WorldWideScience

Sample records for flow-based microfluidic device

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. A network-flow based valve-switching aware binding algorithm for flow-based microfluidic biochips

    DEFF Research Database (Denmark)

    Tseng, Kai-Han; You, Sheng-Chi; Minhass, Wajid Hassan

    2013-01-01

    -flow based resource binding algorithm based on breadth-first search (BFS) and minimum cost maximum flow (MCMF) in architectural-level synthesis. The experimental results show that our methodology not only makes significant reduction of valve-switching activities but also diminishes the application completion......Designs of flow-based microfluidic biochips are receiving much attention recently because they replace conventional biological automation paradigm and are able to integrate different biochemical analysis functions on a chip. However, as the design complexity increases, a flow-based microfluidic...... biochip needs more chip-integrated micro-valves, i.e., the basic unit of fluid-handling functionality, to manipulate the fluid flow for biochemical applications. Moreover, frequent switching of micro-valves results in decreased reliability. To minimize the valve-switching activities, we develop a network...

  9. 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...

  10. Integrated lenses in polystyrene microfluidic devices

    KAUST Repository

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

    2013-01-01

    This paper reports a new method for integrating microlenses into microfluidic devices for improved observation. Two demonstration microfluidic devices were provided which were fabricated using this new technique. The integrated microlenses were

  11. 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.

  12. 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.

  13. 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...

  14. Synthesis of Biochemical Applications on Flow-Based Microfluidic Biochips using Constraint Programming

    DEFF Research Database (Denmark)

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

    2012-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis on-chip. In this paper we are interested in flow-based biochips, in which the flow of liquid is manipulated using integrated microvalves. By combin...

  15. 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.

  16. Integrated lenses in polystyrene microfluidic devices

    KAUST Repository

    Fan, Yiqiang

    2013-04-01

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

  17. Architectural Synthesis of Flow-Based Microfluidic Large-Scale Integration Biochips

    DEFF Research Database (Denmark)

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

    2012-01-01

    ,we propose a top-down architectural synthesis methodology for the flow-based biochips. Starting from a given biochemical application and a microfluidic component library, we are interested in synthesizing a biochip architecture, i.e., performing component allocation from the library based on the biochemical....... By combining several microvalves, more complex units, such as micropumps, switches, mixers, and multiplexers, can be built. The manufacturing technology, soft lithography, used for the flow-based biochips is advancing faster than Moore's law, resulting in increased architectural complexity. However...... by synthesizing architectures for real-life applications as well as synthetic benchmarks....

  18. 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.

  19. 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

  20. 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...

  1. 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

  2. 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)

  3. 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...

  4. 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

  5. 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.

  6. Microfluidic Devices for Blood Fractionation

    OpenAIRE

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

    2011-01-01

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

  7. Microfluidic chip-capillary electrophoresis devices

    CERN Document Server

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

    2015-01-01

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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Streamline-based microfluidic device

    Science.gov (United States)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Kasdan, Harvey (Inventor)

    2013-01-01

    The present invention provides a streamline-based device and a method for using the device for continuous separation of particles including cells in biological fluids. The device includes a main microchannel and an array of side microchannels disposed on a substrate. The main microchannel has a plurality of stagnation points with a predetermined geometric design, for example, each of the stagnation points has a predetermined distance from the upstream edge of each of the side microchannels. The particles are separated and collected in the side microchannels.

  15. 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.

  16. 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

  17. Optial sensing systems for microfluidic devices: a review

    NARCIS (Netherlands)

    Kuswandi, Bambang; Nuriman, [Unknown; Huskens, Jurriaan; Verboom, Willem

    2007-01-01

    This review deals with the application of optical sensing systems for microfluidic devices. In the “off-chip approach” macro-scale optical infrastructure is coupled, while the “on-chip approach” comprises the integration of micro-optical functions into microfluidic devices. The current progress of

  18. Microfluidic devices and methods for integrated flow cytometry

    Science.gov (United States)

    Srivastava, Nimisha [Goleta, CA; Singh, Anup K [Danville, CA

    2011-08-16

    Microfluidic devices and methods for flow cytometry are described. In described examples, various sample handling and preparation steps may be carried out within a same microfluidic device as flow cytometry steps. A combination of imaging and flow cytometry is described. In some examples, spiral microchannels serve as incubation chambers. Examples of automated sample handling and flow cytometry are described.

  19. 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

  20. 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.

  1. Desktop aligner for fabrication of multilayer microfluidic devices.

    Science.gov (United States)

    Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

    2015-07-01

    Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm(-1). To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices.

  2. 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.

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

    KAUST Repository

    Perozziello, Gerardo; Candeloro, Patrizio; De Grazia, Antonio; Esposito, Francesco; Allione, Marco; Coluccio, Maria Laura; Tallerico, Rossana; Valpapuram, Immanuel; Tirinato, Luca; Das, Gobind; Giugni, Andrea; Torre, Bruno; Veltri, Pierangelo; Kruhne, Ulrich; Della Valle, Giuseppe; Di Fabrizio, Enzo M.

    2015-01-01

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where

  4. 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.

  5. 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.

  6. Integration of Capacitive Micromachined Ultrasound Transducers to Microfluidic Devices

    KAUST Repository

    Viržonis, Darius; Kodzius, Rimantas; Vanagas, Galius

    2013-01-01

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

  7. Integration of Capacitive Micromachined Ultrasound Transducers to Microfluidic Devices

    KAUST Repository

    Viržonis, Darius

    2013-10-22

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

  8. 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

  9. Fast architecture-level synthesis of fault-tolerant flow-based microfluidic biochips

    DEFF Research Database (Denmark)

    Huang, Wei Lun; Gupta, Ankur; Roy, Sudip

    2017-01-01

    Microfluidic-based lab-on-a-chips have emerged as a popular technology for implementation of different biochemical test protocols used in medical diagnostics. However, in the manufacturing process or during operation of such chips, some faults may occur that leads to damage of the chip, which...

  10. Scheduling and Fluid Routing for Flow-Based Microfluidic Laboratories-on-a-Chip

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan; McDaniel, Jeffrey; Raagaard, Michael Lander

    2017-01-01

    Microfluidic laboratories-on-chip (LoCs) are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis onchip. There are several types of LoCs, each having its advantages and limitations. In this paper we are interested in flow-bas...

  11. 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.

  12. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing.

    Science.gov (United States)

    Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

    2016-11-23

    Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  13. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing

    Directory of Open Access Journals (Sweden)

    Mohammed-Baker Habhab

    2016-11-01

    Full Text Available Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  14. System-Level Modeling and Synthesis Techniques for Flow-Based Microfluidic Very Large Scale Integration Biochips

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan

    Microfluidic biochips integrate different biochemical analysis functionalities on-chip and offer several advantages over the conventional biochemical laboratories. In this thesis, we focus on the flow-based biochips. The basic building block of such a chip is a valve which can be fabricated at very...... propose a framework for mapping the biochemical applications onto the mVLSI biochips, binding and scheduling the operations and performing fluid routing. A control synthesis framework for determining the exact valve activation sequence required to execute the application is also proposed. In order...... to reduce the macro-assembly around the chip and enhance chip scalability, we propose an approach for the biochip pin count minimization. We also propose a throughput maximization scheme for the cell culture mVLSI biochips, saving time and reducing costs. We have extensively evaluated the proposed...

  15. 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

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. A microfluidic device with a diffusion barrier

    DEFF Research Database (Denmark)

    2014-01-01

    The invention provides a microfiuidic device for macromoiecuie amplification by sequential addition of liquid reagents. The device of the invention comprises a chip forming a plurality of reaction chambers each extending between an inlet and an outlet, each inlet being in fluid communication with...

  12. Methods for integrating a functional component into a microfluidic device

    Science.gov (United States)

    Simmons, Blake; Domeier, Linda; Woo, Noble; Shepodd, Timothy; Renzi, Ronald F.

    2014-08-19

    Injection molding is used to form microfluidic devices with integrated functional components. One or more functional components are placed in a mold cavity, which is then closed. Molten thermoplastic resin is injected into the mold and then cooled, thereby forming a solid substrate including the functional component(s). The solid substrate including the functional component(s) is then bonded to a second substrate, which may include microchannels or other features.

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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....

  18. Method for a microfluidic weaklink device

    Science.gov (United States)

    Shepodd, Timothy J [Livermore, CA; Duncan, Matthew P [Augusta, GA

    2009-12-01

    The present invention relates to an electrokinetic (EK) pump capable of creating high pressures electroosmotically, and capable of retaining high pressures. Both pressure creation and retention are accomplished without the need for moving parts. The EK pump uses a polymerizable fluid that creates the pressure-retaining seal within the EK pump when polymerization is initiated, typically by exposure to UV radiation. Weaklink devices are advantageously constructed including such a pressure-retaining EK pump since, among other advantages, the response of the weaklink device relies on predictable and reliable chemical polymerization reactions.

  19. [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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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…

  8. 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.

  9. 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)

  10. 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.

  11. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  13. 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.

  14. 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.

  15. 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.

  16. Fully automatic flow-based device for monitoring of drug permeation across a cell monolayer.

    Science.gov (United States)

    Zelená, Lucie; Marques, Sara S; Segundo, Marcela A; Miró, Manuel; Pávek, Petr; Sklenářová, Hana; Solich, Petr

    2016-01-01

    A novel flow-programming setup based on the sequential injection principle is herein proposed for on-line monitoring of temporal events in cell permeation studies. The permeation unit consists of a Franz cell with its basolateral compartment mixed under mechanical agitation and thermostated at 37 °C. The apical compartment is replaced by commercially available Transwell inserts with a precultivated cell monolayer. The transport of drug substances across epithelial cells genetically modified with the P-glycoprotein membrane transporter (MDCKII-MDR1) is monitored on-line using rhodamine 123 as a fluorescent marker. The permeation kinetics of the marker is obtained in a fully automated mode by sampling minute volumes of solution from the basolateral compartment in short intervals (10 min) up to 4 h. The effect of a P-glycoprotein transporter inhibitor, verapamil as a model drug, on the efficiency of the marker transport across the cell monolayer is thoroughly investigated. The analytical features of the proposed flow method for cell permeation studies in real time are critically compared against conventional batch-wise procedures and microfluidic devices.

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

    Science.gov (United States)

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

    2017-11-01

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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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)

  4. 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.

  5. 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....

  6. 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.

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

    Science.gov (United States)

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

    2015-12-01

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

  8. 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.

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

    Science.gov (United States)

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

    2014-09-21

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

  10. 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.

  11. Microfluidic device for cell capture and impedance measurement.

    Science.gov (United States)

    Jang, Ling-Sheng; Wang, Min-How

    2007-10-01

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

  12. Microfluidic paper-based analytical device for particulate metals.

    Science.gov (United States)

    Mentele, Mallory M; Cunningham, Josephine; Koehler, Kirsten; Volckens, John; Henry, Charles S

    2012-05-15

    A microfluidic paper-based analytical device (μPAD) fabricated by wax printing was designed to assess occupational exposure to metal-containing aerosols. This method employs rapid digestion of particulate metals using microliters of acid added directly to a punch taken from an air sampling filter. Punches were then placed on a μPAD, and digested metals were transported to detection reservoirs upon addition of water. These reservoirs contained reagents for colorimetric detection of Fe, Cu, and Ni. Dried buffer components were used to set the optimal pH in each detection reservoir, while precomplexation agents were deposited in the channels between the sample and detection zones to minimize interferences from competing metals. Metal concentrations were quantified from color intensity images using a scanner in conjunction with image processing software. Reproducible, log-linear calibration curves were generated for each metal, with method detection limits ranging from 1.0 to 1.5 μg for each metal (i.e., total mass present on the μPAD). Finally, a standard incineration ash sample was aerosolized, collected on filters, and analyzed for the three metals of interest. Analysis of this collected aerosol sample using a μPAD showed good correlation with known amounts of the metals present in the sample. This technology can provide rapid assessment of particulate metal concentrations at or below current regulatory limits and at dramatically reduced cost.

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

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    2010-07-01

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

  14. Capacitive Sensors for Feedback Control of Microfluidic Devices

    Science.gov (United States)

    Chen, J. Z.; Darhuber, A. A.; Troian, S. M.; Wagner, S.

    2003-11-01

    Automation of microfluidic devices based on thermocapillary flow [1] requires feedback control and detection techniques for monitoring the location, and ideally also composition and volume of liquid droplets. For this purpose we have developed a co-planar capacitance technique with a sensitivity of 0.07 pF at a frequency of 370 kHz. The variation in capacitance due to the presence of a droplet is monitored by the output frequency of an RC relaxation oscillator consisting of two inverters, one resistor and one capacitor. We discuss the performance of this coplanar sensor as a function of the electrode dimensions and geometry. These geometric variables determine the electric field penetration depth within the liquid, which in our studies ranged from 30 to 450 microns. Numerical solutions for the capacitance corresponding to the exact fabricated geometry agree very well with experimental data. An approximate analytic solution, which ignores fringe field effects, provides a simple but excellent guide for design development. [1] A. A. Darhuber et al., Appl. Phys. Lett. 82, 657 (2003).

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. 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.

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

    KAUST Repository

    Perozziello, Gerardo

    2015-12-11

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

  1. 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.

  2. 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.

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

    CSIR Research Space (South Africa)

    Hugo, S

    2013-10-01

    Full Text Available can be achieved. This work provides a complete centrifugal microfluidic platform and the building blocks on which to develop a variety of microfluidic applications and potential products rapidly and at a low cost. ... stream_source_info Hugo_2015_ABSTRACT.pdf.txt stream_content_type text/plain stream_size 1281 Content-Encoding UTF-8 stream_name Hugo_2015_ABSTRACT.pdf.txt Content-Type text/plain; charset=UTF-8 Rapid Product Development...

  4. 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.

  5. 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…

  6. 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.

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

    Science.gov (United States)

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

    2013-07-01

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

  8. 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.

  9. 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.

  10. Fabricating a multi-level barrier-integrated microfluidic device using grey-scale photolithography

    International Nuclear Information System (INIS)

    Nam, Yoonkwang; Kim, Minseok; Kim, Taesung

    2013-01-01

    Most polymer-replica-based microfluidic devices are mainly fabricated by using standard soft-lithography technology so that multi-level masters (MLMs) require multiple spin-coatings, mask alignments, exposures, developments, and bakings. In this paper, we describe a simple method for fabricating MLMs for planar microfluidic channels with multi-level barriers (MLBs). A single photomask is necessary for standard photolithography technology to create a polydimethylsiloxane grey-scale photomask (PGSP), which adjusts the total amount of UV absorption in a negative-tone photoresist via a wide range of dye concentrations. Since the PGSP in turn adjusts the degree of cross-linking of the photoresist, this method enables the fabrication of MLMs for an MLB-integrated microfluidic device. Since the PGSP-based soft-lithography technology provides a simple but powerful fabrication method for MLBs in a microfluidic device, we believe that the fabrication method can be widely used for micro total analysis systems that benefit from MLBs. We demonstrate an MLB-integrated microfluidic device that can separate microparticles. (paper)

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. 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…

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

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

    KAUST Repository

    Perozziello, Gerardo; Candeloro, Patrizio; Gentile, Francesco T.; Nicastri, Annalisa; Perri, Angela Mena; Coluccio, Maria Laura; Adamo, A.; Pardeo, Francesca; Catalano, Rossella; Parrotta, Elvira; Espinosa, Horacio Dante; Cuda, Giovanni; Di Fabrizio, Enzo M.

    2014-01-01

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

  9. 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.

  10. 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.

  11. Heterogenous integration of a thin-film GaAs photodetector and a microfluidic device on a silicon substrate

    International Nuclear Information System (INIS)

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

    2011-01-01

    In this paper, heterogeneous integration of a III–V semiconductor thin-film photodetector (PD) with a microfluidic device is demonstrated on a SiO 2 –Si substrate. Thin-film format of optical devices provides an intimate integration of optical functions with microfluidic devices. As a demonstration of a multi-material and functional system, the biphasic flow structure in the polymeric microfluidic channels was co-integrated with a III–V semiconductor thin-film PD. The fluorescent drops formed in the microfluidic device are successfully detected with an integrated thin-film PD on a silicon substrate. The proposed three-dimensional integration structure is an alternative approach to combine optical functions with microfluidic functions on silicon-based electronic functions.

  12. 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

  13. 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.

  14. 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…

  15. 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…

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

    DEFF Research Database (Denmark)

    Ahlford, Annika; Kjeldsen, Bastian; Reimers, Jakob

    2010-01-01

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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

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

    Science.gov (United States)

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

    2016-03-21

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

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

    Science.gov (United States)

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

    2016-01-01

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

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. Comparison of Pectin Hydrogel Collection Methods in Microfluidic Device

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

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

    KAUST Repository

    Kodzius, Rimantas

    2011-01-22

    employed in the fabrication of microfluidic chips including: silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives, etc. 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. This work provides a simple low cost fabrication method for creating microfluidic devices for biological analysis. Example assays were undertaken and the biocompatibility of our technology was studied, both of which demonstrated the utility of our approach.

  12. 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.

  13. 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.

  14. 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.

  15. Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device.

    Science.gov (United States)

    Abelha, T F; Phillips, T W; Bannock, J H; Nightingale, A M; Dreiss, C A; Kemal, E; Urbano, L; deMello, J C; Green, M; Dailey, L A

    2017-02-02

    This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG 5K -PLGA 55K ) matrix. The influence of PEG 5K -PLGA 55K and conjugated polymers cyano-substituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (∼70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (∼70-100 nm) with similar optical properties (quantum yields ∼35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG 5K -PLGA 55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flow-based device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Development of a real-world direct interface for integrated DNA extraction and amplification in a microfluidic device.

    Science.gov (United States)

    Shaw, Kirsty J; Joyce, Domino A; Docker, Peter T; Dyer, Charlotte E; Greenway, Gillian M; Greenman, John; Haswell, Stephen J

    2011-02-07

    Integrated DNA extraction and amplification have been carried out in a microfluidic device using electro-osmotic pumping (EOP) for fluidic control. All the necessary reagents for performing both DNA extraction and polymerase chain reaction (PCR) amplification were pre-loaded into the microfluidic device following encapsulation in agarose gel. Buccal cells were collected using OmniSwabs [Whatman™, UK] and manually added to a chaotropic binding/lysis solution pre-loaded into the microfluidic device. The released DNA was then adsorbed onto a silica monolith contained within the DNA extraction chamber and the microfluidic device sealed using polymer electrodes. The washing and elution steps for DNA extraction were carried out using EOP, resulting in transfer of the eluted DNA into the PCR chamber. Thermal cycling, achieved using a Peltier element, resulted in amplification of the Amelogenin locus as confirmed using conventional capillary gel electrophoresis. It was demonstrated that the PCR reagents could be stored in the microfluidic device for at least 8 weeks at 4 °C with no significant loss of activity. Such methodology lends itself to the production of 'ready-to-use' microfluidic devices containing all the necessary reagents for sample processing, with many obvious applications in forensics and clinical medicine.

  2. 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 ...

  3. 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, ...

  4. 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.

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

    Science.gov (United States)

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

    2017-06-06

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

  6. 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.

  7. 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.

  8. 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.

  9. Review on microfluidic paper-based analytical devices towards commercialisation.

    Science.gov (United States)

    Akyazi, Tugce; Basabe-Desmonts, Lourdes; Benito-Lopez, Fernando

    2018-02-25

    Paper-based analytical devices introduce an innovative platform technology for fluid handling and analysis, with wide range of applications, promoting low cost, ease of fabrication/operation and equipment independence. This review gives a general overview on the fabrication techniques reported to date, revealing and discussing their weak points as well as the newest approaches in order to overtake current mass production limitations and therefore commercialisation. Moreover, this review aims especially to highlight novel technologies appearing in literature for the effective handling and controlling of fluids. The lack of flow control is the main problem of paper-based analytical devices, which generates obstacles for marketing and slows down the transition of paper devices from the laboratory into the consumers' hands. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. An automated fluid-transport device for a microfluidic system.

    Science.gov (United States)

    Feng, Jun; Yang, Xiu-Juan; Li, Xin-Chun; Yang, Hui; Chen, Zuan-Guang

    2011-01-01

    An automated fluid-transport device for a chip-based capillary electrophoresis system has been developed. The device mainly consists of six peristaltic micropumps, two vacuum micropumps, microvalves, multi-way joints, titanium tubes, and a macro-to-micro connector. Various solutions used for the cleaning and activation of chip channels, and electrophoresis separation, are allowed to automatically transport to chip reservoirs by the electric control module. The performance of the whole system was characterized by the analysis of fluorescein sodium using chip electrophoresis with LED-induced fluorescence detection. The peak-height variation (RSD) was 3.8% in six cycles of analyses. Additionally, compared with conventional manual operation, the developed device can spare 60% time for chip pretreatment. This microdevice offers high-efficiency pretreatment for microchips, thereby resulting in a remarkable improvement of analytical capacity for batch samples.

  11. Fabrication of polyimide based microfluidic channels for biosensor devices

    DEFF Research Database (Denmark)

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

    2015-01-01

    The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabr...... 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....

  12. 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.

  13. 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...

  14. 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....

  15. 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)

  16. 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.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Ryan Wimbles

    2016-07-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Kathryn E McCormick

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

  6. 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.

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

    KAUST Repository

    Kodzius, Rimantas; Gong, Xiuqing; Li, Shunbo; Qin, Jianhua; Wen, Weijia; Wu, Jinbo; Xiao, Kang; Yi, Xin

    2011-01-01

    from the standpoint of adsorption. Most of the materials did not inhibit the DNA, whereas they did show noticeable interaction with the DNA polymerase. This work provides a simple low cost fabrication method for creating microfluidic devices for biological analysis. Example assays were undertaken and the biocompatibility of our technology was studied, both of which demonstrated the utility of our approach.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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)

  13. 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.

  14. 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.

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

    Science.gov (United States)

    Soh, Hyongsok; Lou, Xinhui; Lagally, Eric

    2015-12-01

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

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

    Science.gov (United States)

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

    2014-10-28

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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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).

  4. 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.

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

    DEFF Research Database (Denmark)

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2010-01-01

    they are highly reconfigurable and scalable. A digital biochip is composed of a two-dimensional array of cells, together with reservoirs for storing the samples and reagents. Several adjacent cells are dynamically grouped to form a virtual device, on which operations are performed. So far, researchers have...... assumed that throughout its execution, an operation is performed on a rectangular virtual device, whose position remains fixed. However, during the execution of an operation, the virtual device can be reconfigured to occupy a different group of cells on the array, forming any shape, not necessarily...... rectangular. In this paper, we present a Tabu Search metaheuristic for the synthesis of digital microfluidic biochips, which, starting from a biochemical application and a given biochip architecture, determines the allocation, resource binding, scheduling and placement of the operations in the application...

  6. 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.

