Sample preparation system for microfluidic applications

Science.gov (United States)

Mosier, Bruce P [San Francisco, CA; Crocker, Robert W [Fremont, CA; Patel, Kamlesh D [Dublin, CA; Harnett, Cindy K [Livermore, CA

2007-05-08

An apparatus that couples automated injection with flow feedback to provide nanoliter accuracy in controlling microliter volumes. The apparatus comprises generally a source of hydraulic fluid pressure, a fluid isolator joined to the outlet of the hydraulic pressure source and a flow sensor to provide pressure-driven analyte metering. For operation generally and particularly in microfluidic systems the hydraulic pressure source is typically an electrokinetic (EK) pump that incorporates gasless electrodes. The apparatus is capable of metering sub-microliter volumes at flowrates of 1 100 .mu.L/min into microsystem load pressures of up to 1000 50 psi, respectively. Flowrates can be specified within 0.5 .mu.L/min and volumes as small as 80 nL can be metered.

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

Optical two-beam traps in microfluidic systems

DEFF Research Database (Denmark)

Berg-Sørensen, Kirstine

2016-01-01

An attractive solution for optical trapping and stretching by means of two counterpropagating laser beams is to embed waveguides or optical fibers in a microfluidic system. The microfluidic system can be constructed in different materials, ranging from soft polymers that may easily be cast...... written waveguides and in an injection molded polymer chip with grooves for optical fibers. (C) 2016 The Japan Society of Applied Physics....

Basic principles of electrolyte chemistry for microfluidic electrokinetics. Part II: Coupling between ion mobility, electrolysis, and acid-base equilibria.

Science.gov (United States)

Persat, Alexandre; Suss, Matthew E; Santiago, Juan G

2009-09-07

We present elements of electrolyte dynamics and electrochemistry relevant to microfluidic electrokinetics experiments. In Part I of this two-paper series, we presented a review and introduction to the fundamentals of acid-base chemistry. Here, we first summarize the coupling between acid-base equilibrium chemistry and electrophoretic mobilities of electrolytes, at both infinite and finite dilution. We then discuss the effects of electrode reactions on microfluidic electrokinetic experiments and derive a model for pH changes in microchip reservoirs during typical direct-current electrokinetic experiments. We present a model for the potential drop in typical microchip electrophoresis device. The latter includes finite element simulation to estimate the relative effects of channel and reservoir dimensions. Finally, we summarize effects of electrode and electrolyte characteristics on potential drop in microfluidic devices. As a whole, the discussions highlight the importance of the coupling between electromigration and electrophoresis, acid-base equilibria, and electrochemical reactions.

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.

CMOS Enabled Microfluidic Systems for Healthcare Based Applications

KAUST Repository

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

2018-01-01

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

CMOS Enabled Microfluidic Systems for Healthcare Based Applications

KAUST Repository

Khan, Sherjeel M.

2018-02-27

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

Integrated thin film Si fluorescence sensor coupled with a GaN microLED for microfluidic point-of-care testing

Science.gov (United States)

Robbins, Hannah; Sumitomo, Keiko; Tsujimura, Noriyuki; Kamei, Toshihiro

2018-02-01

An integrated fluorescence sensor consisting of a SiO2/Ta2O5 multilayer optical interference filter and hydrogenated amorphous silicon (a-Si:H) pin photodiode was coupled with a GaN microLED to construct a compact fluorescence detection module for point-of-care microfluidic biochemical analysis. The combination of the small size of the GaN microLED and asymmetric microlens resulted in a focal spot diameter of the excitation light of approximately 200 µm. The limit of detection of the sensor was as high as 36 nM for fluorescein solution flowing in a 100 µm deep microfluidic channel because of the lack of directionality of the LED light. Nevertheless, we used the GaN microLED coupled with the a-Si:H fluorescence sensor to successfully detect fluorescence from a streptavidin R-phycoerythrin conjugate that bound to biotinylated antibody-coated microbeads trapped by the barrier in the microfluidic channel.

Modular microfluidic system for biological sample preparation

Science.gov (United States)

Rose, Klint A.; Mariella, Jr., Raymond P.; Bailey, Christopher G.; Ness, Kevin Dean

2015-09-29

A reconfigurable modular microfluidic system for preparation of a biological sample including a series of reconfigurable modules for automated sample preparation adapted to selectively include a) a microfluidic acoustic focusing filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter.

A smartphone controlled handheld microfluidic liquid handling system.

Science.gov (United States)

Li, Baichen; Li, Lin; Guan, Allan; Dong, Quan; Ruan, Kangcheng; Hu, Ronggui; Li, Zhenyu

2014-10-21

Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems.

CMOS Enabled Microfluidic Systems for Healthcare Based Applications.

Science.gov (United States)

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

2018-04-01

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

Microfluidic systems for stem cell-based neural tissue engineering.

Science.gov (United States)

Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

2016-07-05

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

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

Science.gov (United States)

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

2010-02-21

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

Development of Microfluidic Systems Enabling High-Throughput Single-Cell Protein Characterization

OpenAIRE

Fan, Beiyuan; Li, Xiufeng; Chen, Deyong; Peng, Hongshang; Wang, Junbo; Chen, Jian

2016-01-01

This article reviews recent developments in microfluidic systems enabling high-throughput characterization of single-cell proteins. Four key perspectives of microfluidic platforms are included in this review: (1) microfluidic fluorescent flow cytometry; (2) droplet based microfluidic flow cytometry; (3) large-array micro wells (microengraving); and (4) large-array micro chambers (barcode microchips). We examine the advantages and limitations of each technique and discuss future research oppor...

Microfluidic biofunctionalisation protocols to form multi-valent interactions for cell rolling and phenotype modification investigations

KAUST Repository

Perozziello, Gerardo

2013-07-01

In this study, we propose a fast, simple method to biofunctionalise microfluidic systems for cellomic investigations based on micro-fluidic protocols. Many available processes either require expensive and time-consuming protocols or are incompatible with the fabrication of microfluidic systems. Our method differs from the existing since it is applicable to an assembled system, uses few microlitres of reagents and it is based on the use of microbeads. The microbeads have specific surface moieties to link the biomolecules and couple cell receptors. Furthermore, the microbeads serve as arm spacer and offer the benefit of the multi-valent interaction. Microfluidics was adapted together with topology and biochemistry surface modifications to offer the microenvironment for cellomic studies. Based on this principle, we exploit the streptavidin-biotin interaction to couple antibodies to the biofunctionalised microfluidic environment within 5 h using 200 μL of reagents and biomolecules. We selected the antibodies able to form complexes with the MHC class I (MHC-I) molecules present on the cell membrane and involved in the immune surveillance. To test the microfluidic system, tumour cell lines (RMA) were rolled across the coupled antibodies to recognise and strip MHC-I molecules. As result, we show that cell rolling performed inside a microfluidic chamber functionalised with beads and the opportune antibody facilitate the removal of MHC class I molecules. We showed that the level of median fluorescent intensity of the MHC-I molecules is 300 for cells treated in a not biofunctionalised surface. It decreased to 275 for cells treated in a flat biofunctionalised surface and to 250 for cells treated on a surface where biofunctionalised microbeads were immobilised. The cells with reduced expression of MHC-I molecules showed, after cytotoxicity tests, susceptibility 3.5 times higher than normal cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of nanoparticle focusing by coupling thermophoresis and engineered vortex in a microfluidic channel

Science.gov (United States)

Zhao, Chao; Cao, Zhibo; Fraser, John; Oztekin, Alparslan; Cheng, Xuanhong

2017-01-01

Enriching nanoparticles in an aqueous solution is commonly practiced for various applications. Despite recent advances in microfluidic technologies, a general method to concentrate nanoparticles in a microfluidic channel in a label free and continuous flow fashion is not yet available, due to strong Brownian motion on the nanoscale. Recent research of thermophoresis indicates that thermophoretic force can overcome the Brownian force to direct nanoparticle movement. Coupling thermophoresis with natural convection on the microscale has been shown to induce significant enrichment of biomolecules in a thermal diffusion column. However, the column operates in a batch process, and the concentrated samples are inconvenient to retrieve. We have recently designed a microfluidic device that combines a helical fluid motion and simple one-dimensional temperature gradient to achieve effective nanoparticle focusing in a continuous flow. The helical convection is introduced by microgrooves patterned on the channel floor, which directly controls the focusing speed and power. Here, COMSOL simulations are conducted to study how the device geometry and flow rate influence transport and subsequent nanoparticle focusing, with a constant temperature gradient. The results demonstrate a complex dependence of nanoparticle accumulation on the microgroove tilting angle, depth, and spacing, as well as channel width and flow rate. Further dimensional analyses reveal that the ratio between particle velocities induced by thermophoretic and fluid inertial forces governs the particle concentration factor, with a maximum concentration at a ratio of approximately one. This simple relationship provides fundamental insights about nanoparticle transport in coupled flow and thermal fields. The study also offers a useful guideline to the design and operation of nanoparticle concentrators based on combining engineered helical fluid motion subject to phoretic fields.

Synthesis of hexagonal gold nanoparticles using a microfluidic reaction system

International Nuclear Information System (INIS)

Weng, Chen-Hsun; Lee, Gwo-Bin; Huang, Chih-Chia; Yeh, Chen-Sheng; Lei, Huan-Yao

2008-01-01

A new microfluidic reaction system capable of mixing, transporting and reacting is developed for the synthesis of gold nanoparticles. It allows for a rapid and a cost-effective approach to accelerate the synthesis of gold nanoparticles. The microfluidic reaction chip is made from micro-electro-mechanical-system technologies which integrate a micro-mixer, micro-pumps, a micro-valve, micro-heaters and a micro temperature sensor on a single chip. Successful synthesis of dispersed gold nanoparticles has been demonstrated within a shorter period of time, as compared to traditional methods. It is experimentally found that precise control of the mixing/heating time for gold salts and reducing agents plays an essential role in the synthesis of gold nanoparticles. The growth process of hexagonal gold nanoparticles by a thermal aqueous approach is also systematically studied by using the same microfluidic reaction system. The development of the microfluidic reaction system could be promising for the synthesis of functional nanoparticles for future biomedical applications

Integrated Microfluidic Sensor System with Magnetostrictive Resonators

KAUST Repository

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

2011-01-01

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

Integrated Microfluidic Sensor System with Magnetostrictive Resonators

KAUST Repository

Liang, Cai

2011-12-08

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

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

Science.gov (United States)

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

2001-09-15

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

Rapid prototyping of microfluidic systems using a PDMS/polymer tape composite.

Science.gov (United States)

Kim, Jungkyu; Surapaneni, Rajesh; Gale, Bruce K

2009-05-07

Rapid prototyping of microfluidic systems using a combination of double-sided tape and PDMS (polydimethylsiloxane) is introduced. PDMS is typically difficult to bond using adhesive tapes due to its hydrophobic nature and low surface energy. For this reason, PDMS is not compatible with the xurography method, which uses a knife plotter and various adhesive coated polymer tapes. To solve these problems, a PDMS/tape composite was developed and demonstrated in microfluidic applications. The PDMS/tape composite was created by spinning it to make a thin layer of PDMS over double-sided tape. Then the PDMS/tape composite was patterned to create channels using xurography, and bonded to a PDMS slab. After removing the backing paper from the tape, a complete microfluidic system could be created by placing the construct onto nearly any substrate; including glass, plastic or metal-coated glass/silicon substrates. The bond strength was shown to be sufficient for the pressures that occur in typical microfluidic channels used for chemical or biological analysis. This method was demonstrated in three applications: standard microfluidic channels and reactors, a microfluidic system with an integrated membrane, and an electrochemical biosensor. The PDMS/tape composite rapid prototyping technique provides a fast and cost effective fabrication method and can provide easy integration of microfluidic channels with sensors and other components without the need for a cleanroom facility.

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.

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.

A disposable and multifunctional capsule for easy operation of microfluidic elastomer systems

International Nuclear Information System (INIS)

Thorslund, Sara; Läräng, Thomas; Kreuger, Johan; Nguyen, Hugo; Barkefors, Irmeli

2011-01-01

The global lab-on-chip and microfluidic markets for cell-based assays have been predicted to grow considerably, as novel microfluidic systems enable cell biologists to perform in vitro experiments at an unprecedented level of experimental control. Nevertheless, microfluidic assays must, in order to compete with conventional assays, be made available at easily affordable costs, and in addition be made simple to operate for users having no previous experience with microfluidics. We have to this end developed a multifunctional microfluidic capsule that can be mass-produced at low cost in thermoplastic material. The capsule enables straightforward operation of elastomer inserts of optional design, here exemplified with insert designs for molecular gradient formation in microfluidic cell culture systems. The integrated macro–micro interface of the capsule ensures reliable connection of the elastomer fluidic structures to an external perfusion system. A separate compartment in the capsule filled with superabsorbent material is used for internal waste absorption. The capsule assembly process is made easy by integrated snap-fits, and samples within the closed capsule can be analyzed using both inverted and upright microscopes. Taken together, the capsule concept presented here could help accelerate the use of microfluidic-based biological assays in the life science sector. (technical note)

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

Grating-Coupled Surface Plasmon Resonance (GC-SPR) Optimization for Phase-Interrogation Biosensing in a Microfluidic Chamber.

Science.gov (United States)

Rossi, Stefano; Gazzola, Enrico; Capaldo, Pietro; Borile, Giulia; Romanato, Filippo

2018-05-18

Surface Plasmon Resonance (SPR)-based sensors have the advantage of being label-free, enzyme-free and real-time. However, their spreading in multidisciplinary research is still mostly limited to prism-coupled devices. Plasmonic gratings, combined with a simple and cost-effective instrumentation, have been poorly developed compared to prism-coupled system mainly due to their lower sensitivity. Here we describe the optimization and signal enhancement of a sensing platform based on phase-interrogation method, which entails the exploitation of a nanostructured sensor. This technique is particularly suitable for integration of the plasmonic sensor in a lab-on-a-chip platform and can be used in a microfluidic chamber to ease the sensing procedures and limit the injected volume. The careful optimization of most suitable experimental parameters by numerical simulations leads to a 30⁻50% enhancement of SPR response, opening new possibilities for applications in the biomedical research field while maintaining the ease and versatility of the configuration.

