647 tagged antibody particles and the experimentalresults prove that silicon is a compatible material for the present application given thevarious advantages it offers such as cost-effectiveness, ease of bulk microfabrication,superior surface affinity to biomolecules, ease of disposability of the device etc., and is thussuitable for fabricating Lab-on-a-chip type devices.

  19. Microfluidic devices obtained by thermal toner transferring on glass substrate.

    Science.gov (United States)

    do Lago, Claudimir L; Neves, Carlos A; Pereira de Jesus, Dosil; da Silva, Heron D T; Brito-Neto, José G A; Fracassi da Silva, José A

    2004-11-01

    A new process for the manufacture of microfluidic devices based on deposition of laser-printing toner on glass substrates is described. It is an alternative method to the toner on polyester film (toner-polyester) one, previously introduced. Commercial laser printers cannot print directly on glass, thus the toner must first be printed on a special paper and then transferred by heating under pressure to the glass surface. Although this procedure is more complex than the toner-polyester one, it can be repeated several times, yielding multiple toner layers. Even without special alignment equipment, up to four layers could be satisfactorily piled up. Characterization tests revealed that the toner-glass devices have similar behavior as toner-polyester ones regarding the toner layer porosity. The main advantages of the toner-glass technology are improved mechanical stability, possibility of multiple toner layers, augmented electroosmotic flow (EOF), and improved heat transfer. On the other hand, toner adhesion to glass is weaker than to polyester, which limits the device lifetime and usable liquid media. The measured EOF mobility (3.5 x 10(-4) cm2.V(-1).s(-1) for pH 7) suggests that it is mainly determined by the glass surface, being little influenced by the toner walls. Microchip electrophoresis with contactless conductivity detection and photometric detection were implemented using toner-glass devices.

  20. Integrated microwave resonant device for dielectric analysis of microfluidic systems

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, D J; Porch, A; Barrow, D A [School of Engineering, Cardiff University, Cardiff CF24 3AA (United Kingdom); Allender, C J, E-mail: rowedj@cf.ac.uk [Welsh School of Pharmacy, Cardiff University, Cardiff CF24 3NB (United Kingdom)

    2011-08-12

    Herein we present a device for performing non-contact dielectric spectroscopy upon liquids in a microfluidic environment. The device is comprised of a compression-sealed polytetrafluoroethylene (PTFE) chip with an embedded coaxial resonator, which is overmoded for dielectric measurements at six discrete frequencies between 1 and 8 GHz. A novel capacitive coupling structure allows transmission measurements to be taken from one end of the resonator, and an optimised microchannel design maximises sensitivity and repeatability. The use of a PTFE substrate and a non-contact measurement gives excellent chemical and biological compatibility. A simple 'fingerprint' method for identifying solvents is demonstrated, whereby a sample is characterised by air-referenced changes in complex frequency. Complex permittivity values are also obtained via a perturbation theory-based inversion. A combination of experimental and simulated results is used to characterise the device behaviour, limits of operation and measurement uncertainty. The high stability of temporal measurements, coupled with the robustness of the design, make this device ideal for analytical chemistry and industrial process control.

  1. Rapid, low-cost prototyping of centrifugal microfluidic devices for effective implementation of various microfluidic operations

    CSIR Research Space (South Africa)

    Hugo, S

    2013-10-01

    Full Text Available Association of South Africa (RAPDASA) 2013 Conference, SANParks Golden Gate Hotel, 30 October-1 November 2013 RAPID, LOW-COST PROTOTYPING OF CENTRIFUGAL MICROFLUIDIC DEVICES FOR EFFECTIVE IMPLEMENTATION OF VARIOUS MICROFLUIDIC COMPONENTS† S. Smith1...∗, K. Land2, M. Madou3 & H. Kido4 1,2Department of Materials Science and Manufacturing Council for Scientific and Industrial Research, South Africa 1ssmith@csir.co.za, 2kland@csir.co.za 3,4Department of Mechanical and Aerospace Engineering...

  2. Efficient gas-liquid contact using microfluidic membrane devices with staggered herringbone mixers.

    Science.gov (United States)

    Femmer, Tim; Eggersdorfer, Max L; Kuehne, Alexander J C; Wessling, Matthias

    2015-08-07

    We describe a novel membrane based gas-liquid-contacting device with increased mass transport and reduced pressure loss by combining a membrane with a staggered herringbone static mixer. Herringbone structures are imposed on the microfluidic channel geometry via soft lithography, acting as mixers which introduce secondary flows at the membrane interface. Such flows include Dean vortices and Taylor flows generating effective mixing while improving mass transport and preventing concentration polarization in microfluidic channels. Furthermore, our static herringbone mixer membranes effectively reduce pressure losses leading to devices with enhanced transfer properties for microfluidic gas-liquid contact. We investigate the red blood cell distribution to tailor our devices towards miniaturised extracorporeal membrane oxygenation and improved comfort of patients with lung insufficiencies.

  3. Development of paper-based microfluidic analytical device for iron assay using photomask printed with 3D printer for fabrication of hydrophilic and hydrophobic zones on paper by photolithography.

    Science.gov (United States)

    Asano, Hitoshi; Shiraishi, Yukihide

    2015-07-09

    This paper describes a paper-based microfluidic analytical device for iron assay using a photomask printed with a 3D printer for fabrication of hydrophilic and hydrophobic zones on the paper by photolithography. Several designed photomasks for patterning paper-based microfluidic analytical devices can be printed with a 3D printer easily, rapidly and inexpensively. A chromatography paper was impregnated with the octadecyltrichlorosilane n-hexane solution and hydrophobized. After the hydrophobic zone of the paper was exposed to the UV light through the photomask, the hydrophilic zone was generated. The smallest functional hydrophilic channel and hydrophobic barrier were ca. 500 μm and ca. 100 μm in width, respectively. The fabrication method has high stability, resolution and precision for hydrophilic channel and hydrophobic barrier. This test paper was applied to the analysis of iron in water samples using a colorimetry with phenanthroline. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Integrated high pressure manifold for thermoplastic microfluidic devices

    Science.gov (United States)

    Aghvami, S. Ali; Fraden, Seth

    2017-11-01

    We introduce an integrated tubing manifold for thermoplastic microfluidic chips that tolerates high pressure. In contrast to easy tubing in PDMS microfluidic devices, tube connection has been challenging for plastic microfluidics. Our integrated manifold connection tolerates 360 psi while conventional PDMS connections fail at 50 psi. Important design considerations are incorporation of a quick-connect, leak-free and high-pressure manifold for the inlets and outlets on the lid and registration marks that allow the precise alignment of the inlets and outlets. In our method, devices are comprised of two molded pieces joined together to create a sealed device. The first piece contains the microfluidic features and the second contains the inlet and outlet manifold, a frame for rigidity and a viewing window. The mold for the lid with integrated manifold is CNC milled from aluminium. A cone shape PDMS component which acts as an O-ring, seals the connection between molded manifold and tubing. The lid piece with integrated inlet and outlets will be a standard piece and can be used for different chips and designs. Sealing the thermoplastic device is accomplished by timed immersion of the lid in a mixture of volatile and non-volatile solvents followed by application of heat and pressure.

  5. Development, characterization, and analytical applications of microfluidic devices and nanostructured materials

    Science.gov (United States)

    Bhakta, Samir A.

    Compared to conventional benchtop instruments, microfluidic devices possess advantageous characteristics including portability, reduced analysis time, and relatively inexpensive production, making them attractive analytical devices. The goals of our research lab include the design, operation, and application of microfluidic techniques and the rational design of biosensors. In line with these goals, the objectives of my research are to develop and characterize novel microfluidic platforms and to improve their overall efficiency towards the analysis of a wide range of biologically active and environmentally-relevant compounds. Specifically, the research projects discussed herein are based on the development of novel strategies enabling the miniaturization of traditional analytical protocols using microfluidic devices. In addition, the development and characterization of novel biosensors incorporating thin-films of nanoporous materials that can be potentially used in series with the microfluidic platforms is discussed. A critical review of the field involving adsorption of proteins to nanomaterials for the use of biosensors is also discussed. Results related to the design, characterization, and applications of the devices and biosensors are discussed along with the advantages of these technologies.

  6. Rapid Prototyping of a Cyclic Olefin Copolymer Microfluidic Device for Automated Oocyte Culturing.

    Science.gov (United States)

    Berenguel-Alonso, Miguel; Sabés-Alsina, Maria; Morató, Roser; Ymbern, Oriol; Rodríguez-Vázquez, Laura; Talló-Parra, Oriol; Alonso-Chamarro, Julián; Puyol, Mar; López-Béjar, Manel

    2017-10-01

    Assisted reproductive technology (ART) can benefit from the features of microfluidic technologies, such as the automation of time-consuming labor-intensive procedures, the possibility to mimic in vivo environments, and the miniaturization of the required equipment. To date, most of the proposed approaches are based on polydimethylsiloxane (PDMS) as platform substrate material due to its widespread use in academia, despite certain disadvantages, such as the elevated cost of mass production. Herein, we present a rapid fabrication process for a cyclic olefin copolymer (COC) monolithic microfluidic device combining hot embossing-using a low-temperature cofired ceramic (LTCC) master-and micromilling. The microfluidic device was suitable for trapping and maturation of bovine oocytes, which were further studied to determine their ability to be fertilized. Furthermore, another COC microfluidic device was fabricated to store sperm and assess its quality parameters over time. The study herein presented demonstrates a good biocompatibility of the COC when working with gametes, and it exhibits certain advantages, such as the nonabsorption of small molecules, gas impermeability, and low fabrication costs, all at the prototyping and mass production scale, thus taking a step further toward fully automated microfluidic devices in ART.

  7. A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices.

    Science.gov (United States)

    Fan, Yan; Liu, Juntao; Wang, Yang; Luo, Jinping; Xu, Huiren; Xu, Shengwei; Cai, Xinxia

    2017-09-15

    Neuron-specific enolase (NSE) had clinical significance on diagnosis, staging, monitoring effect and judging prognosis of small cell lung cancer. Thus, there had a growing demand for the on-site testing of NSE. Here, a wireless point-of-care testing (POCT) system with electrochemical measurement for NSE detection was developed and verified. The wireless POCT system consisted of microfluidic paper-based analytical devices (μPADs), electrochemical detector and Android's smartphone. Differential pulse voltammetry (DPV) measurement was adopted by means of electrochemical detector which including a potentiostat and current-to-voltage converter. μPADs were modified with nanocomposites synthesized by Amino functional graphene, thionine and gold nanoparticles (NH 2 -G/Thi/AuNPs) as immunosensors for NSE detection. Combined with μPADs, the performance of the wireless POCT system was evaluated. The peak currents showed good linear relationship of the logarithm of NSE concentration ranging from 1 to 500ngmL -1 with the limit of detection (LOD) of 10pgmL -1 . The detection results were automatically stored in EEPROM memory and could be displayed on Android's smartphone through Bluetooth in real time. The detection results were comparable to those measured by a commercial electrochemical workstation. The wireless POCT system had the potential for on-site testing of other tumor markers. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. On demand nanoliter-scale microfluidic droplet generation, injection, and mixing using a passive microfluidic device.

    Science.gov (United States)

    Tangen, Uwe; Sharma, Abhishek; Wagler, Patrick; McCaskill, John S

    2015-01-01

    We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s-1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library.

  9. Storage and Caching: Synthesis of Flow-based Microfluidic Biochips

    OpenAIRE

    Tseng, Tsun-Ming; Li, Bing; Ho, Tsung-Yi; Schlichtmann, Ulf

    2017-01-01

    Flow-based microfluidic biochips are widely used in lab- on-a-chip experiments. In these chips, devices such as mixers and detectors connected by micro-channels execute specific operations. Intermediate fluid samples are saved in storage temporarily until target devices become avail- able. However, if the storage unit does not have enough capacity, fluid samples must wait in devices, reducing their efficiency and thus increasing the overall execution time. Consequently, storage and caching of...

  10. A Sensitive Chemotaxis Assay Using a Novel Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Chen Zhang

    2013-01-01

    Full Text Available Existing chemotaxis assays do not generate stable chemotactic gradients and thus—over time—functionally measure only nonspecific random motion (chemokinesis. In comparison, microfluidic technology has the capacity to generate a tightly controlled microenvironment that can be stably maintained for extended periods of time and is, therefore, amenable to adaptation for assaying chemotaxis. We describe here a novel microfluidic device for sensitive assay of cellular migration and show its application for evaluating the chemotaxis of smooth muscle cells in a chemokine gradient.

  11. A new UV-curing elastomeric substrate for rapid prototyping of microfluidic devices

    International Nuclear Information System (INIS)

    Alvankarian, Jafar; Majlis, Burhanuddin Yeop

    2012-01-01

    Rapid prototyping in the design cycle of new microfluidic devices is very important for shortening time-to-market. Researchers are facing the challenge to explore new and suitable substrates with simple and efficient microfabrication techniques. In this paper, we introduce and characterize a UV-curing elastomeric polyurethane methacrylate (PUMA) for rapid prototyping of microfluidic devices. The swelling and solubility of PUMA in different chemicals is determined. Time-dependent measurements of water contact angle show that the native PUMA is hydrophilic without surface treatment. The current monitoring method is used for measurement of the electroosmotic flow mobility in the microchannels made from PUMA. The optical, physical, thermal and mechanical properties of PUMA are evaluated. The UV-lithography and molding process is used for making micropillars and deep channel microfluidic structures integrated to the supporting base layer. Spin coating is characterized for producing different layer thicknesses of PUMA resin. A device is fabricated and tested for examining the strength of different bonding techniques such as conformal, corona treating and semi-curing of two PUMA layers in microfluidic application and the results show that the bonding strengths are comparable to that of PDMS. We also report fabrication and testing of a three-layer multi inlet/outlet microfluidic device including a very effective fluidic interconnect for application demonstration of PUMA as a promising new substrate. A simple micro-device is developed and employed for observing the pressure deflection of membrane made from PUMA as a very effective elastomeric valve in microfluidic devices. (paper)

  12. Microfluidic device for carrying out a reaction

    NARCIS (Netherlands)

    Iordanov, V.; Bastemeijer, J.; Bossche, A.; Sarro, P.M.

    2005-01-01

    A device for carrying out a reaction, which device comprises a wafer provided with a group of at least two wells. The wells are thermally separate from each other by means of a groove in a layer of the device, while parts separated by the groove are locally connected by bridges. In this way a device

  13. Dynamical phase separation using a microfluidic device: experiments and modeling

    Science.gov (United States)

    Aymard, Benjamin; Vaes, Urbain; Radhakrishnan, Anand; Pradas, Marc; Gavriilidis, Asterios; Kalliadasis, Serafim; Complex Multiscale Systems Team

    2017-11-01

    We study the dynamical phase separation of a binary fluid by a microfluidic device both from the experimental and from the modeling points of view. The experimental device consists of a main channel (600 μm wide) leading into an array of 276 trapezoidal capillaries of 5 μm width arranged on both sides and separating the lateral channels from the main channel. Due to geometrical effects as well as wetting properties of the substrate, and under well chosen pressure boundary conditions, a multiphase flow introduced into the main channel gets separated at the capillaries. Understanding this dynamics via modeling and numerical simulation is a crucial step in designing future efficient micro-separators. We propose a diffuse-interface model, based on the classical Cahn-Hilliard-Navier-Stokes system, with a new nonlinear mobility and new wetting boundary conditions. We also propose a novel numerical method using a finite-element approach, together with an adaptive mesh refinement strategy. The complex geometry is captured using the same computer-aided design files as the ones adopted in the fabrication of the actual device. Numerical simulations reveal a very good qualitative agreement between model and experiments, demonstrating also a clear separation of phases.

  14. A Comprehensive Microfluidics Device Construction and Characterization Module for the Advanced Undergraduate Analytical Chemistry Laboratory

    Science.gov (United States)

    Piunno, Paul A. E.; Zetina, Adrian; Chu, Norman; Tavares, Anthony J.; Noor, M. Omair; Petryayeva, Eleonora; Uddayasankar, Uvaraj; Veglio, Andrew

    2014-01-01

    An advanced analytical chemistry undergraduate laboratory module on microfluidics that spans 4 weeks (4 h per week) is presented. The laboratory module focuses on comprehensive experiential learning of microfluidic device fabrication and the core characteristics of microfluidic devices as they pertain to fluid flow and the manipulation of samples.…

  15. Viton-based fluoroelastomer microfluidics

    International Nuclear Information System (INIS)

    Sharma, G; Klintberg, L; Hjort, K

    2011-01-01

    Viton is an elastomer with low permeability and high chemical resistance. This paper presents the main characteristics and technical issues involved in fabricating Viton-based microfluidics by micromoulding, bonding and metallization. A PDMS (polydimethylsiloxane) mould is used to imprint the Viton compound in a curing step that is followed by a post-curing without the mould. Viton was fusion bonded, with high quality, to itself and to stainless steel when clamped together during a post-curing step. Having low permeability to hydrocarbon liquids, Viton is a well-suited elastomer for making paraffin membrane microactuators, as demonstrated here. These kinds of microactuators may find their applications in fluid handling with hydraulic oils, in vacuum systems or in reactors and analytical systems, where Viton comes in direct contact with fluids that would permeate or degrade other elastomers.

  16. Dried reagents for multiplex genotyping by tag-array minisequencing to be used in microfluidic devices

    DEFF Research Database (Denmark)

    Ahlford, Annika; Kjeldsen, Bastian; Reimers, Jakob

    2010-01-01

    was carried out with freeze-dried reagents stored in reaction chambers fabricated by micromilling in a cyclic olefin copolymer substrate. The results reported in this study are a key step towards the development of an integrated microfluidic device for point-of-care DNA-based diagnostics....

  17. Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

    KAUST Repository

    Wang, Xiang

    2013-01-01

    We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS) and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

  18. Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    2013-01-01

    Full Text Available We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

  19. Flash μ-fluidics: a rapid prototyping method for fabricating microfluidic devices

    KAUST Repository

    Buttner, Ulrich

    2016-08-01

    Microfluidics has advanced in terms of design and structures; however, fabrication methods are time-consuming or expensive relative to facility costs and equipment needed. This work demonstrates a fast and economically viable 2D/3D maskless digital light-projection method based on a stereolithography process. Unlike other fabrication methods, one exposure step is used to form the whole device. Flash microfluidics is achieved by incorporating bonding and channel fabrication of complex structures in just 2.5 s to 4 s and by fabricating channel heights between 25 μm and 150 μm with photopolymer resin. The features of this fabrication technique, such as time and cost saving and easy fabrication, are used to build devices that are mostly needed in microfluidic/lab-on-chip systems. Due to the fast production method and low initial setup costs, the process could be used for point of care applications. © 2016 The Royal Society of Chemistry.

  20. Routing-based synthesis of digital microfluidic biochips

    DEFF Research Database (Denmark)

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2012-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the necessary functions for biochemical analysis. The “digital” biochips are manipulating liquids as discrete droplets on a two-dimensional array of electrodes. Basic microfluidic...... of virtual devices and allow the droplets to move on the chip on any route during operation execution. Thus, the synthesis problem is transformed into a routing problem. We develop an algorithm based on a Greedy Randomized Adaptive Search Procedure (GRASP) and we show that routing-based synthesis leads...

  1. A microfluidic device with a diffusion barrier

    DEFF Research Database (Denmark)

    2014-01-01

    with a common junction via micro channels. To enable amplification of DNA, e.g. by MDA, the device comprises a diffusion barrier at each inlet configured to increase the pressure threshold for a reagent to cross the resistor. The invention further provides a method of mixing liquid reagents by use of the device...

  2. Polymeric salt bridges for conducting electric current in microfluidic devices

    Science.gov (United States)

    Shepodd, Timothy J [Livermore, CA; Tichenor, Mark S [San Diego, CA; Artau, Alexander [Humacao, PR

    2009-11-17

    A "cast-in-place" monolithic microporous polymer salt bridge for conducting electrical current in microfluidic devices, and methods for manufacture thereof is disclosed. Polymeric salt bridges are formed in place in capillaries or microchannels. Formulations are prepared with monomer, suitable cross-linkers, solvent, and a thermal or radiation responsive initiator. The formulation is placed in a desired location and then suitable radiation such as UV light is used to polymerize the salt bridge within a desired structural location. Embodiments are provided wherein the polymeric salt bridges have sufficient porosity to allow ionic migration without bulk flow of solvents therethrough. The salt bridges form barriers that seal against fluid pressures in excess of 5000 pounds per square inch. The salt bridges can be formulated for carriage of suitable amperage at a desired voltage, and thus microfluidic devices using such salt bridges can be specifically constructed to meet selected analytical requirements.

  3. Microfluidic Dye Lasers

    DEFF Research Database (Denmark)

    Kristensen, Anders; Balslev, Søren; Gersborg-Hansen, Morten

    2006-01-01

    A technology for miniaturized, polymer based lasers, suitable for integration with planar waveguides and microfluidic networks is presented. The microfluidic dye laser device consists of a microfluidic channel with an embedded optical resonator. The devices are fabricated in a thin polymer film...

  4. Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices.

    Science.gov (United States)

    Wiklund, Martin; Green, Roy; Ohlin, Mathias

    2012-07-21

    In part 14 of the tutorial series "Acoustofluidics--exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we provide a qualitative description of acoustic streaming and review its applications in lab-on-a-chip devices. The paper covers boundary layer driven streaming, including Schlichting and Rayleigh streaming, Eckart streaming in the bulk fluid, cavitation microstreaming and surface-acoustic-wave-driven streaming.

  5. A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

    Science.gov (United States)

    Cook, Andrew; Belsare, Sayali; Giorgio, Todd; Mu, Richard

    2014-11-01

    Analysis of circulating tumor cells (CTCs) can be critical for studying how tumors grow and metastasize, in addition to personalizing treatment for cancer patients. CTCs are rare events in blood, making it difficult to remove CTCs from the blood stream. Two microfluidic devices have been developed to separate CTCs from blood. The first is a double spiral device that focuses cells into streams, the positions of which are determined by cell diameter. The second device uses ligand-coated magnetic nanoparticles that selectively attach to CTCs. The nanoparticles then pull CTCs out of solution using a magnetic field. These two devices will be combined into a single 2-stage microfluidic device that will capture CTCs more efficiently than either device on its own. The first stage depletes the number of blood cells in the sample by size-based separation. The second stage will magnetically remove CTCs from solution for study and culturing. Thus far, size-based separation has been achieved. Research will also focus on understanding the equations that govern fluid dynamics and magnetic fields in order to determine how the manipulation of microfluidic parameters, such as dimensions and flow rate, will affect integration and optimization of the 2-stage device. NSF-CREST: Center for Physics and Chemistry of Materials. HRD-0420516; Department of Defense, Peer Reviewed Medical Research Program Award W81XWH-13-1-0397.

  6. Microfluidic electronics.

    Science.gov (United States)

    Cheng, Shi; Wu, Zhigang

    2012-08-21

    Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.

  7. Polymer-based microfluidic chips for isothermal amplification of nucleic acids

    Science.gov (United States)

    Posmitnaya, Y. S.; Rudnitskaya, G. E.; Tupik, A. N.; Lukashenko, T. A.; Bukatin, A. C.; Evstrapov, A. A.

    2017-11-01

    Creation of low-cost compact devices based on microfluidic platforms for biological and medical research depends on the degree of development and enhancement of prototyping technologies. Two designs of polymer and hybrid microfluidic devices fabricated by soft lithography and intended for isothermal amplification and polymerase chain reaction are presented in this paper. The digital helicase-dependent isothermal amplification was tested in the device containing a droplet generator. Polymerase chain reaction was carried out in the hybrid microfluidic device having ten reaction chambers. A synthesized cDNA fragment of GAPDH housekeeping gene was used as a target.

  8. A simple method of fabricating mask-free microfluidic devices for biological analysis.

    KAUST Repository

    Yi, Xin

    2010-09-07

    We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip\\'s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches.

  9. Operation of Droplet-Microfluidic Devices with a Lab Centrifuge

    Directory of Open Access Journals (Sweden)

    Noorsher Ahmed

    2016-09-01

    Full Text Available Microfluidic devices are valuable for a variety of biotechnology applications, such as synthesizing biochemical libraries, screening enzymes, and analyzing single cells. However, normally, the devices are controlled using specialized pumps, which require expert knowledge to operate. Here, we demonstrate operation of poly(dimethylsiloxane devices without pumps. We build a scaffold that holds the device and reagents to be infused in a format that can be inserted into a 50 mL falcon tube and spun in a common lab centrifuge. By controlling the device design and centrifuge spin speed, we infuse the reagents at controlled flow rates. We demonstrate the encapsulation and culture of clonal colonies of red and green Escherichia coli in droplets seeded from single cells.

  10. A microfluidic device with fluorimetric detection for intracellular components analysis

    DEFF Research Database (Denmark)

    Kwapiszewski, Radosław; Skolimowski, Maciej; Ziółkowska, Karina

    2011-01-01

    An integrated microfluidic system that coupled lysis of two cell lines: L929 fibroblasts and A549 epithelial cells, with fluorescence-based enzyme assay was developed to determine β-glucocerebrosidase activity. The microdevice fabricated in poly(dimethylsiloxane) consists of three main parts: a c...

  11. Generation of emulsion droplets and micro-bubbles in microfluidic devices

    KAUST Repository

    Zhang, Jiaming

    2016-04-01

    Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology to manipulate small amounts of liquid samples. In addition to microdroplets, microbubbles are also needed for various pro- cesses in the food, healthcare and cosmetic industries. Polydimethylsiloxane (PDMS) soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. In ad- dition, current methods have the limited capabilities for fabrication of microfluidic devices within three dimensional (3D) structures. Novel methods for fabrication of droplet-based microfluidic devices for the generation microdroplets and microbubbles are therefore of great interest in current research. In this thesis, we have developed several simple, rapid and low-cost methods for fabrication of microfluidic devices, especially for generation of microdroplets and mi- crobubbles. We first report an inexpensive full-glass microfluidic devices with as- sembly of glass capillaries, for generating monodisperse multiple emulsions. Different types of devices have been designed and tested and the experimental results demon- strated the robust capability of preparing monodisperse single, double, triple and multi-component emulsions. Second, we propose a similar full-glass device for generation of microbubbles, but with assembly of a much smaller nozzle of a glass capillary. Highly monodisperse microbubbles with diameter range from 3.5 to 60 microns have been successfully produced, at rates up to 40 kHz. A simple scaling law based on the capillary number and liquid-to-gas flow rate ratio, successfully predicts the bubble size. Recently, the emergent 3D printing technology provides an attractive fabrication technique, due to its simplicity and low cost. A handful of studies have already demonstrated droplet production through 3D-printed microfluidic devices. However, two

  12. From screen to structure with a harvestable microfluidic device

    International Nuclear Information System (INIS)

    Stojanoff, Vivian; Jakoncic, Jean; Oren, Deena A.; Nagarajan, V.; Navarro Poulsen, Jens-Christian; Adams-Cioaba, Melanie A.; Bergfors, Terese; Sommer, Morten O. A.

    2011-01-01

    Microfluidic crystallization using the Crystal Former improves the identification of initial crystallization conditions relative to screening via vapour diffusion. Advances in automation have facilitated the widespread adoption of high-throughput vapour-diffusion methods for initial crystallization screening. However, for many proteins, screening thousands of crystallization conditions fails to yield crystals of sufficient quality for structural characterization. Here, the rates of crystal identification for thaumatin, catalase and myoglobin using microfluidic Crystal Former devices and sitting-drop vapour-diffusion plates are compared. It is shown that the Crystal Former results in a greater number of identified initial crystallization conditions compared with vapour diffusion. Furthermore, crystals of thaumatin and lysozyme obtained in the Crystal Former were used directly for structure determination both in situ and upon harvesting and cryocooling. On the basis of these results, a crystallization strategy is proposed that uses multiple methods with distinct kinetic trajectories through the protein phase diagram to increase the output of crystallization pipelines

  13. Liquid Crystal Foams Generated by Pressure-Driven Microfluidic Devices.

    Science.gov (United States)

    Shi, Shuojia; Yokoyama, Hiroshi

    2015-04-21

    Thermotropic liquid crystals possess superior foaming capability without the aid of surfactants because of the anisotropic molecular structures. We developed a T-junction microfluidic device to inject gas bubbles of uniform size into a liquid crystal in the nematic and the smectic phases. The bubble size is primarily determined by the dimension of microfluidic channel regardless of the phase, and air bubbles of a few tens of micrometer diameter were stably injected at the rate up to 110 Hz to the close packing density with a polydispersity less than 4%. It is shown that an efficient path to fabricate stable liquid crystal foams is to inject bubbles in the nematic phase, where the highest injection rate is possible, and promptly cool it down to the smectic phase.

  14. In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

    KAUST Repository

    Kodzius, Rimantas

    2011-01-22

    In this body of work we have been developing and characterizing paper based microfluidic fabrication technologies to produce low cost biological analysis. Specifically we investigated the performance of paper microfluidics that had been bonded using wax or acrylic glue, and characterized the affect of these and other microfluidic materials on the polymerase chain reaction (PCR). We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax or cyanoacrylate-based resin as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes. The hot-melt adhesive wax or simple cyanoacrylate-based resin can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate film, glass sheets, or metal plate. The wax bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by evacuating the channels of adhesive material in a hot-water. We applied the wax-paper based microfluidic chip to HeLa cell electroporation. Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein recombinant E. coli bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration. The chip bonded with cyanoacrylate-based resin was tested by measuring protein concentration and carrying out DNA capillary electrophoresis. To study the biocompatibility and applicability of our microfluidic chip fabrication technology, we tested the PCR compatibility of our chip materials along with various other common materials

  15. Development of a PMMA Electrochemical Microfluidic Device for Carcinoembryonic Antigen Detection

    Science.gov (United States)

    Van Anh, Nguyen; Van Trung, Hoang; Tien, Bui Quang; Binh, Nguyen Hai; Ha, Cao Hong; Le Huy, Nguyen; Loc, Nguyen Thai; Thu, Vu Thi; Lam, Tran Dai

    2016-05-01

    In this study, a poly(methyl methacrylate) (PMMA) microfluidic device fabricated by an inexpensive CO2 laser etching system was developed for detection of carcino-embryonic antigens (CEA). The device was capable of working in continuous mode and was designed with the aid of numerical simulation. The detection of target CEA was based on immuno-assay via magnetic particles and electrochemical sensing. The as-prepared microfluidic can be used to detect CEA at the relatively low concentration of 150 pg mL-1. The device could be reused many times, since the capture and removal of magnetic particles in the assay could be manipulated by an external magnetic field. The proposed approach appears to be suitable for high-throughput and automated analysis of large biomolecules such as tumor markers and pathogens.

  16. A versatile valving toolkit for automating fluidic operations in paper microfluidic devices.

    Science.gov (United States)

    Toley, Bhushan J; Wang, Jessica A; Gupta, Mayuri; Buser, Joshua R; Lafleur, Lisa K; Lutz, Barry R; Fu, Elain; Yager, Paul

    2015-03-21

    Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically after a) a certain period of time, or b) the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50 s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods - both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device.

  17. A microfluidic device for separation of amniotic fluid mesenchymal stem cells utilizing louver-array structures.

    Science.gov (United States)

    Wu, Huei-Wen; Lin, Xi-Zhang; Hwang, Shiaw-Min; Lee, Gwo-Bin

    2009-12-01

    Human mesenchymal stem cells can differentiate into multiple lineages for cell therapy and, therefore, have attracted considerable research interest recently. This study presents a new microfluidic device for bead and cell separation utilizing a combination of T-junction focusing and tilted louver-like structures. For the first time, a microfluidic device is used for continuous separation of amniotic stem cells from amniotic fluids. An experimental separation efficiency as high as 82.8% for amniotic fluid mesenchymal stem cells is achieved. Furthermore, a two-step separation process is performed to improve the separation efficiency to 97.1%. These results are based on characterization experiments that show that this microfluidic chip is capable of separating beads with diameters of 5, 10, 20, and 40 microm by adjusting the volume-flow-rate ratio between the flows in the main and side channels of the T-junction focusing structure. An optimal volume-flow-rate ratio of 0.5 can lead to high separation efficiencies of 87.8% and 85.7% for 5-microm and 10-microm beads, respectively, in a one-step separation process. The development of this microfluidic chip may be promising for future research into stem cells and for cell therapy.

  18. Sex identification of ancient DNA samples using a microfluidic device.

    Science.gov (United States)

    Shaw, Kirsty J; Brown, Keri A; Brown, Terence A; Haswell, Stephen J

    2015-01-01

    Ancient DNA is the name given to the degraded, fragmented, and chemically damaged biomolecules that can be recovered from archaeological remains of plants, animals, and humans. Where ancient human DNA has survived at archaeological sites, it can give valuable information and is especially useful for its potential to identify kinship, population affinities, pathogens, and biological sex. Here, we describe the operation of a microfluidic device for the sex identification of ancient DNA samples using an efficient sample handling process. DNA is extracted from powdered bone samples and abasic sites labeled with biotin. Streptavidin-coated superparamagnetic particles are used to isolate the labeled DNA prior to amplification of the Amelogenin sex marker.

  19. An integrated microfluidic device for the sorting of yeast cells using image processing.

    Science.gov (United States)

    Yu, Bo Yang; Elbuken, Caglar; Shen, Chong; Huissoon, Jan Paul; Ren, Carolyn L

    2018-02-23

    The process of detection and separation of yeast cells based on their morphological characteristics is critical to the understanding of cell division cycles, which is of vital importance to the understanding of some diseases such as cancer. The traditional process of manual detection is usually tedious and inconsistent. This paper presents a microfluidic device integrated with microvalves for fluid control for the sorting of yeast cells using image processing algorithms and confirmation based on their fluorescent tag. The proposed device is completely automated, low cost and easy to implement in an academic research setting. Design details of the integrated microfluidic system are highlighted in this paper, along with experimental validation. Real time cell sorting was demonstrated with a cell detection rate of 12 cells per minute.

  20. Chemical and physical processes for integrated temperature control in microfluidic devices

    NARCIS (Netherlands)

    Guijt, Rosanne M.; Dodge, Arash; Van Dedem, Gijs W. K.; De Rooij, Nico F.; Verpoorte, Elisabeth

    2003-01-01

    Microfluidic devices are a promising new tool for studying and optimizing (bio)chemical reactions and analyses. Many (bio)chemical reactions require accurate temperature control, such as for example thermocycling for PCR. Here, a new integrated temperature control system for microfluidic devices is

  1. A Student-Made Microfluidic Device for Electrophoretic Separation of Food Dyes

    Science.gov (United States)

    Teerasong, Saowapak; McClain, Robert L.

    2011-01-01

    We have developed an undergraduate laboratory activity to introduce students to microfluidics. In the activity, each student constructs their own microfluidic device using simple photolithographic techniques and then uses the device to separate a food dye mixture by electrophoresis. Dyes are used so that students are able to visually observe the…

  2. In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

    KAUST Repository

    Kodzius, Rimantas

    2011-11-04

    In this body of work we have been developing and characterizing paper based microfluidic fabrication technologies to produce low cost biological analysis. Specifically we investigated the performance of paper microfluidics that had been bonded using wax o

  3. Review on recent and advanced applications of monoliths and related porous polymer gels in micro-fluidic devices.

    Science.gov (United States)

    Vázquez, Mercedes; Paull, Brett

    2010-06-04

    This review critically summarises recent novel and advanced achievements in the application of monolithic materials and related porous polymer gels in micro-fluidic devices appearing within the literature over the period of the last 5 years (2005-2010). The range of monolithic materials has developed rapidly over the past decade, with a diverse and highly versatile class of materials now available, with each exhibiting distinct porosities, pore sizes, and a wide variety of surface functionalities. A major advantage of these materials is their ease of preparation in micro-fluidic channels by in situ polymerisation, leading to monolithic materials being increasingly utilised for a larger variety of purposes in micro-fluidic platforms. Applications of porous polymer monoliths, silica-based monoliths and related homogeneous porous polymer gels in the preparation of separation columns, ion-permeable membranes, preconcentrators, extractors, electrospray emitters, micro-valves, electrokinetic pumps, micro-reactors and micro-mixers in micro-fluidic devices are discussed herein. Procedures used in the preparation of monolithic materials in micro-channels, as well as some practical aspects of the micro-fluidic chip fabrication are addressed. Recent analytical/bioanalytical and catalytic applications of the final micro-fluidic devices incorporating monolithic materials are also reviewed. Copyright 2010 Elsevier B.V. All rights reserved.

  4. Multimodal Microchannel and Nanowell-Based Microfluidic Platforms for Bioimaging

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Tao; Smallwood, Chuck R.; Zhu, Ying; Bredeweg, Erin L.; Baker, Scott E.; Evans, James E.; Kelly, Ryan T.

    2017-03-30

    Modern live-cell imaging approaches permit real-time visualization of biological processes. However, limitations for unicellular organism trapping, culturing and long-term imaging can preclude complete understanding of how such microorganisms respond to perturbations in their local environment or linking single-cell variability to whole population dynamics. We have developed microfluidic platforms to overcome prior technical bottlenecks to allow both chemostat and compartmentalized cellular growth conditions using the same device. Additionally, a nanowell-based platform enables a high throughput approach to scale up compartmentalized imaging optimized within the microfluidic device. These channel and nanowell platforms are complementary, and both provide fine control over the local environment as well as the ability to add/replace media components at any experimental time point.

  5. Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

    Directory of Open Access Journals (Sweden)

    Ana Rubina Perestrelo

    2015-12-01

    Full Text Available Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

  6. Solvent Bonding for Fabrication of PMMA and COP Microfluidic Devices.

    Science.gov (United States)

    Wan, Alwin M D; Moore, Thomas A; Young, Edmond W K

    2017-01-17

    Thermoplastic microfluidic devices offer many advantages over those made from silicone elastomers, but bonding procedures must be developed for each thermoplastic of interest. Solvent bonding is a simple and versatile method that can be used to fabricate devices from a variety of plastics. An appropriate solvent is added between two device layers to be bonded, and heat and pressure are applied to the device to facilitate the bonding. By using an appropriate combination of solvent, plastic, heat, and pressure, the device can be sealed with a high quality bond, characterized as having high bond coverage, bond strength, optical clarity, durability over time, and low deformation or damage to microfeature geometry. We describe the procedure for bonding devices made from two popular thermoplastics, poly(methyl-methacrylate) (PMMA), and cyclo-olefin polymer (COP), as well as a variety of methods to characterize the quality of the resulting bonds, and strategies to troubleshoot low quality bonds. These methods can be used to develop new solvent bonding protocols for other plastic-solvent systems.

  7. Toner and paper-based fabrication techniques for microfluidic applications.

    Science.gov (United States)

    Coltro, Wendell Karlos Tomazelli; de Jesus, Dosil Pereira; da Silva, José Alberto Fracassi; do Lago, Claudimir Lucio; Carrilho, Emanuel

    2010-08-01

    The interest in low-cost microfluidic platforms as well as emerging microfabrication techniques has increased considerably over the last years. Toner- and paper-based techniques have appeared as two of the most promising platforms for the production of disposable devices for on-chip applications. This review focuses on recent advances in the fabrication techniques and in the analytical/bioanalytical applications of toner and paper-based devices. The discussion is divided in two parts dealing with (i) toner and (ii) paper devices. Examples of miniaturized devices fabricated by using direct-printing or toner transfer masking in polyester-toner, glass, PDMS as well as conductive platforms as recordable compact disks and printed circuit board are presented. The construction and the use of paper-based devices for off-site diagnosis and bioassays are also described to cover this emerging platform for low-cost diagnostics.

  8. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers

    DEFF Research Database (Denmark)

    Perozziello, Gerardo; Candeloro, Patrizio; De Grazia, Antonio

    2016-01-01

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels-where the cells can flow one-by-one -, allowing single...... cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm...

  9. Breaking new boundaries with microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2010-09-01

    Full Text Available Microfluidics is an important emerging research platform in South Africa. It deals with the control and manipulation of very small quantities of fluids (typically microlitre and smaller) inside micro-channels. Microfluidic-based devices show great...

  10. Designer polymer-based microcapsules made using microfluidics.

    Science.gov (United States)

    Chen, Philipp W; Erb, Randall M; Studart, André R

    2012-01-10

    Filled microcapsules made from double emulsion templates in microfluidic devices are attractive delivery systems for a variety of applications. The microfluidic approach allows facile tailoring of the microcapsules through a large number of variables, which in turn makes these systems more challenging to predict. To elucidate these dependencies, we start from earlier theoretical predictions for the size of double emulsions and present quantitative design maps that correlate parameters such as fluid flow rates and device geometry with the size and shell thickness of monodisperse polymer-based capsules produced in microcapillary devices. The microcapsules are obtained through in situ photopolymerization of the middle oil phase of water-in-oil-in-water double emulsions. Using polymers with selected glass transition temperatures as the shell material, we show through single capsule compression testing that hollow capsules can be prepared with tunable mechanical properties ranging from elastomeric to brittle. A quantitative statistical analysis of the load at rupture of brittle capsules is also provided to evaluate the variability of the microfluidic route and assist the design of capsules in applications involving mechanically triggered release. Finally, we demonstrate that the permeability and microstructure of the capsule shell can also be tailored through the addition of cross-linkers and silica nanoparticles in the middle phase of the double emulsion templates.

  11. Review of microfluidic cell culture devices for the control of gaseous microenvironments in vitro

    Science.gov (United States)

    Wu, H.-M.; Lee, T.-A.; Ko, P.-L.; Chiang, H.-J.; Peng, C.-C.; Tung, Y.-C.

    2018-04-01

    Gaseous microenvironments play important roles in various biological activities in vivo. However, it is challenging to precisely control gaseous microenvironments in vitro for cell culture due to the high diffusivity nature of gases. In recent years, microfluidics has paved the way for the development of new types of cell culture devices capable of manipulating cellular microenvironments, and provides a powerful tool for in vitro cell studies. This paper reviews recent developments of microfluidic cell culture devices for the control of gaseous microenvironments, and discusses the advantages and limitations of current devices. We conclude with suggestions for the future development of microfluidic cell culture devices for the control of gaseous microenvironments.

  12. A microfluidic device for rapid screening of E. coli O157:H7 based on IFAST and ATP bioluminescence assay for water analysis

    CSIR Research Space (South Africa)

    Ngamsom, B

    2017-08-01

    Full Text Available We present a simple microfluidic system for rapid screening of Escherichia coli (E. coli) O157:H7 employing the specificity of immunomagnetic separation (IMS) via immiscible filtration assisted by surface tension (IFAST), and the sensitivity...

  13. Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

    Science.gov (United States)

    Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

    2017-02-01

    The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

  14. Application of a microfluidic device for counting of bacteria.

    Science.gov (United States)

    Inatomi, K-I; Izuo, S-I; Lee, S-S

    2006-09-01

    To develop a miniaturized analytical system for counting of bacteria. Escherichia coli cells were used throughout the experiments. The system consists of a microfluidic chamber, a fluorescence microscope with a charge-coupled device (CCD) camera and syringe pumps. The chamber was made of a silicone rubber (30 x 30 mm and 4 mm high). The E. coli cells were flowed from a micro-nozzle fabricated in the chamber and detected with the CCD camera. The individual cells were indicated as signal peaks on a computer. The cell counts showed a good correlation compared with that of a conventional plate counting method, and results of the simultaneous detection of live and dead cells were also presented. The system having a small disposable nozzle has the advantages for low cost and safe medical or environmental analysis, when compared with a conventional flow cytometer. This is the first step of the development of a one-chip microbe analyzer.

  15. Easy monitoring of velocity fields in microfluidic devices using spatiotemporal image correlation spectroscopy.

    Science.gov (United States)

    Travagliati, Marco; Girardo, Salvatore; Pisignano, Dario; Beltram, Fabio; Cecchini, Marco

    2013-09-03

    Spatiotemporal image correlation spectroscopy (STICS) is a simple and powerful technique, well established as a tool to probe protein dynamics in cells. Recently, its potential as a tool to map velocity fields in lab-on-a-chip systems was discussed. However, the lack of studies on its performance has prevented its use for microfluidics applications. Here, we systematically and quantitatively explore STICS microvelocimetry in microfluidic devices. We exploit a simple experimental setup, based on a standard bright-field inverted microscope (no fluorescence required) and a high-fps camera, and apply STICS to map liquid flow in polydimethylsiloxane (PDMS) microchannels. Our data demonstrates optimal 2D velocimetry up to 10 mm/s flow and spatial resolution down to 5 μm.

  16. Capillary-composited microfluidic device for heat shock transformation of Escherichia coli.

    Science.gov (United States)

    Sha, Jun; Wang, Yaolei; Wang, Jianchun; Ren, Li; Tu, Qin; Liu, Wenming; Wang, Xueqin; Liu, Ajing; Wang, Lei; Wang, Jinyi

    2011-10-01

    This work describes chemical heat shock transformation of foreign plasmid DNA into bacterial host Escherichia coli cells using a capillary-composited microfluidic device. Transformation processes of the loading, mixing, heat shock and recovery of the transformation mixture were carried out automatically in a linear fashion. In addition, by utilizing the capillary with a hollow cylindrical chamber as heating source, simple, low cost local heat shock with accurate heat shock time to transformation mixture was obtained on the microdevice. Results demonstrated that plasmid DNA could be effectively transformed into E. coli, and the transformation efficiency and frequency were as the same level or better than conventional tube-based method. This work complements other microfluidic technologies for potential gene cloning and functional genomics studies. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Manufacturing microstructured tool inserts for the production of polymeric microfluidic devices

    Science.gov (United States)

    Zhang, Nan; Srivastava, Amit; Kirwan, Brendan; Byrne, Richard; Fang, Fengzhou; Browne, David J.; Gilchrist, Michael D.

    2015-09-01

    Tooling is critical in defining multi-scale patterns for mass production of polymeric microfluidic devices using the microinjection molding process. In the present work, fabrication of various microstructured tool inserts using stainless steel, nickel and bulk metallic glasses (BMGs) is discussed based on die-sinking EDM (electrical discharge machining), electroforming, focused ion beam milling and thermoplastic forming processes. Tool performance is evaluated in terms of surface roughness, hardness and tool life. Compared to stainless steel, nickel and BMGs are capable of integrating length scales from 100 to 10-8 m and are good candidates for producing polymeric microfluidics. Selection of tool materials and manufacturing technologies should consider the end-user requirements of actual applications.