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

    Science.gov (United States)

    Chen, Shao-Tuan; Sun, Chen-li

    2016-08-01

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

  8. 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

  9. Study on invadopodia formation for lung carcinoma invasion with a microfluidic 3D culture device.

    Science.gov (United States)

    Wang, Shanshan; Li, Encheng; Gao, Yanghui; Wang, Yan; Guo, Zhe; He, Jiarui; Zhang, Jianing; Gao, Zhancheng; Wang, Qi

    2013-01-01

    Invadopodia or invasive feet, which are actin-rich membrane protrusions with matrix degradation activity formed by invasive cancer cells, are a key determinant in the malignant invasive progression of tumors and represent an important target for cancer therapies. In this work, we presented a microfluidic 3D culture device with continuous supplement of fresh media via a syringe pump. The device mimicked tumor microenvironment in vivo and could be used to assay invadopodia formation and to study the mechanism of human lung cancer invasion. With this device, we investigated the effects of epidermal growth factor (EGF) and matrix metalloproteinase (MMP) inhibitor, GM6001 on invadopodia formation by human non-small cell lung cancer cell line A549 in 3D matrix model. This device was composed of three units that were capable of achieving the assays on one control group and two experimental groups' cells, which were simultaneously pretreated with EGF or GM6001 in parallel. Immunofluorescence analysis of invadopodia formation and extracellular matrix degradation was conducted using confocal imaging system. We observed that EGF promoted invadopodia formation by A549 cells in 3D matrix and that GM6001 inhibited the process. These results demonstrated that epidermal growth factor receptor (EGFR) signaling played a significant role in invadopodia formation and related ECM degradation activity. Meanwhile, it was suggested that MMP inhibitor (GM6001) might be a powerful therapeutic agent targeting invadopodia formation in tumor invasion. This work clearly demonstrated that the microfluidic-based 3D culture device provided an applicable platform for elucidating the mechanism of cancer invasion and could be used in testing other anti-invasion agents.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Increased drop formation frequency via reduction of surfactant interactions in flow-focusing microfluidic devices.

    Science.gov (United States)

    Josephides, Dimitris N; Sajjadi, Shahriar

    2015-01-27

    Glass capillary based microfluidic devices are able to create extremely uniform droplets, when formed under the dripping regime, at low setup costs due to their ease of manufacture. However, as they are rarely parallelized, simple methods to increase droplet production from a single device are sought. Surfactants used to stabilize drops in such systems often limit the maximum flow rate that highly uniform drops can be produced due to the lowering interfacial tension causing jetting. In this paper we show that by simple design changes we can limit the interactions of surfactants and maximize uniform droplet production. Three flow-focused configurations are explored: a standard glass capillary device (consisting of a single round capillary inserted into a square capillary), a nozzle fed device, and a surfactant shielding device (both consisting of two round capillaries inserted into either end of a square capillary). In principle, the maximum productivity of uniform droplets is achieved if surfactants are not present. It was found that surfactants in the standard device greatly inhibit droplet production by means of interfacial tension lowering and tip-streaming phenomena. In the nozzle fed configuration, surfactant interactions were greatly limited, yielding flow rates comparable to, but lower than, a surfactant-free system. In the surfactant shielding configuration, flow rates were equal to that of a surfactant-free system and could make uniform droplets at rates an order of magnitude above the standard surfactant system.

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

    Science.gov (United States)

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

    2018-04-01

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

  19. 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.

  20. 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.

  1. 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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Niels Tommerup

    2010-11-01

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

  4. 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.

  5. 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.

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

    KAUST Repository

    Kodzius, Rimantas

    2011-11-04

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

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

    KAUST Repository

    Kodzius, Rimantas

    2011-01-01

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

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

    KAUST Repository

    Catalano, Rossella; Perozziello, Gerardo; Simone, Giuseppina; Candeloro, Patrizio; Gentile, Francesco T.; Coluccio, Maria Laura; Pardeo, Francesca; Burghammer, Manfred C.; Cuda, Giovanni; Riekel, Christian; Di Fabrizio, Enzo M.

    2014-01-01

    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

  9. 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.

  10. Over a century of neuron culture: from the hanging drop to microfluidic devices.

    Science.gov (United States)

    Millet, Larry J; Gillette, Martha U

    2012-12-01

    The brain is the most intricate, energetically active, and plastic organ in the body. These features extend to its cellular elements, the neurons and glia. Understanding neurons, or nerve cells, at the cellular and molecular levels is the cornerstone of modern neuroscience. The complexities of neuron structure and function require unusual methods of culture to determine how aberrations in or between cells give rise to brain dysfunction and disease. Here we review the methods that have emerged over the past century for culturing neurons in vitro, from the landmark finding by Harrison (1910) - that neurons can be cultured outside the body - to studies utilizing culture vessels, micro-islands, Campenot and brain slice chambers, and microfluidic technologies. We conclude with future prospects for neuronal culture and considerations for advancement. We anticipate that continued innovation in culture methods will enhance design capabilities for temporal control of media and reagents (chemotemporal control) within sub-cellular environments of three-dimensional fluidic spaces (microfluidic devices) and materials (e.g., hydrogels). They will enable new insights into the complexities of neuronal development and pathology.

  11. 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

  12. Electromechanical model to predict the movability of liquids in an electrowetting-on-dielectric microfluidic device

    Science.gov (United States)

    Torabinia, Matin; Farzbod, Ali; Moon, Hyejin

    2018-04-01

    In electrowetting-on-dielectric (EWOD) microfluidics, a motion of a fluid is created by a voltage applied to the fluid/surface interface. Water and aqueous solutions are the most frequently used fluids in EWOD devices. In order for EWOD microfluidics to be a versatile platform for various applications, however, movability of different types of fluids other than aqueous solutions should be understood. An electromechanical model using a simple RC circuit has been used to predict the mechanical force exerted on a liquid droplet upon voltage application. In this present study, two important features missed in previous works are addressed. Energy dissipation by contact line friction is considered in the new model as the form of resistor. The phase angle is taken into account in the analysis of the AC circuit. The new electromechanical model and computation results are validated with experimental measurements of forces on two different liquids. The model is then used to explain influences of contact angle hysteresis, surface tension, conductivity, and dielectric constant of fluids to the mechanical force on a liquid droplet.

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2016-11-01

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

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

    NARCIS (Netherlands)

    Kieslinger, Dorit C.; Hao, Zhenxia; Vergouw, Carlijn G.; Kostelijk, Elisabeth H.; Lambalk, Cornelis B.; le Gac, Severine

    Objective: To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. Design: Prospective randomized controlled trial. Setting: In vitro fertilization laboratory. Patient(s): One hundred eighteen donated frozen-thawed

  17. 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.

  18. 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.

  19. HistoFlex-a microfluidic device providing uniform flow conditions enabling highly sensitive, reproducible and quantitative in situ hybridizations

    DEFF Research Database (Denmark)

    Søe, Martin Jensen; Okkels, Fridolin; Sabourin, David

    2011-01-01

    A microfluidic device (the HistoFlex) designed to perform and monitor molecular biological assays under dynamic flow conditions on microscope slide-substrates, with special emphasis on analyzing histological tissue sections, is presented. Microscope slides were reversibly sealed onto a cast polyd...

  20. High-throughput deterministic single-cell encapsulation and droplet pairing, fusion, and shrinkage in a single microfluidic device

    NARCIS (Netherlands)

    Schoeman, R.M.; Kemna, Evelien; Wolbers, F.; van den Berg, Albert

    In this article, we present a microfluidic device capable of successive high-yield single-cell encapsulation in droplets, with additional droplet pairing, fusion, and shrinkage. Deterministic single-cell encapsulation is realized using Dean-coupled inertial ordering of cells in a Yin-Yang-shaped

  1. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Directory of Open Access Journals (Sweden)

    Yu Lu

    2016-05-01

    Full Text Available Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  2. 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.

  3. 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

  4. 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...

  5. Evaluation of biofouling in stainless microfluidic channels for implantable multilayered dialysis device

    Science.gov (United States)

    Ota, Takashi; To, Naoya; Kanno, Yoshihiko; Miki, Norihisa

    2017-06-01

    An implantable artificial kidney can markedly improve the quality of life of renal disease patients. Our group has developed an implantable multilayered dialysis system consisting of microfluidic channels and dialysis membranes. Long-term evaluation is necessary for implant devices where biofouling is a critical factor, culminating in the deterioration of dialysis performance. Our previous work revealed that surface conditions, which depend on the manufacturing process, determine the amount of biofouling, and that electrolytic etching is the most suitable technique for forming a channel wall free of biofouling. In this study, we investigated the electrolytic etching conditions in detail. We conducted in vitro experiments for 7 d and evaluated the adhesion of biomaterials by scanning electron microscopy. The experiments revealed that a surface mirror-finished by electrolytic etching effectively prevents biofouling.

  6. Microfluidic device to study cell transmigration under physiological shear stress conditions

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Kiilerich-Pedersen, Katrine; Moresco, Jacob Lange

    2011-01-01

    The development of new drug therapies relies on studies of cell transmigration in in vitro systems. Migration has traditionally been studied using two methods, the Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell transmigration studies, they are far from imitating a...... of the developed microfluidic migration assay. The presented device is inexpensive, easy to fabricate and disposable, having a potential to be applied in basic research as well as in the drug development process.......The development of new drug therapies relies on studies of cell transmigration in in vitro systems. Migration has traditionally been studied using two methods, the Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell transmigration studies, they are far from imitating...

  7. Measurement of buried undercut structures in microfluidic devices by laser fluorescent confocal microscopy

    International Nuclear Information System (INIS)

    Li Shiguang; Liu Jing; Nguyen, Nam-Trung; Fang Zhongping; Yoon, Soon Fatt

    2009-01-01

    Measuring buried, undercut microstructures is a challenging task in metrology. These structures are usually characterized by measuring their cross sections after physically cutting the samples. This method is destructive and the obtained information is incomplete. The distortion due to cutting also affects the measurement accuracy. In this paper, we first apply the laser fluorescent confocal microscopy and intensity differentiation algorithm to obtain the complete three-dimensional profile of the buried, undercut structures in microfluidic devices, which are made by the soft lithography technique and bonded by the oxygen plasma method. The impact of material wettability and the refractive index (n) mismatch among the liquid, samples, cover layer, and objective on the measurement accuracy are experimentally investigated.

  8. 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.

  9. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    International Nuclear Information System (INIS)

    Zhang, Hanyuan; Sun, Jianbo; Li, Xiang; Liu, Yuxin; Lohcharoenkal, Warangkana; Rojanasakul, Yon; Wang, Liying; Wu, Nianqiang

    2015-01-01

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 µg cm −2 ) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the

  10. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    Science.gov (United States)

    Zhang, Hanyuan; Lohcharoenkal, Warangkana; Sun, Jianbo; Li, Xiang; Wang, Liying; Wu, Nianqiang; Rojanasakul, Yon; Liu, Yuxin

    2015-07-01

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 µg cm-2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the

  11. Enhanced intracellular delivery of a model drug using microbubbles produced by a microfluidic device.

    Science.gov (United States)

    Dixon, Adam J; Dhanaliwala, Ali H; Chen, Johnny L; Hossack, John A

    2013-07-01

    Focal drug delivery to a vessel wall facilitated by intravascular ultrasound and microbubbles holds promise as a potential therapy for atherosclerosis. Conventional methods of microbubble administration result in rapid clearance from the bloodstream and significant drug loss. To address these limitations, we evaluated whether drug delivery could be achieved with transiently stable microbubbles produced in real time and in close proximity to the therapeutic site. Rat aortic smooth muscle cells were placed in a flow chamber designed to simulate physiological flow conditions. A flow-focusing microfluidic device produced 8 μm diameter monodisperse microbubbles within the flow chamber, and ultrasound was applied to enhance uptake of a surrogate drug (calcein). Acoustic pressures up to 300 kPa and flow rates up to 18 mL/s were investigated. Microbubbles generated by the flow-focusing microfluidic device were stabilized with a polyethylene glycol-40 stearate shell and had either a perfluorobutane (PFB) or nitrogen gas core. The gas core composition affected stability, with PFB and nitrogen microbubbles exhibiting half-lives of 40.7 and 18.2 s, respectively. Calcein uptake was observed at lower acoustic pressures with nitrogen microbubbles (100 kPa) than with PFB microbubbles (200 kPa) (p 3). In addition, delivery was observed at all flow rates, with maximal delivery (>70% of cells) occurring at a flow rate of 9 mL/s. These results demonstrate the potential of transiently stable microbubbles produced in real time and in close proximity to the intended therapeutic site for enhancing localized drug delivery. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  12. A laser-based technology for fabricating a soda-lime glass based microfluidic device for circulating tumour cell capture.

    Science.gov (United States)

    Nieto, Daniel; Couceiro, Ramiro; Aymerich, Maria; Lopez-Lopez, Rafael; Abal, Miguel; Flores-Arias, María Teresa

    2015-10-01

    We developed a laser-based technique for fabricating microfluidic microchips on soda-lime glass substrates. The proposed methodology combines a laser direct writing, as a manufacturing tool for the fabrication of the microfluidics structures, followed by a post-thermal treatment with a CO2 laser. This treatment will allow reshaping and improving the morphological (roughness) and optical qualities (transparency) of the generated microfluidics structures. The use of lasers commonly implemented for material processing makes this technique highly competitive when compared with other glass microstructuring approaches. The manufactured chips were tested with tumour cells (Hec 1A) after being functionalized with an epithelial cell adhesion molecule (EpCAM) antibody coating. Cells were successfully arrested on the pillars after being flown through the device giving our technology a translational application in the field of cancer research. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 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)

  14. 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.

  15. 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.

  16. An agar gel membrane-PDMS hybrid microfluidic device for long term single cell dynamic study.

    Science.gov (United States)

    Wong, Ieong; Atsumi, Shota; Huang, Wei-Chih; Wu, Tung-Yun; Hanai, Taizo; Lam, Miu-Ling; Tang, Ping; Yang, Jian; Liao, James C; Ho, Chih-Ming

    2010-10-21

    Significance of single cell measurements stems from the substantial temporal fluctuations and cell-cell variability possessed by individual cells. A major difficulty in monitoring surface non-adherent cells such as bacteria and yeast is that these cells tend to aggregate into clumps during growth, obstructing the tracking or identification of single-cells over long time periods. Here, we developed a microfluidic platform for long term single-cell tracking and cultivation with continuous media refreshing and dynamic chemical perturbation capability. The design highlights a simple device-assembly process between PDMS microchannel and agar membrane through conformal contact, and can be easily adapted by microbiologists for their routine laboratory use. The device confines cell growth in monolayer between an agar membrane and a glass surface. Efficient nutrient diffusion through the membrane and reliable temperature maintenance provide optimal growth condition for the cells, which exhibited fast exponential growth and constant distribution of cell sizes. More than 24 h of single-cell tracking was demonstrated on a transcription-metabolism integrated synthetic biological model, the gene-metabolic oscillator. Single cell morphology study under alcohol toxicity allowed us to discover and characterize cell filamentation exhibited by different E. coli isobutanol tolerant strains. We believe this novel device will bring new capabilities to quantitative microbiology, providing a versatile platform for single cell dynamic studies.

  17. 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.

  18. 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.

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

    Science.gov (United States)

    Menolascina, Filippo; Bellomo, Domenico; Maiwald, Thomas; Bevilacqua, Vitoantonio; Ciminelli, Caterina; Paradiso, Angelo; Tommasi, Stefania

    2009-10-15

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

  20. 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.

  1. Dynamic bioprocessing and microfluidic transport control with smart magnetic nanoparticles in laminar-flow devices.

    Science.gov (United States)

    Lai, James J; Nelson, Kjell E; Nash, Michael A; Hoffman, Allan S; Yager, Paul; Stayton, Patrick S

    2009-07-21

    In the absence of applied forces, the transport of molecules and particulate reagents across laminar flowstreams in microfluidic devices is dominated by the diffusivities of the transported species. While the differential diffusional properties between smaller and larger diagnostic targets and reagents have been exploited for bioseparation and assay applications, there are limitations to methods that depend on these intrinsic size differences. Here a new strategy is described for exploiting the sharply reversible change in size and magnetophoretic mobility of "smart" magnetic nanoparticles (mNPs) to perform bioseparation and target isolation under continuous flow processing conditions. The isolated 5 nm mNPs do not exhibit significant magnetophoretic velocities, but do exhibit high magnetophoretic velocities when aggregated by the action of a pH-responsive polymer coating. A simple external magnet is used to magnetophorese the aggregated mNPs that have captured a diagnostic target from a lower pH laminar flowstream (pH 7.3) to a second higher pH flowstream (pH 8.4) that induces rapid mNP disaggregation. In this second dis-aggregated state and flowstream, the mNPs continue to flow past the magnet rather than being immobilized at the channel surface near the magnet. This stimuli-responsive reagent system has been shown to transfer 81% of a model protein target from an input flowstream to a second flowstream in a continuous flow H-filter device.

  2. 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)

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

    Science.gov (United States)

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

    2016-03-01

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

  4. 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.

  5. Integration of single oocyte trapping, in vitro fertilization and embryo culture in a microwell-structured microfluidic device.

    Science.gov (United States)

    Han, Chao; Zhang, Qiufang; Ma, Rui; Xie, Lan; Qiu, Tian; Wang, Lei; Mitchelson, Keith; Wang, Jundong; Huang, Guoliang; Qiao, Jie; Cheng, Jing

    2010-11-07

    In vitro fertilization (IVF) therapy is an important treatment for human infertility. However, the methods for clinical IVF have only changed slightly over decades: culture medium is held in oil-covered drops in Petri dishes and manipulation occurs by manual pipetting. Here we report a novel microwell-structured microfluidic device that integrates single oocyte trapping, fertilization and subsequent embryo culture. A microwell array was used to capture and hold individual oocytes during the flow-through process of oocyte and sperm loading, medium substitution and debris cleaning. Different microwell depths were compared by computational modeling and flow washing experiments for their effectiveness in oocyte trapping and debris removal. Fertilization was achieved in the microfluidic devices with similar fertilization rates to standard oil-covered drops in Petri dishes. Embryos could be cultured to blastocyst stages in our devices with developmental status individually monitored and tracked. The results suggest that the microfluidic device may bring several advantages to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing, and enabling automated tracking of any single embryo development.

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

    KAUST Repository

    Li, Huawei

    2011-11-01

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

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

    KAUST Repository

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

    2011-01-01

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

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

    OpenAIRE

    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 i...

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

    Science.gov (United States)

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

    2016-01-07

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

  10. [Development of molecular detection of food-borne pathogenic bacteria using miniaturized microfluidic devices].

    Science.gov (United States)

    Iván, Kristóf; Maráz, Anna

    2015-12-20

    Detection and identification of food-borne pathogenic bacteria are key points for the assurance of microbiological food safety. Traditional culture-based methods are more and more replaced by or supplemented with nucleic acid based molecular techniques, targeting specific (preferably virulence) genes in the genomes. Internationally validated DNA amplification - most frequently real-time polymerase chain reaction - methods are applied by the food microbiological testing laboratories for routine analysis, which will result not only in shortening the time for results but they also improve the performance characteristics (e.g. sensitivity, specificity) of the methods. Beside numerous advantages of the polymerase chain reaction based techniques for routine microbiological analysis certain drawbacks have to be mentioned, such as the high cost of the equipment and reagents, as well as the risk of contamination of the laboratory environment by the polymerase chain reaction amplicons, which require construction of an isolated laboratory system. Lab-on-a-chip systems can integrate most of these laboratory processes within a miniaturized device that delivers the same specificity and reliability as the standard protocols. The benefits of miniaturized devices are: simple - often automated - use, small overall size, portability, sterility due to single use possibility. These miniaturized rapid diagnostic tests are being researched and developed at the best research centers around the globe implementing various sample preparation and molecular DNA amplification methods on-chip. In parallel, the aim of the authors' research is to develop microfluidic Lab-on-a-chip devices for the detection and identification of food-borne pathogenic bacteria.

  11. 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.

  12. 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.

  13. 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.

  14. A mathematical model of breast cancer cell motion through a microfluidic device

    Science.gov (United States)

    Barber, Jared

    2017-11-01

    Deaths due to breast cancer are usually caused by metastases at other locations (e.g. bone), not by the primary tumor. Much research has targeted understanding how to lower the metastatic potential of individual breast cancer cells with the end goal being the mitigation of the effects of breast cancer on the 3.5 million people in the US affected by the disease. Experiments show that metastatic potential correlates well with the physical properties of a cell and its surrounding environment. Biology also suggests that mechanotransduction of cellular pathways (e.g. apoptosis, division) can affect metastatic potential. Because of these insights, we are developing a mechanical model of breast cancer cell translocation in microvessels. Our first model is a two-dimensional model with interconnected viscoelastic elements submersed in a surrounding Stokes flow. This model has been used to consider breast cancer cell translocation through a microfluidic device that was designed as a diagnostic tool for assessing the metastatic potential of breast cells. We will present this current model and share results. We believe that further development of this model will allow consideration of metastatic potential in both in vitro and in vivo settings.

  15. Determination of aminoglycoside antibiotics using an on-chip microfluidic device with chemiluminescence detection

    International Nuclear Information System (INIS)

    Sierra-Rodero, M.; Fernandez-Romero, J.M.; Gomez-Hens, A.

    2012-01-01

    We describe an on-chip microflow injection (μFI) approach for the determination of aminoglycoside antibiotics using chemiluminescence (CL) detection. The method is based on the inhibition of the Cu(II)-catalyzed CL reaction of luminol and hydrogen peroxide by the aminoglycosides due to the formation of a complex between the antibiotic and Cu(II). The main features of the method include small sample volumes and a fast response. Syringe pumps were used to insert the sample and the reagents into the microfluidic device. CL was collected using a fiber optic bundle connected to a luminescence detector. All instrumental, hydrodynamic and chemical variables involved in the system were optimized using neomycin as the aminoglycoside model. Inhibition is proportional to the concentration of the antibiotics. The dynamic ranges of the calibration graphs obtained for neomycin, streptomycin and amikacin are 0.3-3.3, 0.9-13.7, and 0.8-8.5 μmol L -1 , and the detection limits are 0.09, 0.28 and 0.24 μmol L -1 , respectively. The precision of the methods, expressed as relative standard deviation, is in the range from 0.8 to 5.0 %. The method was successfully applied to the determination of neomycin in water samples, with recoveries ranging from 80 to 120 %. (author)

  16. Determination of glucose and uric acid with bienzyme colorimetry on microfluidic paper-based analysis devices.

    Science.gov (United States)

    Chen, Xi; Chen, Jin; Wang, Fubin; Xiang, Xia; Luo, Ming; Ji, Xinghu; He, Zhike

    2012-05-15

    In this work, we first employ a drying method combining with the bienzyme colorimetric detection of glucose and uric acid on microfluidic paper-based analysis devices (μPADs). The channels of 3D μPADs are also designed by us to get better results. The color results are recorded by both Gel Documentation systems and a common camera. By using Gel Documentation systems, the limits of detection (LOD) of glucose and uric acid are 3.81 × 10(-5)M and 4.31 × 10(-5)M, respectively one order of magnitude lower than that of the reported methods on μPADs. By using a common camera, the limits of detection (LOD) of glucose and uric acid are 2.13 × 10(-4)M and 2.87 × 10(-4)M, respectively. Furthermore, the effects of detection conditions have been investigated and discussed comprehensively. Human serum samples are detected with satisfactory results, which are comparable with the clinical testing results. A low-cost, simple and rapid colorimetric method for the simultaneous detection of glucose and uric acid on the μPADs has been developed with enhanced sensitivity. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ken-Ichi Wada

    2017-12-01

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

  18. Investigation of the Effect of Plasma Polymerized Siloxane Coating for Enzyme Immobilization and Microfluidic Device Conception

    Directory of Open Access Journals (Sweden)

    Kalim Belhacene

    2016-12-01

    Full Text Available This paper describes the impact of a physical immobilization methodology, using plasma polymerized 1,1,3,3, tetramethyldisiloxane, on the catalytic performance of β-galactosidase from Aspergillus oryzae in a microfluidic device. The β-galactosidase was immobilized by a polymer coating grown by Plasma Enhanced Chemical Vapor Deposition (PEVCD. Combined with a microchannel patterned in the silicone, a microreactor was obtained with which the diffusion through the plasma polymerized layer and the hydrolysis of a synthetic substrate, the resorufin-β-d-galactopyranoside, were studied. A study of the efficiency of the immobilization procedure was investigated after several uses and kinetic parameters of immobilized β-galactosidase were calculated and compared with those of soluble enzyme. Simulation and a modelling approach were also initiated to understand phenomena that influenced enzyme behavior in the physical immobilization method. Thus, the catalytic performances of immobilized enzymes were directly influenced by immobilization conditions and particularly by the diffusion behavior and availability of substrate molecules in the enzyme microenvironment.