Development of a microfluidic perfusion 3D cell culture system

Science.gov (United States)

Park, D. H.; Jeon, H. J.; Kim, M. J.; Nguyen, X. D.; Morten, K.; Go, J. S.

2018-04-01

Recently, 3-dimensional in vitro cell cultures have gained much attention in biomedical sciences because of the closer relevance between in vitro cell cultures and in vivo environments. This paper presents a microfluidic perfusion 3D cell culture system with consistent control of long-term culture conditions to mimic an in vivo microenvironment. It consists of two sudden expansion reservoirs to trap incoming air bubbles, gradient generators to provide a linear concentration, and microchannel mixers. Specifically, the air bubbles disturb a flow in the microfluidic channel resulting in the instability of the perfusion cell culture conditions. For long-term stable operation, the sudden expansion reservoir is designed to trap air bubbles by using buoyancy before they enter the culture system. The performance of the developed microfluidic perfusion 3D cell culture system was examined experimentally and compared with analytical results. Finally, it was applied to test the cytotoxicity of cells infected with Ewing’s sarcoma. Cell death was observed for different concentrations of H2O2. For future work, the developed microfluidic perfusion 3D cell culture system can be used to examine the behavior of cells treated with various drugs and concentrations for high-throughput drug screening.

Standardized and modular microfluidic platform for fast lab on chip system development

NARCIS (Netherlands)

Dekker, Stefan; van den Berg, Albert; Odijk, Mathieu; Lee, Abraham; DeVoe, Don

2017-01-01

This paper reports a modular microfluidic system with standardized parts, enabling rapid prototyping of lab on chip systems. Herewith contributing to the technology transfer from academy to industry. The use of standardized parts also makes it possible to design a microfluidic systems in a top down

Fabrication of a multiplexed microfluidic system for scaled up production of cross-linked biocatalytic microspheres

CSIR Research Space (South Africa)

Mbanjwa, M

2014-06-01

Full Text Available the design and fabrication of a multiplexed microfluidic system for producing biocatalytic microspheres. The microfluidic system consists of an array of 10 parallel microfluidic circuits, for simultaneous operation to demonstrate increased production...

Novel Budesonide Particles for Dry Powder Inhalation Prepared Using a Microfluidic Reactor Coupled With Ultrasonic Spray Freeze Drying.

Science.gov (United States)

Saboti, Denis; Maver, Uroš; Chan, Hak-Kim; Planinšek, Odon

2017-07-01

Budesonide (BDS) is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers, nebulizers, and dry powder inhalers. Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of this study was therefore to develop a novel method for preparation of fine BDS particles using a microfluidic reactor coupled with ultrasonic spray freeze drying, and hence avoiding the need of additional homogenization or stabilizer use. A T-junction microfluidic reactor was employed to produce particle suspension (using an ethanol-water, methanol-water, and an acetone-water system), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final preparation step. The result was fine crystalline BDS powders which, when blended with lactose and dispersed in an Aerolizer at 100 L/min, generated fine particle fraction in the range 47.6% ± 2.8% to 54.9% ± 1.8%, thus exhibiting a good aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a viable solution for particle isolation in microfluidics in general. Copyright © 2017 American Pharmacists Association®. All rights reserved.

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...

Integration of microelectronic chips in microfluidic systems on printed circuit board

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Science.gov (United States)

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

2010-06-01

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

Usability and Applicability of Microfluidic Cell Culture Systems

DEFF Research Database (Denmark)

Hemmingsen, Mette

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

Magnetic separation in microfluidic systems

DEFF Research Database (Denmark)

Smistrup, Kristian

2007-01-01

to facilitate real-time monitoring of the experiments. The set-up and experimental protocol are described in detail. Results are presented for ’active’ magnetic bead separators, where on-chip microfabricated electromagnets supply the magnetic field and field gradients necessary for magnetic bead separation....... It is shown conceptually how such a system can be applied for parallel biochemical processing in a microfluidic system. ’Passive’ magnetic separators are presented, where on-chip soft magnetic elements are magnetized by an external magnetic field and create strong magnetic fields and gradients inside...

Multilayer microfluidic systems with indium-tin-oxide microelectrodes for studying biological cells

International Nuclear Information System (INIS)

Wu, Hsiang-Chiu; Chen, Hsin; Lyau, Jia-Bo; Lin, Min-Hsuan; Chuang, Yung-Jen

2017-01-01

Contemporary semiconductor and micromachining technologies have been exploited to develop lab-on-a-chip microsystems, which enable parallel and efficient experiments in molecular and cellular biology. In these microlab systems, microfluidics play an important role for automatic transportation or immobilization of cells and bio-molecules, as well as for separation or mixing of different chemical reagents. However, seldom microlab systems allow both morphology and electrophysiology of biological cells to be studied in situ . This kind of study is important, for example, for understanding how neuronal networks grow in response to environmental stimuli. To fulfill this application need, this paper investigates the possibility of fabricating multi-layer photoresists as microfluidic systems directly above a glass substrate with indium-tin-oxide (ITO) electrodes. The microfluidic channels are designed to guide and trap biological cells on top of ITO electrodes, through which the electrical activities of cells can be recorded or elicited. As both the microfluidic system and ITO electrodes are transparent, the cellular morphology is observable easily during electrophysiological studies. Two fabrication processes are proposed and compared. One defines the structure and curing depth of each photoresist layer simply by controlling the exposure time in lithography, while the other further utilizes a sacrificial layer to defines the structure of the bottom layer. The fabricated microfluidic system is proved bio-compatible and able to trap blood cells or neurons. Therefore, the proposed microsystem will be useful for studying cultured cells efficiently in applications such as drug-screening. (paper)

Bridging Flows: Microfluidic End‐User Solutions

DEFF Research Database (Denmark)

Sabourin, David

Microfluidic applications hold promise for many different end‐users both within and outside, and across many different research communities. Despite the benefits of microfluidic approaches, adoption and implementation thereof is often hindered by practical issues. Microfluidic components which......‐integrated interconnection and miniaturized peristaltic pump solutions were then combined into modular microfluidic systems. One system provides high interconnection numbers/density and allows many possible configurations. Additionally, and apart from many other accounts of modular microfluidic solutions, methods...... for control and actuation of microfluidic networks built from the modular components is described. Prototypes of the microfluidic system have begun to be distributed to external collaborators and researcher parties. These end‐users will assist in the validation of the approach and ultimately fulfil the key...

Testing of a Microfluidic Sampling System for High Temperature Electrochemical MC&A

Energy Technology Data Exchange (ETDEWEB)

Pereira, Candido [Argonne National Lab. (ANL), Argonne, IL (United States); Nichols, Kevin [Argonne National Lab. (ANL), Argonne, IL (United States)

2013-11-27

This report describes the preliminary validation of a high-temperature microfluidic chip system for sampling of electrochemical process salt. Electroanalytical and spectroscopic techniques are attractive candidates for improvement through high-throughput sample analysis via miniaturization. Further, microfluidic chip systems are amenable to micro-scale chemical processing such as rapid, automated sample purification to improve sensor performance. The microfluidic chip was tested to determine the feasibility of the system for high temperature applications and conditions under which microfluidic systems can be used to generate salt droplets at process temperature to support development of material balance and control systems in a used fuel treatment facility. In FY13, the project focused on testing a quartz microchip device with molten salts at near process temperatures. The equipment was installed in glove box and tested up to 400°C using commercial thermal transfer fluids as the carrier phase. Preliminary tests were carried out with a low-melting halide salt to initially characterize the properties of this novel liquid-liquid system and to investigate the operating regimes for inducing droplet flow within candidate carrier fluids. Initial results show that the concept is viable for high temperature sampling but further development is required to optimize the system to operate with process relevant molten salts.

Controllable Ag nanostructure patterning in a microfluidic channel for real-time SERS systems.

Science.gov (United States)

Leem, Juyoung; Kang, Hyun Wook; Ko, Seung Hwan; Sung, Hyung Jin

2014-03-07

We present a microfluidic patterning system for fabricating nanostructured Ag thin films via a polyol method. The fabricated Ag thin films can be used immediately in a real-time SERS sensing system. The Ag thin films are formed on the inner surfaces of a microfluidic channel so that a Ag-patterned Si wafer and a Ag-patterned PDMS channel are produced by the fabrication. The optimum sensing region and fabrication duration for effective SERS detection were determined. As SERS active substrates, the patterned Ag thin films exhibit an enhancement factor (EF) of 4.25 × 10(10). The Ag-patterned polymer channel was attached to a glass substrate and used as a microfluidic sensing system for the real-time monitoring of biomolecule concentrations. This microfluidic patterning system provides a low-cost process for the fabrication of materials that are useful in medical and pharmaceutical detection and can be employed in mass production.

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...

[Micro-droplet characterization and its application for amino acid detection in droplet microfluidic system].

Science.gov (United States)

Yuan, Huiling; Dong, Libing; Tu, Ran; Du, Wenbin; Ji, Shiru; Wang, Qinhong

2014-01-01

Recently, the droplet microfluidic system attracts interests due to its high throughput and low cost to detect and screen. The picoliter micro-droplets from droplet microfluidics are uniform with respect to the size and shape, and could be used as monodispensed micro-reactors for encapsulation and detection of single cell or its metabolites. Therefore, it is indispensable to characterize micro-droplet and its application from droplet microfluidic system. We first constructed the custom-designed droplet microfluidic system for generating micro-droplets, and then used the micro-droplets to encapsulate important amino acids such as glutamic acid, phenylalanine, tryptophan or tyrosine to test the droplets' properties, including the stability, diffusivity and bio-compatibility for investigating its application for amino acid detection and sorting. The custom-designed droplet microfluidic system could generate the uniformed micro-droplets with a controllable size between 20 to 50 microm. The micro-droplets could be stable for more than 20 h without cross-contamination or fusion each other. The throughput of detection and sorting of the system is about 600 micro-droplets per minute. This study provides a high-throughput platform for the analysis and screening of amino acid-producing microorganisms.

Closed-loop feedback control for microfluidic systems through automated capacitive fluid height sensing.

Science.gov (United States)

Soenksen, L R; Kassis, T; Noh, M; Griffith, L G; Trumper, D L

2018-03-13

Precise fluid height sensing in open-channel microfluidics has long been a desirable feature for a wide range of applications. However, performing accurate measurements of the fluid level in small-scale reservoirs (sensor contact needs to be avoided. In particular, gravity-driven systems used in several microfluidic applications to establish pressure gradients and impose flow remain open-loop and largely unmonitored due to these sensing limitations. Here we present an optimized self-shielded coplanar capacitive sensor design and automated control system to provide submillimeter fluid-height resolution (∼250 μm) and control of small-scale open reservoirs without the need for direct fluid contact. Results from testing and validation of our optimized sensor and system also suggest that accurate fluid height information can be used to robustly characterize, calibrate and dynamically control a range of microfluidic systems with complex pumping mechanisms, even in cell culture conditions. Capacitive sensing technology provides a scalable and cost-effective way to enable continuous monitoring and closed-loop feedback control of fluid volumes in small-scale gravity-dominated wells in a variety of microfluidic applications.

Simulation and fabrication of integrated polystyrene microlens in microfluidic system

KAUST Repository

Fan, Yiqiang

2013-05-17

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

Simulation and fabrication of integrated polystyrene microlens in microfluidic system

KAUST Repository

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

2013-01-01

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

The MainSTREAM Component Platform: A Holistic Approach to Microfluidic System Design

DEFF Research Database (Denmark)

Sabourin, David; Skafte-Pedersen, Peder; Søe, Martin Jensen

2013-01-01

A microfluidic component library for building systems driving parallel or serial microfluidic-based assays is presented. The components are a miniaturized eight-channel peristaltic pump, an eight-channel valve, sample-to-waste liquid management, and interconnections. The library of components...... of reaction chips; (2) highly parallel pumping and routing/valving capability; (3) methods to interface pumps and chip-to-liquid management systems; (4) means to construct a portable system; (5) reconfigurability/flexibility in system design; (6) means to interface to microscopes; and (7) compatibility...

Multichannel Bipotentiostat Integrated With a Microfluidic Platform for Electrochemical Real-Time Monitoring of Cell Cultures

DEFF Research Database (Denmark)

Vergani, Marco; Carminati, Marco; Ferrari, Giorgio

2012-01-01

An electrochemical detection system specifically designed for multi-parameter real-time monitoring of stem cell culturing/differentiation in a microfluidic system is presented. It is composed of a very compact 24-channel electronic board, compatible with arrays of microelectrodes and coupled...... to a microfluidic cell culture system. A versatile data acquisition software enables performing amperometry, cyclic voltammetry and impedance spectroscopy in each of the 12 independent chambers over a 100 kHz bandwidth with current resolution down to 5 pA for 100 ms measuring time. The design of the platform, its...... realization and experimental characterization are reported, with emphasis on the analysis of impact of input capacitance (i.e., microelectrode size) and microfluidic pump operation on current noise. Programmable sequences of successive injections of analytes (ferricyanide and dopamine) and rinsing buffer...

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.

Rapid microfluidic thermal cycler for nucleic acid amplification

Science.gov (United States)

Beer, Neil Reginald; Vafai, Kambiz

2015-10-27

A system for thermal cycling a material to be thermal cycled including a microfluidic heat exchanger; a porous medium in the microfluidic heat exchanger; a microfluidic thermal cycling chamber containing the material to be thermal cycled, the microfluidic thermal cycling chamber operatively connected to the microfluidic heat exchanger; a working fluid at first temperature; a first system for transmitting the working fluid at first temperature to the microfluidic heat exchanger; a working fluid at a second temperature, a second system for transmitting the working fluid at second temperature to the microfluidic heat exchanger; a pump for flowing the working fluid at the first temperature from the first system to the microfluidic heat exchanger and through the porous medium; and flowing the working fluid at the second temperature from the second system to the heat exchanger and through the porous medium.

3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

Science.gov (United States)

Knowlton, Stephanie; Yu, Chu Hsiang; Ersoy, Fulya; Emadi, Sharareh; Khademhosseini, Ali; Tasoglu, Savas

2016-06-20

Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering.