  18. Combining Electro-Osmotic Flow and FTA® Paper for DNA Analysis on Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Ryan Wimbles

    2016-07-01

    Full Text Available FTA® paper can be used to protect a variety of biological samples prior to analysis, facilitating ease-of-transport to laboratories or long-term archive storage. The use of FTA® paper as a solid phase eradicates the need to elute the nucleic acids from the matrix prior to DNA amplification, enabling both DNA purification and polymerase chain reaction (PCR-based DNA amplification to be performed in a single chamber on the microfluidic device. A disc of FTA® paper, containing a biological sample, was placed within the microfluidic device on top of wax-encapsulated DNA amplification reagents. The disc containing the biological sample was then cleaned up using Tris-EDTA (TE buffer, which was passed over the disc, via electro-osmotic flow, in order to remove any potential inhibitors of downstream processes. DNA amplification was successfully performed (from buccal cells, whole blood and semen using a Peltier thermal cycling system, whereupon the stored PCR reagents were released during the initial denaturing step due to the wax barrier melting between the FTA® disc and PCR reagents. Such a system offers advantages in terms of a simple sample introduction interface and the ability to process archived samples in an integrated microfluidic environment with minimal risk of contamination.

  19. Investigating the fluid dynamics of rapid processes within microfluidic devices using bright-field microscopy.

    Science.gov (United States)

    Pirbodaghi, Tohid; Vigolo, Daniele; Akbari, Samin; deMello, Andrew

    2015-05-07

    The widespread application of microfluidic devices in the biological and chemical sciences requires the implementation of complex designs and geometries, which in turn leads to atypical fluid dynamic phenomena. Accordingly, a complete understanding of fluid dynamics in such systems is key in the facile engineering of novel and efficient analytical tools. Herein, we present an accurate approach for studying the fluid dynamics of rapid processes within microfluidic devices using bright-field microscopy with white light illumination and a standard high-speed camera. Specifically, we combine Ghost Particle Velocimetry and the detection of moving objects in automated video surveillance to track submicron size tracing particles via cross correlation between the speckle patterns of successive images. The efficacy of the presented technique is demonstrated by measuring the flow field over a square pillar (80 μm × 80 μm) in a 200 μm wide microchannel at high volumetric flow rates. Experimental results are in excellent agreement with those obtained via computational fluid dynamics simulations. The method is subsequently used to study the dynamics of droplet generation at a flow focusing microfluidic geometry. A unique feature of the presented technique is the ability to perform velocimetry analysis of high-speed phenomena, which is not possible using micron-resolution particle image velocimetry (μPIV) approaches based on confocal or fluorescence microscopy.

  20. Integration of Stable Droplet Formation on a CD Microfluidic Device for Extreme Point of Care Applications

    Science.gov (United States)

    Ganesh, Shruthi Vatsyayani

    With the advent of microfluidic technologies for molecular diagnostics, a lot of emphasis has been placed on developing diagnostic tools for resource poor regions in the form of Extreme Point of Care devices. To ensure commercial viability of such a device there is a need to develop an accurate sample to answer system, which is robust, portable, isolated yet highly sensitive and cost effective. This need has been a driving force for research involving integration of different microsystems like droplet microfluidics, Compact-disc (CD)microfluidics along with sample preparation and detection modules on a single platform. This work attempts to develop a proof of concept prototype of one such device using existing CD microfluidics tools to generate stable droplets used in point of care diagnostics (POC diagnostics). Apart from using a fairly newer technique for droplet generation and stabilization, the work aims to develop this method focused towards diagnostics for rural healthcare. The motivation for this work is first described with an emphasis on the current need for diagnostic testing in rural health-care and the general guidelines prescribed by WHO for such a sample to answer system. Furthermore, a background on CD and droplet microfluidics is presented to understand the merits and de-merits of each system and the need for integrating the two. This phase of the thesis also includes different methods employed/demonstrated to generate droplets on a spinning platform. An overview on the detection platforms is also presented to understand the challenges involved in building an extreme point of care device. In the third phase of the thesis, general manufacturing techniques and materials used to accomplish this work is presented. Lastly, design trials for droplet generation is presented. The shortcomings of these trials are solved by investigating mechanisms pertaining to design modification and use of agarose based droplet generation to ensure a more robust sample

  1. Microfluidic device for DNA amplification of single cancer cells isolated from whole blood by self-seeding microwells

    NARCIS (Netherlands)

    Yang, Yoon Sun; Rho, Hoon Suk; Stevens, Michiel; Tibbe, Arjan G.J.; Gardeniers, Johannes G.E.; Terstappen, Leonardus Wendelinus Mathias Marie

    2015-01-01

    Self-seeding microwell chips can sort single cells into 6400 wells based on cell size and their identity verified by immunofluorescence staining. Here, we developed a microfluidic device in which these single cells can be placed, lysed and their DNA amplified for further interrogation. Whole blood

  2. Rapid, Semiautomated Quantification of Bacterial Cells in Freshwater by Using a Microfluidic Device for On-Chip Staining and Counting▿

    OpenAIRE

    Yamaguchi, Nobuyasu; Torii, Masashi; Uebayashi, Yuko; Nasu, Masao

    2010-01-01

    A microfluidic device-based system for the rapid and semiautomated counting of bacteria in freshwater was fabricated and examined. Bacteria in groundwater and in potable water, as well as starved Escherichia coli O157:H7 spiked in pond water, were able to be on-chip stained and enumerated within 1 h using this system.

  3. Biofunctionalization of PDMS-based microfluidic systems

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Bergoi Ibarlucea, Cesar Fernández-Sánchez, Stefanie Demming, Stephanus Büttgenbach & Andreu Llobera ### Abstract Three simple approaches for the selective immobilization of biomolecules on the surface of poly(dimethylsiloxane) (PDMS) microfluidic systems that do not require any specific instrumentation, are described and compared. They are based in the introduction of hydroxyl groups on the PDMS surface by direct adsorption of either polyethylene glycol (PEG) or polyvinyl alc...

  4. Pressure-actuated microfluidic devices for electrophoretic separation of pre-term birth biomarkers.

    Science.gov (United States)

    Sahore, V; Kumar, S; Rogers, C I; Jensen, J K; Sonker, M; Woolley, A T

    2016-01-01

    We have developed microfluidic devices with pressure-driven injection for electrophoretic analysis of amino acids, peptides, and proteins. The novelty of our approach lies in the use of an externally actuated on-chip peristaltic pump and closely spaced pneumatic valves that allow well-defined, small-volume sample plugs to be injected and separated by microchip electrophoresis. We fabricated three-layer poly(dimethylsiloxane) (PDMS) microfluidic devices. The fluidic layer had injection and separation channels, and the control layer had an externally actuated on-chip peristaltic pump and four pneumatic valves around the T-intersection to carry out sample injection. An unpatterned PDMS membrane layer was sandwiched between the fluidic and control layers as the actuated component in pumps and valves. Devices with the same peristaltic pump design but different valve spacings (100, 200, 300, and 400 μm) from the injection intersection were fabricated using soft lithographic techniques. Devices were characterized through fluorescent imaging of captured plugs of a fluorescein-labeled amino acid mixture and through microchip electrophoresis separations. A suitable combination of peak height, separation efficiency, and analysis time was obtained with a peristaltic pump actuation rate of 50 ms, an injection time of 30 s, and a 200-μm valve spacing. We demonstrated the injection of samples in different solutions and were able to achieve a 2.4-fold improvement in peak height and a 2.8-fold increase in separation efficiency though sample stacking. A comparison of pressure-driven injection and electrokinetic injection with the same injection time and separation voltage showed a 3.9-fold increase in peak height in pressure-based injection with comparable separation efficiency. Finally, the microchip systems were used to separate biomarkers implicated in pre-term birth. Although these devices have initially been demonstrated as a stand-alone microfluidic separation tool, they

  5. Fabrication of an Open Microfluidic Device for Immunoblotting.

    Science.gov (United States)

    Abdel-Sayed, Philippe; Yamauchi, Kevin A; Gerver, Rachel E; Herr, Amy E

    2017-09-19

    Given the wide adoption of polydimethylsiloxane (PDMS) for the rapid fabrication of microfluidic networks and the utility of polyacrylamide gel electrophoresis (PAGE), we develop a technique for fabrication of PAGE molecular sieving gels in PDMS microchannel networks. In developing the fabrication protocol, we trade-off constraints on materials properties of these two polymer materials: PDMS is permeable to O 2 and the presence of O 2 inhibits the polymerization of polyacrylamide. We present a fabrication method compatible with performing PAGE protein separations in a composite PDMS-glass microdevice, that toggles from an "enclosed" microchannel for PAGE and blotting to an "open" PA gel lane for immunoprobing and readout. To overcome the inhibitory effects of O 2 , we coat the PDMS channel with a 10% benzophenone solution, which quenches the inhibiting effect of O 2 when exposed to UV, resulting in a PAGE-in-PDMS device. We then characterize the PAGE separation performance. Using a ladder of small-to-mid mass proteins (Trypsin Inhibitor (TI); Ovalbumin (OVA); Bovine Serum Albumin (BSA)), we observe resolution of the markers in TI, with comparable reproducibility to glass microdevice PAGE. We show that benzophenone groups incorporated into the gel through methacrylamide can be UV-activated multiple times to photocapture protein. PDMS microchannel network is reversibly bonded to a glass slide allowing direct access to separated proteins and subsequent in situ diffusion-driven immunoprobing and total protein Sypro red staining. We see this PAGE-in-PDMS fabrication technique as expanding the application and use of microfluidic PAGE without the need for a glass microfabrication infrastructure.

  6. Fabrication of polystyrene microfluidic devices using a pulsed CO2 laser system

    KAUST Repository

    Li, Huawei

    2013-10-10

    In this article, we described a simple and rapid method for fabrication of droplet microfluidic devices on polystyrene substrate using a CO2 laser system. The effects of the laser power and the cutting speed on the depth, width and aspect ratio of the microchannels fabricated on polystyrene were investigated. The polystyrene microfluidic channels were encapsulated using a hot press bonding technique. The experimental results showed that both discrete droplets and laminar flows could be obtained in the device.

  7. Bacterial Response to Antibiotic Gradients in a Porous Microfluidic Device

    Science.gov (United States)

    Deng, J.; Shechtman, L. A.; Sanford, R. A.; Dong, Y.; Werth, C. J.; Fouke, B. W.

    2015-12-01

    Microorganisms in nature have evolved survival strategies to cope with a wide variety of environmental stresses, including gradients in temperature, pH, substrate availability and aqueous chemistry. Microfluidic devices provide a consistently reliable real-time means to quantitatively measure, control and reproduce the dynamic nature of these stresses. As an example, accelerated adaptation from genetic mutations have been observed in E. coli as it responds to gradients of Ciprofloxacin (Zhang et. al. 2011). However, the mechanisms by which bacteria respond to antibiotic gradients, as well as the effect of changes in how the stressor is applied, have not been systematically studied. In this study, newly designed and fabricated microfluidic devices with porous media have been utilized to determine the chemical stress fields that enhance adaptation and thus to test how E. coli bacterial communities adapt to antibiotic stresses. By applying antibiotic and nutrient into inlet channels adjacent to either side of the porous media inoculated with E. coli, a gradient of antibiotic was formed. Hydrogel barriers were selectively photo-polymerized in between of the inlet channels and the porous media to prevent any undesired convection. Hence, chemical solute can only be transported by diffusion, creating a reproducible antibiotic gradient over the porous media. The bacteria were also constrained by the hydrogel boundary barriers from escaping the porous media. Preliminary results suggest that E. coli moves freely with respect to Ciprofloxacin concentrations. In addition, and unexpectedly, the E. coli colonies exhibit a concentric pulsed growth front radiating away from the point of inoculation within the micromodel ecosystem and pulse over the porous media containing antibiotic. The bacteria at the growth front grow into long filaments (up to 100μm) while the bacteria in the inner concentric area are normal size. We hypothesize that the frontier bacteria, which are first

  8. Hot embossing of plastic microfluidic devices using poly(dimethylsiloxane) molds

    Science.gov (United States)

    Goral, Vasiliy N.; Hsieh, Yi-Cheng; Petzold, Odessa N.; Faris, Ronald A.; Yuen, Po Ki

    2011-01-01

    We present a poly(dimethylsiloxane) (PDMS)-based hot embossing process for low-cost rapid prototyping of plastic microfluidic devices. Unlike the conventional hot embossing process, the process presented here uses a 2 mm thick PDMS mold, two 3/4" wide binder clips, two standard 1 mm thick 1" × 3" microscope glass slides and a standard laboratory oven. Micro-scale features were successfully replicated in 1.5 mm thick polystyrene slides from various PDMS molds. Also, the PDMS molds can be reused for many replications without any damage.

  9. Hot embossing of plastic microfluidic devices using poly(dimethylsiloxane) molds

    International Nuclear Information System (INIS)

    Goral, Vasiliy N; Petzold, Odessa N; Faris, Ronald A; Yuen, Po Ki; Hsieh, Yi-Cheng

    2011-01-01

    We present a poly(dimethylsiloxane) (PDMS)-based hot embossing process for low-cost rapid prototyping of plastic microfluidic devices. Unlike the conventional hot embossing process, the process presented here uses a 2 mm thick PDMS mold, two 3/4'' wide binder clips, two standard 1 mm thick 1 x 3 microscope glass slides and a standard laboratory oven. Micro-scale features were successfully replicated in 1.5 mm thick polystyrene slides from various PDMS molds. Also, the PDMS molds can be reused for many replications without any damage. (technical note)

  10. Microfluidic device for cell capture and impedance measurement.

    Science.gov (United States)

    Jang, Ling-Sheng; Wang, Min-How

    2007-10-01

    This work presents a microfluidic device to capture physically single cells within microstructures inside a channel and to measure the impedance of a single HeLa cell (human cervical epithelioid carcinoma) using impedance spectroscopy. The device includes a glass substrate with electrodes and a PDMS channel with micro pillars. The commercial software CFD-ACE+ is used to study the flow of the microstructures in the channel. According to simulation results, the probability of cell capture by three micro pillars is about 10%. An equivalent circuit model of the device is established and fits closely to the experimental results. The circuit can be modeled electrically as cell impedance in parallel with dielectric capacitance and in series with a pair of electrode resistors. The system is operated at low frequency between 1 and 100 kHz. In this study, experiments show that the HeLa cell is successfully captured by the micro pillars and its impedance is measured by impedance spectroscopy. The magnitude of the HeLa cell impedance declines at all operation voltages with frequency because the HeLa cell is capacitive. Additionally, increasing the operation voltage reduces the magnitude of the HeLa cell because a strong electric field may promote the exchange of ions between the cytoplasm and the isotonic solution. Below an operating voltage of 0.9 V, the system impedance response is characteristic of a parallel circuit at under 30 kHz and of a series circuit at between 30 and 100 kHz. The phase of the HeLa cell impedance is characteristic of a series circuit when the operation voltage exceeds 0.8 V because the cell impedance becomes significant.

  11. Rapid Fabrication of Electrophoretic Microfluidic Devices from Polyester, Adhesives and Gold Leaf

    Directory of Open Access Journals (Sweden)

    Christopher Birch

    2017-01-01

    Full Text Available In the last decade, the microfluidic community has witnessed an evolution in fabrication methodologies that deviate from using conventional glass and polymer-based materials. A leading example within this group is the print, cut and laminate (PCL approach, which entails the laser cutting of microfluidic architecture into ink toner-laden polyester sheets, followed by the lamination of these layers for device assembly. Recent success when applying this method to human genetic fingerprinting has highlighted that it is now ripe for the refinements necessary to render it amenable to mass-manufacture. In this communication, we detail those modifications by identifying and implementing a suitable heat-sensitive adhesive (HSA material to equip the devices with the durability and resilience required for commercialization and fieldwork. Importantly, this augmentation is achieved without sacrificing any of the characteristics which make the PCL approach attractive for prototyping. Exemplary HSA-devices performed DNA extraction, amplification and separation which, when combined, constitute the complete sequence necessary for human profiling and other DNA-based analyses.

  12. Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

    Science.gov (United States)

    Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

    2016-11-01

    Realizing that current microfluidic chip fabrication techniques are time consuming and labor intensive as well as always have material leftover after chip fabrication, this research work proposes an innovative approach for rapid microfluidic chip production. The key idea relies on a combination of a widely-used inkjet printing method and a heat-based polymer curing technique with an electronic-mechanical control, thus eliminating the need of masking and molds compared to typical microfluidic fabrication processes. In addition, as the appropriate amount of polymer is utilized during printing, there is much less amount of material wasted. Our inkjet-based microfluidic printer can print out the desired microfluidic chip pattern directly onto a heated glass surface, where the printed polymer is suddenly cured. Our proof-of-concept demonstration for widely-used single-flow channel, Y-junction, and T-junction microfluidic chips shows that the whole microfluidic chip fabrication process requires only 3 steps with a fabrication time of 6 minutes.

  13. All-polymer microfluidic systems for droplet based sample analysis

    DEFF Research Database (Denmark)

    Poulsen, Carl Esben

    In this PhD project, I pursued to develop an all-polymer injection moulded microfluidic platform with integrated droplet based single cell interrogation. To allow for a proper ”one device - one experiment” methodology and to ensure a high relevancy to non-academic settings, the systems presented...... here were fabricated exclusive using commercially relevant fabrication methods such as injection moulding and ultrasonic welding. Further, to reduce the complexity of the final system, I have worked towards an all-in-one device which includes sample loading, priming (removal of air), droplet formation......, droplet packing, imaging and amplification (heating). The project has been broken into sub-projects, in which several devices of simpler application have been developed. Most of these employ gravity for concentrating and packing droplets, which has been made possible by the use of large area chambers...

  14. A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods

    Directory of Open Access Journals (Sweden)

    Monuki Edwin S

    2007-09-01

    Full Text Available Abstract Background Microfluidics is an enabling technology with a number of advantages over traditional tissue culture methods when precise control of cellular microenvironment is required. However, there are a number of practical and technical limitations that impede wider implementation in routine biomedical research. Specialized equipment and protocols required for fabrication and setting up microfluidic experiments present hurdles for routine use by most biology laboratories. Results We have developed and validated a novel microfluidic device that can directly interface with conventional tissue culture methods to generate and maintain controlled soluble environments in a Petri dish. It incorporates separate sets of fluidic channels and vacuum networks on a single device that allows reversible application of microfluidic gradients onto wet cell culture surfaces. Stable, precise concentration gradients of soluble factors were generated using simple microfluidic channels that were attached to a perfusion system. We successfully demonstrated real-time optical live/dead cell imaging of neural stem cells exposed to a hydrogen peroxide gradient and chemotaxis of metastatic breast cancer cells in a growth factor gradient. Conclusion This paper describes the design and application of a versatile microfluidic device that can directly interface with conventional cell culture methods. This platform provides a simple yet versatile tool for incorporating the advantages of a microfluidic approach to biological assays without changing established tissue culture protocols.

  15. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    2010-07-01

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  16. SAXS on a chip: from dynamics of phase transitions to alignment phenomena at interfaces studied with microfluidic devices.

    Science.gov (United States)

    Silva, Bruno F B

    2017-09-13

    The field of microfluidics offers attractive possibilities to perform novel experiments that are difficult (or even impossible) to perform using conventional bulk and surface-based methods. Such attractiveness comes from several important aspects inherent to these miniaturized devices. First, the flow of fluids under submillimeter confinement typically leads to a drop of inertial forces, meaning that turbulence is practically suppressed. This leads to predictable and controllable flow profiles, along with well-defined chemical gradients and stress fields that can be used for controlled mixing and actuation on the micro and nanoscale. Secondly, intricate microfluidic device designs can be fabricated using cleanroom standard procedures. Such intricate geometries can take diverse forms, designed by researchers to perform complex tasks, that require exquisite control of flow of several components and gradients, or to mimic real world examples, facilitating the establishment of more realistic models. Thirdly, microfluidic devices are usually compatible with in situ or integrated characterization methods that allow constant real-time monitoring of the processes occurring inside the microchannels. This is very different from typical bulk-based methods, where usually one can only observe the final result, or otherwise, take quick snapshots of the evolving process or take aliquots to be analyzed separately. Altogether, these characteristics inherent to microfluidic devices provide researchers with a set of tools that allow not only exquisite control and manipulation of materials at the micro and nanoscale, but also observation of these effects. In this review, we will focus on the use and prospects of combining microfluidic devices with in situ small-angle X-ray scattering (and related techniques such as small-angle neutron scattering and X-ray photon correlation spectroscopy), and their enormous potential for physical-chemical research, mainly in self-assembly and phase

  17. Oxygen tension and riboflavin gradients cooperatively regulate the migration of Shewanella oneidensis MR-1 revealed by a hydrogel-based microfluidic device

    Directory of Open Access Journals (Sweden)

    Beum Jun Kim

    2016-09-01

    Full Text Available Shewanella oneidensis (S. oneidensis is a model bacterial strain for studies of bioelectrochemical systems (BESs. It has two extracellular electron transfer pathways: 1 shuttling electrons via an excreted mediator riboflavin; and 2 direct contact between the c-type cytochromes at the cell membrane and the electrode. Despite the extensive use of S. oneidensis in bioelectrochemical systems such as microbial fuel cells and biosensors, many basic microbiology questions about S. oneidensis in the context of BES remain unanswered. Here, we present studies of motility and chemotaxis of S. oneidensis under well controlled concentration gradients of two electron acceptors, oxygen and oxidized form of riboflavin (flavin+ using a newly developed microfluidic platform. Experimental results demonstrate that either oxygen or flavin+ is a chemoattractant to S. oneidensis. The chemotactic tendency of S. oneidensis in a flavin+ concentration gradient is significantly enhanced in an anaerobic in contrast to an aerobic condition. Furthermore, either a low oxygen tension or a high flavin+ concentration considerably enhances the speed of S. oneidensis. This work presents a robust microfluidic platform for generating oxygen and/or flavin+ gradients in an aqueous environment, and demonstrates that two important electron acceptors, oxygen and oxidized riboflavin, cooperatively regulate S. oneidensis migration patterns. The microfluidic tools presented as well as the knowledge gained in this work can be used to guide the future design of BESs for efficient electron production.

  18. Electrical Impedance Spectroscopy for Detection of Cells in Suspensions Using Microfluidic Device with Integrated Microneedles

    Directory of Open Access Journals (Sweden)

    Muhammad Asraf Mansor

    2017-02-01

    Full Text Available In this study, we introduce novel method of flow cytometry for cell detection based on impedance measurements. The state of the art method for impedance flow cytometry detection utilizes an embedded electrode in the microfluidic to perform measurement of electrical impedance of the presence of cells at the sensing area. Nonetheless, this method requires an expensive and complicated electrode fabrication process. Furthermore, reuse of the fabricated electrode also requires an intensive and tedious cleaning process. Due to that, we present a microfluidic device with integrated microneedles. The two microneedles are placed at the half height of the microchannel for cell detection and electrical measurement. A commercially-available Tungsten needle was utilized for the microneedles. The microneedles are easily removed from the disposable PDMS (Polydimethylsiloxane microchannel and can be reused with a simple cleaning process, such as washing by ultrasonic cleaning. Although this device was low cost, it preserves the core functionality of the sensor, which is capable of detecting passing cells at the sensing area. Therefore, this device is suitable for low-cost medical and food safety screening and testing process in developing countries.

  19. A Transdermal Measurement Platform Based on Microfluidics

    Directory of Open Access Journals (Sweden)

    Wen-Ying Huang

    2017-01-01

    Full Text Available The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

  20. Scintillation particle detection based on microfluidics

    CERN Document Server

    Mapelli, A; Renaud, P; Gorini, B; Trivino, N Vico; Jiguet, S; Vandelli, W; Haguenauer, M

    2010-01-01

    A novel type of particle detector based on scintillation, with precise spatial resolution and high radiation hardness, is being studied. It consists of a single microfluidic channel filled with a liquid scintillator and is designed to define an array of scintillating waveguides each independently coupled to a photodetector. Prototype detectors built using an SU-8 epoxy resin have been tested with electrons from a radioactive source. The experimental results show a light yield compatible with the theoretical expectations and confirm the validity of the approach. (C) 2010 Elsevier B.V. All rights reserved.

  1. Nanoscale surface modifications to control capillary flow characteristics in PMMA microfluidic devices

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Subhadeep

    2011-01-01

    Full Text Available Abstract Polymethylmethacrylate (PMMA microfluidic devices have been fabricated using a hot embossing technique to incorporate micro-pillar features on the bottom wall of the device which when combined with either a plasma treatment or the coating of a diamond-like carbon (DLC film presents a range of surface modification profiles. Experimental results presented in detail the surface modifications in the form of distinct changes in the static water contact angle across a range from 44.3 to 81.2 when compared to pristine PMMA surfaces. Additionally, capillary flow of water (dyed to aid visualization through the microfluidic devices was recorded and analyzed to provide comparison data between filling time of a microfluidic chamber and surface modification characteristics, including the effects of surface energy and surface roughness on the microfluidic flow. We have experimentally demonstrated that fluid flow and thus filling time for the microfluidic device was significantly faster for the device with surface modifications that resulted in a lower static contact angle, and also that the incorporation of micro-pillars into a fluidic device increases the filling time when compared to comparative devices.

  2. A guiding light: spectroscopy on digital microfluidic devices using in-plane optical fibre waveguides.

    Science.gov (United States)

    Choi, Kihwan; Mudrik, Jared M; Wheeler, Aaron R

    2015-09-01

    We present a novel method for in-plane digital microfluidic spectroscopy. In this technique, a custom manifold (.stl file available online as ESM) aligns optical fibres with a digital microfluidic device, allowing optical measurements to be made in the plane of the device. Because of the greater width vs thickness of a droplet on-device, the in-plane alignment of this technique allows it to outperform the sensitivity of vertical absorbance measurements on digital microfluidic (DMF) devices by ∼14×. The new system also has greater calibration sensitivity for thymol blue measurements than the popular NanoDrop system by ∼2.5×. The improvements in absorbance sensitivity result from increased path length, as well as from additional effects likely caused by liquid lensing, in which the presence of a water droplet between optical fibres increases fibre-to-fibre transmission of light by ∼2× through refraction and internal reflection. For interrogation of dilute samples, stretching of droplets using digital microfluidic electrodes and adjustment of fibre-to-fibre gap width allows absorbance path length to be changed on-demand. We anticipate this new digital microfluidic optical fibre absorbance and fluorescence measurement system will be useful for a wide variety of analytical applications involving microvolume samples with digital microfluidics.

  3. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers

    KAUST Repository

    Perozziello, Gerardo

    2015-12-11

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562). © 2015 Optical Society of America.

  4. An integrated, multiparametric flow cytometry chip using "microfluidic drifting" based three-dimensional hydrodynamic focusing.

    Science.gov (United States)

    Mao, Xiaole; Nawaz, Ahmad Ahsan; Lin, Sz-Chin Steven; Lapsley, Michael Ian; Zhao, Yanhui; McCoy, J Philip; El-Deiry, Wafik S; Huang, Tony Jun

    2012-06-01

    In this work, we demonstrate an integrated, single-layer, miniature flow cytometry device that is capable of multi-parametric particle analysis. The device integrates both particle focusing and detection components on-chip, including a "microfluidic drifting" based three-dimensional (3D) hydrodynamic focusing component and a series of optical fibers integrated into the microfluidic architecture to facilitate on-chip detection. With this design, multiple optical signals (i.e., forward scatter, side scatter, and fluorescence) from individual particles can be simultaneously detected. Experimental results indicate that the performance of our flow cytometry chip is comparable to its bulky, expensive desktop counterpart. The integration of on-chip 3D particle focusing with on-chip multi-parametric optical detection in a single-layer, mass-producible microfluidic device presents a major step towards low-cost flow cytometry chips for point-of-care clinical diagnostics.

  5. Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays

    Science.gov (United States)

    Young, Edmond W.K.; Berthier, Erwin; Guckenberger, David J.; Sackmann, Eric; Lamers, Casey; Meyvantsson, Ivar; Huttenlocher, Anna; Beebe, David J.

    2011-01-01

    Microfluidic cell-based systems have enabled the study of cellular phenomena with improved spatiotemporal control of the microenvironment and at increased throughput. While PDMS has emerged as the most popular material in microfluidics research, it has specific limitations that prevent microfluidic platforms from achieving their full potential. We present here a complete process, ranging from mold design to embossing and bonding, that describes the fabrication of polystyrene (PS) microfluidic devices with similar cost and time expenditures as PDMS-based devices. Emphasis was placed on creating methods that can compete with PDMS fabrication methods in terms of robustness, complexity and time requirements. To achieve this goal several improvements were made to remove critical bottlenecks in existing PS embossing methods. First, traditional lithography techniques were adapted to fabricate bulk epoxy molds capable of resisting high temperatures and pressures. Second, a method was developed to emboss through-holes in a PS layer, enabling creation of large arrays of independent microfluidic systems on a single device without need to manually create access ports. Third, thermal bonding of PS layers was optimized in order to achieve quality bonding over large arrays of microsystems. The choice of materials and methods were validated for biological function using two different cell-based applications to demonstrate the versatility of our streamlined fabrication process. PMID:21261280

  6. Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices.

    Science.gov (United States)

    Hamad, E M; Bilatto, S E R; Adly, N Y; Correa, D S; Wolfrum, B; Schöning, M J; Offenhäusser, A; Yakushenko, A

    2016-01-07

    Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.

  7. Portable audio electronics for impedance-based measurements in microfluidics

    International Nuclear Information System (INIS)

    Wood, Paul; Sinton, David

    2010-01-01

    We demonstrate the use of audio electronics-based signals to perform on-chip electrochemical measurements. Cell phones and portable music players are examples of consumer electronics that are easily operated and are ubiquitous worldwide. Audio output (play) and input (record) signals are voltage based and contain frequency and amplitude information. A cell phone, laptop soundcard and two compact audio players are compared with respect to frequency response; the laptop soundcard provides the most uniform frequency response, while the cell phone performance is found to be insufficient. The audio signals in the common portable music players and laptop soundcard operate in the range of 20 Hz to 20 kHz and are found to be applicable, as voltage input and output signals, to impedance-based electrochemical measurements in microfluidic systems. Validated impedance-based measurements of concentration (0.1–50 mM), flow rate (2–120 µL min −1 ) and particle detection (32 µm diameter) are demonstrated. The prevailing, lossless, wave audio file format is found to be suitable for data transmission to and from external sources, such as a centralized lab, and the cost of all hardware (in addition to audio devices) is ∼10 USD. The utility demonstrated here, in combination with the ubiquitous nature of portable audio electronics, presents new opportunities for impedance-based measurements in portable microfluidic systems. (technical note)

  8. Characterization of the Stiffness of Multiple Particles Trapped by Dielectrophoretic Tweezers in a Microfluidic Device.

    Science.gov (United States)

    Son, Myeonggu; Choi, Seungyeop; Ko, Kwan Hwi; Kim, Min Hyung; Lee, Sei-Young; Key, Jaehong; Yoon, Young-Ro; Park, In Soo; Lee, Sang Woo

    2016-01-26

    Characterization of the stiffness of multiple particles trapped by tweezers-based force spectroscopy is a key step in building simple, high-throughput, and robust systems that can investigate the molecular interactions in a biological process, but the technology to characterize it in a given environment simultaneously is still lacking. We first characterized the stiffness of multiple particles trapped by dielectrophoretic (DEP) tweezers inside a microfluidic device. In this characterization, we developed a method to measure the thermal fluctuations of the trapped multiple particles with DEP tweezers by varying the heights of the particles in the given environment at the same time. Using the data measured in this controlled environment, we extracted the stiffness of the trapped particles and calculated their force. This study not only provides a simple and high-throughput method to measure the trap stiffness of multiple particles inside a microfluidic device using DEP tweezers but also inspires the application of the trapped multiple particles to investigate the dynamics in molecular interactions.

  9. Foil assisted replica molding for fabrication of microfluidic devices and their application in vitro.

    Science.gov (United States)

    Micheal, Issac J; Vidyasagar, Aditya J; Bokara, Kiran Kumar; Mekala, Naveen Kumar; Asthana, Amit; Rao, Ch Mohan

    2014-10-07

    We present a simple, rapid, benchtop, Foil Assisted Rapid Molding (FARM) method for the fabrication of microfluidic devices. This novel technique involves the use of aluminium foil, pen and an X-Y plotter to create semi-circular or plano-concave, shallow microchannels. It is an easy do-it-yourself (DIY) technique for creating a microfluidic device in three simple steps: (1) create a channel design using the CAD software, (2) plot the patterns on aluminium foil and (3) use the reverse of the engraved foil as a mold to create microfluidic devices. In this report, we present a detailed study of the proposed method by varying a range of parameters such as foil thickness, tip material, and tip sizes and by investigating their effect on the creation of channels with varying geometry. Furthermore, we demonstrated the cytocompatibility of these devices in vitro.

  10. Liquid phase solvent bonding of plastic microfluidic devices assisted by retention grooves.

    Science.gov (United States)

    Wan, Alwin M D; Sadri, Amir; Young, Edmond W K

    2015-01-01

    We report a novel method for achieving consistent liquid phase solvent bonding of plastic microfluidic devices via the use of retention grooves at the bonding interface. The grooves are patterned during the regular microfabrication process, and can be placed at the periphery of a device, or surrounding microfluidic features with open ports, where they effectively mitigate solvent evaporation, and thus substantially reduce poor bond coverage. This method is broadly applicable to a variety of plastics and solvents, and produces devices with high bond quality (i.e., coverage, strength, and microfeature fidelity) that are suitable for studies in physics, chemistry, and cell biology at the microscale.

  11. A novel technology: microfluidic devices for microbubble ultrasound contrast agent generation.

    Science.gov (United States)

    Lin, Hangyu; Chen, Junfang; Chen, Chuanpin

    2016-09-01

    Microbubbles are used as ultrasound contrast agents, which enhance ultrasound imaging techniques. In addition, microbubbles currently show promise in disease therapeutics. Microfluidic devices have increased the ability to produce microbubbles with precise size, and high monodispersity compared to microbubbles created using traditional methods. This paper will review several variations in microfluidic device structures used to produce microbubbles as ultrasound contrast agents. Microfluidic device structures include T-junction, and axisymmetric and asymmetric flow-focusing. These devices have made it possible to produce microbubbles that can enter the vascular space; these microbubbles must be less than 10 μm in diameter and have high monodispersity. For different demands of microbubbles production rate, asymmetric flow-focusing devices were divided into individual and integrated devices. In addition, asymmetric flow-focusing devices can produce double layer and multilayer microbubbles loaded with drug or biological components. Details on the mechanisms of both bubble formation and device structures are provided. Finally, microfluidically produced microbubble acoustic responses, microbubble stability, and microbubble use in ultrasound imaging are discussed.

  12. Surface modification of PDMS microfluidic devices by controlled sulfuric acid treatment and the application in chip electrophoresis.

    Science.gov (United States)

    Gitlin, Leonid; Schulze, Philipp; Ohla, Stefan; Bongard, Hans-Josef; Belder, Detlev

    2015-02-01

    Herein, we present a straightforward surface modification technique for PDMS-based microfluidic devices. The method takes advantage of the high reactivity of concentrated sulfuric acid to enhance the surface properties of PDMS bulk material. This results in alteration of the surface morphology and chemical composition that is in-depth characterized by ATR-FTIR, EDX, SEM, and XPS. In comparison to untreated PDMS, modified substrates exhibit a significantly reduced diffusive uptake of small organic molecules while retaining its low electroosmotic properties. This was demonstrated by exposing the channels of a microfluidic device to concentrated rhodamine B solution followed by fluorescence microscopy. The surface modification procedure was used to improve chip-based electrophoretic separations. Separation efficiencies of FITC-labeled amines/amino acids obtained in treated and untreated PDMS-devices as well as in glass chips were compared. We obtained higher efficiencies in H2 SO4 treated PDMS chips compared to untreated ones but lower efficiencies than those obtained in commercial microfluidic glass devices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

    Science.gov (United States)

    Zhu, Jun; Cao, Ying; Wang, Hong; Li, Yigui; Chen, Xiang; Chen, Di

    2013-07-01

    Although microfluidic devices that integrate microfluidic chips with hollow out-of-plane microneedle arrays have many advantages in transdermal drug delivery applications, difficulties exist in their fabrication due to the special three-dimensional structures of hollow out-of-plane microneedles. A new, cost-effective process for the fabrication of a hollow out-of-plane Ni microneedle array is presented. The integration of PDMS microchips with the Ni hollow microneedle array and the properties of microfluidic devices are also presented. The integrated microfluidic devices provide a new approach for transdermal drug delivery.

  14. A 3D printed microfluidic perfusion device for multicellular spheroid cultures.

    Science.gov (United States)

    Ong, Louis Jun Ye; Islam, Anik; DasGupta, Ramanuj; Iyer, Narayanan Gopalakkrishna; Leo, Hwa Liang; Toh, Yi-Chin

    2017-09-11

    The advent of 3D printing technologies promises to make microfluidic organ-on-chip technologies more accessible for the biological research community. To date, hydrogel-encapsulated cells have been successfully incorporated into 3D printed microfluidic devices. However, there is currently no 3D printed microfluidic device that can support multicellular spheroid culture, which facilitates extensive cell-cell contacts important for recapitulating many multicellular functional biological structures. Here, we report a first instance of fabricating a 3D printed microfluidic cell culture device capable of directly immobilizing and maintaining the viability and functionality of 3D multicellular spheroids. We evaluated the feasibility of two common 3D printing technologies i.e. stereolithography (SLA) and PolyJet printing, and found that SLA could prototype a device comprising of cell immobilizing micro-structures that were housed within a microfluidic network with higher fidelity. We have also implemented a pump-free perfusion system, relying on gravity-driven flow to perform medium perfusion in order to reduce the complexity and footprint of the device setup, thereby improving its adaptability into a standard biological laboratory. Finally, we demonstrated the biological performance of the 3D printed device by performing pump-free perfusion cultures of patient-derived parental and metastatic oral squamous cell carcinoma tumor and liver cell (HepG2) spheroids with good cell viability and functionality. This paper presents a proof-of-concept in simplifying and integrating the prototyping and operation of a microfluidic spheroid culture device, which will facilitate its applications in various drug efficacy, metabolism and toxicity studies.

  15. A cell sorting and trapping microfluidic device with an interdigital channel

    Directory of Open Access Journals (Sweden)

    Jing Tu

    2016-12-01

    Full Text Available The growing interest in cell sorting and trapping is driving the demand for high performance technologies. Using labeling techniques or external forces, cells can be identified by a series of methods. However, all of these methods require complicated systems with expensive devices. Based on inherent differences in cellular morphology, cells can be sorted by specific structures in microfluidic devices. The weir filter is a basic and efficient cell sorting and trapping structure. However, in some existing weir devices, because of cell deformability and high flow velocity in gaps, trapped cells may become stuck or even pass through the gaps. Here, we designed and fabricated a microfluidic device with interdigital channels for cell sorting and trapping. The chip consisted of a sheet of silicone elastomer polydimethylsiloxane and a sheet of glass. A square-wave-like weir was designed in the middle of the channel, comprising the interdigital channels. The square-wave pattern extended the weir length by three times with the channel width remaining constant. Compared with a straight weir, this structure exhibited a notably higher trapping capacity. Interdigital channels provided more space to slow down the rate of the pressure decrease, which prevented the cells from becoming stuck in the gaps. Sorting a mixture K562 and blood cells to trap cells demonstrated the efficiency of the chip with the interdigital channel to sort and trap large and less deformable cells. With stable and efficient cell sorting and trapping abilities, the chip with an interdigital channel may be widely applied in scientific research fields.

  16. Fabrication of 3D Microfluidic Devices by Thermal Bonding of Thin Poly(methyl methacrylate) Films

    KAUST Repository

    Perez, Paul

    2012-07-01

    The use of thin-film techniques for the fabrication of microfluidic devices has gained attention over the last decade, particularly for three-dimensional channel structures. The reasons for this include effective use of chip volume, mechanical flexibility, dead volume reduction, enhanced design capabilities, integration of passive elements, and scalability. Several fabrication techniques have been adapted for use on thin films: laser ablation and hot embossing are popular for channel fabrication, and lamination is widely used for channel enclosure. However, none of the previous studies have been able to achieve a strong bond that is reliable under moderate positive pressures. The present work aims to develop a thin-film process that provides design versatility, speed, channel profile homogeneity, and the reliability that others fail to achieve. The three building blocks of the proposed baseline were fifty-micron poly(methyl methacrylate) thin films as substrates, channel patterning by laser ablation, and device assembly by thermal-fusion bonding. Channel fabrication was characterized and tuned to produce the desired dimensions and surface roughness. Thermal bonding was performed using an adapted mechanical testing device and optimized to produce the maximum bonding strength without significant channel deformation. Bonding multilayered devices, incorporating conduction lines, and integrating various types of membranes as passive elements demonstrated the versatility of the process. Finally, this baseline was used to fabricate a droplet generator and a DNA detection chip based on micro-bead agglomeration. It was found that a combination of low laser power and scanning speed produced channel surfaces with better uniformity than those obtained with higher values. In addition, the implemented bonding technique provided the process with the most reliable bond strength reported, so far, for thin-film microfluidics. Overall, the present work proved to be versatile

  17. Printable microfluidic systems using pressure sensitive adhesive material for biosensing devices.

    Science.gov (United States)

    Wang, Xin; Nilsson, David; Norberg, Petronella

    2013-09-01

    In biosensors with a fluid analyte, the integration of a microfluidic system, which guides the analyte into the sensing area, is critical. Quicker and economical ways to build up microfluidic systems will make point of care diagnostics viable. Printing is a low-cost technology that is increasingly used in emerging organic and flexible electronics and biosensors. In this paper, we present printed fluidic systems on flexible substrates made with pressure sensitive adhesive materials. Printable pressure sensitive adhesive materials have been used for making microfluidic systems. Flexible substrates have been used, and two types of adhesive materials, one thermally dried and another UV curable, have been tested. Top sealing layer was laminated directly on top of the printed microfluidic structure. Flow tests were done with deionized water. Flow tests with deionized water show that both adhesive materials are suitable for capillary flow driven fluidic devices. Flow test using water as dielectric material was also done successfully on a printed electrolyte gated organic field effect transistor with an integrated microfluidic system. Due to its ease of process and low cost, printed microfluidic system is believed to find more applications in biosensing devices. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Ligation-based mutation detection and RCA in surface un-modified OSTE+ polymer microfluidic chambers

    DEFF Research Database (Denmark)

    Saharil, Farizah; Ahlford, Annika; Kuhnemund, Malte

    2013-01-01

    For the first time, we demonstrate DNA mutation detection in surface un-modified polymeric microfluidic chambers without suffering from bubble trapping or bubble formation. Microfluidic devices were manufactured in off-stoichiometry thiol-ene epoxy (OSTE+) polymer using an uncomplicated and rapid...... during bio-operation at elevated temperatures. In contrast, PMMA, PDMS and COP microfluidic devices required specific surface treatment....

  19. Microfabrication of plastic-PDMS microfluidic devices using polyimide release layer and selective adhesive bonding

    Science.gov (United States)

    Wang, Shuyu; Yu, Shifeng; Lu, Ming; Zuo, Lei

    2017-05-01

    In this paper, we present an improved method to bond poly(dimethylsiloxane) (PDMS) with polyimide (PI) to develop flexible substrate microfluidic devices. The PI film was separately fabricated on a silicon wafer by spin coating followed by thermal treatment to avoid surface unevenness of the flexible substrate. In this way, we could also integrate flexible substrate into standard micro-electromechanical systems (MEMS) fabrication. Meanwhile, the adhesive epoxy was selectively transferred to the PDMS microfluidic device by a stamp-and-stick method to avoid epoxy clogging the microfluidic channels. To spread out the epoxy evenly on the transferring substrate, we used superhydrophilic vanadium oxide film coated glass as the transferring substrate. After the bonding process, the flexible substrate could easily be peeled off from the rigid substrate. Contact angle measurement was used to characterize the hydrophicity of the vanadium oxide film. X-ray photoelectron spectroscopy analysis was conducted to study the surface of the epoxy. We further evaluated the bonding quality by peeling tests, which showed a maximum bonding strength of 100 kPa. By injecting with black ink, the plastic microfluidic device was confirmed to be well bonded with no leakage for a day under 1 atm. This proposed versatile method could bond the microfluidic device and plastic substrate together and be applied in the fabrication of some biosensors and lab-on-a-chip systems.

  20. CMOS Enabled Microfluidic Systems for Healthcare Based Applications.

    Science.gov (United States)

    Khan, Sherjeel M; Gumus, Abdurrahman; Nassar, Joanna M; Hussain, Muhammad M

    2018-02-27

    With the increased global population, it is more important than ever to expand accessibility to affordable personalized healthcare. In this context, a seamless integration of microfluidic technology for bioanalysis and drug delivery and complementary metal oxide semiconductor (CMOS) technology enabled data-management circuitry is critical. Therefore, here, the fundamentals, integration aspects, and applications of CMOS-enabled microfluidic systems for affordable personalized healthcare systems are presented. Critical components, like sensors, actuators, and their fabrication and packaging, are discussed and reviewed in detail. With the emergence of the Internet-of-Things and the upcoming Internet-of-Everything for a people-process-data-device connected world, now is the time to take CMOS-enabled microfluidics technology to as many people as possible. There is enormous potential for microfluidic technologies in affordable healthcare for everyone, and CMOS technology will play a major role in making that happen. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. CMOS Enabled Microfluidic Systems for Healthcare Based Applications

    KAUST Repository

    Khan, Sherjeel M.