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

    Directory of Open Access Journals (Sweden)

    Jurriaan Huskens

    2011-10-01

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

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

    Science.gov (United States)

    Nekouei, Mehdi; Vanapalli, Siva

    2014-11-01

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

  1. Features in Microfluidic Paper-Based Devices Made by Laser Cutting: How Small Can They Be?

    Directory of Open Access Journals (Sweden)

    Md. Almostasim Mahmud

    2018-05-01

    Full Text Available In this paper, we determine the smallest feature size that enables fluid flow in microfluidic paper-based analytical devices (µPADs fabricated by laser cutting. The smallest feature sizes fabricated from five commercially available paper types: Whatman filter paper grade 50 (FP-50, Whatman 3MM Chr chromatography paper (3MM Chr, Whatman 1 Chr chromatography paper (1 Chr, Whatman regenerated cellulose membrane 55 (RC-55 and Amershan Protran 0.45 nitrocellulose membrane (NC, were 139 ± 8 µm, 130 ± 11 µm, 103 ± 12 µm, 45 ± 6 µm, and 24 ± 3 µm, respectively, as determined experimentally by successful fluid flow. We found that the fiber width of the paper correlates with the smallest feature size that has the capacity for fluid flow. We also investigated the flow speed of Allura red dye solution through small-scale channels fabricated from different paper types. We found that the flow speed is significantly slower through microscale features and confirmed the similar trends that were reported previously for millimeter-scale channels, namely that wider channels enable quicker flow speed.

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

    Science.gov (United States)

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

    2015-10-07

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

  3. Automated tracking and quantification of angiogenic vessel formation in 3D microfluidic devices.

    Science.gov (United States)

    Wang, Mengmeng; Ong, Lee-Ling Sharon; Dauwels, Justin; Asada, H Harry

    2017-01-01

    Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a critical step in cancer invasion. Better understanding of the angiogenic mechanisms is required to develop effective antiangiogenic therapies for cancer treatment. We culture angiogenic vessels in 3D microfluidic devices under different Sphingosin-1-phosphate (S1P) conditions and develop an automated vessel formation tracking system (AVFTS) to track the angiogenic vessel formation and extract quantitative vessel information from the experimental time-lapse phase contrast images. The proposed AVFTS first preprocesses the experimental images, then applies a distance transform and an augmented fast marching method in skeletonization, and finally implements the Hungarian method in branch tracking. When applying the AVFTS to our experimental data, we achieve 97.3% precision and 93.9% recall by comparing with the ground truth obtained from manual tracking by visual inspection. This system enables biologists to quantitatively compare the influence of different growth factors. Specifically, we conclude that the positive S1P gradient increases cell migration and vessel elongation, leading to a higher probability for branching to occur. The AVFTS is also applicable to distinguish tip and stalk cells by considering the relative cell locations in a branch. Moreover, we generate a novel type of cell lineage plot, which not only provides cell migration and proliferation histories but also demonstrates cell phenotypic changes and branch information.

  4. High-Efficiency Multiscale Modeling of Cell Deformations in Confined Microenvironments in Microcirculation and Microfluidic Devices

    Science.gov (United States)

    Lu, Huijie; Peng, Zhangli

    2017-11-01

    Our goal is to develop a high-efficiency multiscale modeling method to predict the stress and deformation of cells during the interactions with their microenvironments in microcirculation and microfluidic devices, including red blood cells (RBCs) and circulating tumor cells (CTCs). There are more than 1 billion people in the world suffering from RBC diseases, e.g. anemia, sickle cell diseases, and malaria. The mechanical properties of RBCs are changed in these diseases due to molecular structure alternations, which is not only important for understanding the disease pathology but also provides an opportunity for diagnostics. On the other hand, the mechanical properties of cancer cells are also altered compared to healthy cells. This can lead to acquired ability to cross the narrow capillary networks and endothelial gaps, which is crucial for metastasis, the leading cause of cancer mortality. Therefore, it is important to predict the deformation and stress of RBCs and CTCs in microcirculations. We are developing a high-efficiency multiscale model of cell-fluid interaction to study these two topics.

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

    Science.gov (United States)

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

    2013-08-01

    The nematode Caenorhabditis elegans (C. elegans) receives attention as a bioindicator, and the C. elegans condition has been recently analyzed using microfluidic devices equipped with an imaging system. To establish a method without an imaging system, we have proposed a novel microfluidic device with which to analyze the condition of C. elegans from the capacitance change using a pair of micro-electrodes. The device was designed to culture C. elegans, to expose C. elegans to an external stimulus, such as a chemical or toxicant, and to measure the capacitance change which indicates the condition of C. elegans. In this study, to demonstrate the capability of our device in a toxic aqueous environment, the device was applied to examine the effect of cadmium on C. elegans. Thirty L4 larval stage C. elegans were divided into three groups. One group was a control group and the other groups were exposed to cadmium solutions with concentrations of 5% and 10% LC50 for 24 h. The capacitance change and the body volume of C. elegans as a reference were measured four times and we confirmed the correlation between them. It shows that our device can analyze the condition of C. elegans without an imaging system.

  6. 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)

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  8. Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices.

    Directory of Open Access Journals (Sweden)

    David A Selck

    Full Text Available Nucleic acid amplification tests that are coupled with a digital readout enable the absolute quantification of single molecules, even at ultralow concentrations. Digital methods are robust, versatile and compatible with many amplification chemistries including isothermal amplification, making them particularly invaluable to assays that require sensitive detection, such as the quantification of viral load in occult infections or detection of sparse amounts of DNA from forensic samples. A number of microfluidic platforms are being developed for carrying out digital amplification. However, the mechanistic investigation and optimization of digital assays has been limited by the lack of real-time kinetic information about which factors affect the digital efficiency and analytical sensitivity of a reaction. Commercially available instruments that are capable of tracking digital reactions in real-time are restricted to only a small number of device types and sample-preparation strategies. Thus, most researchers who wish to develop, study, or optimize digital assays rely on the rate of the amplification reaction when performed in a bulk experiment, which is now recognized as an unreliable predictor of digital efficiency. To expand our ability to study how digital reactions proceed in real-time and enable us to optimize both the digital efficiency and analytical sensitivity of digital assays, we built a custom large-format digital real-time amplification instrument that can accommodate a wide variety of devices, amplification chemistries and sample-handling conditions. Herein, we validate this instrument, we provide detailed schematics that will enable others to build their own custom instruments, and we include a complete custom software suite to collect and analyze the data retrieved from the instrument. We believe assay optimizations enabled by this instrument will improve the current limits of nucleic acid detection and quantification, improving our

  9. Electrowetting-based microfluidic operations on rapid-manufactured devices for heat pipe applications

    Science.gov (United States)

    Hale, Renee S.; Bahadur, Vaibhav

    2017-07-01

    The heat transport capacity of traditional heat pipes is limited by the capillary pressure generated in the internal wick that pumps condensate to the evaporator. Recently, the authors conceptualized a novel heat pipe architecture, wherein wick-based pumping is replaced by electrowetting (EW)-based pumping of microliter droplets in the adiabatic section. An electrowetting heat pipe (EHP) can overcome the capillary limit to heat transport capacity and enable compact, planar, gravity-insensitive, and ultralow power consumption heat pipes that transport kiloWatt heat loads over extended distances. This work develops a novel technique for rapid, scalable fabrication of EW-based devices and studies critical microfluidic operations underlying the EHP, with the objective of predicting the key performance parameters of the EHP. Devices are fabricated on a printed circuit board (PCB) substrate with mechanically-milled electrodes, and a removable polyimide dielectric film. The first set of experiments uncovers the maximum channel gap (1 mm) for reliable EW-based pumping; this parameter determines the heat transport capacity of the EHP, which scales linearly with the channel gap. The second set of experiments uncovers the maximum channel gap (375 microns) at which EW voltages can successfully split droplets. This is an important consideration which ensures EHP operability in the event of unintentional droplet merging. The third set of experiments demonstrate and study EW-induced droplet generation from an open-to-air reservoir, which mimics the interface between the condenser and adiabatic sections of the EHP. The experimental findings predict that planar, water-based EHPs with a (10 cm by 4 mm) cross section can transport 1.6 kW over extended distances (>1 m), with a thermal resistance of 0.01 K W-1.

  10. 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.

  11. 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.

  12. 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)

  13. A novel temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

    DEFF Research Database (Denmark)

    Bu, Minqiang; R. Perch-Nielsen, Ivan; Sørensen, Karen Skotte

    steps to achieve a rapid ramping between the temperature steps for DNA denaturation, annealing and extension. The temperature dynamics within the microfluidic PCR chamber was characterized and the overshooting and undershooting parameters were optimized using the temperature dependent fluorescence......We present a new temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with external heater and temperature sensor. The method employs optimized temperature overshooting and undershooting...

  14. A temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

    DEFF Research Database (Denmark)

    Bu, Minqiang; Perch-Nielsen, Ivan R.; Sørensen, Karen Skotte

    2013-01-01

    steps to achieve a rapid ramping between the temperature steps for DNA denaturation, annealing and extension. The temperature dynamics within the microfluidic PCR chamber was characterized and the overshooting and undershooting parameters were optimized using the temperature-dependent fluorescence......We present a temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with an external heater and a temperature sensor. The method employs optimized temperature overshooting and undershooting...

  15. 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.

  16. Miniaturized microscope for high throughput screening of tumor spheroids in microfluidic devices

    Science.gov (United States)

    Uranga, Javier; Rodríguez-Pena, Alejandro; Gahigiro, Desiré; Ortiz-de-Solorzano, Carlos

    2018-02-01

    High-throughput in vitro screening of highly physiological three-dimensional cell cultures (3D-HTS) is rapidly gaining importance in preclinical studies, to study the effect of the microenvironment in tumor development, and to evaluate the efficacy of new anticancer drugs. Furthermore, it could also be envisioned the use of 3D-HTS systems in personalized anti-cancer treatment planning, based on tumor organoids or spheroids grown from tumor biopsies or isolated tumor circulating cells. Most commercial, multi-well plate based 3D-HTS systems are large, expensive, and are based on the use of multi-well plates that hardly provide a physiological environment and require the use of large amounts of biological material and reagents. In this paper we present a novel, miniaturized inverted microscope (hereinafter miniscospe), made up of low-cost, mass producible parts, that can be used to monitor the growth of living tumor cell spheroids within customized three-dimensional microfluidic platforms. Our 3D-HTS miniscope combines phase contrast imaging based on oblique back illumination technique with traditional widefield epi-fluorescence imaging, implemented using miniaturized electro-optical parts and gradient-index refraction lenses. This small (3x6x2cm), lightweight device can effectively image overtime the growth of (>200) tumor spheroids in a controlled and reproducible environment. Our miniscope can be used to acquire time-lapse images of cellular living spheroids over the course of several hours and captures their growth before and after drug treatment, to evaluate the effectiveness of the drug.

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

    Science.gov (United States)

    Karita, Shingo; Kaneta, Takashi

    2014-12-16

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

  18. 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.

  19. A novel microfluidic rapid freeze-quench device for trapping reactions intermediates for high field EPR analysis.

    Science.gov (United States)

    Kaufmann, Royi; Yadid, Itamar; Goldfarb, Daniella

    2013-05-01

    Rapid freeze quench electron paramagnetic resonance (RFQ)-EPR is a method for trapping short lived intermediates in chemical reactions and subjecting them to EPR spectroscopy investigation for their characterization. Two (or more) reacting components are mixed at room temperature and after some delay the mixture is sprayed into a cold trap and transferred into the EPR tube. A major caveat in using commercial RFQ-EPR for high field EPR applications is the relatively large amount of sample needed for each time point, a major part of which is wasted as the dead volume of the instrument. The small sample volume (∼2μl) needed for high field EPR spectrometers, such as W-band (∼3.5T, 95GHz), that use cavities calls for the development of a microfluidic based RFQ-EPR apparatus. This is particularly important for biological applications because of the difficulties often encountered in producing large amounts of intrinsically paramagnetic proteins and spin labeled nucleic acid and proteins. Here we describe a dedicated microfluidic based RFQ-EPR apparatus suitable for small volume samples in the range of a few μl. The device is based on a previously published microfluidic mixer and features a new ejection mechanism and a novel cold trap that allows collection of a series of different time points in one continuous experiment. The reduction of a nitroxide radical with dithionite, employing the signal of Mn(2+) as an internal standard was used to demonstrate the performance of the microfluidic RFQ apparatus. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Microfluidic devices, systems, and methods for quantifying particles using centrifugal force

    Science.gov (United States)

    Schaff, Ulrich Y.; Sommer, Gregory J.; Singh, Anup K.

    2015-11-17

    Embodiments of the present invention are directed toward microfluidic systems, apparatus, and methods for measuring a quantity of cells in a fluid. Examples include a differential white blood cell measurement using a centrifugal microfluidic system. A method may include introducing a fluid sample containing a quantity of cells into a microfluidic channel defined in part by a substrate. The quantity of cells may be transported toward a detection region defined in part by the substrate, wherein the detection region contains a density media, and wherein the density media has a density lower than a density of the cells and higher than a density of the fluid sample. The substrate may be spun such that at least a portion of the quantity of cells are transported through the density media. Signals may be detected from label moieties affixed to the cells.

  1. 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

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

    Science.gov (United States)

    Ali, Haider; Park, Cheol Woo

    2016-11-01

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

  3. Surface texture change on-demand and microfluidic devices based on thickness mode actuation of dielectric elastomer actuators (DEAs)

    Science.gov (United States)

    Ankit, Ankit; Nguyen, Anh Chien; Mathews, Nripan

    2017-04-01

    Tactile feedback devices and microfluidic devices have huge significance in strengthening the area of robotics, human machine interaction and low cost healthcare. Dielectric Elastomer Actuators (DEAs) are an attractive alternative for both the areas; offering the advantage of low cost and simplistic fabrication in addition to the high actuation strains. The inplane deformations produced by the DEAs can be used to produce out-of-plane deformations by what is known as the thickness mode actuation of DEAs. The thickness mode actuation is achieved by adhering a soft passive layer to the DEA. This enables a wide area of applications in tactile applications without the need of complex systems and multiple actuators. But the thickness mode actuation has not been explored enough to understand how the deformations can be improved without altering the material properties; which is often accompanied with increased cost and a trade off with other closely associated material properties. We have shown the effect of dimensions of active region and non-active region in manipulating the out-of-plane deformation. Making use of this, we have been able to demonstrate large area devices and complex patterns on the passive top layer for the surface texture change on-demand applications. We have also been able to demonstrate on-demand microfluidic channels and micro-chambers without the need of actually fabricating the channels; which is a cost incurring and cumbersome process.

  4. Chromatographic Separation and Visual Detection on Wicking Microfluidic Devices: Quantitation of Cu2+ in Surface, Ground, and Drinking Water.

    Science.gov (United States)

    Bandara, Gayan C; Heist, Christopher A; Remcho, Vincent T

    2018-02-20

    Copper is widely applied in industrial and technological applications and is an essential micronutrient for humans and animals. However, exposure to high environmental levels of copper, especially through drinking water, can lead to copper toxicity, resulting in severe acute and chronic health effects. Therefore, regular monitoring of aqueous copper ions has become necessary as recent anthropogenic activities have led to elevated environmental concentrations of copper. On-site monitoring processes require an inexpensive, simple, and portable analytical approach capable of generating reliable qualitative and quantitative data efficiently. Membrane-based lateral flow microfluidic devices are ideal candidates as they facilitate rapid, inexpensive, and portable measurements. Here we present a simple, chromatographic separation approach in combination with a visual detection method for Cu 2+ quantitation, performed in a lateral flow microfluidic channel. This method appreciably minimizes interferences by incorporating a nonspecific polymer inclusion membrane (PIM) based assay with a "dot-counting" approach to quantification. In this study, hydrophobic polycaprolactone (PCL)-filled glass microfiber (GMF) membranes were used as the base substrate onto which the PIM was evenly dispensed as an array of dots. The devices thus prepared were then selectively exposed to oxygen radicals through a mask to generate a hydrophilic surface path along which the sample was wicked. Using this approach, copper concentrations from 1 to 20 ppm were quantified from 5 μL samples using only visual observation of the assay device.

  5. 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

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

    CSIR Research Space (South Africa)

    Hugo

    2013-10-01

    Full Text Available -of-care diagnostic systems, particularly in under-resourced settings to enable instant diagnosis and improve healthcare. Although numerous and varied advances in the field of microfluidics have enabled point-of-care systems to be realized, there is often a trade...

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

    KAUST Repository

    Yi, Xin; Kodzius, Rimantas; Gong, Xiuqing; Xiao, Kang; Wen, Weijia

    2010-01-01

    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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  9. Microfluidic devices for analysis and active optical sorting of individual cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Jan; Pilát, Zdeněk; Šerý, Mojmír; Kaňka, Jan; Samek, Ota; Bernatová, Silvie; Zemánek, Pavel

    2013-01-01

    Roč. 58, č. 2 (2013), s. 55-59 ISSN 0447-6441 R&D Projects: GA MPO FR-TI1/433; GA MŠk ED0017/01/01; GA ČR GAP205/11/1687 Institutional support: RVO:68081731 Keywords : microfluidic * cell sorting * optical tweezers * Raman spectroscopy Subject RIV: EI - Biotechnology ; Bionics

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

    NARCIS (Netherlands)

    Moolman, M.C.; Huang, Z.; Krishnan, S.T.; Kerssemakers, J.W.J.; Dekker, N.H.

    2013-01-01

    Background: Controlled restriction of cellular movement using microfluidics allows one to study individual cells to gain insight into aspects of their physiology and behaviour. For example, the use of micron-sized growth channels that confine individual Escherichia coli has yielded novel insights

  11. A low-cost, manufacturable method for fabricating capillary and optical fiber interconnects for microfluidic devices.

    Science.gov (United States)

    Hartmann, Daniel M; Nevill, J Tanner; Pettigrew, Kenneth I; Votaw, Gregory; Kung, Pang-Jen; Crenshaw, Hugh C

    2008-04-01

    Microfluidic chips require connections to larger macroscopic components, such as light sources, light detectors, and reagent reservoirs. In this article, we present novel methods for integrating capillaries, optical fibers, and wires with the channels of microfluidic chips. The method consists of forming planar interconnect channels in microfluidic chips and inserting capillaries, optical fibers, or wires into these channels. UV light is manually directed onto the ends of the interconnects using a microscope. UV-curable glue is then allowed to wick to the end of the capillaries, fibers, or wires, where it is cured to form rigid, liquid-tight connections. In a variant of this technique, used with light-guiding capillaries and optical fibers, the UV light is directed into the capillaries or fibers, and the UV-glue is cured by the cone of light emerging from the end of each capillary or fiber. This technique is fully self-aligned, greatly improves both the quality and the manufacturability of the interconnects, and has the potential to enable the fabrication of interconnects in a fully automated fashion. Using these methods, including a semi-automated implementation of the second technique, over 10,000 interconnects have been formed in almost 2000 microfluidic chips made of a variety of rigid materials. The resulting interconnects withstand pressures up to at least 800psi, have unswept volumes estimated to be less than 10 femtoliters, and have dead volumes defined only by the length of the capillary.

  12. 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...

  13. Microfluidic interconnects

    Science.gov (United States)

    Benett, William J.; Krulevitch, Peter A.

    2001-01-01

    A miniature connector for introducing microliter quantities of solutions into microfabricated fluidic devices. The fluidic connector, for example, joins standard high pressure liquid chromatography (HPLC) tubing to 1 mm diameter holes in silicon or glass, enabling ml-sized volumes of sample solutions to be merged with .mu.l-sized devices. The connector has many features, including ease of connect and disconnect; a small footprint which enables numerous connectors to be located in a small area; low dead volume; helium leak-tight; and tubing does not twist during connection. Thus the connector enables easy and effective change of microfluidic devices and introduction of different solutions in the devices.

  14. 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.

  15. 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.

  16. Measurement of in-plane elasticity of live cell layers using a pressure sensor embedded microfluidic device

    Science.gov (United States)

    Lin, Chien-Han; Wang, Chien-Kai; Chen, Yu-An; Peng, Chien-Chung; Liao, Wei-Hao; Tung, Yi-Chung

    2016-11-01

    In various physiological activities, cells experience stresses along their in-plane direction when facing substrate deformation. Capability of continuous monitoring elasticity of live cell layers during a period is highly desired to investigate cell property variation during various transformations under normal or disease states. This paper reports time-lapsed measurement of live cell layer in-plane elasticity using a pressure sensor embedded microfluidic device. The sensor converts pressure-induced deformation of a flexible membrane to electrical signals. When cells are cultured on top of the membrane, flexural rigidity of the composite membrane increases and further changes the output electrical signals. In the experiments, human embryonic lung fibroblast (MRC-5) cells are cultured and analyzed to estimate the in-plane elasticity. In addition, the cells are treated with a growth factor to simulate lung fibrosis to study the effects of cell transformation on the elasticity variation. For comparison, elasticity measurement on the cells by atomic force microscopy (AFM) is also performed. The experimental results confirm highly anisotropic configuration and material properties of cells. Furthermore, the in-plane elasticity can be monitored during the cell transformation after the growth factor stimulation. Consequently, the developed microfluidic device provides a powerful tool to study physical properties of cells for fundamental biophysics and biomedical researches.

  17. Simultaneous determination of renal function biomarkers in urine using a validated paper-based microfluidic analytical device.

