Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis.

Science.gov (United States)

Sahore, Vishal; Sonker, Mukul; Nielsen, Anna V; Knob, Radim; Kumar, Suresh; Woolley, Adam T

2018-01-01

We have developed multichannel integrated microfluidic devices for automated preconcentration, labeling, purification, and separation of preterm birth (PTB) biomarkers. We fabricated multilayer poly(dimethylsiloxane)-cyclic olefin copolymer (PDMS-COC) devices that perform solid-phase extraction (SPE) and microchip electrophoresis (μCE) for automated PTB biomarker analysis. The PDMS control layer had a peristaltic pump and pneumatic valves for flow control, while the PDMS fluidic layer had five input reservoirs connected to microchannels and a μCE system. The COC layers had a reversed-phase octyl methacrylate porous polymer monolith for SPE and fluorescent labeling of PTB biomarkers. We determined μCE conditions for two PTB biomarkers, ferritin (Fer) and corticotropin-releasing factor (CRF). We used these integrated microfluidic devices to preconcentrate and purify off-chip-labeled Fer and CRF in an automated fashion. Finally, we performed a fully automated on-chip analysis of unlabeled PTB biomarkers, involving SPE, labeling, and μCE separation with 1 h total analysis time. These integrated systems have strong potential to be combined with upstream immunoaffinity extraction, offering a compact sample-to-answer biomarker analysis platform. Graphical abstract Pressure-actuated integrated microfluidic devices have been developed for automated solid-phase extraction, fluorescent labeling, and microchip electrophoresis of preterm birth biomarkers.

Magnet-assisted device-level alignment for the fabrication of membrane-sandwiched polydimethylsiloxane microfluidic devices

International Nuclear Information System (INIS)

Lu, J-C; Liao, W-H; Tung, Y-C

2012-01-01

Polydimethylsiloxane (PDMS) microfluidic device is one of the most essential techniques that advance microfluidics research in recent decades. PDMS is broadly exploited to construct microfluidic devices due to its unique and advantageous material properties. To realize more functionalities, PDMS microfluidic devices with multi-layer architectures, especially those with sandwiched membranes, have been developed for various applications. However, existing alignment methods for device fabrication are mainly based on manual observations, which are time consuming, inaccurate and inconsistent. This paper develops a magnet-assisted alignment method to enhance device-level alignment accuracy and precision without complicated fabrication processes. In the developed alignment method, magnets are embedded into PDMS layers at the corners of the device. The paired magnets are arranged in symmetric positions at each PDMS layer, and the magnetic attraction force automatically pulls the PDMS layers into the aligned position during assembly. This paper also applies the method to construct a practical microfluidic device, a tunable chaotic micromixer. The results demonstrate the successful operation of the device without failure, which suggests the accurate alignment and reliable bonding achieved by the method. Consequently, the fabrication method developed in this paper is promising to be exploited to construct various membrane-sandwiched PDMS microfluidic devices with more integrated functionalities to advance microfluidics research. (paper)

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...... pressures above 250 psi and therefore supports applications with high flow rates or highly viscous fluids. The ease of incorporation, configuration, fabrication and use make this interconnection system ideal for the rapid prototyping of simple microfluidic devices or other integrated systems that require...... microfluidic interfaces. It provides a valuable addition to the toolbox of individual and small arrays of connectors suitable for micromachined or template-based injection molded devices since it does not require protruding, threaded or glued modifications on the inlet and avoids bulky and expensive fittings....

A microfluidic cell culture device with integrated microelectrodes for barrier studies

DEFF Research Database (Denmark)

Tan, Hsih-Yin; Dufva, Martin; Kutter, Jörg P.

We present an eight cell culture microfluidic device fabricated using thiol-ene ‘click’ chemistry with embedded microelectrodes for evaluating barrier properties of human intestinal epithelial cells. The capability of the microelectrodes for trans-epithelial electrical resistance (TEER) measureme......) measurements was demonstrated by using confluent human colorectal epithelial cells (Caco-2) and rat fibroblast (CT 26) cells cultured in the microfluidic device....

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.

Femtosecond Laser Direct Write Integration of Multi-Protein Patterns and 3D Microstructures into 3D Glass Microfluidic Devices

Directory of Open Access Journals (Sweden)

Daniela Serien

2018-01-01

Full Text Available Microfluidic devices and biochips offer miniaturized laboratories for the separation, reaction, and analysis of biochemical materials with high sensitivity and low reagent consumption. The integration of functional or biomimetic elements further functionalizes microfluidic devices for more complex biological studies. The recently proposed ship-in-a-bottle integration based on laser direct writing allows the construction of microcomponents made of photosensitive polymer inside closed microfluidic structures. Here, we expand this technology to integrate proteinaceous two-dimensional (2D and three-dimensional (3D microstructures with the aid of photo-induced cross-linking into glass microchannels. The concept is demonstrated with bovine serum albumin and enhanced green fluorescent protein, each mixed with photoinitiator (Sodium 4-[2-(4-Morpholino benzoyl-2-dimethylamino] butylbenzenesulfonate. Unlike the polymer integration, fabrication over the entire channel cross-section is challenging. Two proteins are integrated into the same channel to demonstrate multi-protein patterning. Using 50% w/w glycerol solvent instead of 100% water achieves almost the same fabrication resolution for in-channel fabrication as on-surface fabrication due to the improved refractive index matching, enabling the fabrication of 3D microstructures. A glycerol-water solvent also reduces the risk of drying samples. We believe this technology can integrate diverse proteins to contribute to the versatility of microfluidics.

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.

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

KAUST Repository

Perozziello, Gerardo; Catalano, Rossella; Francardi, Marco; Rondanina, Eliana; Pardeo, Francesca; De Angelis, Francesco De; Malara, Natalia Maria; Candeloro, Patrizio; Morrone, Giovanni; Di Fabrizio, Enzo M.

2013-01-01

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.

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.

Microfluidic device for acoustic cell lysis

Science.gov (United States)

Branch, Darren W.; Cooley, Erika Jane; Smith, Gennifer Tanabe; James, Conrad D.; McClain, Jaime L.

2015-08-04

A microfluidic acoustic-based cell lysing device that can be integrated with on-chip nucleic acid extraction. Using a bulk acoustic wave (BAW) transducer array, acoustic waves can be coupled into microfluidic cartridges resulting in the lysis of cells contained therein by localized acoustic pressure. Cellular materials can then be extracted from the lysed cells. For example, nucleic acids can be extracted from the lysate using silica-based sol-gel filled microchannels, nucleic acid binding magnetic beads, or Nafion-coated electrodes. Integration of cell lysis and nucleic acid extraction on-chip enables a small, portable system that allows for rapid analysis in the field.

Transfection in perfused microfluidic cell culture devices: A case study.

Science.gov (United States)

Raimes, William; Rubi, Mathieu; Super, Alexandre; Marques, Marco P C; Veraitch, Farlan; Szita, Nicolas

2017-08-01

Automated microfluidic devices are a promising route towards a point-of-care autologous cell therapy. The initial steps of induced pluripotent stem cell (iPSC) derivation involve transfection and long term cell culture. Integration of these steps would help reduce the cost and footprint of micro-scale devices with applications in cell reprogramming or gene correction. Current examples of transfection integration focus on maximising efficiency rather than viable long-term culture. Here we look for whole process compatibility by integrating automated transfection with a perfused microfluidic device designed for homogeneous culture conditions. The injection process was characterised using fluorescein to establish a LabVIEW-based routine for user-defined automation. Proof-of-concept is demonstrated by chemically transfecting a GFP plasmid into mouse embryonic stem cells (mESCs). Cells transfected in the device showed an improvement in efficiency (34%, n = 3) compared with standard protocols (17.2%, n = 3). This represents a first step towards microfluidic processing systems for cell reprogramming or gene therapy.

Microfluidic Devices for Forensic DNA Analysis: A Review.

Science.gov (United States)

Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

2016-08-05

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 point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10-20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook.

A simple and cost-effective method for fabrication of integrated electronic-microfluidic devices using a laser-patterned PDMS layer

KAUST Repository

Li, Ming

2011-12-03

We report a simple and cost-effective method for fabricating integrated electronic-microfluidic devices with multilayer configurations. A CO 2 laser plotter was employed to directly write patterns on a transferred polydimethylsiloxane (PDMS) layer, which served as both a bonding and a working layer. The integration of electronics in microfluidic devices was achieved by an alignment bonding of top and bottom electrode-patterned substrates fabricated with conventional lithography, sputtering and lift-off techniques. Processes of the developed fabrication method were illustrated. Major issues associated with this method as PDMS surface treatment and characterization, thickness-control of the transferred PDMS layer, and laser parameters optimization were discussed, along with the examination and testing of bonding with two representative materials (glass and silicon). The capability of this method was further demonstrated by fabricating a microfluidic chip with sputter-coated electrodes on the top and bottom substrates. The device functioning as a microparticle focusing and trapping chip was experimentally verified. It is confirmed that the proposed method has many advantages, including simple and fast fabrication process, low cost, easy integration of electronics, strong bonding strength, chemical and biological compatibility, etc. © Springer-Verlag 2011.

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.

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.

Integrated Microfluidic Gas Sensors for Water Monitoring

Science.gov (United States)

Zhu, L.; Sniadecki, N.; DeVoe, D. L.; Beamesderfer, M.; Semancik, S.; DeVoe, D. L.

2003-01-01

A silicon-based microhotplate tin oxide (SnO2) gas sensor integrated into a polymer-based microfluidic system for monitoring of contaminants in water systems is presented. This device is designed to sample a water source, control the sample vapor pressure within a microchannel using integrated resistive heaters, and direct the vapor past the integrated gas sensor for analysis. The sensor platform takes advantage of novel technology allowing direct integration of discrete silicon chips into a larger polymer microfluidic substrate, including seamless fluidic and electrical interconnects between the substrate and silicon chip.

Simple Check Valves for Microfluidic Devices

Science.gov (United States)

Willis, Peter A.; Greer, Harold F.; Smith, J. Anthony

2010-01-01

A simple design concept for check valves has been adopted for microfluidic devices that consist mostly of (1) deformable fluorocarbon polymer membranes sandwiched between (2) borosilicate float glass wafers into which channels, valve seats, and holes have been etched. The first microfluidic devices in which these check valves are intended to be used are micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. In this application, it will be necessary to store some liquid samples in reservoirs in the devices for subsequent laboratory analysis, and check valves are needed to prevent cross-contamination of the samples. The simple check-valve design concept is also applicable to other microfluidic devices and to fluidic devices in general. These check valves are simplified microscopic versions of conventional rubber- flap check valves that are parts of numerous industrial and consumer products. These check valves are fabricated, not as separate components, but as integral parts of microfluidic devices. A check valve according to this concept consists of suitably shaped portions of a deformable membrane and the two glass wafers between which the membrane is sandwiched (see figure). The valve flap is formed by making an approximately semicircular cut in the membrane. The flap is centered over a hole in the lower glass wafer, through which hole the liquid in question is intended to flow upward into a wider hole, channel, or reservoir in the upper glass wafer. The radius of the cut exceeds the radius of the hole by an amount large enough to prevent settling of the flap into the hole. As in a conventional rubber-flap check valve, back pressure in the liquid pushes the flap against the valve seat (in this case, the valve seat is the adjacent surface of the lower glass wafer), thereby forming a seal that prevents backflow.

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.

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.

Engineering and evaluating drug delivery particles in microfluidic devices.

Science.gov (United States)

Björnmalm, Mattias; Yan, Yan; Caruso, Frank

2014-09-28

The development of new and improved particle-based drug delivery is underpinned by an enhanced ability to engineer particles with high fidelity and integrity, as well as increased knowledge of their biological performance. Microfluidics can facilitate these processes through the engineering of spatiotemporally highly controlled environments using designed microstructures in combination with physical phenomena present at the microscale. In this review, we discuss microfluidics in the context of addressing key challenges in particle-based drug delivery. We provide an overview of how microfluidic devices can: (i) be employed to engineer particles, by providing highly controlled interfaces, and (ii) be used to establish dynamic in vitro models that mimic in vivo environments for studying the biological behavior of engineered particles. Finally, we discuss how the flexible and modular nature of microfluidic devices provides opportunities to create increasingly realistic models of the in vivo milieu (including multi-cell, multi-tissue and even multi-organ devices), and how ongoing developments toward commercialization of microfluidic tools are opening up new opportunities for the engineering and evaluation of drug delivery particles. Copyright © 2014 Elsevier B.V. All rights reserved.

Microfluidic Device

Science.gov (United States)

Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

2017-01-01

Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

Nanoplasmonic and Microfluidic Devices for Biological Sensing

KAUST Repository

Perozziello, G.; Giugni, Andrea; Allione, Marco; Torre, Bruno; Das, Gobind; Coluccio, M. L.; Marini, Monica; Tirinato, Luca; Moretti, Manola; Limongi, Tania; Candeloro, P.; Di Fabrizio, Enzo M.

2017-01-01

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.

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.

Fabrication of polyimide based microfluidic channels for biosensor devices

Science.gov (United States)

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

2015-03-01

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 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 microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

Wirelessly powered microfluidic dielectrophoresis devices using printable RF circuits.

Science.gov (United States)

Qiao, Wen; Cho, Gyoujin; Lo, Yu-Hwa

2011-03-21

We report the first microfluidic device integrated with a printed RF circuit so the device can be wirelessly powered by a commercially available RFID reader. For conventional dielectrophoresis devices, electrical wires are needed to connect the electric components on the microchip to external equipment such as power supplies, amplifiers, function generators, etc. Such a procedure is unfamiliar to most clinicians and pathologists who are used to working with a microscope for examination of samples on microscope slides. The wirelessly powered device reported here eliminates the entire need for wire attachments and external instruments so the operators can use the device in essentially the same manner as they do with microscope slides. The integrated circuit can be fabricated on a flexible plastic substrate at very low cost using a roll-to-roll printing method. Electrical power at 13.56 MHz transmitted by a radio-frequency identification (RFID) reader is inductively coupled to the printed RFIC and converted into 10 V DC (direct current) output, which provides sufficient power to drive a microfluidic device to manipulate biological particles such as beads and proteins via the DC dielectrophoresis (DC-DEP) effect. To our best knowledge, this is the first wirelessly powered microfluidic dielectrophoresis device. Although the work is preliminary, the device concept, the architecture, and the core technology are expected to stimulate many efforts in the future and transform the technology to a wide range of clinical and point-of-care applications. This journal is © The Royal Society of Chemistry 2011

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.

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.

Fuel cell-powered microfluidic platform for lab-on-a-chip applications: Integration into an autonomous amperometric sensing device.

Science.gov (United States)

Esquivel, J P; Colomer-Farrarons, J; Castellarnau, M; Salleras, M; del Campo, F J; Samitier, J; Miribel-Català, P; Sabaté, N

2012-11-07

The present paper reports for the first time the integration of a microfluidic system, electronics modules, amperometric sensor and display, all powered by a single micro direct methanol fuel cell. In addition to activating the electronic circuitry, the integrated power source also acts as a tuneable micropump. The electronics fulfil several functions. First, they regulate the micro fuel cell output power, which off-gas controls the flow rate of different solutions toward an electrochemical sensor through microfluidic channels. Secondly, as the fuel cell powers a three-electrode electrochemical cell, the electronics compare the working electrode output signal with a set reference value. Thirdly, if the concentration measured by the sensor exceeds this threshold value, the electronics switch on an integrated organic display. This integrated approach pushes forward the development of truly autonomous point-of-care devices relying on electrochemical detection.

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.

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.

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

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...... 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...... 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...

Microfluidic Devices for Chemical and Biochemical Analysis in Microgravity

Science.gov (United States)

Roman, Gregory T.; Culbertson, Christopher T.; Meyer, Amanda; Ramsey, J. Michael; Gonda, Steven R.

2004-01-01

One often touted benefit of "Lab-on-a-Chip" devices is their potential for use in remote environments. The ultimate remote environment is outer space, and NASA has multiple needs in the area of analytical sensing capability in such an environment. In particular, we are interested in integrating microfluidic devices with NASA bioreactor systems. In such an integrated system, the microfluidic device will serve as a biosensor and be used for both feedback control and for detecting various bioproducts produced by cells cultured in the NASA bioreactors. As a first step in demonstrating the ability of microfluidic devices to operate under the extreme environmental conditions found in outer space, we constructed a portable, battery operated platform for testing under reduced gravity conditions on a NASA KC-135 reduced gravity research aircraft, (AKA "the vomit comet"). The test platform consisted of a microchip, two 0-8kV high voltage power supplies, a high voltage switch, a solid-state diode-pumped green laser, a channel photomultiplier, and an inertial mass measurement unit, all under the control of a laptop computer and powered by 10 D-cell alkaline batteries. Over the course of 4 KC-135 flights, 1817 fast electrophoretic separations of 4 amino acids and/or proteins were performed in a variety of gravitational environments including zero-G, Martian-G, lunar-G, and 2-G. Results from these experiments will be presented and discussed.

Downstream bioprocess characterisation within microfluidic devices

DEFF Research Database (Denmark)

Marques, Marco; Krühne, Ulrich; Szita, Nicolas

2016-01-01

developed which has, to some extent, hindered their implementation as early process development tools. Microfluidic devices are particularly attractive for using fewer resources, for having the possibility of parallelisation and for requiring fewer mechanical manipulations. The expectation...... is that these devices will facilitate the rapid definition of critical process parameters, and thus ultimately reduce production costs. We have developed several microfluidic mDUOs and combined them with advanced and novel analytical approaches, resulting in devices that can potentially be employed for both analytical...... for the liquid–liquid extraction of pharmaceuticals, for the purification and concentration of drug delivery vehicles, and for the flocculation of yeast cells in microfluidic devices. For the latter, we will present for the first time the capability to study flocculation-growth independent from the floc breakage...

Microfluidic device, and related methods

Science.gov (United States)

Wong, Eric W. (Inventor)

2010-01-01

A method of making a microfluidic device is provided. The method features patterning a permeable wall on a substrate, and surrounding the permeable wall with a solid, non-permeable boundary structure to establish a microfluidic channel having a cross-sectional dimension less than 5,000 microns and a cross-sectional area at least partially filled with the permeable wall so that fluid flowing through the microfluidic channel at least partially passes through the permeable wall.

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

Science.gov (United States)

Alvankarian, Jafar; Yeop Majlis, Burhanuddin

2012-03-01

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.

Modular integration of electronics and microfluidic systems using flexible printed circuit boards.

Science.gov (United States)

Wu, Amy; Wang, Lisen; Jensen, Erik; Mathies, Richard; Boser, Bernhard

2010-02-21

Microfluidic systems offer an attractive alternative to conventional wet chemical methods with benefits including reduced sample and reagent volumes, shorter reaction times, high-throughput, automation, and low cost. However, most present microfluidic systems rely on external means to analyze reaction products. This substantially adds to the size, complexity, and cost of the overall system. Electronic detection based on sub-millimetre size integrated circuits (ICs) has been demonstrated for a wide range of targets including nucleic and amino acids, but deployment of this technology to date has been limited due to the lack of a flexible process to integrate these chips within microfluidic devices. This paper presents a modular and inexpensive process to integrate ICs with microfluidic systems based on standard printed circuit board (PCB) technology to assemble the independently designed microfluidic and electronic components. The integrated system can accommodate multiple chips of different sizes bonded to glass or PDMS microfluidic systems. Since IC chips and flex PCB manufacturing and assembly are industry standards with low cost, the integrated system is economical for both laboratory and point-of-care settings.

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...

Bioanalysis in microfluidic devices.

Science.gov (United States)

Khandurina, Julia; Guttman, András

2002-01-18

Microfabricated bioanalytical devices (also referred to as laboratory-on-a-chip or micro-TAS) offer highly efficient platforms for simultaneous analysis of a large number of biologically important molecules, possessing great potential for genome, proteome and metabolome studies. Development and implementation of microfluidic-based bioanalytical tools involves both established and evolving technologies, including microlithography, micromachining, micro-electromechanical systems technology and nanotechnology. This article provides an overview of the latest developments in the key device subject areas and the basic interdisciplinary technologies. Important aspects of DNA and protein analysis, interfacing issues and system integration are all thoroughly discussed, along with applications for this novel "synergized" technology in high-throughput separations of biologically important molecules. This review also gives a better understanding of how to utilize these technologies as well as to provide appropriate technical solutions to problems perceived as being more fundamental.

3D Ceramic Microfluidic Device Manufacturing

International Nuclear Information System (INIS)

Natarajan, Govindarajan; Humenik, James N

2006-01-01

Today, semiconductor processing serves as the backbone for the bulk of micromachined devices. Precision lithography and etching technology used in the semiconductor industry are also leveraged by alternate techniques like electroforming and molding. The nature of such processing is complex, limited and expensive for any manufacturing foundry. This paper details the technology elements developed to manufacture cost effective and versatile microfluidic devices for applications ranging from medical diagnostics to characterization of bioassays. Two applications using multilayer ceramic technology to manufacture complex 3D microfluidic devices are discussed

Integrated bioassays in microfluidic devices: botulinum toxin assays.

Science.gov (United States)

Mangru, Shakuntala; Bentz, Bryan L; Davis, Timothy J; Desai, Nitin; Stabile, Paul J; Schmidt, James J; Millard, Charles B; Bavari, Sina; Kodukula, Krishna

2005-12-01

A microfluidic assay was developed for screening botulinum neurotoxin serotype A (BoNT-A) by using a fluorescent resonance energy transfer (FRET) assay. Molded silicone microdevices with integral valves, pumps, and reagent reservoirs were designed and fabricated. Electrical and pneumatic control hardware were constructed, and software was written to automate the assay protocol and data acquisition. Detection was accomplished by fluorescence microscopy. The system was validated with a peptide inhibitor, running 2 parallel assays, as a feasibility demonstration. The small footprint of each bioreactor cell (0.5 cm2) and scalable fluidic architecture enabled many parallel assays on a single chip. The chip is programmable to run a dilution series in each lane, generating concentration-response data for multiple inhibitors. The assay results showed good agreement with the corresponding experiments done at a macroscale level. Although the system has been developed for BoNT-A screening, a wide variety of assays can be performed on the microfluidic chip with little or no modification.

A microfluidic device with pillars

DEFF Research Database (Denmark)

2014-01-01

The invention provides a microfluidic device for mixing liquid reagents, the device comprises, a chip forming at least one reaction chamber between a bottom and a top and extending between an inlet and an outlet. To enable manufacturing from less rigid materials, the device comprises pillars...

Tunable Microfluidic Devices for Hydrodynamic Fractionation of Cells and Beads: A Review

Directory of Open Access Journals (Sweden)

Jafar Alvankarian

2015-11-01

Full Text Available The adjustable microfluidic devices that have been developed for hydrodynamic-based fractionation of beads and cells are important for fast performance tunability through interaction of mechanical properties of particles in fluid flow and mechanically flexible microstructures. In this review, the research works reported on fabrication and testing of the tunable elastomeric microfluidic devices for applications such as separation, filtration, isolation, and trapping of single or bulk of microbeads or cells are discussed. Such microfluidic systems for rapid performance alteration are classified in two groups of bulk deformation of microdevices using external mechanical forces, and local deformation of microstructures using flexible membrane by pneumatic pressure. The main advantage of membrane-based tunable systems has been addressed to be the high capability of integration with other microdevice components. The stretchable devices based on bulk deformation of microstructures have in common advantage of simplicity in design and fabrication process.

Integrated electrofluidic circuits: pressure sensing with analog and digital operation functionalities for microfluidics.

Science.gov (United States)

Wu, Chueh-Yu; Lu, Jau-Ching; Liu, Man-Chi; Tung, Yi-Chung

2012-10-21

Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Science.gov (United States)

Halldorsson, Skarphedinn; Lucumi, Edinson; Gómez-Sjöberg, Rafael; Fleming, Ronan M T

2015-01-15

Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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.

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.

A PEG-DA microfluidic device for chemotaxis studies

International Nuclear Information System (INIS)

Traore, Mahama Aziz; Behkam, Bahareh

2013-01-01

The study of cells in a well-defined and chemically programmable microenvironment is essential for a complete and fundamental understanding of the cell behaviors with respect to specific chemical compounds. Flow-free microfluidic devices that generate quasi-steady chemical gradients (spatially varying but temporally constant) have been demonstrated as effective chemotaxis assay platforms due to dissociating the effect of chemical cues from mechanical shear forces caused by fluid flow. In this work, we demonstrate the fabrication and characterization of a flow-free microfluidic platform made of polyethylene glycol diacrylate (PEG-DA) hydrogel. We have demonstrated that the mass transport properties of these devices can be customized by fabricating them from PEG-DA gels of four distinct molecular weights. In contrast to microfluidic devices developed using soft lithography; this class of devices can be realized using a more cost-effective approach of direct photopolymerization with fewer microfabrication steps. This microfluidic platform was tested by conducting a quantitative study of the chemotactic behavior of Escherichia coli (E. coli) RP437, a model microorganism, in presence of the chemo-effector, casamino-acids. Using the microfabrication and characterization methodology presented in this work, microfluidic platforms with well-defined and customizable diffusive properties can be developed to accommodate the study of a wide range of cell types. (paper)

Mixing in a Microfluid Device

DEFF Research Database (Denmark)

Hjorth, Poul G.; Deryabin, Mikhail

Mixing of fluids in microchannels cannot rely on turbulence since the flow takes place at extremly low Reynolds numbers. Various active and passive devices have been developed to induce mixing in microfluid flow devices. We describe here a model of an active mixer where a transverse periodic flow...

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.

Integrated optical waveguides and inertial focussing microfluidics in silica for microflow cytometry applications

International Nuclear Information System (INIS)

Butement, Jonathan T; Rowe, David J; Sessions, Neil P; Hua, Ping; Murugan, G Senthil; Wilkinson, James S; Clark, Owain; Chad, John E; Hunt, Hamish C

2016-01-01

A key challenge in the development of a microflow cytometry platform is the integration of the optical components with the fluidics as this requires compatible micro-optical and microfluidic technologies. In this work a microflow cytometry platform is presented comprising monolithically integrated waveguides and deep microfluidics in a rugged silica chip. Integrated waveguides are used to deliver excitation light to an etched microfluidic channel and also collect transmitted light. The fluidics are designed to employ inertial focussing, a particle positioning technique, to reduce signal variation by bringing the flowing particles onto the same plane as the excitation light beam. A fabrication process is described which exploits microelectronics mass production techniques including: sputtering, ICP etching and PECVD. Example devices were fabricated and the effectiveness of inertial focussing of 5.6 µ m fluorescent beads was studied showing lateral and vertical confinement of flowing beads within the microfluidic channel. The fluorescence signals from flowing calibration beads were quantified demonstrating a CV of 26%. Finally the potential of this type of device for measuring the variation in optical transmission from input to output waveguide as beads flowed through the beam was evaluated. (paper)

A piezo-ring-on-chip microfluidic device for simple and low-cost mass spectrometry interfacing.

Science.gov (United States)

Tsao, Chia-Wen; Lei, I-Chao; Chen, Pi-Yu; Yang, Yu-Liang

2018-02-12

Mass spectrometry (MS) interfacing technology provides the means for incorporating microfluidic processing with post MS analysis. In this study, we propose a simple piezo-ring-on-chip microfluidic device for the controlled spraying of MALDI-MS targets. This device uses a low-cost, commercially-available ring-shaped piezoelectric acoustic atomizer (piezo-ring) directly integrated into a polydimethylsiloxane microfluidic device to spray the sample onto the MS target substrate. The piezo-ring-on-chip microfluidic device's design, fabrication, and actuation, and its pulsatile pumping effects were evaluated. The spraying performance was examined by depositing organic matrix samples onto the MS target substrate by using both an automatic linear motion motor, and manual deposition. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was performed to analyze the peptide samples on the MALDI target substrates. Using our technique, model peptides with 10 -6 M concentration can be successfully detected. The results also indicate that the piezo-ring-on-chip approach forms finer matrix crystals and presents better MS signal uniformity with little sample consumption compared to the conventional pipetting method.

Integrated microchip incorporating atomic magnetometer and microfluidic channel for NMR and MRI

Science.gov (United States)

Ledbetter, Micah P [Oakland, CA; Savukov, Igor M [Los Alamos, NM; Budker, Dmitry [El Cerrito, CA; Shah, Vishal K [Plainsboro, NJ; Knappe, Svenja [Boulder, CO; Kitching, John [Boulder, CO; Michalak, David J [Berkeley, CA; Xu, Shoujun [Houston, TX; Pines, Alexander [Berkeley, CA

2011-08-09

An integral microfluidic device includes an alkali vapor cell and microfluidic channel, which can be used to detect magnetism for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Small magnetic fields in the vicinity of the vapor cell can be measured by optically polarizing and probing the spin precession in the small magnetic field. This can then be used to detect the magnetic field of in encoded analyte in the adjacent microfluidic channel. The magnetism in the microfluidic channel can be modulated by applying an appropriate series of radio or audio frequency pulses upstream from the microfluidic chip (the remote detection modality) to yield a sensitive means of detecting NMR and MRI.

Discrete microfluidics based on aluminum nitride surface acoustic wave devices

OpenAIRE

Zhou, J.; Pang, H.F.; Garcia-Gancedo, L.; Iborra, E.; Clement, M.; De Miguel-Ramos, M.; Jin, H.; Luo, J.K.; Smith, S.; Dong, S.R.; Wang, D.M.; Fu, Y.Q.