Development of an Integrated Polymer Microfluidic Stack

International Nuclear Information System (INIS)

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

2006-01-01

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

A Microfluidics-HPLC/Differential Mobility Spectrometer Macromolecular Detection System for Human and Robotic Missions

Science.gov (United States)

Coy, S. L.; Killeen, K.; Han, J.; Eiceman, G. A.; Kanik, I.; Kidd, R. D.

2011-01-01

Our goal is to develop a unique, miniaturized, solute analyzer based on microfluidics technology. The analyzer consists of an integrated microfluidics High Performance Liquid Chromatographic chip / Differential Mobility Spectrometer (?HPLCchip/ DMS) detection system

Tunable-angle wedge transducer for improved acoustophoretic control in a microfluidic chip

DEFF Research Database (Denmark)

Iranmanesh, I.; Barnkob, Rune; Bruus, Henrik

2012-01-01

We present a tunable-angle wedge ultrasound transducer for improved control of microparticle acoustophoresis in a microfluidic chip. The transducer is investigated by analyzing the pattern of aligned particles and induced acoustic energy density while varying the system geometry, transducer...... in geometry and that the coupling angle may be used as an additional tuning parameter for improved acoustophoretic control with single-frequency actuation. Further, we find that frequency-modulation actuation is suitable for diminishing such tuning effects and that it is a robust method to produce uniform...... coupling angle, and transducer actuation method (single-frequency actuation or frequency-modulation actuation). The energy-density analysis is based on measuring the transmitted light intensity through a microfluidic channel filled with a suspension of 5-μm-diameter beads and the results with the tunable-angle...

Biofunctionalization of PDMS-based microfluidic systems

OpenAIRE

sprotocols

2015-01-01

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

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...

A Microfluidic Immunostaining System Enables Quality Assured and Standardized Immunohistochemical Biomarker Analysis

Science.gov (United States)

Kwon, Seyong; Cho, Chang Hyun; Kwon, Youngmee; Lee, Eun Sook; Park, Je-Kyun

2017-04-01

Immunohistochemistry (IHC) plays an important role in biomarker-driven cancer therapy. Although there has been a high demand for standardized and quality assured IHC, it has rarely been achieved due to the complexity of IHC testing and the subjective validation-based process flow of IHC quality control. We present here a microfluidic immunostaining system for the standardization of IHC by creating a microfluidic linearly graded antibody (Ab)-staining device and a reference cell microarray. Unlike conventional efforts, our system deals primarily with the screening of biomarker staining conditions for quantitative quality assurance testing in IHC. We characterized the microfluidic matching of Ab staining intensity using three HER2 Abs produced by different manufacturers. The quality of HER2 Ab was also validated using tissues of breast cancer patients, demonstrating that our system is an efficient and powerful tool for the standardization and quality assurance of IHC.

Photonic crystal resonator integrated in a microfluidic system

DEFF Research Database (Denmark)

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

2008-01-01

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

Microwave frequency sensor for detection of biological cells in microfluidic channels.

Science.gov (United States)

Nikolic-Jaric, M; Romanuik, S F; Ferrier, G A; Bridges, G E; Butler, M; Sunley, K; Thomson, D J; Freeman, M R

2009-08-12

We present details of an apparatus for capacitive detection of biomaterials in microfluidic channels operating at microwave frequencies where dielectric effects due to interfacial polarization are minimal. A circuit model is presented, which can be used to adapt this detection system for use in other microfluidic applications and to identify ones where it would not be suitable. The detection system is based on a microwave coupled transmission line resonator integrated into an interferometer. At 1.5 GHz the system is capable of detecting changes in capacitance of 650 zF with a 50 Hz bandwidth. This system is well suited to the detection of biomaterials in a variety of suspending fluids, including phosphate-buffered saline. Applications involving both model particles (polystyrene microspheres) and living cells-baker's yeast (Saccharomyces cerevisiae) and Chinese hamster ovary cells-are presented.

Microfluidics on liquid handling stations (μF-on-LHS): a new industry-compatible microfluidic platform

Science.gov (United States)

Kittelmann, Jörg; Radtke, Carsten P.; Waldbaur, Ansgar; Neumann, Christiane; Hubbuch, Jürgen; Rapp, Bastian E.

2014-03-01

Since the early days microfluidics as a scientific discipline has been an interdisciplinary research field with a wide scope of potential applications. Besides tailored assays for point-of-care (PoC) diagnostics, microfluidics has been an important tool for large-scale screening of reagents and building blocks in organic chemistry, pharmaceutics and medical engineering. Furthermore, numerous potential marketable products have been described over the years. However, especially in industrial applications, microfluidics is often considered only an alternative technology for fluid handling, a field which is industrially mostly dominated by large-scale numerically controlled fluid and liquid handling stations. Numerous noteworthy products have dominated this field in the last decade and have been inhibited the widespread application of microfluidics technology. However, automated liquid handling stations and microfluidics do not have to be considered as mutually exclusive approached. We have recently introduced a hybrid fluidic platform combining an industrially established liquid handling station and a generic microfluidic interfacing module that allows probing a microfluidic system (such as an essay or a synthesis array) using the instrumentation provided by the liquid handling station. We term this technology "Microfluidic on Liquid Handling Stations (μF-on-LHS)" - a classical "best of both worlds"- approach that allows combining the highly evolved, automated and industry-proven LHS systems with any type of microfluidic assay. In this paper we show, to the best of our knowledge, the first droplet microfluidics application on an industrial LHS using the μF-on-LHS concept.

Passive microfluidic array card and reader

Science.gov (United States)

Dugan, Lawrence Christopher [Modesto, CA; Coleman, Matthew A [Oakland, CA

2011-08-09

A microfluidic array card and reader system for analyzing a sample. The microfluidic array card includes a sample loading section for loading the sample onto the microfluidic array card, a multiplicity of array windows, and a transport section or sections for transporting the sample from the sample loading section to the array windows. The microfluidic array card reader includes a housing, a receiving section for receiving the microfluidic array card, a viewing section, and a light source that directs light to the array window of the microfluidic array card and to the viewing section.

Modular microfluidic system as a model of cystic fibrosis airways

DEFF Research Database (Denmark)

Skolimowski, Maciej; Weiss Nielsen, Martin; Abeille, Fabien

2012-01-01

A modular microfluidic airways model system that can simulate the changes in oxygen tension in different compartments of the cystic fibrosis (CF) airways was designed, developed, and tested. The fully reconfigurable system composed of modules with different functionalities: multichannel peristalt...

Moving-part-free microfluidic systems for lab-on-a-chip

International Nuclear Information System (INIS)

Luo, J K; Fu, Y Q; Du, X Y; Flewitt, A J; Milne, W I; Li, Y; Walton, A J

2009-01-01

Microfluidic systems are part of an emerging technology which deals with minute amounts of liquids (biological samples and reagents) on a small scale. They are fast, compact and can be made into a highly integrated system to deliver sample purification, separation, reaction, immobilization, labelling, as well as detection, thus are promising for applications such as lab-on-a-chip and handheld healthcare devices. Miniaturized micropumps typically consist of a moving-part component, such as a membrane structure, to deliver liquids, and are often unreliable, complicated in structure and difficult to be integrated with other control electronics circuits. The trend of new-generation micropumps is moving-part-free micropumps operated by advanced techniques, such as electrokinetic force, surface tension/energy, acoustic waves. This paper reviews the development and advances of relevant technologies, and introduces electrowetting-on-dielectrics and acoustic wave-based microfluidics. The programmable electrowetting micropump has been realized to dispense and manipulate droplets in 2D with up to 1000 addressable electrodes and electronics built underneath. The acoustic wave-based microfluidics can be used not only for pumping, mixing and droplet generation but also for biosensors, suitable for single-mechanism-based lab-on-a-chip applications

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

Directory of Open Access Journals (Sweden)

Daniel Ahmed

2015-09-01

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

Microfluidic hubs, systems, and methods for interface fluidic modules

Science.gov (United States)

Bartsch, Michael S; Claudnic, Mark R; Kim, Hanyoup; Patel, Kamlesh D; Renzi, Ronald F; Van De Vreugde, James L

2015-01-27

Embodiments of microfluidic hubs and systems are described that may be used to connect fluidic modules. A space between surfaces may be set by fixtures described herein. In some examples a fixture may set substrate-to-substrate spacing based on a distance between registration surfaces on which the respective substrates rest. Fluidic interfaces are described, including examples where fluid conduits (e.g. capillaries) extend into the fixture to the space between surfaces. Droplets of fluid may be introduced to and/or removed from microfluidic hubs described herein, and fluid actuators may be used to move droplets within the space between surfaces. Continuous flow modules may be integrated with the hubs in some examples.

Micro-optics for microfluidic analytical applications.

Science.gov (United States)

Yang, Hui; Gijs, Martin A M

2018-02-19

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

On capillary self-focusing in a microfluidic system

Energy Technology Data Exchange (ETDEWEB)

Hein, M; Seemann, R [Experimental Physics, Saarland University, D-66123 Saarbrücken (Germany); Afkhami, S, E-mail: r.seemann@physik.uni-saarland.de, E-mail: shahriar.afkhami@njit.edu [Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, NJ 07102 (United States)

2016-12-15

A computational framework is developed to address capillary self-focusing in step emulsification. The microfluidic system consists of a single shallow and wide microchannel that merges into a deep reservoir. A continuum approach coupled with a volume of fluid method is used to model the capillary self-focusing effect. The original governing equations are reduced using the Hele-Shaw approximation. We show that the interface between the two fluids takes the shape of a neck narrowing in the flow direction just before entering the reservoir, in agreement with our experimental observations. Our computational model relies on the assumption that the pressure at the boundary, where the fluid exits into the reservoir, is the uniform pressure in the reservoir. We investigate this hypothesis by comparing the numerical results with experimental data. We conjecture that the pressure boundary condition becomes important when the width of the neck is comparable to the depth of the microchannel. A correction to the exit pressure boundary condition is then proposed, which is determined by comparison with experimental data. We also present the experimental observations and the numerical results of the transitions of breakup regimes. (paper)

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

Science.gov (United States)

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

2018-06-13

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

Label-free all-electronic biosensing in microfluidic systems

Science.gov (United States)

Stanton, Michael A.

Label-free, all-electronic detection techniques offer great promise for advancements in medical and biological analysis. Electrical sensing can be used to measure both interfacial and bulk impedance changes in conducting solutions. Electronic sensors produced using standard microfabrication processes are easily integrated into microfluidic systems. Combined with the sensitivity of radiofrequency electrical measurements, this approach offers significant advantages over competing biological sensing methods. Scalable fabrication methods also provide a means of bypassing the prohibitive costs and infrastructure associated with current technologies. We describe the design, development and use of a radiofrequency reflectometer integrated into a microfluidic system towards the specific detection of biologically relevant materials. We developed a detection protocol based on impedimetric changes caused by the binding of antibody/antigen pairs to the sensing region. Here we report the surface chemistry that forms the necessary capture mechanism. Gold-thiol binding was utilized to create an ordered alkane monolayer on the sensor surface. Exposed functional groups target the N-terminus, affixing a protein to the monolayer. The general applicability of this method lends itself to a wide variety of proteins. To demonstrate specificity, commercially available mouse anti- Streptococcus Pneumoniae monoclonal antibody was used to target the full-length recombinant pneumococcal surface protein A, type 2 strain D39 expressed by Streptococcus Pneumoniae. We demonstrate the RF response of the sensor to both the presence of the surface decoration and bound SPn cells in a 1x phosphate buffered saline solution. The combined microfluidic sensor represents a powerful platform for the analysis and detection of cells and biomolecules.

Microfluidic electrochemical sensor for on-line monitoring of aerosol oxidative activity.

Science.gov (United States)

Sameenoi, Yupaporn; Koehler, Kirsten; Shapiro, Jeff; Boonsong, Kanokporn; Sun, Yele; Collett, Jeffrey; Volckens, John; Henry, Charles S

2012-06-27

Particulate matter (PM) air pollution has a significant impact on human morbidity and mortality; however, the mechanisms of PM-induced toxicity are poorly defined. A leading hypothesis states that airborne PM induces harm by generating reactive oxygen species in and around human tissues, leading to oxidative stress. We report here a system employing a microfluidic electrochemical sensor coupled directly to a particle-into-liquid sampler (PILS) system to measure aerosol oxidative activity in an on-line format. The oxidative activity measurement is based on the dithiothreitol (DTT) assay, where, after being oxidized by PM, the remaining reduced DTT is analyzed by the microfluidic sensor. The sensor consists of an array of working, reference, and auxiliary electrodes fabricated in a poly(dimethylsiloxane)-based microfluidic device. Cobalt(II) phthalocyanine-modified carbon paste was used as the working electrode material, allowing selective detection of reduced DTT. The electrochemical sensor was validated off-line against the traditional DTT assay using filter samples taken from urban environments and biomass burning events. After off-line characterization, the sensor was coupled to a PILS to enable on-line sampling/analysis of aerosol oxidative activity. Urban dust and industrial incinerator ash samples were aerosolized in an aerosol chamber and analyzed for their oxidative activity. The on-line sensor reported DTT consumption rates (oxidative activity) in good correlation with aerosol concentration (R(2) from 0.86 to 0.97) with a time resolution of approximately 3 min.

A review on optical actuators for microfluidic systems

Science.gov (United States)

Yang, Tie; Chen, Yue; Minzioni, Paolo

2017-12-01

During the last few decades microfluidic systems have become more and more popular and their relevance in different fields is continually growing. In fact, the use of microchannels allows a significant reduction of the required sample-volume and opens the way to a completely new set of possible investigations, including the study of the properties of cells, the development of new cells’ separation techniques and the analysis of single-cell proteins. One of the main differences between microscopic and macroscopic systems is obviously dictated by the need for suitable actuation mechanisms, which should allow precise control of microscopic fluid volumes and of micro-samples inside the fluid. Even if both syringe-pump and pneumatic-pump technologies significantly evolved and they currently enable sub-μL samples control, completely new approaches were recently developed for the manipulation of samples inside the microchannel. This review is dedicated to describing different kinds of optical actuators that can be applied in microfluidic systems for sample manipulation as well as for pumping. The basic principles underlying the optical actuation mechanisms will be described first, and then several experimental demonstrations will be reviewed and compared.