    Science.gov (United States)

    Rossini, Eduardo Luiz; Milani, Maria Izabel; Carrilho, Emanuel; Pezza, Leonardo; Pezza, Helena Redigolo

    2018-01-02

    In this paper, we describe a validated paper-based microfluidic analytical device for the simultaneous quantification of two important biomarkers of renal function in urine. This paper platform provides an inexpensive, simple, and easy to use colorimetric method for the quantification of creatinine (CRN) and uric acid (UA) in urine samples. The microfluidic paper-based analytical device (μPAD) consists of a main channel with three identical arms, each containing a circular testing zone and a circular uptake zone. Creatinine detection is based on the Jaffé reaction, in which CRN reacts with picrate to form an orange-red product. Uric acid quantification is based on the reduction of Fe 3+ to Fe 2+ by UA, which is detected in a colorimetric reaction using 1,10-phenanthroline. Under optimum conditions, obtained through chemometrics, the concentrations of the analytes showed good linear correlations with the effective intensities, and the method presented satisfactory repeatability. The limits of detection and the linear ranges, respectively, were 15.7 mg L -1 and 50-600 mg L -1 for CRN and 16.5 mg L -1 and 50-500 mg L -1 for UA. There were no statistically significant differences between the results obtained using the μPAD and a chromatographic comparative method (Student's t-test at 95% confidence level). Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Development of Multiscale Materials in Microfluidic Devices: Case Study for Viral Separation from Whole Blood

    Science.gov (United States)

    Surawathanawises, Krissada

    such as blood cells, and the nanoscale pores promote permeation for affinity capture of bionanoparticles. Consequently, particles with a size difference of 3--4 orders of magnitude can be separated in a simple flow-through process. Computational analyses are employed to study the effect of micropattern shape and layout. A half-ring pattern is shown to reduce flow resistance and promote fluid permeation compared to a circular pattern. In the experiment, the micropatterned porous arrays yield around 4 times higher viral capture from whole blood compared with a micropatterned solid array. The micropatterned porous devices are capable of handling a large volume of fluid sample without clogging by cells. Therefore they can be used for nanoparticle concentration. Our study also indicates that the layout of micropatterns can be adjusted to improve the capture yield. For example, an increase in pattern radius, or a decrease in gap distance between each post and in width of half ring will enhance fluid permeation in the porous structure. When combined with downstream detection, these materials integrated into microfluidic platforms can be created as point-of-care diagnostics, as well as other applications for particle separation and analysis. (Abstract shortened by UMI.).

  19. Controlled and tunable polymer particles' production using a single microfluidic device

    Science.gov (United States)

    Amoyav, Benzion; Benny, Ofra

    2018-04-01

    Microfluidics technology offers a new platform to control liquids under flow in small volumes. The advantage of using small-scale reactions for droplet generation along with the capacity to control the preparation parameters, making microfluidic chips an attractive technology for optimizing encapsulation formulations. However, one of the drawback in this methodology is the ability to obtain a wide range of droplet sizes, from sub-micron to microns using a single chip design. In fact, typically, droplet chips are used for micron-dimension particles, while nanoparticles' synthesis requires complex chips design (i.e., microreactors and staggered herringbone micromixer). Here, we introduce the development of a highly tunable and controlled encapsulation technique, using two polymer compositions, for generating particles ranging from microns to nano-size using the same simple single microfluidic chip design. Poly(lactic-co-glycolic acid) (PLGA 50:50) or PLGA/polyethylene glycol polymeric particles were prepared with focused-flow chip, yielding monodisperse particle batches. We show that by varying flow rate, solvent, surfactant and polymer composition, we were able to optimize particles' size and decrease polydispersity index, using simple chip designs with no further related adjustments or costs. Utilizing this platform, which offers tight tuning of particle properties, could offer an important tool for formulation development and can potentially pave the way towards a better precision nanomedicine.

  20. 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.

  1. 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.

  2. Non-invasive paper-based microfluidic device for ultra-low detection of urea through enzyme catalysis

    Science.gov (United States)

    Suresh, Vignesh; Qunya, Ong; Kanta, Bera Lakshmi; Yuh, Lee Yeong; Chong, Karen S. L.

    2018-03-01

    This work describes the design, fabrication and characterization of a paper-based microfluidic device for ultra-low detection of urea through enzyme catalysis. The microfluidic system comprises an entry port, a fluidic channel, a reaction zone and two electrodes (contacts). Wax printing was used to create fluidic channels on the surface of a chromatography paper. Pre-conceptualized designs of the fluidic channel are wax-printed on the paper substrate while the electrodes are screen-printed. The paper printed with wax is heated to cause the wax reflow along the thickness of the paper that selectively creates hydrophilic and hydrophobic zones inside the paper. Urease immobilized in the reaction zone catalyses urea into releasing ions and, thereby, generating a current flow between the electrodes. A measure of current with respect to time at a fixed potential enables the detection of urea. The methodology enabled urea concentration down to 1 pM to be detected. The significance of this work lies in the use of simple and inexpensive paper-based substrates to achieve detection of ultra-low concentrations of analytes such as urea. The process is non-invasive and employs a less cumbersome two-electrode assembly.

  3. Volume-of-fluid simulations in microfluidic T-junction devices: Influence of viscosity ratio on droplet size

    Science.gov (United States)

    Nekouei, Mehdi; Vanapalli, Siva A.

    2017-03-01

    We used volume-of-fluid (VOF) method to perform three-dimensional numerical simulations of droplet formation of Newtonian fluids in microfluidic T-junction devices. To evaluate the performance of the VOF method we examined the regimes of drop formation and determined droplet size as a function of system parameters. Comparison of the simulation results with four sets of experimental data from the literature showed good agreement, validating the VOF method. Motivated by the lack of adequate studies investigating the influence of viscosity ratio (λ) on the generated droplet size, we mapped the dependence of drop volume on capillary number (0.001 1. In addition, we find that at a given capillary number, the size of droplets does not vary appreciably when λ 1. We develop an analytical model for predicting the droplet size that includes a viscosity-dependent breakup time for the dispersed phase. This improved model successfully predicts the effects of the viscosity ratio observed in simulations. Results from this study are useful for the design of lab-on-chip technologies and manufacture of microfluidic emulsions, where there is a need to know how system parameters influence the droplet size.

  4. Integrated electrokinetically driven microfluidic devices with pH-mediated solid-phase extraction coupled to microchip electrophoresis for preterm birth biomarkers.

    Science.gov (United States)

    Sonker, Mukul; Knob, Radim; Sahore, Vishal; Woolley, Adam T

    2017-07-01

    Integration in microfluidics is important for achieving automation. Sample preconcentration integrated with separation in a microfluidic setup can have a substantial impact on rapid analysis of low-abundance disease biomarkers. Here, we have developed a microfluidic device that uses pH-mediated solid-phase extraction (SPE) for the enrichment and elution of preterm birth (PTB) biomarkers. Furthermore, this SPE module was integrated with microchip electrophoresis for combined enrichment and separation of multiple analytes, including a PTB peptide biomarker (P1). A reversed-phase octyl methacrylate monolith was polymerized as the SPE medium in polyethylene glycol diacrylate modified cyclic olefin copolymer microfluidic channels. Eluent for pH-mediated SPE of PTB biomarkers on the monolith was optimized using different pH values and ionic concentrations. Nearly 50-fold enrichment was observed in single channel SPE devices for a low nanomolar solution of P1, with great elution time reproducibility (electrophoresis in our integrated device with ∼15-fold enrichment. This device shows important progress towards an integrated electrokinetically operated platform for preconcentration and separation of biomarkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Effect of gold nanoparticles on thermal gradient generation and thermotaxis of E. coli cells in microfluidic device.

    Science.gov (United States)

    Murugesan, Nithya; Panda, Tapobrata; Das, Sarit K

    2016-08-01

    Bacteria responds to changing chemical and thermal environment by moving towards or away from a particular location. In this report, we looked into thermal gradient generation and response of E. coli DH5α cells to thermal gradient in the presence and in the absence of spherical gold nanoparticles (size: 15 to 22 nm) in a static microfluidic environment using a polydimethylsiloxane (PDMS) made microfluidic device. A PDMS-agarose based microfluidic device for generating thermal gradient has been developed and the thermal gradient generation in the device has been validated with the numerical simulation. Our studies revealed that the presence of gold nanoparticles, AuNPs (0.649 μg/mL) has no effect on the thermal gradient generation. The E. coli DH5α cells have been treated with AuNPs of two different concentrations (0.649 μg/mL and 0.008 μg/mL). The thermotaxis behavior of cells in the presence of AuNPs has been studied and compared to the thermotaxis of E.coli DH5α cells in the absence of AuNPs. In case of thermotaxis, in the absence of the AuNPs, the E. coli DH5α cells showed better thermotaxis towards lower temperature range, whereas in the presence of AuNPs (0.649 μg/mL and 0.008 μg/mL) thermotaxis of the E. coli DH5α cells has been inhibited. The results show that the spherical AuNPs intervenes in the themotaxis of E. coli DH5α cells and inhibits the cell migration. The reason for the failure in thermotaxis response mechanism may be due to decreased F-type ATP synthase activity and collapse of membrane potential by AuNPs, which, in turn, leads to decreased ATP levels. This has been hypothesized since both thermotaxis and chemotaxis follows the same response mechanism for migration in which ATP plays critical role.

  6. 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.

  7. 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.

  8. 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.

  9. Rapid characterization of the biomechanical properties of drug-treated cells in a microfluidic device

    International Nuclear Information System (INIS)

    Zhang, Xiaofei; Zhang, Yang; Bai, Guohua; Tan, Qiulin; Sun, Dong; Chu, Henry K; Wang, Kaiqun

    2015-01-01

    Cell mechanics is closely related to many cell functions. Recent studies have suggested that the deformability of cells can be an effective biomarker to indicate the onset and progression of diseases. In this paper, a microfluidic chip is designed for rapid characterization of the mechanics of drug-treated cells through stretching with dielectrophoresis (DEP) force. This chip was fabricated using PDMS and micro-electrodes were integrated and patterned on the ITO layer of the chip. Leukemia NB4 cells were considered and the effect of all-trans retinoic acid (ATRA) drug on NB4 cells were examined via the microfluidic chip. To induce a DEP force onto the cell, a relatively weak ac voltage was utilized to immobilize a cell at one side of the electrodes. The applied voltage was then increased to 3.5 V pp and the cell started to be stretched along the applied electric field lines. The elongation of the cell was observed using an optical microscope and the results showed that both types of cells were deformed by the induced DEP force. The strain of the NB4 cell without the drug treatment was recorded to be about 0.08 (time t = 180 s) and the drug-treated NB4 cell was about 0.21 (time t = 180 s), indicating a decrease in the stiffness after drug treatment. The elastic modulus of the cell was also evaluated and the modulus changed from 140 Pa to 41 Pa after drug treatment. This microfluidic chip can provide a simple and rapid platform for measuring the change in the biomechanical properties of cells and can potentially be used as the tool to determine the biomechanical effects of different drug treatments for drug discovery and development applications. (paper)

  10. Micro-scale experimental study of Microbial-Induced Carbonate Precipitation (MICP) by using microfluidic devices

    Science.gov (United States)

    Wang, Y.; Soga, K.; DeJong, J. T.; Kabla, A.

    2017-12-01

    Microbial-induced carbonate precipitation (MICP), one of the bio-mineralization processes, is an innovative subsurface improvement technique for enhancing the strength and stiffness of soils, and controlling their hydraulic conductivity. These macro-scale engineering properties of MICP treated soils controlled by micro-scale factors of the precipitated carbonate, such as its content, amount and distribution in the soil matrix. The precipitation process itself is affected by bacteria amount, reaction kinetics, porous medium geometry and flow distribution in the soils. Accordingly, to better understand the MICP process at the pore scale a new experimental technique that can observe the entire process of MICP at the pore-scale was developed. In this study, a 2-D transparent microfluidic chip made of Polydimethylsiloxane (PDMS) representing the soil matrix was designed and fabricated. A staged-injection MICP treatment procedure was simulated inside the microfluidic chip while continuously monitored using microscopic techniques. The staged-injection MICP treatment procedure started with the injection of bacteria suspension, followed with the bacteria setting for attachment, and then ended with the multiple injections of cementation liquid. The main MICP processes visualized during this procedure included the bacteria transport and attachment during the bacteria injection, the bacteria attachment and growth during the bacteria settling, the bacteria detachment during the cementation liquid injection, the cementation development during the cementation liquid injection, and the cementation development after the completion of cementation liquid injection. It is suggested that the visualization of the main MICP processes using the microfluidic technique can improve understating of the fundamental mechanisms of MICP and consequently help improve the treatment technique for in situ implementation of MICP.

  11. Microfluidic devices for investigation of biomimetic membranes for sensor and separation applications

    DEFF Research Database (Denmark)

    Pszon-Bartosz, Kamila Justyna

    to microfluidic designs involving protein delivery to biomimetic membranes developed for sensor and separation applications. Finally, an OMP functionality modulation with β-cyclodextrin (β-CD) was shown and revealed the protein potential application as a sensor. Moreover, the β-CD blocker may be used to prevent...... for industrial applications. Among them are the inherent fragility of lipid membranes, the challenge of up-scaling the effective membrane area and the quantification of the protein delivery to the lipid membrane which may determined the biomimetic membrane application. This PhD thesis addresses the above...

  12. Rapid fabrication of pressure-driven open-channel microfluidic devices in omniphobic R(F) paper.

    Science.gov (United States)

    Glavan, Ana C; Martinez, Ramses V; Maxwell, E Jane; Subramaniam, Anand Bala; Nunes, Rui M D; Soh, Siowling; Whitesides, George M

    2013-08-07

    This paper describes the fabrication of pressure-driven, open-channel microfluidic systems with lateral dimensions of 45-300 microns carved in omniphobic paper using a craft-cutting tool. Vapor phase silanization with a fluorinated alkyltrichlorosilane renders paper omniphobic, but preserves its high gas permeability and mechanical properties. When sealed with tape, the carved channels form conduits capable of guiding liquid transport in the low-Reynolds number regime (i.e. laminar flow). These devices are compatible with complex fluids such as droplets of water in oil. The combination of omniphobic paper and a craft cutter enables the development of new types of valves and switches, such as "fold valves" and "porous switches," which provide new methods to control fluid flow.

  13. Capacitance variation induced by microfluidic two-phase flow across insulated interdigital electrodes in lab-on-chip devices.

    Science.gov (United States)

    Dong, Tao; Barbosa, Cátia

    2015-01-26

    Microfluidic two-phase flow detection has attracted plenty of interest in various areas of biology, medicine and chemistry. This work presents a capacitive sensor using insulated interdigital electrodes (IDEs) to detect the presence of droplets in a microchannel. This droplet sensor is composed of a glass substrate, patterned gold electrodes and an insulation layer. A polydimethylsiloxane (PDMS) cover bonded to the multilayered structure forms a microchannel. Capacitance variation induced by the droplet passage was thoroughly investigated with both simulation and experimental work. Olive oil and deionized water were employed as the working fluids in the experiments to demonstrate the droplet sensor. The results show a good sensitivity of the droplet with the appropriate measurement connection. This capacitive droplet sensor is promising to be integrated into a lab-on-chip device for in situ monitoring/counting of droplets or bubbles.

  14. One-step patterning of hollow microstructures in paper by laser cutting to create microfluidic analytical devices.

    Science.gov (United States)

    Nie, Jinfang; Liang, Yuanzhi; Zhang, Yun; Le, Shangwang; Li, Dunnan; Zhang, Songbai

    2013-01-21

    In this paper, we report a simple, low-cost method for rapid, highly reproductive fabrication of paper-based microfluidics by using a commercially available, minitype CO(2) laser cutting/engraving machine. This method involves only one operation of cutting a piece of paper by laser according to a predesigned pattern. The hollow microstructures formed in the paper are used as the 'hydrophobic barriers' to define the hydrophilic flowing paths. A typical paper device on a 4 cm × 4 cm piece of paper can be fabricated within ∼7-20 s; it is ready for use once the cutting process is finished. The main fabrication parameters such as the applied current and cutting rate of the laser were optimized. The fabrication resolution and multiplexed analytical capability of the hollow microstructure-patterned paper were also characterized.

  15. High-throughput deterministic single-cell encapsulation and droplet pairing, fusion, and shrinkage in a single microfluidic device.

    Science.gov (United States)

    Schoeman, Rogier M; Kemna, Evelien W M; Wolbers, Floor; van den Berg, Albert

    2014-02-01

    In this article, we present a microfluidic device capable of successive high-yield single-cell encapsulation in droplets, with additional droplet pairing, fusion, and shrinkage. Deterministic single-cell encapsulation is realized using Dean-coupled inertial ordering of cells in a Yin-Yang-shaped curved microchannel using a double T-junction, with a frequency over 2000 Hz, followed by controlled droplet pairing with a 100% success rate. Subsequently, droplet fusion is realized using electrical actuation resulting in electro-coalescence of two droplets, each containing a single HL60 cell, with 95% efficiency. Finally, volume reduction of the fused droplet up to 75% is achieved by a triple pitchfork structure. This droplet volume reduction is necessary to obtain close cell-cell membrane contact necessary for final cell electrofusion, leading to hybridoma formation, which is the ultimate aim of this research. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release.

    Directory of Open Access Journals (Sweden)

    Gurinder K Vinner

    Full Text Available The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly difficult to treat with existing antibiotics; phage therapy may offer a viable alternative. The punitive environment within the gastrointestinal tract can inactivate orally delivered phages. C. difficile specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive polymer (Eudragit® S100 with and without alginate using a flow focussing glass microcapillary device. Highly monodispersed core-shell microparticles containing phages trapped within the particle core were produced by in situ polymer curing using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated microparticles could be precisely controlled in the range 80 μm to 160 μm through design of the microfluidic device geometry and by varying flow rates of the dispersed and continuous phase. In contrast to free 'naked' phages, those encapsulated within the microparticles could withstand a 3 h exposure to simulated gastric fluid at pH 2 and then underwent a subsequent pH triggered burst release at pH 7. The significance of our research is in demonstrating that C. difficile specific phage can be formulated and encapsulated in highly uniform pH responsive microparticles using a microfluidic system. The microparticles were shown to afford significant protection to the encapsulated phage upon prolonged exposure to an acid solution mimicking the human stomach environment. Phage encapsulation and subsequent release kinetics revealed that the microparticles prepared using Eudragit® S100 formulations possess pH responsive characteristics with phage release triggered in an intestinal pH range suitable for therapeutic

  17. 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.

  18. Different migration patterns of sea urchin and mouse sperm revealed by a microfluidic chemotaxis device.

    Directory of Open Access Journals (Sweden)

    Haixin Chang

    Full Text Available Chemotaxis refers to a process whereby cells move up or down a chemical gradient. Sperm chemotaxis is known to be a strategy exploited by marine invertebrates such as sea urchins to reach eggs efficiently in moving water. Less is understood about how or whether chemotaxis is used by mammalian sperm to reach eggs, where fertilization takes place within the confinement of a reproductive tract. In this report, we quantitatively assessed sea urchin and mouse sperm chemotaxis using a recently developed microfluidic model and high-speed imaging. Results demonstrated that sea urchin Arbacia punctulata sperm were chemotactic toward the peptide resact with high chemotactic sensitivity, with an average velocity Vx up the chemical gradient as high as 20% of its average speed (238 μm/s, while mouse sperm displayed no statistically significant chemotactic behavior in progesterone gradients, which had been proposed to guide mammalian sperm toward eggs. This work demonstrates the validity of a microfluidic model for quantitative sperm chemotaxis studies, and reveals a biological insight that chemotaxis up a progesterone gradient may not be a universal strategy for mammalian sperm to reach eggs.

  19. "Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

    Science.gov (United States)

    Schütte, Julia; Hagmeyer, Britta; Holzner, Felix; Kubon, Massimo; Werner, Simon; Freudigmann, Christian; Benz, Karin; Böttger, Jan; Gebhardt, Rolf; Becker, Holger; Stelzle, Martin

    2011-06-01

    In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

  20. Mass-manufacturable polymer microfluidic device for dual fiber optical trapping.

    Science.gov (United States)

    De Coster, Diane; Ottevaere, Heidi; Vervaeke, Michael; Van Erps, Jürgen; Callewaert, Manly; Wuytens, Pieter; Simpson, Stephen H; Hanna, Simon; De Malsche, Wim; Thienpont, Hugo

    2015-11-30

    We present a microfluidic chip in Polymethyl methacrylate (PMMA) for optical trapping of particles in an 80µm wide microchannel using two counterpropagating single-mode beams. The trapping fibers are separated from the sample fluid by 70µm thick polymer walls. We calculate the optical forces that act on particles flowing in the microchannel using wave optics in combination with non-sequential ray-tracing and further mathematical processing. Our results are compared with a theoretical model and the Mie theory. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we show the trapping capabilities of the hot embossed chip by trapping spherical beads with a diameter of 6µm, 8µm and 10µm and use the power spectrum analysis of the trapped particle displacements to characterize the trap strength.

  1. A facile and fast approach for the synthesis of doped nanoparticles using a microfluidic device

    International Nuclear Information System (INIS)

    Singh, Akanksha; Limaye, Mukta; Singh, Shashi; Kulkarni, Sulabha; Lalla, Niranjan Prasad; Malek, Chantal Khan

    2008-01-01

    The microfluidic approach emerges as a new and promising technology for the synthesis of nanomaterials. A microreactor allows a variety of reaction conditions to be quickly scanned without consuming large amounts of raw material. In this study, we investigated the synthesis of water soluble 1-thioglycerol-capped Mn-doped ZnS nanocrystalline semiconductor nanoparticles (TG-capped ZnS:Mn) via a microfluidic approach. This is the first report for the successful doping of Mn in a ZnS semiconductor at room temperature as well as at 80 deg. C using a microreactor. Transmission electron microscopy and x-ray diffraction analysis show that the average particle size of Mn-doped ZnS nanoparticles is ∼3.0 nm with a zinc-blende structure. Photoluminescence, x-ray photoelectron spectroscopy, atomic absorption spectroscopy and electron paramagnetic resonance studies were carried out to confirm that the Mn 2+ dopants are present in the ZnS nanoparticles

  2. Porous Polymeric Films from Microbubbles Generated Using a T-Junction Microfluidic Device.

    Science.gov (United States)

    Elsayed, M; Kothandaraman, A; Edirisinghe, M; Huang, J

    2016-12-20

    In this work, a simple microfluidic junction with a T geometry and coarse (200 μm diameter) capillaries was used to generate monodisperse microbubbles with an alginate polymer shell. Subsequently, these bubbles were used to prepare porous alginate films with good control over the pore structure. The lack of pore size, shape, and surface control in scalable forming of polymeric films is a major application-limiting drawback at present. Controlling the thinning process of the shell of the bubbles to tune the surface of the resulting structures was also explored. Films were prepared with nanopatterned surfaces by controlling the thinning of the bubble shell, with the aid of surfactants, to induce efficient bursting (fragmentation) of bubbles to generate nanodroplets, which become embedded within the film surface. This novel feature greatly expands and enhances the use of hydrophilic polymers in a wide range of biomedical applications, particularly in drug delivery and tissue engineering, such as studying cellular responses to different morphological surfaces.

  3. Development of microfluidic cell culture devices towards an in vitro human intestinal barrier model

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin

    to enable real-time detection of cell responses, adjustment of cellular stimulation etc. leading to establishment of conditional experiments. In this project, microfluidic systems engineering was leveraged to develop an eight chamber multi-layer microchip for intestinal barrier studies. Sandwiched between...... the layers was a modified Teflon porous membrane for cell culture. The novelty lies in modifying the surface of the porous Teflon support membrane using thiol-ene ‘click’ chemistry, thus allowing the modified Teflon membrane to be bonded between the chip layers to form an enclosed microchip. Successful...... application of the multi-layer microchip was demonstrated by integrating the microchip to an existing cell culture fluidic system to culture the human intestinal epithelial cells, Caco-2, for long term studies. Under the continuous low flow conditions, the cells differentiated into columnar cells displaying...

  4. Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a-Chip Applications

    Directory of Open Access Journals (Sweden)

    Qi Tang

    2016-04-01

    Full Text Available THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.