    2018-02-27

    With the increased global population, it is more important than ever to expand accessibility to affordable personalized healthcare. In this context, a seamless integration of microfluidic technology for bioanalysis and drug delivery and complementary metal oxide semiconductor (CMOS) technology enabled data-management circuitry is critical. Therefore, here, the fundamentals, integration aspects, and applications of CMOS-enabled microfluidic systems for affordable personalized healthcare systems are presented. Critical components, like sensors, actuators, and their fabrication and packaging, are discussed and reviewed in detail. With the emergence of the Internet-of-Things and the upcoming Internet-of-Everything for a people-process-data-device connected world, now is the time to take CMOS-enabled microfluidics technology to as many people as possible. There is enormous potential for microfluidic technologies in affordable healthcare for everyone, and CMOS technology will play a major role in making that happen.

  2. Product qualification: a barrier to point-of-care microfluidic-based diagnostics?

    Science.gov (United States)

    Tantra, Ratna; van Heeren, Henne

    2013-06-21

    One of the most exciting applications of microfluidics-based diagnostics is its potential use in next generation point-of-care (POC) devices. Many prototypes are already in existence, but, as of yet, few have achieved commercialisation. In this article, we consider the issue surrounding product qualification as a potential barrier to market success. The study discusses, in the context of POC microfluidics-based diagnostics, what the generic issues are and potential solutions. Our findings underline the need for a community-based effort that is necessary to speed up the product qualification process.

  3. Plasma free reversible and irreversible microfluidic bonding.

    Science.gov (United States)

    Chu, M; Nguyen, T T; Lee, E K; Morival, J L; Khine, M

    2017-01-17

    We demonstrate a facile, plasma free process to fabricate both reversibly and irreversibly sealed microfluidic chips using a PDMS-based adhesive polymer mixture. This is a versatile method that is compatible with current PDMS microfluidics processes. It allows for easier fabrication of multilayer microfluidic devices and is compatible with micropatterning of proteins for cell culturing. When combined with our Shrinky-Dink microfluidic prototyping, complete microfluidic device fabrication can be performed without the need for any capital equipment, making microfluidics accessible to the classroom.

  4. Water-based alkyl ketene dimer ink for user-friendly patterning in paper microfluidics

    NARCIS (Netherlands)

    Hamidon, Nurul Nadiah; Hong, Yumiao; Salentijn, Gert Ij; Verpoorte, Elisabeth

    2018-01-01

    We propose the use of water-based alkyl ketene dimer (AKD) ink for fast and user-friendly patterning of paper microfluidic devices either manually or using an inexpensive XY-plotter. The ink was produced by dissolving hydrophobic AKD in chloroform and emulsifying the solution in water. The

  5. FLASH: A rapid method for prototyping paper-based microfluidic devices‡

    Science.gov (United States)

    Martinez, Andres W.; Phillips, Scott T.; Wiley, Benjamin J.; Gupta, Malancha

    2011-01-01

    This article describes FLASH (Fast Lithographic Activation of Sheets), a rapid method for laboratory prototyping of microfluidic devices in paper. Paper-based microfluidic devices are emerging as a new technology for applications in diagnostics for the developing world, where low cost and simplicity are essential. FLASH is based on photolithography, but requires only a UV lamp and a hotplate; no clean-room or special facilities are required (FLASH patterning can even be performed in sunlight if a UV lamp and hotplate are unavailable). The method provides channels in paper with dimensions as small as 200 μm in width and 70 μm in height; the height is defined by the thickness of the paper. Photomasks for patterning paper-based microfluidic devices can be printed using an ink-jet printer or photocopier, or drawn by hand using a waterproof black pen. FLASH provides a straightforward method for prototyping paper-based microfluidic devices in regions where the technological support for conventional photolithography is not available. PMID:19023478

  6. One-Step Fabrication of a Microfluidic Device with an Integrated Membrane and Embedded Reagents by Multimaterial 3D Printing.

    Science.gov (United States)

    Li, Feng; Smejkal, Petr; Macdonald, Niall P; Guijt, Rosanne M; Breadmore, Michael C

    2017-04-18

    One of the largest impediments in the development of microfluidic-based smart sensing systems is the manufacturability of integrated, complex devices. Here we propose multimaterial 3D printing for the fabrication of such devices in a single step. A microfluidic device containing an integrated porous membrane and embedded liquid reagents was made by 3D printing and applied for the analysis of nitrate in soil. The manufacture of the integrated, sealed device was realized as a single print within 30 min. The body of the device was printed in transparent acrylonitrile butadiene styrene (ABS) and contained a 400 μm wide structure printed from a commercially available composite filament. The composite filament can be turned into a porous material through dissolution of a water-soluble material. Liquid reagents were integrated by briefly pausing the printing before resuming for sealing the device. The devices were evaluated by the determination of nitrate in a soil slurry containing zinc particles for the reduction of nitrate to nitrite using the Griess reagent. Using a consumer digital camera, the linear range of the detector response ranged from 0 to 60 ppm, covering the normal range of nitrate in soil. To ensure that the sealing of the reagent chamber is maintained, aqueous reagents should be avoided. When using the nonaqueous reagent, the multimaterial device containing the Griess reagent could be stored for over 4 days but increased the detection range to 100-500 ppm. Multimaterial 3D printing is a potentially new approach for the manufacture of microfluidic devices with multiple integrated functional components.

  7. Metaphase FISH on a Chip: Miniaturized Microfluidic Device for Fluorescence in situ Hybridization

    Directory of Open Access Journals (Sweden)

    Niels Tommerup

    2010-11-01

    Full Text Available Fluorescence in situ Hybridization (FISH is a major cytogenetic technique for clinical genetic diagnosis of both inherited and acquired chromosomal abnormalities. Although FISH techniques have evolved and are often used together with other cytogenetic methods like CGH, PRINS and PNA-FISH, the process continues to be a manual, labour intensive, expensive and time consuming technique, often taking over 3–5 days, even in dedicated labs. We have developed a novel microFISH device to perform metaphase FISH on a chip which overcomes many shortcomings of the current laboratory protocols. This work also introduces a novel splashing device for preparing metaphase spreads on a microscope glass slide, followed by a rapid adhesive tape-based bonding protocol leading to rapid fabrication of the microFISH device. The microFISH device allows for an optimized metaphase FISH protocol on a chip with over a 20-fold reduction in the reagent volume. This is the first demonstration of metaphase FISH on a microfluidic device and offers a possibility of automation and significant cost reduction of many routine diagnostic tests of genetic anomalies.

  8. Functional patterning of PDMS microfluidic devices using integrated chemo-masks.

    Science.gov (United States)

    Romanowsky, Mark B; Heymann, Michael; Abate, Adam R; Krummel, Amber T; Fraden, Seth; Weitz, David A

    2010-06-21

    Microfluidic devices can be molded easily from PDMS using soft lithography. However, the softness of the resulting microchannels makes it difficult to photolithographically pattern their surface properties, as is needed for applications such as double emulsification. We introduce a new patterning method for PDMS devices, using integrated oxygen reservoirs fabricated simultaneously with the microfluidic channels, which serve as "chemo-masks". Oxygen diffuses through the PDMS to the nearby channel segments and there inhibits functional polymer growth; by placement of the chemo-masks, we thus control the polymerization pattern. This patterning method is simple, scalable, and compatible with a variety of surface chemistries.

  9. QR-on-a-chip: a computer-recognizable micro-pattern engraved microfluidic device for high-throughput image acquisition.

    Science.gov (United States)

    Yun, Kyungwon; Lee, Hyunjae; Bang, Hyunwoo; Jeon, Noo Li

    2016-02-21

    This study proposes a novel way to achieve high-throughput image acquisition based on a computer-recognizable micro-pattern implemented on a microfluidic device. We integrated the QR code, a two-dimensional barcode system, onto the microfluidic device to simplify imaging of multiple ROIs (regions of interest). A standard QR code pattern was modified to arrays of cylindrical structures of polydimethylsiloxane (PDMS). Utilizing the recognition of the micro-pattern, the proposed system enables: (1) device identification, which allows referencing additional information of the device, such as device imaging sequences or the ROIs and (2) composing a coordinate system for an arbitrarily located microfluidic device with respect to the stage. Based on these functionalities, the proposed method performs one-step high-throughput imaging for data acquisition in microfluidic devices without further manual exploration and locating of the desired ROIs. In our experience, the proposed method significantly reduced the time for the preparation of an acquisition. We expect that the method will innovatively improve the prototype device data acquisition and analysis.

  10. A fast and low-cost spray method for prototyping and depositing surface-enhanced Raman scattering arrays on microfluidic paper based device.

    Science.gov (United States)

    Li, Bowei; Zhang, Wei; Chen, Lingxin; Lin, Bingcheng

    2013-08-01

    In this study, a fast, low-cost, and facile spray method was proposed. This method deposits highly sensitive surface-enhanced Raman scattering (SERS) silver nanoparticles (AgNPs) on the paper-microfluidic scheme. The procedures for substrate preparation were studied including different strategies to synthesize AgNPs and the optimization of spray cycles. In addition, the morphologies of the different kinds of paper substrates were characterized by SEM and investigated by their SERS signals. The established method was found to be favorable for obtaining good sensitivity and reproducible results. The RSDs of Raman intensity of randomly analyzing 20 spots on the same paper or different filter papers depositing AgNPs are both below 15%. The SERS enhancement factor is approximately 2 × 10(7) . The whole fabrication is very rapid, robust, and does not require specific instruments. Furthermore, the total cost for 1000 pieces of chip is less than $20. These advantages demonstrated the potential for growing SERS applications in the area of environmental monitoring, food safety, and bioanalysis in the future. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Scintillation Particle Detectors Based on Plastic Optical Fibres and Microfluidics

    CERN Document Server

    Mapelli, Alessandro; Renaud, Philippe

    2011-01-01

    This thesis presents the design, development, and experimental validation of two types of scintillation particle detectors with high spatial resolution. The first one is based on the well established scintillating fibre technology. It will complement the ATLAS (A Toroidal Large ApparatuS) detector at the CERN Large Hadron Collider (LHC). The second detector consists in a microfabricated device used to demonstrate the principle of operation of a novel type of scintillation detector based on microfluidics. The first part of the thesis presents the work performed on a scintillating fibre tracking system for the ATLAS experiment. It will measure the trajectory of protons elastically scattered at very small angles to determine the absolute luminosity of the CERN LHC collider at the ATLAS interaction point. The luminosity of an accelerator characterizes its performance. It is a process-independent parameter that is completely determined by the properties of the colliding beams and it relates the cross section of a ...

  12. Fabrication of a Microfluidic Device with Boron-doped Diamond Electrodes for Electrochemical Analysis

    International Nuclear Information System (INIS)

    Watanabe, Takeshi; Shibano, Shuhei; Maeda, Hideto; Sugitani, Ai; Katayama, Michinobu; Matsumoto, Yoshinori; Einaga, Yasuaki

    2016-01-01

    A prototype microfluidic device using boron-doped diamond (BDD) electrodes patterned on an alumina chip was designed and fabricated. Electrochemical microfluidic devices have advantages in that the amount of sample required is small, the measurement throughput is high, different functions can be integrated on a single device, and they are highly durable. In using the device for the flow injection analysis of oxalic acid, the application of a brief conditioning step ensured that the reproducibility of the current signal was excellent. Furthermore, the fabricated system also performed as a prototype of “elimination-detection flow system”, in which interfering species are eliminated using “elimination electrodes” prior to the species reaching the “detection electrode”. The fabricated device reduced the current due to interfering species by 78%. Designs of devices to improve this efficiency are also discussed.

  13. Roll-to-plate fabrication of microfluidic devices with rheology-modified thiol-ene resins

    International Nuclear Information System (INIS)

    Senkbeil, Silja; Aho, Johanna; Rantanen, Jukka; Lafleur, Josiane P; Kutter, Jörg P; Yde, Leif; Lindvold, Lars R; Stensborg, Jan F

    2016-01-01

    In this paper, the replication possibilities of microfluidic channels by UV-roll-to-plate fabrication were investigated and a study of rheology-modified thiol-ene for the application in such a UV-roll-to-plate setup was conducted. The system allows the manufacture of channels with aspect ratios of 2:1 and a maximal channel depth of 90 μ m as well as the sealing of the finished devices with patterning and sealing speeds of up to 19 m min −1 . By adding fumed silica nanoparticles to the uncured resins, it was possible to alter the rheological behavior of the resin system to fabricate shallow microfluidic channels with 40  ×  95 μ m cross-sectional dimensions. Moreover, deeper (90 μ m) channels can be fabricated with highly viscous resins based on thiol-terminated oligomers. As a demonstration, capillary electrophoresis chips were prepared and tested for a simple separation of two fluorescent dyes. (paper)

  14. Electro-Deformation of Fused Cells in a Microfluidic Array Device

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2016-11-01

    Full Text Available We present a new method of analyzing the deformability of fused cells in a microfluidic array device. Electrical stresses—generated by applying voltages (4–20 V across discrete co-planar microelectrodes along the side walls of a microfluidic channel—have been used to electro-deform fused and unfused stem cells. Under an electro-deformation force induced by applying an alternating current (AC signal, we observed significant electro-deformation phenomena. The experimental results show that the fused stem cells were stiffer than the unfused stem cells at a relatively low voltage (<16 V. However, at a relatively high voltage, the fused stem cells were more easily deformed than were the unfused stem cells. In addition, the electro-deformation process is modeled based on the Maxwell stress tensor and structural mechanics of cells. The theoretical results show that a positive correlation is found between the deformation of the cell and the applied voltage, which is consistent with the experimental results. Combined with a numerical analysis and experimental study, the results showed that the significant difference of the deformation ratio of the fused and unfused cells is not due to their size difference. This demonstrates that some other properties of cell membranes (such as the membrane structure were also changed in the electrofusion process, in addition to the size modification of that process.

  15. Fabrication and Characterization of a Microfluidic Device to Ultrapurify Blood Samples

    KAUST Repository

    Tallerico, Marco

    2015-05-04

    The improvement of blood cell sorting techniques in recent years have attracted the attention of many researchers due to the possible benefits that these methods can lead in biology, regenerative medicine, materials science and therapeutic area. In this work a cell sorting technique based on filtration is described. The separation occurs by means of a microfluidic device, suitably designed, manufactured and tested, that is connected to an external experimental set-up. The fabrication process can be divided in two parts: at first it is described the manufacturing process of a filtering membrane, with holes of specific size that allow the passage of only certain cell types. Following the microfluidic device is fabricated through the mechanical micromilling. The membrane and the microdevice are suitably bonded and tested by means of an external connection with syringe pumps that inject blood samples at specific flow rates. The device is designed to separate blood cells and tumor cells only by using differences in size and shape. In particular during the first experiments red blood cells and platelets are sorted from white blood cells; in the other experiments red blood cells and platelets are separated from white blood cells and tumor cells. The microdevice has proven to be very efficient, in fact a capture efficiency of 99% is achieved. For this reason it could be used in identification and isolation of circulating tumor cells, a very rare cancer cell type whose presence in the bloodstream could be symptom of future solid tumor formation. The various experiments have also demonstrated that tumor cells survive even after the separation treatment, and then the suffered stress during the sorting process does not harm the biological sample.

  16. Organ/body-on-a-chip based on microfluidic technology for drug discovery.

    Science.gov (United States)

    Kimura, Hiroshi; Sakai, Yasuyuki; Fujii, Teruo

    2018-02-01

    Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  17. Micromilling: a method for ultra-rapid prototyping of plastic microfluidic devices.

    Science.gov (United States)

    Guckenberger, David J; de Groot, Theodorus E; Wan, Alwin M D; Beebe, David J; Young, Edmond W K

    2015-06-07

    This tutorial review offers protocols, tips, insight, and considerations for practitioners interested in using micromilling to create microfluidic devices. The objective is to provide a potential user with information to guide them on whether micromilling would fill a specific need within their overall fabrication strategy. Comparisons are made between micromilling and other common fabrication methods for plastics in terms of technical capabilities and cost. The main discussion focuses on "how-to" aspects of micromilling, to enable a user to select proper equipment and tools, and obtain usable microfluidic parts with minimal start-up time and effort. The supplementary information provides more extensive discussion on CNC mill setup, alignment, and programming. We aim to reach an audience with minimal prior experience in milling, but with strong interests in fabrication of microfluidic devices.

  18. Microfluidics & nanotechnology: Towards fully integrated analytical devices for the detection of cancer biomarkers

    KAUST Repository

    Perozziello, Gerardo

    2014-01-01

    In this paper, we describe an innovative modular microfluidic platform allowing filtering, concentration and analysis of peptides from a complex mixture. The platform is composed of a microfluidic filtering device and a superhydrophobic surface integrating surface enhanced Raman scattering (SERS) sensors. The microfluidic device was used to filter specific peptides (MW 1553.73 D) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancers, from albumin (66.5 KD), the most represented protein in human plasma. The filtering process consisted of driving the complex mixture through a porous membrane having a cut-off of 12-14 kD by hydrodynamic flow. The filtered samples coming out of the microfluidic device were subsequently deposited on a superhydrophobic surface formed by micro pillars on top of which nanograins were fabricated. The nanograins coupled to a Raman spectroscopy instrument acted as a SERS sensor and allowed analysis of the filtered sample on top of the surface once it evaporated. By using the presented platform, we demonstrate being able to sort small peptides from bigger proteins and to detect them by using a label-free technique at a resolution down to 0.1 ng μL-1. The combination of microfluidics and nanotechnology to develop the presented microfluidic platform may give rise to a new generation of biosensors capable of detecting low concentration samples from complex mixtures without the need for any sample pretreatment or labelling. The developed devices could have future applications in the field of early diagnosis of severe illnesses, e.g. early cancer detection. This journal is

  19. Fabrication of a hybrid plastic-silicon microfluidic device for high-throughput genotyping

    Science.gov (United States)

    Chartier, Isabelle; Sudor, J.; Fouillet, Yves; Sarrut, N.; Bory, C.; Gruss, A.

    2003-01-01

    The lab-on-a-chip approach has been increasingly present in biological research over the last ten years, high-throughput analyses being one of the promising utilization. The work presented here has consisted in developing an automated genotyping system based on a continuous flow analysis which integrates all the steps of the genotyping process (PCR, purification and sequencing). The genotyping device consists of a disposable hybrid silicon-plastic microfluidic chip, equipped with a permanent external, heating/cooling system, syringe-pumps based injection systems and on-line fluorescence detection. High throughput is obtained by performing the reaction in a continuous flow (1 reaction every 6min per channel) and in parallel (48 channels). We are presenting here the technical solutions developed to fabricate the hybrid silicon-plastic microfluidic device. It includes a polycarbonate substrate having 48 parallel grooves sealed by film lamination techniques to create the channels. Two different solutions for the sealing of the channels are compared in relation to their biocompatibility, fluidic behavior and fabrication process yield. Surface roughness of the surface of the channels is the key point of this step. Silicon fluidic chips are used for thermo-cycled reactions. A specific bonding technique has been developed to bond silicon chips onto the plastic part which ensures alignment and hermetic fluidic connexion. Surface coatings are studied to enhance the PCR biocompatibility and fluidic behavior of the two-phase liquid flow. We then demonstrate continuous operation over more than 20 hours of the component and validate PCR protocol on microliter samples in a continuous flow reaction.

  20. Manufacturing and testing flexible microfluidic devices with optical and electrical detection mechanisms

    NARCIS (Netherlands)

    Ivan, M.G.; Vivet, F.; Meinders, E.R.

    2010-01-01

    Flexible microfluidic devices made of poly(dimethylsiloxane) (PDMS) were manufactured by soft lithography, and tested in detection of ionic species using optical absorption spectroscopy and electrical measurements. PDMS was chosen due to its flexibility and ease of surface modification by exposure

  1. Capillary instability, squeezing, and shearing in head-on microfluidic devices

    NARCIS (Netherlands)

    Shui, Lingling; van den Berg, Albert; Eijkel, Jan C.T.

    2009-01-01

    We investigate two-phase (oil and water) flow in head-on microfluidic devices, which consist of two identical channels as inlets and the "long leg" as a constriction channel leading to a wider outlet section. Over an exceptionally broad range of flow rates of 10(-4)-10 mu l/min in 10-100 mu m

  2. Development of a gel monolithic column polydimethylsiloxane microfluidic device for rapid electrophoresis separation.

    Science.gov (United States)

    Zeng, Hu-Lie; Li, Hai-Fang; Wang, Xu; Lin, Jin-Ming

    2006-03-15

    A beta-cyclodextrin (beta-CD)-bonded gel monolithic column polydimethylsiloxane (PDMS) microfluidic device was developed in a simple and feasible way. Before preparation of gel monolithic column in PDMS microchannel, PDMS surface was activated by UV light to create silanol groups, which is an active molecule to covalently bond 3-(trimethoxysilyl)-propyl methacrylate (Bind-Silane) and seal microfluidic device. By the way, Bind-Silane is a bifunctional molecule to link polyacrylamide (PAA) gel and inner wall of PDMS microchannel covalently. Allyl-beta-CD was used not only as a multifunctional crosslinker in PAA gel to control the size of the pores, but also as a chiral selector for the enantioseparation. The stability, transferring heat and optical characteristic of the microfluidic device were examined. The separation capability of the gel monolithic column was confirmed by the successful separation of fluorescein isothiocyanate (FITC)-labeled arginine (Arg), glutamine acid (Glu), tryptophan (Try), cysteine (Cysteine) and phenylalanine (Phe) in the PDMS microfluidic device less than 100 s at 36 mm effective separation length. A maximum of 2.06 x 10(5) theoretical plates was obtained by the potential strength of 490 V/cm. A pair of FITC-labeled dansyl-D,L-threonine (Dns-Thr) was separated absolutely.

  3. Student-Fabricated Microfluidic Devices as Flow Reactors for Organic and Inorganic Synthesis

    Science.gov (United States)

    Feng, Z. Vivian; Edelman, Kate R.; Swanson, Benjamin P.

    2015-01-01

    Flow synthesis in microfluidic devices has been rapidly adapted in the pharmaceutical industry and in many research laboratories. Yet, the cost of commercial flow reactors is a major factor limiting the dissemination of this technology in the undergraduate curriculum. Here, we present a laboratory activity where students design and fabricate…

  4. Characterization of microfluidic components for low-cost point-of-care devices

    CSIR Research Space (South Africa)

    Hugo, S

    2013-10-01

    Full Text Available This paper presents the characterization of microfluidic components for the realization of low-cost point-of-care diagnostic devices, with focus on full blood count applications. Increasing emphasis is being placed on low-cost point...

  5. Low-Cost Rapid Prototyping of Whole-Glass Microfluidic Devices

    Science.gov (United States)

    Yuen, Po Ki; Goral, Vasiliy N.

    2012-01-01

    A low-cost, straightforward, rapid prototyping of whole-glass microfluidic devices is presented using glass-etching cream that can be easily purchased in local stores. A self-adhered vinyl stencil cut out by a desktop digital craft cutter was used as an etching mask for patterning microstructures in glass using the glass-etching cream. A specific…

  6. The design and fabrication of autonomous polymer-based surface tension-confined microfluidic platforms

    Science.gov (United States)

    Swickrath, Michael J.

    The field of microfluidics, lab-on-a-chip technologies in particular, promises the capacity to automate sophisticated laboratory analyses into a platform that can be implemented by a user with minimal analytical experience. However, the fabrication methods traditionally employed to manufacture microfluidic devices are cost ineffective and time intensive. Consequently, current production techniques render exploiting this technology for clinical application problematic. This work describes an alternative fabrication technique to mitigate the aforementioned problems through surface tension-driven flow. Hydrophilic conduits are patterned on a variety of commodity polymeric substrates. The opposing two-dimensionally patterned devices are brought within close proximity for the fabrication of a parallel plate configured microfluidic device. The microfluidic platforms demonstrate the ability to facilitate spontaneous capillary pumping with a high degree of precision and minimal expenditure of fluid reagent. In particular, several cost-effective fabrication procedures are illustrated as well as the capacity to manipulate fluids within the platforms utilizing volumes less than 20 total microliters. Furthermore, applications are demonstrated within the devices such as enzymatic-catalysis, on-chip urinalysis (i.e. glucose and protein detection), and micromixing; demonstrating the efficacy of the platform to automate fluid transport concomitantly with reaction processes. In addition, preliminary designs and protocols are suggested in the last chapter of this work for surface tension-confined devices capable of performing enzyme-linked immunosorbent assay (ELISA) and fluorescence resonance energy transfer (FRET). Moreover, theoretical aspects of microfluidic flow are explored within this document including the physics of wetting and wetting energetics, factors influencing surface tension (and thereby the system driving force), the conservative level set method coupling two

  7. Preparing mono-dispersed liquid core PDMS microcapsules from thiol–ene–epoxy-tailored flow-focusing microfluidic devices

    DEFF Research Database (Denmark)

    Mazurek, Piotr Stanislaw; Daugaard, Anders Egede; Skolimowski, Maciej

    2015-01-01

    An applied dual-cure system based on thiol–ene and thiol–epoxy “click chemistry” reactions was proved to be an extremely effective and easy to use tool for preparing microfluidic chips, thereby allowing for precise control over material properties and providing the possibility of covalently bonding...... chip wafers. Different thiol–ene–epoxy-based polymer compositions were tested with the help of DSC and ATR FTIR, in order to investigate their physical and chemical properties. Water contact angles were determined, thus verifying the high efficiency and selectivity of the chemical surface modification...... of compositions in relation to high hydrophilicity and hydrophobicity. An obtained microfluidic device was subsequently used in order to produce PDMS microcapsules of very narrow size distribution and which contained various common liquids, such as water and ethanol, as well as an ionic liquid 2...

  8. Paper-based smart microfluidics for education and low-cost diagnostics

    Directory of Open Access Journals (Sweden)

    Suzanne Smith

    2015-11-01

    Full Text Available Current centralised healthcare models pose many challenges, particularly for developing countries such as South Africa, where travel and time costs make it difficult for patients to seek healthcare, even when urgently needed. To address this issue, point-of-care (PoC tests, which are performed at or near the site of clinical care, have gained popularity and are actively being developed. Microfluidic systems, in which small volumes of fluids can be processed, provide an ideal platform on which to develop PoC diagnostic solutions. Specifically, the emerging field of paper-based microfluidics, with advantages such as low-cost, disposability and minimal external equipment requirements, provides unique opportunities for addressing healthcare issues in developing countries. This work explores the field of paper-based microfluidics, with step-by-step instructions on the design, manufacture and testing processes to realise paper-based devices towards diagnostic applications. Paper-based microfluidic and electronic components are presented, as well as the integration of these components to provide smart paper-based devices. This serves as an educational tool, enabling both beginners and experts in the field to fast-track development of unique paper-based solutions towards PoC diagnostics, with emphasis on the South African context, where both the need for and impact of these solutions are great.

  9. Microfluidic device for high-yield pairing and fusion of stem cells with somatic cells

    Science.gov (United States)

    Gel, Murat; Hirano, Kunio; Oana, Hidehiro; Kotera, Hidetoshi; Tada, Takashi; Washizu, Masao

    2011-12-01

    Electro cell fusion has significant potential as a biotechnology tool with applications ranging from antibody production to cellular reprogramming. However due to low fusion efficiency of the conventional electro fusion methodology the true potential of the technique has not been reached. In this paper, we report a new method which takes cell fusion efficiency two orders magnitude higher than the conventional electro fusion method. The new method, based on one-toone pairing, fusion and selection of fused cells was developed using a microfabricated device. The device was composed of two microfluidic channels, a micro slit array and a petri dish integrated with electrodes. The electrodes positioned in each channel were used to generate electric field lines concentrating in the micro slits. Cells were introduced into channels and brought in to contact through the micro slit array using dielectrophoresis. The cells in contact were fused by applying a DC pulse to electrodes. As the electric field lines were concentrated at the micro slits the membrane potential was induced only at the vicinity of the micro slits, namely only at the cell-cell contact point. This mechanism assured the minimum damage to cells in the fusion as well as the ability to control the strength and location of induced membrane potential. We introduced mouse embryonic stem cells and mouse embryonic fibroblasts to the microfluidic channels and demonstrated high-yield fusion (> 80%). Post-fusion study showed the method can generate viable hybrids of stem cells and embryonic fibroblasts. Multinucleated hybrid cells adhering on the chip surface were routinely obtained by using this method and on-chip culturing.

  10. Identification of microfluidic two-phase flow patterns in lab-on-chip devices.

    Science.gov (United States)

    Yang, Zhaochu; Dong, Tao; Halvorsen, Einar

    2014-01-01

    This work describes a capacitive sensor for identification of microfluidic two-phase flow in lab-on-chip devices. With interdigital electrodes and thin insulation layer utilized, this sensor is capable of being integrated with the microsystems easily. Transducing principle and design considerations are presented with respect to the microfluidic gas/liquid flow patterns. Numerical simulation results verify the operational principle. And the factors affecting the performance of the sensor are discussed. Besides, a feasible process flow for the fabrication is also proposed.

  11. In situ fabrication of macroporous polymer networks within microfluidic devices by living radical photopolymerization and leaching.

    Science.gov (United States)

    Simms, Helen M; Brotherton, Christopher M; Good, Brian T; Davis, Robert H; Anseth, Kristi S; Bowman, Christopher N

    2005-02-01

    Novel fabrication techniques and polymer systems are being explored to enable mass production of low cost microfluidic devices. In this contribution we discuss a new fabrication scheme for making microfluidic devices containing porous polymer components in situ. Contact lithography, a living radical photopolymer (LRPP) system and salt leaching were used to fabricate multilayer microfluidic devices rapidly with various channel geometries and covalently attached porous polymer plugs made of various photopolymerizable substrates. LRPP systems offer the advantages of covalent attachment of microfluidic device layers and facile surface modification via grafting. Several applications of the porous plugs are also explored, including a static mixer, a high surface area-to-volume reactor and a rapidly responding hydrogel valve. Quantitative and qualitative data show an increase in mixing of a fluorescein and a water stream for channels containing porous plugs relative to channels with no porous plugs. Confocal laser scanning microscopy images demonstrate the ability to graft a functional material onto porous plug surfaces. A reaction was carried out on the grafted pore surfaces, which resulted in fluorescent labelling of the grafted material throughout the pores of the plug. Homogenous fluorescence throughout the depth of the porous plug and along pore surfaces indicated that the porous plugs were surface modified by grafting and that reactions can be carried out on the pore surfaces. Finally, porous hydrogel valves were fabricated which swelled in response to contact with various pH solutions. Results indicate that a porous hydrogel valve will swell and close more rapidly than other valve geometries made with the same polymer formulation. The LRPP-salt leaching method provides a means for rapidly incorporating porous polymer components into microfluidic devices, which can be utilized for a variety of pertinent applications upon appropriate selection of porous plug

  12. Single cell analysis of yeast replicative aging using a new generation of microfluidic device.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available A major limitation to yeast aging study has been the inability to track mother cells and observe molecular markers during the aging process. The traditional lifespan assay relies on manual micro-manipulation to remove daughter cells from the mother, which is laborious, time consuming, and does not allow long term tracking with high resolution microscopy. Recently, we have developed a microfluidic system capable of retaining mother cells in the microfluidic chambers while removing daughter cells automatically, making it possible to observe fluorescent reporters in single cells throughout their lifespan. Here we report the development of a new generation of microfluidic device that overcomes several limitations of the previous system, making it easier to fabricate and operate, and allowing functions not possible with the previous design. The basic unit of the device consists of microfluidic channels with pensile columns that can physically trap the mother cells while allowing the removal of daughter cells automatically by the flow of the fresh media. The whole microfluidic device contains multiple independent units operating in parallel, allowing simultaneous analysis of multiple strains. Using this system, we have reproduced the lifespan curves for the known long and short-lived mutants, demonstrating the power of the device for automated lifespan measurement. Following fluorescent reporters in single mother cells throughout their lifespan, we discovered a surprising change of expression of the translation elongation factor TEF2 during aging, suggesting altered translational control in aged mother cells. Utilizing the capability of the new device to trap mother-daughter pairs, we analyzed mother-daughter inheritance and found age dependent asymmetric partitioning of a general stress response reporter between mother and daughter cells.

  13. Continuous separation of multiple size microparticles using alternating current dielectrophoresis in microfluidic device with acupuncture needle electrodes

    Science.gov (United States)

    Tao, Ye; Ren, Yukun; Yan, Hui; Jiang, Hongyuan

    2016-03-01

    The need to continuously separate multiple microparticles is required for the recent development of lab-on-chip technology. Dielectrophoresis(DEP)-based separation device is extensively used in kinds of microfluidic applications. However, such conventional DEP-based device is relatively complicated and difficult for fabrication. A concise microfluidic device is presented for effective continuous separation of multiple size particle mixtures. A pair of acupuncture needle electrodes are creatively employed and embedded in a PDMS(poly-dimethylsiloxane) hurdle for generating non-uniform electric field thereby achieving a continuous DEP separation. The separation mechanism is that the incoming particle samples with different sizes experience different negative DEP(nDEP) forces and then they can be transported into different downstream outlets. The DEP characterizations of particles are calculated, and their trajectories are numerically predicted by considering the combined action of the incoming laminar flow and the nDEP force field for guiding the separation experiments. The device performance is verified by successfully separating a three-sized particle mixture, including polystyrene microspheres with diameters of 3 μm, 10 μm and 25 μm. The separation purity is below 70% when the flow rate ratio is less than 3.5 or more than 5.1, while the separation purity can be up to more than 90% when the flow rate ratio is between 3.5 and 5.1 and meanwhile ensure the voltage output falls in between 120 V and 150 V. Such simple DEP-based separation device has extensive applications in future microfluidic systems.

  14. Photoinitiated grafting of porous polymer monoliths and thermoplastic polymers for microfluidic devices

    Science.gov (United States)

    Frechet, Jean M. J. [Oakland, CA; Svec, Frantisek [Alameda, CA; Rohr, Thomas [Leiden, NL

    2008-10-07

    A microfluidic device preferably made of a thermoplastic polymer that includes a channel or a multiplicity of channels whose surfaces are modified by photografting. The device further includes a porous polymer monolith prepared via UV initiated polymerization within the channel, and functionalization of the pore surface of the monolith using photografting. Processes for making such surface modifications of thermoplastic polymers and porous polymer monoliths are set forth.

  15. Chiral separation of FITC-labeled amino acids with gel electrochromatography using a polydimethylsiloxane microfluidic device.

    Science.gov (United States)

    Zeng, Hu-Lie; Li, Haifang; Wang, Xu; Lin, Jin-Ming

    2007-01-01

    A chiral separation model of gel electrochromatography in a polydimethylsiloxane (PDMS) microfluidic device for amino acids (AAs) is presented. Six pairs of fluorescein isothiocyanate (FITC)-labeled dansyl amino acids (Dns-AAs) were separated in a 36-mm effectual separation channel in less than 120 sec, with resolutions all above 0.96. This highly efficient PDMS chiral microfluidic chip was prepared by inserting the mixture solution of monomers, crosslinkers, and radical initiation into the microchannel via syringe. Specifically, allyl-gamma-cyclodextrin (CD) as a chiral selector and crosslinker was bonded in gamma-CD-bonded polyacrylamide (PAA) gel, which was the separation media, and was immobilized in a PDMS microchannel through the stable linkage of 3-(trimethoxysilyl)-propyl methacrylate (Bind-Silane, Sigma, St. Louis, MO, U.S.A.). The preparation not only permitted the prompt chiral separation of AAs, but also extended application of the PDMS microfluidic device by restraining its hydrophobicity through the PAA gel monolithic column. Furthermore, the longevity of the PDMS microfluidic device was prolonged significantly. This can also be a powerful way to develop a rapid and efficient bioanalysis method and portable analytical apparatus.

  16. Droplet-based microfluidic washing module for magnetic particle-based assays.

    Science.gov (United States)

    Lee, Hun; Xu, Linfeng; Oh, Kwang W

    2014-07-01

    In this paper, we propose a continuous flow droplet-based microfluidic platform for magnetic particle-based assays by employing in-droplet washing. The droplet-based washing was implemented by traversing functionalized magnetic particles across a laterally merged droplet from one side (containing sample and reagent) to the other (containing buffer) by an external magnetic field. Consequently, the magnetic particles were extracted to a parallel-synchronized train of washing buffer droplets, and unbound reagents were left in an original train of sample droplets. To realize the droplet-based washing function, the following four procedures were sequentially carried in a droplet-based microfluidic device: parallel synchronization of two trains of droplets by using a ladder-like channel network; lateral electrocoalescence by an electric field; magnetic particle manipulation by a magnetic field; and asymmetrical splitting of merged droplets. For the stable droplet synchronization and electrocoalescence, we optimized droplet generation conditions by varying the flow rate ratio (or droplet size). Image analysis was carried out to determine the fluorescent intensity of reagents before and after the washing step. As a result, the unbound reagents in sample droplets were significantly removed by more than a factor of 25 in the single washing step, while the magnetic particles were successfully extracted into washing buffer droplets. As a proof-of-principle, we demonstrate a magnetic particle-based immunoassay with streptavidin-coated magnetic particles and fluorescently labelled biotin in the proposed continuous flow droplet-based microfluidic platform.

  17. Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip.

    Science.gov (United States)

    Zhang, Jie; Wei, Xiaofeng; Zeng, Rui; Xu, Feng; Li, XiuJun

    2017-06-01

    Microfluidic lab-on-a-chip provides a new platform with unique advantages to mimic complex physiological microenvironments in vivo and has been increasingly exploited to stem cell research. In this review, we highlight recent advances of microfluidic devices for stem cell culture and differentiation toward the development of organ-on-a-chip, especially with an emphasis on vital innovations within the last 2 years. Various aspects for improving on-chip stem-cell culture and differentiation, particularly toward organ-on-a-chip, are discussed, along with microenvironment control, surface modification, extracellular scaffolds, high throughput and stimuli. The combination of microfluidic technologies and stem cells hold great potential toward versatile systems of 'organ-on-a-chip' as desired. Adapted with permission from [1-8].

  18. Magnetic optical sensor particles: a flexible analytical tool for microfluidic devices.

    Science.gov (United States)

    Ungerböck, Birgit; Fellinger, Siegfried; Sulzer, Philipp; Abel, Tobias; Mayr, Torsten

    2014-05-21

    In this study we evaluate magnetic optical sensor particles (MOSePs) with incorporated sensing functionalities regarding their applicability in microfluidic devices. MOSePs can be separated from the surrounding solution to form in situ sensor spots within microfluidic channels, while read-out is accomplished outside the chip. These magnetic sensor spots exhibit benefits of sensor layers (high brightness and convenient usage) combined with the advantages of dispersed sensor particles (ease of integration). The accumulation characteristics of MOSePs with different diameters were investigated as well as the in situ sensor spot stability at varying flow rates. Magnetic sensor spots were stable at flow rates specific to microfluidic applications. Furthermore, MOSePs were optimized regarding fiber optic and imaging read-out systems, and different referencing schemes were critically discussed on the example of oxygen sensors. While the fiber optic sensing system delivered precise and accurate results for measurement in microfluidic channels, limitations due to analyte consumption were found for microscopic oxygen imaging. A compensation strategy is provided, which utilizes simple pre-conditioning by exposure to light. Finally, new application possibilities were addressed, being enabled by the use of MOSePs. They can be used for microscopic oxygen imaging in any chip with optically transparent covers, can serve as flexible sensor spots to monitor enzymatic activity or can be applied to form fixed sensor spots inside microfluidic structures, which would be inaccessible to integration of sensor layers.

  19. Getting started with open-hardware: development and control of microfluidic devices.

    Science.gov (United States)

    da Costa, Eric Tavares; Mora, Maria F; Willis, Peter A; do Lago, Claudimir L; Jiao, Hong; Garcia, Carlos D

    2014-08-01

    Understanding basic concepts of electronics and computer programming allows researchers to get the most out of the equipment found in their laboratories. Although a number of platforms have been specifically designed for the general public and are supported by a vast array of on-line tutorials, this subject is not normally included in university chemistry curricula. Aiming to provide the basic concepts of hardware and software, this article is focused on the design and use of a simple module to control a series of PDMS-based valves. The module is based on a low-cost microprocessor (Teensy) and open-source software (Arduino). The microvalves were fabricated using thin sheets of PDMS and patterned using CO2 laser engraving, providing a simple and efficient way to fabricate devices without the traditional photolithographic process or facilities. Synchronization of valve control enabled the development of two simple devices to perform injection (1.6 ± 0.4 μL/stroke) and mixing of different solutions. Furthermore, a practical demonstration of the utility of this system for microscale chemical sample handling and analysis was achieved performing an on-chip acid-base titration, followed by conductivity detection with an open-source low-cost detection system. Overall, the system provided a very reproducible (98%) platform to perform fluid delivery at the microfluidic scale. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

    Directory of Open Access Journals (Sweden)

    Maiwald Thomas

    2009-10-01

    Full Text Available Abstract Background Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. Results We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. Conclusion We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability

  1. NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae.

    Directory of Open Access Journals (Sweden)

    Chunxiao Hu

    Full Text Available Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.

  2. A simple, disposable microfluidic device for rapid protein concentration and purification via direct-printing.

    Science.gov (United States)

    Yu, Hui; Lu, Yu; Zhou, Yi-ge; Wang, Feng-bin; He, Feng-yun; Xia, Xing-hua

    2008-09-01

    A facile and disposable microfluidic device for rapid protein concentration was fabricated by using a direct printing process. Two printed V-shaped microchannels in mirror image orientation were separated by a 100 mum wide toner gap. When a high electric field was applied across the two channels, nanofissures were formed by electric breakdown at the junction toner gap. This microfluidic device with nanofissures was used as a concentrator for protein. Negatively charged proteins were observed to concentrate at the anode side of the nanofissures upon application of an electric field across this junction. Using this device, about 10(3)-10(5)-fold protein concentration was achieved within 10 min. Systematic investigation showed that the concentration mechanism could be explained by the ion exclusion-enrichment effect of the nanofissures. In addition, the present microchip device integrated both functions of concentration and purification were confirmed. This simple on chip protein preconcentration and purification device could be a disposable sample preparation component in printed microfluidic systems used for practical biochemical assays.

  3. 3-D LTCC microfluidic device as a tool for studying nanoprecipitation

    Science.gov (United States)

    Schianti, J. N.; Cerize, N. P. N.; Oliveira, A. M.; Derenzo, S.; Góngora-Rubio, M. R.

    2013-03-01

    Nanoparticles have been used to improve the properties of many cosmetic products, mainly the sunscreens materials using nanoencapsulation or nanosuspensions, improving the contact with active molecules, enhancing the sun protection effect and facilitating formulations in industrial products. Microfluidic devices offer an important possibility in producing nanoparticles in a simple way, in one step bottom up technique, continuum process with low polidispersivity, low consumption of reagents and additives. In this work, we microfabricated a 3-D LTCC microfluidic device to study the nanoprecipitation of Benzophenone-3, used as a sunscreen in pharmaceutical products. It was observed that some parameters influence the particle size related to the total fluid flow on device, the ratio between phases, and the Benzophenone-3 initial concentration. The influence of applied voltages on particle sizes was tested also. For the processing, a high voltage was applied in a Kovar tube inserted in the 3D device. The use of microfluidic device resulted in particles with 100 up to 800 nm of size, with polispersivity index below 0.3 and offering an interesting way to obtain nanoparticles. These studies are still ongoing, but early results indicate the possibility of obtaining B-3 nanostructured material.

  4. Comparison of Pectin Hydrogel Collection Methods in Microfluidic Device

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chaeyeon; Park, Ki-Su; Kang, Sung-Min; Kim, Jongmin; Song, YoungShin; Lee, Chang-Soo [Chungnam National University, Daejeon (Korea, Republic of)

    2015-12-15

    This study investigated the effect of different collection methods on physical properties of pectin hydrogels in microfluidic synthetic approach. The pectin hydrogels were simply produced by the incorporation of calcium ions dissolved in continuous mineral oil. Then, different collection methods, pipetting, tubing, and settling, for harvesting pectin hydrogels were applied. The settling method showed most uniform and monodispersed hydrogels. In the case of settling, a coefficient of variation was 3.46 which was lower than pipetting method (18.60) and tubing method (14.76). Under the settling method, we could control the size of hydrogels, ranging from 30 μm to 180 μm, by simple manipulation of the viscosity of pectin and volumetric flow rate of dispersed and continuous phase. Finally, according to the characteristics of simple encapsulation of biological materials, we envision that the pectin hydrogels can be applied to drug delivery, food, and biocompatible materials.

  5. Flow field effect transistors with polarisable interface for EOF tunable microfluidic separation devices.

    Science.gov (United States)

    Plecis, A; Tazid, J; Pallandre, A; Martinhon, P; Deslouis, C; Chen, Y; Haghiri-Gosnet, A M

    2010-05-21

    A method is proposed to control the zeta potential in microchannels using electrically polarisable interfaces in direct contact with the electrolyte. The approach is based on the use of conducting layers exhibiting minimal electrochemical reactions with aqueous electrolytes but a large potential window (typically from -2 V to +2 V) enabling tuning their zeta potential without detrimental faradic reactions. SiC, Al and CN(x) interfaces were deposited on glass surfaces and then integrated into glass-PDMS-glass devices. The effect of the zeta potential control was monitored by measuring the electro-osmotic flow using a microfluidic Wheatstone Bridge. The experimental results are in good agreement with theoretical predictions based on a one dimensional modeling. The electro-osmotic flow control obtained at high pH values suggests that it should be possible to use such devices as Polarisable Interface Flow-Field Effect Transistors (PI-FFETs) to overcome the difficulties met with conventional metal-isolator-electrolyte systems (MIE-FFETs) for electrokinetic separation applications.

  6. Comparison of Chip Inlet Geometry in Microfluidic Devices for Cell Studies

    Directory of Open Access Journals (Sweden)

    Yung-Shin Sun

    2016-06-01

    Full Text Available Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading inlet and the parallel (in-line inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies.

  7. Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

    Science.gov (United States)

    Pearce, J M; Anzalone, N C; Heldt, C L

    2016-08-01

    The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs. © 2016 Society for Laboratory Automation and Screening.