2015-01-01

To date, most surface acoustic wave (SAW) devices have been made from bulk piezoelectric materials, such as quartz, lithium niobate or lithium tantalite. These bulk materials are brittle, less easily integrated with electronics for control and signal processing, and difficult to realize multiple wave modes or apply complex electrode designs. Using thin film SAWs makes it convenient to integrate microelectronics and multiple sensing or microfluidics techniques into a lab-on-a-chip with low cos...

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.

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

A microfluidic dialysis device for complex biological mixture SERS analysis

KAUST Repository

Perozziello, Gerardo; Candeloro, Patrizio; Gentile, Francesco T.; Coluccio, Maria Laura; Tallerico, Marco; De Grazia, Antonio; Nicastri, Annalisa; Perri, Angela Mena; Parrotta, Elvira; Pardeo, Francesca; Catalano, Rossella; Cuda, Giovanni; Di Fabrizio, Enzo M.

2015-01-01

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

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.

[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.

Ultra-Portable Smartphone Controlled Integrated Digital Microfluidic System in a 3D-Printed Modular Assembly

OpenAIRE

Yafia, Mohamed; Ahmadi, Ali; Hoorfar, Mina; Najjaran, Homayoun

2015-01-01

Portable sensors and biomedical devices are influenced by the recent advances in microfluidics technologies, compact fabrication techniques, improved detection limits and enhanced analysis capabilities. This paper reports the development of an integrated ultraportable, low-cost, and modular digital microfluidic (DMF) system and its successful integration with a smartphone used as a high-level controller and post processing station. Low power and cost effective electronic circuits are designed...

Magnetic particle diverter in an integrated microfluidic format

Energy Technology Data Exchange (ETDEWEB)

Pekas, Nikola [Institute for Combinatorial Discovery, Departments of Chemistry and Chemical Engineering, and Ames Laboratory-USDOE, Iowa State University, Ames, IA 50011-3111 (United States); Granger, Michael [Institute for Combinatorial Discovery, Departments of Chemistry and Chemical Engineering, and Ames Laboratory-USDOE, Iowa State University, Ames, IA 50011-3111 (United States); Tondra, Mark [NVE Corporation, Eden Prairie, Minnesota 55344 (United States); Popple, Anthony [NVE Corporation, Eden Prairie, Minnesota 55344 (United States); Porter, Marc D. [Institute for Combinatorial Discovery, Departments of Chemistry and Chemical Engineering, and Ames Laboratory-USDOE, Iowa State University, Ames, IA 50011-3111 (United States)]. E-mail: mporter@porter1.ameslab.gov

2005-05-15

A fully integrated micromagnetic particle diverter and microfluidic system are described. Particles are diverted via an external uniform magnetic field perturbed at the microscale by underlying current straps. The resulting magnetic force deflects particles across a flow stream into one of the two channels at a Y-shaped junction. The basic theoretical framework, design, and operational demonstration of the device are presented.

Magnetic particle diverter in an integrated microfluidic format

International Nuclear Information System (INIS)

Pekas, Nikola; Granger, Michael; Tondra, Mark; Popple, Anthony; Porter, Marc D.

2005-01-01

A fully integrated micromagnetic particle diverter and microfluidic system are described. Particles are diverted via an external uniform magnetic field perturbed at the microscale by underlying current straps. The resulting magnetic force deflects particles across a flow stream into one of the two channels at a Y-shaped junction. The basic theoretical framework, design, and operational demonstration of the device are presented

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.

Acoustically and Electrokinetically Driven Transport in Microfluidic Devices

Science.gov (United States)

Sayar, Ersin

Electrokinetically driven flows are widely employed as a primary method for liquid pumping in micro-electromechanical systems. Mixing of analytes and reagents is limited in microfluidic devices due to the low Reynolds number of the flows. Acoustic excitations have recently been suggested to promote mixing in the microscale flow systems. Electrokinetic flows through straight microchannels were investigated using the Poisson-Boltzmann and Nernst-Planck models. The acoustic wave/fluid flow interactions in a microchannel were investigated via the development of two and three-dimensional dynamic predictive models for flows with field couplings of the electrical, mechanical and fluid flow quantities. The effectiveness and applicability of electrokinetic augmentation in flexural plate wave micropumps for enhanced capabilities were explored. The proposed concept can be exploited to integrate micropumps into complex microfluidic chips improving the portability of micro-total-analysis systems along with the capabilities of actively controlling acoustics and electrokinetics for micro-mixer applications. Acoustically excited flows in microchannels consisting of flexural plate wave devices and thin film resonators were considered. Compressible flow fields were considered to accommodate the acoustic excitations produced by a vibrating wall. The velocity and pressure profiles for different parameters including frequency, channel height, wave amplitude and length were investigated. Coupled electrokinetics and acoustics cases were investigated while the electric field intensity of the electrokinetic body forces and actuation frequency of acoustic excitations were varied. Multifield analysis of a piezoelectrically actuated valveless micropump was also presented. The effect of voltage and frequency on membrane deflection and flow rate were investigated. Detailed fluid/solid deformation coupled simulations of piezoelectric valveless micropump have been conducted to predict the

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)

Integrated acoustic and magnetic separation in microfluidic channels

DEFF Research Database (Denmark)

Adams, Jonathan; Thevoz, Patrick; Bruus, Henrik

2009-01-01

With a growing number of cell-based biotechnological applications, there is a need for particle separation systems capable of multiparameter separations at high purity and throughput, beyond what is presently offered by traditional methods including fluorescence activated cell sorting and column......-based magnetic separation. Toward this aim, we report on the integration of microfluidic acoustic and magnetic separation in a monolithic device for multiparameter particle separation. Using our device, we demonstrate high-purity separation of a multicomponent particle mixture at a throughput of up to 10...

Diffusion phenomena of cells and biomolecules in microfluidic devices.

Science.gov (United States)

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-09-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules.

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.

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.

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.

Integrated optical detection of autonomous capillary microfluidic immunoassays:a hand-held point-of-care prototype.

Science.gov (United States)

Novo, P; Chu, V; Conde, J P

2014-07-15

The miniaturization of biosensors using microfluidics has potential in enabling the development of point-of-care devices, with the added advantages of reduced time and cost of analysis with limits-of-detection comparable to those obtained through traditional laboratory techniques. Interfacing microfluidic devices with the external world can be difficult especially in aspects involving fluid handling and the need for simple sample insertion that avoids special equipment or trained personnel. In this work we present a point-of-care prototype system by integrating capillary microfluidics with a microfabricated photodiode array and electronic instrumentation into a hand-held unit. The capillary microfluidic device is capable of autonomous and sequential fluid flow, including control of the average fluid velocity at any given point of the analysis. To demonstrate the functionality of the prototype, a model chemiluminescence ELISA was performed. The performance of the integrated optical detection in the point-of-care prototype is equal to that obtained with traditional bench-top instrumentation. The photodiode signals were acquired, displayed and processed by a simple graphical user interface using a computer connected to the microcontroller through USB. The prototype performed integrated chemiluminescence ELISA detection in about 15 min with a limit-of-detection of ≈2 nM with an antibody-antigen affinity constant of ≈2×10(7) M(-1). Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

Monolithic integration of microfluidic channels and semiconductor lasers

Science.gov (United States)

Cran-McGreehin, Simon J.; Dholakia, Kishan; Krauss, Thomas F.

2006-08-01

We present a fabrication method for the monolithic integration of microfluidic channels into semiconductor laser material. Lasers are designed to couple directly into the microfluidic channel, allowing submerged particles pass through the output beams of the lasers. The interaction between particles in the channel and the lasers, operated in either forward or reverse bias, allows for particle detection, and the optical forces can be used to trap and move particles. Both interrogation and manipulation are made more amenable for lab-on-a-chip applications through monolithic integration. The devices are very small, they require no external optical components, have perfect intrinsic alignment, and can be created with virtually any planar configuration of lasers in order to perform a variety of tasks. Their operation requires no optical expertise and only low electrical power, thus making them suitable for computer interfacing and automation. Insulating the pn junctions from the fluid is the key challenge, which is overcome by using photo-definable SU8-2000 polymer.

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

Science.gov (United States)

Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

2015-01-01

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

Directory of Open Access Journals (Sweden)

George Luka

2015-12-01

Full Text Available A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter, increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture.

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

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.

Sperm quality assessment via separation and sedimentation in a microfluidic device.

Science.gov (United States)

Chen, Chang-Yu; Chiang, Tsun-Chao; Lin, Cheng-Ming; Lin, Shu-Sheng; Jong, De-Shien; Tsai, Vincent F-S; Hsieh, Ju-Ton; Wo, Andrew M

2013-09-07

A major reason for infertility is due to male factors, including the quality of spermatozoa, which is a primary factor and often difficult to assess, particularly the total sperm concentration and its motile percentage. This work presents a simple microfluidic device to assess sperm quality by quantifying both total and motile sperm counts. The key design feature of the microfluidic device is two channels separated by a permeative phase-guide structure, where one channel is filled with raw semen and the other with pure buffer. The semen sample was allowed to reach equilibrium in both chambers, whereas non-motile sperms remained in the original channel, and roughly half of the motile sperms would swim across the phase-guide barrier into the buffer channel. Sperms in each channel agglomerated into pellets after centrifugation, with the corresponding area representing total and motile sperm concentrations. Total sperm concentration up to 10(8) sperms per ml and motile percentage in the range of 10-70% were tested, encompassing the cutoff value of 40% stated by World Health Organization standards. Results from patient samples show compact and robust pellets after centrifugation. Comparison of total sperm concentration between the microfluidic device and the Makler chamber reveal they agree within 5% and show strong correlation, with a coefficient of determination of R(2) = 0.97. Motile sperm count between the microfluidic device and the Makler chamber agrees within 5%, with a coefficient of determination of R(2) = 0.84. Comparison of results from the Makler Chamber, sperm quality analyzer, and the microfluidic device revealed that results from the microfluidic device agree well with the Makler chamber. The sperm microfluidic chip analyzes both total and motile sperm concentrations in one spin, is accurate and easy to use, and should enable sperm quality analysis with ease.

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.

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.

Microfluidic Devices for Drug Delivery Systems and Drug Screening

Science.gov (United States)

Kompella, Uday B.; Damiati, Safa A.

2018-01-01

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

Clear Castable Polyurethane Elastomer for Fabrication of Microfluidic Devices

Science.gov (United States)

Domansky, Karel; Leslie, Daniel C.; McKinney, James; Fraser, Jacob P.; Sliz, Josiah D.; Hamkins-Indik, Tiama; Hamilton, Geraldine A.; Bahinski, Anthony; Ingber, Donald E.

2013-01-01

Polydimethylsiloxane (PDMS) has numerous desirable properties for fabricating microfluidic devices, including optical transparency, flexibility, biocompatibility, and fabrication by casting; however, partitioning of small hydrophobic molecules into the bulk of PDMS hinders industrial acceptance of PDMS microfluidic devices for chemical processing and drug development applications. Here we describe an attractive alternative material that is similar to PDMS in terms of optical transparency, flexibility and castability, but that is also resistant to absorption of small hydrophobic molecules. PMID:23954953

Printing-based fabrication method using sacrificial paper substrates for flexible and wearable microfluidic devices

International Nuclear Information System (INIS)

Chung, Daehan; Gray, Bonnie L

2017-01-01

We present a simple, fast, and inexpensive new printing-based fabrication process for flexible and wearable microfluidic channels and devices. Microfluidic devices are fabricated on textiles (fabric) for applications in clothing-based wearable microfluidic sensors and systems. The wearable and flexible microfluidic devices are comprised of water-insoluable screen-printable plastisol polymer. Sheets of paper are used as sacrificial substrates for multiple layers of polymer on the fabric’s surface. Microfluidic devices can be made within a short time using simple processes and inexpensive equipment that includes a laser cutter and a thermal laminator. The fabrication process is characterized to demonstrate control of microfluidic channel thickness and width. Film thickness smaller than 100 micrometers and lateral dimensions smaller than 150 micrometers are demonstrated. A flexible microfluidic mixer is also developed on fabric and successfully tested on both flat and curved surfaces at volumetric flow rates ranging from 5.5–46 ml min −1 . (paper)

Printing-based fabrication method using sacrificial paper substrates for flexible and wearable microfluidic devices

Science.gov (United States)

Chung, Daehan; Gray, Bonnie L.

2017-11-01

We present a simple, fast, and inexpensive new printing-based fabrication process for flexible and wearable microfluidic channels and devices. Microfluidic devices are fabricated on textiles (fabric) for applications in clothing-based wearable microfluidic sensors and systems. The wearable and flexible microfluidic devices are comprised of water-insoluable screen-printable plastisol polymer. Sheets of paper are used as sacrificial substrates for multiple layers of polymer on the fabric’s surface. Microfluidic devices can be made within a short time using simple processes and inexpensive equipment that includes a laser cutter and a thermal laminator. The fabrication process is characterized to demonstrate control of microfluidic channel thickness and width. Film thickness smaller than 100 micrometers and lateral dimensions smaller than 150 micrometers are demonstrated. A flexible microfluidic mixer is also developed on fabric and successfully tested on both flat and curved surfaces at volumetric flow rates ranging from 5.5-46 ml min-1.

Finite element modeling simulation-assisted design of integrated microfluidic chips for heavy metal ion stripping analysis

International Nuclear Information System (INIS)

Hong, Ying; Zou, Jianhua; Ge, Gang; Xiao, Wanyue; Shao, Jinjun; Dong, Xiaochen; Gao, Ling

2017-01-01

In this article, a transparent integrated microfluidic device composed of a 3D-printed thin-layer flow cell (3D-PTLFC) and an S-shaped screen-printed electrode (SPE) has been designed and fabricated for heavy metal ion stripping analysis. A finite element modeling (FEM) simulation is employed to optimize the shape of the electrode, the direction of the inlet pipeline, the thin-layer channel height and the sample flow rate to enhance the electron-enrichment efficiency for stripping analysis. The results demonstrate that the S-shaped SPE configuration matches the channel in 3D-PTLFC perfectly for the anodic stripping behavior of the heavy metal ions. Under optimized conditions, a wide linear range of 1–80 µ g l −1 is achieved for Pb 2+ detection with a limit of 0.3 µ g l −1 for the microfluidic device. Thus, the obtained integrated microfluidic device proves to be a promising approach for heavy metal ions stripping analysis with low cost and high performance. (paper)

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…

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.

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.

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....

An investigation of paper based microfluidic devices for size based separation and extraction applications.

Science.gov (United States)

Zhong, Z W; Wu, R G; Wang, Z P; Tan, H L

2015-09-01

Conventional microfluidic devices are typically complex and expensive. The devices require the use of pneumatic control systems or highly precise pumps to control the flow in the devices. This work investigates an alternative method using paper based microfluidic devices to replace conventional microfluidic devices. Size based separation and extraction experiments conducted were able to separate free dye from a mixed protein and dye solution. Experimental results showed that pure fluorescein isothiocyanate could be separated from a solution of mixed fluorescein isothiocyanate and fluorescein isothiocyanate labeled bovine serum albumin. The analysis readings obtained from a spectrophotometer clearly show that the extracted tartrazine sample did not contain any amount of Blue-BSA, because its absorbance value was 0.000 measured at a wavelength of 590nm, which correlated to Blue-BSA. These demonstrate that paper based microfluidic devices, which are inexpensive and easy to implement, can potentially replace their conventional counterparts by the use of simple geometry designs and the capillary action. These findings will potentially help in future developments of paper based microfluidic devices. Copyright © 2015 Elsevier B.V. All rights reserved.

OLED Hybrid Integrated Polymer Microfluidic Biosensing for Point of Care Testing

Directory of Open Access Journals (Sweden)

Ashwin Acharya

2015-09-01

Full Text Available This paper reports a microfluidic platform with external hybrid integration of an organic light emitting diode (OLED as an excitation source. This device can be used as a simple and cost effective biosensing element. The device is capable of rapid in-situ detection of biological elements such as sensing of interaction of antigen with fluorescent tagged antibody conjugates. These portable microfluidic systems have great potential for use an OLED in a single chip with very high accuracy and sensitivity for various point-of-care (POC diagnosis and lab on a chip (LOC applications, as the miniaturization of the biosensor is essential for handling smaller sample volumes in order to achieve high throughput. The biosensing element was successfully tested to detect anti-sheep IgG conjugates tagged to Alexafluor using a fluorescence based immunoassay method.

High content screening in microfluidic devices

Science.gov (United States)

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

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.

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.

Fabrication of a microfluidic chip by UV bonding at room temperature for integration of temperature-sensitive layers

Science.gov (United States)

Schlautmann, S.; Besselink, G. A. J.; Radhakrishna Prabhu, G.; Schasfoort, R. B. M.

2003-07-01

A method for the bonding of a microfluidic device at room temperature is presented. The wafer with the fluidic structures was bonded to a sensor wafer with gold pads by means of adhesive bonding, utilizing an UV-curable glue layer. To avoid filling the fluidic channels with the glue, a stamping process was developed which allows the selective application of a thin glue layer. In this way a microfluidic glass chip was fabricated that could be used for performing surface plasmon resonance measurements without signs of leakage. The advantage of this method is the possibility of integration of organic layers as well as other temperature-sensitive layers into a microfluidic glass device.

Rapid prototyping of 2D glass microfluidic devices based on femtosecond laser assisted selective etching process

Science.gov (United States)

Kim, Sung-Il; Kim, Jeongtae; Koo, Chiwan; Joung, Yeun-Ho; Choi, Jiyeon

2018-02-01

Microfluidics technology which deals with small liquid samples and reagents within micro-scale channels has been widely applied in various aspects of biological, chemical, and life-scientific research. For fabricating microfluidic devices, a silicon-based polymer, PDMS (Polydimethylsiloxane), is widely used in soft lithography, but it has several drawbacks for microfluidic applications. Glass has many advantages over PDMS due to its excellent optical, chemical, and mechanical properties. However, difficulties in fabrication of glass microfluidic devices that requires multiple skilled steps such as MEMS technology taking several hours to days, impedes broad application of glass based devices. Here, we demonstrate a rapid and optical prototyping of a glass microfluidic device by using femtosecond laser assisted selective etching (LASE) and femtosecond laser welding. A microfluidic droplet generator was fabricated as a demonstration of a microfluidic device using our proposed prototyping. The fabrication time of a single glass chip containing few centimeter long and complex-shaped microfluidic channels was drastically reduced in an hour with the proposed laser based rapid and simple glass micromachining and hermetic packaging technique.

A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection.

Science.gov (United States)

Zuo, Peng; Li, XiuJun; Dominguez, Delfina C; Ye, Bang-Ce

2013-10-07

Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL(-1). We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step 'turn on' pathogen assay in a ready-to-use microfluidic device only takes ~10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens.

A review of electrochemiluminescence (ECL) in and for microfluidic analytical devices.

Science.gov (United States)

Kirschbaum, Stefanie E K; Baeumner, Antje J

2015-05-01

The concept and realization of microfluidic total analysis systems (microTAS) have revolutionized the analytical process by integrating the whole breadth of analytical techniques into miniaturized systems. Paramount for efficient and competitive microTAS are integrated detection strategies, which lead to low limits of detection while reducing the sample volume. The concept of electrochemiluminescence (ECL) has been intriguing ever since its introduction based on Ru(bpy)3 (2+) by Tokel and Bard [1] (J Am Chem Soc 1853:2862-2863, 1972), especially because of its immense sensitivity, nonexistent auto-luminescent background signal, and simplicity in experimental design. Therefore, integrating ECL detection into microTAS is a logical consequence to achieve simple, yet highly sensitive, sensors. However, published microanalytical devices employing ECL detection focus in general on traditional ECL chemistry and have yet to take advantage of advances made in standard bench-top ECL strategies. This review will therefore focus on the most recent advancements in microfluidic ECL approaches, but also evaluate the potential impact of bench-top ECL research progress that would further improve performance and lower limits of detection of micro analytical ECL systems, ensuring their desirability as detection principle for microTAS applications.

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.

Microfluidic high gradient magnetic cell separation

Science.gov (United States)

Inglis, David W.; Riehn, Robert; Sturm, James C.; Austin, Robert H.

2006-04-01

Separation of blood cells by native susceptibility and by the selective attachment of magnetic beads has recently been demonstrated on microfluidic devices. We discuss the basic principles of how forces are generated via the magnetic susceptibility of an object and how microfluidics can be combined with micron-scale magnetic field gradients to greatly enhance in principle the fractionating power of magnetic fields. We discuss our efforts and those of others to build practical microfluidic devices for the magnetic separation of blood cells. We also discuss our attempts to integrate magnetic separation with other microfluidic features for developing handheld medical diagnostic tools.

An inkjet-printed microfluidic device for liquid-liquid extraction.

Science.gov (United States)

Watanabe, Masashi

2011-04-07

A microfluidic device for liquid-liquid extraction was quickly produced using an office inkjet printer. An advantage of this method is that normal end users, who are not familiar with microfabrication, can produce their original microfluidic devices by themselves. In this method, the printer draws a line on a hydrophobic and oil repellent surface using hydrophilic ink. This line directs a fluid, such as water or xylene, to form a microchannel along the printed line. Using such channels, liquid-liquid extraction was successfully performed under concurrent and countercurrent flow conditions. © The Royal Society of Chemistry 2011

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.

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

Science.gov (United States)

Perestrelo, Ana Rubina; Águas, Ana C. P.; Rainer, Alberto; Forte, Giancarlo

2015-01-01

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. PMID:26690442

Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity.

Science.gov (United States)

Kong, Xianming; Chong, Xinyuan; Squire, Kenny; Wang, Alan X

2018-04-15

The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30µm 2 . As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.

Microfluidic-integrated biosensors: prospects for point-of-care diagnostics.

Science.gov (United States)

Kumar, Suveen; Kumar, Saurabh; Ali, Md Azahar; Anand, Pinki; Agrawal, Ved Varun; John, Renu; Maji, Sagar; Malhotra, Bansi D

2013-11-01

There is a growing demand to integrate biosensors with microfluidics to provide miniaturized platforms with many favorable properties, such as reduced sample volume, decreased processing time, low cost analysis and low reagent consumption. These microfluidics-integrated biosensors would also have numerous advantages such as laminar flow, minimal handling of hazardous materials, multiple sample detection in parallel, portability and versatility in design. Microfluidics involves the science and technology of manipulation of fluids at the micro- to nano-liter level. It is predicted that combining biosensors with microfluidic chips will yield enhanced analytical capability, and widen the possibilities for applications in clinical diagnostics. The recent developments in microfluidics have helped researchers working in industries and educational institutes to adopt some of these platforms for point-of-care (POC) diagnostics. This review focuses on the latest advancements in the fields of microfluidic biosensing technologies, and on the challenges and possible solutions for translation of this technology for POC diagnostic applications. We also discuss the fabrication techniques required for developing microfluidic-integrated biosensors, recently reported biomarkers, and the prospects of POC diagnostics in the medical industry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfluidics and Lab-on-a-Chip Devices

DEFF Research Database (Denmark)

Castillo, Jaime

2015-01-01

The rapid advances in microfabrication and nanofabrication in combination with the synthesis and discovery of new materials have propelled the drive to develop new technological devices such as smartphones, personal and tablet computers. These devices have changed the way humankind interacts......TAS technologies need to join forces with those behind the new communication devices which provide sources of power, detection and data transmission complementing the features that lab-on-a-chip and microTAS platforms can offer. An increasing number of microfluidic-based devices, developed both in small start...

Development of an Integrated Polymer Microfluidic Stack

International Nuclear Information System (INIS)

Datta, Proyag; Hammacher, Jens; Pease, Mark; Gurung, Sitanshu; Goettert, Jost

2006-01-01

Microfluidic is a field of considerable interest. While significant research has been carried out to develop microfluidic components, very little has been done to integrate the components into a complete working system. We present a flexible modular system platform that addresses the requirements of a complete microfluidic system. A microfluidic stack system is demonstrated with the layers of the stack being modular for specific functions. The stack and accompanying infrastructure provides an attractive platform for users to transition their design concepts into a working microfluidic system quickly with very little effort. The concept is demonstrated by using the system to carry out a chemilumiscence experiment. Details regarding the fabrication, assembly and experimental methods are presented

Pneumatic oscillator circuits for timing and control of integrated microfluidics.

Science.gov (United States)

Duncan, Philip N; Nguyen, Transon V; Hui, Elliot E

2013-11-05

Frequency references are fundamental to most digital systems, providing the basis for process synchronization, timing of outputs, and waveform synthesis. Recently, there has been growing interest in digital logic systems that are constructed out of microfluidics rather than electronics, as a possible means toward fully integrated laboratory-on-a-chip systems that do not require any external control apparatus. However, the full realization of this goal has not been possible due to the lack of on-chip frequency references, thus requiring timing signals to be provided from off-chip. Although microfluidic oscillators have been demonstrated, there have been no reported efforts to characterize, model, or optimize timing accuracy, which is the fundamental metric of a clock. Here, we report pneumatic ring oscillator circuits built from microfluidic valves and channels. Further, we present a compressible-flow analysis that differs fundamentally from conventional circuit theory, and we show the utility of this physically based model for the optimization of oscillator stability. Finally, we leverage microfluidic clocks to demonstrate circuits for the generation of phase-shifted waveforms, self-driving peristaltic pumps, and frequency division. Thus, pneumatic oscillators can serve as on-chip frequency references for microfluidic digital logic circuits. On-chip clocks and pumps both constitute critical building blocks on the path toward achieving autonomous laboratory-on-a-chip devices.

Microfluidics and thin-film processes: a recipe for organic integrated photonics based on 3D microresonators

Science.gov (United States)

Huby, N.; Pluchon, D.; Belloul, M.; Moreac, A.; Coulon, N.; Gaviot, E.; Panizza, P.; B"che, B.

2010-02-01

We report on the design and realization of photonic integrated devices based on 3D organic microresonators. This has been achieved by combining microfluidics techniques and thin-film processes. The microfluidic device and the control of the flow rates of the continuous and dispersed phases allow the fabrication of organic microresonators with diameter ranging from 30 to 200 μm. The resonance of the sphere in air has been first investigated by using the Raman spectroscopy set-up demonstrating the appropriate photonic properties. Then the microresonators have been integrated on an organic chip made of the photosensitive resin SU-8 and positioned at the extremity of a taper and alongside a rib waveguide. The realization of these structures by thin-film processes needs one step UV-lithography leading to 6μm width and 30μm height. Both devices have proved the efficient evanescent coupling leading to the excitation of the whispering gallery modes confined at the surface of the organic 3D microresonators. Finally, a band-stop filter has been used to detect the resonance spectra of the resonators once integrated.

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.

Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

Science.gov (United States)

Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

2018-04-11

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

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.

An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications.

Science.gov (United States)

Chabinyc, M L; Chiu, D T; McDonald, J C; Stroock, A D; Christian, J F; Karger, A M; Whitesides, G M

2001-09-15

This paper describes a prototype of an integrated fluorescence detection system that uses a microavalanche photodiode (microAPD) as the photodetector for microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype device consisted of a reusable detection system and a disposable microfluidic system that was fabricated using rapid prototyping. The first step of the procedure was the fabrication of microfluidic channels in PDMS and the encapsulation of a multimode optical fiber (100-microm core diameter) in the PDMS; the tip of the fiber was placed next to the side wall of one of the channels. The optical fiber was used to couple light into the microchannel for the excitation of fluorescent analytes. The photodetector, a prototype solid-state microAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80 microm) colored polycarbonate filter was placed on the top of the embedded microAPD to absorb scattered excitation light before it reached the detector. The microAPD was placed below the microchannel and orthogonal to the axis of the optical fiber. The close proximity (approximately 200 microm) of the microAPD to the microchannel made it unnecessary to incorporate transfer optics; the pixel size of the microAPD (30 microm) matched the dimensions of the channels (50 microm). A blue light-emitting diode was used for fluorescence excitation. The microAPD was operated in Geiger mode to detect the fluorescence. The detection limit of the prototype (approximately 25 nM) was determined by finding the minimum detectable concentration of a solution of fluorescein. The device was used to detect the separation of a mixture of proteins and small molecules by capillary electrophoresis; the separation illustrated the suitability of this integrated fluorescence detection system for bioanalytical applications.

Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels.

Science.gov (United States)

Liu, Ruxiu; Wang, Ningquan; Kamili, Farhan; Sarioglu, A Fatih

2016-04-21

Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays. In this paper, we introduce a scalable electronic sensor technology, called microfluidic CODES, that utilizes resistive pulse sensing to orthogonally detect particles in multiple microfluidic channels from a single electrical output. Combining the techniques from telecommunications and microfluidics, we route three coplanar electrodes on a glass substrate to create multiple Coulter counters producing distinct orthogonal digital codes when they detect particles. We specifically design a digital code set using the mathematical principles of Code Division Multiple Access (CDMA) telecommunication networks and can decode signals from different microfluidic channels with >90% accuracy through computation even if these signals overlap. As a proof of principle, we use this technology to detect human ovarian cancer cells in four different microfluidic channels fabricated using soft lithography. Microfluidic CODES offers a simple, all-electronic interface that is well suited to create integrated, low-cost lab-on-a-chip devices for cell- or particle-based assays in resource-limited settings.