  5. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    Energy Technology Data Exchange (ETDEWEB)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri, E-mail: d.pappas@ttu.edu

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  6. Battery-operated, portable, and flexible air microplasma generation device for fabrication of microfluidic paper-based analytical devices on demand.

    Science.gov (United States)

    Kao, Peng-Kai; Hsu, Cheng-Che

    2014-09-02

    A portable microplasma generation device (MGD) operated in ambient air is introduced for making a microfluidic paper-based analytical device (μPAD) that serves as a primary healthcare platform. By utilizing a printed circuit board fabrication process, a flexible and lightweight MGD can be fabricated within 30 min with ultra low-cost. This MGD can be driven by a portable power supply (less than two pounds), which can be powered using 12 V-batteries or ac-dc converters. This MGD is used to perform maskless patterning of hydrophilic patterns with sub-millimeter spatial resolution on hydrophobic paper substrates with good pattern transfer fidelity. Using this MGD to fabricate μPADs is demonstrated. With a proper design of the MGD electrode geometry, μPADs with 500-μm-wide flow channels can be fabricated within 1 min and with a cost of less than $USD 0.05/device. We then test the μPADs by performing quantitative colorimetric assay tests and establish a calibration curve for detection of glucose and nitrite. The results show a linear response to a glucose assay for 1-50 mM and a nitrite assay for 0.1-5 mM. The low cost, miniaturized, and portable MGD can be used to fabricate μPADs on demand, which is suitable for in-field diagnostic tests. We believe this concept brings impact to the field of biomedical analysis, environmental monitoring, and food safety survey.

  7. Transverse Chemotactic Migration of Bacteria from High to Low Permeability Regions in a Dual Permeability Porous Microfluidic Device

    Science.gov (United States)

    Singh, R.; Olson, M. S.

    2011-12-01

    Low permeability regions sandwiched between high permeability regions such as clay lenses are difficult to treat using conventional treatment methods. Trace concentrations of contaminants such as non-aqueous phase liquids (NAPLs) remain trapped in these regions and over the time diffuse out into surrounding water thereby acting as a long term source of groundwater contamination. Bacterial chemotaxis (directed migration toward a contaminant source), may be helpful in enhancing bioremediation of such contaminated sites. This study is focused on simulating a two-dimensional dual-permeability groundwater contamination scenario using microfluidic devices and evaluating transverse chemotactic migration of bacteria from high to low permeability regions. A novel bi-layer polydimethylsiloxane (PDMS) microfluidic device was fabricated using photolithography and soft lithography techniques to simulate contamination of a dual- permeability region due to leakage from an underground storage tank into a low permeability region. This device consists of a porous channel through which a bacterial suspension (Escherchia Coli HCB33) is flown and another channel for injecting contaminant/chemo-attractant (DL-aspertic acid) into the porous channel. The pore arrangement in the porous channel contains a 2-D low permeability region surrounded by high permeability regions on both sides. Experiments were performed under chemotactic and non-chemotactic (replacing attractant with buffer solution in the non porous channel) conditions. Images were captured in transverse pore throats at cross-sections 4.9, 9.8, and 19.6 mm downstream from the attractant injection point and bacteria were enumerated in the middle of each pore throat. Bacterial chemotaxis was quantified in terms of the change in relative bacterial counts in each pore throat at cross-sections 9.8 and 19.6 mm with respect to counts at the cross-section at 4.9 mm. Under non-chemotactic conditions, relative bacterial count was observed

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

    Science.gov (United States)

    Yao, Yong; Zhang, Chunsun

    2016-10-01

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

  9. 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...

  10. Rapid detection of Cu(2+) by a paper-based microfluidic device coated with bovine serum albumin (BSA)-Au nanoclusters.

    Science.gov (United States)

    Fang, Xueen; Zhao, Qianqian; Cao, Hongmei; Liu, Juan; Guan, Ming; Kong, Jilie

    2015-11-21

    In this work, bovine serum albumin (BSA)-Au nanoclusters were used to coat a paper-based microfluidic device. This device acted as a Cu(2+) biosensor that showed fluorescence quenching on detection of copper ions. The detection limit of this sensor could be adjusted by altering the water absorbing capacity of the device. Qualitative and semi-quantitative results could be obtained visually without the aid of any advanced instruments. This sensor could test Cu(2+) rapidly with high specificity and sensitivity, which would be useful for point-of-care testing (POCT).

  11. Magnetic filtration of phase separating ferrofluids: From basic concepts to microfluidic device

    Science.gov (United States)

    Kuzhir, P.; Magnet, C.; Ezzaier, H.; Zubarev, A.; Bossis, G.

    2017-06-01

    In this work, we briefly review magnetic separation of ferrofluids composed of large magnetic particles (60 nm of the average size) possessing an induced dipole moment. Such ferrofluids exhibit field-induced phase separation at relatively low particle concentrations (∼0.8 vol%) and magnetic fields (∼10 kA/m). Particle aggregates appearing during the phase separation are extracted from the suspending fluid by magnetic field gradients much easier than individual nanoparticles in the absence of phase separation. Nanoparticle capture by a single magnetized microbead and by multi-collector systems (packed bed of spheres and micro-pillar array) has been studied both experimentally and theoretically. Under flow and magnetic fields, the particle capture efficiency Λ decreases with an increasing Mason number for all considered geometries. This decrease may become stronger for aggregated magnetic particles (Λ ∝Ma-1.7) than for individual ones (Λ ∝Ma-1) if the shear fields are strong enough to provoke aggregate rupture. These results can be useful for development of new magneto-microfluidic immunoassays based on magnetic nanoparticles offering a much better sensitivity as compared to presently used magnetic microbeads.

  12. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device.

    Science.gov (United States)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Fast cholesterol detection using flow injection microfluidic device with functionalized carbon nanotubes based electrochemical sensor.

    Science.gov (United States)

    Wisitsoraat, A; Sritongkham, P; Karuwan, C; Phokharatkul, D; Maturos, T; Tuantranont, A

    2010-12-15

    This work reports a new cholesterol detection scheme using functionalized carbon nanotube (CNT) electrode in a polydimethylsiloxane/glass based flow injection microfluidic chip. CNTs working, silver reference and platinum counter electrode layers were fabricated on the chip by sputtering and low temperature chemical vapor deposition methods. Cholesterol oxidase prepared in polyvinyl alcohol solution was immobilized on CNTs by in-channel flow technique. Cholesterol analysis based on flow injection chronoamperometric measurement was performed in 150-μm-wide and 150-μm-deep microchannels. Fast and sensitive real-time detection was achieved with high throughput of more than 60 samples per hour and small sample volume of 15 μl. The cholesterol sensor had a linear detection range between 50 and 400 mg/dl. In addition, low cross-sensitivities toward glucose, ascorbic acid, acetaminophen and uric acid were confirmed. The proposed system is promising for clinical diagnostics of cholesterol with high speed real-time detection capability, very low sample consumption, high sensitivity, low interference and good stability. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. A microfluidic device for study of the effect of tumor vascular structures on the flow field and HepG2 cellular flow behaviors.

    Science.gov (United States)

    Ke, Ming; Cai, Shaoxi; Zou, Misha; Zhao, Yi; Li, Bo; Chen, Sijia; Chen, Longcong

    2018-01-29

    To build a microfluidic device with various morphological features of the tumor vasculature for study of the effects of tumor vascular structures on the flow field and tumor cellular flow behaviors. The designed microfluidic device was able to approximatively simulate the in vivo structures of tumor vessels and the flow within it. In this models, the influences of the angle of bifurcation, the number of branches, and the narrow channels on the flow field and the influence of vorticity on the retention of HepG2 cells were significant. Additionally, shear stress below physiological conditions of blood circulation has considerable effect on the formation of the lumen-like structures (LLSs) of HepG2 cells. These results can provide some data and reference in the understanding of the interaction between hemorheological properties and tumor vascular structures in solid tumors. Copyright © 2018. Published by Elsevier Inc.

  15. Covalent immobilisation of antibodies in Teflon-FEP microfluidic devices for the sensitive quantification of clinically relevant protein biomarkers.

    Science.gov (United States)

    Pivetal, Jeremy; Pereira, Filipa M; Barbosa, Ana I; Castanheira, Ana P; Reis, Nuno M; Edwards, Alexander D

    2017-03-13

    This study reports for the first time the sensitive colorimetric and fluorescence detection of clinically relevant protein biomarkers by sandwich immunoassays using the covalent immobilisation of antibodies onto the fluoropolymer surface inside Teflon®-FEP microfluidic devices. Teflon®-FEP has outstanding optical transparency ideal for high-sensitivity colorimetric and fluorescence bioassays, however this thermoplastic is regarded as chemically inert and very hydrophobic. Covalent immobilisation can offer benefits over passive adsorption to plastic surfaces by allowing better control over antibody density, orientation and analyte binding capacity, and so we tested a range of different and novel covalent immobilisation strategies. We first functionalised the inner surface of a 10-bore, 200 μm internal diameter FEP microcapillary film with high-molecular weight polyvinyl alcohol (PVOH) without changing the outstanding optical transparency of the device delivered by the matched refractive index of FEP and water. Glutaraldehyde immobilisation was compared with the use of photoactivated linkers and NHS-ester crosslinkers for covalently immobilising capture antibodies onto PVOH. Three clinically relevant sandwich ELISAs were tested against the cytokine IL-1β, the myocardial infarct marker cardiac troponin I (cTnI), and the chronic heart failure marker brain natriuretic peptide (BNP). Overall, glutaraldehyde immobilisation was effective for BNP assays, but yielded unacceptable background for IL-1β and cTnI assays caused by direct binding of the biotinylated detection antibody to the modified PVOH surface. We found NHS-ester groups reacted with APTES-treated PVOH coated fluoropolymers. This facilitated a novel method for capture antibody immobilisation onto fluoropolymer devices using a bifunctional NHS-maleimide crosslinker. The density of covalently immobilised capture antibodies achieved using PVOH/APTES/NHS/maleimide approached levels seen with passive adsorption

  16. 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.

  17. 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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  19. 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.

  20. 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.

  1. Study on the Optimum Cutting Parameters of an Aluminum Mold for Effective Bonding Strength of a PDMS Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Caffiyar Mohamed Yousuff

    2017-08-01

    Full Text Available Master mold fabricated using micro milling is an easy way to develop the polydimethylsiloxane (PDMS based microfluidic device. Achieving high-quality micro-milled surface is important for excellent bonding strength between PDMS and glass slide. The aim of our experiment is to study the optimal cutting parameters for micro milling an aluminum mold insert for the production of a fine resolution microstructure with the minimum surface roughness using conventional computer numerical control (CNC machine systems; we also aim to measure the bonding strength of PDMS with different surface roughnesses. Response surface methodology was employed to optimize the cutting parameters in order to obtain high surface smoothness. The cutting parameters were demonstrated with the following combinations: 20,000 rpm spindle speed, 50 mm/min feed rate, depth of cut 5 µm with tool size 200 µm or less; this gives a fine resolution microstructure with the minimum surface roughness and strong bonding strength between PDMS–PDMS and PDMS–glass.

  2. Tandem sulfur chemiluminescence and flame ionization detection with planar microfluidic devices for the characterization of sulfur compounds in hydrocarbon matrices.

    Science.gov (United States)

    Luong, J; Gras, R; Shellie, R A; Cortes, H J

    2013-07-05

    The detection of sulfur compounds in different hydrocarbon matrices, from light hydrocarbon feedstocks to medium synthetic crude oil feeds provides meaningful information for optimization of refining processes as well as demonstration of compliance with petroleum product specifications. With the incorporation of planar microfluidic devices in a novel chromatographic configuration, sulfur compounds from hydrogen sulfide to alkyl dibenzothiophenes and heavier distributions of sulfur compounds over a wide range of matrices spanning across a boiling point range of more than 650°C can be characterized, using one single analytical configuration in less than 25min. In tandem with a sulfur chemiluminescence detector for sulfur analysis is a flame ionization detector. The flame ionization detector can be used to establish the boiling point range of the sulfur compounds in various hydrocarbon fractions for elemental specific simulated distillation analysis as well as profiling the hydrocarbon matrices for process optimization. Repeatability of less than 3% RSD (n=20) over a range of 0.5-1000 parts per million (v/v) was obtained with a limit of detection of 50 parts per billion and a linear range of 0.5-1000 parts per million with a correlation co-efficient of 0.998. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Microfluidic Device to Measure the Speed of C. elegans Using the Resistance Change of the Flexible Electrode

    Directory of Open Access Journals (Sweden)

    Jaehoon Jung

    2016-03-01

    Full Text Available This work presents a novel method to assess the condition of Caenorhabditis elegans (C. elegans through a resistance measurement of its undulatory locomotion speed inside a micro channel. As the worm moves over the electrode inside the micro channel, the length of the electrode changes, consequently behaving like a strain gauge. In this paper, the electrotaxis was applied for controlling the direction of motion of C. elegans as an external stimulus, resulting in the worm moving towards the cathode of the circuit. To confirm the proposed measurement method, a microfluidic device was developed that employs a sinusoidal channel and a thin polydimethylsiloxane (PDMS layer with an electrode. The PDMS layer maintains a porous structure to enable the flexibility of the electrode. In this study, 6 measurements were performed to obtain the speed of an early adult stage C. elegans, where the measured average speed was 0.35 (±0.05 mm/s. The results of this work demonstrate the application of our method to measure the speed of C. elegans undulatory locomotion. This novel approach can be applied to make such measurements without an imaging system, and more importantly, allows directly to detect the locomotion of C. elegans using an electrical signal (i.e., the change in resistance.

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

    OpenAIRE

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

    2016-01-01

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

  5. A microfabricated microfluidic bioMEMS device to model human brain aneurisms: the aneurysm-on-a-chip

    Science.gov (United States)

    Reece, Lisa M.; Khor, Jian Wei; Thakur, Raviraj; Amin, Ahmed; Wereley, Steven T.; Leary, James F.

    2015-03-01

    Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. There is little information concerning the causes of intracranial aneurysm formation, growth, and rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. Further, the evolution of any aneurysm is assumed to be caused by the remodeling of the affected blood vessel's material constituents (tunica intima, tunica media, or tunica adventitia). Velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, while the shear force mechanisms effecting wound closure are elusive. To study aneurysm pathogenesis, a lab-on-a-chip device is the key to discovering the underlying mechanisms of these lesions. A two-dimensional microfluidic model, the Aneurysm-on-a-Chip™ (AOC), was the logical answer to study particle flow within an aneurysm "sac". The AOC apparatus can track particles/cells when it is coupled to particle image velocimetry software (PIV) package. The AOC fluid flow was visualized using standard microscopy techniques with commercial microparticles and human aortic smooth muscle cells (HASMC). Images were taken during fluid flow experiments and PIV was utilized to monitor the flow of particles within the "sac" region, as well as particles entering and exiting the device. Quiver plots were generated from fluid flow experiments using standard 7 μm latex particles and fixed HASMC in PBS. PIV analysis shows that the particles flowed nicely from input to output. Wall shear stress provided evidence that there was some back flow at the edges of the "sac" - an indicator of aneurysm development in human patients.

  6. Numerical simulation of 3D boundary-driven acoustic streaming in microfluidic devices.

    Science.gov (United States)

    Lei, Junjun; Hill, Martyn; Glynne-Jones, Peter

    2014-02-07

    This article discusses three-dimensional (3D) boundary-driven streaming in acoustofluidic devices. Firstly, the 3D Rayleigh streaming pattern in a microchannel is simulated and its effect on the movement of microparticles of various sizes is demonstrated. The results obtained from this model show good comparisons with 3D experimental visualisations and demonstrate the fully 3D nature of the acoustic streaming field and the associated acoustophoretic motion of microparticles in acoustofluidic devices. This method is then applied to another acoustofluidic device in order to gain insights into an unusual in-plane streaming pattern. The origin of this streaming has not been fully described and its characteristics cannot be explained from the classical theory of Rayleigh streaming. The simulated in-plane streaming pattern was in good agreement with the experimental visualisation. The mechanism behind it is shown to be related to the active sound intensity field, which supports our previous findings on the mechanism of the in-plane acoustic streaming pattern visualised and modelled in a thin-layered capillary device.

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

    NARCIS (Netherlands)

    Mihailovic, M.

    2011-01-01

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

  8. Wafer-scale fabrication of glass-FEP-glass microfluidic devices for lipid bilayer experiments

    NARCIS (Netherlands)

    Bomer, Johan G.; Prokofyev, A.V.; van den Berg, Albert; le Gac, Severine

    2014-01-01

    We report a wafer-scale fabrication process for the production of glass-FEP-glass microdevices using UV-curable adhesive (NOA81) as gluing material, which is applied using a novel "spin & roll" approach. Devices are characterized for the uniformity of the gluing layer, presence of glue in the

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

    DEFF Research Database (Denmark)

    Senkbeil, Silja; Aho, Johanna; Yde, Leif

    2016-01-01

    of 2:1 and a maximal channel depth of 90 μm as well as the sealing of the finished devices with patterning and sealing speeds of up to 19 m min-1. By adding fumed silica nanoparticles to the uncured resins, it was possible to alter the rheological behavior of the resin system to fabricate shallow...

  10. Microfluidic device and methods for focusing fluid streams using electroosmotically induced pressures

    Science.gov (United States)

    Jacobson, Stephen C.; Ramsey, J. Michael

    2010-06-01

    A microfabricated device employing a bridging membrane and methods for electrokinetic transport of a liquid phase biological or chemical material using the same are described. The bridging membrane is deployed in or adjacent to a microchannel and permits either electric current flow or the transport of gas species, while inhibiting the bulk flow of material. The use of bridging membranes in accordance with this invention is applicable to electrokinetically inducing fluid flow to confine a selected material in a region of a microchannel that is not influenced by an electric field. Other structures for inducing fluid flow in accordance with this invention include nanochannel bridging membranes and alternating current fluid pumping devices. Applications of the bridging membranes according to this invention include the separation of species from a sample material, valving of fluids in a microchannel network, mixing of different materials in a microchannel, and the pumping of fluids.

  11. Wafer-scale fabrication of glass-FEP-glass microfluidic devices for lipid bilayer experiments.

    Science.gov (United States)

    Bomer, Johan G; Prokofyev, Alexander V; van den Berg, Albert; Le Gac, Séverine

    2014-12-07

    We report a wafer-scale fabrication process for the production of glass-FEP-glass microdevices using UV-curable adhesive (NOA81) as gluing material, which is applied using a novel "spin & roll" approach. Devices are characterized for the uniformity of the gluing layer, presence of glue in the microchannels, and alignment precision. Experiments on lipid bilayers with electrophysiological recordings using a model pore-forming polypeptide are demonstrated.

  12. A microfluidic device for continuous manipulation of biological cells using dielectrophoresis.

    Science.gov (United States)

    Das, Debanjan; Biswas, Karabi; Das, Soumen

    2014-06-01

    The present study demonstrates the design, simulation, fabrication and testing of a label-free continuous manipulation and separation micro-device of particles/biological cells suspended on medium based on conventional dielectrophoresis. The current dielectrophoretic device uses three planner electrodes to generate non-uniform electric field and induces both p-DEP and n-DEP force simultaneously depending on the dielectric properties of the particles and thus influencing at least two types of particles at a time. Numerical simulations were performed to predict the distribution of non-uniform electric field, DEP force and particle trajectories. The device is fabricated utilizing the advantage of bonding between PDMS and SU8 polymer. The p-DEP particles move away from the center of the streamline, while the n-DEP particles will follow the central streamline along the channel length. Dielectrophoretic effects were initially tested using polystyrene beads followed by manipulation of HeLa cells. In the experiment, it was observed that polystyrene beads in DI water always response as n-DEP up to 1MHz frequency, whereas HeLa cells in PBS medium response as n-DEP up to 400kHz frequency and then it experiences p-DEP up to 1MHz. Further, the microscopic observations of DEP responses of HeLa cells were verified by performing trapping experiment at static condition. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  13. Materials challenges for repeatable RF wireless device reconfiguration with microfluidic channels

    Science.gov (United States)

    Griffin, Anthony S.; Sottos, Nancy R.; White, Scott R.

    2018-03-01

    Recently, adaptive wireless devices have utilized displacement of EGaIn within microchannels as an electrical switching mechanism to enable reconfigurable electronics. Device reconfiguration using EGaIn in microchannels overcomes many challenges encountered by more traditional reconfiguration mechanisms such as diodes and microelectromechanical systems (MEMS). Reconfiguration using EGaIn is severely limited by undesired permanent shorting due to retention of the liquid in microchannels caused by wetting and rapid oxide skin formation. Here, we investigate the conditions which prevent repeatable electrical switching using EGaIn in microchannels. Initial contact angle tests of EGaIn on epoxy surfaces demonstrate the wettability of EGaIn on flat surfaces. SEM cross-sections of microchannels reveal adhesion of EGaIn residue to channel walls. Micro-computed tomography (microCT) scans of provide volumetric measurements of EGaIn remaining inside channels after flow cycling. Non-wetting coatings are proposed as materials based strategy to overcome these issues in future work.

  14. Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads.

    Science.gov (United States)

    Veerla, Sarath Chandra; Kim, Da Reum; Yang, Sung Yun

    2018-01-01

    Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications. A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week. The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system

  15. Rapid bonding enhancement by auxiliary ultrasonic actuation for the fabrication of cyclic olefin copolymer (COC) microfluidic devices

    International Nuclear Information System (INIS)

    Yu, H; Tor, S B; Loh, N H

    2014-01-01

    Thermal compression bonding is a straightforward, inexpensive and widely used method for enclosing open microchannels in thermoplastic microfluidic devices. It is advantageous over adhesive, solvent and grafting bonding methods in retaining material homogeneity. However, the trade-off between high bond strength and low microchannel deformation is always a crucial consideration in thermal compression bonding. In this study, an effective method for improving bond strength while retaining the microchannel integrity with negligible distortion is proposed and analyzed. Longitudinal ultrasonic actuation was applied to the preheated cyclic olefin copolymer (COC) substrates to achieve accelerated and enhanced bonding with an ultrasonic welding system. Intimate contact between the bonding surfaces before the ultrasonic actuation was found to be an important prior condition. With improper contact, several bonding defects would occur, such as voids, localized spot melting and edge melting. Under auxiliary ultrasonic vibration, within 10 s, the bond strength developed at the bonding interface could be dramatically improved compared with those achieved without ultrasonic actuation. The enhanced bond strength obtained at a preheating temperature of 20 °C lower than its T g could be comparable to the strength for pure thermal compression at 5 °C higher than its T g . It is believed that the ultrasonic energy introduced could elevate the interfacial temperature and facilitate the interdiffusion of molecular chain segments at the interface, consequently resulting in rapidly enhanced bonding. Also, the microchannel distortion after ultrasonic actuation was found to be satisfactory—another important requirement. From dynamic mechanical analysis, the glass transition temperature of COC was found to increase with increasing frequency, and the temperature of the bulk polymer under ultrasonic actuation was still well under T g ; therefore the deformation is minor under ultrasonic

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

    Directory of Open Access Journals (Sweden)

    Mosfera A. Chowdury

    2017-03-01

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

  17. Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

    Science.gov (United States)

    Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

    2014-06-05

    The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Distance-Based Tear Lactoferrin Assay on Microfluidic Paper Device Using Interfacial Interactions on Surface-Modified Cellulose.