Microfluidic system for enhanced cardiac tissue formation

Directory of Open Access Journals (Sweden)

Busek Mathias

2017-09-01

Full Text Available Hereby a microfluidic system for cell cultivation is presented in which human pluripotent stem cell-derived cardiomyocytes were cultivated under perfusion. Besides micro-perfusion this system is also capable to produce well-defined oxygen contents, apply defined forces and has excellent imaging characteristics. Cardiomyocytes attach to the surface, start spontaneous beating and stay functional for up to 14 days under perfusion. The cell motion was subsequently analysed using an adapted video analysis script to calculate beating rate, beating direction and contraction or relaxation speed.

Microfluidic systems and methods for transport and lysis of cells and analysis of cell lysate

Science.gov (United States)

Culbertson, Christopher T [Oak Ridge, TN; Jacobson, Stephen C [Knoxville, TN; McClain, Maxine A [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2008-09-02

Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

Two-Phase Microfluidic Systems for High Throughput Quantification of Agglutination Assays

KAUST Repository

Castro, David

2018-04-01

Lab-on-Chip, the miniaturization of the chemical and analytical lab, is an endeavor that seems to come out of science fiction yet is slowly becoming a reality. It is a multidisciplinary field that combines different areas of science and engineering. Within these areas, microfluidics is a specialized field that deals with the behavior, control and manipulation of small volumes of fluids. Agglutination assays are rapid, single-step, low-cost immunoassays that use microspheres to detect a wide variety molecules and pathogens by using a specific antigen-antibody interaction. Agglutination assays are particularly suitable for the miniaturization and automation that two-phase microfluidics can offer, a combination that can help tackle the ever pressing need of high-throughput screening for blood banks, epidemiology, food banks diagnosis of infectious diseases. In this thesis, we present a two-phase microfluidic system capable of incubating and quantifying agglutination assays. The microfluidic channel is a simple fabrication solution, using laboratory tubing. These assays are incubated by highly efficient passive mixing with a sample-to-answer time of 2.5 min, a 5-10 fold improvement over traditional agglutination assays. It has a user-friendly interface that that does not require droplet generators, in which a pipette is used to continuously insert assays on-demand, with no down-time in between experiments at 360 assays/h. System parameters are explored, using the streptavidin-biotin interaction as a model assay, with a minimum detection limit of 50 ng/mL using optical image analysis. We compare optical image analysis and light scattering as quantification methods, and demonstrate the first light scattering quantification of agglutination assays in a two-phase ow format. The application can be potentially applied to other biomarkers, which we demonstrate using C-reactive protein (CRP) assays. Using our system, we can take a commercially available CRP qualitative slide

Coupling liquid chromatography/mass spectrometry detection with microfluidic droplet array for label-free enzyme inhibition assay.

Science.gov (United States)

Wang, Xiu-Li; Zhu, Ying; Fang, Qun

2014-01-07

In this work, the combination of droplet-based microfluidics with liquid chromatography/mass spectrometry (LC/MS) was achieved, for providing a fast separation and high-information-content detection method for the analysis of nanoliter-scale droplets with complex compositions. A novel interface method was developed using an oil-covered droplet array chip to couple with an LC/MS system via a capillary sampling probe and a 4 nL injection valve without the need of a droplet extraction device. The present system can perform multistep operations including parallel enzyme inhibition reactions in nanoliter droplets, 4 nL sample injection, fast separation with capillary LC, and label-free detection with ESI-MS, and has significant flexibility in the accurate addressing and sampling of droplets of interest on demand. The system performance was evaluated using angiotensin I and angiotensin II as model samples, and the repeatabilities of peak area for angiotensin I and angiotensin II were 2.7% and 7.5% (RSD, n = 4), respectively. The present system was further applied to the screening for inhibitors of cytochrome P450 (CYP1A2) and measurement of the IC50 value of the inhibitor. The sample consumption for each droplet assay was 100 nL, which is reduced 10-100 times compared with conventional 384-multi-well plate systems usually used in high-throughput drug screening.

A microfluidic renal proximal tubule with active reabsorptive function.

Directory of Open Access Journals (Sweden)

Else M Vedula

Full Text Available In the kidney, the renal proximal tubule (PT reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier. Co-culturing epithelial and endothelial cells in the microfluidic architecture enhanced viability, metabolic activity, and compactness of the epithelial layer. The resulting tissue expressed tight junctions, kidney-specific morphology, and polarized expression of kidney markers. The microfluidic PT actively performed sodium-coupled glucose transport, which could be modulated by administration of a sodium-transport inhibiting drug. The microfluidic PT reproduces human physiology at the cellular and tissue levels, and measurable tissue function which can quantify kidney pharmaceutical efficacy and toxicity.

Easy route to superhydrophobic copper-based wire-guided droplet microfluidic systems.

Science.gov (United States)

Mumm, Florian; van Helvoort, Antonius T J; Sikorski, Pawel

2009-09-22

Droplet-based microfluidic systems are an expansion of the lab on a chip concept toward flexible, reconfigurable setups based on the modification and analysis of individual droplets. Superhydrophobic surfaces are one suitable candidate for the realization of droplet-based microfluidic systems as the high mobility of aqueous liquids on such surfaces offers possibilities to use novel or more efficient approaches to droplet movement. Here, copper-based superhydrophobic surfaces were produced either by the etching of polycrystalline copper samples along the grain boundaries using etchants common in the microelectronics industry, by electrodeposition of copper films with subsequent nanowire decoration based on thermal oxidization, or by a combination of both. The surfaces could be easily hydrophobized with thiol-modified fluorocarbons, after which the produced surfaces showed a water contact angle as high as 171 degrees +/- 2 degrees . As copper was chosen as the base material, established patterning techniques adopted from printed circuit board fabrication could be used to fabricate macrostructures on the surfaces with the intention to confine the droplets and, thus, to reduce the system's sensitivity to tilting and vibrations. A simple droplet-based microfluidic chip with inlets, outlets, sample storage, and mixing areas was produced. Wire guidance, a relatively new actuation method applicable to aqueous liquids on superhydrophobic surfaces, was applied to move the droplets.

Microfluidics for chemical processing

NARCIS (Netherlands)

Gardeniers, Johannes G.E.

2006-01-01

Microfluidic systems, and more specifically, microfluidic chips, have a number of features that make them particularly useful for the study of chemical reactions on-line. The present paper will discuss two examples, the study of fluidic behaviour at high pressures and the excitation and detection of

All-polymer microfluidic systems for droplet based sample analysis

DEFF Research Database (Denmark)

Poulsen, Carl Esben

In this PhD project, I pursued to develop an all-polymer injection moulded microfluidic platform with integrated droplet based single cell interrogation. To allow for a proper ”one device - one experiment” methodology and to ensure a high relevancy to non-academic settings, the systems presented ...

Fabrication of polystyrene microfluidic devices using a pulsed CO2 laser system

KAUST Repository

Li, Huawei

2013-10-10

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

Fabrication of polystyrene microfluidic devices using a pulsed CO2 laser system

KAUST Repository

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

2013-01-01

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

Fast infectious diseases diagnostics based on microfluidic biochip system

Directory of Open Access Journals (Sweden)

Qin Huang

2017-03-01

Full Text Available Molecular diagnostics is one of the most important tools currently in use for clinical pathogen detection due to its high sensitivity, specificity, and low consume of sample and reagent is keyword to low cost molecular diagnostics. In this paper, a sensitive DNA isothermal amplification method for fast clinical infectious diseases diagnostics at aM concentrations of DNA was developed using a polycarbonate (PC microfluidic chip. A portable confocal optical fluorescence detector was specifically developed for the microfluidic chip that was capable of highly sensitive real-time detection of amplified products for sequence-specific molecular identification near the optical diffraction limit with low background. The molecular diagnostics of Listeria monocytogenes with nucleic acid extracted from stool samples was performed at a minimum DNA template concentration of 3.65aM, and a detection limit of less than five copies of genomic DNA. Contrast to the general polymerase chain reaction (PCR at eppendorf (EP tube, the detection time in our developed method was reduced from 1.5h to 45min for multi-target parallel detection, the consume of sample and reagent was dropped from 25μL to 1.45μL. This novel microfluidic chip system and method can be used to develop a micro total analysis system as a clinically relevant pathogen molecular diagnostics method via the amplification of targets, with potential applications in biotechnology, medicine, and clinical molecular diagnostics.

A micro-fluidic sub-microliter sample introduction system for direct analysis of Chinese rice wine by inductively coupled plasma mass spectrometry using external aqueous calibration

Energy Technology Data Exchange (ETDEWEB)

Cheng, Heyong [Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou, 310027 (China); College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, 310036 (China); Liu, Jinhua [College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, 310036 (China); Xu, Zigang [Institute of Analytical and Applied Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310027 (China); Yin, Xuefeng, E-mail: yinxf@zju.edu.cn [Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou, 310027 (China); College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, 310036 (China)

2012-07-15

A microfluidic sub-microliter sample introducing system was developed for direct analysis of Chinese rice wine by inductively coupled plasma mass spectrometry (ICP-MS). It consisted of a microfluidic chip integrating variable-volume sampling channels (0.1-0.8 {mu}L), an eight-way multi-functional valve used in flow injection analysis (FIA), a syringe pump and a peristaltic pump of the Ar ICP-MS instrument. Three solutions, i.e., 15, 40 and 100 g L{sup -1} glucose in 20% ethanol were used to simulate Chinese rice wine of the dry type, the semidry type and the semisweet type, each. The effects of their volume introduced into ICP-MS on the plasma stability and ICP-MS intensities were studied. The experimental results showed that neither alteration of plasma stability nor carbon deposition was observed when the sampling volume of 20% ethanol containing 100 g L{sup -1} glucose was downscaled to 0.8 {mu}L. Further reducing the sampling volume to 0.4 {mu}L, no significant difference between the intensities of multi-element standard prepared in three simulated Chinese rice wine matrices and those in aqueous solution was observed. It indicated no negative effect of Chinese rice wine matrix on the ICP-MS intensities. A sampling volume of 0.4 {mu}L was considered to be a good compromise between sensitivity and matrix effect. The flow rate of the carrier was chosen as 20 {mu}L min{sup -1} for obtaining peaks with the highest peak height within the shortest time. Based on these observations, a microflow injection ({mu}FI) method for the direct determination of cadmium and lead in Chinese rice wine by ICP-MS using an external aqueous calibration was developed. The sample throughput was 45 h{sup -1} with the detection limit of 19.8 and 10.4 ng L{sup -1} for Cd and Pb, respectively. The contents of Cd and Pb in 10 Chinese rice wine samples were measured. The results agreed well with those determined by ICP-MS with the conventional sampling system after microwave assisted digestion

A micro-fluidic sub-microliter sample introduction system for direct analysis of Chinese rice wine by inductively coupled plasma mass spectrometry using external aqueous calibration

International Nuclear Information System (INIS)

Cheng, Heyong; Liu, Jinhua; Xu, Zigang; Yin, Xuefeng

2012-01-01

A microfluidic sub-microliter sample introducing system was developed for direct analysis of Chinese rice wine by inductively coupled plasma mass spectrometry (ICP-MS). It consisted of a microfluidic chip integrating variable-volume sampling channels (0.1–0.8 μL), an eight-way multi-functional valve used in flow injection analysis (FIA), a syringe pump and a peristaltic pump of the Ar ICP-MS instrument. Three solutions, i.e., 15, 40 and 100 g L −1 glucose in 20% ethanol were used to simulate Chinese rice wine of the dry type, the semidry type and the semisweet type, each. The effects of their volume introduced into ICP-MS on the plasma stability and ICP-MS intensities were studied. The experimental results showed that neither alteration of plasma stability nor carbon deposition was observed when the sampling volume of 20% ethanol containing 100 g L −1 glucose was downscaled to 0.8 μL. Further reducing the sampling volume to 0.4 μL, no significant difference between the intensities of multi-element standard prepared in three simulated Chinese rice wine matrices and those in aqueous solution was observed. It indicated no negative effect of Chinese rice wine matrix on the ICP-MS intensities. A sampling volume of 0.4 μL was considered to be a good compromise between sensitivity and matrix effect. The flow rate of the carrier was chosen as 20 μL min −1 for obtaining peaks with the highest peak height within the shortest time. Based on these observations, a microflow injection (μFI) method for the direct determination of cadmium and lead in Chinese rice wine by ICP-MS using an external aqueous calibration was developed. The sample throughput was 45 h −1 with the detection limit of 19.8 and 10.4 ng L −1 for Cd and Pb, respectively. The contents of Cd and Pb in 10 Chinese rice wine samples were measured. The results agreed well with those determined by ICP-MS with the conventional sampling system after microwave assisted digestion. The recoveries of three

A microfluidic approach for hemoglobin detection in whole blood

Directory of Open Access Journals (Sweden)

Nikita Taparia

2017-10-01

Full Text Available Diagnosis of anemia relies on the detection of hemoglobin levels in a blood sample. Conventional blood analyzers are not readily available in most low-resource regions where anemia is prevalent, so detection methods that are low-cost and point-of-care are needed. Here, we present a microfluidic approach to measure hemoglobin concentration in a sample of whole blood. Unlike conventional approaches, our microfluidic approach does not require hemolysis. We detect the level of hemoglobin in a blood sample optically by illuminating the blood in a microfluidic channel at a peak wavelength of 540 nm and measuring its absorbance using a CMOS sensor coupled with a lens to magnify the image onto the detector. We compare measurements in microchannels with channel heights of 50 and 115 μm and found the channel with the 50 μm height provided a better range of detection. Since we use whole blood and not lysed blood, we fit our data to an absorption model that includes optical scattering in order to obtain a calibration curve for our system. Based on this calibration curve and data collected, we can measure hemoglobin concentration within 1 g/dL for severe cases of anemia. In addition, we measured optical density for blood flowing at a shear rate of 500 s-1 and observed it did not affect the nonlinear model. With this method, we provide an approach that uses microfluidic detection of hemoglobin levels that can be integrated with other microfluidic approaches for blood analysis.