Computational analysis of integrated biosensing and shear flow in a microfluidic vascular model

Science.gov (United States)

Wong, Jeremy F.; Young, Edmond W. K.; Simmons, Craig A.

2017-11-01

Fluid flow and flow-induced shear stress are critical components of the vascular microenvironment commonly studied using microfluidic cell culture models. Microfluidic vascular models mimicking the physiological microenvironment also offer great potential for incorporating on-chip biomolecular detection. In spite of this potential, however, there are few examples of such functionality. Detection of biomolecules released by cells under flow-induced shear stress is a significant challenge due to severe sample dilution caused by the fluid flow used to generate the shear stress, frequently to the extent where the analyte is no longer detectable. In this work, we developed a computational model of a vascular microfluidic cell culture model that integrates physiological shear flow and on-chip monitoring of cell-secreted factors. Applicable to multilayer device configurations, the computational model was applied to a bilayer configuration, which has been used in numerous cell culture applications including vascular models. Guidelines were established that allow cells to be subjected to a wide range of physiological shear stress while ensuring optimal rapid transport of analyte to the biosensor surface and minimized biosensor response times. These guidelines therefore enable the development of microfluidic vascular models that integrate cell-secreted factor detection while addressing flow constraints imposed by physiological shear stress. Ultimately, this work will result in the addition of valuable functionality to microfluidic cell culture models that further fulfill their potential as labs-on-chips.

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.

Integrated microfluidic device for single-cell trapping and spectroscopy

KAUST Repository

Liberale, Carlo; Cojoc, G.; Bragheri, F.; Minzioni, P.; Perozziello, G.; La Rocca, R.; Ferrara, L.; Rajamanickam, V.; Di Fabrizio, Enzo M.; Cristiani, I.

2013-01-01

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.

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.

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

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.

A microfluidic device for precise pipetting

International Nuclear Information System (INIS)

Huang, Chun-Wei; Huang, Song-Bin; Lee, Gwo-Bin

2008-01-01

This paper presents a new microfluidic device capable of pipetting a small amount of fluid. This microfluidic device comprises a series of pneumatic microvalves and a multi-width microchannel. The pneumatic valves are designed with specific ratios to control the volumes of the channel. Ratios of 1×, 5× and 30× are used in this study to demonstrate the multi-volume dispensing capability of the proposed device. The corresponding volumes at these ratios are 0.06, 0.3 and 1.8 µl, respectively. By means of proper combinations of these ratios, liquids with volume ranging from 1× to 100× can be dispensed. In order to avoid bubble formation while the liquid is being loaded into the channel, an 'escape side-channel' is designed to allow the trapped gas to exhaust without liquid loss into the escape side-channel due to the hydrophobic effect. It is experimentally found that the capillary valve can sustain a pressure of 165 mm H 2 O (1.6 kPa). The performance of the microdispenser is investigated and is compared with a commercial pipette. Experimental results show that the accuracy of the developed microdevice is comparable or even superior to the commercial one. The development of this microdevice could be crucial for automating miniature biomedical and chemical analysis systems

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

Effects of surface properties on droplet formation inside a microfluidic device

Science.gov (United States)

Steinhaus, Ben; Shen, Amy

2004-11-01

Micro-fluidic devices offer a unique method of creating and controlling droplets on small length scales. A microfluidic device is used to study the effects of surface properties on droplet formation of a 2-phase flow system. Four phase diagrams are generated to compare the dynamics of the 2 immiscible fluid system (silicone oil and water) inside microchannels with different surface properties. Results show that the channel surface plays an important role in determining the flow patterns and the droplet formation of the 2-phase fluid system.

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.

Principles, Techniques, and Applications of Tissue Microfluidics

Science.gov (United States)

Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

2011-01-01

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called "tissue microfluidics" because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets.

Integrated Microfluidic Membrane Transistor Utilizing Chemical Information for On-Chip Flow Control

Science.gov (United States)

Frank, Philipp; Schreiter, Joerg; Haefner, Sebastian; Paschew, Georgi; Voigt, Andreas; Richter, Andreas

2016-01-01

Microfluidics is a great enabling technology for biology, biotechnology, chemistry and general life sciences. Despite many promising predictions of its progress, microfluidics has not reached its full potential yet. To unleash this potential, we propose the use of intrinsically active hydrogels, which work as sensors and actuators at the same time, in microfluidic channel networks. These materials transfer a chemical input signal such as a substance concentration into a mechanical output. This way chemical information is processed and analyzed on the spot without the need for an external control unit. Inspired by the development electronics, our approach focuses on the development of single transistor-like components, which have the potential to be used in an integrated circuit technology. Here, we present membrane isolated chemical volume phase transition transistor (MIS-CVPT). The device is characterized in terms of the flow rate from source to drain, depending on the chemical concentration in the control channel, the source-drain pressure drop and the operating temperature. PMID:27571209

Integrated Microfluidic Membrane Transistor Utilizing Chemical Information for On-Chip Flow Control.

Science.gov (United States)

Frank, Philipp; Schreiter, Joerg; Haefner, Sebastian; Paschew, Georgi; Voigt, Andreas; Richter, Andreas

2016-01-01

Microfluidics is a great enabling technology for biology, biotechnology, chemistry and general life sciences. Despite many promising predictions of its progress, microfluidics has not reached its full potential yet. To unleash this potential, we propose the use of intrinsically active hydrogels, which work as sensors and actuators at the same time, in microfluidic channel networks. These materials transfer a chemical input signal such as a substance concentration into a mechanical output. This way chemical information is processed and analyzed on the spot without the need for an external control unit. Inspired by the development electronics, our approach focuses on the development of single transistor-like components, which have the potential to be used in an integrated circuit technology. Here, we present membrane isolated chemical volume phase transition transistor (MIS-CVPT). The device is characterized in terms of the flow rate from source to drain, depending on the chemical concentration in the control channel, the source-drain pressure drop and the operating temperature.

Recent Advances in Magnetic Microfluidic Biosensors

Directory of Open Access Journals (Sweden)

Ioanna Giouroudi

2017-07-01

Full Text Available The development of portable biosening devices for the detection of biological entities such as biomolecules, pathogens, and cells has become extremely significant over the past years. Scientific research, driven by the promise for miniaturization and integration of complex laboratory equipment on inexpensive, reliable, and accurate devices, has successfully shifted several analytical and diagnostic methods to the submillimeter scale. The miniaturization process was made possible with the birth of microfluidics, a technology that could confine, manipulate, and mix very small volumes of liquids on devices integrated on standard silicon technology chips. Such devices are then directly translating the presence of these entities into an electronic signal that can be read out with a portable instrumentation. For the aforementioned tasks, the use of magnetic markers (magnetic particles—MPs—functionalized with ligands in combination with the application of magnetic fields is being strongly investigated by research groups worldwide. The greatest merits of using magnetic fields are that they can be applied either externally or from integrated microconductors and they can be well-tuned by adjusting the applied current on the microconductors. Moreover, the magnetic markers can be manipulated inside microfluidic channels by high gradient magnetic fields that can in turn be detected by magnetic sensors. All the above make this technology an ideal candidate for the development of such microfluidic biosensors. In this review, focus is given only to very recent advances in biosensors that use microfluidics in combination with magnetic sensors and magnetic markers/nanoparticles.

Surface-Enhanced Raman Spectroscopy Integrated Centrifugal Microfluidics Platform

DEFF Research Database (Denmark)

Durucan, Onur

This PhD thesis demonstrates (i) centrifugal microfluidics disc platform integrated with Au capped nanopillar (NP) substrates for surface-enhanced Raman spectroscopy (SERS) based sensing, and (ii) novel sample analysis concepts achieved by synergistical combination of sensing techniques and minia......This PhD thesis demonstrates (i) centrifugal microfluidics disc platform integrated with Au capped nanopillar (NP) substrates for surface-enhanced Raman spectroscopy (SERS) based sensing, and (ii) novel sample analysis concepts achieved by synergistical combination of sensing techniques...... dense array of NP structures. Furthermore, the wicking assisted nanofiltration procedure was accomplished in centrifugal microfluidics platform and as a result additional sample purification was achieved through the centrifugation process. In this way, the Au coated NP substrate was utilized...

Accurately tracking single-cell movement trajectories in microfluidic cell sorting devices.

Science.gov (United States)

Jeong, Jenny; Frohberg, Nicholas J; Zhou, Enlu; Sulchek, Todd; Qiu, Peng

2018-01-01

Microfluidics are routinely used to study cellular properties, including the efficient quantification of single-cell biomechanics and label-free cell sorting based on the biomechanical properties, such as elasticity, viscosity, stiffness, and adhesion. Both quantification and sorting applications require optimal design of the microfluidic devices and mathematical modeling of the interactions between cells, fluid, and the channel of the device. As a first step toward building such a mathematical model, we collected video recordings of cells moving through a ridged microfluidic channel designed to compress and redirect cells according to cell biomechanics. We developed an efficient algorithm that automatically and accurately tracked the cell trajectories in the recordings. We tested the algorithm on recordings of cells with different stiffness, and showed the correlation between cell stiffness and the tracked trajectories. Moreover, the tracking algorithm successfully picked up subtle differences of cell motion when passing through consecutive ridges. The algorithm for accurately tracking cell trajectories paves the way for future efforts of modeling the flow, forces, and dynamics of cell properties in microfluidics applications.

Accurately tracking single-cell movement trajectories in microfluidic cell sorting devices.

Directory of Open Access Journals (Sweden)

Jenny Jeong

Full Text Available Microfluidics are routinely used to study cellular properties, including the efficient quantification of single-cell biomechanics and label-free cell sorting based on the biomechanical properties, such as elasticity, viscosity, stiffness, and adhesion. Both quantification and sorting applications require optimal design of the microfluidic devices and mathematical modeling of the interactions between cells, fluid, and the channel of the device. As a first step toward building such a mathematical model, we collected video recordings of cells moving through a ridged microfluidic channel designed to compress and redirect cells according to cell biomechanics. We developed an efficient algorithm that automatically and accurately tracked the cell trajectories in the recordings. We tested the algorithm on recordings of cells with different stiffness, and showed the correlation between cell stiffness and the tracked trajectories. Moreover, the tracking algorithm successfully picked up subtle differences of cell motion when passing through consecutive ridges. The algorithm for accurately tracking cell trajectories paves the way for future efforts of modeling the flow, forces, and dynamics of cell properties in microfluidics applications.

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

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 functional assay for testing cell migration (the Mkit). 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 Mkit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the Mkit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the Mkit. In addition to research applications, we demonstrated the effective use of the Mkit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed Mkit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. PMID:28772229

Integrated cantilever-based flow sensors with tunable sensitivity for in-line monitoring of flow fluctuations in microfluidic systems

DEFF Research Database (Denmark)

Noeth, Nadine-Nicole; Keller, Stephan Sylvest; Boisen, Anja

2014-01-01

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...... 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...

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.

Fabrication of polystyrene microfluidic devices using a pulsed CO2 laser system

KAUST Repository

Li, Huawei; Fan, Yiqiang; Foulds, Ian G.; Kodzius, Rimantas

2013-01-01

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.

Direct immobilization of DNA probes on non-modified plastics by UV irradiation and integration in microfluidic devices for rapid bioassay

DEFF Research Database (Denmark)

Yi, Sun; Perch-Nielsen, Ivan R.; Dufva, Martin

2012-01-01

that simple UV irradiation can be used to directly immobilize poly(T)poly(C)-tagged DNA oligonucleotide probes on many different types of plastics without any surface modification. On average, five- and fourfold improvement in immobilization and hybridization efficiency have been achieved compared to surface......DNA microarrays have become one of the most powerful tools in the field of genomics and medical diagnosis. Recently, there has been increased interest in combining microfluidics with microarrays since this approach offers advantages in terms of portability, reduced analysis time, low consumption...... of reagents, and increased system integration. Polymers are widely used for microfluidic systems, but fabrication of microarrays on such materials often requires complicated chemical surface modifications, which hinders the integration of microarrays into microfluidic systems. In this paper, we demonstrate...

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.

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.

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.

Facile fabrication of microfluidic surface-enhanced Raman scattering devices via lift-up lithography

Science.gov (United States)

Wu, Yuanzi; Jiang, Ye; Zheng, Xiaoshan; Jia, Shasha; Zhu, Zhi; Ren, Bin; Ma, Hongwei

2018-04-01

We describe a facile and low-cost approach for a flexibly integrated surface-enhanced Raman scattering (SERS) substrate in microfluidic chips. Briefly, a SERS substrate was fabricated by the electrostatic assembling of gold nanoparticles, and shaped into designed patterns by subsequent lift-up soft lithography. The SERS micro-pattern could be further integrated within microfluidic channels conveniently. The resulting microfluidic SERS chip allowed ultrasensitive in situ SERS monitoring from the transparent glass window. With its advantages in simplicity, functionality and cost-effectiveness, this method could be readily expanded into optical microfluidic fabrication for biochemical applications.

Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

Science.gov (United States)

Sakai, Yusuke; Hattori, Koji; Yanagawa, Fumiki; Sugiura, Shinji; Kanamori, Toshiyuki; Nakazawa, Kohji

2014-07-01

Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multi-unit Integration in Microfluidic Processes: Current Status and Future Horizons

Directory of Open Access Journals (Sweden)

Pratap R. Patnaik

2011-07-01

Full Text Available Microfluidic processes, mainly for biological and chemical applications, have expanded rapidly in recent years. While the initial focus was on single units, principally microreactors, technological and economic considerations have caused a shift to integrated microchips in which a number of microdevices function coherently. These integrated devices have many advantages over conventional macro-scale processes. However, the small scale of operation, complexities in the underlying physics and chemistry, and differences in the time constants of the participating units, in the interactions among them and in the outputs of interest make it difficult to design and optimize integrated microprocesses. These aspects are discussed here, current research and applications are reviewed, and possible future directions are considered.

Pyrolyzed Photoresist Electrodes for Integration in Microfluidic Chips for Transmitter Detection from Biological Cells

DEFF Research Database (Denmark)

Larsen, Simon Tylsgaard; Argyraki, Aikaterini; Amato, Letizia

2013-01-01

In this study, we show how pyrolyzed photoresist carbon electrodes can be used for amperometric detection of potassium-induced transmitter release from large groups of neuronal PC 12 cells. This opens the way for the use of carbon film electrodes in microfabricated devices for neurochemical drug ...... by the difference in photoresist viscosity. By adding a soft bake step to the fabrication procedure, the flatness of pyrolyzed AZ 5214 electrodes could be improved which would facilitate their integration in microfluidic chip devices....

Isothermal circular-strand-displacement polymerization of DNA and microRNA in digital microfluidic devices.

Science.gov (United States)

Giuffrida, Maria Chiara; Zanoli, Laura Maria; D'Agata, Roberta; Finotti, Alessia; Gambari, Roberto; Spoto, Giuseppe

2015-02-01

Nucleic-acid amplification is a crucial step in nucleic-acid-sequence-detection assays. The use of digital microfluidic devices to miniaturize amplification techniques reduces the required sample volume and the analysis time and offers new possibilities for process automation and integration in a single device. The recently introduced droplet polymerase-chain-reaction (PCR) amplification methods require repeated cycles of two or three temperature-dependent steps during the amplification of the nucleic-acid target sequence. In contrast, low-temperature isothermal-amplification methods have no need for thermal cycling, thus requiring simplified microfluidic-device features. Here, the combined use of digital microfluidics and molecular-beacon (MB)-assisted isothermal circular-strand-displacement polymerization (ICSDP) to detect microRNA-210 sequences is described. MicroRNA-210 has been described as the most consistently and predominantly upregulated hypoxia-inducible factor. The nmol L(-1)-pmol L(-1) detection capabilities of the method were first tested by targeting single-stranded DNA sequences from the genetically modified Roundup Ready soybean. The ability of the droplet-ICSDP method to discriminate between full-matched, single-mismatched, and unrelated sequences was also investigated. The detection of a range of nmol L(-1)-pmol L(-1) microRNA-210 solutions compartmentalized in nanoliter-sized droplets was performed, establishing the ability of the method to detect as little as 10(-18) mol of microRNA target sequences compartmentalized in 20 nL droplets. The suitability of the method for biological samples was tested by detecting microRNA-210 from transfected K562 cells.

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.

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.

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.

Thin film metal sensors in fusion bonded glass chips for high-pressure microfluidics

International Nuclear Information System (INIS)

Andersson, Martin; Ek, Johan; Hedman, Ludvig; Johansson, Fredrik; Sehlstedt, Viktor; Stocklassa, Jesper; Snögren, Pär; Pettersson, Victor; Larsson, Jonas; Vizuete, Olivier; Hjort, Klas; Klintberg, Lena

2017-01-01

High-pressure microfluidics offers fast analyses of thermodynamic parameters for compressed process solvents. However, microfluidic platforms handling highly compressible supercritical CO 2 are difficult to control, and on-chip sensing would offer added control of the devices. Therefore, there is a need to integrate sensors into highly pressure tolerant glass chips. In this paper, thin film Pt sensors were embedded in shallow etched trenches in a glass wafer that was bonded with another glass wafer having microfluidic channels. The devices having sensors integrated into the flow channels sustained pressures up to 220 bar, typical for the operation of supercritical CO 2 . No leakage from the devices could be found. Integrated temperature sensors were capable of measuring local decompression cooling effects and integrated calorimetric sensors measured flow velocities over the range 0.5–13.8 mm s −1 . By this, a better control of high-pressure microfluidic platforms has been achieved. (paper)

Spintronic microfluidic platform for biomedical and environmental applications

Science.gov (United States)

Cardoso, F. A.; Martins, V. C.; Fonseca, L. P.; Germano, J.; Sousa, L. A.; Piedade, M. S.; Freitas, P. P.

2010-09-01

Faster, more sensitive and easy to operate biosensing devices still are a need at important areas such as biomedical diagnostics, food control and environmental monitoring. Recently, spintronic-devices have emerged as a promising alternative to the existent technologies [1-3]. A number of advantages, namely high sensitivity, easy integration, miniaturization, scalability, robustness and low cost make these devices potentially capable of responding to the existent technological need. In parallel, the field of microfluidics has shown great advances [4]. Microfluidic systems allow the analysis of small sample volumes (from micro- down to pico-liters), often by automate sample processing with the ability to integrate several steps into a single device (analyte amplification, concentration, separation and/or labeling), all in a reduced assay time (minutes to hours) and affordable cost. The merging of these two technologies, magnetoresistive biochips and microfluidics, will enable the development of highly competitive devices. This work reports the integration of a magnetoresistive biochip with a microfluidic system inside a portable and autonomous electronic platform aiming for a fully integrated device. A microfluidic structure fabricated in polydimethylsiloxane with dimensions of W: 0.5mm, H: 0.1mm, L: 10mm, associated to a mechanical system to align and seal the channel by pressure is presented (Fig. 1) [5]. The goal is to perform sample loading and transportation over the chip and simultaneously control the stringency and uniformity of the wash-out process. The biochip output is acquired by an electronic microsystem incorporating the circuitry to control, address and read-out the 30 spin-valve sensors sequentially (Fig. 1) [2]. This platform is being applied to the detection of water-borne microbial pathogens (e.g. Salmonella and Escherichia coli) and genetic diseases diagnosis (e.g. cystic fibrosis) through DNA hybridization assays. Open chamber measurements were

Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication.

Directory of Open Access Journals (Sweden)

Alex J L Morgan

Full Text Available The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components.

Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication.

Science.gov (United States)

Morgan, Alex J L; Hidalgo San Jose, Lorena; Jamieson, William D; Wymant, Jennifer M; Song, Bing; Stephens, Phil; Barrow, David A; Castell, Oliver K

2016-01-01

The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components.

Efficient generation of hepatic cells from mesenchymal stromal cells by an innovative bio-microfluidic cell culture device.

Science.gov (United States)

Yen, Meng-Hua; Wu, Yuan-Yi; Liu, Yi-Shiuan; Rimando, Marilyn; Ho, Jennifer Hui-Chun; Lee, Oscar Kuang-Sheng

2016-08-19

Mesenchymal stromal cells (MSCs) are multipotent and have great potential in cell therapy. Previously we reported the differentiation potential of human MSCs into hepatocytes in vitro and that these cells can rescue fulminant hepatic failure. However, the conventional static culture method neither maintains growth factors at an optimal level constantly nor removes cellular waste efficiently. In addition, not only is the duration of differentiating hepatocyte lineage cells from MSCs required to improve, but also the need for a large number of hepatocytes for cell therapy has not to date been addressed fully. The purpose of this study is to design and develop an innovative microfluidic device to overcome these shortcomings. We designed and fabricated a microfluidic device and a culture system for hepatic differentiation of MSCs using our protocol reported previously. The microfluidic device contains a large culture chamber with a stable uniform flow to allow homogeneous distribution and expansion as well as efficient induction of hepatic differentiation for MSCs. The device enables real-time observation under light microscopy and exhibits a better differentiation efficiency for MSCs compared with conventional static culture. MSCs grown in the microfluidic device showed a higher level of hepatocyte marker gene expression under hepatic induction. Functional analysis of hepatic differentiation demonstrated significantly higher urea production in the microfluidic device after 21 days of hepatic differentiation. The microfluidic device allows the generation of a large number of MSCs and induces hepatic differentiation of MSCs efficiently. The device can be adapted for scale-up production of hepatic cells from MSCs for cellular therapy.

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.

Microfluidic device for the assembly and transport of microparticles

Science.gov (United States)

James, Conrad D [Albuquerque, NM; Kumar, Anil [Framingham, MA; Khusid, Boris [New Providence, NJ; Acrivos, Andreas [Stanford, CA

2010-06-29

A microfluidic device comprising independently addressable arrays of interdigitated electrodes can be used to assembly and transport large-scale microparticle structures. The device and method uses collective phenomena in a negatively polarized suspension exposed to a high-gradient strong ac electric field to assemble the particles into predetermined locations and then transport them collectively to a work area for final assembly by sequentially energizing the electrode arrays.

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.

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

KAUST Repository

Buttner, Ulrich; Sivashankar, Shilpa; Agambayev, Sumeyra; Mashraei, Yousof; Salama, Khaled N.

2016-01-01

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.

A self-loading microfluidic device for determining the minimum inhibitory concentration of antibiotics.

Science.gov (United States)

Cira, Nate J; Ho, Jack Y; Dueck, Megan E; Weibel, Douglas B

2012-03-21

This article describes a portable microfluidic technology for determining the minimum inhibitory concentration (MIC) of antibiotics against bacteria. The microfluidic platform consists of a set of chambers molded in poly(dimethylsiloxane) (PDMS) that are preloaded with antibiotic, dried, and reversibly sealed to a second layer of PDMS containing channels that connect the chambers. The assembled device is degassed via vacuum prior to its use, and the absorption of gas by PDMS provides the mechanism for actuating and metering the flow of fluid in the microfluidic channels and chambers. During the operation of the device, degas driven flow introduces a suspension of bacterial cells, dissolves the antibiotic, and isolates cells in individual chambers without cross contamination. The growth of bacteria in the chambers in the presence of a pH indicator produces a colorimetric change that can be detected visually using ambient light. Using this device we measured the MIC of vancomycin, tetracycline, and kanamycin against Enterococcus faecalis 1131, Proteus mirabilis HI4320, Klebsiella pneumoniae, and Escherichia coli MG1655 and report values that are comparable to standard liquid broth dilution measurements. The device provides a simple method for MIC determination of individual antibiotics against human pathogens that will have applications for clinical and point-of-care medicine. Importantly, this device is designed around simplicity: it requires a single pipetting step to introduce the sample, no additional components or external equipment for its operation, and provides a straightforward visual measurement of cell growth. As the device introduces a novel approach for filling and isolating dead-end microfluidic chambers that does not require valves and actuators, this technology should find applications in other portable assays and devices.

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.

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.

Microfluidic device and method for focusing, segmenting, and dispensing of a fluid stream

Science.gov (United States)

Jacobson, Stephen C [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2008-09-09

A microfluidic device and method for forming and dispensing minute volume segments of a material are described. In accordance with the present invention, a microfluidic device and method are provided for spatially confining the material in a focusing element. The device is also adapted for segmenting the confined material into minute volume segments, and dispensing a volume segment to a waste or collection channel. The device further includes means for driving the respective streams of sample and focusing fluids through respective channels into a chamber, such that the focusing fluid streams spatially confine the sample material. The device may also include additional means for driving a minute volume segment of the spatially confined sample material into a collection channel in fluid communication with the waste reservoir.

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.

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

KAUST Repository

Wang, Xiang; Li, Shunbo; Wang, Limu; Yi, Xin; Hui, Yu Sanna; Qin, Jianhua; Wen, Weijia

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.

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.

Generation of emulsion droplets and micro-bubbles in microfluidic devices

KAUST Repository

Zhang, Jiaming

2016-01-01

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

A Pneumatic Actuated Microfluidic Beads-Trapping Device

Energy Technology Data Exchange (ETDEWEB)

Shao, Guocheng; Cai, Ziliang; Wang, Jun; Wang, Wanjun; Lin, Yuehe

2011-08-20

The development of a polydimethylsiloxane (PDMS) microfluidic microbeads trapping device is reported in this paper. Besides fluid channels, the proposed device includes a pneumatic control chamber and a beads-trapping chamber with a filter array structure. The pneumatic flow control chamber and the beads-trapping chamber are vertically stacked and separated by a thin membrane. By adjusting the pressure in the pneumatic control chamber, the membrane can either be pushed against the filter array to set the device in trapping mode or be released to set the device in releasing mode. In this paper, a computational fluid dynamics simulation was conducted to optimize the geometry design of the filter array structure; the device fabrication was also carried out. The prototype device was tested and the preliminary experimental results showed that it can be used as a beads-trapping unit for various biochemistry and analytical chemistry applications, especially for flow injection analysis systems.

Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection.

Science.gov (United States)

Hosseini, Samira; Aeinehvand, Mohammad M; Uddin, Shah M; Benzina, Abderazak; Rothan, Hussin A; Yusof, Rohana; Koole, Leo H; Madou, Marc J; Djordjevic, Ivan; Ibrahim, Fatimah

2015-11-09

The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.

Integrating Carbon Nanotubes into Microfluidic Chip for Separating Biochemical Compounds

DEFF Research Database (Denmark)

Chen, Miaoxiang Max; Mogensen, Klaus Bo; Bøggild, Peter

2012-01-01

We present a new type of device to separate biochemical compounds wherein carbon nanotubes (CNTs) are integrated as chromatographic stationary phase. The CNTs were directly grown on the bottom of microfluidic channels on Si/SiO2 substrates by chemical vapor deposition (CVD). Acetylene was used...... as carbon source and Ni was employed as catalyst. For electrokinetic separations, higher electrical field strength is usually required; therefore, the CNTs were constructed in pillar-array-form by patterning the catalyst layer. Electrical field strength of 2.0 kV/cm has been realized, which is more than one...

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.

Fabrication, Metrology, and Transport Characteristics of Single Polymeric Nanopores in Three-Dimensional Hybrid Microfluidic/Nanofluidic Devices

Science.gov (United States)

King, Travis L.

2009-01-01

The incorporation of nanofluidic elements between microfluidic channels to form hybrid microfluidic/nanofluidic architectures allows the extension of microfluidic systems into the third dimension, thus removing the constraints imposed by planarity. Measuring and understanding the behavior of these devices creates new analytical challenges due to…

Integration of micro-optics and microfluidics in a glass chip by fs-laser for optofluidic applications

Science.gov (United States)

Osellame, Roberto; Martinez, Rebeca; Laporta, Paolo; Ramponi, Roberta; Cerullo, Giulio

2009-02-01

A lab-on-a-chip (LOC) is a device that incorporates in a single substrate the functionalities of a biological laboratory, i.e. a network of fluidic channels, reservoirs, valves, pumps and sensors, all with micrometer dimensions. Its main advantages are the possibility of working with small samples quantities (from nano- to picoliters), high sensitivity, speed of analysis and the possibility of measurement automation and standardization. They are becoming the most powerful tools of analytical chemistry with a broad application in life sciences, biotechnology and drug development. The next technological challenge of LOCs is direct on-chip integration of photonic functionalities for sensing of biomolecules flowing in the microchannels. Ultrafast laser processing of the bulk of a dielectric material is a very flexible and simple method to produce photonic devices inside microfluidic chips for capillary electrophoresis (CE) or chemical microreactors. By taking advantage of the unique three-dimensional capabilities of this fabrication technique, more complex functionalities, such as splitters or Mach-Zehnder interferometers, can be implemented. In this work we report on the use of femtosecond laser pulses to fabricate photonic devices (as waveguides, splitters and interferometers) inside commercial CE chips, without affecting the manufacturing procedure of the microfluidic part of the device. The fabrication of single waveguides intersecting the channels allows one to perform absorption or Laser Induced Fluorescence (LIF) sensing of the molecules separated inside the microchannels. Waveguide splitters are used for multipoint excitation of the microfluidic channel for parallel or higher sensitivity measurements. Finally, Mach-Zehnder interferometers are used for label-free sensing of the samples flowing in the microfluidic channels by means of refractive index changes detection.

A review on recent developments for biomolecule separation at analytical scale using microfluidic devices.