    Science.gov (United States)

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

    2015-11-11

    "Distance-based" detection motifs on microfluidic paper-based analytical devices (μPADs) allow quantitative analysis without using signal readout instruments in a similar manner to classical analogue thermometers. To realize a cost-effective and calibration-free distance-based assay of lactoferrin in human tear fluid on a μPAD not relying on antibodies or enzymes, we investigated the fluidic mobilities of the target protein and Tb(3+) cations used as the fluorescent detection reagent on surface-modified cellulosic filter papers. Chromatographic elution experiments in a tear-like sample matrix containing electrolytes and proteins revealed a collapse of attractive electrostatic interactions between lactoferrin or Tb(3+) and the cellulosic substrate, which was overcome by the modification of the paper surface with the sulfated polysaccharide ι-carrageenan. The resulting μPAD based on the fluorescence emission distance successfully analyzed 0-4 mg mL(-1) of lactoferrin in complex human tear matrix with a lower limit of detection of 0.1 mg mL(-1) by simple visual inspection. Assay results of 18 human tear samples including ocular disease patients and healthy volunteers showed good correlation to the reference ELISA method with a slope of 0.997 and a regression coefficient of 0.948. The distance-based quantitative signal and the good batch-to-batch fabrication reproducibility relying on printing methods enable quantitative analysis by simply reading out "concentration scale marks" printed on the μPAD without performing any calibration and using any signal readout instrument.

  19. Sample pre-concentration with high enrichment factors at a fixed location in paper-based microfluidic devices.

    Science.gov (United States)

    Yeh, Shih-Hao; Chou, Kuang-Hua; Yang, Ruey-Jen

    2016-03-07

    The lack of sensitivity is a major problem among microfluidic paper-based analytical devices (μPADs) for early disease detection and diagnosis. Accordingly, the present study presents a method for improving the enrichment factor of low-concentration biomarkers by using shallow paper-based channels realized through a double-sided wax-printing process. In addition, the enrichment factor is further enhanced by exploiting the ion concentration polarization (ICP) effect on the cathodic side of the nanoporous membrane, in which a stationary sample plug is obtained. The occurrence of ICP on the shallow-channel μPAD is confirmed by measuring the current-voltage response as the external voltage is increased from 0 to 210 V (or the field strength from 0 to 1.05 × 10(4) V m(-1)) over 600 s. In addition, to the best of our knowledge, the electroosmotic flow (EOF) speed on the μPAD fabricated with a wax-channel is measured for the first time using a current monitoring method. The experimental results show that for a fluorescein sample, the concentration factor is increased from 130-fold in a conventional full-thickness paper channel to 944-fold in the proposed shallow channel. Furthermore, for a fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) sample, the proposed shallow-channel μPAD achieves an 835-fold improvement in the concentration factor. The concentration technique presented here provides a novel strategy for enhancing the detection sensitivity of μPAD applications.

  20. Combination of a Sample Pretreatment Microfluidic Device with a Photoluminescent Graphene Oxide Quantum Dot Sensor for Trace Lead Detection.

    Science.gov (United States)

    Park, Minsu; Ha, Hyun Dong; Kim, Yong Tae; Jung, Jae Hwan; Kim, Shin-Hyun; Kim, Do Hyun; Seo, Tae Seok

    2015-11-03

    A novel trace lead ion (Pb(2+)) detection platform by combining a microfluidic sample pretreatment device with a DNA aptamer linked photoluminescent graphene oxide quantum dot (GOQD) sensor was proposed. The multilayered microdevice included a microchamber which was packed with cation exchange resins for preconcentrating metal ions. The sample loading and recovery were automatically actuated by a peristaltic polydimethylsiloxane micropump with a flow rate of 84 μL/min. Effects of the micropump actuation time, metal ion concentration, pH, and the volumes of the sample and eluent on the metal ion capture and preconcentration efficiency were investigated on a chip. The Pb(2+) samples whose concentrations ranged from 0.48 nM to 1.2 μM were successfully recovered with a preconcentration factor value between 4 and 5. Then, the preconcentrated metal ions were quantitatively analyzed with a DNA aptamer modified GOQD. The DNA aptamer on the GOQD specifically captured the target Pb(2+) which can induce electron transfer from GOQD to Pb(2+) upon UV irradiation, thereby resulting in the fluorescence quenching of the GOQD. The disturbing effect of foreign anions on the Pb(2+) detection and the spiked Pb(2+) real samples were also analyzed. The proposed GOQD metal ion sensor exhibited highly sensitive Pb(2+) detection with a detection limit of 0.64 nM and a dynamic range from 1 to 1000 nM. The on-chip preconcentration of the trace metal ions from a large-volume sample followed by the metal ion detection by the fluorescent GOQD sensor can provide an advanced platform for on-site water pollution screening.

  1. Development of continuous processes for vegetable oil alcoholysis in microfluidic devices

    Directory of Open Access Journals (Sweden)

    Richard Romain

    2013-01-01

    Full Text Available Biodiesel can be produced from vegetable oils, animal fats, and waste cooking oils by transesterification with ethanol (also called ethanolysis in order to substitute fossil fuels. In this work, we were interested in the transesterification reaction of sunflower oil with ethanol, which leads to ethyl esters, used to date for applications principally in food and cosmetic industry. To open the application field to biofuels (to substitute current fuels resulting from fossil resources, the process efficiency has to be developed to be economically profitable. The batch reaction of vegetable oil ethanolysis was transposed to a micro-scaled continuous device (PFA tube of 508 μm internal diameter, inducing better heat and mass transfer. Study of the influence of the operational conditions (reactants flow, initial ethanol to oil molar ratio, temperature. . . revealed the favourable reaction parameters necessary to reach high conversions and yields. In these conditions, it is possible to acquire kinetics data at the first seconds of the reaction, which was not feasible in a conventional batch process. These data were used to model occurring phenomena and to determine kinetic constants and transfer coefficients. The model was subsequently used to simulate reactions with other operational conditions. To acquire these data in microreactors, an on-line analysis method by Near InfraRed (NIR spectroscopy was developed by using gas chromatography as a reference method. PLS models were then set up to quantify on-line the major compounds contents during the reaction.

  2. On-chip mitochondrial assay microfluidic devices and protein nanopore/nanotube hybrid transistor

    Science.gov (United States)

    Lim, Taesun

    Tremendous efforts to understand the cause, mechanism of development and the way to treat various diseases as well as an early diagnosis have been made so far and people are still working hardly on these researches. Even now, countless people are suffering from diseases such as Alzhemer's disease, Parkinson's disease, diabetes and cancer without knowing clues to cure their diseases completely. Generally speaking, we still have a long way to go through to comprehensively figure out these our long-lasting homeworks. One of possible solutions is to merge current advanced technology and science together to find a powerful synergetic effect for a specific purpose that can be tailored depending on user's need. Here this research tried to put nanotechnology and biological science together to find a way to resolve current challenges by developing a new generation of the analytical sensing device. Mitochondrial functions and biological roles in regulating life and death control will be discussed indicating mitochondrion is a crucial organism to monitor to obtain important information regarding degenerative diseases and aging process. On-chip mitochondrial functional assay microsensor that could facilitate the mitochondrial evaluation will be extensively demonstrated and discussed in both technical and biological perspectives. The novel fusion technological approach will be demonstrated by combining artificial cell membrane with carbon nanotube electronics to interrogate interactions between biomolecules and electronic circuitries. In addition, molecular dynamics at the cell membrane could be investigated closely which can help understand the cell-cell communication and the regulation of ion transport.

  3. Microfluidic paper-based device for colorimetric determination of glucose based on a metal-organic framework acting as peroxidase mimetic.

    Science.gov (United States)

    Ortiz-Gómez, Inmaculada; Salinas-Castillo, Alfonso; García, Amalia García; Álvarez-Bermejo, José Antonio; de Orbe-Payá, Ignacio; Rodríguez-Diéguez, Antonio; Capitán-Vallvey, Luis Fermín

    2017-12-13

    This work presents a microfluidic paper-based analytical device (μPAD) for glucose determination using a supported metal-organic framework (MOF) acting as a peroxidase mimic. The catalytic action of glucose oxidase (GOx) on glucose causes the formation of H 2 O 2 , and the MOF causes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H 2 O 2 to form a blue-green product with an absorption peak at 650 nm in the detection zone. A digital camera and the iOS feature of a smartphone are used for the quantitation of glucose with the S coordinate of the HSV color space as the analytical parameter. Different factors such as the concentration of TMB, GOx and MOF, pH and buffer, sample volume, reaction time and reagent position in the μPAD were optimized. Under optimal conditions, the value for the S coordinate increases linearly up to 150 μmol·L -1 glucose concentrations, with a 2.5 μmol·L -1 detection limit. The μPAD remains stable for 21 days under conventional storage conditions. Such an enzyme mimetic-based assay to glucose determination using Fe-MIL-101 MOF implemented in a microfluidic paper-based device possesses advantages over enzyme-based assays in terms of costs, durability and stability compared to other existing glucose determination methods. The procedure was applied to the determination of glucose in (spiked) serum and urine. Graphical abstract Schematic representation of microfluidic paper-based analytical device using metal-organic framework as a peroxidase mimic for colorimetric glucose detection with digital camera or smartphone and iOS app readout.

  4. 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.

  5. Aberration-free FTIR spectroscopic imaging of live cells in microfluidic devices.

    Science.gov (United States)

    Chan, K L Andrew; Kazarian, Sergei G

    2013-07-21

    The label-free, non-destructive chemical analysis offered by FTIR spectroscopic imaging is a very attractive and potentially powerful tool for studies of live biological cells. FTIR imaging of live cells is a challenging task, due to the fact that cells are cultured in an aqueous environment. While the synchrotron facility has proven to be a valuable tool for FTIR microspectroscopic studies of single live cells, we have demonstrated that high quality infrared spectra of single live cells using an ordinary Globar source can also be obtained by adding a pair of lenses to a common transmission liquid cell. The lenses, when placed on the transmission cell window, form pseudo hemispheres which removes the refraction of light and hence improve the imaging and spectral quality of the obtained data. This study demonstrates that infrared spectra of single live cells can be obtained without the focus shifting effect at different wavenumbers, caused by the chromatic aberration. Spectra of the single cells have confirmed that the measured spectral region remains in focus across the whole range, while spectra of the single cells measured without the lenses have shown some erroneous features as a result of the shift of focus. It has also been demonstrated that the addition of lenses can be applied to the imaging of cells in microfabricated devices. We have shown that it was not possible to obtain a focused image of an isolated cell in a droplet of DPBS in oil unless the lenses are applied. The use of the approach described herein allows for well focused images of single cells in DPBS droplets to be obtained.

  6. 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.

  7. Development of a bi-functional silica monolith for electro-osmotic pumping and DNA clean-up/extraction using gel-supported reagents in a microfluidic device.

    Science.gov (United States)

    Oakley, Jennifer A; Shaw, Kirsty J; Docker, Peter T; Dyer, Charlotte E; Greenman, John; Greenway, Gillian M; Haswell, Stephen J

    2009-06-07

    A silica monolith used to support both electro-osmotic pumping (EOP) and the extraction/elution of DNA coupled with gel-supported reagents is described. The benefits of the combined EOP extraction/elution system were illustrated by combining DNA extraction and gene amplification using the polymerase chain reaction (PCR) process. All the reagents necessary for both processes were supported within pre-loaded gels that allow the reagents to be stored at 4 degrees C for up to four weeks in the microfluidic device. When carrying out an analysis the crude sample only needed to be hydrodynamically introduced into the device which was connected to an external computer controlled power supply via platinum wire electrodes. DNA was extracted with 65% efficiency after loading lysed cells onto a silica monolith. Ethanol contained within an agarose gel matrix was then used to wash unwanted debris away from the sample by EOP (100 V cm(-1) for 5 min). The retained DNA was subsequently eluted from the monolith by water contained in a second agarose gel, again by EOP using an electric field of 100 V cm(-1) for 5 min, and transferred into the PCR reagent containing gel. The eluted DNA in solution was successfully amplified by PCR, confirming that the concept of a complete self-contained microfluidic device could be realised for DNA sample clean up and amplification, using a simple pumping and on-chip reagent storage methodology.

  8. Microfluidic-chip platform for cell sorting

    Science.gov (United States)

    Malik, Sarul; Balyan, Prerna; Akhtar, J.; Agarwal, Ajay

    2016-04-01

    Cell sorting and separation are considered to be very crucial preparatory steps for numerous clinical diagnostics and therapeutics applications in cell biology research arena. Label free cell separation techniques acceptance rate has been increased to multifold by various research groups. Size based cell separation method focuses on the intrinsic properties of the cell which not only avoids clogging issues associated with mechanical and centrifugation filtration methods but also reduces the overall cost for the process. Consequentially flow based cell separation method for continuous flow has attracted the attention of millions. Due to the realization of structures close to particle size in micro dimensions, the microfluidic devices offer precise and rapid particle manipulation which ultimately leads to an extraordinary cell separation results. The proposed microfluidic device is fabricated to separate polystyrene beads of size 1 µm, 5 µm, 10 µm and 20 µm. The actual dimensions of blood corpuscles were kept in mind while deciding the particle size of polystyrene beads which are used as a model particles for study.

  9. 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.

  10. USING OXYGEN-CONSUMING THERMOSET PLASTICS TO GENERATE HYPOXIC CONDITIONS IN MICROFLUIDIC DEVICES FOR POTENTIAL CELL CULTURE APPLICATIONS

    DEFF Research Database (Denmark)

    Sticker, Drago; Rothbauer, Mario; Ehgartner, Josef

    The precise control of the oxygen concentration in a cellular environment allows the study of cells under physiologically relevant conditions. This work reports on a novel method for the generation of reduced dissolved oxygen concentrations in microfluidic chambers for cell- and organ-on-chip app......The precise control of the oxygen concentration in a cellular environment allows the study of cells under physiologically relevant conditions. This work reports on a novel method for the generation of reduced dissolved oxygen concentrations in microfluidic chambers for cell- and organ...

  11. A Microfluidic Device for Preparing Next Generation DNA Sequencing Libraries and for Automating Other Laboratory Protocols That Require One or More Column Chromatography Steps

    Science.gov (United States)

    Tan, Swee Jin; Phan, Huan; Gerry, Benjamin Michael; Kuhn, Alexandre; Hong, Lewis Zuocheng; Min Ong, Yao; Poon, Polly Suk Yean; Unger, Marc Alexander; Jones, Robert C.; Quake, Stephen R.; Burkholder, William F.

    2013-01-01

    Library preparation for next-generation DNA sequencing (NGS) remains a key bottleneck in the sequencing process which can be relieved through improved automation and miniaturization. We describe a microfluidic device for automating laboratory protocols that require one or more column chromatography steps and demonstrate its utility for preparing Next Generation sequencing libraries for the Illumina and Ion Torrent platforms. Sixteen different libraries can be generated simultaneously with significantly reduced reagent cost and hands-on time compared to manual library preparation. Using an appropriate column matrix and buffers, size selection can be performed on-chip following end-repair, dA tailing, and linker ligation, so that the libraries eluted from the chip are ready for sequencing. The core architecture of the device ensures uniform, reproducible column packing without user supervision and accommodates multiple routine protocol steps in any sequence, such as reagent mixing and incubation; column packing, loading, washing, elution, and regeneration; capture of eluted material for use as a substrate in a later step of the protocol; and removal of one column matrix so that two or more column matrices with different functional properties can be used in the same protocol. The microfluidic device is mounted on a plastic carrier so that reagents and products can be aliquoted and recovered using standard pipettors and liquid handling robots. The carrier-mounted device is operated using a benchtop controller that seals and operates the device with programmable temperature control, eliminating any requirement for the user to manually attach tubing or connectors. In addition to NGS library preparation, the device and controller are suitable for automating other time-consuming and error-prone laboratory protocols requiring column chromatography steps, such as chromatin immunoprecipitation. PMID:23894273

  12. A microfluidic device for preparing next generation DNA sequencing libraries and for automating other laboratory protocols that require one or more column chromatography steps.

    Directory of Open Access Journals (Sweden)

    Swee Jin Tan

    Full Text Available Library preparation for next-generation DNA sequencing (NGS remains a key bottleneck in the sequencing process which can be relieved through improved automation and miniaturization. We describe a microfluidic device for automating laboratory protocols that require one or more column chromatography steps and demonstrate its utility for preparing Next Generation sequencing libraries for the Illumina and Ion Torrent platforms. Sixteen different libraries can be generated simultaneously with significantly reduced reagent cost and hands-on time compared to manual library preparation. Using an appropriate column matrix and buffers, size selection can be performed on-chip following end-repair, dA tailing, and linker ligation, so that the libraries eluted from the chip are ready for sequencing. The core architecture of the device ensures uniform, reproducible column packing without user supervision and accommodates multiple routine protocol steps in any sequence, such as reagent mixing and incubation; column packing, loading, washing, elution, and regeneration; capture of eluted material for use as a substrate in a later step of the protocol; and removal of one column matrix so that two or more column matrices with different functional properties can be used in the same protocol. The microfluidic device is mounted on a plastic carrier so that reagents and products can be aliquoted and recovered using standard pipettors and liquid handling robots. The carrier-mounted device is operated using a benchtop controller that seals and operates the device with programmable temperature control, eliminating any requirement for the user to manually attach tubing or connectors. In addition to NGS library preparation, the device and controller are suitable for automating other time-consuming and error-prone laboratory protocols requiring column chromatography steps, such as chromatin immunoprecipitation.

  13. Development of a Microfluidic-Based Optical Sensing Device for Label-Free Detection of Circulating Tumor Cells (CTCs Through Their Lactic Acid Metabolism

    Directory of Open Access Journals (Sweden)

    Tzu-Keng Chiu

    2015-03-01

    Full Text Available This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs, a rare cell species in blood circulation. Based on the metabolic features of cancer cells, live CTCs can be quantified indirectly through their lactic acid production. Compared with the conventional schemes for CTC detection, this label-free approach could prevent the biological bias due to the heterogeneity of the surface antigens on cancer cells. In this study, a microfluidic device was proposed to generate uniform water-in-oil cell-encapsulating micro-droplets, followed by the fluorescence-based optical detection of lactic acid produced within the micro-droplets. To test its feasibility to quantify cancer cells, experiments were carried out. Results showed that the detection signals were proportional to the number of cancer cells within the micro-droplets, whereas such signals were insensitive to the existence and number of leukocytes within. To further demonstrate its feasibility for cancer cell detection, the cancer cells with known cell number in a cell suspension was detected based on the method. Results revealed that there was no significant difference between the detected number and the real number of cancer cells. As a whole, the proposed method opens up a new route to detect live CTCs in a label-free manner.

  14. Numerical Optimization in Microfluidics

    DEFF Research Database (Denmark)

    Jensen, Kristian Ejlebjærg

    2017-01-01

    Numerical modelling can illuminate the working mechanism and limitations of microfluidic devices. Such insights are useful in their own right, but one can take advantage of numerical modelling in a systematic way using numerical optimization. In this chapter we will discuss when and how numerical...... optimization is best used....

  15. Microfluidics for medical applications

    NARCIS (Netherlands)

    van den Berg, Albert; van den Berg, A.; Segerink, L.I.; Segerink, Loes Irene; Unknown, [Unknown

    2015-01-01

    Lab-on-a-chip devices for point of care diagnostics have been present in clinics for several years now. Alongside their continual development, research is underway to bring the organs and tissue on-a-chip to the patient, amongst other medical applications of microfluidics. This book provides the

  16. A microfluidic paper-based analytical device for the assay of albumin-corrected fructosamine values from whole blood samples.

    Science.gov (United States)

    Boonyasit, Yuwadee; Laiwattanapaisal, Wanida

    2015-01-01

    A method for acquiring albumin-corrected fructosamine values from whole blood using a microfluidic paper-based analytical system that offers substantial improvement over previous methods is proposed. The time required to quantify both serum albumin and fructosamine is shortened to 10 min with detection limits of 0.50 g dl(-1) and 0.58 mM, respectively (S/N = 3). The proposed system also exhibited good within-run and run-to-run reproducibility. The results of the interference study revealed that the acceptable recoveries ranged from 95.1 to 106.2%. The system was compared with currently used large-scale methods (n = 15), and the results demonstrated good agreement among the techniques. The microfluidic paper-based system has the potential to continuously monitor glycemic levels in low resource settings.

  17. Flow injection microfluidic device with on-line fluorescent derivatization for the determination of Cr(III) and Cr(VI) in water samples after solid phase extraction

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Guilong [Key Laboratory of Eco-Environment of Three Gorges Region of Ministry of Education, Chongqing University, Chongqing, 400045 (China); Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing, 100084 (China); He, Qiang, E-mail: heqiang0980@163.com [Key Laboratory of Eco-Environment of Three Gorges Region of Ministry of Education, Chongqing University, Chongqing, 400045 (China); Lu, Ying [Department of Mathematics and Physics, Armed Police College, Chengdu, 610213 (China); Huang, Jing [Research Center for Advanced Computation, College of Science, Xihua University, Chengdu, 610039 (China); Lin, Jin-Ming, E-mail: jmlin@mail.tsinghua.edu.cn [Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing, 100084 (China)

    2017-02-22

    In this paper, a rapid and simple method using magnetic multi-walled carbon nanotubes (MWCNTS), as a solid-phase extraction (SPE) sorbent, was successfully developed for extraction and preconcentration trace amounts of Cr(III) in water samples. The synthesized magnetic-MWCNTs nanocomposite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). A rhodamine derivative (R1) was synthesized and characterized as a highly selective and sensitive fluorescent derivatizing agent for Cr(III). After SPE procedure, Cr(III) analysis was performed by flow injection microfluidic chip with on-line fluorescent derivatization and laser-induced fluorescence (LIF) spectroscopy detection. The parameters, which affected the efficiency of the developed method were investigated and optimized. Under the optimized conditions, the method exhibited a linear dynamic range of 0–10.0 nM, with a detection limit of 0.094 nM and an enrichment factor of 38. Furthermore, real water samples were analyzed and good recoveries were obtained from 91.0 to 101.6%. - Graphical abstract: Flow injection microfluidic device with on-line fluorescent derivatization and detection coupled to LIF. - Highlights: • A highly selective and sensitive derivatizing reagent for Cr(III) was synthesized and characterized. • The magnetic-MWCNTs nanocomposite as a SPE sorbent was successfully synthesized and characterized. • A new portable detection system was developed for microfluidic chip FIA platform.

  18. Simple practical approach for sample loading prior to DNA extraction using a silica monolith in a microfluidic device.

    Science.gov (United States)

    Shaw, Kirsty J; Joyce, Domino A; Docker, Peter T; Dyer, Charlotte E; Greenman, John; Greenway, Gillian M; Haswell, Stephen J

    2009-12-07

    A novel DNA loading methodology is presented for performing DNA extraction on a microfluidic system. DNA in a chaotropic salt solution was manually loaded onto a silica monolith orthogonal to the subsequent flow of wash and elution solutions. DNA was successfully extracted from buccal swabs using electro-osmotic pumping (EOP) coupled with in situ reagents contained within a 1.5% agarose gel matrix. The extracted DNA was of sufficient quantity and purity for polymerase chain reaction (PCR) amplification.