A microfluidic approach for hemoglobin detection in whole blood

Science.gov (United States)

Taparia, Nikita; Platten, Kimsey C.; Anderson, Kristin B.; Sniadecki, Nathan J.

2017-10-01

Diagnosis of anemia relies on the detection of hemoglobin levels in a blood sample. Conventional blood analyzers are not readily available in most low-resource regions where anemia is prevalent, so detection methods that are low-cost and point-of-care are needed. Here, we present a microfluidic approach to measure hemoglobin concentration in a sample of whole blood. Unlike conventional approaches, our microfluidic approach does not require hemolysis. We detect the level of hemoglobin in a blood sample optically by illuminating the blood in a microfluidic channel at a peak wavelength of 540 nm and measuring its absorbance using a CMOS sensor coupled with a lens to magnify the image onto the detector. We compare measurements in microchannels with channel heights of 50 and 115 μm and found the channel with the 50 μm height provided a better range of detection. Since we use whole blood and not lysed blood, we fit our data to an absorption model that includes optical scattering in order to obtain a calibration curve for our system. Based on this calibration curve and data collected, we can measure hemoglobin concentration within 1 g/dL for severe cases of anemia. In addition, we measured optical density for blood flowing at a shear rate of 500 s-1 and observed it did not affect the nonlinear model. With this method, we provide an approach that uses microfluidic detection of hemoglobin levels that can be integrated with other microfluidic approaches for blood analysis.

Laser ablated micropillar energy directors for ultrasonic welding of microfluidic systems

International Nuclear Information System (INIS)

Poulsen, Carl Esben; Kistrup, Kasper; Andersen, Nis Korsgaard; Taboryski, Rafael; Hansen, Mikkel Fougt; Wolff, Anders

2016-01-01

We present a new type of energy director (ED) for ultrasonic welding of microfluidic systems. These micropillar EDs are based on the replication of cone like protrusion structures introduced using a pico-second laser and may therefore be added to any mould surface accessible to a pico-second laser beam. The technology is demonstrated on an injection moulded microfluidic device featuring high-aspect ratio ( h   ×   w   =  2000 μ m  ×  550 μ m) and free-standing channel walls, where bonding is achieved with no detectable channel deformation. The bonding strength is similar to conventional EDs and the fabricated system can withstand pressures of over 9.5 bar. (technical note)

Macro to microfluidics system for biological environmental monitoring.

Science.gov (United States)

Delattre, Cyril; Allier, Cédric P; Fouillet, Yves; Jary, Dorothée; Bottausci, Frederic; Bouvier, Denis; Delapierre, Guillaume; Quinaud, Manuelle; Rival, Arnaud; Davoust, Laurent; Peponnet, Christine

2012-01-01

Biological environmental monitoring (BEM) is a growing field of research which challenges both microfluidics and system automation. The aim is to develop a transportable system with analysis throughput which satisfies the requirements: (i) fully autonomous, (ii) complete protocol integration from sample collection to final analysis, (iii) detection of diluted molecules or biological species in a large real life environmental sample volume, (iv) robustness and (v) flexibility and versatility. This paper discusses all these specifications in order to define an original fluidic architecture based on three connected modules, a sampling module, a sample preparation module and a detection module. The sample preparation module highly concentrates on the pathogens present in a few mL samples of complex and unknown solutions and purifies the pathogens' nucleic acids into a few μL of a controlled buffer. To do so, a two-step concentration protocol based on magnetic beads is automated in a reusable macro-to-micro fluidic system. The detection module is a PCR based miniaturized platform using digital microfluidics, where reactions are performed in 64 nL droplets handled by electrowetting on dielectric (EWOD) actuation. The design and manufacture of the two modules are reported as well as their respective performances. To demonstrate the integration of the complete protocol in the same system, first results of pathogen detection are shown. Copyright © 2012 Elsevier B.V. All rights reserved.

Cerenkov radiation imaging as a method for quantitative measurements of beta particles in a microfluidic chip

International Nuclear Information System (INIS)

Cho, Jennifer S; Taschereau, Richard; Olma, Sebastian; Liu Kan; Chen Yichun; Shen, Clifton K-F; Van Dam, R Michael; Chatziioannou, Arion F

2009-01-01

It has been observed that microfluidic chips used for synthesizing 18 F-labeled compounds demonstrate visible light emission without nearby scintillators or fluorescent materials. The origin of the light was investigated and found to be consistent with the emission characteristics from Cerenkov radiation. Since 18 F decays through the emission of high-energy positrons, the energy threshold for beta particles, i.e. electrons or positrons, to generate Cerenkov radiation was calculated for water and polydimethylsiloxane (PDMS), the most commonly used polymer-based material for microfluidic chips. Beta particles emitted from 18 F have a continuous energy spectrum, with a maximum energy that exceeds this energy threshold for both water and PDMS. In addition, the spectral characteristics of the emitted light from 18 F in distilled water were also measured, yielding a broad distribution from 300 nm to 700 nm, with higher intensity at shorter wavelengths. A photograph of the 18 F solution showed a bluish-white light emitted from the solution, further suggesting Cerenkov radiation. In this study, the feasibility of using this Cerenkov light emission as a method for quantitative measurements of the radioactivity within the microfluidic chip in situ was evaluated. A detector previously developed for imaging microfluidic platforms was used. The detector consisted of a charge-coupled device (CCD) optically coupled to a lens. The system spatial resolution, minimum detectable activity and dynamic range were evaluated. In addition, the calibration of a Cerenkov signal versus activity concentration in the microfluidic chip was determined. This novel method of Cerenkov radiation measurements will provide researchers with a simple yet robust quantitative imaging tool for microfluidic applications utilizing beta particles.

A Simple Opto-Fluidic Switch Detecting Liquid Filling in Polymer-Based Microfluidic Systems

DEFF Research Database (Denmark)

Bundgaard, Frederik; Geschke, Oliver; Zengerle, R

2007-01-01

A novel detection scheme for detection of liquid levels and bubbles in microfluidic systems, using the principle of total internal reflection (TIR) is presented. A laser beam impinges on the side walls of a channel which are inclined at 45deg. In an unfilled channel of such a "V-groove", TIR defl...... of the microfluidic channels. The machining of the V-groves can seamlessly be integrated into common polymer microfabrication schemes such as injection molding....

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...

Manipulation of microfluidic droplets by electrorheological fluid

KAUST Repository

Zhang, Menying

2009-09-01

Microfluidics, especially droplet microfluidics, attracts more and more researchers from diverse fields, because it requires fewer materials and less time, produces less waste and has the potential of highly integrated and computer-controlled reaction processes for chemistry and biology. Electrorheological fluid, especially giant electrorheological fluid (GERF), which is considered as a kind of smart material, has been applied to the microfluidic systems to achieve active and precise control of fluid by electrical signal. In this review article, we will introduce recent results of microfluidic droplet manipulation, GERF and some pertinent achievements by introducing GERF into microfluidic system: digital generation, manipulation of "smart droplets" and droplet manipulation by GERF. Once it is combined with real-time detection, integrated chip with multiple functions can be realized. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Construction of programmable interconnected 3D microfluidic networks

International Nuclear Information System (INIS)

Hunziker, Patrick R; Wolf, Marc P; Wang, Xueya; Zhang, Bei; Marsch, Stephan; Salieb-Beugelaar, Georgette B

2015-01-01

Microfluidic systems represent a key-enabling platform for novel diagnostic tools for use at the point-of-care in clinical contexts as well as for evolving single cell diagnostics. The design of 3D microfluidic systems is an active field of development, but construction of true interconnected 3D microfluidic networks is still a challenge, in particular when the goal is rapid prototyping, accurate design and flexibility. We report a novel approach for the construction of programmable 3D microfluidic systems consisting of modular 3D template casting of interconnected threads to allow user-programmable flow paths and examine its structural characteristics and its modular function. To overcome problems with thread template casting reported in the literature, low-surface-energy polymer threads were used, that allow solvent-free production. Connected circular channels with excellent roundness and low diameter variability were created. Variable channel termination allowed programming a flow path on-the-fly, thus rendering the resulting 3D microfluidic systems highly customizable even after production. Thus, construction of programmable/reprogrammable fully 3D microfluidic systems by template casting of a network of interconnecting threads is feasible, leads to high-quality and highly reproducible, complex 3D geometries. (paper)

Analysis system for characterisation of simple, low-cost microfluidic components

CSIR Research Space (South Africa)

Smith, S

2014-03-01

Full Text Available mechanism is used to introduce and dispense a sample of blood, while a reagent is released into the microfluidic system through compression and bursting of a blister pack. Mixing and dispensing of the sample and reagent are facilitated via air actuation...

Closed-loop feedback control for microfluidic systems through automated capacitive fluid height sensing

OpenAIRE

Trumper, David; Kassis, Timothy; Griffith, Linda; Noh, Minkyun; Soenksen, Luis

2018-01-01

Precise fluid height sensing in open-channel microfluidics has long been a desirable feature for a wide range of applications. However, performing accurate measurements of the fluid level in small-scale reservoirs (<1mL) has proven to be an elusive goal, especially if direct fluid-sensor contact needs to be avoided. In particular, gravity-driven systems used in several microfluidic applications to establish pressure gradients and impose flow remain open-loop and largely unmonitored due to ...

Microfluidic technology for molecular diagnostics.

Science.gov (United States)

Robinson, Tom; Dittrich, Petra S

2013-01-01

Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

Preparation of nanoparticles by continuous-flow microfluidics

International Nuclear Information System (INIS)

Jahn, Andreas; Reiner, Joseph E.; Vreeland, Wyatt N.; DeVoe, Don L.; Locascio, Laurie E.; Gaitan, Michael

2008-01-01

We review a variety of micro- and nanoparticle formulations produced with microfluidic methods. A diverse variety of approaches to generate microscale and nanoscale particles has been reported. Here we emphasize the use of microfluidics, specifically microfluidic systems that operate in a continuous flow mode, thereby allowing continuous generation of desired particle formulations. The generation of semiconductor quantum dots, metal colloids, emulsions, and liposomes is considered. To emphasize the potential benefits of the continuous-flow microfluidic methodology for nanoparticle generation, preliminary data on the size distribution of liposomes formed using the microfluidic approach is compared to the traditional bulk alcohol injection method.

Capture of DNA in microfluidic channel using magnetic beads: increasing capture efficiency with integrated microfluidic mixer

DEFF Research Database (Denmark)

Lund-Olesen, Torsten; Dufva, Hans Martin; Hansen, Mikkel Fougt

2007-01-01

We have studied the hybridization of target DNA in solution with probe DNA on magnetic beads immobilized on the channel sidewalls in a magnetic bead separator. The hybridization is carried out under a liquid flow and is diffusion limited. Two systems are compared: one with a straight microfluidic...... place on the surface in a microfluidic system....

New insight on the formation of whey protein microbeads by a microfluidic system

Science.gov (United States)

Andoyo, Robi; Guyomarc'h, Fanny; Tabuteau, Hervé; Famelart, Marie-Hélène

2018-02-01

The current paper describes the formation of whey protein microbeads (WPM) having a spherical shape and a monodispersed size distribution. A microfluidic flow-focusing geometry was used to control the production of whey protein microdroplets in a hydrophobic phase. The microfluidic system consists of two inlet channels where the WPI solution and the lipophilic phase were separately injected towards the flow-focusing (FF) junction where they eventually meet, then co-flow. A whey protein isolate (WPI) solution of 150 g/kg protein and two types of hydrophobic phases, i.e. sunflower oil and n-dodecane, were tested as the continuous phase. The formation of WPM was observed microscopically. The aim of the present study was to describe the production of stable monodisperse WPM in suspension in milk ultrafiltrate using a microfluidic system. Hints to perform the control of the running parameters, i.e. choice of the hydrophobic phase or fluids flowrates, are provided. The results showed that in the sunflower oil, microdroplets had a large polydisperse size distribution, while in n-dodecane, microdroplets with narrow size distribution were obtained. Stabilization of the whey protein microdroplets through heat-gelation at 75 °C for 20 min in n-dodecane produced WPM and no change in shape nor size is observed. Meanwhile replacing the n-dodecane by MUF using centrifugation and washing caused the swelling of the WPM, but dispersity remained low. From this study, microfluidic system seemed to be a suitable method to be used for producing small quantities of monodisperse WPM.

Prototyping of Microfluidic Systems with Integrated Waveguides in Cyclin Olefin Copolymer

DEFF Research Database (Denmark)

Bundgaard, Frederik

2007-01-01

, in a collaboration with IMTEK in Freiburg, Germany, an optical detection principle was developed. Using the principle of total internal reflection of a laser beam incident on a fluidic channel, detection of air bubbles is possible. The principle was used on a rotating platform as well as on non-moving systems....... the substrate, optical layers and the lid in the microfluidic systems. • Thermal bonding of polymer structures, including roll lamination of foil onto substrates. • Laser bonding of two polymer layers, including transparent on black, and transparent on transparent with a particle doped spin coating. • Thermal...... treatment of waveguides to improve the surface roughness and lower the propagation loss. The fabrication methods have been characterised, and have been optimised to minimise parameters like fabrication time, surface roughness and interface bonding strength. Using these fabrication methods, microfluidic...

A micro-pillar array to trap magnetic beads in microfluidic systems

KAUST Repository

Gooneratne, Chinthaka Pasan; Kosel, Jü rgen

2012-01-01

A micro-pillar array (MPA) is proposed in this paper to trap and separate magnetic beads (MBs) in microfluidic systems. MBs are used in many biomedical applications due to being compatible in dimension to biomolecules, the large surface area

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

KAUST Repository

Fan, Yiqiang

2013-12-20

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

Microfluidics as a functional tool for cell mechanics.