Science.gov (United States)

Tetala, Kishore K R; Vijayalakshmi, M A

2016-02-04

Microfluidic devices with their inherent advantages like the ability to handle 10(-9) to 10(-18) L volume, multiplexing of microchannels, rapid analysis and on-chip detection are proving to be efficient systems in various fields of life sciences. This review highlights articles published since 2010 that reports the use of microfluidic devices to separate biomolecules (DNA, RNA and proteins) using chromatography principles (size, charge, hydrophobicity and affinity) along with microchip capillary electrophoresis, isotachophoresis etc. A detailed overview of stationary phase materials and the approaches to incorporate them within the microchannels of microchips is provided as well as a brief overview of chemical methods to immobilize ligand(s). Furthermore, we review research articles that deal with microfluidic devices as analytical tools for biomolecule (DNA, RNA and protein) separation. Copyright © 2015 Elsevier B.V. All rights reserved.

Dual-nozzle microfluidic droplet generator

Science.gov (United States)

Choi, Ji Wook; Lee, Jong Min; Kim, Tae Hyun; Ha, Jang Ho; Ahrberg, Christian D.; Chung, Bong Geun

2018-05-01

The droplet-generating microfluidics has become an important technique for a variety of applications ranging from single cell analysis to nanoparticle synthesis. Although there are a large number of methods for generating and experimenting with droplets on microfluidic devices, the dispensing of droplets from these microfluidic devices is a challenge due to aggregation and merging of droplets at the interface of microfluidic devices. Here, we present a microfluidic dual-nozzle device for the generation and dispensing of uniform-sized droplets. The first nozzle of the microfluidic device is used for the generation of the droplets, while the second nozzle can accelerate the droplets and increase the spacing between them, allowing for facile dispensing of droplets. Computational fluid dynamic simulations were conducted to optimize the design parameters of the microfluidic device.

Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip.

Science.gov (United States)

Godin, Jessica; Chen, Chun-Hao; Cho, Sung Hwan; Qiao, Wen; Tsai, Frank; Lo, Yu-Hwa

2008-10-01

Microfluidics and photonics come together to form a field commonly referred to as 'optofluidics'. Flow cytometry provides the field with a technology base from which both microfluidic and photonic components be developed and integrated into a useful device. This article reviews some of the more recent developments to familiarize a reader with the current state of the technologies and also highlights the requirements of the device and how researchers are working to meet these needs.

Dielectrophoretic Microfluidic Device for in Vitro Fertilization

Directory of Open Access Journals (Sweden)

Hong-Yuan Huang

2018-03-01

Full Text Available The aim of this work was to create a microfluidic platform that uses in vitro fertilization (IVF and avoids unnecessary damage to oocytes due to the dielectrophoretic force manipulation of the sperms and oocytes that occurs in a traditional IVF operation. The device from this research can serve also to decrease medium volumes, as well as the cost of cell culture under evaporation, and to prevent unnecessary risk in intracytoplasmic sperm injection (ICSI. To decrease the impact and destruction of the oocyte and the sperm, we adopted a positive dielectrophoretic force to manipulate both the sperms and the oocyte. The mouse oocytes were trapped with a positive dielectrophoretic (p-DEP force by using Indium Tin Oxide (ITO-glass electrodes; the ITO-glass electrode chip was fabricated by wet etching the ITO-glass. The polydimethylsiloxane (PDMS flow-focusing microfluidic device was used to generate microdroplets of micrometer size to contain the zygotes. The volume of the microdroplets was controlled by adjusting the flow rates of both inlets for oil and the DEP buffer. As a result, the rate of fertilization was increased by about 5% beyond that of the DEP treatment in traditional IVF, and more than 20% developed to the blastocyst stage with a low sperm-oocyte ratio.

Application of Vertical Electrodes in Microfluidic Channels for Impedance Analysis

Directory of Open Access Journals (Sweden)

Qiang Li

2016-05-01

Full Text Available This paper presents a microfluidic device with electroplated vertical electrodes in the side walls for impedance measurement. Based on the proposed device, the impedance of NaCl solutions with different concentrations and polystyrene microspheres with different sizes was measured and analyzed. The electroplating and SU-8-PDMS (SU-8-poly(dimethylsiloxane bonding technologies were firstly integrated for the fabrication of the proposed microfluidic device, resulting in a tightly three-dimensional structure for practical application. The magnitude of impedance of the tested solutions in the frequency range of 1 Hz to 100 kHz was analyzed by the Zennium electrochemical workstation. The results show that the newly designed microfluidic device has potential for impedance analysis with the advantages of ease of fabrication and the integration of 3D electrodes in the side walls. The newly designed impedance sensor can distinguish different concentrations of polystyrene microspheres and may have potential for cell counting in biological areas. By integrating with other techniques such as dielectrophoresis (DEP and biological recognition technology, the proposed device may have potential for the assay to identify foodborne pathogen bacteria.

A "place n play" modular pump for portable microfluidic applications.

Science.gov (United States)

Li, Gang; Luo, Yahui; Chen, Qiang; Liao, Lingying; Zhao, Jianlong

2012-03-01

This paper presents an easy-to-use, power-free, and modular pump for portable microfluidic applications. The pump module is a degassed particle desorption polydimethylsiloxane (PDMS) slab with an integrated mesh-shaped chamber, which can be attached on the outlet port of microfluidic device to absorb the air in the microfluidic system and then to create a negative pressure for driving fluid. Different from the existing monolithic degassed PDMS pumps that are generally restricted to limited pumping capacity and are only compatible with PDMS-based microfluidic devices, this pump can offer various possible configures of pumping power by varying the geometries of the pump or by combining different pump modules and can also be employed in any material microfluidic devices. The key advantage of this pump is that its operation only requires the user to place the degassed PDMS slab on the outlet ports of microfluidic devices. To help design pumps with a suitable pumping performance, the effect of pump module geometry on its pumping capacity is also investigated. The results indicate that the performance of the degassed PDMS pump is strongly dependent on the surface area of the pump chamber, the exposure area and the volume of the PDMS pump slab. In addition, the initial volume of air in the closed microfluidic system and the cross-linking degree of PDMS also affect the performance of the degassed PDMS pump. Finally, we demonstrated the utility of this modular pumping method by applying it to a glass-based microfluidic device and a PDMS-based protein crystallization microfluidic device.

Fluidic interconnections for microfluidic systems: A new integrated fluidic interconnection allowing plug 'n' play functionality

DEFF Research Database (Denmark)

Perozziello, Gerardo; Bundgaard, Frederik; Geschke, Oliver

2008-01-01

A crucial challenge in packaging of microsystems is microfluidic interconnections. These have to seal the ports of the system, and have to provide the appropriate interface to other devices or the external environment. Integrated fluidic interconnections appear to be a good solution for interconn...... external metal ferrules and the system. Theoretical calculations are made to dimension and model the integrated fluidic interconnection. Leakage tests are performed on the interconnections, in order to experimentally confirm the model, and detect its limits....

In vitro development of donated frozen-thawed human embryos in a prototype static microfluidic device: a randomized controlled trial.

Science.gov (United States)

Kieslinger, Dorit C; Hao, Zhenxia; Vergouw, Carlijn G; Kostelijk, Elisabeth H; Lambalk, Cornelis B; Le Gac, Séverine

2015-03-01

To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. Prospective randomized controlled trial. In vitro fertilization laboratory. One hundred eighteen donated frozen-thawed human day-4 embryos. Random allocation of embryos that fulfilled the inclusion criteria to single-embryo culture in a microfluidics device (n = 58) or standard microdrop dish (n = 60). Blastocyst formation rate and quality after 24, 28, 48, and 72 hours of culture. The percentage of frozen-thawed day-4 embryos that developed to the blastocyst stage did not differ significantly in the standard microdrop dishes and microfluidic devices after 28 hours of culture (53.3% vs. 58.6%) or at any of the other time points. The proportion of embryos that would have been suitable for embryo transfer was comparable after 28 hours of culture in the control dishes and microfluidic devices (90.0% vs. 93.1%). Furthermore, blastocyst quality was similar in the two study groups. This study shows that a microfluidic device can successfully support human blastocyst development in vitro under static culture conditions. Future studies need to clarify whether earlier stage embryos will benefit from the culture in microfluidic devices more than the tested day-4 embryos because many important steps in the development of human embryos already take place before day 4. Further improvements of the microfluidic device will include parallel culture of single embryos, application of medium refreshment, and built-in sensors. NTR3867. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Electron beam fabrication of a microfluidic device for studying submicron-scale bacteria

Science.gov (United States)

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 into cell growth and death. To extend this approach to other species of bacteria, many of whom have dimensions in the sub-micron range, or to a larger range of growth conditions, a readily-fabricated device containing sub-micron features is required. Results Here we detail the fabrication of a versatile device with growth channels whose widths range from 0.3 μm to 0.8 μm. The device is fabricated using electron beam lithography, which provides excellent control over the shape and size of different growth channels and facilitates the rapid-prototyping of new designs. Features are successfully transferred first into silicon, and subsequently into the polydimethylsiloxane that forms the basis of the working microfluidic device. We demonstrate that the growth of sub-micron scale bacteria such as Lactococcus lactis or Escherichia coli cultured in minimal medium can be followed in such a device over several generations. Conclusions We have presented a detailed protocol based on electron beam fabrication together with specific dry etching procedures for the fabrication of a microfluidic device suited to study submicron-sized bacteria. We have demonstrated that both Gram-positive and Gram-negative bacteria can be successfully loaded and imaged over a number of generations in this device. Similar devices could potentially be used to study other submicron-sized organisms under conditions in which the height and shape of the growth channels are crucial to the experimental design. PMID:23575419

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.

Optical detection in microfluidic systems

DEFF Research Database (Denmark)

Mogensen, Klaus Bo; Kutter, Jörg Peter

2009-01-01

Optical detection schemes continue to be favoured for measurements in microfluidic systems. A selection of the latest progress mainly within the last two years is critically reviewed. Emphasis is on integrated solutions, such as planar waveguides, coupling schemes to the outside world, evanescent...... to ease commercialisation of the devices. This work will hopefully result in more commercial products that benefit from integrated optics, because the impact on commercial devices so far has been modest....

A microfluidic-based lid device for conventional cell culture dishes to automatically control oxygen level.

Science.gov (United States)

Lee, Seung Yeob; Yang, Sung

2018-04-25

Most conventional hypoxic cell culture systems undergo reoxygenation during experimental manipulations, resulting in undesirable effects including the reduction of cell viability. A lid device was developed herein for conventional cell culture dishes to resolve this limitation. The integration of multilayered microfluidic channels inside a thin membrane was designed to prevent the reoxygenation caused by reagent infusion and automatically control the oxygen level. The experimental data clearly show the reducibility of the dissolved oxygen in the infusing reagent and the controllability of the oxygen level inside the dish. The feasibility of the device for hypoxia studies was confirmed by HIF-1α experiments. Therefore, the device could be used as a compact and convenient hypoxic cell culture system to prevent reoxygenation-related issues.

Microfluidic devices and methods including porous polymer monoliths

Science.gov (United States)

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

2014-04-22

Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

New microfluidic platform for life sciences in South Africa

CSIR Research Space (South Africa)

Hugo, S

2012-10-01

Full Text Available is also offered as numerous devices can be implemented on one disc. A variety of components from sample preparation through to detection can be implemented simply and effectively into an integrated microfluidic solution for life sciences. The lab... in the field of centrifugal microfluidics. New microfluidic platform for life sciences in South Africa S. HUGO, K. LAND CSIR Materials Science and Manufacturing P O Box 395, Pretoria 0001, SOUTH AFRICA Email: kland@csir.co.za INTRODUCTION Microfluidic...

Coalescence kinetics of oil-in-water emulsions studied with microfluidics

NARCIS (Netherlands)

Krebs, T.; Schroen, C.G.P.H.; Boom, R.M.

2013-01-01

We report the results of experiments on the coalescence dynamics in flowing oil-in-water emulsions using an integrated microfluidic device. The microfluidic circuit permits direct observation of shear-induced collisions and coalescence events between emulsion droplets. Three mineral oils with a

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

International Nuclear Information System (INIS)

Vazquez, Mercedes; Paull, Brett

2010-01-01

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.

Integration of microelectronic chips in microfluidic systems on printed circuit board

International Nuclear Information System (INIS)

Burdallo, I; Jimenez-Jorquera, C; Fernández-Sánchez, C; Baldi, A

2012-01-01

A new scheme for the integration of small semiconductor transducer chips with microfluidic structures on printed circuit board (PCB) is presented. The proposed approach is based on a packaging technique that yields a large and flat area with small and shallow (∼44 µm deep) openings over the chips. The photocurable encapsulant material used, based on a diacrylate bisphenol A polymer, enables irreversible bonding of polydimethylsiloxane microfluidic structures at moderate temperatures (80 °C). This integration scheme enables the insertion of transducer chips in microfluidic systems with a lower added volume than previous schemes. Leakage tests have shown that the bonded structures withstand more than 360 kPa of pressure. A prototype microfluidic system with two detection chips, including one inter-digitated electrode (IDE) chip for conductivity and one ion selective field effect transistor (ISFET) chip for pH, has been implemented and characterized. Good electrical insulation of the chip contacts and silicon edge surfaces from the solution in the microchannels has been achieved. This integration procedure opens the door to the low-cost fabrication of complex analytical microsystems that combine the extraordinary potential of both the microfluidics and silicon microtechnology fields. (paper)

Flow characterization and patch clamp dose responses using jet microfluidics in a tubeless microfluidic device.

Science.gov (United States)

Resto, Pedro J; Bhat, Abhishek; Stava, Eric; Lor, Chong; Merriam, Elliot; Diaz-Rivera, Ruben E; Pearce, Robert; Blick, Robert; Williams, Justin C

2017-11-01

Surface tension passive pumping is a way to actuate flow without the need for pumps, tubing or valves by using the pressure inside small drop to move liquid via a microfluidic channel. These types of tubeless devices have typically been used in cell biology. Herein we present the use of tubeless devices as a fluid exchange platform for patch clamp electrophysiology. Inertia from high-speed droplets and jets is used to create flow and perform on-the-fly mixing of solutions. These are then flowed over GABA transfected HEK cells under patch in order to perform a dose response analysis. TIRF imaging and electrical recordings are used to study the fluid exchange properties of the microfluidic device, resulting in 0-90% fluid exchange times of hundreds of milliseconds. COMSOL is used to model flow and fluid exchange within the device. Patch-clamping experiments show the ability to use high-speed passive pumping and its derivatives for studying peak dose responses, but not for studying ion channel kinetics. Our system results in fluid exchange times slower than when using a standard 12-barrel application system and is not as stable as traditional methods, but it offers a new platform with added functionality. Surface tension passive pumping and tubeless devices can be used in a limited fashion for electrophysiology. Users may obtain peak dose responses but the system, in its current form, is not capable of fluid exchange fast enough to study the kinetics of most ion channels. Copyright © 2017 Elsevier B.V. All rights reserved.

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...... of electrodes. Basic microfluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. So far, researchers have assumed that these operations are executed on rectangular virtual devices, formed by grouping several adjacent...

Control Synthesis for the Flow-Based Microfluidic Large-Scale Integration Biochips

DEFF Research Database (Denmark)

Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan

2013-01-01

In this paper we are interested in flow-based microfluidic biochips, which are able to integrate the necessary functions for biochemical analysis on-chip. In these chips, the flow of liquid is manipulated using integrated microvalves. By combining severalmicrovalves, more complex units, such asmi......In this paper we are interested in flow-based microfluidic biochips, which are able to integrate the necessary functions for biochemical analysis on-chip. In these chips, the flow of liquid is manipulated using integrated microvalves. By combining severalmicrovalves, more complex units...

Manually operatable on-chip bistable pneumatic microstructures for microfluidic manipulations.

Science.gov (United States)

Chen, Arnold; Pan, Tingrui

2014-09-07

Bistable microvalves are of particular interest because of their distinct nature of requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries since microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integrability and a small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPMs) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly composed of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), of which users have direct control through finger pressing to switch either to the bistable vacuum state (VS) or the atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that processes blood samples to identify the distinct blood types (A/B/O) on-chip.

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.

Paper-Plastic Hybrid Microfluidic Device for Smartphone-Based Colorimetric Analysis of Urine.

Science.gov (United States)

Jalal, Uddin M; Jin, Gyeong Jun; Shim, Joon S

2017-12-19

In this work, a disposable paper-plastic hybrid microfluidic lab-on-a-chip (LOC) has been developed and successfully applied for the colorimetric measurement of urine by the smartphone-based optical platform using a "UrineAnalysis" Android app. The developed device was cost-effectively implemented as a stand-alone hybrid LOC by incorporating the paper-based conventional reagent test strip inside the plastic-based LOC microchannel. The LOC device quantitatively investigated the small volume (40 μL) of urine analytes for the colorimetric reaction of glucose, protein, pH, and red blood cell (RBC) in integration with the finger-actuating micropump. On the basis of our experiments, the conventional urine strip showed large deviation as the reaction time goes by, because dipping the strip sensor in a bottle of urine could not control the reaction volume. By integrating the strip sensor in the LOC device for urine analysis, our device significantly improves the time-dependent inconstancy of the conventional dipstick-based urine strip, and the smartphone app used for image analysis enhances the visual assessment of the test strip, which is a major user concern for the colorimetric analysis in point-of-care (POC) applications. As a result, the user-friendly LOC, which is successfully implemented in a disposable format with the smartphone-based optical platform, may be applicable as an effective tool for rapid and qualitative POC urinalysis.

High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

KAUST Repository

Li, Shunbo; Li, Ming; Bougot-Robin, Kristelle; Cao, Wenbin; Yeung Yeung Chau, Irene; Li, Weihua; Wen, Weijia

2013-01-01

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

KAUST Repository

Li, Shunbo

2013-03-20

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

Fabrication of a Paper-Based Microfluidic Device to Readily Determine Nitrite Ion Concentration by Simple Colorimetric Assay

Science.gov (United States)

Wang, Bo; Lin, Zhiqiang; Wang, Min

2015-01-01

Paper-based microfluidic devices (µPAD) are a burgeoning platform of microfluidic analysis technology. The method described herein is for use in undergraduate and high school chemistry laboratories. A simple and convenient µPAD was fabricated by easy patterning of filter paper using a permanent marker pen. The usefulness of the device was…

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

KAUST Repository

Fan, Yiqiang; Li, Huawei; Yi, Ying; Foulds, Ian G.

2013-01-01

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

Review of Recent Metamaterial Microfluidic Sensors.

Science.gov (United States)

Salim, Ahmed; Lim, Sungjoon

2018-01-15

Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require only microliter-nanoliter sample for sensing. Simple design, easy fabrication process, light weight prototype, and instant measurements are advantages as compared to conventional (optical, electrochemical and biological) sensing systems. Inkjet-printed flexible sensors find their utilization in rapidly growing wearable electronics and health-monitoring flexible devices. Adequate sensitivity and repeatability of these low profile microfluidic sensors make them a potential candidate for point-of-care testing which novice patients can use reliably. Aside from degraded sensitivity and lack of selectivity in all practical microwave chemical sensors, they require an instrument, such as vector network analyzer for measurements and not readily available as a self-sustained portable sensor. This review article presents state-of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive devices ranging from gigahertz to terahertz range) with an emphasis on metamaterial sensing circuit and microfluidic detection. We also highlight challenges and strategies to cope these issues which set future directions.

Direct spraying method for fabrication of paper-based microfluidic devices

International Nuclear Information System (INIS)

Liu, Ning; An, Hong-Jie; Lew, Wen Siang; Xu, Jing; Phan, Dinh-Tuan; Hashimoto, Michinao

2017-01-01

Direct spraying of hydrophobic materials is an affordable, easy-to-use and equipment-free method for fabrication of flexible microsensors, albeit not yet widely adopted. To explore its application potential, in this paper, we propose and demonstrate two novel hybrid methods to fabricate paper-based components. Firstly, through combing direct spraying with Parafilm embedding, a leak-free paper-based sample preconcentrator for fluorescence sensing was fabricated. The leak-free device worked on the principle of ion concentration polarization (ICP) effect, and achieved enhancement of fluorescent tracer by 220 folds on a paper substrate. Secondly, by using the sprayed hydrophobic patterns, paper-based microsized supercapacitors (mSCs) were fabricated. Vacuum filtration was used to deposit multi-wall carbon nanotubes (MWCNT)-dispersed solution on a porous substrate to form electrodes. A volumetric capacitance of 42.5 mF cm −3 at a current density of 2 mA cm −3 was obtained on the paper-based mSC. Our demonstrations have shown the versatility of direct spraying for the fabrication of integrative paper-based microfluidic devices. (paper)

Brain slice on a chip: opportunities and challenges of applying microfluidic technology to intact tissues.

Science.gov (United States)

Huang, Yu; Williams, Justin C; Johnson, Stephen M

2012-06-21

Isolated brain tissue, especially brain slices, are valuable experimental tools for studying neuronal function at the network, cellular, synaptic, and single channel levels. Neuroscientists have refined the methods for preserving brain slice viability and function and converged on principles that strongly resemble the approach taken by engineers in developing microfluidic devices. With respect to brain slices, microfluidic technology may 1) overcome the traditional limitations of conventional interface and submerged slice chambers and improve oxygen/nutrient penetration into slices, 2) provide better spatiotemporal control over solution flow/drug delivery to specific slice regions, and 3) permit successful integration with modern optical and electrophysiological techniques. In this review, we highlight the unique advantages of microfluidic devices for in vitro brain slice research, describe recent advances in the integration of microfluidic devices with optical and electrophysiological instrumentation, and discuss clinical applications of microfluidic technology as applied to brain slices and other non-neuronal tissues. We hope that this review will serve as an interdisciplinary guide for both neuroscientists studying brain tissue in vitro and engineers as they further develop microfluidic chamber technology for neuroscience research.

Rapid PCR amplification using a microfluidic device with integrated microwave heating and air impingement cooling.

Science.gov (United States)

Shaw, Kirsty J; Docker, Peter T; Yelland, John V; Dyer, Charlotte E; Greenman, John; Greenway, Gillian M; Haswell, Stephen J

2010-07-07

A microwave heating system is described for performing polymerase chain reaction (PCR) in a microfluidic device. The heating system, in combination with air impingement cooling, provided rapid thermal cycling with heating and cooling rates of up to 65 degrees C s(-1) and minimal over- or under-shoot (+/-0.1 degrees C) when reaching target temperatures. In addition, once the required temperature was reached it could be maintained with an accuracy of +/-0.1 degrees C. To demonstrate the functionality of the system, PCR was successfully performed for the amplification of the Amelogenin locus using heating rates and quantities an order of magnitude faster and smaller than current commercial instruments.

Integrated Microfluidic Sensor System with Magnetostrictive Resonators

KAUST Repository

Liang, Cai; Kosel, Jü rgen; Gooneratne, Chinthaka

2011-01-01

The present embodiments describe a method that integrates a magnetostrictive sensor with driving and detecting elements into a microfluidic chip to detect a chemical, biochemical or biomedical species. These embodiments may also measure the properties of a fluid such as viscosity, pH values. The whole system can be referred to lab-on-a-chip (LOC) or micro-total-analysis-systems (.mu.TAS). In particular, this present embodiments include three units, including a microfluidics unit, a magnetostrictive sensor, and driving/detecting elements. An analyzer may also be provided to analyze an electrical signal associated with a feature of a target specimen.

Integrated Microfluidic Sensor System with Magnetostrictive Resonators

KAUST Repository

Liang, Cai

2011-12-08

The present embodiments describe a method that integrates a magnetostrictive sensor with driving and detecting elements into a microfluidic chip to detect a chemical, biochemical or biomedical species. These embodiments may also measure the properties of a fluid such as viscosity, pH values. The whole system can be referred to lab-on-a-chip (LOC) or micro-total-analysis-systems (.mu.TAS). In particular, this present embodiments include three units, including a microfluidics unit, a magnetostrictive sensor, and driving/detecting elements. An analyzer may also be provided to analyze an electrical signal associated with a feature of a target specimen.

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…

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

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.

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)

Ultra-Portable Smartphone Controlled Integrated Digital Microfluidic System in a 3D-Printed Modular Assembly

Directory of Open Access Journals (Sweden)

Mohamed Yafia

2015-09-01

Full Text Available Portable sensors and biomedical devices are influenced by the recent advances in microfluidics technologies, compact fabrication techniques, improved detection limits and enhanced analysis capabilities. This paper reports the development of an integrated ultraportable, low-cost, and modular digital microfluidic (DMF system and its successful integration with a smartphone used as a high-level controller and post processing station. Low power and cost effective electronic circuits are designed to generate the high voltages required for DMF operations in both open and closed configurations (from 100 to 800 V. The smartphone in turn commands a microcontroller that manipulate the voltage signals required for droplet actuation in the DMF chip and communicates wirelessly with the microcontroller via Bluetooth module. Moreover, the smartphone acts as a detection and image analysis station with an attached microscopic lens. The holder assembly is fabricated using three-dimensional (3D printing technology to facilitate rapid prototyping. The holder features a modular design that enables convenient attachment/detachment of a variety of DMF chips to/from an electrical busbar. The electrical circuits, controller and communication system are designed to minimize the power consumption in order to run the device on small lithium ion batteries. Successful controlled DMF operations and a basic colorimetric assay using the smartphone are demonstrated.

Optically induced dielectropheresis sorting with automated medium exchange in an integrated optofluidic device resulting in higher cell viability.

Science.gov (United States)

Lee, Gwo-Bin; Wu, Huan-Chun; Yang, Po-Fu; Mai, John D

2014-08-07

We demonstrated the integration of a microfluidic device with an optically induced dielectrophoresis (ODEP) device such that the critical medium replacement process was performed automatically and the cells could be subsequently manipulated by using digitally projected optical images. ODEP has been demonstrated to generate sufficient forces for manipulating particles/cells by projecting a light pattern onto photoconductive materials which creates virtual electrodes. The production of the ODEP force usually requires a medium that has a suitable electrical conductivity and an appropriate dielectric constant. Therefore, a 0.2 M sucrose solution is commonly used. However, this requires a complicated medium replacement process before one is able to manipulate cells. Furthermore, the 0.2 M sucrose solution is not suitable for the long-term viability of cells. In comparison to conventional manual processes, our automated medium replacement process only took 25 minutes. Experimental data showed that there was up to a 96.2% recovery rate for the manipulated cells. More importantly, the survival rate of the cells was greatly enhanced due to this faster automated process. This newly developed microfluidic chip provided a promising platform for the rapid replacement of the cell medium and this was also the first time that an ODEP device was integrated with other active flow control components in a microfluidic device. By improving cell viability after cell manipulation, this design may contribute to the practical integration of ODEP modules into other lab-on-a-chip devices and biomedical applications in the future.

Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications

Science.gov (United States)

Mark, D.; Haeberle, S.; Roth, G.; von Stetten, F.; Zengerle, R.

This review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-) chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electro-kinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

Separation of magnetic beads in a hybrid continuous flow microfluidic device

Energy Technology Data Exchange (ETDEWEB)

Samanta, Abhishek [Haldia Institute of Technology, Production Engineering Department, Haldia (India); Ganguly, Ranjan; Datta, Amitava [Jadavpur University, Power Engineering Department (India); Modak, Nipu, E-mail: nmechju@gmail.com [Jadavpur University, Mechanical Engineering Department (India)

2017-04-01

Magnetic separation of biological entities in microfluidic environment is a key task for a large number of bio-analytical protocols. In magnetophoretic separation, biochemically functionalized magnetic beads are allowed to bind selectively to target analytes, which are then separated from the background stream using a suitably imposed magnetic field. Here we present a numerical study, characterizing the performance of a magnetophoretic hybrid microfluidic device having two inlets and three outlets for immunomagnetic isolation of three different species from a continuous flow. The hybrid device works on the principle of split-flow thin (SPLITT) fractionation and field flow fractionation (FFF) mechanisms. Transport of the magnetic particles in the microchannel has been predicted following an Eulerian-Lagrangian model and using an in-house numerical code. Influence of the salient geometrical parameters on the performance of the separator is studied by characterizing the particle trajectories and their capture and separation indices. Finally, optimum channel geometry is identified that yields the maximum capture efficiency and separation index. - Highlights: • Immunomagnetic separation in a hybrid microchannel design is investigated numerically. • Influence of salient geometric parameters on the device performance is analysed. • Optimum device dimension for best separation parameters are identified. • Optimized design of hybrid separator performs better than FFF or SPLITT devices.

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.

Design of point-of-care (POC) microfluidic medical diagnostic devices

Science.gov (United States)

Leary, James F.

2018-02-01

Design of inexpensive and portable hand-held microfluidic flow/image cytometry devices for initial medical diagnostics at the point of initial patient contact by emergency medical personnel in the field requires careful design in terms of power/weight requirements to allow for realistic portability as a hand-held, point-of-care medical diagnostics device. True portability also requires small micro-pumps for high-throughput capability. Weight/power requirements dictate use of super-bright LEDs and very small silicon photodiodes or nanophotonic sensors that can be powered by batteries. Signal-to-noise characteristics can be greatly improved by appropriately pulsing the LED excitation sources and sampling and subtracting noise in between excitation pulses. The requirements for basic computing, imaging, GPS and basic telecommunications can be simultaneously met by use of smartphone technologies, which become part of the overall device. Software for a user-interface system, limited real-time computing, real-time imaging, and offline data analysis can be accomplished through multi-platform software development systems that are well-suited to a variety of currently available cellphone technologies which already contain all of these capabilities. Microfluidic cytometry requires judicious use of small sample volumes and appropriate statistical sampling by microfluidic cytometry or imaging for adequate statistical significance to permit real-time (typically medical decisions for patients at the physician's office or real-time decision making in the field. One or two drops of blood obtained by pin-prick should be able to provide statistically meaningful results for use in making real-time medical decisions without the need for blood fractionation, which is not realistic in the field.