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

    Science.gov (United States)

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

    2017-11-08

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

  20. Flow-Based Provenance

    Directory of Open Access Journals (Sweden)

    Sabah Al-Fedaghi

    2017-02-01

    Full Text Available Aim/Purpose: With information almost effortlessly created and spontaneously available, current progress in Information and Communication Technology (ICT has led to the complication that information must be scrutinized for trustworthiness and provenance. Information systems must become provenance-aware to be satisfactory in accountability, reproducibility, and trustworthiness of data. Background:\tMultiple models for abstract representation of provenance have been proposed to describe entities, people, and activities involved in producing a piece of data, including the Open Provenance Model (OPM and the World Wide Web Consortium. These models lack certain concepts necessary for specifying workflows and encoding the provenance of data products used and generated. Methodology: Without loss of generality, the focus of this paper is on OPM depiction of provenance in terms of a directed graph. We have redrawn several case studies in the framework of our proposed model in order to compare and evaluate it against OPM for representing these cases. Contribution: This paper offers an alternative flow-based diagrammatic language that can form a foundation for modeling of provenance. The model described here provides an (abstract machine-like representation of provenance. Findings: The results suggest a viable alternative in the area of diagrammatic representation for provenance applications. Future Research: Future work will seek to achieve more accurate comparisons with current models in the field.

  1. Multiplexed detection of DNA sequences using a competitive displacement assay in a microfluidic SERRS-based device.

    Science.gov (United States)

    Yazdi, Soroush H; Giles, Kristen L; White, Ian M

    2013-11-05

    We demonstrate sensitive and multiplexed detection of DNA sequences through a surface enhanced resonance Raman spectroscopy (SERRS)-based competitive displacement assay in an integrated microsystem. The use of the competitive displacement scheme, in which the target DNA sequence displaces a Raman-labeled reporter sequence that has lower affinity for the immobilized probe, enables detection of unlabeled target DNA sequences with a simple single-step procedure. In our implementation, the displacement reaction occurs in a microporous packed column of silica beads prefunctionalized with probe-reporter pairs. The use of a functionalized packed-bead column in a microfluidic channel provides two major advantages: (i) immobilization surface chemistry can be performed as a batch process instead of on a chip-by-chip basis, and (ii) the microporous network eliminates the diffusion limitations of a typical biological assay, which increases the sensitivity. Packed silica beads are also leveraged to improve the SERRS detection of the Raman-labeled reporter. Following displacement, the reporter adsorbs onto aggregated silver nanoparticles in a microfluidic mixer; the nanoparticle-reporter conjugates are then trapped and concentrated in the silica bead matrix, which leads to a significant increase in plasmonic nanoparticles and adsorbed Raman reporters within the detection volume as compared to an open microfluidic channel. The experimental results reported here demonstrate detection down to 100 pM of the target DNA sequence, and the experiments are shown to be specific, repeatable, and quantitative. Furthermore, we illustrate the advantage of using SERRS by demonstrating multiplexed detection. The sensitivity of the assay, combined with the advantages of multiplexed detection and single-step operation with unlabeled target sequences makes this method attractive for practical applications. Importantly, while we illustrate DNA sequence detection, the SERRS-based competitive

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

    Science.gov (United States)

    Asano, Hitoshi; Shiraishi, Yukihide

    2018-01-01

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

  3. 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.

  4. Reconfigurable microfluidic platform in ice

    OpenAIRE

    Varejka, M.

    2008-01-01

    Microfluidic devices are popular tools in the biotechnology industry where they provide smaller reagent requirements, high speed of analysis and the possibility for automation. The aim of the project is to make a flexible biocompatible microfluidic platform adapted to different specific applications, mainly analytical and separations which parameters and configuration can be changed multiple times by changing corresponding computer programme. The current project has been sup...

  5. 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)

  6. 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)

  7. 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.

  8. Isolation of cancer cells by "in situ" microfluidic biofunctionalization protocols

    DEFF Research Database (Denmark)

    De Vitis, Stefania; Matarise, Giuseppina; Pardeo, Francesca

    2014-01-01

    The aim of this work is the development of a microfluidic immunosensor for the immobilization of cancer cells and their separation from healthy cells by using "in situ" microfluidic biofunctionalization protocols. These protocols allow to link antibodies on microfluidic device surfaces and can be...

  9. Microfluidic Biochip Design

    Science.gov (United States)

    Panzarella, Charles

    2004-01-01

    As humans prepare for the exploration of our solar system, there is a growing need for miniaturized medical and environmental diagnostic devices for use on spacecrafts, especially during long-duration space missions where size and power requirements are critical. In recent years, the biochip (or Lab-on-a- Chip) has emerged as a technology that might be able to satisfy this need. In generic terms, a biochip is a miniaturized microfluidic device analogous to the electronic microchip that ushered in the digital age. It consists of tiny microfluidic channels, pumps and valves that transport small amounts of sample fluids to biosensors that can perform a variety of tests on those fluids in near real time. It has the obvious advantages of being small, lightweight, requiring less sample fluids and reagents and being more sensitive and efficient than larger devices currently in use. Some of the desired space-based applications would be to provide smaller, more robust devices for analyzing blood, saliva and urine and for testing water and food supplies for the presence of harmful contaminants and microorganisms. Our group has undertaken the goal of adapting as well as improving upon current biochip technology for use in long-duration microgravity environments. In addition to developing computational models of the microfluidic channels, valves and pumps that form the basis of every biochip, we are also trying to identify potential problems that could arise in reduced gravity and develop solutions to these problems. One such problem is due to the prevalence of bubbly sample fluids in microgravity. A bubble trapped in a microfluidic channel could be detrimental to the operation of a biochip. Therefore, the process of bubble formation in microgravity needs to be studied, and a model of this process has been developed and used to understand how bubbles develop and move through biochip components. It is clear that some type of bubble filter would be necessary in Space, and

  10. Versatile microfluidic total internal reflection (TIR)-based devices: application to microbeads velocity measurement and single molecule detection with upright and inverted microscope.

    Science.gov (United States)

    Le, Nam Cao Hoai; Yokokawa, Ryuji; Dao, Dzung Viet; Nguyen, Thien Duy; Wells, John C; Sugiyama, Susumu

    2009-01-21

    A poly(dimethylsiloxane) (PDMS) chip for Total Internal Reflection (TIR)-based imaging and detection has been developed using Si bulk micromachining and PDMS casting. In this paper, we report the applications of the chip on both inverted and upright fluorescent microscopes and confirm that two types of sample delivery platforms, PDMS microchannel and glass microchannel, can be easily integrated depending on the magnification of an objective lens needed to visualize a sample. Although any device configuration can be achievable, here we performed two experiments to demonstrate the versatility of the microfluidic TIR-based devices. The first experiment was velocity measurement of Nile red microbeads with nominal diameter of 500 nm in a pressure-driven flow. The time-sequenced fluorescent images of microbeads, illuminated by an evanescent field, were cross-correlated by a Particle Image Velocimetry (PIV) program to obtain near-wall velocity field of the microbeads at various flow rates from 500 nl/min to 3000 nl/min. We then evaluated the capabilities of the device for Single Molecule Detection (SMD) of fluorescently labeled DNA molecules from 30 bp to 48.5 kbp and confirm that DNA molecules as short as 1105 bp were detectable. Our versatile, integrated device could provide low-cost and fast accessibility to Total Internal Reflection Fluorescent Microscopy (TIRFM) on both conventional upright and inverted microscopes. It could also be a useful component in a Micro-Total Analysis System (micro-TAS) to analyze nanoparticles or biomolecules near-wall transport or motion.

  11. A Microfluidic Cell Concentrator

    Science.gov (United States)

    Warrick, Jay; Casavant, Ben; Frisk, Megan; Beebe, David

    2010-01-01

    Cell concentration via centrifugation is a ubiquitous step in many cell culture procedures. At the macroscale, centrifugation suffers from a number of limitations particularly when dealing with small numbers of cells (e.g., less than 50,000). On the other hand, typical microscale methods for cell concentration can affect cell physiology and bias readouts of cell behavior and function. In this paper, we present a microfluidic concentrator device that utilizes the effects of gravity to allow cells to gently settle out of a suspension into a collection region without the use of specific adhesion ligands. Dimensional analysis was performed to compare different device designs and was verified with flow modeling to optimize operational parameters. We are able to concentrate low-density cell suspensions in a microfluidic chamber, achieving a cell loss of only 1.1 ± 0.6% (SD, n=7) with no observed loss during a subsequent cell staining protocol which incorporates ~36 complete device volume replacements. This method provides a much needed interface between rare cell samples and microfluidic culture assays. PMID:20843010

  12. System-level modeling and simulation of the cell culture microfluidic biochip ProCell

    DEFF Research Database (Denmark)

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

    2010-01-01

    Microfluidic biochips offer a promising alternative to a conventional biochemical laboratory. There are two technologies for the microfluidic biochips: droplet-based and flow-based. In this paper we are interested in flow-based microfluidic biochips, where the liquid flows continuously through pre......-defined micro-channels using valves and pumps. We present an approach to the system-level modeling and simulation of a cell culture microfluidic biochip called ProCell, Programmable Cell Culture Chip. ProCell contains a cell culture chamber, which is envisioned to run 256 simultaneous experiments (viewed...

  13. Automating quantum dot barcode assays using microfluidics and magnetism for the development of a point-of-care device.

    Science.gov (United States)

    Gao, Yali; Lam, Albert W Y; Chan, Warren C W

    2013-04-24

    The impact of detecting multiple infectious diseases simultaneously at point-of-care with good sensitivity, specificity, and reproducibility would be enormous for containing the spread of diseases in both resource-limited and rich countries. Many barcoding technologies have been introduced for addressing this need as barcodes can be applied to detecting thousands of genetic and protein biomarkers simultaneously. However, the assay process is not automated and is tedious and requires skilled technicians. Barcoding technology is currently limited to use in resource-rich settings. Here we used magnetism and microfluidics technology to automate the multiple steps in a quantum dot barcode assay. The quantum dot-barcoded microbeads are sequentially (a) introduced into the chip, (b) magnetically moved to a stream containing target molecules, (c) moved back to the original stream containing secondary probes, (d) washed, and (e) finally aligned for detection. The assay requires 20 min, has a limit of detection of 1.2 nM, and can detect genetic targets for HIV, hepatitis B, and syphilis. This study provides a simple strategy to automate the entire barcode assay process and moves barcoding technologies one step closer to point-of-care applications.

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

    Science.gov (United States)

    Asano, Hitoshi; Shiraishi, Yukihide

    2015-07-09

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

  15. 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...

  16. Fiber free plug and play on-chip scattering cytometer module – for implementation in microfluidic point of care devices

    DEFF Research Database (Denmark)

    Jensen, Thomas Glasdam; Kutter, Jörg Peter

    2010-01-01

    In this paper, we report on recent progress toward the development of a plug and play on-chip cytometer based on light scattering. By developing a device that does not depend on the critical alignment and cumbersome handling of fragile optical fibers, we approach a device that is suitable for non...

  17. Design of a microfluidic device with a non-traditional flow profile for on-chip damage to zebrafish sensory cells

    International Nuclear Information System (INIS)

    Kwon, Hyuck-Jin; Xu, Yuhao; Solovitz, Stephen A; Xue, Wei; Xu, Jie; Dimitrov, Alexander G; Coffin, Allison B

    2014-01-01

    Hearing loss affects millions of people worldwide and often results from the death of the sensory hair cells in the inner ear, and exposure to intense noise is one of the leading causes of hair cell damage. Recently, the zebrafish lateral line system has emerged as a powerful in vivo model for real-time studies of hair cell damage and protection. In this research, we designed a microfluidic device for inducing noise damage in hair cells of the zebrafish lateral line. As the first step, a 3D computational fluid dynamics (CFD) simulation was utilized to predict the flow pattern inside the device. An ideal flow pattern for our application should feature higher velocity near the sidewalls to over-stimulate the externally located hair cells, and minimum flow in the middle of the channel to protect the fish from high pressure on the head. Flow induced from ordinary channel geometry with a single inlet/outlet pair would not work because the parabolic velocity profile features the maximum flow speed in the middle of the channel. In order to achieve the desired flow pattern, sidewall inlet/outlet pairs were used to suppress the growth of boundary layers. CFD simulation was used to design parameters such as the dimensions of the microfluidic channel and the angle of the inlets and outlets. It was found that in the case of an empty 2.0 mm wide channel with the inlet/outlet pairs set to 45°, the flow velocity at the side of the channel would be 6.7 times faster than the velocity in the middle, approaching the optimal flow characteristics. In the case of a fish-loaded channel, simulation shows that a 1.0 mm wide channel with a 60° inlet/outlet angle creates the lowest pressure (0.3 Pa) on the fish head while maintaining a reasonably strong shear stress (1.9 Pa) on the lateral line hair cells. (technical note)

  18. Microfluidic Scintillation Detectors

    CERN Multimedia

    Microfluidic scintillation detectors are devices of recent introduction for the detection of high energy particles, developed within the EP-DT group at CERN. Most of the interest for such technology comes from the use of liquid scintillators, which entails the possibility of changing the active material in the detector, leading to an increased radiation resistance. This feature, together with the high spatial resolution and low thickness deriving from the microfabrication techniques used to manufacture such devices, is desirable not only in instrumentation for high energy physics experiments but also in medical detectors such as beam monitors for hadron therapy.

  19. Microfluidics with fluid walls.

    Science.gov (United States)

    Walsh, Edmond J; Feuerborn, Alexander; Wheeler, James H R; Tan, Ann Na; Durham, William M; Foster, Kevin R; Cook, Peter R

    2017-10-10

    Microfluidics has great potential, but the complexity of fabricating and operating devices has limited its use. Here we describe a method - Freestyle Fluidics - that overcomes many key limitations. In this method, liquids are confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin liquids to substrates, and overlaying an immiscible liquid prevents evaporation. Confining fluid walls are pliant and resilient; they self-heal when liquids are pipetted through them. We drive flow through a wide range of circuits passively by manipulating surface tension and hydrostatic pressure, and actively using external pumps. Finally, we validate the technology with two challenging applications - triggering an inflammatory response in human cells and chemotaxis in bacterial biofilms. This approach provides a powerful and versatile alternative to traditional microfluidics.The complexity of fabricating and operating microfluidic devices limits their use. Walsh et al. describe a method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls.

  20. Infrared microspectroscopy of live cells in microfluidic devices (MD-IRMS): toward a powerful label-free cell-based assay.

    Science.gov (United States)

    Vaccari, L; Birarda, G; Businaro, L; Pacor, S; Grenci, G

    2012-06-05

    Until nowadays most infrared microspectroscopy (IRMS) experiments on biological specimens (i.e., tissues or cells) have been routinely carried out on fixed or dried samples in order to circumvent water absorption problems. In this paper, we demonstrate the possibility to widen the range of in-vitro IRMS experiments to vibrational analysis of live cellular samples, thanks to the development of novel biocompatible IR-visible transparent microfluidic devices (MD). In order to highlight the biological relevance of IRMS in MD (MD-IRMS), we performed a systematic exploration of the biochemical alterations induced by different fixation protocols, ethanol 70% and formaldehyde solution 4%, as well as air-drying on U937 leukemic monocytes by comparing their IR vibrational features with the live U937 counterpart. Both fixation and air-drying procedures affected lipid composition and order as well as protein structure at a different extent while they both induced structural alterations in nucleic acids. Therefore, only IRMS of live cells can provide reliable information on both DNA and RNA structure and on their cellular dynamic. In summary, we show that MD-IRMS of live cells is feasible, reliable, and biologically relevant to be recognized as a label-free cell-based assay.

  1. Paper-based enzymatic microfluidic fuel cell: From a two-stream flow device to a single-stream lateral flow strip

    Science.gov (United States)

    González-Guerrero, Maria José; del Campo, F. Javier; Esquivel, Juan Pablo; Giroud, Fabien; Minteer, Shelley D.; Sabaté, Neus

    2016-09-01

    This work presents a first approach towards the development of a cost-effective enzymatic paper-based glucose/O2 microfluidic fuel cell in which fluid transport is based on capillary action. A first fuel cell configuration consists of a Y-shaped paper device with the fuel and the oxidant flowing in parallel over carbon paper electrodes modified with bioelectrocatalytic enzymes. The anode consists of a ferrocenium-based polyethyleneimine polymer linked to glucose oxidase (GOx/Fc-C6-LPEI), while the cathode contains a mixture of laccase, anthracene-modified multiwall carbon nanotubes, and tetrabutylammonium bromide-modified Nafion (MWCNTs/laccase/TBAB-Nafion). Subsequently, the Y-shaped configuration is improved to use a single solution containing both, the anolyte and the catholyte. Thus, the electrolytes pHs of the fuel and the oxidant solutions are adapted to an intermediate pH of 5.5. Finally, the fuel cell is run with this single solution obtaining a maximum open circuit of 0.55 ± 0.04 V and a maximum current and power density of 225 ± 17 μA cm-2 and 24 ± 5 μW cm-2, respectively. Hence, a power source closer to a commercial application (similar to conventional lateral flow test strips) is developed and successfully operated. This system can be used to supply the energy required to power microelectronics demanding low power consumption.

  2. The Microfluidic Jukebox

    Science.gov (United States)

    Tan, Say Hwa; Maes, Florine; Semin, Benoît; Vrignon, Jérémy; Baret, Jean-Christophe

    2014-04-01

    Music is a form of art interweaving people of all walks of life. Through subtle changes in frequencies, a succession of musical notes forms a melody which is capable of mesmerizing the minds of people. With the advances in technology, we are now able to generate music electronically without relying solely on physical instruments. Here, we demonstrate a musical interpretation of droplet-based microfluidics as a form of novel electronic musical instruments. Using the interplay of electric field and hydrodynamics in microfluidic devices, well controlled frequency patterns corresponding to musical tracks are generated in real time. This high-speed modulation of droplet frequency (and therefore of droplet sizes) may also provide solutions that reconciles high-throughput droplet production and the control of individual droplet at production which is needed for many biochemical or material synthesis applications.

  3. 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.

  4. Theoretical microfluidics

    DEFF Research Database (Denmark)

    Bruus, Henrik

    Microfluidics is a young and rapidly expanding scientific discipline, which deals with fluids and solutions in miniaturized systems, the so-called lab-on-a-chip systems. It has applications in chemical engineering, pharmaceutics, biotechnology and medicine. As the lab-on-a-chip systems grow...

  5. Development of a Microfluidic Open Interface with Flow Isolated Desorption Volume for the Direct Coupling of SPME Devices to Mass Spectrometry.

    Science.gov (United States)

    Tascon, Marcos; Alam, Md Nazmul; Gómez-Ríos, Germán Augusto; Pawliszyn, Janusz

    2018-02-20

    Technologies that efficiently integrate the sampling and sample preparation steps with direct introduction to mass spectrometry (MS), providing simple and sensitive analytical workflows as well as capabilities for automation, can generate a great impact in a vast variety of fields, such as in clinical, environmental, and food-science applications. In this study, a novel approach that facilitates direct coupling of Bio-SPME devices to MS using a microfluidic design is presented. This technology, named microfluidic open interface (MOI), which operates under the concept of flow-isolated desorption volume, consists of an open-to-ambient desorption chamber (V ≤ 7 μL) connected to an ionization source. Subsequently, compounds of interest are transported to the ionization source by means of the self-aspiration process intrinsic of these interfaces. Thus, any ionization technology that provides a reliable and constant suction, such as electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), or inductively coupled plasma ionization (ICP), can be hyphenated to MOI. Using this setup, the desorption chamber is used to release target compounds from the coating, while the isolation of the flow enables the ionization source to be continuously fed with solvent, all without the necessity of employment of additional valves. As a proof of concept, the design was applied to an ESI-MS/MS system for experimental validation. Furthermore, numerical simulations were undertaken to provide a detailed understanding of the fluid flow pattern inside the interface, then used to optimize the system for better efficiency. The analytical workflow of the developed Bio-SPME-MOI-MS setup consists of the direct immersion of SPME fibers into the matrix to extract/enrich analytes of interest within a short period of time, followed by a rinsing step with water to remove potentially adhering proteins, salts, and/or other interfering compounds. Next, the fiber is inserted into the

  6. Microfluidic Analytical Separator for Proteomics, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  7. Microfluidic Analytical Separator for Proteomics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SHOT proposes an innovative microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  8. Advancing liquid/liquid extraction through a novel microfluidic device: Theory, instrumentation and applications in gas chromatography

    NARCIS (Netherlands)

    Peroni, D.; van Egmond, W.; Kok, W.T.; Janssen, J.G.M.

    2012-01-01

    A new chip-based liquid-liquid extraction technique for sample preparation of aqueous samples for GC was developed. Extraction is performed in a segmented flow system with additional mixing provided by an etched channel structure. The dimensions of the device are optimized to allow benefiting of the

  9. Novel LTCC-potentiometric microfluidic device for biparametric analysis of organic compounds carrying plastic antibodies as ionophores: application to sulfamethoxazole and trimethoprim.

    Science.gov (United States)

    Almeida, S A A; Arasa, E; Puyol, M; Martinez-Cisneros, C S; Alonso-Chamarro, J; Montenegro, M C B S M; Sales, M G F

    2011-12-15

    Monitoring organic environmental contaminants is of crucial importance to ensure public health. This requires simple, portable and robust devices to carry out on-site analysis. For this purpose, a low-temperature co-fired ceramics (LTCC) microfluidic potentiometric device (LTCC/μPOT) was developed for the first time for an organic compound: sulfamethoxazole (SMX). Sensory materials relied on newly designed plastic antibodies. Sol-gel, self-assembling monolayer and molecular-imprinting techniques were merged for this purpose. Silica beads were amine-modified and linked to SMX via glutaraldehyde modification. Condensation polymerization was conducted around SMX to fill the vacant spaces. SMX was removed after, leaving behind imprinted sites of complementary shape. The obtained particles were used as ionophores in plasticized PVC membranes. The most suitable membrane composition was selected in steady-state assays. Its suitability to flow analysis was verified in flow-injection studies with regular tubular electrodes. The LTCC/μPOT device integrated a bidimensional mixer, an embedded reference electrode based on Ag/AgCl and an Ag-based contact screen-printed under a micromachined cavity of 600 μm depth. The sensing membranes were deposited over this contact and acted as indicating electrodes. Under optimum conditions, the SMX sensor displayed slopes of about -58.7 mV/decade in a range from 12.7 to 250 μg/mL, providing a detection limit of 3.85 μg/mL and a sampling throughput of 36 samples/h with a reagent consumption of 3.3 mL per sample. The system was adjusted later to multiple analyte detection by including a second potentiometric cell on the LTCC/μPOT device. No additional reference electrode was required. This concept was applied to Trimethoprim (TMP), always administered concomitantly with sulphonamide drugs, and tested in fish-farming waters. The biparametric microanalyzer displayed Nernstian behaviour, with average slopes -54.7 (SMX) and +57.8 (TMP) m

  10. 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.

  11. Droplet generation in cross-flow for cost-effective 3D-printed “plug-and-play” microfluidic devices

    KAUST Repository

    Zhang, Jiaming; Aguirre-Pablo, Andres A.; Li, Erqiang; Buttner, Ulrich; Thoroddsen, Sigurdur T

    2016-01-01

    Droplet-based microfluidics is a rapidly growing field of research and involves various applications from chemistry to biology. Droplet generation techniques become the pre-requisite focus. Additive manufacturing (3D printing) technology has

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

    CSIR Research Space (South Africa)

    Ngamsom, B

    2017-08-01

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

  13. Digital microfluidic processing of mammalian embryos for vitrification.

    Directory of Open Access Journals (Sweden)

    Derek G Pyne

    Full Text Available Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

  14. Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.