Science.gov (United States)

Vanapalli, Siva A; Duits, Michel H G; Mugele, Frieder

2009-01-05

Living cells are a fascinating demonstration of nature's most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax-thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both controlling and manipulating the cell microenvironment and measuring the resulting mechanical response. In this review, the power of microfluidics as a functional tool for research in cell mechanics is highlighted. In particular, current literature is discussed to show that microfluidics powered by soft lithographic techniques offers the following capabilities that are of significance for understanding the mechanical behavior of cells: (i) Microfluidics enables the creation of in vitro models of physiological environments in which cell mechanics can be probed. (ii) Microfluidics is an excellent means to deliver physical cues that affect cell mechanics, such as cell shape, fluid flow, substrate topography, and stiffness. (iii) Microfluidics can also expose cells to chemical cues, such as growth factors and drugs, which alter their mechanical behavior. Moreover, these chemical cues can be delivered either at the whole cell or subcellular level. (iv) Microfluidic devices offer the possibility of measuring the intrinsic mechanical properties of cells in a high throughput fashion. (v) Finally, microfluidic methods provide exquisite control over drop size, generation, and manipulation. As a result, droplets are being increasingly used to control the physicochemical environment of cells and as biomimetic analogs of living cells. These powerful attributes of microfluidics should further stimulate novel means of investigating the link between physicochemical cues and the biomechanical

Implementation of Synchronous Micromotor in Developing Integrated Microfluidic Systems

Directory of Open Access Journals (Sweden)

Ala'aldeen Al-Halhouli

2014-07-01

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

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

Science.gov (United States)

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

2017-05-21

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

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

OpenAIRE

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

2015-01-01

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

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.

Fast Prototyping of Sensorized Cell Culture Chips and Microfluidic Systems with Ultrashort Laser Pulses

Directory of Open Access Journals (Sweden)

Sebastian M. Bonk

2015-03-01

Full Text Available We developed a confined microfluidic cell culture system with a bottom plate made of a microscopic slide with planar platinum sensors for the measurement of acidification, oxygen consumption, and cell adhesion. The slides were commercial slides with indium tin oxide (ITO plating or were prepared from platinum sputtering (100 nm onto a 10-nm titanium adhesion layer. Direct processing of the sensor structures (approximately three minutes per chip by an ultrashort pulse laser facilitated the production of the prototypes. pH-sensitive areas were produced by the sputtering of 60-nm Si3N4 through a simple mask made from a circuit board material. The system body and polydimethylsiloxane (PDMS molding forms for the microfluidic structures were manufactured by micromilling using a printed circuit board (PCB milling machine for circuit boards. The microfluidic structure was finally imprinted in PDMS. Our approach avoided the use of photolithographic techniques and enabled fast and cost-efficient prototyping of the systems. Alternatively, the direct production of metallic, ceramic or polymeric molding tools was tested. The use of ultrashort pulse lasers improved the precision of the structures and avoided any contact of the final structures with toxic chemicals and possible adverse effects for the cell culture in lab-on-a-chip systems.

PDMS/glass microfluidic cell culture system for cytotoxicity tests and cells passage

DEFF Research Database (Denmark)

Ziolkowska, K.; Jedrych, E.; Kwapiszewski, R.

2010-01-01

In this paper, hybrid (PDMS/glass) microfluidic cell culture system (MCCS) integrated with the concentration gradient generator (CGG) is presented. PDMS gas permeability enabled cells' respiration in the fabricated microdevices and excellent glass hydrophilicity allowed successful cells' seeding...

A centrifugal microfluidic platform for point-of-care diagnostic applications

Directory of Open Access Journals (Sweden)

Suzanne Hugo

2014-02-01

Full Text Available Microfluidic systems enable precise control over tiny volumes of fluid in a compact and low-cost form, thus providing the ideal platform on which to develop point-of-care diagnostic solutions. Centrifugal microfluidic systems, also referred to as lab-on-a-disc or lab-on-a-CD systems, provide a particularly attractive solution for the implementation of microfluidic point-of-care diagnostic solutions as a result of their simple and compact instrumentation, as well as their functional diversity. Here we detail the implementation of a centrifugal microfluidic platform the first of its kind in South Africa as a foundation for the development of point-of-care diagnostic applications for which both the need and impact is great. The centrifugal microfluidic platform consists of three main components: a microfluidic disc device similar in size and shape to a CD, a system for controlling fluid flow on the device, and a system for recording the results obtained. These components have been successfully implemented and tested. Preliminary test results show that microfluidic functions such as pumping and valving of fluids can be successfully achieved, as well as the generation of monodisperse microfluidic droplets, providing a complete centrifugal microfluidic platform and the building blocks on which to develop a variety of applications, including point-of-care diagnostics. The lab-on-a-disc platform has the potential to provide new diagnostic solutions at the point-of-need in health- and industry-related areas. This paves the way for providing resource limited areas with services such as improved, decentralised health-care access or water-quality monitoring, and reduced diagnosis times at a low cost.

Visual Estimation of Bacterial Growth Level in Microfluidic Culture Systems.

Science.gov (United States)

Kim, Kyukwang; Kim, Seunggyu; Jeon, Jessie S

2018-02-03

Microfluidic devices are an emerging platform for a variety of experiments involving bacterial cell culture, and has advantages including cost and convenience. One inevitable step during bacterial cell culture is the measurement of cell concentration in the channel. The optical density measurement technique is generally used for bacterial growth estimation, but it is not applicable to microfluidic devices due to the small sample volumes in microfluidics. Alternately, cell counting or colony-forming unit methods may be applied, but these do not work in situ; nor do these methods show measurement results immediately. To this end, we present a new vision-based method to estimate the growth level of the bacteria in microfluidic channels. We use Fast Fourier transform (FFT) to detect the frequency level change of the microscopic image, focusing on the fact that the microscopic image becomes rough as the number of cells in the field of view increases, adding high frequencies to the spectrum of the image. Two types of microfluidic devices are used to culture bacteria in liquid and agar gel medium, and time-lapsed images are captured. The images obtained are analyzed using FFT, resulting in an increase in high-frequency noise proportional to the time passed. Furthermore, we apply the developed method in the microfluidic antibiotics susceptibility test by recognizing the regional concentration change of the bacteria that are cultured in the antibiotics gradient. Finally, a deep learning-based data regression is performed on the data obtained by the proposed vision-based method for robust reporting of data.

Visual Estimation of Bacterial Growth Level in Microfluidic Culture Systems

Directory of Open Access Journals (Sweden)

Kyukwang Kim

2018-02-01

Full Text Available Microfluidic devices are an emerging platform for a variety of experiments involving bacterial cell culture, and has advantages including cost and convenience. One inevitable step during bacterial cell culture is the measurement of cell concentration in the channel. The optical density measurement technique is generally used for bacterial growth estimation, but it is not applicable to microfluidic devices due to the small sample volumes in microfluidics. Alternately, cell counting or colony-forming unit methods may be applied, but these do not work in situ; nor do these methods show measurement results immediately. To this end, we present a new vision-based method to estimate the growth level of the bacteria in microfluidic channels. We use Fast Fourier transform (FFT to detect the frequency level change of the microscopic image, focusing on the fact that the microscopic image becomes rough as the number of cells in the field of view increases, adding high frequencies to the spectrum of the image. Two types of microfluidic devices are used to culture bacteria in liquid and agar gel medium, and time-lapsed images are captured. The images obtained are analyzed using FFT, resulting in an increase in high-frequency noise proportional to the time passed. Furthermore, we apply the developed method in the microfluidic antibiotics susceptibility test by recognizing the regional concentration change of the bacteria that are cultured in the antibiotics gradient. Finally, a deep learning-based data regression is performed on the data obtained by the proposed vision-based method for robust reporting of data.

Development of a flexible microfluidic system integrating magnetic micro-actuators for trapping biological species

International Nuclear Information System (INIS)

Fulcrand, R; Jugieu, D; Escriba, C; Bancaud, A; Bourrier, D; Boukabache, A; Gué, A M

2009-01-01

A flexible microfluidic system embedding microelectromagnets has been designed, modeled and fabricated by using a photosensitive resin as structural material. The fabrication process involves the integration of micro-coils in a multilayer SU-8 microfluidic system by combining standard electroplating and dry films lamination. This technique offers numerous advantages in terms of integration, biocompatibility and chemical resistance. Various designs of micro-coils, including spiral, square or serpentine wires, have been simulated and experimentally tested. It has been established that thermal dissipation in micro-coils depends strongly on the number of turns and current density but remains compatible with biological applications. Real-time experimentations show that these micro-actuators are efficient in trapping magnetic micro-beads without any external field source or a permanent magnet and highlight that the size of microfluidic channels has been adequately designed for optimal trapping. Moreover, we trap magnetic beads in less than 2 s and release them instantaneously into the micro-channel. The actuation solely relies on electric fields, which are easier to control than standard magneto-fluidic modules

Development of a flexible microfluidic system integrating magnetic micro-actuators for trapping biological species

Science.gov (United States)

Fulcrand, R.; Jugieu, D.; Escriba, C.; Bancaud, A.; Bourrier, D.; Boukabache, A.; Gué, A. M.

2009-10-01

A flexible microfluidic system embedding microelectromagnets has been designed, modeled and fabricated by using a photosensitive resin as structural material. The fabrication process involves the integration of micro-coils in a multilayer SU-8 microfluidic system by combining standard electroplating and dry films lamination. This technique offers numerous advantages in terms of integration, biocompatibility and chemical resistance. Various designs of micro-coils, including spiral, square or serpentine wires, have been simulated and experimentally tested. It has been established that thermal dissipation in micro-coils depends strongly on the number of turns and current density but remains compatible with biological applications. Real-time experimentations show that these micro-actuators are efficient in trapping magnetic micro-beads without any external field source or a permanent magnet and highlight that the size of microfluidic channels has been adequately designed for optimal trapping. Moreover, we trap magnetic beads in less than 2 s and release them instantaneously into the micro-channel. The actuation solely relies on electric fields, which are easier to control than standard magneto-fluidic modules.

Laser ablated micropillar energy directors for ultrasonic welding of microfluidic systems

DEFF Research Database (Denmark)

Poulsen, Carl Esben; Kistrup, Kasper; Andersen, Nis Korsgaard

2016-01-01

We present a new type of energy director (ED) for ultrasonic welding of microfluidic systems. These micropillar EDs are based on the replication of cone like protrusion structures introduced using a pico-second laser and may therefore be added to any mould surface accessible to a pico-second laser...

Optically transparent diamond-PDMS microfluidic system for electronic monitoring of cells

Czech Academy of Sciences Publication Activity Database

Babchenko, Oleg; Kromka, Alexander; Conde, J.P.; Chu, V.; Schmiedinger, T.; Rezek, Bohuslav

2014-01-01

Roč. 251, č. 12 (2014), s. 2593-2598 ISSN 0370-1972 R&D Projects: GA ČR GAP108/12/0996 Institutional support: RVO:68378271 Keywords : cells culturing * diamond sensor * electrical characterization * microfluidic system * optical monitoring * surface conductivity Subject RIV: BO - Biophysics Impact factor: 1.489, year: 2014

Study on the effect of surfactants on morphologies of trigonal selenium in microfluidic reactor

Energy Technology Data Exchange (ETDEWEB)

Bian, Tian-bin [Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Zheda Lu 38, Hangzhou 310027 (China); Yin, Xue-feng, E-mail: yinxf@zju.edu.cn [Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Zheda Lu 38, Hangzhou 310027 (China); Fan, Jie [Institute of Catalysis, Department of Chemistry, Zhejiang University, Hangzhou 310027 (China); Liu, Jin-hua [College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036 (China)

2010-02-15

The influence of the surfactants on the morphologies of trigonal selenium (t-Se) submicrostructures was studied in a two-step microfluidic system, which is composed of a glass microchip for preparing spherical amorphous selenium (a-Se) colloids coupled with a poly(methyl methacrylate) microchip for transferring a-Se into its t-Se seeds under sonication. The selenious acid containing surfactants and hydrazine solutions were delivered through the two-inlets of the glass microfluidic chip. Submicro-rods, -wires as well as -tubes of t-Se were obtained by simply varying the coexisted surfactants. The as-synthesized products were characterized by powder X-ray diffraction (XRD), Raman spectrum, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and selected-area electron diffraction (SAED).

A multiplexed microfluidic system for evaluation of dynamics of immune-tumor interactions.

Science.gov (United States)

Moore, N; Doty, D; Zielstorff, M; Kariv, I; Moy, L Y; Gimbel, A; Chevillet, J R; Lowry, N; Santos, J; Mott, V; Kratchman, L; Lau, T; Addona, G; Chen, H; Borenstein, J T

2018-05-25

Recapitulation of the tumor microenvironment is critical for probing mechanisms involved in cancer, and for evaluating the tumor-killing potential of chemotherapeutic agents, targeted therapies and immunotherapies. Microfluidic devices have emerged as valuable tools for both mechanistic studies and for preclinical evaluation of therapeutic agents, due to their ability to precisely control drug concentrations and gradients of oxygen and other species in a scalable and potentially high throughput manner. Most existing in vitro microfluidic cancer models are comprised of cultured cancer cells embedded in a physiologically relevant matrix, collocated with vascular-like structures. However, the recent emergence of immune checkpoint inhibitors (ICI) as a powerful therapeutic modality against many cancers has created a need for preclinical in vitro models that accommodate interactions between tumors and immune cells, particularly for assessment of unprocessed tumor fragments harvested directly from patient biopsies. Here we report on a microfluidic model, termed EVIDENT (ex vivo immuno-oncology dynamic environment for tumor biopsies), that accommodates up to 12 separate tumor biopsy fragments interacting with flowing tumor-infiltrating lymphocytes (TILs) in a dynamic microenvironment. Flow control is achieved with a single pump in a simple and scalable configuration, and the entire system is constructed using low-sorption materials, addressing two principal concerns with existing microfluidic cancer models. The system sustains tumor fragments for multiple days, and permits real-time, high-resolution imaging of the interaction between autologous TILs and tumor fragments, enabling mapping of TIL-mediated tumor killing and testing of various ICI treatments versus tumor response. Custom image analytic algorithms based on machine learning reported here provide automated and quantitative assessment of experimental results. Initial studies indicate that the system is capable of

Controlling nonspecific protein adsorption in a plug-based microfluidic system by controlling interfacial chemistry using fluorous-phase surfactants.