CMOS Enabled Microfluidic Systems for Healthcare Based Applications

KAUST Repository

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

2018-01-01

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.

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.

Method for forming polymerized microfluidic devices

Science.gov (United States)

Sommer, Gregory J.; Hatch, Anson V.; Wang, Ying-Chih; Singh, Anup K.; Renzi, Ronald F.; Claudnic, Mark R.

2013-03-12

Methods for making a microfluidic device according to embodiments of the present invention include defining.about.cavity. Polymer precursor solution is positioned in the cavity, and exposed to light to begin the polymerization process and define a microchannel. In some embodiments, after the polymerization process is partially complete, a solvent rinse is performed, or fresh polymer precursor introduced into the microchannel. This may promote removal of unpolymerized material from the microchannel and enable smaller feature sizes. The polymer precursor solution may contain an iniferter. Polymerized features therefore may be capped with the iniferter, which is photoactive. The iniferter may aid later binding of a polyacrylamide gel to the microchannel surface.

Stripline-based microfluidic devices for high-resolution NMR spectroscopy

NARCIS (Netherlands)

Bart, J.

2009-01-01

A novel route towards microchip integrated NMR analysis was studied. For NMR analysis of mass-limited samples, research has focussed for decennia on microsolenoidal or planar helical detection coils on microfluidic substrates. Since these approaches suffer from static field distortion resulting in

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.

Integrated microfluidic probe station.

Science.gov (United States)

Perrault, C M; Qasaimeh, M A; Brastaviceanu, T; Anderson, K; Kabakibo, Y; Juncker, D

2010-11-01

The microfluidic probe (MFP) consists of a flat, blunt tip with two apertures for the injection and reaspiration of a microjet into a solution--thus hydrodynamically confining the microjet--and is operated atop an inverted microscope that enables live imaging. By scanning across a surface, the microjet can be used for surface processing with the capability of both depositing and removing material; as it operates under immersed conditions, sensitive biological materials and living cells can be processed. During scanning, the MFP is kept immobile and centered over the objective of the inverted microscope, a few micrometers above a substrate that is displaced by moving the microscope stage and that is flushed continuously with the microjet. For consistent and reproducible surface processing, the gap between the MFP and the substrate, the MFP's alignment, the scanning speed, the injection and aspiration flow rates, and the image capture need all to be controlled and synchronized. Here, we present an automated MFP station that integrates all of these functionalities and automates the key operational parameters. A custom software program is used to control an independent motorized Z stage for adjusting the gap, a motorized microscope stage for scanning the substrate, up to 16 syringe pumps for injecting and aspirating fluids, and an inverted fluorescence microscope equipped with a charge-coupled device camera. The parallelism between the MFP and the substrate is adjusted using manual goniometer at the beginning of the experiment. The alignment of the injection and aspiration apertures along the scanning axis is performed using a newly designed MFP screw holder. We illustrate the integrated MFP station by the programmed, automated patterning of fluorescently labeled biotin on a streptavidin-coated surface.

Review of Recent Metamaterial Microfluidic Sensors

Directory of Open Access Journals (Sweden)

Ahmed Salim

2018-01-01

Full Text Available Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require only microliter–nanoliter sample for sensing. Simple design, easy fabrication process, light weight prototype, and instant measurements are advantages as compared to conventional (optical, electrochemical and biological sensing systems. Inkjet-printed flexible sensors find their utilization in rapidly growing wearable electronics and health-monitoring flexible devices. Adequate sensitivity and repeatability of these low profile microfluidic sensors make them a potential candidate for point-of-care testing which novice patients can use reliably. Aside from degraded sensitivity and lack of selectivity in all practical microwave chemical sensors, they require an instrument, such as vector network analyzer for measurements and not readily available as a self-sustained portable sensor. This review article presents state-of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive devices ranging from gigahertz to terahertz range with an emphasis on metamaterial sensing circuit and microfluidic detection. We also highlight challenges and strategies to cope these issues which set future directions.

Accurate and rapid micromixer for integrated microfluidic devices

Science.gov (United States)

Van Dam, R. Michael; Liu, Kan; Shen, Kwang -Fu Clifton; Tseng, Hsian -Rong

2015-09-22

The invention may provide a microfluidic mixer having a droplet generator and a droplet mixer in selective fluid connection with the droplet generator. The droplet generator comprises first and second fluid chambers that are structured to be filled with respective first and second fluids that can each be held in isolation for a selectable period of time. The first and second fluid chambers are further structured to be reconfigured into a single combined chamber to allow the first and second fluids in the first and second fluid chambers to come into fluid contact with each other in the combined chamber for a selectable period of time prior to being brought into the droplet mixer.

Thermal Blood Clot Formation and use in Microfluidic Device Valving Applications

Science.gov (United States)

Tai, Yu-Chong (Inventor); Shi, Wendian (Inventor); Guo, Luke (Inventor)

2014-01-01

The present invention provides a method of forming a blood-clot microvalve by heating blood in a capillary tube of a microfluidic device. Also described are methods of modulating liquid flow in a capillary tube by forming and removing a blood-clot microvalve.

Monolayer-functionalized microfluidics devices for optical sensing of acidity

NARCIS (Netherlands)

Mela, P.; Onclin, S.; Goedbloed, M.H.; Levi, S.; Garcia Parajo, M.F.; van Hulst, N.F.; Ravoo, B.J.; Reinhoudt, David; van den Berg, Albert

This paper describes the integration of opto-chemosensors in microfluidics networks. Our technique exploits the internal surface of the network as a platform to build a sensing system by coating the surface with a self-assembled monolayer and subsequently binding a fluorescent sensing molecule to

Low consumption single-use microvalve for microfluidic PCB-based platforms

International Nuclear Information System (INIS)

Flores, G; Aracil, C; Perdigones, F; Quero, J M

2014-01-01

In this paper, a single-use and unidirectional microvalve with low consumption of energy for PCB-based microfluidic platforms is reported. Its activation is easy because it works as a fuse. The fabrication process of the device is based on PCB technology and a typical SU-8 process, using the PCB as a substrate and SU-8 for the microfluidic channels and chambers. The microvalve is intended to be used to impulse small volumes of fluids and it has been designed to be highly integrable in PCB-based microfluidic platforms. The proposed device has been fabricated, integrated and tested in a general purpose microfluidic circuit, resulting in a low activation time, of about 100 μs, and a low consumption of energy, with a maximum of 27 mJ. These results show a significant improvement because the energy consumption is about 84% lower and the time response is about four orders of magnitude shorter if compared with similar microvalves for impulsion of fluids on PCB-based platforms. (paper)

A low cost and hybrid technology for integrating silicon sensors or actuators in polymer microfluidic systems

International Nuclear Information System (INIS)

Charlot, Samuel; Gué, Anne-Marie; Tasselli, Josiane; Marty, Antoine; Abgrall, Patrick; Estève, Daniel

2008-01-01

This paper describes a new technology permitting a hybrid integration of silicon chips in polymer (PDMS and SU8) microfluidic structures. This two-step technology starts with transferring the silicon device onto a rigid substrate (typically PCB) and planarizing it, and then it proceeds with stacking of the polymer-made fluidic network onto the device. The technology is low cost, based on screen printing and lamination, can be applied to treat large surface areas, and is compatible with standard photolithography and vacuum based approaches. We show, as an example, the integration of a thermal sensor inside channels made of PDMS or SU8. The developed structures had no fluid leaks at the Si/polymer interfaces and the electrical circuit was perfectly tightproof. (note)

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

KAUST Repository

Li, Erqiang; Zhang, Jiaming; Thoroddsen, Sigurdur T

2013-01-01

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

Additive manufacturing of three-dimensional (3D) microfluidic-based microelectromechanical systems (MEMS) for acoustofluidic applications.

Science.gov (United States)

Cesewski, Ellen; Haring, Alexander P; Tong, Yuxin; Singh, Manjot; Thakur, Rajan; Laheri, Sahil; Read, Kaitlin A; Powell, Michael D; Oestreich, Kenneth J; Johnson, Blake N

2018-06-13

Three-dimensional (3D) printing now enables the fabrication of 3D structural electronics and microfluidics. Further, conventional subtractive manufacturing processes for microelectromechanical systems (MEMS) relatively limit device structure to two dimensions and require post-processing steps for interface with microfluidics. Thus, the objective of this work is to create an additive manufacturing approach for fabrication of 3D microfluidic-based MEMS devices that enables 3D configurations of electromechanical systems and simultaneous integration of microfluidics. Here, we demonstrate the ability to fabricate microfluidic-based acoustofluidic devices that contain orthogonal out-of-plane piezoelectric sensors and actuators using additive manufacturing. The devices were fabricated using a microextrusion 3D printing system that contained integrated pick-and-place functionality. Additively assembled materials and components included 3D printed epoxy, polydimethylsiloxane (PDMS), silver nanoparticles, and eutectic gallium-indium as well as robotically embedded piezoelectric chips (lead zirconate titanate (PZT)). Electrical impedance spectroscopy and finite element modeling studies showed the embedded PZT chips exhibited multiple resonant modes of varying mode shape over the 0-20 MHz frequency range. Flow visualization studies using neutrally buoyant particles (diameter = 0.8-70 μm) confirmed the 3D printed devices generated bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in a continuous flow format showed suspended particles could be moved toward or away from the walls of microfluidic channels based on selective actuation of in-plane or out-of-plane PZT chips. This work suggests additive manufacturing potentially provides new opportunities for the design and fabrication of acoustofluidic and microfluidic devices.

Multi-depth valved microfluidics for biofilm segmentation

International Nuclear Information System (INIS)

Meyer, M T; Bentley, W E; Ghodssi, R; Subramanian, S; Kim, Y W; Ben-Yoav, H; Gnerlich, M; Gerasopoulos, K

2015-01-01

Bacterial biofilms present a societal challenge, as they occur in the majority of infections but are highly resistant to both immune mechanisms and traditional antibiotics. In the pursuit of better understanding biofilm biology for developing new treatments, there is a need for streamlined, controlled platforms for biofilm growth and evaluation. We leverage advantages of microfluidics to develop a system in which biofilms are formed and sectioned, allowing parallel assays on multiple sections of one biofilm. A microfluidic testbed with multiple depth profiles was developed to accommodate biofilm growth and sectioning by hydraulically actuated valves. In realization of the platform, a novel fabrication technique was developed for creating multi-depth microfluidic molds using sequentially patterned photoresist separated and passivated by conformal coatings using atomic layer deposition. Biofilm thickness variation within three separately tested devices was less than 13% of the average thickness in each device, while variation between devices was 23% of the average thickness. In a demonstration of parallel experiments performed on one biofilm within one device, integrated valves were used to trisect the uniform biofilms with one section maintained as a control, and two sections exposed to different concentrations of sodium dodecyl sulfate. The technology presented here for multi-depth microchannel fabrication can be used to create a host of microfluidic devices with diverse architectures. While this work focuses on one application of such a device in biofilm sectioning for parallel experimentation, the tailored architectures enabled by the fabrication technology can be used to create devices that provide new biological information. (paper)

Multi-depth valved microfluidics for biofilm segmentation

Science.gov (United States)

Meyer, M. T.; Subramanian, S.; Kim, Y. W.; Ben-Yoav, H.; Gnerlich, M.; Gerasopoulos, K.; Bentley, W. E.; Ghodssi, R.

2015-09-01

Bacterial biofilms present a societal challenge, as they occur in the majority of infections but are highly resistant to both immune mechanisms and traditional antibiotics. In the pursuit of better understanding biofilm biology for developing new treatments, there is a need for streamlined, controlled platforms for biofilm growth and evaluation. We leverage advantages of microfluidics to develop a system in which biofilms are formed and sectioned, allowing parallel assays on multiple sections of one biofilm. A microfluidic testbed with multiple depth profiles was developed to accommodate biofilm growth and sectioning by hydraulically actuated valves. In realization of the platform, a novel fabrication technique was developed for creating multi-depth microfluidic molds using sequentially patterned photoresist separated and passivated by conformal coatings using atomic layer deposition. Biofilm thickness variation within three separately tested devices was less than 13% of the average thickness in each device, while variation between devices was 23% of the average thickness. In a demonstration of parallel experiments performed on one biofilm within one device, integrated valves were used to trisect the uniform biofilms with one section maintained as a control, and two sections exposed to different concentrations of sodium dodecyl sulfate. The technology presented here for multi-depth microchannel fabrication can be used to create a host of microfluidic devices with diverse architectures. While this work focuses on one application of such a device in biofilm sectioning for parallel experimentation, the tailored architectures enabled by the fabrication technology can be used to create devices that provide new biological information.

Microfluidic redox battery.

Science.gov (United States)

Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

2013-07-07

A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

Disposable world-to-chip interface for digital microfluidics

Science.gov (United States)

Van Dam, R. Michael; Shah, Gaurav; Keng, Pei-Yuin

2017-05-16

The present disclosure sets forth incorporating microfluidic chips interfaces for use with digital microfluidic processes. Methods and devices according to the present disclosure utilize compact, integrated platforms that interface with a chip upstream and downstream of the reaction, as well as between intermediate reaction steps if needed. In some embodiments these interfaces are automated, including automation of a multiple reagent process. Various reagent delivery systems and methods are also disclosed.

Fabricating PFPE Membranes for Microfluidic Valves and Pumps

Science.gov (United States)

Greer, Frank; White, Victor E.; Lee, Michael C.; Willis, Peter A.; Grunthaner, Frank J.; Rolland, Jason; Rolland, Jason

2009-01-01

A process has been developed for fabricating membranes of a perfluoropolyether (PFPE) and integrating them into valves and pumps in laboratory-on-achip microfluidic devices. Membranes of poly(tetrafluoroethylene) [PTFE] and poly(dimethylsilane) [PDMS] have been considered for this purpose and found wanting. By making it possible to use PFPE instead of PTFE or PDMS, the present process expands the array of options for further development of microfluidic devices for diverse applications that could include detection of biochemicals of interest, detection of toxins and biowarfare agents, synthesis and analysis of proteins, medical diagnosis, and synthesis of fuels.

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.

Simulation and fabrication of integrated polystyrene microlens in microfluidic system

KAUST Repository

Fan, Yiqiang

2013-05-17

This paper presents a simple and quick method to integrate microlens with the microfluidics systems. The polystyrene (PS) based microlens is fabricated with the free surface thermal compression molding methods, a thin PS sheet with the microlens is bonded to a PMMA substrate which contains the laser ablated microchannels. The convex profiler of the microlens will give a magnified images of the microchannels for easier observation. Optical simulation software is being used for the design and simulation of the microlens to have optimal optical performance with the desired focal length. A microfluidic system with the integrated PS microlens is also fabricated for demonstration.

Simulation and fabrication of integrated polystyrene microlens in microfluidic system

KAUST Repository

Fan, Yiqiang; Li, Huawei; Conchouso Gonzalez, David; Foulds, Ian G.

2013-01-01

This paper presents a simple and quick method to integrate microlens with the microfluidics systems. The polystyrene (PS) based microlens is fabricated with the free surface thermal compression molding methods, a thin PS sheet with the microlens is bonded to a PMMA substrate which contains the laser ablated microchannels. The convex profiler of the microlens will give a magnified images of the microchannels for easier observation. Optical simulation software is being used for the design and simulation of the microlens to have optimal optical performance with the desired focal length. A microfluidic system with the integrated PS microlens is also fabricated for demonstration.

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.

An open-source, programmable pneumatic setup for operation and automated control of single- and multi-layer microfluidic devices

Directory of Open Access Journals (Sweden)

Kara Brower

2018-04-01

Full Text Available Microfluidic technologies have been used across diverse disciplines (e.g. high-throughput biological measurement, fluid physics, laboratory fluid manipulation but widespread adoption has been limited in part due to the lack of openly disseminated resources that enable non-specialist labs to make and operate their own devices. Here, we report the open-source build of a pneumatic setup capable of operating both single and multilayer (Quake-style microfluidic devices with programmable scripting automation. This setup can operate both simple and complex devices with 48 device valve control inputs and 18 sample inputs, with modular design for easy expansion, at a fraction of the cost of similar commercial solutions. We present a detailed step-by-step guide to building the pneumatic instrumentation, as well as instructions for custom device operation using our software, Geppetto, through an easy-to-use GUI for live on-chip valve actuation and a scripting system for experiment automation. We show robust valve actuation with near real-time software feedback and demonstrate use of the setup for high-throughput biochemical measurements on-chip. This open-source setup will enable specialists and novices alike to run microfluidic devices easily in their own laboratories. Keywords: Microfluidics, Pneumatics, Laboratory automation, Biochip, BioMEMs, Biohacking, Fluid handling, Micro total analysis systems (μTAS, Quake-style valves

Fluorescence detection system for microfluidic droplets

Science.gov (United States)

Chen, Binyu; Han, Xiaoming; Su, Zhen; Liu, Quanjun

2018-05-01

In microfluidic detection technology, because of the universality of optical methods in laboratory, optical detection is an attractive solution for microfluidic chip laboratory equipment. In addition, the equipment with high stability and low cost can be realized by integrating appropriate optical detection technology on the chip. This paper reports a detection system for microfluidic droplets. Photomultiplier tubes (PMT) is used as a detection device to improve the sensitivity of detection. This system improves the signal to noise ratio by software filtering and spatial filter. The fluorescence intensity is proportional to the concentration of the fluorescence and intensity of the laser. The fluorescence micro droplets of different concentrations can be distinguished by this system.

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

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.

Integration of Curved D-Type Optical Fiber Sensor with Microfluidic Chip.

Science.gov (United States)

Sun, Yung-Shin; Li, Chang-Jyun; Hsu, Jin-Cherng

2016-12-30

A curved D-type optical fiber sensor (OFS) combined with a microfluidic chip is proposed. This OFS, based on surface plasmon resonance (SPR) of the Kretchmann's configuration, is applied as a biosensor to measure the concentrations of different bio-liquids such as ethanol, methanol, and glucose solutions. The SPR phenomenon is attained by using the optical fiber to guide the light source to reach the side-polished, gold-coated region. Integrating this OFS with a polymethylmethacrylate (PMMA)-based microfluidic chip, the SPR spectra for liquids with different refractive indices are recorded. Experimentally, the sensitivity of the current biosensor was calculated to be in the order of 10 -5 RIU. This microfluidic chip-integrated OFS could be valuable for monitoring subtle changes in biological samples such as blood sugar, allergen, and biomolecular interactions.

Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

Science.gov (United States)

Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-04-01

Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a- Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two ''control plates'' are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (glass/water) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

Single-cell cloning and expansion of human induced pluripotent stem cells by a microfluidic culture device.

Science.gov (United States)

Matsumura, Taku; Tatsumi, Kazuya; Noda, Yuichiro; Nakanishi, Naoyuki; Okonogi, Atsuhito; Hirano, Kunio; Li, Liu; Osumi, Takashi; Tada, Takashi; Kotera, Hidetoshi

2014-10-10

The microenvironment of cells, which includes basement proteins, shear stress, and extracellular stimuli, should be taken into consideration when examining physiological cell behavior. Although microfluidic devices allow cellular responses to be analyzed with ease at the single-cell level, few have been designed to recover cells. We herein demonstrated that a newly developed microfluidic device helped to improve culture conditions and establish a clonality-validated human pluripotent stem cell line after tracing its growth at the single-cell level. The device will be a helpful tool for capturing various cell types in the human body that have not yet been established in vitro. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

A hybrid approach to device integration on a genetic analysis platform

International Nuclear Information System (INIS)

Brennan, Des; Justice, John; Aherne, Margaret; Galvin, Paul; Jary, Dorothee; Kurg, Ants; Berik, Evgeny; Macek, Milan

2012-01-01

Point-of-care (POC) systems require significant component integration to implement biochemical protocols associated with molecular diagnostic assays. Hybrid platforms where discrete components are combined in a single platform are a suitable approach to integration, where combining multiple device fabrication steps on a single substrate is not possible due to incompatible or costly fabrication steps. We integrate three devices each with a specific system functionality: (i) a silicon electro-wetting-on-dielectric (EWOD) device to move and mix sample and reagent droplets in an oil phase, (ii) a polymer microfluidic chip containing channels and reservoirs and (iii) an aqueous phase glass microarray for fluorescence microarray hybridization detection. The EWOD device offers the possibility of fully integrating on-chip sample preparation using nanolitre sample and reagent volumes. A key challenge is sample transfer from the oil phase EWOD device to the aqueous phase microarray for hybridization detection. The EWOD device, waveguide performance and functionality are maintained during the integration process. An on-chip biochemical protocol for arrayed primer extension (APEX) was implemented for single nucleotide polymorphism (SNiP) analysis. The prepared sample is aspirated from the EWOD oil phase to the aqueous phase microarray for hybridization. A bench-top instrumentation system was also developed around the integrated platform to drive the EWOD electrodes, implement APEX sample heating and image the microarray after hybridization. (paper)

3D Printed Multimaterial Microfluidic Valve.

Directory of Open Access Journals (Sweden)

Steven J Keating

Full Text Available We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics.

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

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.

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

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.

Integration of Multiplexed Microfluidic Electrokinetic Concentrators with a Morpholino Microarray via Reversible Surface Bonding for Enhanced DNA Hybridization.

Science.gov (United States)

Martins, Diogo; Wei, Xi; Levicky, Rastislav; Song, Yong-Ak

2016-04-05

We describe a microfluidic concentration device to accelerate the surface hybridization reaction between DNA and morpholinos (MOs) for enhanced detection. The microfluidic concentrator comprises a single polydimethylsiloxane (PDMS) microchannel onto which an ion-selective layer of conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) ( PSS) was directly printed and then reversibly surface bonded onto a morpholino microarray for hybridization. Using this electrokinetic trapping concentrator, we could achieve a maximum concentration factor of ∼800 for DNA and a limit of detection of 10 nM within 15 min. In terms of the detection speed, it enabled faster hybridization by around 10-fold when compared to conventional diffusion-based hybridization. A significant advantage of our approach is that the fabrication of the microfluidic concentrator is completely decoupled from the microarray; by eliminating the need to deposit an ion-selective layer on the microarray surface prior to device integration, interfacing between both modules, the PDMS chip for electrokinetic concentration and the substrate for DNA sensing are easier and applicable to any microarray platform. Furthermore, this fabrication strategy facilitates a multiplexing of concentrators. We have demonstrated the proof-of-concept for multiplexing by building a device with 5 parallel concentrators connected to a single inlet/outlet and applying it to parallel concentration and hybridization. Such device yielded similar concentration and hybridization efficiency compared to that of a single-channel device without adding any complexity to the fabrication and setup. These results demonstrate that our concentrator concept can be applied to the development of a highly multiplexed concentrator-enhanced microarray detection system for either genetic analysis or other diagnostic assays.

CMOS Enabled Microfluidic Systems for Healthcare Based Applications.

Science.gov (United States)

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

2018-04-01

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.

A microfluidic device for 2D to 3D and 3D to 3D cell navigation

International Nuclear Information System (INIS)

Shamloo, Amir; Amirifar, Leyla

2016-01-01

Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be obtained by diffusion. The device was designed by a numerical simulation so that the uniformity of the concentration gradients throughout the cell culture chamber was obtained. Adult neural cells were cultured within this device and they showed different branching and axonal navigation phenotypes within varying nerve growth factor (NGF) concentration profiles. Neural stem cells were also cultured within varying collagen matrix densities while exposed to NGF concentrations and they experienced 3D to 3D collective migration. By generating vascular endothelial growth factor concentration gradients, adult human dermal microvascular endothelial cells also migrated in a 2D to 3D manner and formed a stable lumen within a specific collagen matrix density. It was observed that a minimum absolute concentration and concentration gradient were required to stimulate migration of all types of the cells. This device has the advantage of changing multiple parameters simultaneously and is expected to have wide applicability in cell studies. (paper)

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.

A microfluidic device for studying cell signaling with multiple inputs and adjustable amplitudes and frequencies

Science.gov (United States)

Ningsih, Zubaidah; Chon, James W. M.; Clayton, Andrew H. A.

2013-12-01

Cell function is largely controlled by an intricate web of macromolecular interactions called signaling networks. It is known that the type and the intensity (concentration) of stimulus affect cell behavior. However, the temporal aspect of the stimulus is not yet fully understood. Moreover, the process of distinguishing between two stimuli by a cell is still not clear. A microfluidic device enables the delivery of a precise and exact stimulus to the cell due to the laminar flow established inside its micro-channel. The slow stream delivers a constant stimulus which is adjustable according to the experiment set up. Moreover, with controllable inputs, microfluidic facilitates the stimuli delivery according to a certain pattern with adjustable amplitude, frequency and phase. Several designs of PDMS microfluidic device has been produced in this project via photolithography and soft lithography processes. To characterize the microfluidic performance, two experiments has been conducted. First, by comparing the fluorescence intensity and the lifetime of fluorescein in the present of KI, mixing extent between two inputs was observed using Frequency Lifetime Imaging Microscopy (FLIM). Furthermore, the input-output relationship of fluorescein concentration delivered was also drawn to characterize the amplitude, frequency and phase of the inputs. Second experiment involved the cell culturing inside microfluidic. Using NG108-15 cells, proliferation and differentiation were observed based on the cell number and cell physiological changes. Our results demonstrate that hurdle design gives 86% mixing of fluorescein and buffer. Relationship between inputoutput fluorescein concentrations delivered has also been demonstrated and cells were successfully cultured inside the microfluidic.

Integrated microfluidic capillary in a waveguide resonator for chemical and biomedical sensing

International Nuclear Information System (INIS)

Pavuluri, S K; Lopez-Villarroya, R; McKeever, E; Goussetis, G; Desmulliez, M P Y; Kavanagh, D

2009-01-01

A novel microfluidic sensing device based on waveguide cavity filters is proposed for the characterisation, detection of cells in solution and chemical substances in micro-litre volumes. The sensor consists of a micromachined microfluidic channel within a waveguide-based resonator localised increased near-fields and could potentially be designed for different frequency regimes to improve the sensitivity. The present sensor has been proposed for fabrication in different manufacturing platforms and an initial prototype with a 100μm micromachined channel that is embedded within an X-band E-plane waveguide has been fabricated and tested. The design methodology for the microfluidic channel and the E-plane filter is also presented.

Integration of Curved D-Type Optical Fiber Sensor with Microfluidic Chip

Directory of Open Access Journals (Sweden)

Yung-Shin Sun

2016-12-01

Full Text Available A curved D-type optical fiber sensor (OFS combined with a microfluidic chip is proposed. This OFS, based on surface plasmon resonance (SPR of the Kretchmann’s configuration, is applied as a biosensor to measure the concentrations of different bio-liquids such as ethanol, methanol, and glucose solutions. The SPR phenomenon is attained by using the optical fiber to guide the light source to reach the side-polished, gold-coated region. Integrating this OFS with a polymethylmethacrylate (PMMA-based microfluidic chip, the SPR spectra for liquids with different refractive indices are recorded. Experimentally, the sensitivity of the current biosensor was calculated to be in the order of 10−5 RIU. This microfluidic chip-integrated OFS could be valuable for monitoring subtle changes in biological samples such as blood sugar, allergen, and biomolecular interactions.

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...

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).

Novel immunoassay formats for integrated microfluidic circuits: diffusion immunoassays (DIA)

Science.gov (United States)

Weigl, Bernhard H.; Hatch, Anson; Kamholz, Andrew E.; Yager, Paul

2000-03-01

Novel designs of integrated fluidic microchips allow separations, chemical reactions, and calibration-free analytical measurements to be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples. This technology lends itself to applications such as clinical diagnostics, including tumor marker screening, and environmental sensing in remote locations. Lab-on-a-Chip based systems offer many *advantages over traditional analytical devices: They consume extremely low volumes of both samples and reagents. Each chip is inexpensive and small. The sampling-to-result time is extremely short. They perform all analytical functions, including sampling, sample pretreatment, separation, dilution, and mixing steps, chemical reactions, and detection in an integrated microfluidic circuit. Lab-on-a-Chip systems enable the design of small, portable, rugged, low-cost, easy to use, yet extremely versatile and capable diagnostic instruments. In addition, fluids flowing in microchannels exhibit unique characteristics ('microfluidics'), which allow the design of analytical devices and assay formats that would not function on a macroscale. Existing Lab-on-a-chip technologies work very well for highly predictable and homogeneous samples common in genetic testing and drug discovery processes. One of the biggest challenges for current Labs-on-a-chip, however, is to perform analysis in the presence of the complexity and heterogeneity of actual samples such as whole blood or contaminated environmental samples. Micronics has developed a variety of Lab-on-a-Chip assays that can overcome those shortcomings. We will now present various types of novel Lab- on-a-Chip-based immunoassays, including the so-called Diffusion Immunoassays (DIA) that are based on the competitive laminar diffusion of analyte molecules and tracer molecules into a region of the chip containing antibodies that target the analyte molecules. Advantages of this

Versatile fabrication of paper-based microfluidic devices with high chemical resistance using scholar glue and magnetic masks.