  8. Tapered Microfluidic for Continuous Micro-Object Separation Based on Hydrodynamic Principle.

    Science.gov (United States)

    Ahmad, Ida Laila; Ahmad, Mohd Ridzuan; Takeuchi, Masaru; Nakajima, Masahiro; Hasegawa, Yasuhisa

    2017-12-01

    Recent advances in microfluidic technologies have created a demand for a simple and efficient separation intended for various applications such as food industries, biological preparation, and medical diagnostic. In this paper, we report a tapered microfluidic device for passive continuous separation of microparticles by using hydrodynamic separation. By exploiting the hydrodynamic properties of the fluid flow and physical characteristics of micro particles, effective size based separation is demonstrated. The tapered microfluidic device has widening geometries with respect to specific taper angle which amplify the sedimentation effect experienced by particles of different sizes. A mixture of 3-μm and 10-μm polystyrene microbeads are successfully separated using 20° and 25° taper angles. The results obtained are in agreement with three-dimensional finite element simulation conducted using Abaqus 6.12. Moreover, the feasibility of this mechanism for biological separation is demonstrated by using polydisperse samples consists of 3-μm polystyrene microbeads and human epithelial cervical carcinoma (HeLa) cells. 98% of samples purity is recovered at outlet 1 and outlet 3 with flow rate of 0.5-3.0 μl/min. Our device is interesting despite adopting passive separation approach. This method enables straightforward, label-free, and continuous separation of multiparticles in a stand-alone device without the need for bulky apparatus. Therefore, this device may become an enabling technology for point of care diagnosis tools and may hold potential for micrototal analysis system applications.

  9. Chitosan-mediated in situ biomolecule assembly in completely packaged microfluidic devices.

    Science.gov (United States)

    Park, Jung Jin; Luo, Xiaolong; Yi, Hyunmin; Valentine, Theresa M; Payne, Gregory F; Bentley, William E; Ghodssi, Reza; Rubloff, Gary W

    2006-10-01

    We report facile in situ biomolecule assembly at readily addressable sites in microfluidic channels after complete fabrication and packaging of the microfluidic device. Aminopolysaccharide chitosan's pH responsive and chemically reactive properties allow electric signal-guided biomolecule assembly onto conductive inorganic surfaces from the aqueous environment, preserving the activity of the biomolecules. A transparent and nonpermanently packaged device allows consistently leak-free sealing, simple in situ and ex situ examination of the assembly procedures, fluidic input/outputs for transport of aqueous solutions, and electrical ports to guide the assembly onto the patterned gold electrode sites within the channel. Both in situ fluorescence and ex situ profilometer results confirm chitosan-mediated in situ biomolecule assembly, demonstrating a simple approach to direct the assembly of biological components into a completely fabricated device. We believe that this strategy holds significant potential as a simple and generic biomolecule assembly approach for future applications in complex biomolecular or biosensing analyses as well as in sophisticated microfluidic networks as anticipated for future lab-on-a-chip devices.

  10. Maskless fabrication of a microfluidic device with interdigitated electrodes on PCB using laser ablation

    Science.gov (United States)

    Contreras-Saenz, Michael; Hassard, Christian; Vargas-Chacon, Rafael; Gordillo, Jose Luis; Camacho-Leon, Sergio

    2016-03-01

    This paper reports the maskless fabrication of a microfluidic device with interdigitated electrodes (IDE) based on the technology of MicroElectroMechanical Systems on Printed Circuit Board (PCB-MEMS) and laser ablation. The device has flame retardant (FR)-4 resin as substrate, cooper (Cu) as active material and SU-8 polymer as structural material. By adjusting the laser parameters, Cu IDEs and SU-8 microchannels were successfully patterned onto the FR-4 substrate. The respective width, gap and overlap of the IDEs were 50 μm, 25 μm and 500 μm. The respective width, depth and length of the microchannels were 210 μm, 24.6 μm and 6.3 mm. The resolution and repeatability achieved in this approach, along with the low cost of the involved materials and techniques, enable an affordable micromachining platform with rapid fabrication-test cycle to develop active multiphysic microdevices with several applications in the fields of biosensing, cell culture, drug delivery, transport and sorting of molecules, among others.

  11. A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

    Directory of Open Access Journals (Sweden)

    Xinyan Zhao

    2013-12-01

    Full Text Available A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+, zinc (Zn2+, potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety.

  12. From Lateral Flow Devices to a Novel Nano-Color Microfluidic Assay

    Directory of Open Access Journals (Sweden)

    Thomas Schalkhammer

    2009-07-01

    Full Text Available Improving the performance of traditional diagnostic lateral flow assays combined with new manufacturing technologies is a primary goal in the research and development plans of diagnostic companies. Taking into consideration the components of lateral flow diagnostic test kits; innovation can include modification of labels, materials and device design. In recent years, Resonance-Enhanced Absorption (REA of metal nano-particles has shown excellent applicability in bio-sensing for the detection of a variety of bio-molecular binding interactions. In a novel approach, we have now integrated REA-assays in a diagnostic microfluidic setup thus resolving the bottleneck of long incubation times inherent in previously existing REA-assays and simultaneously integrated automated fabrication techniques for diagnostics manufacture. Due to the roller-coating based technology and chemical resistance, we used PET-co-polyester as a substrate and a CO2 laser ablation system as a fast, highly precise and contactless alternative to classical micro-milling. It was possible to detect biological binding within three minutes – visible to the eye as colored text readout within the REA-fluidic device. A two-minute in-situ silver enhancement was able to enhance the resonant color additionally, if required.

  13. Papers Based Electrochemical Biosensors: From Test Strips to Paper-Based Microfluidics

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bingwen; Du, Dan; Hua, Xin; Yu, Xiao-Ying; Lin, Yuehe

    2014-05-08

    Papers based biosensors such as lateral flow test strips and paper-based microfluidic devices (or paperfluidics) are inexpensive, rapid, flexible, and easy-to-use analytical tools. An apparent trend in their detection is to interpret sensing results from qualitative assessment to quantitative determination. Electrochemical detection plays an important role in quantification. This review focuses on electrochemical (EC) detection enabled biosensors. The first part provides detailed examples in paper test strips. The second part gives an overview of paperfluidics engaging EC detections. The outlook and recommendation of future directions of EC enabled biosensors are discussed in the end.

  14. Soft Lithographic Procedure for Producing Plastic Microfluidic Devices with View-ports Transparent to Visible and Infrared Light.

    Science.gov (United States)

    Suryana, Mona; Shanmugarajah, Jegan V; Maniam, Sivakumar M; Grenci, Gianluca

    2017-08-17

    Infrared (IR) spectro-microscopy of living biological samples is hampered by the absorption of water in the mid-IR range and by the lack of suitable microfluidic devices. Here, a protocol for the fabrication of plastic microfluidic devices is demonstrated, where soft lithographic techniques are used to embed transparent Calcium Fluoride (CaF2) view-ports in connection with observation chamber(s). The method is based on a replica casting approach, where a polydimethylsiloxane (PDMS) mold is produced through standard lithographic procedures and then used as the template to produce a plastic device. The plastic device features ultraviolet/visible/infrared (UV/Vis/IR) -transparent windows made of CaF2 to allow for direct observation with visible and IR light. The advantages of the proposed method include: a reduced need for accessing a clean room micro-fabrication facility, multiple view-ports, an easy and versatile connection to an external pumping system through the plastic body, flexibility of the design, e.g., open/closed channels configuration, and the possibility to add sophisticated features such as nanoporous membranes.

  15. Integrated microfluidic device for single-cell trapping and spectroscopy

    KAUST Repository

    Liberale, Carlo

    2013-02-13

    Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

  16. Topographic structures and chromatographic supports in microfluidic separation devices

    NARCIS (Netherlands)

    de Pra, M.; Kok, W.Th.; Schoenmakers, P.J.

    2008-01-01

    A review is given of the literature on the design, development and use of micromachined devices for separations in the liquid phase. The emphasis is on those devices that offer more than just an empty channel for, e.g., electrophoretic separation. Topographic structures have been incorporated in the

  17. Tissue culture on a chip: Developmental biology applications of self-organized capillary networks in microfluidic devices.

    Science.gov (United States)

    Miura, Takashi; Yokokawa, Ryuji

    2016-08-01

    Organ culture systems are used to elucidate the mechanisms of pattern formation in developmental biology. Various organ culture techniques have been used, but the lack of microcirculation in such cultures impedes the long-term maintenance of larger tissues. Recent advances in microfluidic devices now enable us to utilize self-organized perfusable capillary networks in organ cultures. In this review, we will overview past approaches to organ culture and current technical advances in microfluidic devices, and discuss possible applications of microfluidics towards the study of developmental biology. © 2016 Japanese Society of Developmental Biologists.

  18. High throughput production of single core double emulsions in a parallelized microfluidic device.

    Science.gov (United States)

    Romanowsky, Mark B; Abate, Adam R; Rotem, Assaf; Holtze, Christian; Weitz, David A

    2012-02-21

    Double emulsions are useful templates for microcapsules and complex particles, but no method yet exists for making double emulsions with both high uniformity and high throughput. We present a parallel numbering-up design for microfluidic double emulsion devices, which combines the excellent control of microfluidics with throughput suitable for mass production. We demonstrate the design with devices incorporating up to 15 dropmaker units in a two-dimensional or three-dimensional array, producing single-core double emulsion drops at rates over 1 kg day(-1) and with diameter variation less than 6%. This design provides a route to integrating hundreds of dropmakers or more in a single chip, facilitating industrial-scale production rates of many tons per year.

  19. Manufacturing and testing flexible microfluidic devices with optical and electrical detection mechanisms

    OpenAIRE

    Ivan, M.G.; Vivet, F.; Meinders, E.R.

    2010-01-01

    Flexible microfluidic devices made of poly(dimethylsiloxane) (PDMS) were manufactured by soft lithography, and tested in detection of ionic species using optical absorption spectroscopy and electrical measurements. PDMS was chosen due to its flexibility and ease of surface modification by exposure to plasma and UV treatment, its transparency in UV-Vis regions of the light spectrum, and biocompatibility. The dual-detection mechanism allows the user more freedom in choosing the detection tool, ...

  20. Self-Propelled Motion of Monodisperse Underwater Oil Droplets Formed by a Microfluidic Device.

    Science.gov (United States)

    Ueno, Naoko; Banno, Taisuke; Asami, Arisa; Kazayama, Yuki; Morimoto, Yuya; Osaki, Toshihisa; Takeuchi, Shoji; Kitahata, Hiroyuki; Toyota, Taro

    2017-06-06

    We evaluated the speed profile of self-propelled underwater oil droplets comprising a hydrophobic aldehyde derivative in terms of their diameter and the surrounding surfactant concentration using a microfluidic device. We found that the speed of the oil droplets is dependent on not only the surfactant concentration but also the droplet size in a certain range of the surfactant concentration. This tendency is interpreted in terms of combination of the oil and surfactant affording spontaneous emulsification in addition to the Marangoni effect.

  1. An integrated, multiparametric flow cytometry chip using “microfluidic drifting” based three-dimensional hydrodynamic focusing

    Science.gov (United States)

    Mao, Xiaole; Nawaz, Ahmad Ahsan; Lin, Sz-Chin Steven; Lapsley, Michael Ian; Zhao, Yanhui; McCoy, J. Philip; El-Deiry, Wafik S.; Huang, Tony Jun

    2012-01-01

    In this work, we demonstrate an integrated, single-layer, miniature flow cytometry device that is capable of multi-parametric particle analysis. The device integrates both particle focusing and detection components on-chip, including a “microfluidic drifting” based three-dimensional (3D) hydrodynamic focusing component and a series of optical fibers integrated into the microfluidic architecture to facilitate on-chip detection. With this design, multiple optical signals (i.e., forward scatter, side scatter, and fluorescence) from individual particles can be simultaneously detected. Experimental results indicate that the performance of our flow cytometry chip is comparable to its bulky, expensive desktop counterpart. The integration of on-chip 3D particle focusing with on-chip multi-parametric optical detection in a single-layer, mass-producible microfluidic device presents a major step towards low-cost flow cytometry chips for point-of-care clinical diagnostics. PMID:22567082

  2. Mapping the Salinity Gradient in a Microfluidic Device with Schlieren Imaging

    Directory of Open Access Journals (Sweden)

    Chen-li Sun

    2015-05-01

    Full Text Available This work presents the use of the schlieren imaging to quantify the salinity gradients in a microfluidic device. By partially blocking the back focal plane of the objective lens, the schlieren microscope produces an image with patterns that correspond to spatial derivative of refractive index in the specimen. Since salinity variation leads to change in refractive index, the fluid mixing of an aqueous salt solution of a known concentration and water in a T-microchannel is used to establish the relation between salinity gradients and grayscale readouts. This relation is then employed to map the salinity gradients in the target microfluidic device from the grayscale readouts of the corresponding micro-schlieren image. For saline solution with salinity close to that of the seawater, the grayscale readouts vary linearly with the salinity gradient, and the regression line is independent of the flow condition and the salinity of the injected solution. It is shown that the schlieren technique is well suited to quantify the salinity gradients in microfluidic devices, for it provides a spatially resolved, non-invasive, full-field measurement.

  3. A microfluidic device integrating plasmonic nanodevices for Raman spectroscopy analysis on trapped single living cells

    KAUST Repository

    Perozziello, Gerardo

    2013-11-01

    In this work we developed a microfluidic device integrating nanoplasmonic devices combined with fluidic trapping regions. The microfuidic traps allow to capture single cells in areas where plasmonic sensors are placed. In this way it is possible to perform Enhanced Raman analysis on the cell membranes. Moreover, by changing direction of the flux it is possible to change the orientation of the cell in the trap, so that it is possible to analyze different points of the membrane of the same cell. We shows an innovative procedure to fabricate and assembly the microfluidic device which combine photolithography, focused ion beam machining, and hybrid bonding between a polymer substrate and lid of Calcium fluoride. This procedure is compatible with the fabrication of the plasmonic sensors in close proximity of the microfluidic traps. Moreover, the use of Calcium fluoride as lid allows full compatibility with Raman measurements producing negligible Raman background signal and avoids Raman artifacts. Finally, we performed Raman analysis on cells to monitor their oxidative stress under particular non physiological conditions. © 2013 Elsevier B.V. All rights reserved.

  4. Design, fabrication and test of a pneumatically controlled, renewable, microfluidic bead trapping device for sequential injection analysis applications.

    Science.gov (United States)

    Shao, Guocheng; Lu, Donglai; Fu, Zhifeng; Du, Dan; Ozanich, Richard M; Wang, Wanjun; Lin, Yuehe

    2016-01-07

    This paper describes the design, fabrication, and testing of a pneumatically controlled, renewable, microfluidic device for conducting bead-based assays in an automated sequential injection analysis system. The device used a "brick wall"-like pillar array (pillar size: 20 μm length × 50 μm width × 45 μm height) with 5 μm gaps between the pillars serving as the micro filter. The flow channel where bead trapping occurred is 500 μm wide × 75 μm deep. An elastomeric membrane and an air chamber were located underneath the flow channel. By applying pressure to the air chamber, the membrane is deformed and pushed upward against the filter structure. This effectively traps beads larger than 5 μm and creates a "bed" or micro column of beads that can be perfused and washed with liquid samples and reagents. Upon completion of the assay process, the pressure is released and the beads are flushed out from underneath the filter structure to renew the device. Mouse IgG was used as a model analyte to test the feasibility of using the proposed device for immunoassay applications. Resulting microbeads from an on-chip fluorescent immunoassay were individually examined using flow cytometry. The results show that the fluorescence signal intensity distribution is fairly narrow indicating high chemical reaction uniformity among the beads population. Electrochemical on-chip assay was also conducted. A detection limit of 1 ppb was achieved and good device reliability and repeatability were demonstrated. The novel microfluidic-based beads-trapping device thus opens up a new pathway to design micro-bead based immunoassays for various applications.

  5. Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms

    Directory of Open Access Journals (Sweden)

    Piyush Dak

    2016-04-01

    Full Text Available Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with “open” digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

  6. Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

    Science.gov (United States)

    Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A

    2016-04-14

    Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with "open" digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

  7. A microfluidic device providing continuous-flow polymerase chain reaction heating and cooling

    Science.gov (United States)

    Harandi, A.; Farquhar, T.

    2014-11-01

    The objective of this study is to describe a new type of microfluidic device that could be used to manipulate fluid temperature in many microfluidic applications. The key component is a composite material containing a thermally conductive phase placed in a purposeful manner to manipulate heat flow into and out of an embedded microchannel. In actual use, the device is able to vary temperature along a defined flow path with remarkable precision. As a demonstration of capability, a functional prototype was designed and fabricated using four layers of patterned copper laminated between alternating layers of polyimide and acrylic. The key fabrication steps included laser micromachining, acid etching, microchannel formation, and hot lamination. In order to achieve the desired temperature variations along the microchannel, an outer optimization loop and an inner finite element analysis loop were used to iteratively obtain a near-optimal copper pattern. With a minor loss of generality, admissible forms were restricted to comb-like patterns. For a given temperature profile, the pattern was found by refining a starting guess based on a deterministic rubric. Thermal response was measured using fine thermocouples placed at critical locations along the microchannel wall. At most of these points, the agreement between measured and predicted temperatures was within 1 °C, and temperature gradients as high as ±45 °C mm-1 (equivalent to ±90 °C s-1 at 2 μl min-1 flow rate) were obtained within the range of 59-91 °C. The particular profile chosen for case study makes it possible to perform five cycles of continuous-flow polymerase chain reaction (PCR) in less than 15 s, i.e. it entails five successive cycles of cooling from 91 to 59 °C, rapid reheating from 59 to 73 °C, slow reheating from 73 to 76 °C, and a final reheating from 73 to 91 °C, using a resistively heated source at 100 °C at and a thermoelectrically cooled sink at 5 °C.

  8. Numerical simulation of droplet formation regimes and sizes in microfluidic T-junction devices

    Science.gov (United States)

    Nekouei, Mehdi; Vanapalli, Siva

    2014-11-01

    The T-junction geometry has been widely used for producing monodisperse droplets in microfluidic devices. Droplet formation regimes and sizes are expected to depend on a variety of conditions including flow rates, capillary number, channel geometry and viscosity ratio. Experiments have investigated drop production at a T-junction in a narrow control parameter space and developed analytical models for specific operating regimes. In this study, we take advantage of numerical simulations based on volume-of-fluid method to explore this broad parameter space systematically, and contrast our results with prior experimental data. We find our simulations predict well the regimes of squeezing, dripping and jetting. We also observe that our drop size data is in good agreement with three different experimental reports. Although our results match experimental data, the analytical models do not agree with each other since they are based on specific operating conditions. We use numerical simulations to elucidate the missing components in the physics of drop formation at a T-junction, with an attempt to reconcile existing analytical models.

  9. Numerical study on the complete blood cell sorting using particle tracing and dielectrophoresis in a microfluidic device

    Science.gov (United States)

    Ali, Haider; Park, Cheol Woo

    2016-11-01

    In this study, a numerical model of a microfluidic device with particle tracing and dielectrophoresis field-flow fractionation was employed to perform a complete and continuous blood cell sorting. A low voltage was applied to electrodes to separate the red blood cells, white blood cells, and platelets based on their cell size. Blood cell sorting and counting were performed by evaluating the cell trajectories, displacements, residence times, and recovery rates in the device. A novel numerical technique was used to count the number of separated blood cells by estimating the displacement and residence time of the cells in a microfluidic device. For successful blood cell sorting, the value of cells displacement must be approximately equal to or higher than the corresponding maximum streamwise distance. The study also proposed different outlet designs to improve blood cell separation. The basic outlet design resulted in a higher cells recovery rate than the other outlets design. The recovery rate decreased as the number of inlet cells and flow rates increased because of the high particle-particle interactions and collisions with walls. The particle-particle interactions significantly affect blood cell sorting and must therefore be considered in future work.

  10. Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Silvia Lopa

    2018-01-01

    Full Text Available Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects.

  11. A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network.

    Science.gov (United States)

    Jun Kang, Yang; Yeom, Eunseop; Lee, Sang-Joon

    2013-01-01

    Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity

  12. Microfluidic device for rapid solution exchange to study kinetics of cell physiology

    Science.gov (United States)

    Hu, Howard; Honnatti, Meghana; Gillis, Kevin

    2006-11-01

    Exchanging the extracellular solution of the cell rapidly (less than 10ms) is an important requirement in study the kinetics of cell physiology. A microfluidic device is developed to exchange the solution around the cells as they flow through a junction at the intersection of two microfluidic channels. The solution exchange time is measured experimentally by fluorescently labeling the cell surface membranes with a styryl dye, FM1-43 or FM 2-10, and then observing the time course of cell fluorescence decay following the rapid drop in the extracellular concentration of the FM dye that occurs as the cell flows past the fluidic junction. A numerical model is developed to guide the experimental design of microfluidic device. In the model, the motion of a single cell through a fluid junction is simulated and the mixing process of the solutions is solved. The model also includes the kinetics of departitioning of FM dyes from the cell membrane. The departitioning time constants for the FM dyes are determined from fitting the measured data of the cell fluorescence decay. This departitioning kinetics is important as FM dyes are commonly used to label cell membranes for the purpose of measuring the release of neurotransmitter from synaptic vesicles via exocytosis and the subsequent reuptake of vesicular membrane by endocytosis.

  13. Designing and modeling a centrifugal microfluidic device to separate target blood cells

    International Nuclear Information System (INIS)

    Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

    2016-01-01

    The objective of this study is to design a novel and efficient portable lab-on-a-CD (LOCD) microfluidic device for separation of specific cells (target cells) using magnetic beads. In this study the results are shown for neutrophils as target cells. However, other kinds of target cells can be separated in a similar approach. The designed microfluidics can be utilized as a point of care system for neutrophil detection. This microfluidic system employs centrifugal and magnetic forces for separation. After model validation by the experimental data in the literature (that may be used as a design tool for developing centrifugo-magnetophoretic devices), two models are presented for separation of target cells using magnetic beads. The first model consists of one container in the inlet section and two containers in the outlets. Initially, the inlet container is filled with diluted blood sample which is a mixture of red blood cells (RBCs) plus neutrophils which are attached to Magnetic beads. It is shown that by using centrifugal and magnetic forces, this model can separate all neutrophils with recovery factor of ∼100%. In the second model, due to excess of magnetic beads in usual experimental analysis (to ensure that all target cells are attached to them) the geometry is improved by adding a third outlet for these free magnetic beads. It is shown that at angular velocity of 45 rad s −1 , recovery factor of 100% is achievable for RBCs, free magnetic beads and neutrophils as target cells. (paper)

  14. Designing and modeling a centrifugal microfluidic device to separate target blood cells

    Science.gov (United States)

    Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

    2016-03-01

    The objective of this study is to design a novel and efficient portable lab-on-a-CD (LOCD) microfluidic device for separation of specific cells (target cells) using magnetic beads. In this study the results are shown for neutrophils as target cells. However, other kinds of target cells can be separated in a similar approach. The designed microfluidics can be utilized as a point of care system for neutrophil detection. This microfluidic system employs centrifugal and magnetic forces for separation. After model validation by the experimental data in the literature (that may be used as a design tool for developing centrifugo-magnetophoretic devices), two models are presented for separation of target cells using magnetic beads. The first model consists of one container in the inlet section and two containers in the outlets. Initially, the inlet container is filled with diluted blood sample which is a mixture of red blood cells (RBCs) plus neutrophils which are attached to Magnetic beads. It is shown that by using centrifugal and magnetic forces, this model can separate all neutrophils with recovery factor of ~100%. In the second model, due to excess of magnetic beads in usual experimental analysis (to ensure that all target cells are attached to them) the geometry is improved by adding a third outlet for these free magnetic beads. It is shown that at angular velocity of 45 rad s-1, recovery factor of 100% is achievable for RBCs, free magnetic beads and neutrophils as target cells.

  15. Solid-phase extraction microfluidic devices for matrix removal in trace element assay of actinide materials.

    Science.gov (United States)

    Gao, Jun; Manard, Benjamin T; Castro, Alonso; Montoya, Dennis P; Xu, Ning; Chamberlin, Rebecca M

    2017-05-15

    Advances in sample nebulization and injection technology have significantly reduced the volume of solution required for trace impurity analysis in plutonium and uranium materials. Correspondingly, we have designed and tested a novel chip-based microfluidic platform, containing a 100-µL or 20-µL solid-phase microextraction column, packed by centrifugation, which supports nuclear material mass and solution volume reductions of 90% or more compared to standard methods. Quantitative recovery of 28 trace elements in uranium was demonstrated using a UTEVA chromatographic resin column, and trace element recovery from thorium (a surrogate for plutonium) was similarly demonstrated using anion exchange resin AG MP-1. Of nine materials tested, compatibility of polyvinyl chloride (PVC), polypropylene (PP), and polytetrafluoroethylene (PTFE) chips with the strong nitric acid media was highest. The microcolumns can be incorporated into a variety of devices and systems, and can be loaded with other solid-phase resins for trace element assay in high-purity metals. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Jurriaan Huskens

    2011-10-01

    Full Text Available A supramolecular platform based on self-assembled monolayers (SAMs has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP and pyrophosphate, as well as dipicolinic acid (DPA which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with µM and nM detection sensitivity for ATP and DPA, respectively.

  17. Quantitative control of mitochondria transfer between live single cells using a microfluidic device

    Directory of Open Access Journals (Sweden)

    Ken-Ichi Wada

    2017-12-01

    Full Text Available Quantitative control of mitochondria transfer between live cells is a promising approach for genetic manipulation of mitochondrial DNA (mtDNA because single mitochondrion transfer to a mtDNA-less (ρ0 cell potentially leads to homoplasmy of mtDNA. In this paper, we describe a method for quantitative control of mitochondria transfer between live single cells. For this purpose, we fabricated novel microfluidic devices having cell paring structures with a 4.1, 5.6 or 10.0 μm-length microtunnel. When cells were fused through a microtunnel using the Sendai virus envelope-based method, a strictured cytoplasmic connection was achieved with a length corresponding to that of the microtunnel. Elongation of the cytoplasmic connection led to a decrease in mitochondria transfer to the fusion partner. Moreover, some cell pairs that fused through a 10.0 μm-length microtunnel showed single mitochondrion transfer. Fused cells were spontaneously disconnected from each other when they were recovered in a normal culture medium. These results suggest that our cell fusion method can perform quantitative control of mitochondria transfer that includes a single mitochondrion transfer.

  18. An instrument-free, screen-printed paper microfluidic device that enables bio and chemical sensing.

    Science.gov (United States)

    Mohammadi, Saeed; Maeki, Masatoshi; Mohamadi, Reza M; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

    2015-10-07

    This paper describes a simple and instrument-free screen-printing method to fabricate hydrophilic channels by patterning polydimethylsiloxane (PDMS) onto chromatography paper. Clearly recognizable border lines were formed between hydrophilic and hydrophobic areas. The minimum width of the printed channel to deliver an aqueous sample was 600 μm, as obtained by this method. Fabricated microfluidic paper-based analytical devices (μPADs) were tested for several colorimetric assays of pH, glucose, and protein in both buffer and artificial urine samples and results were obtained in less than 30 min. The limits of detection (LODs) for glucose and bovine serum albumin (BSA) were 5 mM and 8 μM, respectively. Furthermore, the pH values of different solutions were visually recognised with the naked eye by using a sensitive ink. Ultimately, it is expected that this PDMS-screen-printing (PSP) methodology for μPADs can be readily translated to other colorimetric detection and hydrophilic channels surrounded by a hydrophobic polymer can be formed to transport fluids toward target zones.

  19. Topology optimization of flexible micro-fluidic devices

    DEFF Research Database (Denmark)

    Kreissl, Sebastian; Pingen, Georg; Evgrafov, Anton

    2010-01-01

    A multi-objective topology optimization formulation for the design of dynamically tunable fluidic devices is presented. The flow is manipulated via external and internal mechanical actuation, leading to elastic deformations of flow channels. The design objectives characterize the performance...... in the undeformed and deformed configurations. The layout of fluid channels is determined by material topology optimization. In addition, the thickness distribution, the distribution of active material for internal actuation, and the support conditions are optimized. The coupled fluid-structure response...

  20. A microfluidic device to establish concentration gradients using reagent density differences.

    Science.gov (United States)

    Kong, Qingjun; Able, Richard A; Dudu, Veronica; Vazquez, Maribel

    2010-12-01

    Microfabrication has become widely utilized to generate controlled microenvironments that establish chemical concentration gradients for a variety of engineering and life science applications. To establish microfluidic flow, the majority of existing devices rely upon additional facilities, equipment, and excessive reagent supplies, which together limit device portability as well as constrain device usage to individuals trained in technological disciplines. The current work presents our laboratory-developed bridged μLane system, which is a stand-alone device that runs via conventional pipette loading and can operate for several days without need of external machinery or additional reagent volumes. The bridged μLane is a two-layer polydimethylsiloxane microfluidic device that is able to establish controlled chemical concentration gradients over time by relying solely upon differences in reagent densities. Fluorescently labeled Dextran was used to validate the design and operation of the bridged μLane by evaluating experimentally measured transport properties within the microsystem in conjunction with numerical simulations and established mathematical transport models. Results demonstrate how the bridged μLane system was used to generate spatial concentration gradients that resulted in an experimentally measured Dextran diffusivity of (0.82 ± 0.01) × 10(-6) cm(2)/s.

  1. A versatile microfluidic device for high throughput production of microparticles and cell microencapsulation.

    Science.gov (United States)

    Akbari, Samin; Pirbodaghi, Tohid; Kamm, Roger D; Hammond, Paula T

    2017-06-13

    Biocompatible microparticles are valuable tools in biomedical research for applications such as drug delivery, cell transplantation therapy, and analytical assays. However, their translation into clinical research and the pharmaceutical industry has been slow due to the lack of techniques that can produce microparticles with controlled physicochemical properties at high throughput. We introduce a robust microfluidic platform for the production of relatively homogeneous microdroplets at a generation frequency of up to 3.1 MHz, which is about three orders of magnitude higher than the production rate of a conventional microfluidic drop maker. We demonstrated the successful implementation of our device for production of biocompatible microparticles with various crosslinking mechanisms and cell microencapsulation with high cell viability.

  2. Drop break-up and pressure measurements in a microfluidic device

    Science.gov (United States)

    Protiere, Suzie; Stone, Howard A.; Weitz, David A.

    2008-11-01

    We study experimentally the flow of an emulsion passing through one or a few constrictions placed in a microfluidic channel. Using a high-speed differential manometer placed in the same device (M. Abkarian et al. PNAS 200:16407104 (2006)) we have measured the dynamic pressure as a drop breaks up when it meets one or several constrictions. We can then study how a global measurement of the pressure drop indicates the sequence of phenomena occurring in the channel (breakup, trapped and squeezed drops etc.). In a separate set of experiments with a microfluidic model of a two-dimensional porous medium through which drops flow we can observe the various phenomena and thus correlate the pressure fluctuations to single events at the pore scale.

  3. Single cell array impedance analysis in a microfluidic device

    Science.gov (United States)

    Altinagac, Emre; Taskin, Selen; Kizil, Huseyin

    2016-10-01

    Impedance analysis of single cells is presented in this paper. Following the separation of a target cell type by dielectrophoresis in our previous work, this paper focuses on capturing the cells as a single array and performing impedance analysis to point out the signature difference between each cell type. Lab-on-a-chip devices having a titanium interdigitated electrode layer on a glass substrate and a PDMS microchannel are fabricated to capture each cell in a single form and perform impedance analysis. HCT116 (homosapiens colon colorectal carcin) and HEK293 (human embryonic kidney) cells are used in our experiments.

  4. Microfluidics and Lab-on-a-Chip Devices

    DEFF Research Database (Denmark)

    Castillo, Jaime

    2015-01-01

    at a slower pace. LOC and microTAS applications have principally been utilized in the biomedical, food and environmental fields. But lately they have also found their place in the synthesis of new chemical compounds and the fabrication of nanostructures. It has become obvious that the LOC and micro......-ups and large pharmaceutical and biomedical companies, is being released and entering the market. This chapter offers an overview of the first events in the history of LOC and microTAS devices, the biggest achievements and the challenges that still need to be overcome in order to accelerate the use...

  5. Approaching near real-time biosensing: microfluidic microsphere based biosensor for real-time analyte detection.

    Science.gov (United States)

    Cohen, Noa; Sabhachandani, Pooja; Golberg, Alexander; Konry, Tania

    2015-04-15

    In this study we describe a simple lab-on-a-chip (LOC) biosensor approach utilizing well mixed microfluidic device and a microsphere-based assay capable of performing near real-time diagnostics of clinically relevant analytes such cytokines and antibodies. We were able to overcome the adsorption kinetics reaction rate-limiting mechanism, which is diffusion-controlled in standard immunoassays, by introducing the microsphere-based assay into well-mixed yet simple microfluidic device with turbulent flow profiles in the reaction regions. The integrated microsphere-based LOC device performs dynamic detection of the analyte in minimal amount of biological specimen by continuously sampling micro-liter volumes of sample per minute to detect dynamic changes in target analyte concentration. Furthermore we developed a mathematical model for the well-mixed reaction to describe the near real time detection mechanism observed in the developed LOC method. To demonstrate the specificity and sensitivity of the developed real time monitoring LOC approach, we applied the device for clinically relevant analytes: Tumor Necrosis Factor (TNF)-α cytokine and its clinically used inhibitor, anti-TNF-α antibody. Based on the reported results herein, the developed LOC device provides continuous sensitive and specific near real-time monitoring method for analytes such as cytokines and antibodies, reduces reagent volumes by nearly three orders of magnitude as well as eliminates the washing steps required by standard immunoassays. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Microfluidic devices for analysis of spatial orientation behaviors in semi-restrained Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Kathryn E McCormick

    Full Text Available This article describes the fabrication and use of microfluidic devices for investigating spatial orientation behaviors in nematode worms (Caenorhabditis elegans. Until now, spatial orientation has been studied in freely moving nematodes in which the frequency and nature of encounters with the gradient are uncontrolled experimental variables. In the new devices, the nematode is held in place by a restraint that aligns the longitudinal axis of the body with the border between two laminar fluid streams, leaving the animal's head and tail free to move. The content of the fluid streams can be manipulated to deliver step gradients in space or time. We demonstrate the utility of the device by identifying previously uncharacterized aspects of the behavioral mechanisms underlying chemotaxis, osmotic avoidance, and thermotaxis in this organism. The new devices are readily adaptable to behavioral and imaging studies involving fluid borne stimuli in a wide range of sensory modalities.

  7. Microfluidic device and method for processing of macromolecules

    DEFF Research Database (Denmark)

    2012-01-01

    . The device further comprises first inlet and outlet channels for filling the reaction channels via the manifolds with one or more macromolecule containers suspended in a first carrier fluid, wherein the first inlet and outlet channels are configured such that a flow established from the first set of inlets...... to the first set of outlets is guided through the reaction channels, and second inlet and outlet channels for feeding an enzymatic reagent to the reaction chamber essentially without displacing the macromolecule containers trapped in the reaction channels, wherein the second set of inlets and outlets...... are configured such that a flow established from the second inlet to the second outlet is guided through at least one of the manifolds and bypasses the reaction channels....

  8. High-throughput rapid-prototyping of low-cost paper-based microfluidics.

    Science.gov (United States)

    Ghaderinezhad, Fariba; Amin, Reza; Temirel, Mikail; Yenilmez, Bekir; Wentworth, Adam; Tasoglu, Savas

    2017-06-15

    Paper-based micro analytical devices offer significant advantages compared to the conventional microfluidic chips including cost-effectiveness, ease of fabrication, and ease of use while preserving critical features including strong capillary action and biological compatibility. In this work, we demonstrate an inexpensive, rapid method for high-throughput fabrication of paper-based microfluidics by patterning hydrophobic barriers using a desktop pen plotter integrated with a custom-made, low-cost paper feeder. We tested various types of commercial permanent markers and compared their water-resistant capabilities for creating hydrophobic barriers. Additionally, we studied the performance of markers with different types of paper, plotting speeds, and pattern dimensions. To verify the effectiveness of the presented fabrication method, colorimetric analysis was performed on the results of a glucose assay.

  9. Microfluidic Paper-Based Sample Concentration Using Ion Concentration Polarization with Smartphone Detection

    Directory of Open Access Journals (Sweden)

    Xue Li

    2016-11-01

    Full Text Available A simple method for microfluidic paper-based sample concentration using ion concentration polarization (ICP with smartphone detection is developed. The concise and low-cost microfluidic paper-based ICP analytical device, which consists of a black backing layer, a nitrocellulose membrane, and two absorbent pads, is fabricated with the simple lamination method which is widely used for lateral flow strips. Sample concentration on the nitrocellulose membrane is monitored in real time by a smartphone whose camera is used to collect the fluorescence images from the ICP device. A custom image processing algorithm running on the smartphone is used to track the concentrated sample and obtain its fluorescence signal intensity for quantitative analysis. Two different methods for Nafion coating are evaluated and their performances are compared. The characteristics of the ICP analytical device especially with intentionally adjusted physical properties are fully evaluated to optimize its performance as well as to extend its potential applications. Experimental results show that significant concentration enhancement with fluorescence dye sample is obtained with the developed ICP device when a fast depletion of fluorescent dye is observed. The platform based on the simply laminated ICP device with smartphone detection is desired for point-of-care testing in settings with poor resources.

  10. High-Density Microfluidic Particle-Cluster-Array Device for Parallel and Dynamic Study of Interaction between Engineered Particles.

    Science.gov (United States)

    Kim, Hojin; Lee, Sanghyun; Lee, Wonhyung; Kim, Joonwon

    2017-08-01

    A high-density and high-performance microfluidic particle-cluster-array device utilizing a novel hydrodynamically tunable pneumatic valve (HTPV) is reported for parallel and dynamic monitoring of the interactions taking place in particle clusters. The key concept involves passive operation of the HTPV through elastic deformation of a thin membrane using only the hydrodynamic force inherent in microchannel flows. This unique feature allows the discrete and high-density (≈30 HTPVs mm -2 ) arrangement of numerous HTPVs in a microfluidic channel without any pneumatic connection. In addition, the HTPV achieves high-performance clustering (≈92%) of three different particles in an array format through the optimization of key design and operating parameters. Finally, a contamination-free, parallel, and dynamic biochemical analysis strategy is proposed, which employs a simple one-inlet-one-outlet device operated by the effective combination of several techniques, including particle clustering, the interactions between engineered particles, two-phase partitioning and dehydration control of aqueous plugs, and shape/color-based particle identification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Low-temperature bonded glass-membrane microfluidic device for in vitro organ-on-a-chip cell culture models

    Science.gov (United States)

    Pocock, Kyall J.; Gao, Xiaofang; Wang, Chenxi; Priest, Craig; Prestidge, Clive A.; Mawatari, Kazuma; Kitamori, Takehiko; Thierry, Benjamin

    2015-12-01

    The integration of microfluidics with living biological systems has paved the way to the exciting concept of "organson- a-chip", which aims at the development of advanced in vitro models that replicate the key features of human organs. Glass based devices have long been utilised in the field of microfluidics but the integration of alternative functional elements within multi-layered glass microdevices, such as polymeric membranes, remains a challenge. To this end, we have extended a previously reported approach for the low-temperature bonding of glass devices that enables the integration of a functional polycarbonate porous membrane. The process was initially developed and optimised on specialty low-temperature bonding equipment (μTAS2001, Bondtech, Japan) and subsequently adapted to more widely accessible hot embosser units (EVG520HE Hot Embosser, EVG, Austria). The key aspect of this method is the use of low temperatures compatible with polymeric membranes. Compared to borosilicate glass bonding (650 °C) and quartz/fused silica bonding (1050 °C) processes, this method maintains the integrity and functionality of the membrane (Tg 150 °C for polycarbonate). Leak tests performed showed no damage or loss of integrity of the membrane for up to 150 hours, indicating sufficient bond strength for long term cell culture. A feasibility study confirmed the growth of dense and functional monolayers of Caco-2 cells within 5 days.

  12. Enhanced Analytical Performance of Paper Microfluidic Devices by Using Fe3O4 Nanoparticles, MWCNT, and Graphene Oxide.

    Science.gov (United States)

    Figueredo, Federico; Garcia, Paulo T; Cortón, Eduardo; Coltro, Wendell K T

    2016-01-13

    Spheres, tubes, and planar-shaped nanomaterials as Fe3O4 nanoparticles (MNPs), multiwalled carbon nanotubes (MWCNT), and graphene oxide (GO) were used for the first time to treat microfluidic paper-based analytical devices (μPADs) and create a biocompatible layer with high catalytic surface. Once glucose measurements are critical for diabetes or glycosuria detection and monitoring, the analytical performance of the proposed devices was studied by using bienzymatic colorimetric detection of this carbohydrate. The limit of detection values achieved for glucose with μPADs treated with MNPs, MWCNT, and GO were 43, 62, and 18 μM, respectively. The paper surface modification solves problems associated with the lack of homogeneity on color measurements that compromise the sensitivity and detectability levels in clinical diagnosis.

  13. The Separation of Blood Components Using Standing Surface Acoustic Waves (SSAWs Microfluidic Devices: Analysis and Simulation

    Directory of Open Access Journals (Sweden)

    Ahmed M. Soliman

    2017-03-01

    Full Text Available The separation of blood components (WBCs, RBCs, and platelets is important for medical applications. Recently, standing surface acoustic wave (SSAW microfluidic devices are used for the separation of particles. In this paper, the design analysis of SSAW microfluidics is presented. Also, the analysis of SSAW force with Rayleigh angle effect and its attenuation in liquid-loaded substrate, viscous drag force, hydrodynamic force, and diffusion force are explained and analyzed. The analyses are provided for selecting the piezoelectric material, width of the main microchannel, working area of SAW, wavelength, minimum input power required for the separation process, and widths of outlet collecting microchannels. The design analysis of SSAW microfluidics is provided for determining the minimum input power required for the separation process with appropriated the displacement contrast of the particles.The analyses are applied for simulation the separation of blood components. The piezoelectric material, width of the main microchannel, working area of SAW, wavelength, and minimum input power required for the separation process are selected as LiNbO3, 120 μm, 1.08 mm2, 300 μm, 371 mW. The results are compared to other published results. The results of these simulations achieve minimum power consumption, less complicated setup, and high collecting efficiency. All simulation programs are built by MATLAB.

  14. Holographic optical tweezers combined with a microfluidic device for exposing cells to fast environmental changes

    Science.gov (United States)

    Eriksson, Emma; Scrimgeour, Jan; Enger, Jonas; Goksör, Mattias

    2007-05-01

    Optical manipulation techniques have become an important research tool for single cell experiments in microbiology. Using optical tweezers, single cells can be trapped and held during long experiments without risk of cross contamination or compromising viability. However, it is often desirable to not only control the position of a cell, but also to control its environment. We have developed a method that combines optical tweezers with a microfluidic device. The microfluidic system is fabricated by soft lithography in which a constant flow is established by a syringe pump. In the microfluidic system multiple laminar flows of different media are combined into a single channel, where the fluid streams couple viscously. Adjacent media will mix only by diffusion, and consequently two different environments will be separated by a mixing region a few tens of micrometers wide. Thus, by moving optically trapped cells from one medium to another we are able to change the local environment of the cells in a fraction of a second. The time needed to establish a change in environment depends on several factors such as the strength of the optical traps and the steepness of the concentration gradient in the mixing region. By introducing dynamic holographic optical tweezers several cells can be trapped and analyzed simultaneously, thus shortening data acquisition time. The power of this system is demonstrated on yeast (Saccharomyces cerevisiae) subjected to osmotic stress, where the volume of the yeast cell and the spatial localization of green fluorescent proteins (GFP) are monitored using fluorescence microscopy.

  15. Microfluidic dielectrophoresis device for trapping, counting and detecting Shewanella oneidensis at the cell level.

    Science.gov (United States)

    Chen, Xiangyu; Liang, Zhiting; Li, Daobo; Xiong, Ying; Xiong, Penghui; Guan, Yong; Hou, Shuangyue; Hu, Yue; Chen, Shan; Liu, Gang; Tian, Yangchao

    2018-01-15

    Shewanella oneidensis, a model organism for electrochemical activity bacteria, has been widely studied at the biofilm level. However, to obtain more information regarding this species, it is essential to develop an approach to trap and detect S. oneidensis at the cell level. In this study, we report a rapid and label-free microfluidic platform for trapping, counting and detecting S. oneidensis cells. A microfluidic chip was integrated with a modified dielectrophoresis (DEP) trapping technique and hole arrays of different hole sizes. By numerical simulation and an elaborate electric field distribution design, S. oneidensis cells were successfully trapped and positioned in the hole arrays. Real time fluorescence imaging was also used to observe the trapping process. With the aid of a homemade image program, the trapped bacteria were accurately counted, and the results demonstrated that the amount of bacteria correlated with the hole sizes. As one of the significant applications of the device, Raman identification and detection of countable S. oneidensis cells was accomplished in two kinds of holes. The microfluidic platform provides a quantitative sample preparation and analysis method at the cell level that could be widely applied in the environmental and energy fields. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Simulation of the Cystic Fibrosis patient airway habitats using microfluidic devices

    DEFF Research Database (Denmark)

    Skolimowski, Maciej

    2013-01-01

    affecting human airways is cystic fibrosis. Cystic fibrosis (CF) patients suffer from a genetic defect that influences the salt transport over the cell membranes. Due to this effect, the mucus layer becomes very viscous as the defect in salt transport inhibit diffusion of and establishment of the important...... of treating infections in CF patients. Therefore, in this work we propose novel microfluidic devices that on one hand can mimic different airway environments by controlling the oxygen levels and on the other hand can mimic the microenvironment of the cystic fibrosis bronchi....

  17. High-stringency screening of target-binding partners using a microfluidic device

    Science.gov (United States)

    Soh, Hyongsok; Lou, Xinhui; Lagally, Eric

    2015-12-01

    The invention provides a method of screening a library of candidate agents by contacting the library with a target in a reaction mixture under a condition of high stringency, wherein the target includes a tag that responds to a controllable force applied to the tag, and passing the members of the library through a microfluidic device in a manner that exposes the library members to the controllable force, thereby displacing members of the library that are bound to the target relative to their unbound counterparts. Kits and systems for use with the methods of the invention are also provided.