Science.gov (United States)

Roach, L Spencer; Song, Helen; Ismagilov, Rustem F

2005-02-01

Control of surface chemistry and protein adsorption is important for using microfluidic devices for biochemical analysis and high-throughput screening assays. This paper describes the control of protein adsorption at the liquid-liquid interface in a plug-based microfluidic system. The microfluidic system uses multiphase flows of immiscible fluorous and aqueous fluids to form plugs, which are aqueous droplets that are completely surrounded by fluorocarbon oil and do not come into direct contact with the hydrophobic surface of the microchannel. Protein adsorption at the aqueous-fluorous interface was controlled by using surfactants that were soluble in fluorocarbon oil but insoluble in aqueous solutions. Three perfluorinated alkane surfactants capped with different functional groups were used: a carboxylic acid, an alcohol, and a triethylene glycol group that was synthesized from commercially available materials. Using complementary methods of analysis, adsorption was characterized for several proteins (bovine serum albumin (BSA) and fibrinogen), including enzymes (ribonuclease A (RNase A) and alkaline phosphatase). These complementary methods involved characterizing adsorption in microliter-sized droplets by drop tensiometry and in nanoliter plugs by fluorescence microscopy and kinetic measurements of enzyme catalysis. The oligoethylene glycol-capped surfactant prevented protein adsorption in all cases. Adsorption of proteins to the carboxylic acid-capped surfactant in nanoliter plugs could be described by using the Langmuir model and tensiometry results for microliter drops. The microfluidic system was fabricated using rapid prototyping in poly(dimethylsiloxane) (PDMS). Black PDMS microfluidic devices, fabricated by curing a suspension of charcoal in PDMS, were used to measure the changes in fluorescence intensity more sensitively. This system will be useful for microfluidic bioassays, enzymatic kinetics, and protein crystallization, because it does not require

Integrated Cantilever-Based Flow Sensors with Tunable Sensitivity for In-Line Monitoring of Flow Fluctuations in Microfluidic Systems

Directory of Open Access Journals (Sweden)

Nadine Noeth

2013-12-01

Full Text Available For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different materials (SU-8 and SiN and with different thicknesses. The integration of arrays of holes with different hole size and number of holes allows the modification of device sensitivity, theoretical detection limit and measurement range. For an average flow in the microliter range, the cantilever deflection is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external pumps connected to the microfluidic system.

Valve Concepts for Microfluidic Cell Handling

Directory of Open Access Journals (Sweden)

M. Grabowski

2010-01-01

Full Text Available In this paper we present various pneumatically actuated microfluidic valves to enable user-defined fluid management within a microfluidic chip. To identify a feasible valve design, certain valve concepts are simulated in ANSYS to investigate the pressure dependent opening and closing characteristics of each design. The results are verified in a series of tests. Both the microfluidic layer and the pneumatic layer are realized by means of soft-lithographic techniques. In this way, a network of channels is fabricated in photoresist as a molding master. By casting these masters with PDMS (polydimethylsiloxane we get polymeric replicas containing the channel network. After a plasma-enhanced bonding process, the two layers are irreversibly bonded to each other. The bonding is tight for pressures up to 2 bar. The valves are integrated into a microfluidic cell handling system that is designed to manipulate cells in the presence of a liquid reagent (e.g. PEG – polyethylene glycol, for cell fusion. For this purpose a user-defined fluid management system is developed. The first test series with human cell lines show that the microfluidic chip is suitable for accumulating cells within a reaction chamber, where they can be flushed by a liquid medium.

Equilibrium and Nonequilibrium States in Microfluidic Double Emulsions

DEFF Research Database (Denmark)

Pannacci, N.; Bruus, Henrik; Bartolo, D.

2008-01-01

We describe experimental and theoretical studies dedicated to establishing the physics of formation of double droplets in microfluidic systems. We show that the morphologies (complete engulfing, partial engulfing, and nonengulfing) obtained at late times minimize the interfacial energy of the sys......We describe experimental and theoretical studies dedicated to establishing the physics of formation of double droplets in microfluidic systems. We show that the morphologies (complete engulfing, partial engulfing, and nonengulfing) obtained at late times minimize the interfacial energy...... of the system. We explain that nonequilibrium morphologies generated in the system can have long lifetimes. Remarkably, the physics of formation of the double droplets with microfluidics allows the synthesis of particles with new morphologies....

A micro-fluidic sub-microliter sample introduction system for direct analysis of Chinese rice wine by inductively coupled plasma mass spectrometry using external aqueous calibration

Science.gov (United States)

Cheng, Heyong; Liu, Jinhua; Xu, Zigang; Yin, Xuefeng

2012-07-01

A microfluidic sub-microliter sample introducing system was developed for direct analysis of Chinese rice wine by inductively coupled plasma mass spectrometry (ICP-MS). It consisted of a microfluidic chip integrating variable-volume sampling channels (0.1-0.8 μL), an eight-way multi-functional valve used in flow injection analysis (FIA), a syringe pump and a peristaltic pump of the Ar ICP-MS instrument. Three solutions, i.e., 15, 40 and 100 g L- 1 glucose in 20% ethanol were used to simulate Chinese rice wine of the dry type, the semidry type and the semisweet type, each. The effects of their volume introduced into ICP-MS on the plasma stability and ICP-MS intensities were studied. The experimental results showed that neither alteration of plasma stability nor carbon deposition was observed when the sampling volume of 20% ethanol containing 100 g L- 1 glucose was downscaled to 0.8 μL. Further reducing the sampling volume to 0.4 μL, no significant difference between the intensities of multi-element standard prepared in three simulated Chinese rice wine matrices and those in aqueous solution was observed. It indicated no negative effect of Chinese rice wine matrix on the ICP-MS intensities. A sampling volume of 0.4 μL was considered to be a good compromise between sensitivity and matrix effect. The flow rate of the carrier was chosen as 20 μL min- 1 for obtaining peaks with the highest peak height within the shortest time. Based on these observations, a microflow injection (μFI) method for the direct determination of cadmium and lead in Chinese rice wine by ICP-MS using an external aqueous calibration was developed. The sample throughput was 45 h- 1 with the detection limit of 19.8 and 10.4 ng L- 1 for Cd and Pb, respectively. The contents of Cd and Pb in 10 Chinese rice wine samples were measured. The results agreed well with those determined by ICP-MS with the conventional sampling system after microwave assisted digestion. The recoveries of three Chinese

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.

"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

Basic principles of electrolyte chemistry for microfluidic electrokinetics. Part I: Acid-base equilibria and pH buffers.

Science.gov (United States)

Persat, Alexandre; Chambers, Robert D; Santiago, Juan G

2009-09-07

We review fundamental and applied acid-base equilibrium chemistry useful to microfluidic electrokinetics. We present elements of acid-base equilibrium reactions and derive rules for pH calculation for simple buffers. We also present a general formulation to calculate pH of more complex, arbitrary mixtures of electrolytes, and discuss the effects of ionic strength and temperature on pH calculation. More practically, we offer advice on buffer preparation and on buffer reporting. We also discuss "real world" buffers and likely contamination sources. In particular, we discuss the effects of atmospheric carbon dioxide on buffer systems, namely, the increase in ionic strength and acidification of typical electrokinetic device buffers. In Part II of this two-paper series, we discuss the coupling of acid-base equilibria with electrolyte dynamics and electrochemistry in typical microfluidic electrokinetic systems.

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...

A PDMS-based cylindrical hybrid lens for enhanced fluorescence detection in microfluidic systems.

Science.gov (United States)

Lin, Bor-Shyh; Yang, Yu-Ching; Ho, Chong-Yi; Yang, Han-Yu; Wang, Hsiang-Yu

2014-02-13

Microfluidic systems based on fluorescence detection have been developed and applied for many biological and chemical applications. Because of the tiny amount of sample in the system; the induced fluorescence can be weak. Therefore, most microfluidic systems deploy multiple optical components or sophisticated equipment to enhance the efficiency of fluorescence detection. However, these strategies encounter common issues of complex manufacturing processes and high costs. In this study; a miniature, cylindrical and hybrid lens made of polydimethylsiloxane (PDMS) to improve the fluorescence detection in microfluidic systems is proposed. The hybrid lens integrates a laser focusing lens and a fluorescence collecting lens to achieve dual functions and simplify optical setup. Moreover, PDMS has advantages of low-cost and straightforward fabrication compared with conventional optical components. The performance of the proposed lens is first examined with two fluorescent dyes and the results show that the lens provides satisfactory enhancement for fluorescence detection of Rhodamine 6G and Nile Red. The overall increments in collected fluorescence signal and detection sensitivity are more than 220% of those without lens, and the detection limits of Rhodamine 6G and Nile red are lowered to 0.01 μg/mL and 0.05 μg/mL, respectively. The hybrid lens is further applied to the detection of Nile red-labeled Chlorella vulgaris cells and it increases both signal intensity and detection sensitivity by more than 520%. The proposed hybrid lens also dramatically reduces the variation in detected signal caused by the deviation in incident angle of excitation light.

Novel localized heating technique on centrifugal microfluidic disc with wireless temperature monitoring system.

Science.gov (United States)

Joseph, Karunan; Ibrahim, Fatimah; Cho, Jongman

2015-01-01

Recent advances in the field of centrifugal microfluidic disc suggest the need for electrical interface in the disc to perform active biomedical assays. In this paper, we have demonstrated an active application powered by the energy harvested from the rotation of the centrifugal microfluidic disc. A novel integration of power harvester disc onto centrifugal microfluidic disc to perform localized heating technique is the main idea of our paper. The power harvester disc utilizing electromagnetic induction mechanism generates electrical energy from the rotation of the disc. This contributes to the heat generation by the embedded heater on the localized heating disc. The main characteristic observed in our experiment is the heating pattern in relative to the rotation of the disc. The heating pattern is monitored wirelessly with a digital temperature sensing system also embedded on the disc. Maximum temperature achieved is 82 °C at rotational speed of 2000 RPM. The technique proves to be effective for continuous heating without the need to stop the centrifugal motion of the disc.

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.

Spontaneous oscillations in microfluidic networks

Science.gov (United States)

Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

2017-11-01

Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

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

DEFF Research Database (Denmark)

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

2014-01-01

For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different...... is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external...

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

Directory of Open Access Journals (Sweden)

Rasha Al-Hujazy

2018-03-01

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

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.

Leveraging liquid dielectrophoresis for microfluidic applications

International Nuclear Information System (INIS)

Chugh, Dipankar; Kaler, Karan V I S

2008-01-01

Miniaturized fluidic systems have been developed in recent years and offer new and novel means of leveraging the domain of microfluidics for the development of micro-total analysis systems (μTAS). Initially, such systems employed closed microchannels in order to facilitate chip-based biochemical assays, requiring very small quantities of sample and/or reagents and furthermore providing rapid and low-cost analysis on a compact footprint. More recently, advancements in the domain of surface microfluidics have suggested that similar low volume sample handling and manipulation capabilities for bioassays can be attained by leveraging the phenomena of liquid dielectrophoresis and droplet dielectrophoresis (DEP), without the need for separate pumps or valves. Some of the key aspects of this surface microfluidic technology and its capabilities are discussed and highlighted in this paper. We, furthermore, examine the integration and utility of liquid DEP and droplet DEP in providing rapid and automated sample handling and manipulation capabilities on a compact chip-based platform

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

Science.gov (United States)

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

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

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.

Study on stair-step liquid triggered capillary valve for microfluidic systems

Science.gov (United States)

Zhang, Lei; Jones, Ben; Majeed, Bivragh; Nishiyama, Yukari; Okumura, Yasuaki; Stakenborg, Tim

2018-06-01

In lab-on-a-chip systems, various microfluidic technologies are being developed to handle fluids at very small quantities, e.g. in the scale of nano- or pico-liter. To achieve autonomous fluid handling at a low cost, passive fluidic control, based on the capillary force between the liquid and microchannel surface, is of the utmost interest in the microsystem. Valves are an essential component for flow control in many microfluidic systems, which enables a sequence of fluidic operations to be performed. In this paper, we present a new passive valve structure for a capillary driven microfluidic device. It is a variation of a capillary trigger valve that is amenable to silicon microfabrication; it will be referred to as a stair-step liquid triggered valve. In this paper, the valve functionality and its dependencies on channel geometry, surface contact angle, and surface roughness are studied both experimentally and with numerical modeling. The effect of the contact angle was explored in experiments on the silicon microfabricated valve structure; a maximal working contact angle, above which the valve fails to be triggered, was demonstrated. The fluidic behavior in the stair-step channel structure was further explored computationally using the finite volume method with the volume-of-fluid approach. Surface roughness due to scalloping of the sidewall during the Bosch etch process was hypothesized to reduce the sidewall contact angle. The reduced contact angle has considerable impacts on the capillary pressure as the liquid vapor interface traverses the stair-step structure of the valve. An improved match in the maximal working contact angle between the experiments and model was obtained when considering this surface roughness effect.

DropBot: An open-source digital microfluidic control system with precise control of electrostatic driving force and instantaneous drop velocity measurement

International Nuclear Information System (INIS)

Fobel, Ryan; Fobel, Christian; Wheeler, Aaron R.

2013-01-01

We introduce DropBot: an open-source instrument for digital microfluidics (http://microfluidics.utoronto.ca/dropbot). DropBot features two key functionalities for digital microfluidics: (1) real-time monitoring of instantaneous drop velocity (which we propose is a proxy for resistive forces), and (2) application of constant electrostatic driving forces through compensation for amplifier-loading and device capacitance. We anticipate that this system will enhance insight into failure modes and lead to new strategies for improved device reliability, and will be useful for the growing number of users who are adopting digital microfluidics for automated, miniaturized laboratory operation.

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

A centrifugal microfluidic platform for point-of-care diagnostic applications

CSIR Research Space (South Africa)

Hugo, S

2014-02-01

Full Text Available Microfluidic systems enable precise control over tiny volumes of fluid in a compact and low-cost form, thus providing the ideal platform on which to develop point-of-care diagnostic solutions. Centrifugal microfluidic systems, also referred...

Microfluidic Liquid-Liquid Contactors

Energy Technology Data Exchange (ETDEWEB)

Mcculloch, Quinn [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-07-25

This report describes progress made on the microfluidic contactor. A model was developed to predict its failure, a surrogate chemical system was selected to demonstrate mass transfer, and an all-optical system has been invented and implemented to monitor carryover and flowrates.