Science.gov (United States)

Cardoso, Thiago M G; de Souza, Fabrício R; Garcia, Paulo T; Rabelo, Denilson; Henry, Charles S; Coltro, Wendell K T

2017-06-29

Simple methods have been developed for fabricating microfluidic paper-based analytical devices (μPADs) but few of these devices can be used with organic solvents and/or aqueous solutions containing surfactants. This study describes a simple fabrication strategy for μPADs that uses readily available scholar glue to create the hydrophobic flow barriers that are resistant to surfactants and organic solvents. Microfluidic structures were defined by magnetic masks designed with either neodymium magnets or magnetic sheets to define the patter, and structures were created by spraying an aqueous solution of glue on the paper surface. The glue-coated paper was then exposed to UV/Vis light for cross-linking to maximize chemical resistance. Examples of microzone arrays and microfluidic devices are demonstrated. μPADs fabricated with scholar glue retained their barriers when used with surfactants, organic solvents, and strong/weak acids and bases unlike common wax-printed barriers. Paper microzones and microfluidic devices were successfully used for colorimetric assays of clinically relevant analytes commonly detected in urinalysis to demonstrate the low background of the barrier material and generally applicability to sensing. The proposed fabrication method is attractive for both its ability to be used with diverse chemistries and the low cost and simplicity of the materials and process. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels

Science.gov (United States)

Liu, Bin; Kim, Eric; Meggo, Anika; Gandhi, Sachin; Luo, Hao; Kallakuri, Srinivas; Xu, Yong; Zhang, Jinsheng

2017-04-01

Objective. Biocompatibility is a major issue for chronic neural implants, involving inflammatory and wound healing responses of neurons and glial cells. To enhance biocompatibility, we developed silicon-parylene hybrid neural probes with open architecture electrodes, microfluidic channels and a reservoir for drug delivery to suppress tissue responses. Approach. We chronically implanted our neural probes in the rat auditory cortex and investigated (1) whether open architecture electrode reduces inflammatory reaction by measuring glial responses; and (2) whether delivery of antibiotic minocycline reduces inflammatory and tissue reaction. Four weeks after implantation, immunostaining for glial fibrillary acid protein (astrocyte marker) and ionizing calcium-binding adaptor molecule 1 (macrophages/microglia cell marker) were conducted to identify immunoreactive astrocyte and microglial cells, and to determine the extent of astrocytes and microglial cell reaction/activation. A comparison was made between using traditional solid-surface electrodes and newly-designed electrodes with open architecture, as well as between deliveries of minocycline and artificial cerebral-spinal fluid diffused through microfluidic channels. Main results. The new probes with integrated micro-structures induced minimal tissue reaction compared to traditional electrodes at 4 weeks after implantation. Microcycline delivered through integrated microfluidic channels reduced tissue response as indicated by decreased microglial reaction around the neural probes implanted. Significance. The new design will help enhance the long-term stability of the implantable devices.

Paper Capillary Enables Effective Sampling for Microfluidic Paper Analytical Devices.

Science.gov (United States)

Shangguan, Jin-Wen; Liu, Yu; Wang, Sha; Hou, Yun-Xuan; Xu, Bi-Yi; Xu, Jing-Juan; Chen, Hong-Yuan

2018-06-06

Paper capillary is introduced to enable effective sampling on microfluidic paper analytical devices. By coupling mac-roscale capillary force of paper capillary and microscale capillary forces of native paper, fluid transport can be flexibly tailored with proper design. Subsequently, a hybrid-fluid-mode paper capillary device was proposed, which enables fast and reliable sampling in an arrayed form, with less surface adsorption and bias for different components. The resulting device thus well supports high throughput, quantitative, and repeatable assays all by hands operation. With all these merits, multiplex analysis of ions, proteins, and microbe have all been realized on this platform, which has paved the way to level-up analysis on μPADs.

Accessing microfluidics through feature-based design software for 3D printing

Science.gov (United States)

Shankles, Peter G.; Millet, Larry J.; Aufrecht, Jayde A.

2018-01-01

Additive manufacturing has been a cornerstone of the product development pipeline for decades, playing an essential role in the creation of both functional and cosmetic prototypes. In recent years, the prospects for distributed and open source manufacturing have grown tremendously. This growth has been enabled by an expanding library of printable materials, low-cost printers, and communities dedicated to platform development. The microfluidics community has embraced this opportunity to integrate 3D printing into the suite of manufacturing strategies used to create novel fluidic architectures. The rapid turnaround time and low cost to implement these strategies in the lab makes 3D printing an attractive alternative to conventional micro- and nanofabrication techniques. In this work, the production of multiple microfluidic architectures using a hybrid 3D printing-soft lithography approach is demonstrated and shown to enable rapid device fabrication with channel dimensions that take advantage of laminar flow characteristics. The fabrication process outlined here is underpinned by the implementation of custom design software with an integrated slicer program that replaces less intuitive computer aided design and slicer software tools. Devices are designed in the program by assembling parameterized microfluidic building blocks. The fabrication process and flow control within 3D printed devices were demonstrated with a gradient generator and two droplet generator designs. Precise control over the printing process allowed 3D microfluidics to be printed in a single step by extruding bridge structures to ‘jump-over’ channels in the same plane. This strategy was shown to integrate with conventional nanofabrication strategies to simplify the operation of a platform that incorporates both nanoscale features and 3D printed microfluidics. PMID:29596418

Accessing microfluidics through feature-based design software for 3D printing.

Science.gov (United States)

Shankles, Peter G; Millet, Larry J; Aufrecht, Jayde A; Retterer, Scott T

2018-01-01

Additive manufacturing has been a cornerstone of the product development pipeline for decades, playing an essential role in the creation of both functional and cosmetic prototypes. In recent years, the prospects for distributed and open source manufacturing have grown tremendously. This growth has been enabled by an expanding library of printable materials, low-cost printers, and communities dedicated to platform development. The microfluidics community has embraced this opportunity to integrate 3D printing into the suite of manufacturing strategies used to create novel fluidic architectures. The rapid turnaround time and low cost to implement these strategies in the lab makes 3D printing an attractive alternative to conventional micro- and nanofabrication techniques. In this work, the production of multiple microfluidic architectures using a hybrid 3D printing-soft lithography approach is demonstrated and shown to enable rapid device fabrication with channel dimensions that take advantage of laminar flow characteristics. The fabrication process outlined here is underpinned by the implementation of custom design software with an integrated slicer program that replaces less intuitive computer aided design and slicer software tools. Devices are designed in the program by assembling parameterized microfluidic building blocks. The fabrication process and flow control within 3D printed devices were demonstrated with a gradient generator and two droplet generator designs. Precise control over the printing process allowed 3D microfluidics to be printed in a single step by extruding bridge structures to 'jump-over' channels in the same plane. This strategy was shown to integrate with conventional nanofabrication strategies to simplify the operation of a platform that incorporates both nanoscale features and 3D printed microfluidics.

Photonic crystal resonator integrated in a microfluidic system

DEFF Research Database (Denmark)

Rodrigues de Sousa Nunes, Pedro André; Mortensen, Niels Asger; Kutter, Jörg Peter

2008-01-01

We report on a novel optofluidic system consisting of a silica-based 1D photonic crystal, integrated planar waveguides, and electrically insulated fluidic channels. An array of pillars in a microfluidic channel designed for electrochromatography is used as a resonator for on-column label...

Materials for microfluidic chip fabrication.

Science.gov (United States)

Ren, Kangning; Zhou, Jianhua; Wu, Hongkai

2013-11-19

Through manipulating fluids using microfabricated channel and chamber structures, microfluidics is a powerful tool to realize high sensitive, high speed, high throughput, and low cost analysis. In addition, the method can establish a well-controlled microenivroment for manipulating fluids and particles. It also has rapid growing implementations in both sophisticated chemical/biological analysis and low-cost point-of-care assays. Some unique phenomena emerge at the micrometer scale. For example, reactions are completed in a shorter amount of time as the travel distances of mass and heat are relatively small; the flows are usually laminar; and the capillary effect becomes dominant owing to large surface-to-volume ratios. In the meantime, the surface properties of the device material are greatly amplified, which can lead to either unique functions or problems that we would not encounter at the macroscale. Also, each material inherently corresponds with specific microfabrication strategies and certain native properties of the device. Therefore, the material for making the device plays a dominating role in microfluidic technologies. In this Account, we address the evolution of materials used for fabricating microfluidic chips, and discuss the application-oriented pros and cons of different materials. This Account generally follows the order of the materials introduced to microfluidics. Glass and silicon, the first generation microfluidic device materials, are perfect for capillary electrophoresis and solvent-involved applications but expensive for microfabriaction. Elastomers enable low-cost rapid prototyping and high density integration of valves on chip, allowing complicated and parallel fluid manipulation and in-channel cell culture. Plastics, as competitive alternatives to elastomers, are also rapid and inexpensive to microfabricate. Their broad variety provides flexible choices for different needs. For example, some thermosets support in-situ fabrication of

Automated Blood Sample Preparation Unit (ABSPU) for Portable Microfluidic Flow Cytometry.

Science.gov (United States)

Chaturvedi, Akhil; Gorthi, Sai Siva

2017-02-01

Portable microfluidic diagnostic devices, including flow cytometers, are being developed for point-of-care settings, especially in conjunction with inexpensive imaging devices such as mobile phone cameras. However, two pervasive drawbacks of these have been the lack of automated sample preparation processes and cells settling out of sample suspensions, leading to inaccurate results. We report an automated blood sample preparation unit (ABSPU) to prevent blood samples from settling in a reservoir during loading of samples in flow cytometers. This apparatus automates the preanalytical steps of dilution and staining of blood cells prior to microfluidic loading. It employs an assembly with a miniature vibration motor to drive turbulence in a sample reservoir. To validate performance of this system, we present experimental evidence demonstrating prevention of blood cell settling, cell integrity, and staining of cells prior to flow cytometric analysis. This setup is further integrated with a microfluidic imaging flow cytometer to investigate cell count variability. With no need for prior sample preparation, a drop of whole blood can be directly introduced to the setup without premixing with buffers manually. Our results show that integration of this assembly with microfluidic analysis provides a competent automation tool for low-cost point-of-care blood-based diagnostics.

Open-source, community-driven microfluidics with Metafluidics.

Science.gov (United States)

Kong, David S; Thorsen, Todd A; Babb, Jonathan; Wick, Scott T; Gam, Jeremy J; Weiss, Ron; Carr, Peter A

2017-06-07

Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. We present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device. We use Metafluidics to share designs and fabrication instructions for both a microfluidic ring-mixer device and a 32-channel tabletop microfluidic controller. This device and controller are applied to build genetic circuits using standard DNA assembly methods including ligation, Gateway, Gibson, and Golden Gate. Metafluidics is intended to enable a broad community of engineers, DIY enthusiasts, and other nontraditional participants with limited fabrication skills to contribute to microfluidic research.

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.

Label-Free Virus Capture and Release by a Microfluidic Device Integrated with Porous Silicon Nanowire Forest.

Science.gov (United States)

Xia, Yiqiu; Tang, Yi; Yu, Xu; Wan, Yuan; Chen, Yizhu; Lu, Huaguang; Zheng, Si-Yang

2017-02-01

Viral diseases are perpetual threats to human and animal health. Detection and characterization of viral pathogens require accurate, sensitive, and rapid diagnostic assays. For field and clinical samples, the sample preparation procedures limit the ultimate performance and utility of the overall virus diagnostic protocols. This study presents the development of a microfluidic device embedded with porous silicon nanowire (pSiNW) forest for label-free size-based point-of-care virus capture in a continuous curved flow design. The pSiNW forests with specific interwire spacing are synthesized in situ on both bottom and sidewalls of the microchannels in a batch process. With the enhancement effect of Dean flow, this study demonstrates that about 50% H5N2 avian influenza viruses are physically trapped without device clogging. A unique feature of the device is that captured viruses can be released by inducing self-degradation of the pSiNWs in physiological aqueous environment. About 60% of captured viruses can be released within 24 h for virus culture, subsequent molecular diagnosis, and other virus characterization and analyses. This device performs viable, unbiased, and label-free virus isolation and release. It has great potentials for virus discovery, virus isolation and culture, functional studies of virus pathogenicity, transmission, drug screening, and vaccine development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation: SIMPLE.

Science.gov (United States)

Kokalj, Tadej; Park, Younggeun; Vencelj, Matjaž; Jenko, Monika; Lee, Luke P

2014-11-21

Reliable, autonomous, internally self-powered microfluidic pumps are in critical demand for rapid point-of-care (POC) devices, integrated molecular-diagnostic platforms, and drug delivery systems. Here we report on a Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation (SIMPLE), which is disposable, autonomous, easy to use and fabricate, robust, and cost efficient, as a solution for self-powered microfluidic POC devices. The imbibition pump introduces the working liquid which is sucked into a porous material (paper) upon activation. The suction of the working liquid creates a reduced pressure in the analytical channel and induces the sequential sample flow into the microfluidic circuits. It requires no external power or control and can be simply activated by a fingertip press. The flow rate can be programmed by defining the shape of utilized porous material: by using three different paper shapes with circular section angles 20°, 40° and 60°, three different volume flow rates of 0.07 μL s(-1), 0.12 μL s(-1) and 0.17 μL s(-1) are demonstrated at 200 μm × 600 μm channel cross-section. We established the SIMPLE pumping of 17 μL of sample; however, the sample volume can be increased to several hundreds of μL. To demonstrate the design, fabrication, and characterization of SIMPLE, we used a simple, robust and cheap foil-laminating fabrication technique. The SIMPLE can be integrated into hydrophilic or hydrophobic materials-based microfluidic POC devices. Since it is also applicable to large-scale manufacturing processes, we anticipate that a new chapter of a cost effective, disposable, autonomous POC diagnostic chip is addressed with this technical innovation.

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

Regulation of fibrochondrogenesis of mesenchymal stem cells in an integrated microfluidic platform embedded with biomimetic nanofibrous scaffolds.

Directory of Open Access Journals (Sweden)

Weiliang Zhong

Full Text Available In native fibrocartilage, mechanotransduction allows the cells to perceive the physical microenvironment not only through topographical cues from the extracellular matrix, but also through mechanical cues, such as interstitial flow. To create a microenvironment that simultaneously integrates nanotopography and flow stimulus, we developed a biomimetic microfluidic device embedded with aligned nanofibers to contain microchambers of different angles, which enabled the flow direction to form different angles with the fibers. Using this device, we investigated the effects of microfluidic and nanotopographical environment on the morphology and fibrochondrogenesis of mesenchymal stem cells (MSCs and the involvement of RhoA/ROCK pathway and Yes-associated protein (YAP/transcriptional co-activator with PDZ-binding motif (TAZ. The results showed that the flow direction perpendicular to aligned nanofibers was conducive to fibrochondrogenesis of MSCs. In addition, ROCK inhibitor and knockdown of YAP/TAZ disrupted fibrochondrogenic differentiation of MSCs. In conclusion, our data suggest the crucial role of mechanotransduction in regulating fibrochondrogenic differentiation of MSCs, which may be mediated by RhoA/ROCK pathway and YAP/TAZ.

Continuous flow synthesis of nanoparticles using ceramic microfluidic devices

Energy Technology Data Exchange (ETDEWEB)

Gomez-de Pedro, S; Puyol, M; Alonso-Chamarro, J, E-mail: julian.alonso@uab.es [Grup de Sensors i Biosensors, Departament de Quimica, Facultat de Ciencies, Edifici Cn, Universitat Autonoma de Barcelona, Bellaterra 08193 (Spain)

2010-10-15

A microfluidic system based on the low-temperature co-fired ceramics technology (LTCC) is proposed to reproducibly carry out a simple one-phase synthesis and functionalization of monodispersed gold nanoparticles. It takes advantage of the LTCC technology, offering a fast prototyping without the need to use sophisticated facilities, reducing significantly the cost and production time of microfluidic systems. Some other interesting advantages of the ceramic materials compared to glass, silicon or polymers are their versatility and chemical resistivity. The technology enables the construction of multilayered systems, which can integrate other mechanical, electronic and fluidic components in a single substrate. This approach allows rapid, easy, low cost and automated synthesis of the gold colloidal, thus it becomes a useful approach in the progression from laboratory scale to pilot-line scale processes, which is currently demanded.

Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification

Directory of Open Access Journals (Sweden)

Michael G. Mauk

2015-10-01

Full Text Available Microfluidic components and systems for rapid (<60 min, low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs are described. A microfluidic point-of-care (POC diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1 nucleic acids (NAs are extracted from relatively large (~mL volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane” to capture sample NAs in a flow-through, filtration mode; (2 NAs captured on the membrane are isothermally (~65 °C amplified; (3 amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4 paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD better than 103 virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.

Medicine Delivery Device with Integrated Sterilization and Detection

Science.gov (United States)

Shearn, Michael J.; Greer, Harold F.; Manohara, Harish

2013-01-01

Sterile delivery devices can be created by integrating a medicine delivery instrument with surfaces that are coated with germicidal and anti-fouling material. This requires that a large-surface-area template be developed within a constrained volume to ensure good contact between the delivered medicine and the germicidal material. Both of these can be integrated using JPL-developed silicon nanotip or cryo-etch black silicon technologies with atomic layer deposition (ALD) coating of specific germicidal layers. The application of semiconductor processing techniques and technologies to the problems of fluid manipulation and delivery has enabled the integration of chemical, electrical, and mechanical manipulation of samples all within a single microfluidic device. This approach has been successfully applied at JPL to the automated processing, detection, and analysis of minute quantities (parts per trillion level) of biomaterials to develop instruments for in situ exploration or extraterrestrial bodies. The same nanofabrication techniques that are used to produce a microfluidics device are also capable of synthesizing extremely high-surface-area templates in precise locations, and coating those surfaces with conformal films to manipulate their surface properties. This methodology has been successfully applied at JPL to produce patterned and coated silicon nanotips (also known as black silicon) to manipulate the hydrophilicity of surfaces to direct the spreading of fluids in microdevices. JPL's ALD technique is an ideal method to produce the highly conformal coatings required for this type of application. Certain materials, such as TiO2, have germicidal and anti-fouling properties when they are illuminated with UV light. The proposed delivery device contacts medicine with this high-surface-area black silicon surface coated with a thin-film germicidal deposited conformally with ALD. The coating can also be illuminated with ultraviolet light for the purpose of sterilization

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.

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.

Microcontact printing with aminosilanes: creating biomolecule micro- and nanoarrays for multiplexed microfluidic bioassays.

Science.gov (United States)

Sathish, Shivani; Ricoult, Sébastien G; Toda-Peters, Kazumi; Shen, Amy Q

2017-05-21

Microfluidic systems integrated with protein and DNA micro- and nanoarrays have been the most sought-after technologies to satisfy the growing demand for high-throughput disease diagnostics. As the sensitivity of these systems relies on the bio-functionalities of the patterned recognition biomolecules, the primary concern has been to develop simple technologies that enable biomolecule immobilization within microfluidic devices whilst preserving bio-functionalities. To address this concern, we introduce a two-step patterning approach to create micro- and nanoarrays of biomolecules within microfluidic devices. First, we introduce a simple aqueous based microcontact printing (μCP) method to pattern arrays of (3-aminopropyl)triethoxysilane (APTES) on glass substrates, with feature sizes ranging from a few hundred microns down to 200 nm (for the first time). Next, these substrates are integrated with microfluidic channels to then covalently couple DNA aptamers and antibodies with the micro- and nanopatterned APTES. As these biomolecules are covalently tethered to the device substrates, the resulting bonds enable them to withstand the high shear stresses originating from the flow in these devices. We further demonstrated the flexibility of this technique, by immobilizing multiple proteins onto these APTES-patterned substrates using liquid-dispensing robots to create multiple microarrays. Next, to validate the functionalities of these microfluidic biomolecule microarrays, we perform (i) aptamer-based sandwich immunoassays to detect human interleukin 6 (IL6); and (ii) antibody-based sandwich immunoassays to detect human c-reactive protein (hCRP) with the limit of detection at 5 nM, a level below the range required for clinical screening. Lastly, the shelf-life potential of these ready-to-use microfluidic microarray devices is validated by effectively functionalizing the patterns with biomolecules up to 3 months post-printing. In summary, with a single printing step, this

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.

Comparison of roll-to-roll replication approaches for microfluidic and optical functions in lab-on-a-chip diagnostic devices

Science.gov (United States)

Brecher, Christian; Baum, Christoph; Bastuck, Thomas

2015-03-01

Economically advantageous microfabrication technologies for lab-on-a-chip diagnostic devices substituting commonly used glass etching or injection molding processes are one of the key enablers for the emerging market of microfluidic devices. On-site detection in fields of life sciences, point of care diagnostics and environmental analysis requires compact, disposable and highly functionalized systems. Roll-to-roll production as a high volume process has become the emerging fabrication technology for integrated, complex high technology products within recent years (e.g. fuel cells). Differently functionalized polymer films enable researchers to create a new generation of lab-on-a-chip devices by combining electronic, microfluidic and optical functions in multilayer architecture. For replication of microfluidic and optical functions via roll-to-roll production process competitive approaches are available. One of them is to imprint fluidic channels and optical structures of micro- or nanometer scale from embossing rollers into ultraviolet (UV) curable lacquers on polymer substrates. Depending on dimension, shape and quantity of those structures there are alternative manufacturing technologies for the embossing roller. Ultra-precise diamond turning, electroforming or casting polymer materials are used either for direct structuring or manufacturing of roller sleeves. Mastering methods are selected for application considering replication quality required and structure complexity. Criteria for the replication quality are surface roughness and contour accuracy. Structure complexity is evaluated by shapes producible (e.g. linear, circular) and aspect ratio. Costs for the mastering process and structure lifetime are major cost factors. The alternative replication approaches are introduced and analyzed corresponding to the criteria presented. Advantages and drawbacks of each technology are discussed and exemplary applications are presented.

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.

Acousto-plasmofluidics: Acoustic modulation of surface plasmon resonance in microfluidic systems

Directory of Open Access Journals (Sweden)

Daniel Ahmed

2015-09-01

Full Text Available We acoustically modulated the localized surface plasmon resonances (LSPRs of metal nanostructures integrated within microfluidic systems. An acoustically driven micromixing device based on bubble microstreaming quickly and homogeneously mixes multiple laminar flows of different refractive indices. The altered refractive index of the mixed fluids enables rapid modulation of the LSPRs of gold nanodisk arrays embedded within the microfluidic channel. The device features fast response for dynamic operation, and the refractive index within the channel is tailorable. With these unique features, our “acousto-plasmofluidic” device can be useful in applications such as optical switches, modulators, filters, biosensors, and lab-on-a-chip systems.

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.

Integrated nanohole array surface plasmon resonance sensing device using a dual-wavelength source

International Nuclear Information System (INIS)

Escobedo, C; Vincent, S; Choudhury, A I K; Campbell, J; Gordon, R; Brolo, A G; Sinton, D

2011-01-01

In this paper, we demonstrate a compact integrated nanohole array-based surface plasmon resonance sensing device. The unit includes a LED light source, driving circuitry, CCD detector, microfluidic network and computer interface, all assembled from readily available commercial components. A dual-wavelength LED scheme was implemented to increase spectral diversity and isolate intensity variations to be expected in the field. The prototype shows bulk sensitivity of 266 pixel intensity units/RIU and a limit of detection of 6 × 10 −4 RIU. Surface binding tests were performed, demonstrating functionality as a surface-based sensing system. This work is particularly relevant for low-cost point-of-care applications, especially those involving multiple tests and field studies. While nanohole arrays have been applied to many sensing applications, and their suitability to device integration is well established, this is the first demonstration of a fully integrated nanohole array-based sensing device.

Large-Scale Integration of Solid-State Microfluidic Valves With No Moving Parts

National Research Council Canada - National Science Library

Mastangelo, Carlos H; Gianchandani, Yogesh B; Frechet, J. M

2005-01-01

This research concerns the development of a new kind of revolutionary design, solid-state microvalves that will permit the realization of complex microfluidic systems with arrays of hundreds of flow-control devices...

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…

Rapid mask prototyping for microfluidics.

Science.gov (United States)

Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

2016-03-01

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

Recent Developments in Optical Detection Technologies in Lab-on-a-Chip Devices for Biosensing Applications

Directory of Open Access Journals (Sweden)

Nuno Miguel Matos Pires

2014-08-01

Full Text Available The field of microfluidics has yet to develop practical devices that provide real clinical value. One of the main reasons for this is the difficulty in realizing low-cost, sensitive, reproducible, and portable analyte detection microfluidic systems. Previous research has addressed two main approaches for the detection technologies in lab-on-a-chip devices: (a study of the compatibility of conventional instrumentation with microfluidic structures, and (b integration of innovative sensors contained within the microfluidic system. Despite the recent advances in electrochemical and mechanical based sensors, their drawbacks pose important challenges to their application in disposable microfluidic devices. Instead, optical detection remains an attractive solution for lab-on-a-chip devices, because of the ubiquity of the optical methods in the laboratory. Besides, robust and cost-effective devices for use in the field can be realized by integrating proper optical detection technologies on chips. This review examines the recent developments in detection technologies applied to microfluidic biosensors, especially addressing several optical methods, including fluorescence, chemiluminescence, absorbance and surface plasmon resonance.

A multilayered integrated sensor for three-dimensional, micro total analysis systems

International Nuclear Information System (INIS)

Xiao, Jing; Song, Fuchuan; Seo, Sang-Woo

2013-01-01

This paper presents a layer-by-layer integration approach of different functional devices and demonstrates a heterogeneously integrated optical sensor featuring a micro-ring resonator and a high-speed thin-film InGaAs-based photodetector co-integrated with a microfluidic droplet generation device. A thin optical device structure allows a seamless integration with other polymer-based devices on a silicon platform. The integrated sensor successfully demonstrates its transient measurement capability of two-phase liquid flow in a microfluidic droplet generation device. The proposed approach represents an important step toward fully integrated micro total analysis systems. (paper)

Various on-chip sensors with microfluidics for biological applications.

Science.gov (United States)

Lee, Hun; Xu, Linfeng; Koh, Domin; Nyayapathi, Nikhila; Oh, Kwang W

2014-09-12

In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV) and greater depth of field (DOF). As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC) testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.

Characterization of Reagent Pencils for Deposition of Reagents onto Paper-Based Microfluidic Devices

Directory of Open Access Journals (Sweden)

Cheyenne H. Liu

2017-08-01

Full Text Available Reagent pencils allow for solvent-free deposition of reagents onto paper-based microfluidic devices. The pencils are portable, easy to use, extend the shelf-life of reagents, and offer a platform for customizing diagnostic devices at the point of care. In this work, reagent pencils were characterized by measuring the wear resistance of pencil cores made from polyethylene glycols (PEGs with different molecular weights and incorporating various concentrations of three different reagents using a standard pin abrasion test, as well as by measuring the efficiency of reagent delivery from the pencils to the test zones of paper-based microfluidic devices using absorption spectroscopy and digital image colorimetry. The molecular weight of the PEG, concentration of the reagent, and the molecular weight of the reagent were all found to have an inverse correlation with the wear of the pencil cores, but the amount of reagent delivered to the test zone of a device correlated most strongly with the concentration of the reagent in the pencil core. Up to 49% of the total reagent deposited on a device with a pencil was released into the test zone, compared to 58% for reagents deposited from a solution. The results suggest that reagent pencils can be prepared for a variety of reagents using PEGs with molecular weights in the range of 2000 to 6000 g/mol.

A microfluidic device for open loop stripping of volatile organic compounds.

Science.gov (United States)

Cvetković, Benjamin Z; Dittrich, Petra S

2013-03-01

The detection of volatile organic compounds is of great importance for assessing the quality of water. In this contribution, we describe a miniaturized stripping device that allows fast online detection of organic solvents in water. The core component is a glass microfluidic chip that facilitates the creation of an annular-flowing stream of water and nitrogen gas. Volatile compounds are transferred efficiently from the water into the gas phase along the microfluidic pathway at room temperature within less than 5 s. Before exiting the microchip, the liquid phase is separated from the enriched gas phase by incorporating side capillaries through which the hydrophilic water phase is withdrawn. The gas phase is conveniently collected at the outlet reservoir by tubing. Finally, a semiconductor gas sensor analyzes the concentration of (volatile) organic compounds in the nitrogen gas. The operation and use of the stripping device is demonstrated for the organic solvents THF, 1-propanol, toluene, ethylbenzene, benzaldehyde, and methanol. The mobile, inexpensive, and continuously operating system with liquid flow rates in the low range of microliters per minute can be connected to other detectors or implemented in chemical production line for process control.

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.

Polymer microfluidic device replacing fluids using only capillary force

Science.gov (United States)

Chung, Kwang Hyo; Lee, Dae Sik; Yang, Haesik; Kim, Sung Jin; Pyo, Hyun Bong

2005-02-01

A novel polymer microfluidic device for self-wash using only capillary force is presented. A liquid filled in a reaction chamber is replaced by another liquid with no external actuation. All the fluidic actuations in the device is pre-programmed about time and sequence, and accomplished by capillary force naturally. Careful design is necessary for exact actions. The fluidic conduits were designed by the newly derived theoretical equations about the capillary stop pressure and flow time. Simulations using CFD-ACE+ were conducted to check the validity of theory and the performance of the chip. These analytic results were consistent with experimental ones. The chip was made of polymers for the purpose of single use and low price. It was fabricated by sealing the hot-embossed PMMA substrate with a PET film. For simpler fabrication, the chip was of a single height. The embossing master was produced from a nickel-electroplating on a SU8-patterned Ni-plate followed by CMP. The contact angles of liquids on substrates were manipulated through the mixing of surfactants, and the temporal variations were monitored for a more exact design. The real actuation steps in experiment revealed the stable performance of selfwash, and coincided well with the designed ones. The presented microfluidic method can be applicable to other LOCs of special purposes through simple modification. For example, array or serial types would be possible for multiple selfwashes.