  18. Methods, microfluidic devices, and systems for detection of an active enzymatic agent

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, Gregory J; Hatch, Anson V; Singh, Anup K; Wang, Ying-Chih

    2014-10-28

    Embodiments of the present invention provide methods, microfluidic devices, and systems for the detection of an active target agent in a fluid sample. A substrate molecule is used that contains a sequence which may cleave in the presence of an active target agent. A SNAP25 sequence is described, for example, that may be cleaved in the presence of Botulinum Neurotoxin. The substrate molecule includes a reporter moiety. The substrate molecule is exposed to the sample, and resulting reaction products separated using electrophoretic separation. The elution time of the reporter moiety may be utilized to identify the presence or absence of the active target agent.

  19. Manufacturing and testing flexible microfluidic devices with optical and electrical detection mechanisms

    Science.gov (United States)

    Ivan, Marius G.; Vivet, Frédéric; Meinders, Erwin R.

    2010-06-01

    Flexible microfluidic devices made of poly(dimethylsiloxane) (PDMS) were manufactured by soft lithography, and tested in detection of ionic species using optical absorption spectroscopy and electrical measurements. PDMS was chosen due to its flexibility and ease of surface modification by exposure to plasma and UV treatment, its transparency in UV-Vis regions of the light spectrum, and biocompatibility. The dual-detection mechanism allows the user more freedom in choosing the detection tool, and a functional device was successfully tested. Optical lithography was employed for manufacturing templates, which were subsequently used for imprinting liquid PDMS by thermal curing. Gold electrodes having various widths and distances among them were patterned with optical lithography on the top part which sealed the microchannels, and the devices were employed for detection of ionic species in aqueous salt solutions as well as micro-electrolysis cells. Due to the transparency of PDMS in UV-Vis the microfluidics were also used as photoreactors, and the in-situ formed charged species were monitored by applying a voltage between electrodes. Upon addition of a colorimetric pH sensor, acid was detected with absorption spectroscopy.

  20. Immobilization Techniques and Integrated Signal Enhancement for POC Nanocolor Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Marlies Schlauf

    2015-01-01

    Full Text Available Resonance enhanced absorption (REA nanocolor microfluidic devices are new promising bioassay platforms, which employ nanoparticle- (NP- protein conjugates for the immunodetection of medically relevant markers in biologic samples such as blood, urine, and saliva. The core component of a REA test device is a PET chip coated with aluminum and SiO2 thin layers, onto which biorecognitive molecules are immobilized. Upon addition of a sample containing the analyte of interest, a NP-protein-analyte complex is formed in the test device that is captured on the REA chip, for example, via streptavidin-biotin interaction. Thereby, a colored symbol is generated, which allows optical readout. Silver enhancement of the bound nanoparticles may be used to increase the sensitivity of the assay. Herein, we demonstrate that adsorptive immobilization via a cationic polymeric interlayer is a competitive and fast technique for the binding of the capture protein streptavidin onto planar SiO2 surfaces such as REA biochips. Moreover, we report the development of a silver enhancement technology that operates even in the presence of high chloride concentrations as may be encountered in biologic samples. The silver enhancement reagents may be integrated into the microfluidic assay platform to be released upon sample addition. Hereby, a highly sensitive one-step assay can be realized.

  1. Electric Characterization and Modeling of Microfluidic-Based Dye-Sensitized Solar Cell

    Directory of Open Access Journals (Sweden)

    Adriano Sacco

    2012-01-01

    Full Text Available The electric response to an external periodic voltage of small amplitude of dye-sensitized solar cells (DSCs made up with an alternative architecture has been investigated. DSCs have been fabricated with a reversible sealing structure, based on microfluidic concepts, with a precise control on the geometric parameters of the active chamber. Cells with different electrolyte thicknesses have been characterized, without varying the thickness of the TiO2 layer, both under illumination and in dark conditions. Measurements of the electric impedance have been performed in the presence of an external bias ranging from 0 V to 0.8 V. The experimental data have been analyzed in terms of a transmission line model, with two transport channels. The results show that the photovoltaic performances of the microfluidic cell are comparable with those obtained in irreversibly sealed structures, actually demonstrating the reliability of the proposed device.

  2. Microfluidic devices for sample preparation and rapid detection of foodborne pathogens

    DEFF Research Database (Denmark)

    Kant, Krishna; Shahbazi, Mohammad-Ali; Dave, Vivek Priy

    2018-01-01

    diagnosis competences. This has prompted researchers to call the current status of detection approaches into question and leverage new technologies for superior pathogen sensing outcomes. Novel strategies mainly rely on incorporating all the steps from sample preparation to detection in miniaturized devices...... streamlining the sample handling and concentrating procedures, which will subsequently reduce human errors and enhance the accuracy of the sensing methods. Integration of sample preparation techniques into these devices can effectively minimize the impact of complex food matrix on pathogen diagnosis...... recent advances in current state-of-the-art of sample preparation and concentration from food matrices with focus on bacterial capturing methods and sensing technologies, along with their advantages and limitations when integrated into microfluidic devices for online rapid detection of pathogens in foods...

  3. Endothelial Cell Culture Under Perfusion On A Polyester-Toner Microfluidic Device.

    Science.gov (United States)

    Urbaczek, Ana Carolina; Leão, Paulo Augusto Gomes Carneiro; Souza, Fayene Zeferino Ribeiro de; Afonso, Ana; Vieira Alberice, Juliana; Cappelini, Luciana Teresa Dias; Carlos, Iracilda Zeppone; Carrilho, Emanuel

    2017-09-05

    This study presents an inexpensive and easy way to produce a microfluidic device that mimics a blood vessel, serving as a start point for cell culture under perfusion, cardiovascular research, and toxicological studies. Endpoint assays (i.e., MTT reduction and NO assays) were used and revealed that the components making up the microchip, which is made of polyester and toner (PT), did not induce cell death or nitric oxide (NO) production. Applying oxygen plasma and fibronectin improved the adhesion and proliferation endothelial cell along the microchannel. As expected, these treatments showed an increase in vascular endothelial growth factor (VEGF-A) concentration profiles, which is correlated with adherence and cell proliferation, thus promoting endothelialization of the device for neovascularization. Regardless the simplicity of the device, our "vein-on-a-chip" mimetic has a potential to serve as a powerful tool for those that demand a rapid microfabrication method in cell biology or organ-on-a-chip research.

  4. Micro-total analysis system for virus detection: microfluidic pre-concentration coupled to liposome-based detection.

    Science.gov (United States)

    Connelly, John T; Kondapalli, Sowmya; Skoupi, Marc; Parker, John S L; Kirby, Brian J; Baeumner, Antje J

    2012-01-01

    An integrated microfluidic biosensor is presented that combines sample pre-concentration and liposome-based signal amplification for the detection of enteric viruses present in environmental water samples. This microfluidic approach overcomes the challenges of long assay times of cell culture-based methods and the need to extensively process water samples to eliminate inhibitors for PCR-based methods. Here, viruses are detected using an immunoassay sandwich approach with the reporting antibodies tagged to liposomes. Described is the development of the integrated device for the detection of environmentally relevant viruses using feline calicivirus (FCV) as a model organism for human norovirus. In situ fabricated nanoporous membranes in glass microchannels were used in conjunction with electric fields to achieve pre-concentration of virus-liposome complexes and therefore enhance the antibody-virus binding efficiency. The concentrated complexes were eluted to a detection region downstream where captured liposomes were lysed to release fluorescent dye molecules that were then quantified using image processing. This system was compared to an optimized electrochemical liposome-based microfluidic biosensor without pre-concentration. The limit of detection of FCV of the integrated device was at 1.6 × 10(5) PFU/mL, an order of magnitude lower than that obtained using the microfluidic biosensor without pre-concentration. This significant improvement is a key step toward the goal of using this integrated device as an early screening system for viruses in environmental water samples.

  5. Differential Ring Oscillator Based Capacitance Sensor for Microfluidic Applications.

    Science.gov (United States)

    Mohammad, Kaveh; Thomson, Douglas J

    2017-04-01

    A simple high frequency capacitance sensor with 180 aF sensitivity is designed for a wide range of microfluidic applications. The sensor is implemented utilizing differential ring oscillators operating at [Formula: see text] MHz with a differential signal at [Formula: see text] MHz. The sensor occupies [Formula: see text] cm × 2 cm on a printed circuit board. The sensor is tuned using two precision variable capacitors and has a full scale range of [Formula: see text] pF. The sensor was able to detect less than 1% Isopropyl Alcohol in DI water and to detect 15 μm polystyrene spheres flowing over 25 μm lines and spaces coplanar electrodes in a microfluidic channel. The compact differential ring oscillator based architecture of the design makes it suitable to be integrated into microprocessor based systems for detection in Lab on Chip or Lab on Board applications.

  6. Out-of-focus effects on microscale schlieren measurements of mass transport in a microfluidic device

    Science.gov (United States)

    Chen, Shao-Tuan; Sun, Chen-li

    2016-08-01

    The microscale schlieren technique provides a means for a non-invasive, full-field measurement for mixing microfluidics with excellent sensitivity and resolution. Nevertheless, an out-of-focus effect due to microscopic optics may lead to undesirable errors in quantifying the gradient information at high degrees of magnification. If the channel in the microfluidic device under study is too deep, light deflection caused by inhomogeneity located far from the focal plane may contributes little to the intensity change on the image plane. To address this issue, we propose the use of a weighting function that approximates a Gaussian profile with an optical-system-dependable width. We assume that the resultant intensity change is proportional to a weighted sum of the gradient across the channel depth and acquire micro-schlieren images of fluid mixing in a T-junction microchannel at various positions along the optical axis. For each objective, the width of the weighting function is then determined iteratively by curve fitting the ratio of changes in grayscale readouts for out-of-focus and focus micro-schlieren images. The standard deviation in the Gaussian distribution facilitates the quantification of the out-of-focus effect. In addition, we measure the sensitivities of a microscale schlieren system equipped with different objectives and compare the values to the model. Despite its better resolution, we find that an objective with higher magnification suffers from a more severe out-of-focus effect and a loss of sensitivity. Equations are proposed for estimations of the standard deviation and the sensitivity of microscale schlieren measurements. The outcome will facilitate the selection of proper microchannel depths for various microscale schlieren systems or vice versa, thus improving the precision of micro-schlieren measurements in microfluidic devices.

  7. Microfluidic Biopsy Trapping Device for the Real-Time Monitoring of Tumor Microenvironment.

    Directory of Open Access Journals (Sweden)

    Angela Babetski Holton

    Full Text Available The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent clinical drug response as they lack true tumor heterogeneity and are often performed in static culture conditions lacking stromal tumor components that significantly influence the metabolic activity and proliferation of cells. Recent microfluidic approaches aim to overcome such obstacles with the use of cell lines derived in artificial three-dimensional supportive gels or micro-chambers. However, absence of a true tumor microenvironment and full interstitial flow, leads to less than optimal evaluation of tumor response to drug treatment. Here we report a continuous perfusion microfluidic device coupled with microscopy and image analysis for the assessment of drug effects on intact fresh tumor tissue. We have demonstrated that fine needle aspirate biopsies obtained from patient-derived xenograft models of adenocarcinoma of the lung can successfully be analyzed for their response to ex vivo drug treatment within this biopsy trapping microfluidic device, wherein a protein kinase C inhibitor, staurosporine, was used to assess tumor cell death as a proof of principle. This approach has the potential to study tumor tissue within its intact microenvironment to better understand tumor response to drug treatments and

  8. Challenges in the Use of Compact Disc-Based Centrifugal Microfluidics for Healthcare Diagnostics at the Extreme Point of Care

    Directory of Open Access Journals (Sweden)

    Jordon Gilmore

    2016-03-01

    Full Text Available Since its inception, Compact Disc (CD-based centrifugal microfluidic technology has drawn a great deal of interest within research communities due to its potential use in biomedical applications. The technology has been referred to by different names, including compact-disc microfluidics, lab-on-a-disk, lab-on-a-CD and bio-disk. This paper critically reviews the state-of-the-art in CD-based centrifugal microfluidics devices and attempts to identify the challenges that, if solved, would enable their use in the extreme point of care. Sample actuation, manufacturing, reagent storage and implementation, target multiplexing, bio-particle detection, required hardware and system disposal, and sustainability are the topics of focus.

  9. A Modular Microfluidic Device via Multimaterial 3D Printing for Emulsion Generation.

    Science.gov (United States)

    Ji, Qinglei; Zhang, Jia Ming; Liu, Ying; Li, Xiying; Lv, Pengyu; Jin, Dongping; Duan, Huiling

    2018-03-19

    3D-printing (3DP) technology has been developing rapidly. However, limited studies on the contribution of 3DP technology, especially multimaterial 3DP technology, to droplet-microfluidics have been reported. In this paper, multimaterial 3D-printed devices for the pneumatic control of emulsion generation have been reported. A 3D coaxial flexible channel with other rigid structures has been designed and printed monolithically. Numerical and experimental studies have demonstrated that this flexible channel can be excited by the air pressure and then deform in a controllable way, which can provide the active control of droplet generation. Furthermore, a novel modular microfluidic device for double emulsion generation has been designed and fabricated, which consists of three modules: function module, T-junction module, and co-flow module. The function module can be replaced by (1) Single-inlet module, (2) Pneumatic Control Unit (PCU) module and (3) Dual-inlet module. Different modules can be easily assembled for different double emulsion production. By using the PCU module, double emulsions with different number of inner droplets have been successfully produced without complicated operation of flow rates of different phases. By using single and dual inlet module, various double emulsions with different number of encapsulated droplets or encapsulated droplets with different compositions have been successfully produced, respectively.

  10. 3D printed metal molds for hot embossing plastic microfluidic devices.

    Science.gov (United States)

    Lin, Tung-Yi; Do, Truong; Kwon, Patrick; Lillehoj, Peter B

    2017-01-17

    Plastics are one of the most commonly used materials for fabricating microfluidic devices. While various methods exist for fabricating plastic microdevices, hot embossing offers several unique advantages including high throughput, excellent compatibility with most thermoplastics and low start-up costs. However, hot embossing requires metal or silicon molds that are fabricated using CNC milling or microfabrication techniques which are time consuming, expensive and required skilled technicians. Here, we demonstrate for the first time the fabrication of plastic microchannels using 3D printed metal molds. Through optimization of the powder composition and processing parameters, we were able to generate stainless steel molds with superior material properties (density and surface finish) than previously reported 3D printed metal parts. Molds were used to fabricate poly(methyl methacrylate) (PMMA) replicas which exhibited good feature integrity and replication quality. Microchannels fabricated using these replicas exhibited leak-free operation and comparable flow performance as those fabricated from CNC milled molds. The speed and simplicity of this approach can greatly facilitate the development (i.e. prototyping) and manufacture of plastic microfluidic devices for research and commercial applications.

  11. Investigation of injection molding of orthogonal fluidic connector for microfluidic devices

    Directory of Open Access Journals (Sweden)

    Zheng Xu

    2017-02-01

    Full Text Available Orthogonal fluidic connections are essential for developing multilayered microfluidic devices. At present, most orthogonal connectors are realized by a horizontal channel and a vertical channel in different plates. Therefore, some extra alignment and adhesion processes for precise plate assembly are required. In this paper, the method of injection molding is proposed to make a one-body-type orthogonal connector in a single plastic plate. The connector was composed of a cantilevered tube and the other in the substrate. An injection mold was developed in which a side core-pulling mechanism and an ejection mechanism of push-pipes were combined to form the mold for an orthogonal connector. Both the type and the location of gate were optimized for the mold. The results showed that the fan gate in the middle position of the plate was the most suitable in term of both defect control and practicability. The effect of melt temperature was numerically investigated and then verified experimentally. With the optimized parameters, the relative length and the relative wall thickness of a cantilevered tube in the plastic part can reach 98.89% and 99.80%, respectively. Furthermore, using the plastic part as a cover plate, a three-layer plastic microfluidic device was conveniently fabricated for electrochemical detection.

  12. Physisorbed surface coatings for poly(dimethylsiloxane) and quartz microfluidic devices

    Science.gov (United States)

    Viefhues, M.; Manchanda, S.; Chao, T.-C.; Anselmetti, D.; Regtmeier, J.; Ros, A.

    2011-01-01

    Surface modifications of microfluidic devices are of essential importance for successful bioanalytical applications. Here, we investigate three different coatings for quartz and poly(dimethylsiloxane) (PDMS) surfaces. We employed a triblock copolymer with trade name F108, poly (l-lysine)-g-poly(ethylene glycol) (PLL-PEG), as well as the hybrid coating n-dodecyl-β-d-maltoside and methyl cellulose (DDM/MC). The impact of these coatings was characterized by measuring the electroosmotic flow (EOF), contact angle, and prevention of protein adsorption. Furthermore, we investigated the influence of static coatings, i.e., the incubation with the coating agent prior to measurements, and dynamic coatings, where the coating agent was present during the measurement. We found that all coatings on PDMS as well as quartz reduced EOF, increased reproducibility of EOF, reduced protein adsorption, and improved the wettability of the surfaces. Among the coating strategies tested, the dynamic coatings with DDM/MC and F108 demonstrated maximal reduction of EOF and protein adsorption and simultaneously best long-term stability concerning EOF. For PLL-PEG, a reversal in the EOF direction was observed. Interestingly, the static surface coating strategy with F108 proved to be as effective to prevent protein adsorption as dynamic coating with this block copolymer. These findings will allow optimized parameter choices for coating strategies on PDMS and quartz microfluidic devices in which control of EOF and reduced biofouling are indispensable. PMID:21847528

  13. Microfluidic biosensing device for controlled trapping and detection of magnetic microparticles

    KAUST Repository

    Giouroudi, Ioanna

    2013-05-01

    A magnetic microfluidic device is proposed to transport and trap magnetic microparticles (MPs) to a sensing area. Once the MPs are concentrated in the vicinity of the sensing area, a spin valve type giant magnetoresistance (GMR) sensor is used to detect their presence. The device is used for the detection of biological targets once they are labeled with functionalized MPs. Manipulation of the MPs is achieved by employing a microstructure which consists of planar ringshaped conducting microloops. These microloops are designed to produce high magnetic field gradients which are directly proportional to the force applied to manipulate the MPs. Upon sequential application of current, starting from the outermost loop, MPs are directed to move from the outermost to the innermost loop. The speed with which the MPs move towards the sensing area is controlled by the speed with which current is switched between the loops. On top of the microstructure, a microfluidic channel is fabricated using a standard photolithography technique and a dry film resist layer (Ordyl SY355). Experimental results showed that MPs of different diameters were successfully trapped at the sensing area and detected by the GMR sensor located directly under the innermost square loop. © 2013 IEEE.

  14. Exploring bubble oscillation and mass transfer enhancement in acoustic-assisted liquid-liquid extraction with a microfluidic device

    Science.gov (United States)

    Xie, Yuliang; Chindam, Chandraprakash; Nama, Nitesh; Yang, Shikuan; Lu, Mengqian; Zhao, Yanhui; Mai, John D.; Costanzo, Francesco; Huang, Tony Jun

    2015-01-01

    We investigated bubble oscillation and its induced enhancement of mass transfer in a liquid-liquid extraction process with an acoustically-driven, bubble-based microfluidic device. The oscillation of individually trapped bubbles, of known sizes, in microchannels was studied at both a fixed frequency, and over a range of frequencies. Resonant frequencies were analytically identified and were found to be in agreement with the experimental observations. The acoustic streaming induced by the bubble oscillation was identified as the cause of this enhanced extraction. Experiments extracting Rhodanmine B from an aqueous phase (DI water) to an organic phase (1-octanol) were performed to determine the relationship between extraction efficiency and applied acoustic power. The enhanced efficiency in mass transport via these acoustic-energy-assisted processes was confirmed by comparisons against a pure diffusion-based process. PMID:26223474

  15. Nanomaterial based detection and degradation of biological and chemical contaminants in a microfluidic system

    Science.gov (United States)

    Jayamohan, Harikrishnan

    Monitoring and remediation of environmental contaminants (biological and chemical) form the crux of global water resource management. There is an extant need to develop point-of-use, low-power, low-cost tools that can address this problem effectively with minimal environmental impact. Nanotechnology and microfluidics have made enormous advances during the past decade in the area of biosensing and environmental remediation. The "marriage" of these two technologies can effectively address some of the above-mentioned needs. In this dissertation, nanomaterials were used in conjunction with microfluidic techniques to detect and degrade biological and chemical pollutants. In the first project, a point-of-use sensor was developed for detection of trichloroethylene (TCE) from water. A self-organizing nanotubular titanium dioxide (TNA) synthesized by electrochemical anodization and functionalized with photocatalytically deposited platinum (Pt/TNA) was applied to the detection. The morphology and crystallinity of the Pt/TNA sensor was characterized using field emission scanning electron microscope, energy dis- persive x-ray spectroscopy, and X-ray diffraction. The sensor could detect TCE in the concentrations ranging from 10 to 1000 ppm. The room-temperature operation capability of the sensor makes it less power intensive and can potentially be incorporated into a field-based sensor. In the second part, TNA synthesized on a foil was incorporated into a flow-based microfluidic format and applied to degradation of a model pollutant, methylene blue. The system was demonstrated to have enhanced photocatalytic performance at higher flow rates (50-200 muL/min) over the same microfluidic format with TiO2 nanoparticulate (commercial P25) catalyst. The microfluidic format with TNA catalyst was able to achieve 82% fractional conversion of 18 mM methylene blue in comparison to 55% in the case of the TiO2 nanoparticulate layer at a flow rate of 200 L/min. The microfluidic device was

  16. Rapid development of paper-based fluidic diagnostic devices

    CSIR Research Space (South Africa)

    Smith, S

    2014-11-01

    Full Text Available We present a method for rapid and low-cost development of microfluidic diagnostic devices using paper-based techniques. Specifically, the implementation of fluidic flow paths and electronics on paper are demonstrated, with the goal of producing...

  17. [A novel method based on Y-shaped cotton-polyester thread microfluidic channel].

    Science.gov (United States)

    Wang, Lu; Shi, Yan-ru; Yan, Hong-tao

    2014-08-01

    A novel method based on Y-shaped microfluidic channel was firstly proposed in this study. The microfluidic channel was made of two cotton-polyester threads based on the capillary effect of cotton-polyester threads for the determination solutions. A special device was developed to fix the Y-shaped microfluidic channel by ourselves, through which the length and the tilt angle of the channel can be adjusted as requested. The spectrophotometry was compared with Scan-Adobe Photoshop software processing method. The former had a lower detection limit while the latter showed advantages in both convenience and fast operations and lower amount of samples. The proposed method was applied to the determination of nitrite. The linear ranges and detection limits are 1.0-70 micromol x L(-1), 0.66 micromol x L(-1) (spectrophotometry) and 50-450 micromol x L(-1), 45.10 micromol x L(-1) (Scan-Adobe Photoshop software processing method) respectively. This method has been successfully used to the determination of nitrite in soil samples and moat water with recoveries between 96.7% and 104%. It was proved that the proposed method was a low-cost, rapid and convenient analytical method with extensive application prospect.

  18. Microfluidic devices for sample preparation and rapid detection of foodborne pathogens.

    Science.gov (United States)

    Kant, Krishna; Shahbazi, Mohammad-Ali; Dave, Vivek Priy; Ngo, Tien Anh; Chidambara, Vinayaka Aaydha; Than, Linh Quyen; Bang, Dang Duong; Wolff, Anders

    2018-03-10

    Rapid detection of foodborne pathogens at an early stage is imperative for preventing the outbreak of foodborne diseases, known as serious threats to human health. Conventional bacterial culturing methods for foodborne pathogen detection are time consuming, laborious, and with poor pathogen diagnosis competences. This has prompted researchers to call the current status of detection approaches into question and leverage new technologies for superior pathogen sensing outcomes. Novel strategies mainly rely on incorporating all the steps from sample preparation to detection in miniaturized devices for online monitoring of pathogens with high accuracy and sensitivity in a time-saving and cost effective manner. Lab on chip is a blooming area in diagnosis, which exploits different mechanical and biological techniques to detect very low concentrations of pathogens in food samples. This is achieved through streamlining the sample handling and concentrating procedures, which will subsequently reduce human errors and enhance the accuracy of the sensing methods. Integration of sample preparation techniques into these devices can effectively minimize the impact of complex food matrix on pathogen diagnosis and improve the limit of detections. Integration of pathogen capturing bio-receptors on microfluidic devices is a crucial step, which can facilitate recognition abilities in harsh chemical and physical conditions, offering a great commercial benefit to the food-manufacturing sector. This article reviews recent advances in current state-of-the-art of sample preparation and concentration from food matrices with focus on bacterial capturing methods and sensing technologies, along with their advantages and limitations when integrated into microfluidic devices for online rapid detection of pathogens in foods and food production line. Copyright © 2018. Published by Elsevier Inc.

  19. Design and validation of a microfluidic device for blood-brain barrier monitoring and transport studies

    Science.gov (United States)

    Ugolini, Giovanni Stefano; Occhetta, Paola; Saccani, Alessandra; Re, Francesca; Krol, Silke; Rasponi, Marco; Redaelli, Alberto

    2018-04-01

    In vitro blood-brain barrier models are highly relevant for drug screening and drug development studies, due to the challenging task of understanding the transport mechanism of drug molecules through the blood-brain barrier towards the brain tissue. In this respect, microfluidics holds potential for providing microsystems that require low amounts of cells and reagent and can be potentially multiplexed for increasing the ease and throughput of the drug screening process. We here describe the design, development and validation of a microfluidic device for endothelial blood-brain barrier cell transport studies. The device comprises of two microstructured layers (top culture chamber and bottom collection chamber) sandwiching a porous membrane for the cell culture. Microstructured layers include two pairs of physical electrodes, embedded into the device layers by geometrically defined guiding channels with computationally optimized positions. These electrodes allow the use of commercial electrical measurement systems for monitoring trans-endothelial electrical resistance (TEER). We employed the designed device for performing preliminary assessment of endothelial barrier formation with murine brain endothelial cells (Br-bEnd5). Results demonstrate that cellular junctional complexes effectively form in the cultures (expression of VE-Cadherin and ZO-1) and that the TEER monitoring systems effectively detects an increase of resistance of the cultured cell layers indicative of tight junction formation. Finally, we validate the use of the described microsystem for drug transport studies demonstrating that Br-bEnd5 cells significantly hinder the transport of molecules (40 kDa and 4 kDa dextran) from the top culture chamber to the bottom collection chamber.

  20. Digitally controlled droplet microfluidic system based on electrophoretic actuation

    Science.gov (United States)

    Im, Do Jin; Yoo, Byeong Sun; Ahn, Myung Mo; Moon, Dustin; Kang, In Seok

    2012-11-01

    Most researches on direct charging and the subsequent manipulation of a charged droplet were focused on an on-demand sorting in microchannel where carrier fluid transports droplets. Only recently, an individual actuation of a droplet without microchannel and carrier fluid was tried. However, in the previous work, the system size was too large and the actuation voltage was too high (1.5 kV), which limits the applicability of the technology to mobile use. Therefore, in the current research, we have developed a miniaturized digital microfluidic system based on the electrophoresis of a charged droplet (ECD). By using a pin header socket for an array of electrodes, much smaller microfluidic system can be made from simple fabrication process with low cost. A full two dimensional manipulation (0.4 cm/s) of a droplet (300 nL) suspended in silicone oil (6 cSt) and multiple droplet actuation have been performed with reasonable actuation voltage (300 V). By multiple droplet actuation and coalescence, a practical biochemical application also has been demonstrated. We hope the current droplet manipulation method (ECD) can be a good alternative or complimentary technology to the conventional ones and therefore contributes to the development of droplet microfluidics. This work has been supported by BK21 program of the Ministry of Education, Science and Technology (MEST) of Korea.

  1. Inexpensive, rapid prototyping of microfluidic devices using overhead transparencies and a laser print, cut and laminate fabrication method.

    Science.gov (United States)

    Thompson, Brandon L; Ouyang, Yiwen; Duarte, Gabriela R M; Carrilho, Emanuel; Krauss, Shannon T; Landers, James P

    2015-06-01

    We describe a technique for fabricating microfluidic devices with complex multilayer architectures using a laser printer, a CO2 laser cutter, an office laminator and common overhead transparencies as a printable substrate via a laser print, cut and laminate (PCL) methodology. The printer toner serves three functions: (i) it defines the microfluidic architecture, which is printed on the overhead transparencies; (ii) it acts as the adhesive agent for the bonding of multiple transparency layers; and (iii) it provides, in its unmodified state, printable, hydrophobic 'valves' for fluidic flow control. By using common graphics software, e.g., CorelDRAW or AutoCAD, the protocol produces microfluidic devices with a design-to-device time of ∼40 min. Devices of any shape can be generated for an array of multistep assays, with colorimetric detection of molecular species ranging from small molecules to proteins. Channels with varying depths can be formed using multiple transparency layers in which a CO2 laser is used to remove the polyester from the channel sections of the internal layers. The simplicity of the protocol, availability of the equipment and substrate and cost-effective nature of the process make microfluidic devices available to those who might benefit most from expedited, microscale chemistry.

  2. Rapid method for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process.

    Science.gov (United States)

    Liu, Ai-Lin; He, Feng-yun; Wang, Kang; Zhou, Ting; Lu, Yu; Xia, Xing-hua

    2005-09-01

    We developed a facile and rapid one-step technique for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process. A laser printing mechanism was dexterously adopted to pattern the microchannels with different gray levels using vector graphic software. With the present method, periodically ordered specific bas-relief microstructures can be easily fabricated on transparencies by a simple printing process. The size and shape of the resultant microstructures are determined by the gray level of the graphic software and the resolution of the laser printer. Patterns of specific bas-relief microstructures on the floor of a channel act as obstacles in the flow path for advection mixing, which can be used as efficient mixing elements. The mixing effect of the resultant micromixer in microfluidic devices was evaluated using CCD fluorescence spectroscopy. We found that the mixing performance depends strongly on the gray level values. Under optimal conditions, fast passive mixing with our periodic ordered patterns in microfluidic devices has been achieved at the very early stages of the laminar flow. In addition, fabrication of micromixers using the present versatile technique requires less than an hour. The present method is promising for fabrication of micromixers in microfluidic devices at low cost and without complicated devices and environment, providing a simple solution to mixing problems in the micro-total-analysis-systems field.

  3. A rapid, straightforward, and print house compatible mass fabrication method for integrating 3D paper-based microfluidics.

    Science.gov (United States)

    Xiao, Liangpin; Liu, Xianming; Zhong, Runtao; Zhang, Kaiqing; Zhang, Xiaodi; Zhou, Xiaomian; Lin, Bingcheng; Du, Yuguang

    2013-11-01

    Three-dimensional (3D) paper-based microfluidics, which is featured with high performance and speedy determination, promise to carry out multistep sample pretreatment and orderly chemical reaction, which have been used for medical diagnosis, cell culture, environment determination, and so on with broad market prospect. However, there are some drawbacks in the existing fabrication methods for 3D paper-based microfluidics, such as, cumbersome and time-consuming device assembly; expensive and difficult process for manufacture; contamination caused by organic reagents from their fabrication process. Here, we present a simple printing-bookbinding method for mass fabricating 3D paper-based microfluidics. This approach involves two main steps: (i) wax-printing, (ii) bookbinding. We tested the delivery capability, diffusion rate, homogeneity and demonstrated the applicability of the device to chemical analysis by nitrite colorimetric assays. The described method is rapid (method that is common in a print house, making itself an ideal scheme for large-scale production of 3D paper-based microfluidics. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Effect of gold nanoparticles on thermal gradient generation and thermotaxis of E. coli cells in microfluidic device.

    Science.gov (United States)

    Murugesan, Nithya; Panda, Tapobrata; Das, Sarit K

    2016-08-01

    Bacteria responds to changing chemical and thermal environment by moving towards or away from a particular location. In this report, we looked into thermal gradient generation and response of E. coli DH5α cells to thermal gradient in the presence and in the absence of spherical gold nanoparticles (size: 15 to 22 nm) in a static microfluidic environment using a polydimethylsiloxane (PDMS) made microfluidic device. A PDMS-agarose based microfluidic device for generating thermal gradient has been developed and the thermal gradient generation in the device has been validated with the numerical simulation. Our studies revealed that the presence of gold nanoparticles, AuNPs (0.649 μg/mL) has no effect on the thermal gradient generation. The E. coli DH5α cells have been treated with AuNPs of two different concentrations (0.649 μg/mL and 0.008 μg/mL). The thermotaxis behavior of cells in the presence of AuNPs has been studied and compared to the thermotaxis of E.coli DH5α cells in the absence of AuNPs. In case of thermotaxis, in the absence of the AuNPs, the E. coli DH5α cells showed better thermotaxis towards lower temperature range, whereas in the presence of AuNPs (0.649 μg/mL and 0.008 μg/mL) thermotaxis of the E. coli DH5α cells has been inhibited. The results show that the spherical AuNPs intervenes in the themotaxis of E. coli DH5α cells and inhibits the cell migration. The reason for the failure in thermotaxis response mechanism may be due to decreased F-type ATP synthase activity and collapse of membrane potential by AuNPs, which, in turn, leads to decreased ATP levels. This has been hypothesized since both thermotaxis and chemotaxis follows the same response mechanism for migration in which ATP plays critical role.

  5. Development of microfluidic devices for in situ investigation of cells using surface-enhanced Raman spectroscopy (Conference Presentation)

    Science.gov (United States)

    Ho, Yu-Han; Galvan, Daniel D.; Yu, Qiuming

    2016-03-01

    Surface-enhanced Raman spectroscopy (SERS) has immerged as a power analytical and sensing technique for many applications in biomedical diagnosis, life sciences, food safety, and environment monitoring because of its molecular specificity and high sensitivity. The inactive Raman scattering of water molecule makes SERS a suitable tool for studying biological systems. Microfluidic devices have also attracted a tremendous interest for the aforementioned applications. By integrating SERS-active substrates with microfluidic devices, it offers a new capability for in situ investigation of biological systems, their dynamic behaviors, and response to drugs or microenvironment changes. In this work, we designed and fabricated a microfluidic device with SERS-active substrates surrounding by cell traps in microfluidic channels for in situ study of live cells using SERS. The SERS-active substrates are quasi-3D plasmonic nanostructure array (Q3D-PNA) made in h-PDMS/PMDS with physically separated gold film with nanoholes op top and gold nanodisks at the bottom of nanowells. 3D finite-difference time-domain (3D-FDTD) electromagnetic simulations were performed to design Q3D-PNAs with the strongest local electric fields (hot spots) at the top or bottom water/Au interfaces for sensitive analysis of cells and small components, respectively. The Q3D-PNAs with the hot spots on top and bottom were placed at the up and down stream of the microfluidic channel, respectively. Each Q3D-PNA pattern was surrounded with cell trapping structures. The microfluidic device was fabricated via soft lithography. We demonstrated that normal (COS-7) and cancer (HpeG2) cells were captured on the Q3D-PNAs and investigated in situ using SERS.

  6. Geometrical effect characterization of femtosecond-laser manufactured glass microfluidic chips based on optical manipulation of submicroparticles

    Science.gov (United States)

    Kotsifaki, Domna G.; Mackenzie, Mark D.; Polydefki, Georgia; Kar, Ajoy K.; Makropoulou, Mersini; Serafetinides, Alexandros A.

    2017-12-01

    Microfluidic devices provide a platform with wide ranging applications from environmental monitoring to disease diagnosis. They offer substantive advantages but are often not optimized or designed to be used by nonexpert researchers. Microchannels of a microanalysis platform and their geometrical characterization are of eminent importance when designing such devices. We present a method that is used to optimize each microchannel within a device using high-throughput particle manipulation. For this purpose, glass-based microfluidic devices, with three-dimensional channel networks of several geometrical sizes, were fabricated by employing laser fabrication techniques. The effect of channel geometry was investigated by employing an optical tweezer. The optical trapping force depends on the flow velocity that is associated with the dimensions of the microchannel. We observe a linear dependence of the trapping efficiency and of the fluid flow velocity, with the channel dimensions. We determined that the highest trapping efficiency was achieved for microchannels with aspect ratio equal to one. Numerical simulation validated the impact of the device design dimensions on the trapping efficiency. This investigation indicates that the geometrical characteristics, the flow velocity, and trapping efficiency are crucial and should be considered when fabricating microfluidic devices for cell studies.

  7. Electrofluidic Circuit-Based Microfluidic Viscometer for Analysis of Newtonian and Non-Newtonian Liquids under Different Temperatures.

    Science.gov (United States)

    Lee, Tse-Ang; Liao, Wei-Hao; Wu, Yi-Fan; Chen, Yeng-Long; Tung, Yi-Chung

    2018-02-06

    This paper reports a microfluidic viscometer with an integrated pressure sensor based on electrofluidic circuits, which are electrical circuits constructed by ionic liquid-filled microfluidic channels. The electrofluidic circuit provides a pressure-sensing scheme with great long-term and thermal stability. The viscosity of the tested fluidic sample is estimated by its flow resistance, which is a function of pressure drop, flow rate, and the geometry of the microfluidic channel. The viscometer can be exploited to measure viscosity of either Newtonian or non-Newtonian power-law fluid under various shear rates (3-500 1/s) and temperatures (4-70 °C) with small sample volume (less than 400 μL). The developed sensor-integrated microfluidic viscometer is made of poly(dimethylsiloxane) (PDMS) with transparent electrofluidic circuit, which makes it feasible to simultaneously image samples under tests. In addition, the entire device is disposable to prevent cross-contamination between samples, which is desired for various chemical and biomedical applications. In the experiments, viscosities of Newtonian fluids, glycerol water solutions with different concentrations and a mixture of pyrogallol and sodium hydroxide (NaOH), and non-Newtonian fluids, xanthan gum solutions and human blood samples, have been characterized. The results demonstrate that the developed microfluidic viscometer provides a convenient and useful platform for practical viscosity characterization of fluidic samples for a wide variety of applications.

  8. Laser patterning and welding of transparent polymers for microfluidic device fabrication

    Science.gov (United States)

    Pfleging, W.; Baldus, O.

    2006-02-01

    CO II-laser-assisted micro-patterning of polymethylmethacrylate (PMMA) or cyclo-olefin copolymer (COC) has a great potential for the rapid manufacturing of polymeric devices including cutting and structuring. Channel widths of about 50 μm as well as large area patterning of reservoir structures or drilling of vias are established. For this purpose a high quality laser beam is necessary as well as an appropriate beam forming system. In combination with laser transmission welding a fast fabrication of two- and three-dimensional micro-fluidic devices was possible. Welding as well as multilayer welding of transparent polymers was investigated for different polymers such as PMMA, polyvinylidene fluoride (PVDF), COC, and polystyrene (PS). The laser transmission welding process is performed with a high-power diode laser (wavelength 940 nm). An absorption layer with a thickness of several nanometers is deposited onto the polymer surfaces. The welding process has been established for the welding of polymeric parts containing microchannels, if the width of the channels is equal or larger than 100μm. For smaller feature sizes the absorption layer is structured by UV-laser radiation in order to get a highly localized welding seam, e.g., for the limitation of thermal penetration and thermal damaging of functional features such as channels, thin walls or temperature-sensitive substances often contained in micro-fluidic devices. This process strategy was investigated for the welding of capillary electrophoresis chips and capillary blood separation chips, including channel widths of 100 μm and 30 μm. Analysis of the thickness of the absorption layer was carried out with optical transmission spectroscopy.

  9. Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

    Directory of Open Access Journals (Sweden)

    Sarah L. Tao

    2010-03-01

    Full Text Available One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

  10. In vitro development of donated frozen-thawed human embryos in a prototype static microfluidic device: a randomized controlled trial

    NARCIS (Netherlands)

    Kieslinger, Dorit C.; Hao, Zhenxia; Vergouw, Carlijn G.; Kostelijk, Elisabeth H.; Lambalk, Cornelis B.; le Gac, Severine

    Objective: To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. Design: Prospective randomized controlled trial. Setting: In vitro fertilization laboratory. Patient(s): One hundred eighteen donated frozen-thawed

  11. HistoFlex-a microfluidic device providing uniform flow conditions enabling highly sensitive, reproducible and quantitative in situ hybridizations

    DEFF Research Database (Denmark)

    Søe, Martin Jensen; Okkels, Fridolin; Sabourin, David

    2011-01-01

    A microfluidic device (the HistoFlex) designed to perform and monitor molecular biological assays under dynamic flow conditions on microscope slide-substrates, with special emphasis on analyzing histological tissue sections, is presented. Microscope slides were reversibly sealed onto a cast...

  12. High-throughput deterministic single-cell encapsulation and droplet pairing, fusion, and shrinkage in a single microfluidic device

    NARCIS (Netherlands)

    Schoeman, R.M.; Kemna, Evelien; Wolbers, F.; van den Berg, Albert

    In this article, we present a microfluidic device capable of successive high-yield single-cell encapsulation in droplets, with additional droplet pairing, fusion, and shrinkage. Deterministic single-cell encapsulation is realized using Dean-coupled inertial ordering of cells in a Yin-Yang-shaped

  13. IFSA: a microfluidic chip-platform for frit-based immunoassay protocols

    Science.gov (United States)

    Hlawatsch, Nadine; Bangert, Michael; Miethe, Peter; Becker, Holger; Gärtner, Claudia

    2013-03-01

    Point-of-care diagnostics (POC) is one of the key application fields for lab-on-a-chip devices. While in recent years much of the work has concentrated on integrating complex molecular diagnostic assays onto a microfluidic device, there is a need to also put comparatively simple immunoassay-type protocols on a microfluidic platform. In this paper, we present the development of a microfluidic cartridge using an immunofiltration approach. In this method, the sandwich immunoassay takes place in a porous frit on which the antibodies have immobilized. The device is designed to be able to handle three samples in parallel and up to four analytical targets per sample. In order to meet the critical cost targets for the diagnostic market, the microfluidic chip has been designed and manufactured using high-volume manufacturing technologies in mind. Validation experiments show comparable sensitivities in comparison with conventional immunofiltration kits.

  14. Direct current insulator based dielectrophoresis (DC-iDEP) microfluidic chip for blood plasma separation

    OpenAIRE

    Mohammadi, Mahdi

    2015-01-01

    Lab-on-a-Chip (LOC) integrated microfluidics has been a powerful tool for new developments in analytical chemistry. These microfluidic systems enable the miniaturization, integration and automation of complex biochemical assays through the reduction of reagent use and enabling portability.Cell and particle separation in microfluidic systems has recently gained significant attention in many sample preparations for clinical procedures. Direct-current insulator-based dielectrophoresis (DC-iDEP) ...

  15. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Directory of Open Access Journals (Sweden)

    Yu Lu

    2016-05-01

    Full Text Available Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  16. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices.

    Science.gov (United States)

    Lu, Yu; Chowdhury, Danial; Vladisavljević, Goran T; Koutroumanis, Konstantinos; Georgiadou, Stella

    2016-05-25

    Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL(-1) of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF) or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol(-1) and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5-2.5 mg·mL(-1) fluconazole and 1.5 mg·mL(-1) copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  17. PMMA to Polystyrene bonding for polymer based microfluidic systems

    KAUST Repository

    Fan, Yiqiang

    2013-03-29

    A thermal bonding technique for Poly (methylmethacrylate) (PMMA) to Polystyrene (PS) is presented in this paper. The PMMA to PS bonding was achieved using a thermocompression method, and the bonding strength was carefully characterized. The bonding temperature ranged from 110 to 125 C with a varying compression force, from 700 to 1,000 N (0.36-0.51 MPa). After the bonding process, two kinds of adhesion quantification methods were used to measure the bonding strength: the double cantilever beam method and the tensile stress method. The results show that the bonding strength increases with a rising bonding temperature and bonding force. The results also indicate that the bonding strength is independent of bonding time. A deep-UV surface treatment method was also provided in this paper to lower the bonding temperature and compression force. Finally, a PMMA to PS bonded microfluidic device was fabricated successfully. © 2013 Springer-Verlag Berlin Heidelberg.

  18. Evaluation of biofouling in stainless microfluidic channels for implantable multilayered dialysis device

    Science.gov (United States)

    Ota, Takashi; To, Naoya; Kanno, Yoshihiko; Miki, Norihisa

    2017-06-01

    An implantable artificial kidney can markedly improve the quality of life of renal disease patients. Our group has developed an implantable multilayered dialysis system consisting of microfluidic channels and dialysis membranes. Long-term evaluation is necessary for implant devices where biofouling is a critical factor, culminating in the deterioration of dialysis performance. Our previous work revealed that surface conditions, which depend on the manufacturing process, determine the amount of biofouling, and that electrolytic etching is the most suitable technique for forming a channel wall free of biofouling. In this study, we investigated the electrolytic etching conditions in detail. We conducted in vitro experiments for 7 d and evaluated the adhesion of biomaterials by scanning electron microscopy. The experiments revealed that a surface mirror-finished by electrolytic etching effectively prevents biofouling.

  19. Fabric-based alkaline direct formate microfluidic fuel cells.

    Science.gov (United States)

    Domalaon, Kryls; Tang, Catherine; Mendez, Alex; Bernal, Franky; Purohit, Krutarth; Pham, Linda; Haan, John; Gomez, Frank A

    2017-04-01

    Fabric-based microfluidic fuel cells (MFCs) serve as a novel, cost-efficient alternative to traditional FCs and batteries, since fluids naturally travel across fabric via capillary action, eliminating the need for an external pump and lowering production and operation costs. Building on previous research with Y-shaped paper-based MFCs, fabric-based MFCs mitigate fragility and durability issues caused by long periods of fuel immersion. In this study, we describe a microfluidic fabric-based direct formate fuel cell, with 5 M potassium formate and 30% hydrogen peroxide as the anode fuel and cathode oxidant, respectively. Using a two-strip, stacked design, the optimized parameters include the type of encasement, the barrier, and the fabric type. Surface contact of the fabric and laminate sheet expedited flow and respective chemical reactions. The maximum current (22.83 mA/cm 2 ) and power (4.40 mW/cm 2 ) densities achieved with a 65% cotton/35% polyester blend material are a respective 8.7% and 32% higher than previous studies with Y-shaped paper-based MFCs. In series configuration, the MFCs generate sufficient energy to power a handheld calculator, a thermometer, and a spectrum of light-emitting diodes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Enhanced intracellular delivery of a model drug using microbubbles produced by a microfluidic device.