    Science.gov (United States)

    Wallman, Lars; Åkesson, Elisabet; Ceric, Dario; Andersson, Per Henrik; Day, Kelly; Hovatta, Outi; Falci, Scott; Laurell, Thomas; Sundström, Erik

    2011-10-07

    Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes.

  15. Droplet based microfluidics

    International Nuclear Information System (INIS)

    Seemann, Ralf; Brinkmann, Martin; Pfohl, Thomas; Herminghaus, Stephan

    2012-01-01

    Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

  16. Microfluidic flow fractionation device for label-free isolation of circulating tumor cells (CTCs) from breast cancer patients.

    Science.gov (United States)

    Hyun, Kyung-A; Kwon, Kiho; Han, Hyunju; Kim, Seung-Il; Jung, Hyo-Il

    2013-02-15

    Circulating tumor cells (CTCs) are dissociated from primary tumor and circulate in peripheral blood. They are regarded as the genesis of metastasis. Isolation and enumeration of CTCs serve as valuable tools for cancer prognosis and diagnosis. However, the rarity and heterogeneity of CTCs in blood makes it difficult to separate intact CTCs without loss. In this paper, we introduce a parallel multi-orifice flow fractionation (p-MOFF) device in which a series of contraction/expansion microchannels are placed parallel on a chip forming four identical channels. CTCs were continuously isolated from the whole blood of breast cancer patients by hydrodynamic forces and cell size differences. Blood samples from 24 breast cancer patients were analyzed (half were from metastatic breast cancer patients and the rest were from adjuvant breast cancer patients). The number of isolated CTCs varied from 0 to 21 in 7.5 ml of blood. Because our devices do not require any labeling processes (e.g., EpCAM antibody), heterogeneous CTCs can be isolated regardless of EpCAM expression. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Saharil, Farizah; Ahlford, Annika; Kuhnemund, Malte

    2013-01-01

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

  18. Effects of Interfaces on Dynamics in Micro-Fluidic Devices: Slip-Boundaries’ Impact on Rotation Characteristics of Polar Liquid Film Motors

    Science.gov (United States)

    Jiang, Su-Rong; Liu, Zhong-Qiang; Amos Yinnon, Tamar; Kong, Xiang-Mu

    2017-05-01

    A new approach for exploring effects of interfaces on polar liquids is presented. Their impact on the polar liquid film motor (PLFM) - a novel micro-fluidic device - is studied. We account for the interface’s impact by modeling slip boundary effects on the PLFM’s electro-hydro-dynamical rotations. Our analytical results show as k={l}s/R increases (with {l}s denoting the slip length resulting from the interface’s impact on the film’s properties, k > -1 and R denoting the film’s radius): (a) PLFMs subsequently exhibit rotation characteristics under “negative-”, “no-”, “partial-” and “perfect-” slip boundary conditions; (b) The maximum value of the linear velocity of the steady rotating film increases linearly and its location approaches the film’s border; (c) The decay of the angular velocities’ dependency on the distance from the center of the film slows down, resulting in a macroscopic flow near the boundary. With our calculated rotation speed distributions consistent with the existing experimental ones, research aiming at fitting computed to measured distributions promises identifying the factors affecting {l}s, e.g., solid-fluid potential interactions and surface roughness. The consistency also is advantageous for optimizing PLFM’s applications as micro-washers, centrifuges, mixers in the lab-on-a-chip. Supported by National Natural Science Foundation of China under Grant Nos. 11302118, 11275112, and Natural Science Foundation of Shandong Province under Grant No. ZR2013AQ015

  19. A Microfluidic Device with an Integrated Waveguide Beam Splitter for Velocity Measurements of Flowing Particles by Fourier Transformation

    DEFF Research Database (Denmark)

    Mogensen, Klaus Bo; Kwok, Y.C.; Eijkel, J.C.T.

    2003-01-01

    A microfabricated capillary electrophoresis device for velocity measurements of flowing particles is presented. It consists of a 1 x 128 planar waveguide beam splitter monolithically integrated with an electrically insulated fluidic channel network for fluorescence excitation at multiple points...... optics. The integrated planar waveguide beam splitter was, furthermore, permanently connected to the light source by a glued-on optical fiber, to achieve a robust and alignment-free operation of the system. The velocity was measured using a Fourier transformation with a Shah function, since the response...... of the fight array was designed to approximate a square profile. Deviations from this response were observed as a result of the multimode nature of the integrated waveguides....

  20. 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....

  1. Using a Microfluidic-Microelectric Device to Directly Separate Serum/Blood Cells from a Continuous Whole Bloodstream Flow

    Science.gov (United States)

    Wang, Ming-Wen; Jeng, Kuo-Shyang; Yu, Ming-Che; Su, Jui-Chih

    2012-03-01

    To make the rapid separation of serum/blood cells possible in a whole bloodstream flow without centrifugation and Pasteur pipette suction, the first step is to use a microchannel to transport the whole bloodstream into a microdevice. Subsequently, the resulting serum/blood cell is separated from the whole bloodstream by applying other technologies. Creating the serum makes this subsequent separation possible. To perform the actual separation, a microchannel with multiple symmetric curvilinear microelectrodes has been designed on a glass substrate and fabricated with micro-electromechanical system technology. The blood cells can be observed clearly by black-field microscopy imaging. A local dielectrophoretic (DEP) force, obtained from nonuniform electric fields, was used for manipulating and separating the blood cells from a continuous whole bloodstream. The experimental studies show that the blood cells incur a local dielectrophoretic field when they are suspended in a continuous flow (v = 0.02-0.1 cm/s) and exposed to AC fields at a frequency of 200 kHz. Using this device, the symmetric curvilinear microelectrodes provide a local dielectrophoretic field that is sufficiently strong for separating nearby blood cells and purifying the serum in a continuous whole bloodstream flow.

  2. 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...

  3. 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

  4. A Microfluidic Ion Pump for In Vivo Drug Delivery

    KAUST Repository

    Uguz, Ilke; Proctor, Christopher M.; Curto, Vincenzo F.; Pappa, Anna-Maria; Donahue, Mary J.; Ferro, Magali; Owens, Ró isí n M.; Khodagholy, Dion; Inal, Sahika; Malliaras, George G.

    2017-01-01

    Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device

  5. Droplet generation in cross-flow for cost-effective 3D-printed “plug-and-play” microfluidic devices

    KAUST Repository

    Zhang, Jiaming

    2016-08-04

    Droplet-based microfluidics is a rapidly growing field of research and involves various applications from chemistry to biology. Droplet generation techniques become the pre-requisite focus. Additive manufacturing (3D printing) technology has recently been exploited in microfluidics due to its simplicity and low cost. However, only relatively large droplets can be produced in current 3D-printed droplet generators, due to the channel dimension limitations on how fine a channel can be 3D-printed. Here we report a novel design of a 3D-printed

  6. 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.

  7. A Microfluidic Approach for Studying Piezo Channels.

    Science.gov (United States)

    Maneshi, M M; Gottlieb, P A; Hua, S Z

    2017-01-01

    Microfluidics is an interdisciplinary field intersecting many areas in engineering. Utilizing a combination of physics, chemistry, biology, and biotechnology, along with practical applications for designing devices that use low volumes of fluids to achieve high-throughput screening, is a major goal in microfluidics. Microfluidic approaches allow the study of cells growth and differentiation using a variety of conditions including control of fluid flow that generates shear stress. Recently, Piezo1 channels were shown to respond to fluid shear stress and are crucial for vascular development. This channel is ideal for studying fluid shear stress applied to cells using microfluidic devices. We have developed an approach that allows us to analyze the role of Piezo channels on any given cell and serves as a high-throughput screen for drug discovery. We show that this approach can provide detailed information about the inhibitors of Piezo channels. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. Pin-count reduction for continuous flow microfluidic biochips

    DEFF Research Database (Denmark)

    Schneider, Alexander; Pop, Paul; Madsen, Jan

    2017-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers integrating the necessary functions on-chip. We are interested in flow-based biochips, where a continuous flow of liquid is manipulated using integrated microvalves, controlled from external pressure sources via off...

  11. Microfluidic cell culture systems for drug research.

    Science.gov (United States)

    Wu, Min-Hsien; Huang, Song-Bin; Lee, Gwo-Bin

    2010-04-21

    In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.

  12. Light-responsive polymers for microfluidic applications

    NARCIS (Netherlands)

    ter Schiphorst, J.; Saez, J.; Diamond, D.; Benito-Lopez, F.; Schenning, A.P.H.J.

    2018-01-01

    While the microfluidic device itself may be small, often the equipment required to control fluidics in the chip unit is large e.g. pumps, valves and mixing units, which can severely limit practical use and functional scalability. In addition, components associated with fluidic control of the device,

  13. Synthesis of Application-Specific Fault-Tolerant Digital Microfluidic Biochip Architectures

    DEFF Research Database (Denmark)

    Alistar, Mirela; Pop, Paul; Madsen, Jan

    2016-01-01

    Digital microfluidic biochips (DMBs) are microfluidic devices that manipulate droplets on an array of electrodes. Microfluidic operations, such as transport, mixing, and split, are performed on the electrode array to perform a biochemical application. All previous work assumes that the DMB...

  14. Miniaturization of environmental chemical assays in flowing systems: The lab-on-a-valve approach vis-à-vis lab-on-a-chip microfluidic devices

    DEFF Research Database (Denmark)

    Miró, Manuel; Hansen, Elo Harald

    2007-01-01

    The analytical capabilities of the microminiaturised lab-on-a-valve (LOV) module integrated into a microsequential injection (muSI) fluidic system in terms of analytical chemical performance, microfluidic handling and on-line sample processing are compared to those of the micro total analysis...... and the kinetics of the chemical reactions at will, LOV allows accommodation of reactions which, at least at the present stage, are not feasible by application of microfluidic LOC systems. Thus, in LOV one may take advantage of kinetic discriminations schemes, where even subtle differences in reactions...... are utilized for analytical purposes. Furthemore, it is also feasible to handle multi-step sequential reactions of divergent kinetics; to conduct multi-parametric determinations without manifold reconfiguration by utilization of the inherent open architecture of the micromachined unit for the implementation...

  15. Microfluidic technology for PET radiochemistry

    International Nuclear Information System (INIS)

    Gillies, J.M.; Prenant, C.; Chimon, G.N.; Smethurst, G.J.; Dekker, B.A.; Zweit, J.

    2006-01-01

    This paper describes the first application of a microfabricated reaction system to positron emission tomography (PET) radiochemistry. We have applied microfluidic technology to synthesise PET radiopharmaceuticals using 18 F and 124 I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These reactions involved established methods of nucleophilic substitution on a mannose triflate precursor and direct iodination of the protein using iodogen as an oxidant. This has demonstrated a proof of principle of using microfluidic technology to radiochemical reactions involving low and high molecular weight compounds. Using microfluidic reactions, [ 18 F]FDG was synthesised with a 50% incorporation of the available F-18 radioactivity in a very short time of 4 s. The radiolabelling efficiency of 124 I Annexin-V was 40% after 1 min reaction time. Chromatographic analysis showed that such reaction yields are comparable to conventional methods, but in a much shorter time. The yields can be further improved with more optimisation of the microfluidic device itself and its fluid mixing profiles. This demonstrates the potential for this technology to have an impact on rapid and simpler radiopharmaceutical synthesis using short and medium half-life radionuclides

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

    Directory of Open Access Journals (Sweden)

    Beum Jun Kim

    2016-09-01

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

  17. "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

  18. Material Biocompatibility for PCR Microfluidic Chips

    KAUST Repository

    Kodzius, Rimantas; Chang, Donald Choy; Gong, Xiuqing; Wen, Weijia; Wu, Jinbo; Xiao, Kang; Yi, Xin

    2010-01-01

    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.

  19. 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.

  20. 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

  1. Patterning of PMMA microfluidic parts using screen printing process

    Science.gov (United States)

    Ahari Kaleibar, Aminreza; Rahbar, Mona; Haiducu, Marius; Parameswaran, Ash M.

    2010-02-01

    An inexpensive and rapid micro-fabrication process for producing PMMA microfluidic components has been presented. Our proposed technique takes advantages of commercially available economical technologies such as the silk screen printing and UV patterning of PMMA substrates to produce the microfluidic components. As a demonstration of our proposed technique, we had utilized a homemade deep-UV source, λ=254nm, a silk screen mask made using a local screen-printing shop and Isopropyl alcohol - water mixture (IPA-water) as developer to quickly define the microfluidic patterns. The prototyped devices were successfully bonded, sealed, and the device functionality tested and demonstrated. The screen printing based technique can produce microfluidic channels as small as 50 micrometers quite easily, making this technique the most cost-effective, fairly high precision and at the same time an ultra economical plastic microfluidic components fabrication process reported to date.

  2. Multiplexed microfluidic approach for nucleic acid enrichment

    Science.gov (United States)

    VanderNoot, Victoria A.; Langevin, Stanley Alan; Bent, Zachary; Renzi, Ronald F.; Ferko, Scott M.; Van De Vreugde, James L.; Lane, Todd; Patel, Kamlesh; Branda, Steven

    2016-04-26

    A system for enhancing a nucleic acid sample may include a one pump, a denaturing chamber; a microfluidic hydroxyapatite chromatography device configured for performing hydroxyapatite chromatography on the nucleic acid sample, a sample collector, and tubing connecting the pump with the denaturing chamber, the hydroxyapatite chromatography device and the sample collector such that the pump may be used to move the nucleic acid sample from the denaturing chamber to the hydroxyapatite chromatography device and then to the sample collector.

  3. Mechanistic evaluation of the pros and cons of digital RT-LAMP for HIV-1 viral load quantification on a microfluidic device and improved efficiency via a two-step digital protocol.

    Science.gov (United States)

    Sun, Bing; Shen, Feng; McCalla, Stephanie E; Kreutz, Jason E; Karymov, Mikhail A; Ismagilov, Rustem F

    2013-02-05

    Here we used a SlipChip microfluidic device to evaluate the performance of digital reverse transcription-loop-mediated isothermal amplification (dRT-LAMP) for quantification of HIV viral RNA. Tests are needed for monitoring HIV viral load to control the emergence of drug resistance and to diagnose acute HIV infections. In resource-limited settings, in vitro measurement of HIV viral load in a simple format is especially needed, and single-molecule counting using a digital format could provide a potential solution. We showed here that when one-step dRT-LAMP is used for quantification of HIV RNA, the digital count is lower than expected and is limited by the yield of desired cDNA. We were able to overcome the limitations by developing a microfluidic protocol to manipulate many single molecules in parallel through a two-step digital process. In the first step we compartmentalize the individual RNA molecules (based on Poisson statistics) and perform reverse transcription on each RNA molecule independently to produce DNA. In the second step, we perform the LAMP amplification on all individual DNA molecules in parallel. Using this new protocol, we increased the absolute efficiency (the ratio between the concentration calculated from the actual count and the expected concentration) of dRT-LAMP 10-fold, from ∼2% to ∼23%, by (i) using a more efficient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding only the BIP primer during the RT step. We also used this two-step method to quantify HIV RNA purified from four patient samples and found that in some cases, the quantification results were highly sensitive to the sequence of the patient's HIV RNA. We learned the following three lessons from this work: (i) digital amplification technologies, including dLAMP and dPCR, may give adequate dilution curves and yet have low efficiency, thereby providing quantification values that underestimate the true concentration. Careful

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

    Science.gov (United States)

    Jayamohan, Harikrishnan

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

  5. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    Science.gov (United States)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  6. Designing Polymeric Microfluidic Platforms for Biomedical Applications

    DEFF Research Database (Denmark)

    Vedarethinam, Indumathi

    Micro- and Nanotechnology have the potential to offer a smart solution for diagnostics and academia research with rapid, low cost, robust analysis systems to facilitate biological analyses. New, high throughput microfluidic platforms have the potential to surpass in performance the conventional...... analyses systems in use today. The overall goal of this PhD project is to address two different areas using microfluidics : i) Chromosome analysis by metaphase FISH such a platform, if successful, can immediately substitute the routine, labor-intensive, glass slide-based FISH analyses in Clinical...... Cytogenetics laboratories. During the course of this project, initially the suitability of the polymeric chip substrate was tested and a microfluidic device was developed for performing interphase FISH analysis. With this device, the key factors involved in chromosome spreading crucial to FISH analysis were...

  7. 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.

  8. 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.

  9. Digital Microfluidics Sample Analyzer

    Science.gov (United States)

    Pollack, Michael G.; Srinivasan, Vijay; Eckhardt, Allen; Paik, Philip Y.; Sudarsan, Arjun; Shenderov, Alex; Hua, Zhishan; Pamula, Vamsee K.

    2010-01-01

    Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

  10. Parallel imaging microfluidic cytometer.

    Science.gov (United States)

    Ehrlich, Daniel J; McKenna, Brian K; Evans, James G; Belkina, Anna C; Denis, Gerald V; Sherr, David H; Cheung, Man Ching

    2011-01-01

    By adding an additional degree of freedom from multichannel flow, the parallel microfluidic cytometer (PMC) combines some of the best features of fluorescence-activated flow cytometry (FCM) and microscope-based high-content screening (HCS). The PMC (i) lends itself to fast processing of large numbers of samples, (ii) adds a 1D imaging capability for intracellular localization assays (HCS), (iii) has a high rare-cell sensitivity, and (iv) has an unusual capability for time-synchronized sampling. An inability to practically handle large sample numbers has restricted applications of conventional flow cytometers and microscopes in combinatorial cell assays, network biology, and drug discovery. The PMC promises to relieve a bottleneck in these previously constrained applications. The PMC may also be a powerful tool for finding rare primary cells in the clinic. The multichannel architecture of current PMC prototypes allows 384 unique samples for a cell-based screen to be read out in ∼6-10 min, about 30 times the speed of most current FCM systems. In 1D intracellular imaging, the PMC can obtain protein localization using HCS marker strategies at many times for the sample throughput of charge-coupled device (CCD)-based microscopes or CCD-based single-channel flow cytometers. The PMC also permits the signal integration time to be varied over a larger range than is practical in conventional flow cytometers. The signal-to-noise advantages are useful, for example, in counting rare positive cells in the most difficult early stages of genome-wide screening. We review the status of parallel microfluidic cytometry and discuss some of the directions the new technology may take. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Computer-aided design of microfluidic very large scale integration (mVLSI) biochips design automation, testing, and design-for-testability

    CERN Document Server

    Hu, Kai; Ho, Tsung-Yi

    2017-01-01

    This book provides a comprehensive overview of flow-based, microfluidic VLSI. The authors describe and solve in a comprehensive and holistic manner practical challenges such as control synthesis, wash optimization, design for testability, and diagnosis of modern flow-based microfluidic biochips. They introduce practical solutions, based on rigorous optimization and formal models. The technical contributions presented in this book will not only shorten the product development cycle, but also accelerate the adoption and further development of modern flow-based microfluidic biochips, by facilitating the full exploitation of design complexities that are possible with current fabrication techniques. Offers the first practical problem formulation for automated control-layer design in flow-based microfluidic biochips and provides a systematic approach for solving this problem; Introduces a wash-optimization method for cross-contamination removal; Presents a design-for-testability (DfT) technique that can achieve 100...

  12. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available for microfluidics K. LAND, S. HUGO, M MBANJWA, L FOURIE CSIR Materials Science and Manufacturing P O Box 395, Pretoria 0001, SOUTH AFRICA Email: kland@csir.co.za INTRODUCTION Microfluidics refers to the manipulation of very small volumes of fluid.... Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  13. 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.

  14. Design of microfluidic bioreactors using topology optimization

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Bruus, Henrik

    2007-01-01

    We address the design of optimal reactors for supporting biological cultures using the method of topology optimization. For some years this method have been used to design various optimal microfluidic devices.1-4 We apply this method to distribute optimally biologic cultures within a flow...

  15. Microfluidic Sensing Platforms for Medicine and Diagnostics

    DEFF Research Database (Denmark)

    Kiilerich-Pedersen, Katrine

    the specialized laboratory. Microfluidic cell migration devices, imitating in vivo conditions were developed with success, improving the in vitro experimental setup for basic research and drug discovery. Polymer biosensors have reached a new level of maturity, and pathogen detection could benefit from...

  16. 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.

  17. Tunable Microfluidic Dye Laser

    DEFF Research Database (Denmark)

    Olsen, Brian Bilenberg; Helbo, Bjarne; Kutter, Jörg Peter

    2003-01-01

    We present a tunable microfluidic dye laser fabricated in SU-8. The tunability is enabled by integrating a microfluidic diffusion mixer with an existing microfluidic dye laser design by Helbo et al. By controlling the relative flows in the mixer between a dye solution and a solvent......, the concentration of dye in the laser cavity can be adjusted, allowing the wavelength to be tuned. Wavelength tuning controlled by the dye concentration was demonstrated with macroscopic dye lasers already in 1971, but this principle only becomes practically applicable by the use of microfluidic mixing...

  18. Room-temperature serial crystallography using a kinetically optimized microfluidic device for protein crystallization and on-chip X-ray diffraction

    Directory of Open Access Journals (Sweden)

    Michael Heymann

    2014-09-01

    Full Text Available An emulsion-based serial crystallographic technology has been developed, in which nanolitre-sized droplets of protein solution are encapsulated in oil and stabilized by surfactant. Once the first crystal in a drop is nucleated, the small volume generates a negative feedback mechanism that lowers the supersaturation. This mechanism is exploited to produce one crystal per drop. Diffraction data are measured, one crystal at a time, from a series of room-temperature crystals stored on an X-ray semi-transparent microfluidic chip, and a 93% complete data set is obtained by merging single diffraction frames taken from different unoriented crystals. As proof of concept, the structure of glucose isomerase was solved to 2.1 Å, demonstrating the feasibility of high-throughput serial X-ray crystallography using synchrotron radiation.

  19. Microfluidic stretchable RF electronics.

    Science.gov (United States)

    Cheng, Shi; Wu, Zhigang

    2010-12-07

    Stretchable electronics is a revolutionary technology that will potentially create a world of radically different electronic devices and systems that open up an entirely new spectrum of possibilities. This article proposes a microfluidic based solution for stretchable radio frequency (RF) electronics, using hybrid integration of active circuits assembled on flex foils and liquid alloy passive structures embedded in elastic substrates, e.g. polydimethylsiloxane (PDMS). This concept was employed to implement a 900 MHz stretchable RF radiation sensor, consisting of a large area elastic antenna and a cluster of conventional rigid components for RF power detection. The integrated radiation sensor except the power supply was fully embedded in a thin elastomeric substrate. Good electrical performance of the standalone stretchable antenna as well as the RF power detection sub-module was verified by experiments. The sensor successfully detected the RF radiation over 5 m distance in the system demonstration. Experiments on two-dimensional (2D) stretching up to 15%, folding and twisting of the demonstrated sensor were also carried out. Despite the integrated device was severely deformed, no failure in RF radiation sensing was observed in the tests. This technique illuminates a promising route of realizing stretchable and foldable large area integrated RF electronics that are of great interest to a variety of applications like wearable computing, health monitoring, medical diagnostics, and curvilinear electronics.

  20. 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.