Ice matrix in reconfigurable microfluidic systems

Energy Technology Data Exchange (ETDEWEB)

Bossi, A M [Department of Biotechnology, University of Verona, Strada Le Grazie 15, I-37134, Verona (Italy); Vareijka, M; Piletska, E V; Turner, A P F; Piletsky, S A [Cranfield Health, Cranfield University, Vincent Building B52, Cranfield, Bedfordshire, MK43 0AL (United Kingdom); Meglinski, I [Department of Physics, University of Otago, PO Box 56, Dunedin, 9054 (New Zealand)

2013-07-01

Microfluidic devices find many applications in biotechnologies. Here, we introduce a flexible and biocompatible microfluidic ice-based platform with tunable parameters and configuration of microfluidic patterns that can be changed multiple times during experiments. Freezing and melting of cavities, channels and complex relief structures created and maintained in the bulk of ice by continuous scanning of an infrared laser beam are used as a valve action in microfluidic systems. We demonstrate that pre-concentration of samples and transport of ions and dyes through the open channels created can be achieved in ice microfluidic patterns by IR laser-assisted zone melting. The proposed approach can be useful for performing separation and sensing processes in flexible reconfigurable microfluidic devices. (paper)

Ice matrix in reconfigurable microfluidic systems

International Nuclear Information System (INIS)

Bossi, A M; Vareijka, M; Piletska, E V; Turner, A P F; Piletsky, S A; Meglinski, I

2013-01-01

Microfluidic devices find many applications in biotechnologies. Here, we introduce a flexible and biocompatible microfluidic ice-based platform with tunable parameters and configuration of microfluidic patterns that can be changed multiple times during experiments. Freezing and melting of cavities, channels and complex relief structures created and maintained in the bulk of ice by continuous scanning of an infrared laser beam are used as a valve action in microfluidic systems. We demonstrate that pre-concentration of samples and transport of ions and dyes through the open channels created can be achieved in ice microfluidic patterns by IR laser-assisted zone melting. The proposed approach can be useful for performing separation and sensing processes in flexible reconfigurable microfluidic devices. (paper)

Ice matrix in reconfigurable microfluidic systems

Science.gov (United States)

Bossi, A. M.; Vareijka, M.; Piletska, E. V.; Turner, A. P. F.; Meglinski, I.; Piletsky, S. A.

2013-07-01

Microfluidic devices find many applications in biotechnologies. Here, we introduce a flexible and biocompatible microfluidic ice-based platform with tunable parameters and configuration of microfluidic patterns that can be changed multiple times during experiments. Freezing and melting of cavities, channels and complex relief structures created and maintained in the bulk of ice by continuous scanning of an infrared laser beam are used as a valve action in microfluidic systems. We demonstrate that pre-concentration of samples and transport of ions and dyes through the open channels created can be achieved in ice microfluidic patterns by IR laser-assisted zone melting. The proposed approach can be useful for performing separation and sensing processes in flexible reconfigurable microfluidic devices.

Microfluidic PMMA interfaces for rectangular glass capillaries

International Nuclear Information System (INIS)

Evander, Mikael; Tenje, Maria

2014-01-01

We present the design and fabrication of a polymeric capillary fluidic interface fabricated by micro-milling. The design enables the use of glass capillaries with any kind of cross-section in complex microfluidic setups. We demonstrate two different designs of the interface; a double-inlet interface for hydrodynamic focusing and a capillary interface with integrated pneumatic valves. Both capillary interfaces are presented together with examples of practical applications. This communication shows the design optimization and presents details of the fabrication process. The capillary interface opens up for the use of complex microfluidic systems in single-use glass capillaries. They also enable simple fabrication of glass/polymer hybrid devices that can be beneficial in many research fields where a pure polymer chip negatively affects the device's performance, e.g. acoustofluidics. (technical note)

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.

Microfluidic very large-scale integration for biochips: Technology, testing and fault-tolerant design

DEFF Research Database (Denmark)

Araci, Ismail Emre; Pop, Paul; Chakrabarty, Krishnendu

2015-01-01

of this paper is on continuous-flow biochips, where the basic building block is a microvalve. By combining these microvalves, more complex units such as mixers, switches, multiplexers can be built, hence the name of the technology, “microfluidic Very Large-Scale Integration” (mVLSI). A roadblock......Microfluidic biochips are replacing the conventional biochemical analyzers by integrating all the necessary functions for biochemical analysis using microfluidics. Biochips are used in many application areas, such as, in vitro diagnostics, drug discovery, biotech and ecology. The focus...... presents the state-of-the-art in the mVLSI platforms and emerging research challenges in the area of continuous-flow microfluidics, focusing on testing techniques and fault-tolerant design....

Two-ply channels for faster wicking in paper-based microfluidic devices.

Science.gov (United States)

Camplisson, Conor K; Schilling, Kevin M; Pedrotti, William L; Stone, Howard A; Martinez, Andres W

2015-12-07

This article describes the development of porous two-ply channels for paper-based microfluidic devices that wick fluids significantly faster than conventional, porous, single-ply channels. The two-ply channels were made by stacking two single-ply channels on top of each other and were fabricated entirely out of paper, wax and toner using two commercially available printers, a convection oven and a thermal laminator. The wicking in paper-based channels was studied and modeled using a modified Lucas-Washburn equation to account for the effect of evaporation, and a paper-based titration device incorporating two-ply channels was demonstrated.

A versatile technology platform for microfluidic handling systems, part II : channel design and technology

NARCIS (Netherlands)

Groenesteijn, Jarno; de Boer, Meint J.; Lötters, Joost C.; Wiegerink, Remco J.

2017-01-01

Microfluidic devices often require channels of a specific size and shape. These devices are then made in a fabrication process that is often specialized to produce only those (and very similar) channels. As a result, devices requiring channels of different size and shape cannot easily be integrated

Research Progress of Microfluidic Chips Preparation and its Optical Element

Directory of Open Access Journals (Sweden)

Feng WANG

2014-03-01

Full Text Available Microfluidic technology is the emerging technologies in researching fluid channel and related applications in the micro and nano-scale space. Microfluidic chip is a new miniaturized rapid analysis platform by microfluidic technology, it has many characteristics such as liquid flow control, minimal reagent consumption, rapid analysis, which is widely used in physics, chemistry, biology, and engineering science and other fields, it has strong interdisciplinary. This paper mainly discusses research progress of materials used for microfluidic chips and the devices based on microfluidic technology, including microfluidic chip, microfluidic optical devices, microfluidic laser preparation, microfluidic chip applications, focusing on the quasi-molecular laser processing technology and femtosecond laser processing technology in the microfluidic devices preparation, and make development prospects for it.

Design Considerations for Integration of Terahertz Time-Domain Spectroscopy in Microfluidic Platforms

Directory of Open Access Journals (Sweden)

Rasha Al-Hujazy

2018-03-01

Full Text Available Microfluidic platforms have received much attention in recent years. In particular, there is interest in combining spectroscopy with microfluidic platforms. This work investigates the integration of microfluidic platforms and terahertz time-domain spectroscopy (THz-TDS systems. A semiclassical computational model is used to simulate the emission of THz radiation from a GaAs photoconductive THz emitter. This model incorporates white noise with increasing noise amplitude (corresponding to decreasing dynamic range values. White noise is selected over other noise due to its contributions in THz-TDS systems. The results from this semiclassical computational model, in combination with defined sample thicknesses, can provide the maximum measurable absorption coefficient for a microfluidic-based THz-TDS system. The maximum measurable frequencies for such systems can be extracted through the relationship between the maximum measurable absorption coefficient and the absorption coefficient for representative biofluids. The sample thickness of the microfluidic platform and the dynamic range of the THz-TDS system play a role in defining the maximum measurable frequency for microfluidic-based THz-TDS systems. The results of this work serve as a design tool for the development of such systems.

Cost Effective Paper-Based Colorimetric Microfluidic Devices and Mobile Phone Camera Readers for the Classroom

Science.gov (United States)

Koesdjojo, Myra T.; Pengpumkiat, Sumate; Wu, Yuanyuan; Boonloed, Anukul; Huynh, Daniel; Remcho, Thomas P.; Remcho, Vincent T.

2015-01-01

We have developed a simple and direct method to fabricate paper-based microfluidic devices that can be used for a wide range of colorimetric assay applications. With these devices, assays can be performed within minutes to allow for quantitative colorimetric analysis by use of a widely accessible iPhone camera and an RGB color reader application…

A microfluidic device to study neuronal and motor responses to acute chemical stimuli in zebrafish.

Science.gov (United States)

Candelier, Raphaël; Murmu, Meena Sriti; Romano, Sebastián Alejo; Jouary, Adrien; Debrégeas, Georges; Sumbre, Germán

2015-07-21

Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50-500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception.

Various On-Chip Sensors with Microfluidics for Biological Applications

Directory of Open Access Journals (Sweden)

Hun Lee

2014-09-01

Full Text Available In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR and surface-enhanced Raman scattering (SERS to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV and greater depth of field (DOF. As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.

Continuous nucleus extraction by optically-induced cell lysis on a batch-type microfluidic platform.

Science.gov (United States)

Huang, Shih-Hsuan; Hung, Lien-Yu; Lee, Gwo-Bin

2016-04-21

The extraction of a cell's nucleus is an essential technique required for a number of procedures, such as disease diagnosis, genetic replication, and animal cloning. However, existing nucleus extraction techniques are relatively inefficient and labor-intensive. Therefore, this study presents an innovative, microfluidics-based approach featuring optically-induced cell lysis (OICL) for nucleus extraction and collection in an automatic format. In comparison to previous micro-devices designed for nucleus extraction, the new OICL device designed herein is superior in terms of flexibility, selectivity, and efficiency. To facilitate this OICL module for continuous nucleus extraction, we further integrated an optically-induced dielectrophoresis (ODEP) module with the OICL device within the microfluidic chip. This on-chip integration circumvents the need for highly trained personnel and expensive, cumbersome equipment. Specifically, this microfluidic system automates four steps by 1) automatically focusing and transporting cells, 2) releasing the nuclei on the OICL module, 3) isolating the nuclei on the ODEP module, and 4) collecting the nuclei in the outlet chamber. The efficiency of cell membrane lysis and the ODEP nucleus separation was measured to be 78.04 ± 5.70% and 80.90 ± 5.98%, respectively, leading to an overall nucleus extraction efficiency of 58.21 ± 2.21%. These results demonstrate that this microfluidics-based system can successfully perform nucleus extraction, and the integrated platform is therefore promising in cell fusion technology with the goal of achieving genetic replication, or even animal cloning, in the near future.

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)

Printed microfluidic filter for heparinized blood.

Science.gov (United States)

Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

2017-05-01

A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8  μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

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.

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.

Laser-induced heating integrated with a microfluidic platform for real-time DNA replication and detection

Science.gov (United States)

Hung, Min-Sheng; Ho, Chia-Chin; Chen, Chih-Pin

2016-08-01

This study developed a microfluidic platform for replicating and detecting DNA in real time by integrating a laser and a microfluidic device composed of polydimethylsiloxane. The design of the microchannels consisted of a laser-heating area and a detection area. An infrared laser was used as the heating source for DNA replication, and the laser power was adjusted to heat the solutions directly. In addition, strong biotin-avidin binding was used to capture and detect the replicated products. The biotin on one end was bound to avidin and anchored to the surface of the microchannels, whereas the biotin on the other end was bound to the quantum dots (Qdots). The results showed that the fluorescent intensity of the Qdots bound to the replicated products in the detection area increased with the number of thermal cycles created by the laser. When the number of thermal cycles was ≥10, the fluorescent intensity of the Qdots was directly detectable on the surface of the microchannels. The proposed method is more sensitive than detection methods entailing gel electrophoresis.

Acoustofluidics: theory and simulation of radiation forces at ultrasound resonances in microfluidic devices

DEFF Research Database (Denmark)

Barnkob, Rune; Bruus, Henrik

2009-01-01

Theoretical analysis is combined with numerical simulations to optimize designs and functionalities of acoustofluidic devices, i.e. microfluidic devices in which ultrasound waves are used to anipulate biological particles. The resonance frequencies and corresponding modes of the acoustic fields...... are calculated for various specific geometries of glass/silicon chips containing water-filled microchannels. A special emphasis is put on taking the surrounding glass/silicon material into account, thus going beyond the traditional transverse half-wavelength picture. For the resonance frequencies, where...

Fabricating and Characterizing the Microfluidic Solid Phase Extraction Module Coupling with Integrated ESI Emitters

Directory of Open Access Journals (Sweden)

Hangbin Tang

2018-05-01

Full Text Available Microfluidic chips coupling with mass spectrometry (MS will be of great significance to the development of relevant instruments involving chemical and bio-chemical analysis, drug detection, food and environmental applications and so on. In our previous works, we proposed two types of microfluidic electrospray ionization (ESI chip coupling with MS: the two-phase flow focusing (FF ESI microfluidic chip and the corner-integrated ESI emitter, respectively. However the pretreatment module integrated with these ESI emitters is still a challenging problem. In this paper, we concentrated on integrating the solid phase micro-extraction (SPME module with our previous proposed on-chip ESI emitters; the fabrication processes of such SPME module are fully compatible with our previous proposed ESI emitters based on the multi-layer soft lithography. We optimized the structure of the integrated chip and characterized its performance using standard samples. Furthermore, we verified its abilities of salt removal, extraction of multiple analytes and separation through on-chip elution using mimic biological urine spiked with different drugs. The results indicated that our proposed integrated module with ESI emitters is practical and effective for real biological sample pretreatment and MS detection.

Fabrication of microfluidic architectures for optimal flow rate and concentration measurement for lab on chip application

Science.gov (United States)

Adam, Tijjani; Hashim, U.

2017-03-01

Optimum flow in micro channel for sensing purpose is challenging. In this study, The optimizations of the fluid sample flows are made through the design and characterization of the novel microfluidics' architectures to achieve the optimal flow rate in the micro channels. The biocompatibility of the Polydimetylsiloxane (Sylgard 184 silicon elastomer) polymer used to fabricate the device offers avenue for the device to be implemented as the universal fluidic delivery system for bio-molecules sensing in various bio-medical applications. The study uses the following methodological approaches, designing a novel microfluidics' architectures by integrating the devices on a single 4 inches silicon substrate, fabricating the designed microfluidic devices using low-cost solution soft lithography technique, characterizing and validating the flow throughput of urine samples in the micro channels by generating pressure gradients through the devices' inlets. The characterization on the urine samples flow in the micro channels have witnessed the constant flow throughout the devices.

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 ...

Epoxy Chip-in-Carrier Integration and Screen-Printed Metalization for Multichannel Microfluidic Lab-on-CMOS Microsystems.

Science.gov (United States)

Li, Lin; Yin, Heyu; Mason, Andrew J

2018-04-01

The integration of biosensors, microfluidics, and CMOS instrumentation provides a compact lab-on-CMOS microsystem well suited for high throughput measurement. This paper describes a new epoxy chip-in-carrier integration process and two planar metalization techniques for lab-on-CMOS that enable on-CMOS electrochemical measurement with multichannel microfluidics. Several design approaches with different fabrication steps and materials were experimentally analyzed to identify an ideal process that can achieve desired capability with high yield and low material and tool cost. On-chip electrochemical measurements of the integrated assembly were performed to verify the functionality of the chip-in-carrier packaging and its capability for microfluidic integration. The newly developed CMOS-compatible epoxy chip-in-carrier process paves the way for full implementation of many lab-on-CMOS applications with CMOS ICs as core electronic instruments.

Usability and Applicability of Microfluidic Cell Culture Systems

DEFF Research Database (Denmark)

Hemmingsen, Mette

possibilities for, for example, precise control of the chemical environment, 3D cultures, controlled co-culture of different cell types or automated, individual control of up to 96 cell culture chambers in one integrated system. Despite the great new opportunities to perform novel experimental designs......Microfluidic cell culture has been a research area with great attention the last decade due to its potential to mimic the in vivo cellular environment more closely compared to what is possible by conventional cell culture methods. Many exciting and complex devices have been presented providing......, these devices still lack general implementation into biological research laboratories. In this project, the usability and applicability of microfluidic cell culture systems have been investigated. The tested systems display good properties regarding optics and compatibility with standard laboratory equipment...

Liquid crystal droplet formation and anchoring dynamics in a microfluidic device

Science.gov (United States)

Steinhaus, Ben; Shen, Amy; Feng, James; Link, Darren

2004-11-01

Liquid crystal drops dispersed in a continuous phase of silicon oil are generated with a narrow distribution in droplet size in microfluidic devices both above and below the nematic to isotropic transition temperature. For these two cases, we observe not only the different LC droplet generation and coalescence dynamics, but also distinct droplet morphology. Our experiments show that the nematic liquid crystalline order is important for the LC droplet formation and anchoring dynamics.

Ultrasensitive microfluidic solid-phase ELISA using an actuatable microwell-patterned PDMS chip.

Science.gov (United States)

Wang, Tanyu; Zhang, Mohan; Dreher, Dakota D; Zeng, Yong

2013-11-07

Quantitative detection of low abundance proteins is of significant interest for biological and clinical applications. Here we report an integrated microfluidic solid-phase ELISA platform for rapid and ultrasensitive detection of proteins with a wide dynamic range. Compared to the existing microfluidic devices that perform affinity capture and enzyme-based optical detection in a constant channel volume, the key novelty of our design is two-fold. First, our system integrates a microwell-patterned assay chamber that can be pneumatically actuated to significantly reduce the volume of chemifluorescent reaction, markedly improving the sensitivity and speed of ELISA. Second, monolithic integration of on-chip pumps and the actuatable assay chamber allow programmable fluid delivery and effective mixing for rapid and sensitive immunoassays. Ultrasensitive microfluidic ELISA was demonstrated for insulin-like growth factor 1 receptor (IGF-1R) across at least five orders of magnitude with an extremely low detection limit of 21.8 aM. The microwell-based solid-phase ELISA strategy provides an expandable platform for developing the next-generation microfluidic immunoassay systems that integrate and automate digital and analog measurements to further improve the sensitivity, dynamic ranges, and reproducibility of proteomic analysis.

Advances in Microfluidic Platforms for Analyzing and Regulating Human Pluripotent Stem Cells

Science.gov (United States)

Qian, Tongcheng; Shusta, Eric V.; Palecek, Sean P.

2015-01-01

Microfluidic devices employ submillimeter length scale control of flow to achieve high-resolution spatial and temporal control over the microenvironment, providing powerful tools to elucidate mechanisms of human pluripotent stem cell (hPSC) regulation and to elicit desired hPSC fates. In addition, microfluidics allow control of paracrine and juxtracrine signaling, thereby enabling fabrication of microphysiological systems comprised of multiple cell types organized into organs-on-a-chip. Microfluidic cell culture systems can also be integrated with actuators and sensors, permitting construction of high-density arrays of cell-based biosensors for screening applications. This review describes recent advances in using microfluidics to understand mechanisms by which the microenvironment regulates hPSC fates and applications of microfluidics to realize the potential of hPSCs for in vitro modeling and screening applications. PMID:26313850

Real-time isothermal RNA amplification of toxic marine microalgae using preserved reagents on an integrated microfluidic platform.

Science.gov (United States)

Tsaloglou, Maria-Nefeli; Laouenan, Florian; Loukas, Christos-Moritz; Monsalve, Lisandro Gabriel; Thanner, Christine; Morgan, Hywel; Ruano-López, Jesus M; Mowlem, Matthew C

2013-01-21

Quantitation of specific RNA sequences is a useful technique in marine biology that can elucidate cell abundance, speciation and viability, especially for early detection of harmful algal blooms. We are thus developing an integrated microfluidic system for cell concentration and lysis, RNA extraction/purification and quantitative RNA detection for environmental applications. The portable system is based on a microfluidic cartridge, or "lab-card", using a low-cost injection moulded device, with a laminated lid. Here we present real-time isothermal RNA amplification using reagent master-mixes preserved on-chip in a gel at 4 °C for up to eight months. We demonstrate quantitation by reference to an internal control in a competitive assay with 500 cell equivalents of the toxic microalga Karenia brevis. Annealing of primers, amplification at 41 °C and real-time fluorescence detection of the internal control and target using sequence-specific molecular beacons were all performed on-chip.

Implementation of Synchronous Micromotor in Developing Integrated Microfluidic Systems

Directory of Open Access Journals (Sweden)

Ala'aldeen Al-Halhouli

2014-07-01

Full Text Available This paper introduces the synchronous micromotor concept and presents new investigations on its application as an integrated driving mechanism in microfluidic systems. A spiral channel viscous micropump and a microstirrer are considered and tested as examples to verify the concept. The fabrication technology of such integrated systems is based on UV depth lithography, electroplating and soft lithography. The synchronous micromotor consists of a stator including double layer coils, and a rotor disk containing alternate permanent magnets. The coils are distributed evenly around the stator and arranged in three phases. The phases are excited by sinusoidal currents with a corresponding phase shift resulting in a rotating magnetic field. Regarding the spiral channel viscous micropump, a spiral disk was fixed onto the rotor disk and run at different rotational speeds. Tests showed very promising results, with a flow rate up to 1023 µL·min−1 at a motor rotational speed of 4500 rpm. Furthermore, for the application of a microstirred-tank bioreactor, the rotor disk design was modified to work as a stirrer. The performance of the developed microbioreactor was tested over a time period of approximately 10 h under constant stirring. Tests demonstrated the successful cultivation of S. cerevisiae through the integration of the microstirrer in a microbioreactor system. These systems prove that synchronous micromotors are well suited to serve as integrated driving mechanisms of active microfluidic components.

Development of microfluidic devices for biomedical applications of synchrotron radiation infrared microspectroscopy

OpenAIRE

Birarda, Giovanni

2011-01-01

2009/2010 ABSTRACT DEVELOPMENT OF MICROFLUIDIC DEVICES FOR BIOMEDICAL APPLICATIONS OF SYNCHROTRON RADIATION INFRARED MICROSPECTROSCOPY by Birarda Giovanni The detection and measurement of biological processes in a complex living system is a discipline at the edge of Physics, Biology, and Engineering, with major scientific challenges, new technological applications and a great potential impact on dissection of phenomena occurring at tissue, cell, and sub cellular level. The ...

A microfluidic circulatory system integrated with capillary-assisted pressure sensors.

Science.gov (United States)

Chen, Yangfan; Chan, Ho Nam; Michael, Sean A; Shen, Yusheng; Chen, Yin; Tian, Qian; Huang, Lu; Wu, Hongkai

2017-02-14

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and "body-on-a-chip" and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns.

A microfluidic device for the automated derivatization of free fatty acids to fatty acid methyl esters.

Science.gov (United States)

Duong, Cindy T; Roper, Michael G

2012-02-21

Free fatty acid (FFA) compositions are examined in feedstock for biodiesel production, as source-specific markers in soil, and because of their role in cellular signaling. However, sample preparation of FFAs for gas chromatography-mass spectrometry (GC-MS) analysis can be time and labor intensive. Therefore, to increase sample preparation throughput, a glass microfluidic device was developed to automate derivatization of FFAs to fatty acid methyl esters (FAMEs). FFAs were delivered to one input of the device and methanolic-HCl was delivered to a second input. FAME products were produced as the reagents traversed a 29 μL reaction channel held at 55 °C. A Design of Experiment protocol was used to determine the combination of derivatization time (T(der)) and ratio of methanolic-HCl:FFA (R(der)) that maximized the derivatization efficiencies of tridecanoic acid and stearic acid to their methyl ester forms. The combination of T(der) = 0.8 min and R(der) = 4.9 that produced optimal derivatization conditions for both FFAs within a 5 min total sample preparation time was determined. This combination of T(der) and R(der) was used to derivatize 12 FFAs with a range of derivatization efficiencies from 18% to 93% with efficiencies of 61% for tridecanoic acid and 84% for stearic acid. As compared to a conventional macroscale derivatization of FFA to FAME, the microfluidic device decreased the volume of methanolic-HCl and FFA by 20- and 1300-fold, respectively. The developed microfluidic device can be used for automated preparation of FAMEs to analyze the FFA compositions of volume-limited samples.

Design and simulation of a microfluidic device for acoustic cell separation.

Science.gov (United States)

Shamloo, Amir; Boodaghi, Miad

2018-03-01

Experimental acoustic cell separation methods have been widely used to perform separation for different types of blood cells. However, numerical simulation of acoustic cell separation has not gained enough attention and needs further investigation since by using numerical methods, it is possible to optimize different parameters involved in the design of an acoustic device and calculate particle trajectories in a simple and low cost manner before spending time and effort for fabricating these devices. In this study, we present a comprehensive finite element-based simulation of acoustic separation of platelets, red blood cells and white blood cells, using standing surface acoustic waves (SSAWs). A microfluidic channel with three inlets, including the middle inlet for sheath flow and two symmetrical tilted angle inlets for the cells were used to drive the cells through the channel. Two interdigital transducers were also considered in this device and by implementing an alternating voltage to the transducers, an acoustic field was created which can exert the acoustic radiation force to the cells. Since this force is dependent to the size of the cells, the cells are pushed towards the midline of the channel with different path lines. Particle trajectories for different cells were obtained and compared with a theoretical equation. Two types of separations were observed as a result of varying the amplitude of the acoustic field. In the first mode of separation, white blood cells were sorted out through the middle outlet and in the second mode of separation, platelets were sorted out through the side outlets. Depending on the clinical needs and by using the studied microfluidic device, each of these modes can be applied to separate the desired cells. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

MICROFLUIDIC COMPONENT CAPABLE OF SELF-SEALING

DEFF Research Database (Denmark)

2009-01-01

A microfluidic component (100) for building a microfluidic system is provided. The microfluidic component (100) can be mounted on a microf luidic breadboard (202) in a manner that allows it to be connected to other microfluidic components (204, 206) without the requirement of additional devices....... The microfluidic component (100) comprises at least one flexible tube piece (102) for transporting a fluid. The microfluidic component (100) also comprises means for applying and maintaining pressure (104) between the flexible tube piece (102) and a tube piece (208, 210) housed in another microfluidic component...

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.

“Connecting worlds – a view on microfluidics for a wider application”

DEFF Research Database (Denmark)

Fernandes, Ana C.; Gernaey, Krist V.; Krühne, Ulrich

2018-01-01

acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors...... of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient’s skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However...... and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, “plug and play” approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates...

Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

Science.gov (United States)

Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

2017-09-01

The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

Two dimension (2-D) graphene-based nanomaterials as signal amplification elements in electrochemical microfluidic immune-devices: Recent advances

Energy Technology Data Exchange (ETDEWEB)

Hasanzadeh, Mohammad, E-mail: mhmmd_hasanzadeh@yahoo.com [Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 51664 (Iran, Islamic Republic of); Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz 51664 (Iran, Islamic Republic of); Shadjou, Nasrin [Department of Nanochemistry, Nano Technology Center and Faculty of Chemistry, Urmia University, Urmia (Iran, Islamic Republic of); Mokhtarzadeh, Ahad [School of Medicine, Gonabad University of Medical Sciences, Gonabad (Iran, Islamic Republic of); Department of Biotechnology, Higher Education Institute of Rab-Rashid, Tabriz (Iran, Islamic Republic of); Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Ramezani, Mohammad [Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

2016-11-01

Graphene is a 2-D carbon nanomaterial with many distinctive properties that are electrochemically beneficial, such as large surface-to-volume ratio, lowered power usage, high conductivity and electron mobility. Graphene-based electrochemical immune-devices have recently gained much importance for detecting antigens and biomarkers responsible for cancer diagnosis. This review describes fabrication and chemical modification of the surfaces of graphene for immunesensing applications. We also present a comprehensive overview of current developments and key issues in the determination of some biological molecules with particular emphasis on evaluating the models. This review focuses mostly on new developments in the last 5 years in development of chip architecture and integration, different sensing modes that can be used in conjunction with microfluidics, and new applications that have emerged or have been demonstrated; it also aims to point out where future research can be directed to in these areas. - Highlights: • Graphene-based immune-devices have been used for biomedical testing. • Two dimension (2-D) graphene-based immune-devices were discussed. • Current state-of-the-art in graphene-based immune-devices was reflected.

Two dimension (2-D) graphene-based nanomaterials as signal amplification elements in electrochemical microfluidic immune-devices: Recent advances

International Nuclear Information System (INIS)

Hasanzadeh, Mohammad; Shadjou, Nasrin; Mokhtarzadeh, Ahad; Ramezani, Mohammad

2016-01-01

Graphene is a 2-D carbon nanomaterial with many distinctive properties that are electrochemically beneficial, such as large surface-to-volume ratio, lowered power usage, high conductivity and electron mobility. Graphene-based electrochemical immune-devices have recently gained much importance for detecting antigens and biomarkers responsible for cancer diagnosis. This review describes fabrication and chemical modification of the surfaces of graphene for immunesensing applications. We also present a comprehensive overview of current developments and key issues in the determination of some biological molecules with particular emphasis on evaluating the models. This review focuses mostly on new developments in the last 5 years in development of chip architecture and integration, different sensing modes that can be used in conjunction with microfluidics, and new applications that have emerged or have been demonstrated; it also aims to point out where future research can be directed to in these areas. - Highlights: • Graphene-based immune-devices have been used for biomedical testing. • Two dimension (2-D) graphene-based immune-devices were discussed. • Current state-of-the-art in graphene-based immune-devices was reflected.