    Science.gov (United States)

    Dixon, Adam J; Dhanaliwala, Ali H; Chen, Johnny L; Hossack, John A

    2013-07-01

    Focal drug delivery to a vessel wall facilitated by intravascular ultrasound and microbubbles holds promise as a potential therapy for atherosclerosis. Conventional methods of microbubble administration result in rapid clearance from the bloodstream and significant drug loss. To address these limitations, we evaluated whether drug delivery could be achieved with transiently stable microbubbles produced in real time and in close proximity to the therapeutic site. Rat aortic smooth muscle cells were placed in a flow chamber designed to simulate physiological flow conditions. A flow-focusing microfluidic device produced 8 μm diameter monodisperse microbubbles within the flow chamber, and ultrasound was applied to enhance uptake of a surrogate drug (calcein). Acoustic pressures up to 300 kPa and flow rates up to 18 mL/s were investigated. Microbubbles generated by the flow-focusing microfluidic device were stabilized with a polyethylene glycol-40 stearate shell and had either a perfluorobutane (PFB) or nitrogen gas core. The gas core composition affected stability, with PFB and nitrogen microbubbles exhibiting half-lives of 40.7 and 18.2 s, respectively. Calcein uptake was observed at lower acoustic pressures with nitrogen microbubbles (100 kPa) than with PFB microbubbles (200 kPa) (p 3). In addition, delivery was observed at all flow rates, with maximal delivery (>70% of cells) occurring at a flow rate of 9 mL/s. These results demonstrate the potential of transiently stable microbubbles produced in real time and in close proximity to the intended therapeutic site for enhancing localized drug delivery. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  1. DNA Bipedal Motor Achieves a Large Number of Steps Due to Operation Using Microfluidics-Based Interface.

    Science.gov (United States)

    Tomov, Toma E; Tsukanov, Roman; Glick, Yair; Berger, Yaron; Liber, Miran; Avrahami, Dorit; Gerber, Doron; Nir, Eyal

    2017-04-25

    Realization of bioinspired molecular machines that can perform many and diverse operations in response to external chemical commands is a major goal in nanotechnology, but current molecular machines respond to only a few sequential commands. Lack of effective methods for introduction and removal of command compounds and low efficiencies of the reactions involved are major reasons for the limited performance. We introduce here a user interface based on a microfluidics device and single-molecule fluorescence spectroscopy that allows efficient introduction and removal of chemical commands and enables detailed study of the reaction mechanisms involved in the operation of synthetic molecular machines. The microfluidics provided 64 consecutive DNA strand commands to a DNA-based motor system immobilized inside the microfluidics, driving a bipedal walker to perform 32 steps on a DNA origami track. The microfluidics enabled removal of redundant strands, resulting in a 6-fold increase in processivity relative to an identical motor operated without strand removal and significantly more operations than previously reported for user-controlled DNA nanomachines. In the motor operated without strand removal, redundant strands interfere with motor operation and reduce its performance. The microfluidics also enabled computer control of motor direction and speed. Furthermore, analysis of the reaction kinetics and motor performance in the absence of redundant strands, made possible by the microfluidics, enabled accurate modeling of the walker processivity. This enabled identification of dynamic boundaries and provided an explanation, based on the "trap state" mechanism, for why the motor did not perform an even larger number of steps. This understanding is very important for the development of future motors with significantly improved performance. Our universal interface enables two-way communication between user and molecular machine and, relying on concepts similar to that of solid

  2. Microfluidic application-specific integrated device for monitoring direct cell-cell communication via gap junctions between individual cell pairs

    Science.gov (United States)

    Lee, Philip J.; Hung, Paul J.; Shaw, Robin; Jan, Lily; Lee, Luke P.

    2005-05-01

    Direct cell-cell communication between adjacent cells is vital for the development and regulation of functional tissues. However, current biological techniques are difficult to scale up for high-throughput screening of cell-cell communication in an array format. In order to provide an effective biophysical tool for the analysis of molecular mechanisms of gap junctions that underlie intercellular communication, we have developed a microfluidic device for selective trapping of cell-pairs and simultaneous optical characterizations. Two different cell populations can be brought into membrane contact using an array of trapping channels with a 2μm by 2μm cross section. Device operation was verified by observation of dye transfer between mouse fibroblasts (NIH3T3) placed in membrane contact. Integration with lab-on-a-chip technologies offers promising applications for cell-based analytical tools such as drug screening, clinical diagnostics, and soft-state biophysical devices for the study of gap junction protein channels in cellular communications. Understanding electrical transport mechanisms via gap junctions in soft membranes will impact quantitative biomedical sciences as well as clinical applications.

  3. An integrated microfluidic device utilizing dielectrophoresis and multiplex array PCR for point-of-care detection of pathogens.

    Science.gov (United States)

    Cai, Dongyang; Xiao, Meng; Xu, Peng; Xu, Ying-Chun; Du, Wenbin

    2014-10-21

    The early identification of causative pathogens in clinical specimens that require no cultivation is essential for directing evidence-based antimicrobial treatments in resource limited settings. Here, we describe an integrated microfluidic device for the rapid identification of pathogens in complex physiological matrices such as blood. The device was designed and fabricated using SlipChip technologies, which integrated four channels processing independent samples and identifying up to twenty different pathogens. Briefly, diluted whole human blood samples were directly injected into the device for analysis. The pathogens were extracted from the blood by dielectrophoresis, retained in an array of grooves, and identified by multiplex array PCR in nanoliter volumes with end-point fluorescence detection. The universality of the dielectrophoretic separation of pathogens from physiological fluids was evaluated with a panel of clinical isolates covering predominant bacterial and fungal species. Using this system, we simultaneously identified Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli O157:H7 within 3 h. In addition to the prompt diagnosis of bloodstream infections, this method may also be utilized for differentiating microorganisms in contaminated water and environmental samples.

  4. Microfluidic device having an immobilized pH gradient and PAGE gels for protein separation and analysis

    Science.gov (United States)

    Sommer, Gregory J.; Hatch, Anson V.; Singh, Anup K.; Wang, Ying-Chih

    2012-12-11

    Disclosed is a novel microfluidic device enabling on-chip implementation of a two-dimensional separation methodology. Previously disclosed microscale immobilized pH gradients (IPG) are combined with perpendicular polyacrylamide gel electrophoresis (PAGE) microchannels to achieve orthogonal separations of biological samples. Device modifications enable inclusion of sodium dodecyl sulfate (SDS) in the second dimension. The device can be fabricated to use either continuous IPG gels, or the microscale isoelectric fractionation membranes we have also previously disclosed, for the first dimension. The invention represents the first all-gel two-dimensional separation microdevice, with significantly higher resolution power over existing devices.

  5. An agar gel membrane-PDMS hybrid microfluidic device for long term single cell dynamic study.

    Science.gov (United States)

    Wong, Ieong; Atsumi, Shota; Huang, Wei-Chih; Wu, Tung-Yun; Hanai, Taizo; Lam, Miu-Ling; Tang, Ping; Yang, Jian; Liao, James C; Ho, Chih-Ming

    2010-10-21

    Significance of single cell measurements stems from the substantial temporal fluctuations and cell-cell variability possessed by individual cells. A major difficulty in monitoring surface non-adherent cells such as bacteria and yeast is that these cells tend to aggregate into clumps during growth, obstructing the tracking or identification of single-cells over long time periods. Here, we developed a microfluidic platform for long term single-cell tracking and cultivation with continuous media refreshing and dynamic chemical perturbation capability. The design highlights a simple device-assembly process between PDMS microchannel and agar membrane through conformal contact, and can be easily adapted by microbiologists for their routine laboratory use. The device confines cell growth in monolayer between an agar membrane and a glass surface. Efficient nutrient diffusion through the membrane and reliable temperature maintenance provide optimal growth condition for the cells, which exhibited fast exponential growth and constant distribution of cell sizes. More than 24 h of single-cell tracking was demonstrated on a transcription-metabolism integrated synthetic biological model, the gene-metabolic oscillator. Single cell morphology study under alcohol toxicity allowed us to discover and characterize cell filamentation exhibited by different E. coli isobutanol tolerant strains. We believe this novel device will bring new capabilities to quantitative microbiology, providing a versatile platform for single cell dynamic studies.

  6. Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.

    Science.gov (United States)

    Madison, Andrew C; Royal, Matthew W; Vigneault, Frederic; Chen, Liji; Griffin, Peter B; Horowitz, Mark; Church, George M; Fair, Richard B

    2017-09-15

    Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 10 8 cfu·μg -1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm -1 . Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.

  7. Digital microfluidic processing of mammalian embryos for vitrification.

    Science.gov (United States)

    Pyne, Derek G; Liu, Jun; Abdelgawad, Mohamed; Sun, Yu

    2014-01-01

    Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

  8. Digital microfluidic processing of mammalian embryos for vitrification.

    Directory of Open Access Journals (Sweden)

    Derek G Pyne

    Full Text Available Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

  9. Droplet-based microfluidics and the dynamics of emulsions

    Science.gov (United States)

    Baret, Jean-Christophe; Brosseau, Quentin; Semin, Benoit; Qu, Xiaopeng

    2012-02-01

    Emulsions are complex fluids already involved for a long time in a wide-range of industrial processes, such as, for example, food, cosmetics or materials synthesis [1]. More recently, applications of emulsions have been extended to new fields like biotechnology or biochemistry where the compartmentalization of compounds in emulsion droplets is used to parallelise (bio-) chemical reactions [2]. Interestingly, these applications pinpoint to fundamental questions dealing with surfactant dynamics, dynamic surface tension, hydrodynamic interactions and electrohydrodynamics. Droplet-based microfluidics is a very powerful tool to quantitatively study the dynamics of emulsions at the single droplet level or even at the single interface level: well-controlled emulsions are produced and manipulated using hydrodynamics, electrical forces, optical actuation and combination of these effects. We will describe here how droplet-based microfluidics is used to extract quantitative informations on the physical-chemistry of emulsions for a better understanding and control of the dynamics of these systems [3].[4pt] [1] J. Bibette et al. Rep. Prog. Phys., 62, 969-1033 (1999)[0pt] [2] A. Theberge et al., Angewandte Chemie Int. Ed. 49, 5846 (2010)[0pt] [3] J.-C. Baret et al., Langmuir, 25, 6088 (2009)

  10. A Digitally Controllable Polymer-Based Microfluidic Mixing Module Array

    Directory of Open Access Journals (Sweden)

    Raymond H. W. Lam

    2012-03-01

    Full Text Available This paper presents an integrated digitally controllable microfluidic system for continuous solution supply with a real-time concentration control. This system contains multiple independently operating mixing modules, each integrated with two vortex micropumps, two Tesla valves and a micromixer. The interior surface of the system is made of biocompatible materials using a polymer micro-fabrication process and thus its operation can be applied to chemicals and bio-reagents. In each module, pumping of fluid is achieved by the vortex micropump working with the rotation of a micro-impeller. The downstream fluid mixing is based on mechanical vibrations driven by a lead zirconate titanate ceramic diaphragm actuator located below the mixing chamber. We have conducted experiments to prove that the addition of the micro-pillar structures to the mixing chamber further improves the mixing performance. We also developed a computer-controlled automated driver system to control the real-time fluid mixing and concentration regulation with the mixing module array. This research demonstrates the integration of digitally controllable polymer-based microfluidic modules as a fully functional system, which has great potential in the automation of many bio-fluid handling processes in bio-related applications.

  11. Microfluidic Analytical Separator for Proteomics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SHOT proposes an innovative microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  12. Microfluidic Analytical Separator for Proteomics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  13. Microfluidic Analytical Separator for Proteomics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SHOT proposes an innovative microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  14. Microfluidic Analytical Separator for Proteomics, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  15. Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device.

    Science.gov (United States)

    Abelha, T F; Phillips, T W; Bannock, J H; Nightingale, A M; Dreiss, C A; Kemal, E; Urbano, L; deMello, J C; Green, M; Dailey, L A

    2017-02-02

    This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG 5K -PLGA 55K ) matrix. The influence of PEG 5K -PLGA 55K and conjugated polymers cyano-substituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (∼70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (∼70-100 nm) with similar optical properties (quantum yields ∼35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG 5K -PLGA 55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flow-based device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

  16. TECHNICAL NOTE: Portable audio electronics for impedance-based measurements in microfluidics

    Science.gov (United States)

    Wood, Paul; Sinton, David

    2010-08-01

    We demonstrate the use of audio electronics-based signals to perform on-chip electrochemical measurements. Cell phones and portable music players are examples of consumer electronics that are easily operated and are ubiquitous worldwide. Audio output (play) and input (record) signals are voltage based and contain frequency and amplitude information. A cell phone, laptop soundcard and two compact audio players are compared with respect to frequency response; the laptop soundcard provides the most uniform frequency response, while the cell phone performance is found to be insufficient. The audio signals in the common portable music players and laptop soundcard operate in the range of 20 Hz to 20 kHz and are found to be applicable, as voltage input and output signals, to impedance-based electrochemical measurements in microfluidic systems. Validated impedance-based measurements of concentration (0.1-50 mM), flow rate (2-120 µL min-1) and particle detection (32 µm diameter) are demonstrated. The prevailing, lossless, wave audio file format is found to be suitable for data transmission to and from external sources, such as a centralized lab, and the cost of all hardware (in addition to audio devices) is ~10 USD. The utility demonstrated here, in combination with the ubiquitous nature of portable audio electronics, presents new opportunities for impedance-based measurements in portable microfluidic systems.

  17. A Graphene-Based Microfluidic Platform for Electrocrystallization and In Situ X-ray Diffraction

    Directory of Open Access Journals (Sweden)

    Shuo Sui

    2018-02-01

    Full Text Available Here, we describe a novel microfluidic platform for use in electrocrystallization experiments. The device incorporates ultra-thin graphene-based films as electrodes and as X-ray transparent windows to enable in situ X-ray diffraction analysis. Furthermore, large-area graphene films serve as a gas barrier, creating a stable sample environment over time. We characterize different methods for fabricating graphene electrodes, and validate the electrical capabilities of our device through the use of methyl viologen, a redox-sensitive dye. Proof-of-concept electrocrystallization experiments using an internal electric field at constant potential were performed using hen egg-white lysozyme (HEWL as a model system. We observed faster nucleation and crystal growth, as well as a higher signal-to-noise for diffraction data obtained from crystals prepared in the presence of an applied electric field. Although this work is focused on the electrocrystallization of proteins for structural biology, we anticipate that this technology should also find utility in a broad range of both X-ray technologies and other applications of microfluidic technology.

  18. Quantum dot-based microfluidic biosensor for cancer detection

    Energy Technology Data Exchange (ETDEWEB)

    Ghrera, Aditya Sharma [Biomedical Instrumentation Section, CSIR-National Physical Laboratory, New Delhi-110012 (India); School of Engineering and Technology, ITM University, Gurgaon-122017 (India); Pandey, Chandra Mouli; Ali, Md. Azahar [Biomedical Instrumentation Section, CSIR-National Physical Laboratory, New Delhi-110012 (India); Malhotra, Bansi Dhar, E-mail: bansi.malhotra@gmail.com [Department of Biotechnology, Delhi Technological University, Delhi-110042 (India)

    2015-05-11

    We report results of the studies relating to fabrication of an impedimetric microfluidic–based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium–tin–oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir–Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10{sup −15} M to 10{sup −11} M.

  19. Quantum dot-based microfluidic biosensor for cancer detection

    International Nuclear Information System (INIS)

    Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

    2015-01-01

    We report results of the studies relating to fabrication of an impedimetric microfluidic–based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium–tin–oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir–Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10 −15 M to 10 −11 M

  20. Droplet-based microfluidic method for synthesis of microparticles

    CSIR Research Space (South Africa)

    Mbanjwa, MB

    2012-10-01

    Full Text Available biological applications such as drug delivery, cell encapsulation and tissue engineering[1]. GENERATION AND CONTROL OF MICRODROPLETS Water-in-oil (w/o) and oil-in-water (o/w) microdroplets and emulsions can be generated using microfluidic channels...: Generation and control of w/o droplets in flow focusing microfluidic channel MICROFLUIDIC-ASSISTED MICROPARTICLE SYNTHESIS Microparticles, such as biologically-important hydrogel micro- spheres, can be fabricated from various polymers...

  1. Comparing Caenorhabditis elegans gentle and harsh touch response behavior using a multiplexed hydraulic microfluidic device.

    Science.gov (United States)

    McClanahan, Patrick D; Xu, Joyce H; Fang-Yen, Christopher

    2017-10-16

    The roundworm Caenorhabditis elegans is an important model system for understanding the genetics and physiology of touch. Classical assays for C. elegans touch, which involve manually touching the animal with a probe and observing its response, are limited by their low throughput and qualitative nature. We developed a microfluidic device in which several dozen animals are subject to spatially localized mechanical stimuli with variable amplitude. The device contains 64 sinusoidal channels through which worms crawl, and hydraulic valves that deliver touch stimuli to the worms. We used this assay to characterize the behavioral responses to gentle touch stimuli and the less well studied harsh (nociceptive) touch stimuli. First, we measured the relative response thresholds of gentle and harsh touch. Next, we quantified differences in the receptive fields between wild type worms and a mutant with non-functioning posterior touch receptor neurons. We showed that under gentle touch the receptive field of the anterior touch receptor neurons extends into the posterior half of the body. Finally, we found that the behavioral response to gentle touch does not depend on the locomotion of the animal immediately prior to the stimulus, but does depend on the location of the previous touch. Responses to harsh touch, on the other hand, did not depend on either previous velocity or stimulus location. Differences in gentle and harsh touch response characteristics may reflect the different innervation of the respective mechanosensory cells. Our assay will facilitate studies of mechanosensation, sensory adaptation, and nociception.

  2. Formation of biodegradable microcapsules utilizing 3D, selectively surface-modified PDMS microfluidic devices.

    Science.gov (United States)

    Liao, Chung-Yu; Su, Yu-Chuan

    2010-02-01

    We have successfully demonstrated the formation of biodegradable microcapsules utilizing PDMS double-emulsification devices. Specially designed 3D PDMS microchannels with surfaces selectively modified by a self-aligned photografting process are employed to generate monodisperse water-in-organic-solvent-in-water (W/O/W) emulsions in a controlled manner. Mainly by varying the outer and inner fluid flow-rates, the dimensions of resulting double emulsions can be adjusted as desired. Meanwhile, biodegradable materials are dissolved in the middle organic solvent (in this work ethyl acetate is used), and solidified into microcapsules once the solvent is extracted. In the prototype demonstration, microcapsules made up of poly(L-lactic acid), trilaurin, and phosphocholine were successfully fabricated. In addition, it was also demonstrated that gamma-Fe(2)O(3) nanoparticles can be simultaneously embedded into the microcapsules, which consequently become responsive to electromagnetic stimulation. As such, the presented PDMS microfluidic devices could potentially serve as versatile encapsulation apparatus, and the fabricated biodegradable microcapsules could function as controlled delivery systems, which are desired for a variety of biological and pharmaceutical applications.

  3. Dynamic bioprocessing and microfluidic transport control with smart magnetic nanoparticles in laminar-flow devices.

    Science.gov (United States)

    Lai, James J; Nelson, Kjell E; Nash, Michael A; Hoffman, Allan S; Yager, Paul; Stayton, Patrick S

    2009-07-21

    In the absence of applied forces, the transport of molecules and particulate reagents across laminar flowstreams in microfluidic devices is dominated by the diffusivities of the transported species. While the differential diffusional properties between smaller and larger diagnostic targets and reagents have been exploited for bioseparation and assay applications, there are limitations to methods that depend on these intrinsic size differences. Here a new strategy is described for exploiting the sharply reversible change in size and magnetophoretic mobility of "smart" magnetic nanoparticles (mNPs) to perform bioseparation and target isolation under continuous flow processing conditions. The isolated 5 nm mNPs do not exhibit significant magnetophoretic velocities, but do exhibit high magnetophoretic velocities when aggregated by the action of a pH-responsive polymer coating. A simple external magnet is used to magnetophorese the aggregated mNPs that have captured a diagnostic target from a lower pH laminar flowstream (pH 7.3) to a second higher pH flowstream (pH 8.4) that induces rapid mNP disaggregation. In this second dis-aggregated state and flowstream, the mNPs continue to flow past the magnet rather than being immobilized at the channel surface near the magnet. This stimuli-responsive reagent system has been shown to transfer 81% of a model protein target from an input flowstream to a second flowstream in a continuous flow H-filter device.

  4. An Ultraviolet-Visible (UV Photometry System Based on the PDMS-based Microfluidic Chip

    Directory of Open Access Journals (Sweden)

    Xiang Changhua

    2017-01-01

    Full Text Available In order to avoid a problem remains with the low accuracy and poor portability of the photometry system, the system based on the photometry method and microfluidic chip technology was built. As the characteristics of cheap, solid and good transmission, Polydimethylsiloxane (PDMS was chosen as the material of the designed chip in the paper. To the designed UV photometry system, the light-emitting diode with wavelength of 580m is chosen as the light source. The experimental result indicates that there is no significant deviation between the designed UV photometry system and the conventional immuneturbidimetric assay, the correlation coefficient is 0.95 obtained by adopting the linear regression analysis. The linearity of the designed UV photometry system based on the PDMS-based microfluidic chip has increased by 17.3% in comparison with the system based on the silicon-based microfluidic chip.

  5. Integration of single oocyte trapping, in vitro fertilization and embryo culture in a microwell-structured microfluidic device.

    Science.gov (United States)

    Han, Chao; Zhang, Qiufang; Ma, Rui; Xie, Lan; Qiu, Tian; Wang, Lei; Mitchelson, Keith; Wang, Jundong; Huang, Guoliang; Qiao, Jie; Cheng, Jing

    2010-11-07

    In vitro fertilization (IVF) therapy is an important treatment for human infertility. However, the methods for clinical IVF have only changed slightly over decades: culture medium is held in oil-covered drops in Petri dishes and manipulation occurs by manual pipetting. Here we report a novel microwell-structured microfluidic device that integrates single oocyte trapping, fertilization and subsequent embryo culture. A microwell array was used to capture and hold individual oocytes during the flow-through process of oocyte and sperm loading, medium substitution and debris cleaning. Different microwell depths were compared by computational modeling and flow washing experiments for their effectiveness in oocyte trapping and debris removal. Fertilization was achieved in the microfluidic devices with similar fertilization rates to standard oil-covered drops in Petri dishes. Embryos could be cultured to blastocyst stages in our devices with developmental status individually monitored and tracked. The results suggest that the microfluidic device may bring several advantages to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing, and enabling automated tracking of any single embryo development.

  6. A novel temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

    DEFF Research Database (Denmark)

    Bu, Minqiang; R. Perch-Nielsen, Ivan; Sørensen, Karen Skotte

    We present a new temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with external heater and temperature sensor. The method employs optimized temperature overshooting and undershooting...

  7. Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jiandi Wan

    2012-04-01

    Full Text Available Encapsulation of cells in hydrogel particles has been demonstrated as an effective approach to deliver therapeutic agents. The properties of hydrogel particles, such as the chemical composition, size, porosity, and number of cells per particle, affect cellular functions and consequently play important roles for the cell-based drug delivery. Microfluidics has shown unparalleled advantages for the synthesis of polymer particles and been utilized to produce hydrogel particles with a well-defined size, shape and morphology. Most importantly, during the encapsulation process, microfluidics can control the number of cells per particle and the overall encapsulation efficiency. Therefore, microfluidics is becoming the powerful approach for cell microencapsulation and construction of cell-based drug delivery systems. In this article, I summarize and discuss microfluidic approaches that have been developed recently for the synthesis of hydrogel particles and encapsulation of cells. I will start by classifying different types of hydrogel material, including natural biopolymers and synthetic polymers that are used for cell encapsulation, and then focus on the current status and challenges of microfluidic-based approaches. Finally, applications of cell-containing hydrogel particles for cell-based drug delivery, particularly for cancer therapy, are discussed.

  8. Modeling and Simulation Framework for Flow-Based Microfluidic Biochips

    DEFF Research Database (Denmark)

    Schmidt, Morten Foged; Minhass, Wajid Hassan; Pop, Paul

    2013-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis on-chip. In this paper we are interested in flow-based biochips, in which the fluidic flow is manipulated using integrated microvalves. By combining...... several microvalves, more complex units, such as micropumps, switches, mixers, and multiplexers, can be built. Such biochips are becoming increasingly complex, with thousands of components, but are still designed manually using a bottom-up full-custom design approach, which is extremely labor intensive...... developed for the top-down design of flow-based biochips. We show how the IDE can be used to design biochips for several applications....

  9. Novel Polymer Microfluidics Technology for In Situ Planetary Exploration, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Los Gatos Research proposes to develop a novel microfluidic device that combines rigid monolithic porous polymer based micro-capillary electrochromatography...

  10. Basic principles of electrolyte chemistry for microfluidic electrokinetics. Part I: Acid-base equilibria and pH buffers.

    Science.gov (United States)

    Persat, Alexandre; Chambers, Robert D; Santiago, Juan G

    2009-09-07

    We review fundamental and applied acid-base equilibrium chemistry useful to microfluidic electrokinetics. We present elements of acid-base equilibrium reactions and derive rules for pH calculation for simple buffers. We also present a general formulation to calculate pH of more complex, arbitrary mixtures of electrolytes, and discuss the effects of ionic strength and temperature on pH calculation. More practically, we offer advice on buffer preparation and on buffer reporting. We also discuss "real world" buffers and likely contamination sources. In particular, we discuss the effects of atmospheric carbon dioxide on buffer systems, namely, the increase in ionic strength and acidification of typical electrokinetic device buffers. In Part II of this two-paper series, we discuss the coupling of acid-base equilibria with electrolyte dynamics and electrochemistry in typical microfluidic electrokinetic systems.

  11. Large-area, high-aspect-ratio SU-8 molds for the fabrication of PDMS microfluidic devices

    International Nuclear Information System (INIS)

    Natarajan, S; Chang-Yen, D A; Gale, B K

    2008-01-01

    A relatively low-cost fabrication method using soft lithography and molding for large-area, high-aspect-ratio microfluidic devices, which have traditionally been difficult to fabricate, has been developed and is presented in this work. The fabrication process includes novel but simple modifications of conventional microfabrication steps and can be performed in any standard microfabrication facility. Specifically, the fabrication and testing of a microfluidic device for continuous flow deposition of bio-molecules in an array format are presented. The array layout requires high-aspect-ratio elastomeric channels that are 350 µm tall, extend more than 10 cm across the substrate and are separated by as little as 20 µm. The mold from which these channels were fabricated consisted of high-quality, 335 µm tall SU-8 structures with a high-negative aspect ratio of 17 on a 150 mm silicon wafer and was produced using spin coating and UV-lithography. Several unique processing steps are introduced into the lithographic patterning to eliminate many of the problems experienced when fabricating tall, high-aspect-ratio SU-8 structures. In particular, techniques are used to ensure uniform molds, both in height and quality, that are fully developed even in the deep negative-aspect-ratio areas, have no leftover films at the top of the structures caused by overexposure and no bowing or angled sidewalls from diffraction of the applied UV light. Successful microfluidic device creation was demonstrated using these molds by casting, curing and bonding a polydimethylsiloxane (PDMS) elastomer. A unique microfluidic device, requiring these stringent geometries, for continuous flow printing of a linear array of 16 protein and antibody spots has been demonstrated and validated by using surface plasmon resonance imaging of printed arrays

  12. Patterned Fibers Embedded Microfluidic Chips Based on PLA and PDMS for Ag Nanoparticle Safety Testing

    Directory of Open Access Journals (Sweden)

    Yaowen Liu

    2016-11-01

    Full Text Available A new method to integrate poly-dl-lactide (PLA patterned electrospun fibers with a polydimethylsiloxane (PDMS microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP. In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles.

  13. A microfluidic device for the batch adsorption of a protein on adsorbent particles

    NARCIS (Netherlands)

    Rho, Hoon Suk; Hanke, Alexander Thomas; Ottens, Marcel; Gardeniers, J.G.E.

    2017-01-01

    A microfluidic platform or “microfluidic batch adsorption device” is presented, which performs two sets of 9 parallel protein incubations with/without adsorbent particles to achieve an adsorption isotherm of a protein in a single experiment. The stepwise concentration gradient of a target protein

  14. Microfluidic devices as gas – Ionic liquid membrane contactors for CO2 removal from anaesthesia gases

    NARCIS (Netherlands)

    Malankowska, Magdalena; Martins, C. F.; Rho, H. S.; Neves, L. A.; Tiggelaar, R. M.; Crespo, João G.; Pina, M.P.; Mallada, R.; Gardeniers, J.G.E.; Coelhoso, I. M.

    2018-01-01

    This work proposes a microfluidic gas – ionic liquid contactor for CO2 removal from anaesthesia gas, containing Xe. The working principle involves the transport of CO2 through a polymer flat membrane followed by its capture and enzymatic bioconversion in the ionic liquid solvent. Microfluidic

  15. A self assembled monolayer based microfluidic sensor for urea detection

    Science.gov (United States)

    Srivastava, Saurabh; Solanki, Pratima R.; Kaushik, Ajeet; Ali, Md. Azahar; Srivastava, Anchal; Malhotra, B. D.

    2011-07-01

    Urease (Urs) and glutamate dehydrogenase (GLDH) have been covalently co-immobilized onto a self-assembled monolayer (SAM) comprising of 10-carboxy-1-decanthiol (CDT) via EDC-NHS chemistry deposited onto one of the two patterned gold (Au) electrodes for estimation of urea using poly(dimethylsiloxane) based microfluidic channels (2 cm × 200 μm × 200 μm). The CDT/Au and Urs-GLDH/CDT/Au electrodes have been characterized using Fourier transform infrared (FTIR) spectroscopy, contact angle (CA), atomic force microscopy (AFM) and electrochemical cyclic voltammetry (CV) techniques. The electrochemical response measurement of a Urs-GLDH/CDT/Au bioelectrode obtained as a function of urea concentration using CV yield linearity as 10 to 100 mg dl-1, detection limit as 9 mg dl-1 and high sensitivity as 7.5 μA mM-1 cm-2.

  16. Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

    Science.gov (United States)

    Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

    2016-02-01

    Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

  17. Microfluidic sieve valves

    Science.gov (United States)

    Quake, Stephen R; Marcus, Joshua S; Hansen, Carl L

    2015-01-13

    Sieve valves for use in microfluidic device are provided. The valves are useful for impeding the flow of particles, such as chromatography beads or cells, in a microfluidic channel while allowing liquid solution to pass through the valve. The valves find particular use in making microfluidic chromatography modules.

  18. The influence of polydimethylsiloxane curing ratio on capillary pressure in microfluidic devices

    International Nuclear Information System (INIS)

    Viola, Ilenia; Zacheo, Antonella; Arima, Valentina; Aricò, Antonino S.; Cortese, Barbara; Manca, Michele; Zocco, Anna; Taurino, Antonietta; Rinaldi, Ross

    2012-01-01

    Investigations on surface properties of poly(dimethylsiloxane) (PDMS) are justified by its large application ranges especially as coating polymer in fluidic devices. At a micrometer scale, the liquid dynamics is strongly modified by interactions with a solid surface. A crucial parameter for this process is microchannel wettability that can be tuned by acting on surface chemistry and topography. In literature, a number of multi-step, time and cost consuming chemical and physical procedures are reported. Here we selectively modify both wetting and mechanical properties by a single step treatment. Changes of PDMS surface were investigated by X-ray photoelectron spectroscopy and atomic force microscopy and the effects of interface properties on the liquid displacement inside a microfluidic system were evaluated. The negative capillary pressure obtained tailoring the PDMS wettability is believed to be promising to accurately control sample leakage inside integrated lab-on-chip by acting on the liquid confinement and thus to reduce the sample volume, liquid drying as well as cross-contamination during the operation.

  19. Investigation of the Effect of Plasma Polymerized Siloxane Coating for Enzyme Immobilization and Microfluidic Device Conception

    Directory of Open Access Journals (Sweden)

    Kalim Belhacene

    2016-12-01

    Full Text Available This paper describes the impact of a physical immobilization methodology, using plasma polymerized 1,1,3,3, tetramethyldisiloxane, on the catalytic performance of β-galactosidase from Aspergillus oryzae in a microfluidic device. The β-galactosidase was immobilized by a polymer coating grown by Plasma Enhanced Chemical Vapor Deposition (PEVCD. Combined with a microchannel patterned in the silicone, a microreactor was obtained with which the diffusion through the plasma polymerized layer and the hydrolysis of a synthetic substrate, the resorufin-β-d-galactopyranoside, were studied. A study of the efficiency of the immobilization procedure was investigated after several uses and kinetic parameters of immobilized β-galactosidase were calculated and compared with those of soluble enzyme. Simulation and a modelling approach were also initiated to understand phenomena that influenced enzyme behavior in the physical immobilization method. Thus, the catalytic performances of immobilized enzymes were directly influenced by immobilization conditions and particularly by the diffusion behavior and availability of substrate molecules in the enzyme microenvironment.

  20. Protein immobilization on the surface of polydimethylsiloxane and polymethyl methacrylate microfluidic devices.

    Science.gov (United States)

    Khnouf, Ruba; Karasneh, Dina; Albiss, Borhan Aldeen

    2016-02-01

    PDMS and PMMA are two of the most used polymers in the fabrication of lab-on-chip or microfluidic devices. In order to use these polymers in biological applications, it is sometimes essential to be able to bind biomolecules such as proteins and DNA to the surface of these materials. In this work, we have evaluated a number of processes that have been developed to bind protein to PDMS surfaces which include passive adsorption, passive adsorption with glutaraldehyde cross-linking, (3-aminopropyl) triethoxysilane functionalization followed by glutaraldehyde or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride cross-linkers. It has been shown that the latter technique--using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride--results in more than twice the bonding of protein to the surface of PDMS microchannels than proteins binding passively. We have also evaluated a few techniques that have been tested for the functionalization of PMMA microchannels where we have found that the use of polyethyleneimine (PEI) has led to the strongest protein-PMMA microchannel bond. We finally demonstrated the effect of PDMS curing methodology on protein adsorption to its surface, and showed that increased curing time is the factor that reduces passive adsorption the most. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Electrophoretic Concentration and Electrical Lysis of Bacteria in a Microfluidic Device Using a Nanoporous Membrane

    Directory of Open Access Journals (Sweden)

    Md. Shehadul Islam

    2017-02-01

    Full Text Available Pathogenic bacteria such as Escherichia coli O157, Salmonella and Campylobacter are the main causes for food and waterborne illnesses. Lysis of these bacteria is an important component of the sample preparation for molecular identification of these pathogens. The pathogenicity of these bacteria is so high that they cause illness at very low concentrations (1–10 CFU/100 mL. Hence, there is a need to develop methods to collect a small number of such bacterial cells from a large sample volume and process them in an automated reagent-free manner. An electrical method to concentrate the bacteria and lyse them has been chosen here as it is reagent free and hence more conducive for online and automated sample preparation. We use commercially available nanoporous membranes sandwiched between two microfluidic channels to create thousands of parallel nanopore traps for bacteria, electrophoretically accumulate and then lyse them. The nanopores produce a high local electric field for lysis at moderate applied voltages, which could simplify instrumentation and enables lysis of the bacteria as it approaches them under an appropriate range of electric field (>1000 V/cm. Accumulation and lysis of bacteria on the nanoporous membrane is demonstrated by using the LIVE/DEAD BacLight Bacterial Viability Kit and quantified by fluorescence intensity measurements. The efficiency of the device was determined through bacterial culture of the lysate and was found to be 90% when a potential of 300 V was applied for 3 min.

  2. High-Efficiency Multiscale Modeling of Cell Deformations in Confined Microenvironments in Microcirculation and Microfluidic Devices

    Science.gov (United States)

    Lu, Huijie; Peng, Zhangli

    2017-11-01

    Our goal is to develop a high-efficiency multiscale modeling method to predict the stress and deformation of cells during the interactions with their microenvironments in microcirculation and microfluidic devices, including red blood cells (RBCs) and circulating tumor cells (CTCs). There are more than 1 billion people in the world suffering from RBC diseases, e.g. anemia, sickle cell diseases, and malaria. The mechanical properties of RBCs are changed in these diseases due to molecular structure alternations, which is not only important for understanding the disease pathology but also provides an opportunity for diagnostics. On the other hand, the mechanical properties of cancer cells are also altered compared to healthy cells. This can lead to acquired ability to cross the narrow capillary networks and endothelial gaps, which is crucial for metastasis, the leading cause of cancer mortality. Therefore, it is important to predict the deformation and stress of RBCs and CTCs in microcirculations. We are developing a high-efficiency multiscale model of cell-fluid interaction to study these two topics.

  3. A mathematical model of breast cancer cell motion through a microfluidic device

    Science.gov (United States)

    Barber, Jared

    2017-11-01

    Deaths due to breast cancer are usually caused by metastases at other locations (e.g. bone), not by the primary tumor. Much research has targeted understanding how to lower the metastatic potential of individual breast cancer cells with the end goal being the mitigation of the effects of breast cancer on the 3.5 million people in the US affected by the disease. Experiments show that metastatic potential correlates well with the physical properties of a cell and its surrounding environment. Biology also suggests that mechanotransduction of cellular pathways (e.g. apoptosis, division) can affect metastatic potential. Because of these insights, we are developing a mechanical model of breast cancer cell translocation in microvessels. Our first model is a two-dimensional model with interconnected viscoelastic elements submersed in a surrounding Stokes flow. This model has been used to consider breast cancer cell translocation through a microfluidic device that was designed as a diagnostic tool for assessing the metastatic potential of breast cells. We will present this current model and share results. We believe that further development of this model will allow consideration of metastatic potential in both in vitro and in vivo settings.

  4. Optimization of a microfluidic based electromagnetic energy harvester for shoe insoles

    Science.gov (United States)

    Rahman, M. M.; Atkin, R.; Kim, H.

    2015-12-01

    This paper reports improved performance of the 4th generation microfluidic based energy harvester by finding global optimization among various geometric parameters, resulting in the increase of power density by 6.89 times. Specifically, the power output was optimized by varying diameters and spans of a coil at different frequencies. To verify the optimization, a custom testing platform was constructed, which mimicked the periodic linear movement caused by a human foot. The final device produced total power of 455.77mW from a volume of 20×3.74×0.75cm3, resulting in a power density of 8.13mW/cm3 that was identified as one of the highest power densities among human-body-induced vibration based energy harvesters.

  5. A microfluidic device for the continuous culture and analysis of Caenorhabditis elegans in a toxic aqueous environment

    Science.gov (United States)

    Jung, Jaehoon; Nakajima, Masahiro; Tajima, Hirotaka; Huang, Qiang; Fukuda, Toshio

    2013-08-01

    The nematode Caenorhabditis elegans (C. elegans) receives attention as a bioindicator, and the C. elegans condition has been recently analyzed using microfluidic devices equipped with an imaging system. To establish a method without an imaging system, we have proposed a novel microfluidic device with which to analyze the condition of C. elegans from the capacitance change using a pair of micro-electrodes. The device was designed to culture C. elegans, to expose C. elegans to an external stimulus, such as a chemical or toxicant, and to measure the capacitance change which indicates the condition of C. elegans. In this study, to demonstrate the capability of our device in a toxic aqueous environment, the device was applied to examine the effect of cadmium on C. elegans. Thirty L4 larval stage C. elegans were divided into three groups. One group was a control group and the other groups were exposed to cadmium solutions with concentrations of 5% and 10% LC50 for 24 h. The capacitance change and the body volume of C. elegans as a reference were measured four times and we confirmed the correlation between them. It shows that our device can analyze the condition of C. elegans without an imaging system.

  6. Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices.

    Directory of Open Access Journals (Sweden)

    David A Selck

    Full Text Available Nucleic acid amplification tests that are coupled with a digital readout enable the absolute quantification of single molecules, even at ultralow concentrations. Digital methods are robust, versatile and compatible with many amplification chemistries including isothermal amplification, making them particularly invaluable to assays that require sensitive detection, such as the quantification of viral load in occult infections or detection of sparse amounts of DNA from forensic samples. A number of microfluidic platforms are being developed for carrying out digital amplification. However, the mechanistic investigation and optimization of digital assays has been limited by the lack of real-time kinetic information about which factors affect the digital efficiency and analytical sensitivity of a reaction. Commercially available instruments that are capable of tracking digital reactions in real-time are restricted to only a small number of device types and sample-preparation strategies. Thus, most researchers who wish to develop, study, or optimize digital assays rely on the rate of the amplification reaction when performed in a bulk experiment, which is now recognized as an unreliable predictor of digital efficiency. To expand our ability to study how digital reactions proceed in real-time and enable us to optimize both the digital efficiency and analytical sensitivity of digital assays, we built a custom large-format digital real-time amplification instrument that can accommodate a wide variety of devices, amplification chemistries and sample-handling conditions. Herein, we validate this instrument, we provide detailed schematics that will enable others to build their own custom instruments, and we include a complete custom software suite to collect and analyze the data retrieved from the instrument. We believe assay optimizations enabled by this instrument will improve the current limits of nucleic acid detection and quantification, improving our

  7. Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device.

    Directory of Open Access Journals (Sweden)

    Brian J Kirby

    Full Text Available Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI microfluidic device that combines an anti-prostate specific membrane antigen (PSMA antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45- cells revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2-400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new

  8. Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices.

    Science.gov (United States)

    Selck, David A; Ismagilov, Rustem F

    2016-01-01

    Nucleic acid amplification tests that are coupled with a digital readout enable the absolute quantification of single molecules, even at ultralow concentrations. Digital methods are robust, versatile and compatible with many amplification chemistries including isothermal amplification, making them particularly invaluable to assays that require sensitive detection, such as the quantification of viral load in occult infections or detection of sparse amounts of DNA from forensic samples. A number of microfluidic platforms are being developed for carrying out digital amplification. However, the mechanistic investigation and optimization of digital assays has been limited by the lack of real-time kinetic information about which factors affect the digital efficiency and analytical sensitivity of a reaction. Commercially available instruments that are capable of tracking digital reactions in real-time are restricted to only a small number of device types and sample-preparation strategies. Thus, most researchers who wish to develop, study, or optimize digital assays rely on the rate of the amplification reaction when performed in a bulk experiment, which is now recognized as an unreliable predictor of digital efficiency. To expand our ability to study how digital reactions proceed in real-time and enable us to optimize both the digital efficiency and analytical sensitivity of digital assays, we built a custom large-format digital real-time amplification instrument that can accommodate a wide variety of devices, amplification chemistries and sample-handling conditions. Herein, we validate this instrument, we provide detailed schematics that will enable others to build their own custom instruments, and we include a complete custom software suite to collect and analyze the data retrieved from the instrument. We believe assay optimizations enabled by this instrument will improve the current limits of nucleic acid detection and quantification, improving our fundamental

  9. Fabrication of cyclo olefin polymer microfluidic devices for trapping and culturing of yeast cells.

    Science.gov (United States)

    Puza, Sevde; Gencturk, Elif; Odabasi, Irem E; Iseri, Emre; Mutlu, Senol; Ulgen, Kutlu O

    2017-06-01

    A microfluidic platform is designed and fabricated to investigate the role of uncharacterized YOR060C (Sld7) protein in aging in yeast cells for the first time. Saccharomyces cerevisiae yeast cells are trapped in the series of C-shaped regions (0.5 nL) of COP (cyclo olefin polymer), PMMA (poly methylmethacrylate), or PS (polystyrene) microbioreactors. The devices are fabricated using hot embossing and thermo-compression bonding methods. Photolithography and electrochemical etching are used to form the steel mold needed for hot embossing. The cell cycle processes are investigated by monitoring green fluorescent protein (GFP) tagged Sld7 expressions under normal as well as calorie restricted conditions. The cells are loaded at 1 μL/min flowrate and trapped successfully within each chamber. The medium is continuously fed at 0.1 μL/min throughout the experiments. Fluorescent signals of the low abundant Sld7 proteins could be distinguished only on COP devices. The background fluorescence of COP is found 1.22 and 7.24 times lower than that of PMMA, and PS, respectively. Hence, experiments are continued with COP, and lasted for more than 40 h without any contamination. The doubling time of the yeast cells are found as 72 min and 150 min, and the growth rates as 9.63 × 10 -3  min -1 and 4.62 × 10 -3  min -1 , in 2% glucose containing YPD and YNB medium, respectively. The product concentration (Sld7p:GFP) increased in accordance with cell growth. The dual role of Sld7 protein in both cell cycle and chronological aging needs to be further investigated following the preliminary experimental results.

  10. The Evopopbot Chip: Ultra High-throughput Evolutionary Population Bottlenecking using Drop-Based Microfluidics

    Science.gov (United States)

    Chang, Connie; Rotem, Assaf; Serohijos, Adrian; Zhang, Huidan; Tao, Ye; Fischer Hesselbrock, Audrey; Thielen, Peter; Mehoke, Thomas; Wolfe, Joshua; Wobus, Christiane; Feldman, Andrew; Shakhnovich, Eugene; Weitz, David

    2014-03-01

    The study of how viruses propagate is important for curing disease and preventing viral outbreaks. In nature, viruses can compete with one another, and the most evolutionary fit virus usually takes over a population. Yet there exist variants in the population that can escape subjected evolutionary pressures and eventually dominate the population. Successful studies of viral epidemics hinges on the ability to access these variants. Here, we present the use of droplet-based microfluidics as a simple method to segregate and propagate a viral population as individual viral lineages, simultaneously performing millions of in vitroevolutionary bottlenecking experiments. We introduce a novel microfluidic device, called the ``Evopopbot Chip'', that allows for simultaneous passaging of millions of evolutionary bottlenecking events by splitting drops containing previous generations of viruses and merging with drops containing new host cells. After several generations of viral replication in the evolution chip, we discover hundreds of new viruses that are able to escape a neutralizing antibody selection pressure compared to bulk passaging.