Dissolved oxygen sensing using organometallic dyes deposited within a microfluidic environment

Science.gov (United States)

Chen, Q. L.; Ho, H. P.; Jin, L.; Chu, B. W.-K.; Li, M. J.; Yam, V. W.-W.

2008-02-01

This work primarily aims to integrate dissolved oxygen sensing capability with a microfluidic platform containing arrays of micro bio-reactors or bio-activity indicators. The measurement of oxygen concentration is of significance for a variety of bio-related applications such as cell culture and gene expression. Optical oxygen sensors based on luminescence quenching are gaining much interest in light of their low power consumption, quick response and high analyte sensitivity in comparison to similar oxygen sensing devices. In our microfluidic oxygen sensor device, a thin layer of oxygen-sensitive luminescent organometallic dye is covalently bonded to a glass slide. Micro flow channels are formed on the glass slide using patterned PDMS (Polydimethylsiloxane). Dissolved oxygen sensing is then performed by directing an optical excitation probe beam to the area of interest within the microfluidic channel. The covalent bonding approach for sensor layer formation offers many distinct advantages over the physical entrapment method including minimizing dye leaching, ensuring good stability and fabrication simplicity. Experimental results confirm the feasibility of the device.

"Connecting worlds - a view on microfluidics for a wider application".

Science.gov (United States)

Fernandes, Ana C; Gernaey, Krist V; Krühne, Ulrich

From its birth, microfluidics has been referenced as a revolutionary technology and the solution to long standing technological and sociological issues, such as detection of dilute compounds and personalized healthcare. Microfluidics has for example been envisioned as: (1) being capable of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient's skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However, the current state of microfluidics, although technologically advanced, has so far failed to reach the originally promised widespread use. In this paper, some of the aspects are identified and discussed that have prevented microfluidics from reaching its full potential, especially in the chemical engineering and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, "plug and play" approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates, reactions and operation conditions, and other microfluidic systems is indeed of surmount importance and current academic and industrial approaches to modular microfluidics are presented. Furthermore, two views on the commercialization of plug-and-play microfluidics systems, leading towards improved acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors in microfluidics. The proposed guidelines are then applied for the development of two different example platforms, and to three examples taken from literature. With this work, we

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...

An integrated microfluidic analysis microsystems with bacterial capture enrichment and in-situ impedance detection

Science.gov (United States)

Liu, Hai-Tao; Wen, Zhi-Yu; Xu, Yi; Shang, Zheng-Guo; Peng, Jin-Lan; Tian, Peng

2017-09-01

In this paper, an integrated microfluidic analysis microsystems with bacterial capture enrichment and in-situ impedance detection was purposed based on microfluidic chips dielectrophoresis technique and electrochemical impedance detection principle. The microsystems include microfluidic chip, main control module, and drive and control module, and signal detection and processing modulet and result display unit. The main control module produce the work sequence of impedance detection system parts and achieve data communication functions, the drive and control circuit generate AC signal which amplitude and frequency adjustable, and it was applied on the foodborne pathogens impedance analysis microsystems to realize the capture enrichment and impedance detection. The signal detection and processing circuit translate the current signal into impendence of bacteria, and transfer to computer, the last detection result is displayed on the computer. The experiment sample was prepared by adding Escherichia coli standard sample into chicken sample solution, and the samples were tested on the dielectrophoresis chip capture enrichment and in-situ impedance detection microsystems with micro-array electrode microfluidic chips. The experiments show that the Escherichia coli detection limit of microsystems is 5 × 104 CFU/mL and the detection time is within 6 min in the optimization of voltage detection 10 V and detection frequency 500 KHz operating conditions. The integrated microfluidic analysis microsystems laid the solid foundation for rapid real-time in-situ detection of bacteria.

Methods of making microfluidic devices

KAUST Repository

Buttner, Ulrich; Mashraei, Yousof; Agambayev, Sumeyra; Salama, Khaled N.

2017-01-01

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

Integration of polystyrene microlenses with both convex and concave profiles in a polymer-based microfluidic system

KAUST Repository

Fan, Yiqiang

2013-12-20

This paper reports a new technique of fabricating polystyrene microlenses with both convex and concave profiles that are integrated in polymer-based microfluidic system. The polystyrene microlenses, or microlens array, are fabricated using the free-surface thermal compression molding method. The laser fabricated poly(methyl methacrylate) (PMMA) sheet is used as the mold for the thermal compression molding process. With different surface treatment methods of the PMMA mold, microlenses with either convex or concave profiles could be achieved during the thermal molding process. By integrating the microlenses in the microfluidic systems, observing the flow inside the microchannels is easier. This new technique is rapid, low cost, and it does not require cleanroom facilities. Microlenses with both convex and concave profiles can be easily fabricated and integrated in microfluidic system with this technique. © 2013 Springer-Verlag Berlin Heidelberg.

Osmotic actuation for microfluidic components in point-of-care applications

KAUST Repository

Chen, Yu-Chih

2013-01-01

We present a novel design of micropumps and valves driven by osmotic force for point-of-care applications. Although there have been significant progresses in microfluidic components and control devices such as fluidic diodes, switches, resonators and digital-to-analog converters, the ultimate power source still depends on bulky off-chip components, which are expensive and cannot be easily miniaturized. For point-of-care applications, it is critical to integrate all the components in a compact size at low cost. In this work, we report two key active components actuated by osmotic mechanism for total integrated microfluidic system. For the proof of concept, we have demonstrated valve actuation, which can maintain stable ON/OFF switching operations under 125 kPa back pressure. We have also implemented an osmotic pump, which can pump a high flow rate over 30 μL/min for longer than 30 minutes. The experimental data demonstrates the possibility and potential of applying osmotic actuation in point-of-care disposable microfluidics. © 2013 IEEE.

Digital Microfluidic System with Vertical Functionality

Directory of Open Access Journals (Sweden)

Brian F. Bender

2015-11-01

Full Text Available Digital (droplet microfluidics (DµF is a powerful platform for automated lab-on-a-chip procedures, ranging from quantitative bioassays such as RT-qPCR to complete mammalian cell culturing. The simple MEMS processing protocols typically employed to fabricate DµF devices limit their functionality to two dimensions, and hence constrain the applications for which these devices can be used. This paper describes the integration of vertical functionality into a DµF platform by stacking two planar digital microfluidic devices, altering the electrode fabrication process, and incorporating channels for reversibly translating droplets between layers. Vertical droplet movement was modeled to advance the device design, and three applications that were previously unachievable using a conventional format are demonstrated: (1 solutions of calcium dichloride and sodium alginate were vertically mixed to produce a hydrogel with a radially symmetric gradient in crosslink density; (2 a calcium alginate hydrogel was formed within the through-well to create a particle sieve for filtering suspensions passed from one layer to the next; and (3 a cell spheroid formed using an on-chip hanging-drop was retrieved for use in downstream processing. The general capability of vertically delivering droplets between multiple stacked levels represents a processing innovation that increases DµF functionality and has many potential applications.

Microphysiological systems composed of human organoids in microfluidic devices: advances and challenges

Directory of Open Access Journals (Sweden)

Talita Miguel Marin

2018-05-01

Full Text Available Introduction: Models with higher predictive capacity and able to produce results at lower costs and in shorter times are needed for drug development. The microphysiological systems (MPS that cultivate human tissues in three-dimensional histoarchitecture (3D are promising alternatives for these objectives. Objective: This review work aims to address the state of the art of SMF development and illustrate the initial Brazilian experience with this technology. Method: The research and data collection covering the theme “Microphysiological Systems”, and the subtopics “Microfluidic Devices” and “3D Culture of Human Cells”, was based on electronic search in Capes Journals Portal, scientific databases Scopus, PubMed and Science Direct and with the Google Scholar search tool. Results: Among the existing microphysiological systems, those that are characterized by the culture of human tissues organized in three - dimensional histoarchitecture in microfluidic devices were recently introduced, as being the most promising ones. In addition, between the years 2000-2017, we recorded approximately increases of 12, 985 and 380 times in the number of academic publications related to the areas of Microfluidics, Organ-on-a-Chip and MPS respectively, illustrating the impact of this technology today. Conclusions: This relatively recent technology has high potential to overcome the limitations of current in vitro experimental models.

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.

Magnetic force micropiston: An integrated force/microfluidic device for the application of compressive forces in a confined environment

Science.gov (United States)

Fisher, J. K.; Kleckner, N.

2014-02-01

Cellular biology takes place inside confining spaces. For example, bacteria grow in crevices, red blood cells squeeze through capillaries, and chromosomes replicate inside the nucleus. Frequently, the extent of this confinement varies. Bacteria grow longer and divide, red blood cells move through smaller and smaller passages as they travel to capillary beds, and replication doubles the amount of DNA inside the nucleus. This increase in confinement, either due to a decrease in the available space or an increase in the amount of material contained in a constant volume, has the potential to squeeze and stress objects in ways that may lead to changes in morphology, dynamics, and ultimately biological function. Here, we describe a device developed to probe the interplay between confinement and the mechanical properties of cells and cellular structures, and forces that arise due to changes in a structure's state. In this system, the manipulation of a magnetic bead exerts a compressive force upon a target contained in the confining space of a microfluidic channel. This magnetic force microfluidic piston is constructed in such a way that we can measure (a) target compliance and changes in compliance as induced by changes in buffer, extract, or biochemical composition, (b) target expansion force generated by changes in the same parameters, and (c) the effects of compression stress on a target's structure and function. Beyond these issues, our system has general applicability to a variety of questions requiring the combination of mechanical forces, confinement, and optical imaging.

Microfabrication and Applications of Opto-Microfluidic Sensors

Science.gov (United States)

Zhang, Daiying; Men, Liqiu; Chen, Qiying

2011-01-01

A review of research activities on opto-microfluidic sensors carried out by the research groups in Canada is presented. After a brief introduction of this exciting research field, detailed discussion is focused on different techniques for the fabrication of opto-microfluidic sensors, and various applications of these devices for bioanalysis, chemical detection, and optical measurement. Our current research on femtosecond laser microfabrication of optofluidic devices is introduced and some experimental results are elaborated. The research on opto-microfluidics provides highly sensitive opto-microfluidic sensors for practical applications with significant advantages of portability, efficiency, sensitivity, versatility, and low cost. PMID:22163904

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.

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.

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.

A microfluidic device with multi-valves system to enable several simultaneous exposure tests on Caenorhabditis elegans

International Nuclear Information System (INIS)

Jung, Jaehoon; Masaru, Takeuchi; Nakajima, Masahiro; Huang, Qiang; Fukuda, Toshio

2014-01-01

In this paper, we report on a microfluidic device with a multi-valve system to conduct several exposure tests on Caenorhabditis elegans (C. elegans) simultaneously. It has pneumatic valves and no-moving-parts (NMP) valves. An NMP valve is incorporated with a chamber and enables the unidirectional movement of C. elegans in the chamber; once worms are loaded into the chamber, they cannot exit, regardless of the flow direction. To demonstrate the ability of the NMP valve to handle worms, we made a microfluidic device with three chambers. Each chamber was used to expose worms to Cd and Cu solutions, and K-medium. A pair of electrodes was installed in the device and the capacitance in-between the electrode was measured. When a C. elegans passed through the electrodes, the capacitance was changed. The capacitance change was proportional to the body volume of the worm, thus the body volume change by the heavy metal exposure was measured in the device. Thirty worms were divided into three groups and exposed to each solution. We confirmed that the different solutions induced differences in the capacitance changes for each group. These results indicate that our device is a viable method for simultaneously analyzing the effect of multiple stimuli on C. elegans. (paper)

Electric field-decoupled electroosmotic pump for microfluidic devices.

Science.gov (United States)

Liu, Shaorong; Pu, Qiaosheng; Lu, Joann J

2003-09-26

An electric field-free electroosmotic pump has been constructed and its pumping rate has been measured under various experimental conditions. The key component of the pump is an ion-exchange membrane grounding joint that serves two major functions: (i) to maintain fluid continuity between pump channels and microfluidic conduit and (ii) to ground the solution in the microfluidic channel at the joint through an external electrode, and hence to decouple the electric field applied to the pump channels from the rest of the microfluidic system. A theoretical model has been developed to calculate the pumping rates and its validity has been demonstrated.

Generation of monodisperse cell-sized microdroplets using a centrifuge-based axisymmetric co-flowing microfluidic device.

Science.gov (United States)

Yamashita, Hitoyoshi; Morita, Masamune; Sugiura, Haruka; Fujiwara, Kei; Onoe, Hiroaki; Takinoue, Masahiro

2015-04-01

We report an easy-to-use generation method of biologically compatible monodisperse water-in-oil microdroplets using a glass-capillary-based microfluidic device in a tabletop mini-centrifuge. This device does not require complicated microfabrication; furthermore, only a small sample volume is required in experiments. Therefore, we believe that this method will assist biochemical and cell-biological experiments. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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.

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, ...

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...

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

DEFF Research Database (Denmark)

Vedarethinam, Indumathi; Shah, Pranjul Jaykumar; Dimaki, Maria

2010-01-01

-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....

Towards Multiplex Molecular Diagnosis—A Review of Microfluidic Genomics Technologies

Directory of Open Access Journals (Sweden)

Ismail Hussain Kamal Basha

2017-08-01

Full Text Available Highly sensitive and specific pathogen diagnosis is essential for correct and timely treatment of infectious diseases, especially virulent strains, in people. Point-of-care pathogen diagnosis can be a tremendous help in managing disease outbreaks as well as in routine healthcare settings. Infectious pathogens can be identified with high specificity using molecular methods. A plethora of microfluidic innovations in recent years have now made it increasingly feasible to develop portable, robust, accurate, and sensitive genomic diagnostic devices for deployment at the point of care. However, improving processing time, multiplexed detection, sensitivity and limit of detection, specificity, and ease of deployment in resource-limited settings are ongoing challenges. This review outlines recent techniques in microfluidic genomic diagnosis and devices with a focus on integrating them into a lab on a chip that will lead towards the development of multiplexed point-of-care devices of high sensitivity and specificity.

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.

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.

A microfluidic device for the continuous culture and analysis of Caenorhabditis elegans in a toxic aqueous environment

International Nuclear Information System (INIS)

Jung, Jaehoon; Tajima, Hirotaka; Fukuda, Toshio; Nakajima, Masahiro; Huang, Qiang

2013-01-01

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% LC 50 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. (paper)

Micro-optics for microfluidic analytical applications.

Science.gov (United States)

Yang, Hui; Gijs, Martin A M

2018-02-19

This critical review summarizes the developments in the integration of micro-optical elements with microfluidic platforms for facilitating detection and automation of bio-analytical applications. Micro-optical elements, made by a variety of microfabrication techniques, advantageously contribute to the performance of an analytical system, especially when the latter has microfluidic features. Indeed the easy integration of optical control and detection modules with microfluidic technology helps to bridge the gap between the macroscopic world and chip-based analysis, paving the way for automated and high-throughput applications. In our review, we start the discussion with an introduction of microfluidic systems and micro-optical components, as well as aspects of their integration. We continue with a detailed description of different microfluidic and micro-optics technologies and their applications, with an emphasis on the realization of optical waveguides and microlenses. The review continues with specific sections highlighting the advantages of integrated micro-optical components in microfluidic systems for tackling a variety of analytical problems, like cytometry, nucleic acid and protein detection, cell biology, and chemical analysis applications.

Fabrication and Characterization of All-Polystyrene Microfluidic Devices with Integrated Electrodes and Tubing.

Science.gov (United States)

Pentecost, Amber M; Martin, R Scott

2015-01-01

A new method of fabricating all-polystyrene devices with integrated electrodes and fluidic tubing is described. As opposed to expensive polystyrene (PS) fabrication techniques that use hot embossing and bonding with a heated lab press, this approach involves solvent-based etching of channels and lamination-based bonding of a PS cover, all of which do not need to occur in a clean room. PS has been studied as an alternative microchip substrate to PDMS, as it is more hydrophilic, biologically compatible in terms of cell adhesion, and less prone to absorption of hydrophobic molecules. The etching/lamination-based method described here results in a variety of all-PS devices, with or without electrodes and tubing. To characterize the devices, micrographs of etched channels (straight and intersected channels) were taken using confocal and scanning electron microscopy. Microchip-based electrophoresis with repetitive injections of fluorescein was conducted using a three-sided PS (etched pinched, twin-tee channel) and one-sided PDMS device. Microchip-based flow injection analysis, with dopamine and NO as analytes, was used to characterize the performance of all-PS devices with embedded tubing and electrodes. Limits of detection for dopamine and NO were 130 nM and 1.8 μM, respectively. Cell immobilization studies were also conducted to assess all-PS devices for cellular analysis. This paper demonstrates that these easy to fabricate devices can be attractive alternative to other PS fabrication methods for a wide variety of analytical and cell culture applications.

Microprocessor-based integration of microfluidic control for the implementation of automated sensor monitoring and multithreaded optimization algorithms.

Science.gov (United States)

Ezra, Elishai; Maor, Idan; Bavli, Danny; Shalom, Itai; Levy, Gahl; Prill, Sebastian; Jaeger, Magnus S; Nahmias, Yaakov

2015-08-01

Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits.

Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding

Science.gov (United States)

Sandström, Niklas; Zandi Shafagh, Reza; Gylfason, Kristinn B.; Haraldsson, Tommy; van der Wijngaart, Wouter

2017-12-01

Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges make them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+  parts to other OSTE+  substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+  cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of a commercially available QCM biosensor cartridge. The simplified manufacturing of QCM sensors with maintained performance potentializes novel application areas, e.g. as disposable devices in a point of care setting. Moreover, our results can be extended to simplifying the fabrication of other microfluidic devices with multiple heterogeneously integrated components.

A microfluidic microprocessor: controlling biomimetic containers and cells using hybrid integrated circuit/microfluidic chips.

Science.gov (United States)

Issadore, David; Franke, Thomas; Brown, Keith A; Westervelt, Robert M

2010-11-07

We present an integrated platform for performing biological and chemical experiments on a chip based on standard CMOS technology. We have developed a hybrid integrated circuit (IC)/microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picolitre containers for reagents on the chip. The hybrid chip can be programmed to trap, move, and porate individual living cells and vesicles and fuse and deform vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber using 128 × 256 (32,768) 11 × 11 μm(2) metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chip's basic functions can be combined in series to perform complex biological and chemical tasks and can be performed in parallel on the chip's many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research onto automated and inexpensive chips.

Design of Microfluidic Biochips (Dagstuhl Seminar 15352)

OpenAIRE

Chakrabarty, Krishnendu; Ho, Tsung-Yi; Wille, Robert

2016-01-01

Advances in microfluidic technologies have led to the emergence of biochip devices for automating laboratory procedures in biochemistry and molecular biology. Corresponding systems are revolutionizing a diverse range of applications, e.g.~air quality studies, point-of-care clinical diagnostics, drug discovery, and DNA sequencing -- with an increasing market. However, this continued growth depends on advances in chip integration and design-automation tools. Thus, there is a need to deliver the...

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.

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.

Soft tubular microfluidics for 2D and 3D applications

Science.gov (United States)

Xi, Wang; Kong, Fang; Yeo, Joo Chuan; Yu, Longteng; Sonam, Surabhi; Dao, Ming; Gong, Xiaobo; Teck Lim, Chwee

2017-10-01

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs.

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.

Microfluidic "Pouch" Chips for Immunoassays and Nucleic Acid Amplification Tests.

Science.gov (United States)

Mauk, Michael G; Liu, Changchun; Qiu, Xianbo; Chen, Dafeng; Song, Jinzhao; Bau, Haim H

2017-01-01

Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.

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.

In situ microfluidic dialysis for biological small-angle X-ray scattering

DEFF Research Database (Denmark)

Skou, Magda; Skou, Soren; Jensen, Thomas Glasdam

2014-01-01

Owing to the demand for low sample consumption and automated sample changing capabilities at synchrotron small-angle X-ray (solution) scattering (SAXS) beamlines, X-ray microfluidics is receiving continuously increasing attention. Here, a remote-controlled microfluidic device is presented for sim...... in incidental sample purification. Hence, this versatile microfluidic device enables investigation of experimentally induced structural changes under dynamically controllable sample conditions. (C) 2014 International Union of Crystallography......Owing to the demand for low sample consumption and automated sample changing capabilities at synchrotron small-angle X-ray (solution) scattering (SAXS) beamlines, X-ray microfluidics is receiving continuously increasing attention. Here, a remote-controlled microfluidic device is presented...

Microfluidic standardization: Past, present and future

NARCIS (Netherlands)

Heeren, H. van; Atkins, T.; Blom, M.; Bullema, J.E.; Tantra, R.; Verhoeven, D.; Verplanck, N.

2016-01-01

This paper addresses the issue of standardization in microfluidics. It contains the main points of an industry wide agreement about microfluidic port pitches and port nomenclature. It also addresses device classification and future steps.

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.

Design of organic 3D microresonators with microfluidics coupled to thin-film processes for photonic applications

Science.gov (United States)

Huby, N.; Pluchon, D.; Coulon, N.; Belloul, M.; Moreac, A.; Gaviot, E.; Panizza, P.; Bêche, B.

2010-06-01

We report on the design and realization of photonic integrated devices based on 3D organic microresonators (MR) shaped by an applied fluid mechanism technique. Such an interdisciplinary approach has been judiciously achieved by combining microfluidics techniques and thin-film processes, respectively, for the realizations of microfluidic and optical chips. The microfluidic framework with flow rates control allows the fabrication of microresonators with diameters ranging from 30 to 160 μm. The resonance of an isolated sphere in air has been demonstrated by way of a modified Raman spectroscopy devoted to the excitation of Whispering Gallery Modes (WGM). Then the 3D-MR have been integrated onto an organic chip and positioned either close to the extremity of a taper or alongside a rib waveguide. Both devices have proved efficient evanescent coupling mechanisms leading to the excitation of the WGM confined at the surface of the organic 3D-MR. Finally, a band-stop filter has been used to detect the resonance spectra of organic resonators once being integrated. Such spectral resonances have been observed with an integrated configuration and characterized with a Δ λ = 1.4 nm free spectral range (FSR), appearing as stemming from a 78 μm-radius MR structure.

A Multi-Gradient Generator in a Single Microfluidic Device for Optical Microscopy and Interferometry

Science.gov (United States)

Bedrossian, Manuel; Nadeau, Jay; Lindensmith, Chris

2016-11-01

The goal of this work was to create a single microfluidic device capable of establishing multiple types of gradients in a quantifiable manner. Many microbial species are known to exhibit directed motility in the presence of stimuli. This phenomenon, known as taxis, can be used as a bio-signature and a means of identifying microorganisms. Directed microbial motility has been seen as a response to the presence of certain chemicals, light, heat, magnetic fields, and other stimuli. Microbial movement along the gradient vector, that cannot be explained by passive hydrodynamics or Brownian motion, can shed light on whether the sample contains living microbes or not. The ability to create multiple types of gradients in a single microfluidic device allows for high throughput testing of heterogeneous samples to detect taxis. There has been increased interest in the search for life within our solar system where liquid water is known to exist. Induced directional motility can serve as a viable method for detecting living organisms that actively respond to their environment. The device developed here includes a chemical, photonic, thermal, and magnetic gradient generator, while maintaining high optical quality in order to be used for microscopy as well as quantitative phase imaging This work was funded by the Gordon and Betty Moore Foundation, who the authors wish to thank for their generosity.

Microfluidic electrochemical device and process for chemical imaging and electrochemical analysis at the electrode-liquid interface in-situ

Science.gov (United States)

Yu, Xiao-Ying; Liu, Bingwen; Yang, Li; Zhu, Zihua; Marshall, Matthew J.

2016-03-01

A microfluidic electrochemical device and process are detailed that provide chemical imaging and electrochemical analysis under vacuum at the surface of the electrode-sample or electrode-liquid interface in-situ. The electrochemical device allows investigation of various surface layers including diffuse layers at selected depths populated with, e.g., adsorbed molecules in which chemical transformation in electrolyte solutions occurs.

Differential white cell count by centrifugal microfluidics.

Energy Technology Data Exchange (ETDEWEB)

Sommer, Gregory Jon; Tentori, Augusto M.; Schaff, Ulrich Y.

2010-07-01

We present a method for counting white blood cells that is uniquely compatible with centrifugation based microfluidics. Blood is deposited on top of one or more layers of density media within a microfluidic disk. Spinning the disk causes the cell populations within whole blood to settle through the media, reaching an equilibrium based on the density of each cell type. Separation and fluorescence measurement of cell types stained with a DNA dye is demonstrated using this technique. The integrated signal from bands of fluorescent microspheres is shown to be proportional to their initial concentration in suspension. Among the current generation of medical diagnostics are devices based on the principle of centrifuging a CD sized disk functionalized with microfluidics. These portable 'lab on a disk' devices are capable of conducting multiple assays directly from a blood sample, embodied by platforms developed by Gyros, Samsung, and Abaxis. [1,2] However, no centrifugal platform to date includes a differential white blood cell count, which is an important metric complimentary to diagnostic assays. Measuring the differential white blood cell count (the relative fraction of granulocytes, lymphocytes, and monocytes) is a standard medical diagnostic technique useful for identifying sepsis, leukemia, AIDS, radiation exposure, and a host of other conditions that affect the immune system. Several methods exist for measuring the relative white blood cell count including flow cytometry, electrical impedance, and visual identification from a stained drop of blood under a microscope. However, none of these methods is easily incorporated into a centrifugal microfluidic diagnostic platform.

Modular microfluidics for point-of-care protein purifications.

Science.gov (United States)

Millet, L J; Lucheon, J D; Standaert, R F; Retterer, S T; Doktycz, M J

2015-04-21

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.

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 viscosity with respect to varying 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

Hybrid membrane-microfluidic components using a novel ceramic MEMS technology

Science.gov (United States)

Lutz, Brent J.; Polyakov, Oleg; Rinaldo, Chris

2012-03-01

A novel hybrid nano/microfabrication technology has been employed to produce unique MEMS and microfluidic components that integrate nanoporous membranes. The components are made by micromachining a self-organized nanostructured ceramic material that is biocompatible and amenable to surface chemistry modification. Microfluidic structures, such as channels and wells, can be made with a precision of membranes can be integrated into the bottom of these structures, featuring a wide range of possible thicknesses, from 100 micron to membranes may be non-porous or porous (with controllable pore sizes from 200 nm to technology is highly scaleable, and thus can yield low-cost, reliable, disposable microcomponents and devices. Specific applications that can benefit from this technology includes cell culturing and assays, imaging by cryo-electron tomography, environmental sample processing, as well as many others.

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.

Microsphere-based immunoassay integrated with a microfluidic network to perform logic operations

International Nuclear Information System (INIS)

Sabhachandani, Pooja; Cohen, Noa; Sarkar, Saheli; Konry, Tania

2015-01-01

Lab on a chip (LOC) intelligent diagnostics can be described by molecular logic-based circuits. We report on the development of an LOC approach with logic capability for screening combinations of antigen and antibody in the same sample. A microsphere-based immunoassay was integrated with a microfluidic network device to perform the logic operations AND and INHIBIT. Using the clinically relevant biomarkers TNF-α cytokine and anti-TNF-α antibody, we obtained a fluorescent output in the presence of both inputs. This results in an AND operation, while the presence of only one specific input results in a different fluorescent signal, thereby indicating the INHIBIT operation. This approach demonstrates the effective use of molecular logic computation for developing portable, point-of-care technologies for diagnostic purposes due to fast detection times, minimal reagent consumption and low costs. This model system may be further expanded to screening of multiple disease markers, combinatorial logic applications, and developing “smart” sensors and therapeutic technologies. (author)

Material Biocompatibility for PCR Microfluidic Chips

KAUST Repository

Kodzius, Rimantas

2010-04-23

As part of the current miniaturization trend, biological reactions and processes are being adapted to microfluidics devices. PCR is the primary method employed in DNA amplification, its miniaturization is central to efforts to develop portable devices for diagnostics and testing purposes. A problem is the PCR-inhibitory effect due to interaction between PCR reagents and the surrounding environment, which effect is increased in high-surface-are-to-volume ration microfluidics. In this study, we evaluated the biocompatibility of various common materials employed in the fabrication of microfluidic chips, including silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives. Two-temperature PCR was performed with these materials to determine their PCR-inhibitory effect. In most of the cases, addition of bovine serum albumin effectively improved the reaction yield. We also studied the individual PCR components from the standpoint of adsorption. Most of the materials did not inhibit the DNA, whereas they did show noticeable interaction with the DNA polymerase. Our test, instead of using microfluidic devices, can be easily conducted in common PCR tubes using a standard bench thermocycler. Our data supports an overview of the means by which the materials most bio-friendly to microfluidics can be selected.

Material Biocompatibility for PCR Microfluidic Chips