  11. Design, development and characterization of microfluidic media for continuous size-based separation of particles

    Science.gov (United States)

    Devendra, Raghavendra

    Microfluidics is a growing field of research in separations. Microfluidic technologies offer a greater control over system properties with an efficient performance while providing a potential for integration of several processes into one micro-total-analysis system. While several conventional separation technologies have been miniaturized to micro-scale techniques, there is an effort to develop novel processes that take advantage of the features of micro-scale flows, such as similarities in pore-species dimensions and the ability to tailor the geometric structures of the stationary phase to specific applications. In certain cases, the geometric structure of the pore space drives the separative displacement; the advances in microfabrication allow greater control over the geometry as well as the surface chemistry of the media. It is convenient and possible to integrate the microstructure into main separation channel and design autonomous continuous flow separation systems on a lab-on-achip platform. A promising approach to develop passive and continuous flow microfluidic separation devices is to design periodic arrays of obstacles that cause different species to move in different directions within the device, also known as vector chromatography. The principle of separation of small particles in such periodic microstructures is based on the mobility of particles. The mobility of a particle is based on its size, the geometry of the stationary phase and the viscosity of the suspending phase. In the first part of this thesis, we present a study of diffusive transport in periodic anisotropic systems. We designed and fabricated anisotropic periodicities in microfluidic devices and characterized the mobilities in principal directions by directly measuring the one dimensional diffusivities through experiments. In anisotropic periodic microstructures, the mobility has unequal components, by virtue of which the velocity of the particle does not remain collinear with the

  12. A compact and facile microfluidic droplet creation device using a piezoelectric diaphragm micropump for droplet digital PCR platforms.

    Science.gov (United States)

    Okura, Naoaki; Nakashoji, Yuta; Koshirogane, Toshihiro; Kondo, Masaki; Tanaka, Yugo; Inoue, Kohei; Hashimoto, Masahiko

    2017-10-01

    We have exploited a compact and facile microfluidic droplet creation device consisting of a poly(dimethylsiloxane) microfluidic chip possessing T-junction channel geometry, two inlet reservoirs, and one outlet reservoir, and a piezoelectric (PZT) diaphragm micropump with controller. Air was evacuated from the outlet reservoir using the PZT pump, reducing the pressure inside. The reduced pressure within the outlet reservoir pulled oil and aqueous solution preloaded in the inlet reservoirs into the microchannels, which then merged at the T-junction, successfully forming water-in-oil emulsion droplets at a rate of ∼1000 per second with minimal sample loss. We confirmed that the onset of droplet formation occurred immediately after turning on the pump (<1 s). Over repeated runs, droplet formation was highly reproducible, with droplet size purity (polydispersity, <4%) comparable to that achieved using other microfluidic droplet preparation techniques. We also demonstrated single-molecule PCR amplification in the created droplets, suggesting that the device could be used for effective droplet digital PCR platforms in most laboratories without requiring great expense, space, or time for acquiring technical skills. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Paper-based smart microfluidics for education and low-cost diagnostics

    CSIR Research Space (South Africa)

    Smith, S

    2015-11-01

    Full Text Available to develop PoC diagnostic solutions. Specifically, the emerging field of paper-based microfluidics, with advantages such as low-cost, disposability and minimal external equipment requirements, provides unique opportunities for addressing healthcare issues...

  14. Study on the Optimum Cutting Parameters of an Aluminum Mold for Effective Bonding Strength of a PDMS Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Caffiyar Mohamed Yousuff

    2017-08-01

    Full Text Available Master mold fabricated using micro milling is an easy way to develop the polydimethylsiloxane (PDMS based microfluidic device. Achieving high-quality micro-milled surface is important for excellent bonding strength between PDMS and glass slide. The aim of our experiment is to study the optimal cutting parameters for micro milling an aluminum mold insert for the production of a fine resolution microstructure with the minimum surface roughness using conventional computer numerical control (CNC machine systems; we also aim to measure the bonding strength of PDMS with different surface roughnesses. Response surface methodology was employed to optimize the cutting parameters in order to obtain high surface smoothness. The cutting parameters were demonstrated with the following combinations: 20,000 rpm spindle speed, 50 mm/min feed rate, depth of cut 5 µm with tool size 200 µm or less; this gives a fine resolution microstructure with the minimum surface roughness and strong bonding strength between PDMS–PDMS and PDMS–glass.

  15. SAW-Based Phononic Crystal Microfluidic Sensor-Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications.

    Science.gov (United States)

    Oseev, Aleksandr; Lucklum, Ralf; Zubtsov, Mikhail; Schmidt, Marc-Peter; Mukhin, Nikolay V; Hirsch, Soeren

    2017-09-23

    The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept.

  16. Fabrication of continuous flow microfluidics device with 3D electrode structures for high throughput DEP applications using mechanical machining.

    Science.gov (United States)

    Zeinali, Soheila; Çetin, Barbaros; Oliaei, Samad Nadimi Bavil; Karpat, Yiğit

    2015-07-01

    Microfluidics is the combination of micro/nano fabrication techniques with fluid flow at microscale to pursue powerful techniques in controlling and manipulating chemical and biological processes. Sorting and separation of bio-particles are highly considered in diagnostics and biological analyses. Dielectrophoresis (DEP) has offered unique advantages for microfluidic devices. In DEP devices, asymmetric pair of planar electrodes could be employed to generate non-uniform electric fields. In DEP applications, facing 3D sidewall electrodes is considered to be one of the key solutions to increase device throughput due to the generated homogeneous electric fields along the height of microchannels. Despite the advantages, fabrication of 3D vertical electrodes requires a considerable challenge. In this study, two alternative fabrication techniques have been proposed for the fabrication of a microfluidic device with 3D sidewall electrodes. In the first method, both the mold and the electrodes are fabricated using high precision machining. In the second method, the mold with tilted sidewalls is fabricated using high precision machining and the electrodes are deposited on the sidewall using sputtering together with a shadow mask fabricated by electric discharge machining. Both fabrication processes are assessed as highly repeatable and robust. Moreover, the two methods are found to be complementary with respect to the channel height. Only the manipulation of particles with negative-DEP is demonstrated in the experiments, and the throughput values up to 105 particles / min is reached in a continuous flow. The experimental results are compared with the simulation results and the limitations on the fabrication techniques are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Preparing e18 cortical rat neurons for compartmentalization in a microfluidic device.

    Science.gov (United States)

    Harris, Joseph; Lee, Hyuna; Tu, Christina Tu; Cribbs, David; Cotman, Carl; Jeon, Noo Li

    2007-01-01

    In this video, we demonstrate the preparation of E18 cortical rat neurons. E18 cortical rat neurons are obtained from E18 fetal rat cortex previously dissected and prepared. The E18 cortex is, upon dissection, immediately dissociated into individual neurons. It is possible to store E18 cortex in Hibernate E buffer containing B27 at 4 degrees C for up to a week before the dissociation is performed. However, there will be a drop in cell viability. Typically we obtain our E18 Cortex fresh. It is transported to the lab in ice cold Calcium free Magnesium free dissection buffer (CMFM). Upon arrival, trypsin is added to the cortex to a final concentration of 0.125%. The cortex is then incubated at 37 degrees C for 8 minutes. DMEM containing 10% FBS is added to the cortex to stop the reaction. The cortex is then centrifuged at 2500 rpm for 2 minutes. The supernatant is removed and 2 ml of Neural Basal Media (NBM) containing 2% B27 (vol/vol) and 0.25% Glutamax (vol/vol) is added to the cortex which is then re-suspended by pipetting up and down. Next, the cortex is triturated with previously fire polished glass pipettes, each with a successive smaller opening. After triturating, the cortex is once again centrifuged at 2500 rpm for 2 minutes. The supernatant is then removed and the cortex pellet re-suspended with 2 ml of NBM containing B27 and Glutamax. The cell suspension is then passed through a 40 um nylon cell strainer. Next the cells are counted. The neurons are now ready for loading into the neuron microfluidic device.

  18. Sampling and electrophoretic analysis of segmented flow streams using virtual walls in a microfluidic device.

    Science.gov (United States)

    Roman, Gregory T; Wang, Meng; Shultz, Kristin N; Jennings, Colin; Kennedy, Robert T

    2008-11-01

    A method for sampling and electrophoretic analysis of aqueous plugs segmented in a stream of immiscible oil is described. In the method, an aqueous buffer and oil stream flow parallel to each other to form a stable virtual wall in a microfabricated K-shaped fluidic element. As aqueous sample plugs in the oil stream make contact with the virtual wall, coalescence occurs and sample is electrokinetically transferred to the aqueous stream. Using this virtual wall, two methods of injection for channel electrophoresis were developed. In the first, discrete sample zones flow past the inlet of an electrophoresis channel and a portion is injected by electroosmotic flow, termed the "discrete injector". With this approach at least 800 plugs could be injected without interruption from a continuous segmented stream with 5.1% RSD in peak area. This method generated up to 1,050 theoretical plates, although analysis of the injector suggested that improvements may be possible. In a second method, aqueous plugs are sampled in a way that allows them to form a continuous stream that is directed to a microfluidic cross-style injector, termed the "desegmenting injector". This method does not analyze each individual plug but instead allows periodic sampling of a high-frequency stream of plugs. Using this system at least 1000 injections could be performed sequentially with 5.8% RSD in peak area and 53,500 theoretical plates. This method was demonstrated to be useful for monitoring concentration changes from a sampling device with 10 s temporal resolution. Aqueous plugs in segmented flows have been applied to many different chemical manipulations including synthesis, assays, sampling processing and sampling. Nearly all such studies have used optical methods to analyze plug contents. This method offers a new way to analyze such samples and should enable new applications of segmented flow systems.

  19. Integrated microfluidic system for rapid detection of influenza H1N1 virus using a sandwich-based aptamer assay.

    Science.gov (United States)

    Tseng, Yi-Ting; Wang, Chih-Hung; Chang, Chih-Peng; Lee, Gwo-Bin

    2016-08-15

    The rapid spread of influenza-associated H1N1 viruses has caused serious concern in recent years. Therefore, there is an urgent need for the development of automatic, point-of-care devices for rapid diagnosis of the influenza virus. Conventional approaches suffer from several critical issues; notably, they are time-consuming, labor-intensive, and are characterized by relatively low sensitivity. In this work, we present a new approach for fluorescence-based detection of the influenza A H1N1 virus using a sandwich-based aptamer assay that is automatically performed on an integrated microfluidic system. The entire detection process was shortened to 30min using this chip-based system which is much faster than the conventional viral culture method. The limit of detection was significantly improved to 0.032 hemagglutination unit due to the high affinity and high specificity of the H1N1-specific aptamers. The results showed that the two-aptamer microfluidic system had about 10(3) times higher sensitivity than the conventional serological diagnosis. It was demonstrated that the developed microfluidic system may play as a powerful tool in the detection of the H1N1 virus. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Microfluidic multiplexing of solid-state nanopores

    Science.gov (United States)

    Jain, Tarun; Rasera, Benjamin C.; Guerrero, Ricardo Jose S.; Lim, Jong-Min; Karnik, Rohit

    2017-12-01

    Although solid-state nanopores enable electronic analysis of many clinically and biologically relevant molecular structures, there are few existing device architectures that enable high-throughput measurement of solid-state nanopores. Herein, we report a method for microfluidic integration of multiple solid-state nanopores at a high density of one nanopore per (35 µm2). By configuring microfluidic devices with microfluidic valves, the nanopores can be rinsed from a single fluid input while retaining compatibility for multichannel electrical measurements. The microfluidic valves serve the dual purpose of fluidic switching and electric switching, enabling serial multiplexing of the eight nanopores with a single pair of electrodes. Furthermore, the device architecture exhibits low noise and is compatible with electroporation-based in situ nanopore fabrication, providing a scalable platform for automated electronic measurement of a large number of integrated solid-state nanopores.

  1. Embryonic body culturing in an all-glass microfluidic device with laser-processed 4 μm thick ultra-thin glass sheet filter.

    Science.gov (United States)

    Yalikun, Y; Tanaka, N; Hosokawa, Y; Iino, T; Tanaka, Y

    2017-09-19

    In this paper, we report the development and demonstration of a method to fabricate an all-glass microfluidic cell culturing device without circulation flow. On-chip microfluidic cell culturing is an indispensable technique for cellular replacement therapies and experimental cell biology. Polydimethylsiloxane (PDMS) have become a popular material for fabricating microfluidic cell culture devices because it is a transparent, biocompatible, deformable, easy-to-mold, and gas-permeable. However, PDMS is also a chemically and physically unstable material. For example, PDMS undergoes aging easily even in room temperature conditions. Therefore, it is difficult to control long term experimental culturing conditions. On the other hand, glass is expected to be stable not only in physically but also chemically even in the presence of organic solvents. However, cell culturing still requires substance exchanges such as gases and nutrients, and so on, which cannot be done in a closed space of a glass device without circulation flow that may influence cell behavior. Thus, we introduce a filter structure with micropores onto a glass device to improve permeability to the cell culture space. Normally, it is extremely difficult to fabricate a filter structure on a normal glass plate by using a conventional fabrication method. Here, we demonstrated a method for fabricating an all-glass microfluidic cell culturing device having filters structure. The function of this all-glass culturing device was confirmed by culturing HeLa, fibroblast and ES cells. Compared with the closed glass devices without a filter structure, the numbers of cells in our device increased and embryonic bodies (EBs) were formed. This method offers a new tool in microfluidic cell culture technology for biological analysis and it expands the field of microfluidic cell culture.

  2. Bead-Based Microfluidic Sediment Analogues: Fabrication and Colloid Transport.

    Science.gov (United States)

    Guo, Yang; Huang, Jingwei; Xiao, Feng; Yin, Xiaolong; Chun, Jaehun; Um, Wooyong; Neeves, Keith B; Wu, Ning

    2016-09-13

    Mobile colloids can act as carriers for low-solubility contaminants in the environment. However, the dominant mechanism for this colloid-facilitated transport of chemicals is unclear. Therefore, we developed a bead-based microfluidic platform of sediment analogues and measured both single and population transport of model colloids. The porous medium is assembled through a bead-by-bead injection method. This approach has the versatility to build both electrostatically homogeneous and heterogeneous media at the pore scale. A T-junction at the exit also allowed for encapsulation and enumeration of colloids effluent at single particle resolution to give population dynamics. Tortuosity calculated from pore-scale trajectory analysis and its comparison with lattice Boltzmann simulations revealed that transport of colloids was influenced by the size exclusion effect. The porous media packed by positively and negatively charged beads into two layers showed distinctive colloidal particle retention and significant remobilization and re-adsorption of particles during water flushing. We demonstrated the potential of our method to fabricate porous media with surface heterogeneities at the pore scale. With both single and population dynamics measurement, our platform has the potential to connect pore-scale and macroscale colloid transport on a lab scale and to quantify the impact of grain surface heterogeneities that are natural in the subsurface environment.

  3. Benzocyclobutene (BCB) based neural implants with microfluidic channel.

    Science.gov (United States)

    Lee, K; He, J; Wang, L

    2004-01-01

    Benzocyclobutene (BCB) based intracortical neural implants for basic neuroscience research in animal models was fabricated, in which microfluidic channel was embedded to deliver chemical reagents. BCB presents several attractive features for chronic applications: flexibility, biocompatibility, desirable chemical and electrical properties, and can be easily manufactured using existing batch microfabrication technology; The fabricated implants have single shank with three recording sites (20 x 20 microm) and two reservoirs (inlet and outlet). The channel had large volume (40 microm width and 10 microm height), and hydrophobic surface to provide a high degree of chemical inertness. All the recording sites were positioned near the end of the shank in order to increase the probability of recording neural signals from a target volume of tissue. In vitro biocompatibility tests of fabricated implants revealed no adverse toxic effects on cultured cells. The implant with a 5 microm silicon backbone layer penetrated rat's pia without buckling, a major drawback of polymer alone. The averaged impedance value at 1 kHz was approximately 1.2 MOmega. Water flowing through the channel was observed. Depending on the amount of the driving pressure from the syringes, the delivery speed of the water was totally controlled.

  4. Utilizing microfluidics to synthesize polyethylene glycol microbeads for Förster resonance energy transfer based glucose sensing

    Science.gov (United States)

    Kantak, Chaitanya; Zhu, Qingdi; Beyer, Sebastian; Bansal, Tushar; Trau, Dieter

    2012-01-01

    Here, we utilize microfluidic droplet technology to generate photopolymerizeable polyethylene glycol (PEG) hydrogel microbeads incorporating a fluorescence-based glucose bioassay. A microfluidic T-junction and multiphase flow of fluorescein isothiocyanate dextran, tetramethyl rhodamine isothiocyanate concanavalin A, and PEG in water were used to generate microdroplets in a continuous stream of hexadecane. The microdroplets were photopolymerized mid-stream with ultraviolet light exposure to form PEG microbeads and were collected at the outlet for further analysis. Devices were prototyped in PDMS and generated highly monodisperse 72 ± 2 μm sized microbeads (measured after transfer into aqueous phase) at a continuous flow rate between 0.04 ml/h—0.06 ml/h. Scanning electron microscopy analysis was conducted to analyze and confirm microbead integrity and surface morphology. Glucose sensing was carried out using a Förster resonance energy transfer (FRET) based assay. A proportional fluorescence intensity increase was measured within a 1–10 mM glucose concentration range. Microfluidically synthesized microbeads encapsulating sensing biomolecules offer a quick and low cost method to generate monodisperse biosensors for a variety of applications including cell cultures systems, tissue engineering, etc. PMID:22655010

  5. Microfluidic desalination techniques and their potential applications.

    Science.gov (United States)

    Roelofs, S H; van den Berg, A; Odijk, M

    2015-09-07

    In this review we discuss recent developments in the emerging research field of miniaturized desalination. Traditionally desalination is performed to convert salt water into potable water and research is focused on improving performance of large-scale desalination plants. Microfluidic desalination offers several new opportunities in comparison to macro-scale desalination, such as providing a platform to increase fundamental knowledge of ion transport on the nano- and microfluidic scale and new microfluidic sample preparation methods. This approach has also lead to the development of new desalination techniques, based on micro/nanofluidic ion-transport phenomena, which are potential candidates for up-scaling to (portable) drinking water devices. This review assesses microfluidic desalination techniques on their applications and is meant to contribute to further implementation of microfluidic desalination techniques in the lab-on-chip community.

  6. Performance Study of Acoustophoretic Microfluidic Silicon-Glass Devices by Characterization of Material- and Geometry-Dependent Frequency Spectra

    DEFF Research Database (Denmark)

    Garofalo, Fabio; Laurell, Thomas; Bruus, Henrik

    2017-01-01

    The mechanical and electrical response of acoustophoretic microfluidic devices attached to an ac-voltage-driven piezoelectric transducer is studied by means of numerical simulations. The governing equations are formulated in a variational framework that, introducing Lagrangian and Hamiltonian...... of the hard-to-measure mechanical indicators is correlated to that of the easy-to-measure electrical indicators, and, by introducing optimality criteria, it is clarified to which extent the latter suffices to identify optimal driving frequencies as the geometric configuration and the material parameters vary....... The latter have been varied by considering both Pyrex and aluminium nitroxide top-lid materials....

  7. A robust microfluidic device for the synthesis and crystal growth of organometallic polymers with highly organized structures.

    Science.gov (United States)

    Liu, Xiao; Yi, Qiaolian; Han, Yongzhen; Liang, Zhenning; Shen, Chaohua; Zhou, Zhengyang; Sun, Jun-Liang; Li, Yizhi; Du, Wenbin; Cao, Rui

    2015-02-02

    A simple and robust microfluidic device was developed to synthesize organometallic polymers with highly organized structures. The device is compatible with organic solvents. Reactants are loaded into pairs of reservoirs connected by a 15 cm long microchannel prefilled with solvents, thus allowing long-term counter diffusion for self-assembly of organometallic polymers. The process can be monitored, and the resulting crystalline polymers are harvested without damage. The device was used to synthesize three insoluble silver acetylides as single crystals of X-ray diffraction quality. Importantly, for the first time, the single-crystal structure of silver phenylacetylide was determined. The reported approach may have wide applications, such as crystallization of membrane proteins, synthesis and crystal growth of organic, inorganic, and polymeric coordination compounds, whose single crystals cannot be obtained using traditional methods. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Successes and future outlook for microfluidics-based cardiovascular drug discovery.

    Science.gov (United States)

    Skommer, Joanna; Wlodkowic, Donald

    2015-03-01

    The greatest advantage of using microfluidics as a platform for the assessment of cardiovascular drug action is its ability to finely regulate fluid flow conditions, including flow rate, shear stress and pulsatile flow. At the same time, microfluidics provide means for modifying the vessel geometry (bifurcations, stenoses, complex networks), the type of surface of the vessel walls, and for patterning cells in 3D tissue-like architecture, including generation of lumen walls lined with cells and heart-on-a-chip structures for mimicking ventricular cardiomyocyte physiology. In addition, owing to the small volume of required specimens, microfluidics is ideally suited to clinical situations whereby monitoring of drug dosing or efficacy needs to be coupled with minimal phlebotomy-related drug loss. In this review, the authors highlight potential applications for the currently existing and emerging technologies and offer several suggestions on how to close the development cycle of microfluidic devices for cardiovascular drug discovery. The ultimate goal in microfluidics research for drug discovery is to develop 'human-on-a-chip' systems, whereby several organ cultures, including the vasculature and the heart, can mimic complex interactions between the organs and body systems. This would provide in vivo-like pharmacokinetics and pharmacodynamics for drug ADMET assessment. At present, however, the great variety of available designs does not go hand in hand with their use by the pharmaceutical community.

  9. Routing-based Synthesis of Digital Microfluidic Biochips

    DEFF Research Database (Denmark)

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2010-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the basic functsions for biochemical analysis. The "digital" microfluidic biochips are manipulating liquids not as a continuous flow, but as discrete droplets on a two-dimensional array...... the concept of virtual modules and allow the droplets to move on the chip on any route during operation execution. Thus, the synthesis problem is transformed into a routing problem. We propose an approach derived from a Greedy Randomized Adaptive Search Procedure (GRASP) and we show that by considering...

  10. From bioseparation to artificial micro-organs: microfluidic chip based particle manipulation techniques

    Science.gov (United States)

    Stelzle, Martin

    2010-02-01

    Microfluidic device technology provides unique physical phenomena which are not available in the macroscopic world. These may be exploited towards a diverse array of applications in biotechnology and biomedicine ranging from bioseparation of particulate samples to the assembly of cells into structures that resemble the smallest functional unit of an organ. In this paper a general overview of chip-based particle manipulation and separation is given. In the state of the art electric, magnetic, optical and gravitational field effects are utilized. Also, mechanical obstacles often in combination with force fields and laminar flow are employed to achieve separation of particles or molecules. In addition, three applications based on dielectrophoretic forces for particle manipulation in microfluidic systems are discussed in more detail. Firstly, a virus assay is demonstrated. There, antibody-loaded microbeads are used to bind virus particles from a sample and subsequently are accumulated to form a pico-liter sized aggregate located at a predefined position in the chip thus enabling highly sensitive fluorescence detection. Secondly, subcellular fractionation of mitochondria from cell homogenate yields pure samples as was demonstrated by Western Blot and 2D PAGE analysis. Robust long-term operation with complex cell homogenate samples while avoiding electrode fouling is achieved by a set of dedicated technical means. Finally, a chip intended for the dielectrophoretic assembly of hepatocytes and endothelial cells into a structure resembling a liver sinusoid is presented. Such "artificial micro organs" are envisioned as substance screening test systems providing significantly higher predictability with respect to the in vivo response towards a substance under test.

  11. Design and development of electrochemical polymer-based lab-on-a-disc devices for biological applications

    DEFF Research Database (Denmark)

    Sanger, Kuldeep

    detection based centrifugal microfluidic platforms towards applications in bioprocess monitoring, medical diagnostics, food and environmental analysis, etc. Stencil based electrode fabrication approach was developed and optimized to pattern reliable and reproducible electrodes on a polymeric substrate. Also......, enrichment). The applicability of the developed microfluidic systems was demonstrated by monitoring a biological process, namely quantifying the amount of the bacterial metabolite p-Coumaric acid (pHCA) produced by genetically modified E. coli cells. The first generation LoD device (with integrated...

  12. Plastic-Based Structurally Programmable Microfluidic Biochips for Clinical Diagnostics

    National Research Council Canada - National Science Library

    Ahn, Chong H; Nevin, Joseph H; Beaucage, Gregory

    2005-01-01

    .... Through the project, an innovative, fully integrated, plastic microfluidic lab-on-a-chip has been successfully developed and characterized for the dual applications of a stand-alone smart disposable polymer lab-on-a-chip as well as a wrist watch-type blood analyzer.

  13. Interconnection blocks with minimal dead volumes permitting planar interconnection to thin microfluidic devices

    DEFF Research Database (Denmark)

    Sabourin, David; Snakenborg, Detlef; Dufva, Martin

    2010-01-01

    We have previously described 'Interconnection Blocks' which are re-usable, non-integrated PDMS blocks which allowing multiple, aligned and planar microfluidic interconnections. Here, we describe Interconnection Block versions with zero dead volumes that allow fluidic interfacing to flat or thin s...

  14. Electron beam fabrication of a microfluidic device for studying submicron-scale bacteria

    NARCIS (Netherlands)

    Moolman, M.C.; Huang, Z.; Krishnan, S.T.; Kerssemakers, J.W.J.; Dekker, N.H.

    2013-01-01

    Background: Controlled restriction of cellular movement using microfluidics allows one to study individual cells to gain insight into aspects of their physiology and behaviour. For example, the use of micron-sized growth channels that confine individual Escherichia coli has yielded novel insights

  15. Microfluidic devices for analysis and active optical sorting of individual cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Jan; Pilát, Zdeněk; Šerý, Mojmír; Kaňka, Jan; Samek, Ota; Bernatová, Silvie; Zemánek, Pavel

    2013-01-01

    Roč. 58, č. 2 (2013), s. 55-59 ISSN 0447-6441 R&D Projects: GA MPO FR-TI1/433; GA MŠk ED0017/01/01; GA ČR GAP205/11/1687 Institutional support: RVO:68081731 Keywords : microfluidic * cell sorting * optical tweezers * Raman spectroscopy Subject RIV: EI - Biotechnology ; Bionics

  16. Fundamentals of rapid injection molding for microfluidic cell-based assays.

    Science.gov (United States)

    Lee, Ulri N; Su, Xiaojing; Guckenberger, David J; Dostie, Ashley M; Zhang, Tianzi; Berthier, Erwin; Theberge, Ashleigh B

    2018-01-30

    Microscale cell-based assays have demonstrated unique capabilities in reproducing important cellular behaviors for diagnostics and basic biological research. As these assays move beyond the prototyping stage and into biological and clinical research environments, there is a need to produce microscale culture platforms more rapidly, cost-effectively, and reproducibly. 'Rapid' injection molding is poised to meet this need as it enables some of the benefits of traditional high volume injection molding at a fraction of the cost. However, rapid injection molding has limitations due to the material and methods used for mold fabrication. Here, we characterize advantages and limitations of rapid injection molding for microfluidic device fabrication through measurement of key features for cell culture applications including channel geometry, feature consistency, floor thickness, and surface polishing. We demonstrate phase contrast and fluorescence imaging of cells grown in rapid injection molded devices and provide design recommendations to successfully utilize rapid injection molding methods for microscale cell-based assay development in academic laboratory settings.

  17. Fast and accurate enzyme activity measurements using a chip-based microfluidic calorimeter.

    Science.gov (United States)

    van Schie, Morten M C H; Ebrahimi, Kourosh Honarmand; Hagen, Wilfred R; Hagedoorn, Peter-Leon

    2018-03-01

    Recent developments in microfluidic and nanofluidic technologies have resulted in development of new chip-based microfluidic calorimeters with potential use in different fields. One application would be the accurate high-throughput measurement of enzyme activity. Calorimetry is a generic way to measure activity of enzymes, but unlike conventional calorimeters, chip-based calorimeters can be easily automated and implemented in high-throughput screening platforms. However, application of chip-based microfluidic calorimeters to measure enzyme activity has been limited due to problems associated with miniaturization such as incomplete mixing and a decrease in volumetric heat generated. To address these problems we introduced a calibration method and devised a convenient protocol for using a chip-based microfluidic calorimeter. Using the new calibration method, the progress curve of alkaline phosphatase, which has product inhibition for phosphate, measured by the calorimeter was the same as that recorded by UV-visible spectroscopy. Our results may enable use of current chip-based microfluidic calorimeters in a simple manner as a tool for high-throughput screening of enzyme activity with potential applications in drug discovery and enzyme engineering. Copyright © 2017. Published by Elsevier Inc.

  18. Design, fabrication and characterization of nano-filters in silicon microfluidic channels based on MEMS technology.

    Science.gov (United States)

    Chen, Xing; Cui, Dafu; Chen, Jian

    2009-09-01

    Since most clinical assays are performed on cell-free serum or plasma, micro-analytical systems for blood tests require integrated on-chip microfluidics for the isolation of plasma or serum from crude blood samples. In this paper, we present a crossflow filtration method using novel silicon nano-filters for plasma separation. The microfluidic chip is made of a silicon substrate containing micropillar arrays, feed channels, side channels and nano-gap structures, sealed with a PDMS-glass compound cover. The design of the silicon filtration structures were optimized using numerical analysis and the optimal MEMS fabrication procedures were obtained. The filtration structures including nano-filters were characterized using SEM and subsequently used to isolate plasma from whole blood in a continuous manner. Compared with micro-gap structures in silicon microfluidic channels, the nano-gap structures have been used to separate plasma from whole blood samples with higher selectivity, where a maximum plasma selectivity of 97.7% has been obtained. Common problems of clogging and jamming in filtration applications have seldom been noticed in our device. The presented microfluidic filtration device for plasma isolation could be integrated into microTAS for point-of-care diagnostics in the near future.

  19. Microfluidic chemical reaction circuits

    Science.gov (United States)

    Lee, Chung-cheng [Irvine, CA; Sui, Guodong [Los Angeles, CA; Elizarov, Arkadij [Valley Village, CA; Kolb, Hartmuth C [Playa del Rey, CA; Huang, Jiang [San Jose, CA; Heath, James R [South Pasadena, CA; Phelps, Michael E [Los Angeles, CA; Quake, Stephen R [Stanford, CA; Tseng, Hsian-rong [Los Angeles, CA; Wyatt, Paul [Tipperary, IE; Daridon, Antoine [Mont-Sur-Rolle, CH

    2012-06-26

    New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.

  20. Digital microfluidic operations on micro-electrode dot array architecture.

    Science.gov (United States)

    Wang, G; Teng, D; Fan, S-K

    2011-12-01

    As digital microfluidics-based biochips find more applications, their complexity is expected to increase significantly owing to the trend of multiple and concurrent assays on the chip. There is a pressing need to deliver a top-down design methodology that the biochip designer can leverage the same level of computer-aided design support as the semi-conductor industry now does. Moreover, as microelectronics fabrication technology is scaling up and integrated device performance is improving, it is expected that these microfluidic biochips will be integrated with microelectronic components in next-generation system-on-chip designs. This study presents the analysis and experiments of digital microfluidic operations on a novel electrowetting-on-dielectric-based 'micro-electrode dot array architecture' that fosters a development path for hierarchical top-down design approach for digital microfluidics. The proposed architecture allows dynamic configurations and activations of identical basic microfluidic unit called 'micro-electrode cells' to design microfluidic components, layouts, routing, microfluidic operations and applications of the biochip hierarchically. Fundamental microfluidic operations have been successfully performed by the architecture. In addition, this novel architecture demonstrates a number of advantages and flexibilities over the conventional digital microfluidics in performing advanced microfluidic operations.

  1. Hydrophobic marking line used to eliminate the edge effect in a microfluidic point-of-care testing device

    Science.gov (United States)

    Jingmin, Li; Xia, Li; Ziyang, Liu; Chao, Liang; Chong, Liu

    2017-01-01

    The traversal rate for the liquid medium near a point-of-care testing (POCT) device microfluidic channel edge is faster than that through the body of the channel, which makes the fluid front meniscus becomes concave rather than convex or flat. The concave front is unwished due to its influences on quantitative analysis accuracy and the possibility to generate air bubbles. Here, a unique method, named hydrophobic marking line, is demonstrated. This method used a soft pen with hydrophobic ink to draw two lines along the edges of the channel of a POCT device. Results have shown that the marking lines will eliminate the edge effects and generate convex liquid front. The curvature of the liquid front can be changed by adjusting the marking line width or ink solutions.

  2. Droplet-Aware Module-Based Synthesis for Fault-Tolerant Digital Microfluidic Biochips

    DEFF Research Database (Denmark)

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2012-01-01

    , such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a group of electrodes, forming a virtual device. Initially researchers have ignored the locations of droplets during operation execution, and have considered that all electrodes inside devices are occupied.We have...... recently proposed a droplet-aware approach for the execution of operations on the microfluidic array, in which the locations of droplets inside devices are known at each time step. In this article we extend the droplet-aware approach to consider the synthesis of biochips which contain defective electrodes...

  3. Performance Improvements and Congestion Reduction for Routing-based Synthesis for Digital Microfluidic Biochips

    DEFF Research Database (Denmark)

    Windh, Skyler; Phung, Calvin; Grissom, Daniel T.

    2017-01-01

    Routing-based synthesis for digital microfluidic biochips yields faster assay execution times compared to module-based synthesis. We show that routing-based synthesis can lead to deadlocks and livelocks in specific cases, and that dynamically detecting them and adjusting the probabilities...

  4. A centrifugal microfluidic device with integrated gold leaf electrodes for the electrophoretic separation of DNA.

    Science.gov (United States)

    Thompson, Brandon L; Birch, Christopher; Nelson, Daniel A; Li, Jingyi; DuVall, Jacquelyn A; Le Roux, Delphine; Tsuei, An-Chi; Mills, Daniel L; Root, Brian E; Landers, James P

    2016-11-15

    Current conventional methods utilized for forensic DNA analysis are time consuming and labor-intensive requiring large and expensive equipment and instrumentation. While more portable Rapid DNA systems have been developed, introducing them to a working laboratory still necessitates a high cost of initiation followed by the recurrent cost of the devices. This has highlighted the need for an inexpensive, rapid and portable DNA analysis tool for human identification in a forensic setting. In order for an integrated DNA analysis system such as this to be realized, device operations must always be concluded by a rapid separation of short-tandem repeat (STR) DNA fragments. Contributing to this, we report the development of a unique, multi-level, centrifugal microdevice that can perform both reagent loading and DNA separation. The fabrication protocol was inspired by the print, cut and laminate (PCL) technique described previously by our group, and in accordance, offers a rapid and inexpensive option compared with existing approaches. The device comprises multiple polyester-toner fluidic layers, a cyclic olefin copolymer separation domain and integrated gold leaf electrodes. All materials are commercially-available and complement the PCL process in a way that permits fabrication of increasingly sought after single-use devices. All reagents, including a viscous sieving matrix, are loaded centrifugally, eliminating external pneumatic pumping, and the sample is separated in <5 minutes using an effective separation length of only 4 cm (reagent loading to completed separation, is <37 minutes). The protocol for gold leaf electrode manufacture yielded up to 30 electrodes for less than $3 (cost of a 79 mm × 79 mm gold leaf sheet) and when using a device combining these electrodes and centrifugal reagent/polymer loading, the electrophoretic separation of STR fragments with two base resolution was demonstrated. This exemplary performance makes the device an ideal candidate for

  5. Reducing the critical particle diameter in (highly) asymmetric sieve-based lateral displacement devices

    NARCIS (Netherlands)

    Dijkshoorn, J.P.; Schutyser, M.A.I.; Sebris, M.; Boom, R.M.; Wagterveld, R.M.

    2017-01-01

    Deterministic lateral displacement technology was originally developed in the realm of microfluidics, but has potential for larger scale separation as well. In our previous studies, we proposed a sieve-based lateral displacement device inspired on the principle of deterministic lateral

  6. Fast infectious diseases diagnostics based on microfluidic biochip system

    Directory of Open Access Journals (Sweden)

    Qin Huang

    2017-03-01

    Full Text Available Molecular diagnostics is one of the most important tools currently in use for clinical pathogen detection due to its high sensitivity, specificity, and low consume of sample and reagent is keyword to low cost molecular diagnostics. In this paper, a sensitive DNA isothermal amplification method for fast clinical infectious diseases diagnostics at aM concentrations of DNA was developed using a polycarbonate (PC microfluidic chip. A portable confocal optical fluorescence detector was specifically developed for the microfluidic chip that was capable of highly sensitive real-time detection of amplified products for sequence-specific molecular identification near the optical diffraction limit with low background. The molecular diagnostics of Listeria monocytogenes with nucleic acid extracted from stool samples was performed at a minimum DNA template concentration of 3.65aM, and a detection limit of less than five copies of genomic DNA. Contrast to the general polymerase chain reaction (PCR at eppendorf (EP tube, the detection time in our developed method was reduced from 1.5h to 45min for multi-target parallel detection, the consume of sample and reagent was dropped from 25μL to 1.45μL. This novel microfluidic chip system and method can be used to develop a micro total analysis system as a clinically relevant pathogen molecular diagnostics method via the amplification of targets, with potential applications in biotechnology, medicine, and clinical molecular diagnostics.

  7. Gold nanoparticle-based optical microfluidic sensors for analysis of environmental pollutants

    DEFF Research Database (Denmark)

    Lafleur, Josiane P.; Senkbeil, Silja; Jensen, Thomas G.

    2012-01-01

    Conventional methods of environmental analysis can be significantly improved by the development of portable microscale technologies for direct in-field sensing at remote locations. This report demonstrates the vast potential of gold nanoparticle-based microfluidic sensors for the rapid, in......-field, detection of two important classes of environmental contaminants – heavy metals and pesticides. Using gold nanoparticle-based microfluidic sensors linked to a simple digital camera as the detector, detection limits as low as 0.6 μg L−1 and 16 μg L−1 could be obtained for the heavy metal mercury...... and the dithiocarbamate pesticide ziram, respectively. These results demonstrate that the attractive optical properties of gold nanoparticle probes combine synergistically with the inherent qualities of microfluidic platforms to offer simple, portable and sensitive sensors for environmental contaminants....

  8. Microfluidic devices for investigation of biomimetic membranes for sensor and separation applications

    DEFF Research Database (Denmark)

    Pszon-Bartosz, Kamila Justyna

    The term biomimetic membrane denotes membrane that mimics biological cell membrane. Artificially made membranes are powerful tools for the fundamental biophysical studies of membrane proteins. Moreover, they may be used in biomedicine, serving as biosensors in high-throughput screening of potential...... drug candidates and in separation technologies, where an exciting example is water purification device based on biomimetic membranes containing aquaporins (highly water selective proteins). However, there are many challenges that must be overcome in order to build biomimetic membrane-based devices...... for industrial applications. Among them are the inherent fragility of lipid membranes, the challenge of up-scaling the effective membrane area and the quantification of the protein delivery to the lipid membrane which may determined the biomimetic membrane application. This PhD thesis addresses the above...

  9. In situ Gelation of Monodisperse Alginate Hydrogel in Microfluidic Channel Based on Mass Transfer of Calcium Ions

    International Nuclear Information System (INIS)

    Song, YoungShin; Lee, Chang-Soo

    2014-01-01

    A microfluidic method for the in situ production of monodispersed alginate hydrogels using biocompatible polymer gelation by crosslinker mass transfer is described. Gelation of the hydrogel was achieved in situ by the dispersed calcium ion in the microfluidic device. The capillary number (Ca) and the flow rate of the disperse phase which are important operating parameters mainly influenced the formation of three distinctive flow regions, such as dripping, jetting, and unstable dripping. Under the formation of dripping region, monodispersed alginate hydrogels having a narrow size distribution (C.V=2.71%) were produced in the microfluidic device and the size of the hydrogels, ranging from 30 to 60 µm, could be easily controlled by varying the flow rate, viscosity, and interfacial tension. This simple microfluidic method for the production of monodisperse alginate hydrogels shows strong potential for use in delivery systems of foods, cosmetics, inks, and drugs, and spherical alginate hydrogels which have biocompatibility will be applied to cell transplantation

  10. In situ Gelation of Monodisperse Alginate Hydrogel in Microfluidic Channel Based on Mass Transfer of Calcium Ions

    Energy Technology Data Exchange (ETDEWEB)

    Song, YoungShin; Lee, Chang-Soo [Chungnam National University, Daejeon (Korea, Republic of)

    2014-10-15

    A microfluidic method for the in situ production of monodispersed alginate hydrogels using biocompatible polymer gelation by crosslinker mass transfer is described. Gelation of the hydrogel was achieved in situ by the dispersed calcium ion in the microfluidic device. The capillary number (Ca) and the flow rate of the disperse phase which are important operating parameters mainly influenced the formation of three distinctive flow regions, such as dripping, jetting, and unstable dripping. Under the formation of dripping region, monodispersed alginate hydrogels having a narrow size distribution (C.V=2.71%) were produced in the microfluidic device and the size of the hydrogels, ranging from 30 to 60 µm, could be easily controlled by varying the flow rate, viscosity, and interfacial tension. This simple microfluidic method for the production of monodisperse alginate hydrogels shows strong potential for use in delivery systems of foods, cosmetics, inks, and drugs, and spherical alginate hydrogels which have biocompatibility will be applied to cell transplantation.

  11. Integrated Cantilever-Based Flow Sensors with Tunable Sensitivity for In-Line Monitoring of Flow Fluctuations in Microfluidic Systems

    Directory of Open Access Journals (Sweden)

    Nadine Noeth

    2013-12-01

    Full Text Available For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different materials (SU-8 and SiN and with different thicknesses. The integration of arrays of holes with different hole size and number of holes allows the modification of device sensitivity, theoretical detection limit and measurement range. For an average flow in the microliter range, the cantilever deflection is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external pumps connected to the microfluidic system.

  12. Clogging-free microfluidics for continuous size-based separation of microparticles

    Science.gov (United States)

    Yoon, Yousang; Kim, Seonil; Lee, Jusin; Choi, Jaewoong; Kim, Rae-Kwon; Lee, Su-Jae; Sul, Onejae; Lee, Seung-Beck

    2016-01-01

    In microfluidic filtration systems, one of the leading obstacles to efficient, continuous operation is clogging of the filters. Here, we introduce a lateral flow microfluidic sieving (μ-sieving) technique to overcome clogging and to allow continuous operation of filter based microfluidic separation. A low frequency mechanical oscillation was added to the fluid flow, which made possible the release of aggregated unwanted polystyrene (PS) particles trapped between the larger target PS particles in the filter demonstrating continuous μ-sieving operation. We achieved collection of the target PS particles with 100% separation efficiency. Also, on average, more than 98% of the filtered target particles were retrieved after the filtration showing high retrieval rates. Since the oscillation was applied to the fluid but not to the microfluidic filter system, mechanical stresses to the system was minimized and no additional fabrication procedures were necessary. We also applied the μ-sieving technique to the separation of cancer cells (MDA-MB-231) from whole blood and showed that the fluidic oscillations prevented the filters from being blocked by the filtered cancer cells allowing continuous microfluidic separation with high efficiency. PMID:27198601

  13. Clogging-free microfluidics for continuous size-based separation of microparticles.

    Science.gov (United States)

    Yoon, Yousang; Kim, Seonil; Lee, Jusin; Choi, Jaewoong; Kim, Rae-Kwon; Lee, Su-Jae; Sul, Onejae; Lee, Seung-Beck

    2016-05-20

    In microfluidic filtration systems, one of the leading obstacles to efficient, continuous operation is clogging of the filters. Here, we introduce a lateral flow microfluidic sieving (μ-sieving) technique to overcome clogging and to allow continuous operation of filter based microfluidic separation. A low frequency mechanical oscillation was added to the fluid flow, which made possible the release of aggregated unwanted polystyrene (PS) particles trapped between the larger target PS particles in the filter demonstrating continuous μ-sieving operation. We achieved collection of the target PS particles with 100% separation efficiency. Also, on average, more than 98% of the filtered target particles were retrieved after the filtration showing high retrieval rates. Since the oscillation was applied to the fluid but not to the microfluidic filter system, mechanical stresses to the system was minimized and no additional fabrication procedures were necessary. We also applied the μ-sieving technique to the separation of cancer cells (MDA-MB-231) from whole blood and showed that the fluidic oscillations prevented the filters from being blocked by the filtered cancer cells allowing continuous microfluidic separation with high efficiency.

  14. Volume-of-fluid simulations in microfluidic T-junction devices: Influence of viscosity ratio on droplet size

    Science.gov (United States)

    Nekouei, Mehdi; Vanapalli, Siva A.

    2017-03-01

    We used volume-of-fluid (VOF) method to perform three-dimensional numerical simulations of droplet formation of Newtonian fluids in microfluidic T-junction devices. To evaluate the performance of the VOF method we examined the regimes of drop formation and determined droplet size as a function of system parameters. Comparison of the simulation results with four sets of experimental data from the literature showed good agreement, validating the VOF method. Motivated by the lack of adequate studies investigating the influence of viscosity ratio (λ) on the generated droplet size, we mapped the dependence of drop volume on capillary number (0.001 1. In addition, we find that at a given capillary number, the size of droplets does not vary appreciably when λ 1. We develop an analytical model for predicting the droplet size that includes a viscosity-dependent breakup time for the dispersed phase. This improved model successfully predicts the effects of the viscosity ratio observed in simulations. Results from this study are useful for the design of lab-on-chip technologies and manufacture of microfluidic emulsions, where there is a need to know how system parameters influence the droplet size.

  15. Performance of an in-plane detection cell with integrated waveguides for UV/Vis absorbance measurements on microfluidic separation devices

    DEFF Research Database (Denmark)

    Petersen, Nickolaj Jacob; Mogensen, Klaus Bo; Kutter, Jörg Peter

    2002-01-01

    A microfluidic device with integrated waveguides and a long path length detection cell for UV/Vis absorbance detection is presented. The 750 mum U-cell detection geometry was evaluated in terms of its optical performance as well as its influence on efficiency for electrophoretic separations...

  16. Integrated electrokinetically driven microfluidic devices with pH-mediated solid-phase extraction coupled to microchip electrophoresis for preterm birth biomarkers.

    Science.gov (United States)

    Sonker, Mukul; Knob, Radim; Sahore, Vishal; Woolley, Adam T

    2017-07-01

    Integration in microfluidics is important for achieving automation. Sample preconcentration integrated with separation in a microfluidic setup can have a substantial impact on rapid analysis of low-abundance disease biomarkers. Here, we have developed a microfluidic device that uses pH-mediated solid-phase extraction (SPE) for the enrichment and elution of preterm birth (PTB) biomarkers. Furthermore, this SPE module was integrated with microchip electrophoresis for combined enrichment and separation of multiple analytes, including a PTB peptide biomarker (P1). A reversed-phase octyl methacrylate monolith was polymerized as the SPE medium in polyethylene glycol diacrylate modified cyclic olefin copolymer microfluidic channels. Eluent for pH-mediated SPE of PTB biomarkers on the monolith was optimized using different pH values and ionic concentrations. Nearly 50-fold enrichment was observed in single channel SPE devices for a low nanomolar solution of P1, with great elution time reproducibility (electrophoresis in our integrated device with ∼15-fold enrichment. This device shows important progress towards an integrated electrokinetically operated platform for preconcentration and separation of biomarkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

    DEFF Research Database (Denmark)

    Bu, Minqiang; Perch-Nielsen, Ivan R.; Sørensen, Karen Skotte

    2013-01-01

    We present a temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with an external heater and a temperature sensor. The method employs optimized temperature overshooting and undershooting...

  18. Extraction, amplification and detection of DNA in microfluidic chip-based assays

    KAUST Repository

    Wu, Jinbo

    2013-12-20

    This review covers three aspects of PCR-based microfluidic chip assays: sample preparation, target amplification, and product detection. We also discuss the challenges related to the miniaturization and integration of each assay and make a comparison between conventional and microfluidic schemes. In order to accomplish these essential assays without human intervention between individual steps, the micro-components for fluid manipulation become critical. We therefore summarize and discuss components such as microvalves (for fluid regulation), pumps (for fluid driving) and mixers (for blending fluids). By combining the above assays and microcomponents, DNA testing of multi-step bio-reactions in microfluidic chips may be achieved with minimal external control. The combination of assay schemes with the use of micro-components also leads to rapid methods for DNA testing via multi-step bioreactions. Contains 259 references.

  19. Extraction, amplification and detection of DNA in microfluidic chip-based assays

    International Nuclear Information System (INIS)

    Wu, Jinbo; Cao, Wenbin; Wen, Weijia; Kodzius, Rimantas

    2014-01-01

    This review covers three aspects of PCR-based microfluidic chip assays: sample preparation, target amplification, and product detection. We also discuss the challenges related to the miniaturization and integration of each assay and make a comparison between conventional and microfluidic schemes. In order to accomplish these essential assays without human intervention between individual steps, the micro-components for fluid manipulation become critical. We therefore summarize and discuss components such as microvalves (for fluid regulation), pumps (for fluid driving) and mixers (for blending fluids). By combining the above assays and microcomponents, DNA testing of multi-step bio-reactions in microfluidic chips may be achieved with minimal external control. The combination of assay schemes with the use of micro-components also leads to rapid methods for DNA testing via multi-step bioreactions. (author)

  20. Patterning of PMMA microfluidic parts using screen printing process

    Science.gov (United States)

    Ahari Kaleibar, Aminreza; Rahbar, Mona; Haiducu, Marius; Parameswaran, Ash M.

    2010-02-01

    An inexpensive and rapid micro-fabrication process for producing PMMA microfluidic components has been presented. Our proposed technique takes advantages of commercially available economical technologies such as the silk screen printing and UV patterning of PMMA substrates to produce the microfluidic components. As a demonstration of our proposed technique, we had utilized a homemade deep-UV source, λ=254nm, a silk screen mask made using a local screen-printing shop and Isopropyl alcohol - water mixture (IPA-water) as developer to quickly define the microfluidic patterns. The prototyped devices were successfully bonded, sealed, and the device functionality tested and demonstrated. The screen printing based technique can produce microfluidic channels as small as 50 micrometers quite easily, making this technique the most cost-effective, fairly high precision and at the same time an ultra economical plastic microfluidic components fabrication process reported to date.

  1. The Microfluidic Jukebox

    Science.gov (United States)

    Tan, Say Hwa; Maes, Florine; Semin, Benoît; Vrignon, Jérémy; Baret, Jean-Christophe

    2014-04-01

    Music is a form of art interweaving people of all walks of life. Through subtle changes in frequencies, a succession of musical notes forms a melody which is capable of mesmerizing the minds of people. With the advances in technology, we are now able to generate music electronically without relying solely on physical instruments. Here, we demonstrate a musical interpretation of droplet-based microfluidics as a form of novel electronic musical instruments. Using the interplay of electric field and hydrodynamics in microfluidic devices, well controlled frequency patterns corresponding to musical tracks are generated in real time. This high-speed modulation of droplet frequency (and therefore of droplet sizes) may also provide solutions that reconciles high-throughput droplet production and the control of individual droplet at production which is needed for many biochemical or material synthesis applications.

  2. Microfluidic method for measuring viscosity using images from smartphone

    Science.gov (United States)

    Kim, Sooyeong; Kim, Kyung Chun; Yeom, Eunseop

    2018-05-01

    The viscosity of a fluid is the most important characteristic in fluid rheology. Many microfluidic devices have been proposed for easily measuring the fluid viscosity of small samples. A hybrid system consisting of a smartphone and microfluidic device can offer a mobile laboratory for performing a wide range of detection and analysis functions related to healthcare. In this study, a new mobile sensing method based on a microfluidic device was proposed for fluid viscosity measurements. By separately delivering sample and reference fluids into the two inlets of a Y-shaped microfluidic device, an interfacial line is induced at downstream of the device. Because the interfacial width (W) between the sample and reference fluid flows was determined by their pressure ratio, the viscosity (μ) of the sample could be estimated by measuring the interfacial width. To distinguish the interfacial width of a sample, optical images of the flows at downstream of the Y-shaped microfluidic device were acquired using a smartphone. To check the measurement accuracy of the proposed method, the viscosities of glycerol mixtures were compared with those measured by a conventional viscometer. The proposed technique was applied to monitor the variations in blood and oil samples depending on storage or rancidity. We expect that this mobile sensing method based on a microfluidic device could be utilized as a viscometer with significant advantages in terms of mobility, ease-of-operation, and data management.

  3. Multiplex single particle analysis in microfluidics.

    Science.gov (United States)

    Dannhauser, D; Romeo, G; Causa, F; De Santo, I; Netti, P A

    2014-10-21

    A straightforward way to measure separated micrometric sized particles in microfluidic flow is reported. The light scattering profile (LSP) of each single particle is fully characterized by using a CMOS-camera based small angle light scattering (SALS) apparatus, ranging from 2° up to 30°. To ensure controlled particle passage through the incident laser, a viscoelastic 3D alignment effect by viscoelastic induced particle migration has been implemented in a simple and cost-effective microfluidic device. Different polystyrene particle sizes are measured in microfluidic flows and the obtained scattering signatures are matched with the Lorenz-Mie based scattering theory. The results confirm the possibility of using this apparatus for real multiplex particle analyses in microfluidic particle flows.

  4. Capacitance Variation Induced by Microfluidic Two-Phase Flow across Insulated Interdigital Electrodes in Lab-On-Chip Devices

    Directory of Open Access Journals (Sweden)

    Tao Dong

    2015-01-01

    Full Text Available Microfluidic two-phase flow detection has attracted plenty of interest in various areas of biology, medicine and chemistry. This work presents a capacitive sensor using insulated interdigital electrodes (IDEs to detect the presence of droplets in a microchannel. This droplet sensor is composed of a glass substrate, patterned gold electrodes and an insulation layer. A polydimethylsiloxane (PDMS cover bonded to the multilayered structure forms a microchannel. Capacitance variation induced by the droplet passage was thoroughly investigated with both simulation and experimental work. Olive oil and deionized water were employed as the working fluids in the experiments to demonstrate the droplet sensor. The results show a good sensitivity of the droplet with the appropriate measurement connection. This capacitive droplet sensor is promising to be integrated into a lab-on-chip device for in situ monitoring/counting of droplets or bubbles.

  5. Capacitance variation induced by microfluidic two-phase flow across insulated interdigital electrodes in lab-on-chip devices.

    Science.gov (United States)

    Dong, Tao; Barbosa, Cátia

    2015-01-26

    Microfluidic two-phase flow detection has attracted plenty of interest in various areas of biology, medicine and chemistry. This work presents a capacitive sensor using insulated interdigital electrodes (IDEs) to detect the presence of droplets in a microchannel. This droplet sensor is composed of a glass substrate, patterned gold electrodes and an insulation layer. A polydimethylsiloxane (PDMS) cover bonded to the multilayered structure forms a microchannel. Capacitance variation induced by the droplet passage was thoroughly investigated with both simulation and experimental work. Olive oil and deionized water were employed as the working fluids in the experiments to demonstrate the droplet sensor. The results show a good sensitivity of the droplet with the appropriate measurement connection. This capacitive droplet sensor is promising to be integrated into a lab-on-chip device for in situ monitoring/counting of droplets or bubbles.

  6. High-throughput deterministic single-cell encapsulation and droplet pairing, fusion, and shrinkage in a single microfluidic device.

    Science.gov (United States)

    Schoeman, Rogier M; Kemna, Evelien W M; Wolbers, Floor; van den Berg, Albert

    2014-02-01

    In this article, we present a microfluidic device capable of successive high-yield single-cell encapsulation in droplets, with additional droplet pairing, fusion, and shrinkage. Deterministic single-cell encapsulation is realized using Dean-coupled inertial ordering of cells in a Yin-Yang-shaped curved microchannel using a double T-junction, with a frequency over 2000 Hz, followed by controlled droplet pairing with a 100% success rate. Subsequently, droplet fusion is realized using electrical actuation resulting in electro-coalescence of two droplets, each containing a single HL60 cell, with 95% efficiency. Finally, volume reduction of the fused droplet up to 75% is achieved by a triple pitchfork structure. This droplet volume reduction is necessary to obtain close cell-cell membrane contact necessary for final cell electrofusion, leading to hybridoma formation, which is the ultimate aim of this research. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Water-based alkyl ketene dimer ink for user-friendly patterning in paper microfluidics.

    Science.gov (United States)

    Hamidon, Nurul Nadiah; Hong, Yumiao; Salentijn, Gert Ij; Verpoorte, Elisabeth

    2018-02-13

    We propose the use of water-based alkyl ketene dimer (AKD) ink for fast and user-friendly patterning of paper microfluidic devices either manually or using an inexpensive XY-plotter. The ink was produced by dissolving hydrophobic AKD in chloroform and emulsifying the solution in water. The emulsification was performed in a warm water bath, which led to an increased rate of the evaporation of chloroform. Subsequent cooling led to the final product, an aqueous suspension of fine AKD particles. The effects of surfactant and AKD concentrations, emulsification procedure, and cooling approach on final ink properties are presented, along with an optimized protocol for its formulation. This hydrophobic agent was applied onto paper using a plotter pen, after which the paper was heated to allow spreading of AKD molecules and chemical bonding with cellulose. A paper surface patterned with the ink (10 g L -1 AKD) yielded a contact angle of 135.6° for water. Unlike organic solvent-based solutions of AKD, this AKD ink does not require a fume hood for its use. Moreover, it is compatible with plastic patterning tools, due to the effective removal of chloroform in the production process to less than 2% of the total volume. Furthermore, this water-based ink is easy to prepare and use. Finally, the AKD ink can also be used for the fabrication of so-called selectively permeable barriers for use in paper microfluidic networks. These are barriers that stop the flow of water through paper, but are permeable to solvents with lower surface energies. We applied the AKD ink to confine and preconcentrate sample on paper, and demonstrated the use of this approach to achieve higher detection sensitivities in paper spray ionization-mass spectrometry (PSI-MS). Our patterning approach can be employed outside of the analytical lab or machine workshop for fast prototyping and small-scale production of paper-based analytical tools, for use in limited-resource labs or in the field. Copyright

  8. Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction

    Science.gov (United States)

    Goyal, Sachit; Desai, Amit V.; Lewis, Robert W.; Ranganathan, David R.; Li, Hairong; Zeng, Dexing; Reichert, David E.; Kenis, Paul J.A.

    2014-01-01

    Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

  9. Multilayer bonding using a conformal adsorbate film (CAF) for the fabrication of 3D monolithic microfluidic devices in photopolymer

    Science.gov (United States)

    Gutierrez-Rivera, L.; Martinez-Quijada, J.; Johnstone, R.; Elliott, D.; Backhouse, C.; Sameoto, D.

    2012-08-01

    Reliable microfabrication processes and materials compatible with complementary metal-oxide semiconductor (CMOS) technology are required by industry for the mass production of complex and highly miniaturized lab-on-a-chip systems. Photopolymers are commonly used in the semiconductor industry, and are suitable for the integration of multilayer structures onto CMOS substrates. This paper describes a novel photopolymer bonding process compatible with CMOS technology for the fabrication of three-dimensional monolithic microfluidic devices. The process consists of the formation of a conformal adsorbate film (CAF) approximately 15 nm thick on a patterned photopolymer layer (KMPR), thereby increasing the number of open polymer chains at the bonding interface and acting as an ultra-thin adhesive layer. This thin adhesive layer is made of the same photopolymer as the microfluidic structures, but has a substantially lower crosslinking density so it will be able to make better bonds during a thermocompressive bonding step. This CAF treatment substantially improves the bonding yield between two patterned and previously crosslinked photopolymer layers because both optimum structure strength (to resist deformation during bonding) and bonding strength from epoxy crosslinking can be achieved. We demonstrate high bonding yields of up to 99% of the useful area of the substrate after three successive bonding steps. With this technique, up to six layers have been bonded in a single device. Unlike previously reported methods the quality of bonding is mostly decoupled from soft-bake parameters and crosslinking level of the previously patterned layers. Three differentbonding processes were characterized to describe the bonding mechanism and the differences between the presented method and the partial-crosslinking bonding method. Capillary filling experiments were performed in microchannels of multilayer structures built with the CAF technique, without any observable leakage between

  10. Carbon based prosthetic devices

    Energy Technology Data Exchange (ETDEWEB)

    Devlin, D.J.; Carroll, D.W.; Barbero, R.S.; Archuleta, T. [Los Alamos National Lab., NM (US); Klawitter, J.J.; Ogilvie, W.; Strzepa, P. [Ascension Orthopedics (US); Cook, S.D. [Tulane Univ., New Orleans, LA (US). School of Medicine

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project objective was to evaluate the use of carbon/carbon-fiber-reinforced composites for use in endoprosthetic devices. The application of these materials for the metacarpophalangeal (MP) joints of the hand was investigated. Issues concerning mechanical properties, bone fixation, biocompatibility, and wear are discussed. A system consisting of fiber reinforced materials with a pyrolytic carbon matrix and diamond-like, carbon-coated wear surfaces was developed. Processes were developed for the chemical vapor infiltration (CVI) of pyrolytic carbon into porous fiber preforms with the ability to tailor the outer porosity of the device to provide a surface for bone in-growth. A method for coating diamond-like carbon (DLC) on the articulating surface by plasma-assisted chemical vapor deposition (CVD) was developed. Preliminary results on mechanical properties of the composite system are discussed and initial biocompatibility studies were performed.

  11. Fabrication of plastic microfluidic components

    Science.gov (United States)

    Martin, Peter M.; Matson, Dean W.; Bennett, Wendy D.; Hammerstrom, D. J.

    1998-09-01

    Plastic components have many advantages, including ease of fabrication, low cost, chemical inertness, lightweight, and disposability. We report on the fabrication of three plastics-based microfluidic components: a motherboard, a dialysis unit, and a metal sensor. Microchannels, headers, and interconnects were produced in thin sheets (>=50 microns) of polyimide, PMMA, polyethylene, and polycarbonate using a direct-write excimer laser micromachining system. Machined sheets were laminated by thermal and adhesive bonding to form leak-tight microfluidic components. The microfluidic motherboard borrowed the `functionality on a chip' concept from the electronics industry and was the heart of a complex microfluidic analytical device. The motherboard platform was designed to be tightly integrated and self-contained (i.e., liquid flows are all confined within machined microchannels), reducing the need for tubing with fluid distribution and connectivity. This concept greatly facilitated system integration and miniaturization. As fabricated, the motherboard consisted of three fluid reservoirs connected to micropumps by microchannels. The fluids could either be pumped independently or mixed in microchannels prior to being directed to exterior analytical components via outlet ports. The microdialysis device was intended to separate electrolytic solutes from low volume samples prior to mass spectrometric analysis. The device consisted of a dialysis membrane laminated between opposed serpentine microchannels containing the sample fluid and a buffer solution. The laminated metal sensor consisted of fluid reservoirs, micro-flow channels, micropumps, mixing channels, reaction channels, and detector circuitry.

  12. Gold nanoparticle-based microfluidic sensor for mercury detection

    DEFF Research Database (Denmark)

    Lafleur, Josiane P.; Jensen, Thomas Glasdam; Kutter, Jörg Peter

    2011-01-01

    The contamination of natural resources by human activity can have severe socio-economical impacts. Conventional methods of environmental analysis can be significantly improved by the development of portable microscale technologies for remote/field sensing. A gold nanoparticle-based lab-on-a-chip ......-on-a-chip device was developed for the rapid, in-field detection and quantification of mercury in aquatic environments. Rhodamine 6G functionalized gold nanoparticles allowed the on-chip fluorescence detection of mercury in aqueous samples with a limit of detection of 7 nM....

  13. A new microfluidics-based droplet dispenser for ICPMS.

    Science.gov (United States)

    Verboket, Pascal E; Borovinskaya, Olga; Meyer, Nicole; Günther, Detlef; Dittrich, Petra S

    2014-06-17

    In this work, a novel droplet microfluidic sample introduction system for inductively coupled plasma mass spectrometry (ICPMS) is proposed and characterized. The cheap and disposable microfluidic chip generates droplets of an aqueous sample in a stream of perfluorohexane (PFH), which is also used to eject them as a liquid jet. The aqueous droplets remain intact during the ejection and can be transported into the ICP with >50% efficiency. The transport is realized via a custom-built system, which includes a membrane desolvator necessary for the PFH vapor removal. The introduction system presented here can generate highly monodisperse droplets in the size range of 40-60 μm at frequencies from 90 to 300 Hz. These droplets produced very stable signals with a relative standard deviation (RSD) comparable to the one achieved with a commercial droplet dispenser. Using the current system, samples with a total volume of <1 μL can be analyzed. Moreover, the capabilities of the setup for introduction and quantitative elemental analysis of single cells were described using a test system of bovine red blood cells. In the future, other modules of the modern microfludics can be integrated in the chip, such as on-chip sample pretreatment or parallel introduction of different samples.

  14. Integrated microfluidic devices for the synthesis of nanoscale liposomes and lipoplexes.

    Science.gov (United States)

    Balbino, Tiago A; Serafin, Juliana M; Radaic, Allan; de Jesus, Marcelo B; de la Torre, Lucimara G

    2017-04-01

    In this work, pDNA/cationic liposome (CL) lipoplexes for gene delivery were prepared in one-step using multiple hydrodynamic flow-focusing regions. The microfluidic platform was designed with two distinct regions for the synthesis of liposomes and the subsequent assembly with pDNA, forming lipoplexes. The obtained lipoplexes exhibited appropriate physicochemical characteristics for gene therapy applications under varying conditions of flow rate-ratio (FRR), total volumetric flow rate (Q T ) and pDNA content (molar charge ratio, R±). The CLs were able to condense and retain the pDNA in the vesicular structures with sizes ranging from 140nm to 250nm. In vitro transfection assays showed that the lipoplexes prepared in one step by the two-stage configuration achieved similar efficiencies as lipoplexes prepared by conventional bulk processes, in which each step comprises a series of manual operations. The integrated microfluidic platform generates lipoplexes with liposome formation combined in-line with lipoplex assembly, significantly reducing the number of steps usually required to form gene carrier systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A facile and fast approach for the synthesis of doped nanoparticles using a microfluidic device

    International Nuclear Information System (INIS)

    Singh, Akanksha; Limaye, Mukta; Singh, Shashi; Kulkarni, Sulabha; Lalla, Niranjan Prasad; Malek, Chantal Khan

    2008-01-01

    The microfluidic approach emerges as a new and promising technology for the synthesis of nanomaterials. A microreactor allows a variety of reaction conditions to be quickly scanned without consuming large amounts of raw material. In this study, we investigated the synthesis of water soluble 1-thioglycerol-capped Mn-doped ZnS nanocrystalline semiconductor nanoparticles (TG-capped ZnS:Mn) via a microfluidic approach. This is the first report for the successful doping of Mn in a ZnS semiconductor at room temperature as well as at 80 deg. C using a microreactor. Transmission electron microscopy and x-ray diffraction analysis show that the average particle size of Mn-doped ZnS nanoparticles is ∼3.0 nm with a zinc-blende structure. Photoluminescence, x-ray photoelectron spectroscopy, atomic absorption spectroscopy and electron paramagnetic resonance studies were carried out to confirm that the Mn 2+ dopants are present in the ZnS nanoparticles

  16. Different migration patterns of sea urchin and mouse sperm revealed by a microfluidic chemotaxis device.

    Directory of Open Access Journals (Sweden)

    Haixin Chang

    Full Text Available Chemotaxis refers to a process whereby cells move up or down a chemical gradient. Sperm chemotaxis is known to be a strategy exploited by marine invertebrates such as sea urchins to reach eggs efficiently in moving water. Less is understood about how or whether chemotaxis is used by mammalian sperm to reach eggs, where fertilization takes place within the confinement of a reproductive tract. In this report, we quantitatively assessed sea urchin and mouse sperm chemotaxis using a recently developed microfluidic model and high-speed imaging. Results demonstrated that sea urchin Arbacia punctulata sperm were chemotactic toward the peptide resact with high chemotactic sensitivity, with an average velocity Vx up the chemical gradient as high as 20% of its average speed (238 μm/s, while mouse sperm displayed no statistically significant chemotactic behavior in progesterone gradients, which had been proposed to guide mammalian sperm toward eggs. This work demonstrates the validity of a microfluidic model for quantitative sperm chemotaxis studies, and reveals a biological insight that chemotaxis up a progesterone gradient may not be a universal strategy for mammalian sperm to reach eggs.

  17. Fabrication and bonding of thiol-ene-based microfluidic devices

    DEFF Research Database (Denmark)

    Sikanen, Tiina M; Lafleur, Josiane P.; Moilanen, Maria-Elisa

    2013-01-01

    In this work, the bonding strength of microchips fabricated by thiol-ene free-radical polymerization was characterized in detail by varying the monomeric thiol/allyl composition from the stoichiometric ratio (1:1) up to 100% excess of thiol (2:1) or allyl (1:2) functional groups. Four different...

  18. Recent Advances and Future Perspectives on Microfluidic Liquid Handling

    Directory of Open Access Journals (Sweden)

    Nam-Trung Nguyen

    2017-06-01

    Full Text Available The interdisciplinary research field of microfluidics has the potential to revolutionize current technologies that require the handling of a small amount of fluid, a fast response, low costs and automation. Microfluidic platforms that handle small amounts of liquid have been categorised as continuous-flow microfluidics and digital microfluidics. The first part of this paper discusses the recent advances of the two main and opposing applications of liquid handling in continuous-flow microfluidics: mixing and separation. Mixing and separation are essential steps in most lab-on-a-chip platforms, as sample preparation and detection are required for a variety of biological and chemical assays. The second part discusses the various digital microfluidic strategies, based on droplets and liquid marbles, for the manipulation of discrete microdroplets. More advanced digital microfluidic devices combining electrowetting with other techniques are also introduced. The applications of the emerging field of liquid-marble-based digital microfluidics are also highlighted. Finally, future perspectives on microfluidic liquid handling are discussed.

  19. Mass diffusion-based separation of sugars in a microfluidic contactor with nanofiltration membranes.

    Science.gov (United States)

    Kolfschoten, Ruben C; Janssen, Anja E M; Boom, Remko M

    2011-06-01

    Processes such as chromatographic separation and nanofiltration can remove low molecular weight sugars from liquid mixtures of oligosaccharides. As an alternative for the separation of such liquid mixtures, we studied mass diffusion separation of such sugars in a microfluidic device with incorporated nanofiltration membranes. This separation method is based on differences between diffusivities of components and does not require high transmembrane pressures. The effects of channel depth and flow rate were studied in experiments. The key parameters selectivity and rejection increased with increasing channel depth due to increased external mass transfer limitations. Among the studied membranes, the obtained selectivities and rejections correlated to the specified retention values by the manufacturers. Compared to more conventional nanofiltration where high pressure forces solutes through membranes, we obtained corresponding selectivities and fluxes of only an order of magnitude smaller. Simulated results indicated that with optimized microchannel and membrane dimensions, the presented separation process can compete with currently available separation technologies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Blood plasma separation in ZnO nanoflowers-supported paper based microfluidic for glucose sensing

    Science.gov (United States)

    Muhimmah, Luthviyah Choirotul; Roekmono, Hadi, Harsono; Yuwono, Rio Akbar; Wahyuono, Ruri Agung

    2018-04-01

    Blood plasma separation is essential to analyze and quantify the bio-substances in the human blood and hence, allows for diagnosing various diseases. This paper presents the two layer paper-based microfluidic analytical devices coated with ZnO nanoflowers (ZnO NF-µPAD) for a rapid blood plasma separation and glucose sensing. Plasma separation in ZnO NF-µPAD was evaluated experimentally and numerically using computational fluid dynamics package for a flow over porous networks. Glucose detection was carried out using Fourier-transform infrared (FTIR) measurements. The glucose concentrations in the red blood samples investigated here vary in the range of 150 - 310 mg.dl-1. The plasma separation process on ZnO NF-μPAD requires 240 ± 93 s. The spectroscopic data reveals that the IR absorptions and Raman signals at the typical vibrational frequencies of glucose are increasing at higher glucose concentration. After subtraction from absorption background arising from ZnO NF and the paper, linearly increasing IR absorption (913 and 1349 cm-1) and Raman signals (1346 and 1461 cm-1) are observable with a relatively good sensitivity.

  1. A suspending-droplet mode paper-based microfluidic platform for low-cost, rapid, and convenient detection of lead(II) ions in liquid solution.

    Science.gov (United States)

    Sun, Han; Li, Wanbo; Dong, Zhen-Zhen; Hu, Chong; Leung, Chung-Hang; Ma, Dik-Lung; Ren, Kangning

    2018-01-15

    A paper-based microfluidic device based on unconventional principle was developed and used to detect lead ions through a two-step process including heated incubation and subsequent mixing. The device was made by generating a superhydrophobic pattern, which defines channel and reservoir barriers, on a water-impermeable paper substrate, followed by loading and drying the reagents in the defined reservoirs. Different from the conventional paper-based devices that are made of water-permeable paper, the as-prepared device holds water drops in discrete reservoirs, and the water drops will not move unless the device is titled along the direction of the predefined channels. In this way, the liquid samples applied onto the device are handled as individual drops and could be stored, transported, and mixed on demand. Different from the conventional paper-based devices that use capillary force to drive liquid, our new device uses wetting and gravity as driving force. We name this operation principle suspending-droplet mode paper-based device (SD-μPAD). The use of a Teflon contact-printing stamp makes the production of such devices rapid, cost efficient, and mass productive. Utilizing a G-quadruplex-based luminescence switch-on assay, we demonstrated rapid, convenient, highly sensitive, and low cost detection of lead(II) ions in water samples, using a custom made battery-powered portable device, and a smart phone as the detector. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Gravity driven deterministic lateral displacement for particle separation in microfluidic devices.

    Science.gov (United States)

    Devendra, Raghavendra; Drazer, German

    2012-12-18

    We investigate the two-dimensional continuous size-based separation of suspended particles in gravity-driven deterministic lateral displacement (g-DLD) devices. The suspended particles are driven through a periodic array of cylindrical obstacles under the action of gravity. We perform experiments covering the entire range of forcing orientations with respect to the array of obstacles and identify specific forcing angles that would lead to vector separation, in which different particles migrate, on an average, in different directions. A simple model, based on the lateral displacement induced on the trajectory of a particle by irreversible particle-obstacle interactions, accurately predicts the dependence of the migration angle on the forcing direction. The results provide design guidance for the development of g-DLD devices. We observe directional locking, which strongly depends on the size of the particle and suggests that relatively small forcing angles are well suited for size-fractionation purposes. We demonstrate excellent separation resolution for a binary mixture of particles at relatively small forcing angles, that is, forcing angles that are close to but smaller than the first transition angle of the larger particles in the mixture.

  3. Microfluidic device for the detection of glucose using a micro direct methanol fuel cell as an amperometric detection power source.

    Science.gov (United States)

    Ito, Takeshi; Kunimatsu, Masayuki; Kaneko, Satoru; Ohya, Seishiro; Suzuki, Koji

    2007-02-15

    We designed and prepared a novel microbiosensing system consisting of a microbioreactor fabricated using photosensitive sheets intercalated between Pyrex wafers as a dam structure, together with a micro fuel cell as a power source device between the electrodes for amperometric detection. The dam structure retains enzyme (glucose oxidase, GOx)-immobilized microbeads in a microchannel. Microelectrodes are used as an integrated detector within a microchannel located downstream of the dam structure, and these are used to detect the oxidation current of hydrogen peroxide produced from a glucose sample and GOx. A micro direct methanol fuel cell (mu-DMFC, i.d. 500 microm) was fabricated on a polymeric substrate and was used to supply a potential for the electrochemical detector. In this case, two mu-DMFCs were stacked on one substrate to increase the voltage for the oxidation of hydrogen peroxide. A linear response curve was obtained in range from 0.1 to 10 mM glucose for the designed microbiosensing system. These results show that a microfluidic biosensing system designed with a mu-DMFC device is useful and has the potential to assist minuaturization and simplification of the sensing system, in addition to increasing disposability of the device.

  4. Fabrication of user-friendly and biomimetic 1,1'-carbonyldiimidazole cross-linked gelatin/agar microfluidic devices.

    Science.gov (United States)

    Jocic, Simonne; Mestres, Gemma; Tenje, Maria

    2017-07-01

    We have developed a straightforward technique for fabricating user-friendly and biomimetic microfluidic devices out of a gelatin/agar gel cross-linked with 1,1'-carbonyldiimidazole. The fabrication procedure requires only inexpensive starting materials such as glass capillaries and wires to mold 3D cylindrical channels into the gel with the possibility of achieving channel diameters of 375μm and 1000μm. We demonstrate that the channel absent of gel injury can retain fluid within its dimensions for at least 7h. We also show that the device material does not autofluoresce nor provide hindrances with fluorescent imaging. A discussion of the chemical linkage identities of cross-linked gelatin/agar is included via ATR-FTIR studies. Crosslinking of the gelatin/agar is further confirmed by the lack of a gel to sol transition at physiological temperature as assessed by DSC measurements. SEM micrographs that demonstrate the 100nm mean pore width of the cross-linked gelatin/agar are provided. This device is considered biomimetic because it represents components present in the natural extracellular matrix such as collagen and proteoglycans in the form of cross-linked gelatin/agar. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.

    Science.gov (United States)

    Ming, Li; Zhipeng, Yuan; Fei, Yu; Feng, Rao; Jian, Weng; Baoguo, Jiang; Yongqiang, Wen; Peixun, Zhang

    2018-03-26

    Cartilage defect is common in clinical but notoriously difficult to treat for low regenerative and migratory capacity of chondrocytes. Biodegradable tissue engineering nano-scaffold with a lot of advantages has been the direction of material to repair cartilage defect in recent years. The objective of our study is to establish a biodegradable drug-loading synthetic polymer (PLA) and biopolymer (Gelatine) composite 3D nano-scaffold to support the treatment of cartilage defect. We designed a microfluidic chip-based drug-screening device to select the optimum concentration of resveratrol, which has strong protective capability for chondrocyte. Then biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds were fabricated and used to repair the cartilage defects. As a result, we successfully cultured primary chondrocytes and screened the appropriate concentrations of resveratrol by the microfluidic device. We also smoothly obtained superior biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds and compared the properties and therapeutic effects of cartilage defect in rats. In summary, our microfluidic device is a simple but efficient platform for drug screening and resveratrol-loading PLA/Gelatine 3D nano-scaffolds could greatly promote the cartilage formation. It would be possible for materials and medical researchers to explore individualized pharmacotherapy and drug-loading synthetic polymer and biopolymer composite tissue engineering scaffolds for the repair of cartilage defect in future.

  6. Towards One-Step Quantitation of Prostate-Specific Antigen (PSA) in Microfluidic Devices: Feasibility of Optical Detection with Nanoparticle Labels.

    Science.gov (United States)

    Barbosa, Ana I; Wichers, Jan H; van Amerongen, Aart; Reis, Nuno M

    2017-01-01

    Rapid and quantitative prostate-specific antigen (PSA) biomarker detection would be beneficial to cancer diagnostics, improving early detection and therefore increasing chances of survival. Nanoparticle-based detection is routinely used in one-step nitrocellulose-based lateral flow (LF) immunoassays; however, it is well established within the scientific diagnostic community that LF technology lacks sensitivity for measuring biomarkers, such as prostate-specific antigen (PSA). A trend in point-of-care (POC) protein biomarker quantitation is the miniaturization of immunoassays in microfluidic devices. This work aimed at testing the feasibility of carbon and gold nanoparticles as immunoassay labels for PSA detection with cost-effective optical detection in a novel microfluidic POC platform called microcapillary film (MCF), consisting of a parallel array of fluoropolymer microcapillaries with 200-μm internal diameter. With neutravidin-coated carbon, nanoparticles were able to quantify an immobilized biotinylated monoclonal antibody (coating solution from 10 to 40 μg/ml) and PSA was successfully quantified in a sandwich assay using silver-enhanced gold nanoparticles and a flatbed scanner; yet, the dynamic range was limited to 10-100 ng/ml. Although direct optical detection of PSA without enzymatic amplification or fluorophores is possible and technically appealing for the simplified fluidics and signal scanning setups involved, ultimately, the binding of a thin layer of nanoparticles onto the wall of transparent microcapillaries is not sufficient to cause a significant drop on the optical colorimetric signal. Future studies will explore the use of fluorescence nanoparticles.

  7. Highly Stable Liquid Metal-Based Pressure Sensor Integrated with a Microfluidic Channel

    Directory of Open Access Journals (Sweden)

    Taekeon Jung

    2015-05-01

    Full Text Available Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98 using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30–1000 s−1. The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability.

  8. Construction of microscale structures in enclosed microfluidic networks by using a magnetic beads based method.

    Science.gov (United States)

    Wang, Zhenyu; Zhang, Xiaojuan; Yang, Jun; Yang, Zhong; Wan, Xiaoping; Hu, Ning; Zheng, Xiaolin

    2013-08-20

    A large number of microscale structures have been used to elaborate flowing control or complex biological and chemical reaction on microfluidic chips. However, it is still inconvenient to fabricate microstructures with different heights (or depths) on the same substrate. These kinds of microstructures can be fabricated by using the photolithography and wet-etching method step by step, but involves time-consuming design and fabrication process, as well as complicated alignment of different masters. In addition, few existing methods can be used to perform fabrication within enclosed microfluidic networks. It is also difficult to change or remove existing microstructures within these networks. In this study, a magnetic-beads-based approach is presented to build microstructures in enclosed microfluidic networks. Electromagnetic field generated by microfabricated conducting wires (coils) is used to manipulate and trap magnetic beads on the bottom surface of a microchannel. These trapped beads are accumulated to form a microscale pile with desired shape, which can adjust liquid flow, dock cells, modify surface, and do some other things as those fabricated microstructures. Once the electromagnetic field is changed, trapped beads may form new shapes or be removed by a liquid flow. Besides being used in microfabrication, this magnetic-beads-based method can be used for novel microfluidic manipulation. It has been validated by forming microscale dam structure for cell docking and modified surface for cell patterning, as well as guiding the growth of neurons. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Simple Approaches to Minimally-Instrumented, Microfluidic-Based Point-of-Care Nucleic Acid Amplification Tests

    Science.gov (United States)

    Mauk, Michael G.; Song, Jinzhao; Liu, Changchun; Bau, Haim H.

    2018-01-01

    Designs and applications of microfluidics-based devices for molecular diagnostics (Nucleic Acid Amplification Tests, NAATs) in infectious disease testing are reviewed, with emphasis on minimally instrumented, point-of-care (POC) tests for resource-limited settings. Microfluidic cartridges (‘chips’) that combine solid-phase nucleic acid extraction; isothermal enzymatic nucleic acid amplification; pre-stored, paraffin-encapsulated lyophilized reagents; and real-time or endpoint optical detection are described. These chips can be used with a companion module for separating plasma from blood through a combined sedimentation-filtration effect. Three reporter types: Fluorescence, colorimetric dyes, and bioluminescence; and a new paradigm for end-point detection based on a diffusion-reaction column are compared. Multiplexing (parallel amplification and detection of multiple targets) is demonstrated. Low-cost detection and added functionality (data analysis, control, communication) can be realized using a cellphone platform with the chip. Some related and similar-purposed approaches by others are surveyed. PMID:29495424

  10. An integrated rotary microfluidic system with DNA extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-of-care pathogen diagnostics.

    Science.gov (United States)

    Park, Byung Hyun; Oh, Seung Jun; Jung, Jae Hwan; Choi, Goro; Seo, Ji Hyun; Kim, Do Hyun; Lee, Eun Yeol; Seo, Tae Seok

    2017-05-15

    Point-of-care (POC) molecular diagnostics plays a pivotal role for the prevention and treatment of infectious diseases. In spite of recent advancement in microfluidic based POC devices, there are still rooms for development to realize rapid, automatic and cost-effective sample-to-result genetic analysis. In this study, we propose an integrated rotary microfluidic system that is capable of performing glass microbead based DNA extraction, loop mediated isothermal amplification (LAMP), and colorimetric lateral flow strip based detection in a sequential manner with an optimized microfluidic design and a rotational speed control. Rotation direction-dependent coriolis force and siphon valving structures enable us to perform the fluidic control and metering, and the use of the lateral flow strip as a detection method renders all the analytical processes for nucleic acid test simplified and integrated without the need of expensive instruments or human intervention. As a proof of concept for point-of-care DNA diagnostics, we identified the food-borne bacterial pathogen which was contaminated in water or milk. Not only monoplex Salmonella Typhimurium but also multiplex Salmonella Typhimurium and Vibrio parahaemolyticus were analysed on the integrated rotary genetic analysis microsystem with a limit of detection of 50 CFU in 80min. In addition, three multiple samples were simultaneously analysed on a single device. The sample-to-result capability of the proposed microdevice provides great usefulness in the fields of clinical diagnostics, food safety and environment monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Porous Polymeric Films from Microbubbles Generated Using a T-Junction Microfluidic Device.

    Science.gov (United States)

    Elsayed, M; Kothandaraman, A; Edirisinghe, M; Huang, J

    2016-12-20

    In this work, a simple microfluidic junction with a T geometry and coarse (200 μm diameter) capillaries was used to generate monodisperse microbubbles with an alginate polymer shell. Subsequently, these bubbles were used to prepare porous alginate films with good control over the pore structure. The lack of pore size, shape, and surface control in scalable forming of polymeric films is a major application-limiting drawback at present. Controlling the thinning process of the shell of the bubbles to tune the surface of the resulting structures was also explored. Films were prepared with nanopatterned surfaces by controlling the thinning of the bubble shell, with the aid of surfactants, to induce efficient bursting (fragmentation) of bubbles to generate nanodroplets, which become embedded within the film surface. This novel feature greatly expands and enhances the use of hydrophilic polymers in a wide range of biomedical applications, particularly in drug delivery and tissue engineering, such as studying cellular responses to different morphological surfaces.

  12. Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a-Chip Applications.

    Science.gov (United States)

    Tang, Qi; Liang, Min; Lu, Yi; Wong, Pak Kin; Wilmink, Gerald J; Zhang, Donna; Xin, Hao

    2016-04-04

    THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.

  13. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    International Nuclear Information System (INIS)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri

    2016-01-01

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  14. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    Energy Technology Data Exchange (ETDEWEB)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri, E-mail: d.pappas@ttu.edu

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  15. Graphene-polyaniline modified electrochemical droplet-based microfluidic sensor for high-throughput determination of 4-aminophenol.

    Science.gov (United States)

    Rattanarat, Poomrat; Suea-Ngam, Akkapol; Ruecha, Nipapan; Siangproh, Weena; Henry, Charles S; Srisa-Art, Monpichar; Chailapakul, Orawon

    2016-06-21

    We report herein the first development of graphene-polyaniline modified carbon paste electrode (G-PANI/CPE) coupled with droplet-based microfluidic sensor for high-throughput detection of 4-aminophenol (4-AP) in pharmaceutical paracetamol (PA) formulations. A simple T-junction microfluidic platform using an oil flow rate of 1.8 μL/min and an aqueous flow rate of 0.8 μL/min was used to produce aqueous testing microdroplets continuously. The microchannel was designed to extend the aqueous droplet to cover all 3 electrodes, allowing for electrochemical measurements in a single droplet. Parameters including flow rate, water fraction, and applied detection potential (Edet) were investigated to obtain optimal conditions. Using G-PANI/CPE significantly increased the current response for both cyclic voltammetric detections of ferri/ferrocyanide [Fe(CN)6](3-/4-) (10 times) and 4-AP (2 times), compared to an unmodified electrode. Using the optimized conditions in the droplet system, 4-AP in the presence of PA was selectively determined. The linear range of 4-AP was 50-500 μM (R(2) = 0.99), limit of detection (LOD, S/N = 3) was 15.68 μM, and limit of quantification (LOQ, S/N = 10) was 52.28 μM. Finally, the system was used to determine 4-AP spiked in commercial PA liquid samples and the amounts of 4-AP were found in good agreement with those obtained from the conventional capillary zone electrophoresis/UV-Visible spectrophotometry (CZE/UV-Vis). The proposed microfluidic device could be employed for a high-throughput screening (at least 60 samples h(-1)) of pharmaceutical purity requiring low sample and reagent consumption. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Printing silicone-based hydrophobic barriers on paper for microfluidic assays using low-cost ink jet printers.

    Science.gov (United States)

    Rajendra, Vinodh; Sicard, Clémence; Brennan, John D; Brook, Michael A

    2014-12-21

    Paper-based microfluidic devices exhibit many advantages for biological assays. Normally, the assays are restricted to certain areas of the paper by hydrophobic barriers comprised of wax or alkyl ketene dimers (AKD). Neither hydrophobic barrier is able to constrain aqueous solutions of surfactants, which are frequently used in biological assays. We demonstrate that rapidly curing silicone resins can be inkjet printed onto pure cellulose paper using inexpensive thermal ink-jet printers. The Piers-Rubinsztajn (PR) reaction dominates the cure chemistry leading to cellulose fibers that are surface coated with a silicone resin. The resulting barriers are able to resist penetration by surfactant solutions and even by the lower surface energy solvents DMF and DMSO. The utility of the barrier was demonstrated using a coliform assay based on detection of β-galactosidase.

  17. Rapid Detection of Food Allergens by Microfluidics ELISA-Based Optical Sensor

    Directory of Open Access Journals (Sweden)

    Xuan Weng

    2016-06-01

    Full Text Available The risks associated with the presence of hidden allergens in food have increased the need for rapid, sensitive, and reliable methods for tracing food allergens in commodities. Conventional enzyme immunosorbent assay (ELISA has usually been performed in a centralized lab, requiring considerable time and sample/reagent consumption and expensive detection instruments. In this study, a microfluidic ELISA platform combined with a custom-designed optical sensor was developed for the quantitative analysis of the proteins wheat gluten and Ara h 1. The developed microfluidic ELISA biosensor reduced the total assay time from hours (up to 3.5 h to 15–20 min and decreased sample/reagent consumption to 5–10 μL, compared to a few hundred microliters in commercial ELISA kits, with superior sensitivity. The quantitative capability of the presented biosensor is a distinctive advantage over the commercially available rapid methods such as lateral flow devices (LFD and dipstick tests. The developed microfluidic biosensor demonstrates the potential for sensitive and less-expensive on-site determination for rapidly detecting food allergens in a complex sample system.

  18. Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs from Clinical Blood Samples.

    Directory of Open Access Journals (Sweden)

    Priya Gogoi

    Full Text Available Current analysis of circulating tumor cells (CTCs is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity. Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH. In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.

  19. Performance of a Microfluidic Device for In Situ ToF-SIMS Analysis of Selected Organic Molecules at Aqueous Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li; Zhu, Zihua; Yu, Xiao-Ying; Thevuthasan, Suntharampillai; Cowin, James P.

    2013-04-03

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a unique surface analysis technique because it can provide molecular recognition for organic and biological molecules. However, analyzing aqueous solution surfaces by ToF-SIMS is difficult, because ToF-SIMS is a high-vacuum technique, while the vapor pressure of water is about 2.3 kPa at room temperature (20 C). We designed and fabricated a self-contained microfluidic device, enabling in situ analysis of aqueous surfaces by scanning electron microscope (SEM) and ToF-SIMS, which has been briefly reported.1,2 In this study, we report more performance data, focusing on the performance of this device for in situ analysis of organic molecules at aqueous surfaces using ToF-SIMS. Three representative organic compounds (formic acid, glycerol, and glutamic acid) were tested, and their molecular signals were successfully observed. The device can be self-running in vacuum for 8 hours, and SIMS measurements are feasible at any time in this time range. The stability of this device under primary ion beam bombardment is also impressive. High fluence (6 × 1012 ions cm-2 s-1) measurements can be operated continuously for up to 30 minutes without any significant damage to the aperture. However, extra-high fluence measurements (>1 × 1014 ions cm-2 s-1) may lead to liquid bumping in the aperture, and the aqueous solutions may spread out quickly. Signal reproducibility is reasonably good, and relative standard deviation (RSD) for molecular ion signals can be controlled to be smaller than ±15% for consecutive measurements. Measurements at long time intervals (e.g., 60 min) show RSDs of ±40-50%. In addition, the detection limits of formic acid, glycerol, and glutamic acid are estimated to be 0.04%, 0.008%, and 0.002% (weight ratio), respectively.

  20. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    Science.gov (United States)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.