Tunable-angle wedge transducer for improved acoustophoretic control in a microfluidic chip

DEFF Research Database (Denmark)

Iranmanesh, I.; Barnkob, Rune; Bruus, Henrik

2013-01-01

We present a tunable-angle wedge ultrasound transducer for improved control of microparticle acoustophoresis in a microfluidic chip. The transducer is investigated by analyzing the pattern of aligned particles and induced acoustic energy density while varying the transducer geometry, transducer...... change in geometry and that the coupling angle may be used as an additional tuning parameter for improved acoustophoretic control with single-frequency actuation. Further, we find that frequency-modulation actuation is suitable for diminishing such tuning effects and that it is a robust method to produce...... coupling angle, and transducer actuation method (single-frequency actuation or frequency-modulation actuation). The energy-density analysis is based on measuring the transmitted light intensity through a microfluidic channel filled with a suspension of 5 µm diameter beads and the results with the tunable-angle...

Microfluidic size separation of cells and particles using a swinging bucket centrifuge.

Science.gov (United States)

Yeo, Joo Chuan; Wang, Zhiping; Lim, Chwee Teck

2015-09-01

Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency.

Microfluidic Technologies for Synthetic Biology

Directory of Open Access Journals (Sweden)

Sung Kuk Lee

2011-06-01

Full Text Available Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

Advanced combinational microfluidic multiplexer for fuel cell reactors

International Nuclear Information System (INIS)

Lee, D W; Kim, Y; Cho, Y-H; Doh, I

2013-01-01

An advanced combinational microfluidic multiplexer capable to address multiple fluidic channels for fuel cell reactors is proposed. Using only 4 control lines and two different levels of control pressures, the proposed multiplexer addresses up to 19 fluidic channels, at least two times larger than the previous microfluidic multiplexers. The present multiplexer providing high control efficiency and simple structure for channel addressing would be used in the application areas of the integrated microfluidic systems such as fuel cell reactors and dynamic pressure generators

CO2-laser micromachining and back-end processing for rapid production of PMMA-based microfluidic systems

DEFF Research Database (Denmark)

Klank, Henning; Kutter, Jörg Peter; Geschke, Oliver

2002-01-01

, a three-layer polymer microstructure with included optical fibers was fabricated within two days. The use of CO2-laser systems to produce microfluidic systems has not been published before. These systems provide a cost effective alternative to UV-laser systems and they are especially useful......In this article, we focus on the enormous potential of a CO2-laser system for rapidly producing polymer microfluidic structures. The dependence was assessed of the depth and width of laser-cut channels on the laser beam power and on the number of passes of the beam along the same channel...... for microstructured PMMA [poly( methyl methacrylate)] parts were investigated, such as solvent-assisted glueing, melting, laminating and surface activation using a plasma asher. A solvent-assisted thermal bonding method proved to be the most time-efficient one. Using laser micromachining together with bonding...

Sandwich-format 3D printed microfluidic mixers: a flexible platform for multi-probe analysis

International Nuclear Information System (INIS)

Kise, Drew P; Reddish, Michael J; Brian Dyer, R

2015-01-01

We report on a microfluidic mixer fabrication platform that increases the versatility and flexibility of mixers for biomolecular applications. A sandwich-format design allows the application of multiple spectroscopic probes to the same mixer. A polymer spacer is ‘sandwiched’ between two transparent windows, creating a closed microfluidic system. The channels of the mixer are defined by regions in the polymer spacer that lack material and therefore the polymer need not be transparent in the spectral region of interest. Suitable window materials such as CaF 2 make the device accessible to a wide range of optical probe wavelengths, from the deep UV to the mid-IR. In this study, we use a commercially available 3D printer to print the polymer spacers to apply three different channel designs into the passive, continuous-flow mixer, and integrated them with three different spectroscopic probes. All three spectroscopic probes are applicable to each mixer without further changes. The sandwich-format mixer coupled with cost-effective 3D printed fabrication techniques could increase the applicability and accessibility of microfluidic mixing to intricate kinetic schemes and monitoring chemical synthesis in cases where only one probe technique proves insufficient. (paper)

Novel microfluidic system for online monitoring of biofilm dynamics by electrical impedance spectroscopy and amperometry

Science.gov (United States)

Bruchmann, Julia; Sachsenheimer, Kai; Schwartz, Thomas; Rapp, Bastian E.

2016-03-01

Biofilm formation is ubiquitous in nature where microorganisms attach to surfaces and form highly adapted and protected communities. In technical and industrial systems like drinking water supply, food production or shipping industry biofilms are a major cause of product contamination, biofouling, and biocorrosion. Therefore, understanding of biofilm formation and means of preventing biofilm formation is important to develop novel biofilm treatment strategies. A system allowing directly online detection and monitoring biofilm formation is necessary. However, until today, there are little to none technical systems featuring a non-destructive real-time characterization of biofilm formation in a highthroughput manner. This paper presents such a microfluidic system based on electrical impedance spectroscopy (EIS) and amperomertic current measurement. The sensor consists of four modules, each housing 24 independent electrodes within 12 microfluidic channels. Attached biomass on the electrodes is monitored as increased inhibition in charge transfer by EIS and a change in metabolic activity is measured as change in produced electric current by amperometry. This modular sensor system is highly adaptable and suitable for a broad range of microbiological applications. Among others, biofilm formation processes can be characterized online, biofilm manipulation like inactivation or destabilization can be monitored in real-time and gene expression can be analyzed in parallel. The use of different electrode designs allows effective biofilm studies during all biofilm phases. The whole system was recently extended by an integrated pneumatic microfluidic pump which enables easy handling procedures. Further developments of this pumping module will allow a fully- automated computer-controlled valving and pumping.

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...

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.

AAO-CNTs electrode on microfluidic flow injection system for rapid iodide sensing.

Science.gov (United States)

Phokharatkul, Ditsayut; Karuwan, Chanpen; Lomas, Tanom; Nacapricha, Duangjai; Wisitsoraat, Anurat; Tuantranont, Adisorn

2011-06-15

In this work, carbon nanotubes (CNTs) nanoarrays in anodized aluminum oxide (AAO-CNTs) nanopore is integrated on a microfluidic flow injection system for in-channel electrochemical detection of iodide. The device was fabricated from PDMS (polydimethylsiloxane) microchannel bonded on glass substrates that contains three-electrode electrochemical system, including AAO-CNTs as a working electrode, silver as a reference electrode and platinum as an auxiliary electrode. Aluminum, stainless steel catalyst, silver and platinum layers were sputtered on the glass substrate through shadow masks. Aluminum layer was then anodized by two-step anodization process to form nanopore template. CNTs were then grown in AAO template by thermal chemical vapor deposition. The amperometric detection of iodide was performed in 500-μm-wide and 100-μm-deep microchannels on the microfluidic chip. The influences of flow rate, injection volume and detection potential on the current response were optimized. From experimental results, AAO-CNTs electrode on chip offers higher sensitivity and wider dynamic range than CNTs electrode with no AAO template. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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.

Fully integrated microfluidic measurement system for real-time determination of gas and liquid mixtures composition

NARCIS (Netherlands)

Lötters, Joost Conrad; Groenesteijn, Jarno; van der Wouden, E.J.; Sparreboom, Wouter; Lammerink, Theodorus S.J.; Wiegerink, Remco J.

2015-01-01

We have designed and realised a fully integrated microfluidic measurement system for real-time determination of both flow rate and composition of gas- and liquid mixtures. The system comprises relative permittivity sensors, pressure sensors, a Coriolis flow and density sensor, a thermal flow sensor

Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low-Viscosity Bioink.

Science.gov (United States)

Colosi, Cristina; Shin, Su Ryon; Manoharan, Vijayan; Massa, Solange; Costantini, Marco; Barbetta, Andrea; Dokmeci, Mehmet Remzi; Dentini, Mariella; Khademhosseini, Ali

2016-01-27

A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented. The technique incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures. The extrusion system is then coupled to a microfluidic device to control the bioink arrangement deposition, demonstrating the versatility of the bioprinting technique. This low-viscosity cell-responsive bioink promotes cell migration and alignment within each fiber organizing the encapsulated cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biocatalytic process development using microfluidic miniaturized systems

DEFF Research Database (Denmark)

Krühne, Ulrich; Heintz, Søren; Ringborg, Rolf Hoffmeyer

2014-01-01

The increasing interest in biocatalytic processes means there is a clear need for a new systematic development paradigm which encompasses both protein engineering and process engineering. This paper argues that through the use of a new microfluidic platform, data can be collected more rapidly...

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

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.

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.

Design and Testing of Digital Microfluidic Biochips

CERN Document Server

Zhao, Yang

2013-01-01

This book provides a comprehensive methodology for automated design, test and diagnosis, and use of robust, low-cost, and manufacturable digital microfluidic systems. It focuses on the development of a comprehensive CAD optimization framework for digital microfluidic biochips that unifies different design problems. With the increase in system complexity and integration levels, biochip designers can utilize the design methods described in this book to evaluate different design alternatives, and carry out design-space exploration to obtain the best design point. Describes practical design automation tools that address different design problems (e.g., synthesis, droplet routing, control-pin mapping, testing and diagnosis, and error recovery) in a unified manner; Applies test pattern generation and error-recovery techniques for digital microfluidics-based biochips; Uses real bioassays as evaluation examples, e.g., multiplexed in vitro human physiological fluids diagnostics, PCR, protein crystallization.  

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

Science.gov (United States)

Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

2016-11-01

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

Parallelization of Droplet Microfluidic Systems for the Sustainable Production of Micro-Reactors at Industrial Scale

KAUST Repository

Conchouso Gonzalez, David

2017-01-01

fluid mechanics and limitations on the manufacturing capacity have constrained these works to explore only in-plane parallelization. This thesis investigates a three-dimensional parallelization by proposing a microfluidic system that is comprised of a

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

Directory of Open Access Journals (Sweden)

Alex J L Morgan

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

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

Science.gov (United States)

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

2016-01-01

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

Microfluidic Impedance Flow Cytometry Enabling High-Throughput Single-Cell Electrical Property Characterization

Science.gov (United States)

Chen, Jian; Xue, Chengcheng; Zhao, Yang; Chen, Deyong; Wu, Min-Hsien; Wang, Junbo

2015-01-01

This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications. PMID:25938973

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

Science.gov (United States)

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

2015-01-01

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

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...

Integrated Microfluidic Gas Sensors for Water Monitoring

Science.gov (United States)

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

2003-01-01

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

Design of pressure-driven microfluidic networks using electric circuit analogy.

Science.gov (United States)

Oh, Kwang W; Lee, Kangsun; Ahn, Byungwook; Furlani, Edward P

2012-02-07

This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

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.

Hysteresis in multiphase microfluidics at a T-junction.

Science.gov (United States)

Zagnoni, Michele; Anderson, Jamie; Cooper, Jonathan M

2010-06-15

Multiphase microfluidics offer a wide range of functionalities in the fields of fluid dynamics, biology, particle synthesis, and, more recently, also in logical computation. In this article, we describe the hysteresis of immiscible, multiphase flow obtained in hydrophilic, microfluidic systems at a T-junction. Stable and unstable state behaviors, in the form of segmented and parallel flow patterns of oil and water, were reliably produced, depending upon the history of the flow rates applied to the phases. The transition mechanisms between the two states were analyzed both experimentally and using numerical simulations, describing how the physical and fluid dynamic parameters influenced the hysteretic behavior of the flow. The characteristics of these multiphase systems render them suitable to be used as pressure comparators and also for the implementation of microfluidic logic operations.

Digital Microfluidic System with Vertical Functionality

Directory of Open Access Journals (Sweden)

Brian F. Bender

2015-11-01

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

Microfluidic Radiometal Labeling Systems for Biomolecules

Energy Technology Data Exchange (ETDEWEB)

Reichert, D E; Kenis, P J. A.

2011-12-29

In a typical labeling procedure with radiometals, such as Cu-64 and Ga-68; a very large (~ 100-fold) excess of the non-radioactive reactant (precursor) is used to promote rapid and efficient incorporation of the radioisotope into the PET imaging agent. In order to achieve high specific activities, careful control of reaction conditions and extensive chromatographic purifications are required in order to separate the labeled compounds from the cold precursors. Here we propose a microfluidic approach to overcome these problems, and achieve high specific activities in a more convenient, semi-automated fashion and faster time frame. Microfluidic reactors, consisting of a network of micron-sized channels (typical dimensions in the range 10 - 300¼m), filters, separation columns, electrodes and reaction loops/chambers etched onto a solid substrate, are now emerging as an extremely useful technology for the intensification and miniaturization of chemical processes. The ability to manipulate, process and analyze reagent concentrations and reaction interfaces in both space and time within the channel network of a microreactor provides the fine level of reaction control that is desirable in PET radiochemistry practice. These factors can bring radiometal labeling, specifically the preparation of radio-labeled biomolecules such as antibodies, much closer to their theoretical maximum specific activities.

Microfluidic Experiments Studying Pore Scale Interactions of Microbes and Geochemistry

Science.gov (United States)

Chen, M.; Kocar, B. D.

2016-12-01

Understanding how physical phenomena, chemical reactions, and microbial behavior interact at the pore-scale is crucial to understanding larger scale trends in groundwater chemistry. Recent studies illustrate the utility of microfluidic devices for illuminating pore-scale physical-biogeochemical processes and their control(s) on the cycling of iron, uranium, and other important elements 1-3. These experimental systems are ideal for examining geochemical reactions mediated by microbes, which include processes governed by complex biological phenomenon (e.g. biofilm formation, etc.)4. We present results of microfluidic experiments using a model metal reducing bacteria and varying pore geometries, exploring the limitations of the microorganisms' ability to access tight pore spaces, and examining coupled biogeochemical-physical controls on the cycling of redox sensitive metals. Experimental results will provide an enhanced understanding of coupled physical-biogeochemical processes transpiring at the pore-scale, and will constrain and compliment continuum models used to predict and describe the subsurface cycling of redox-sensitive elements5. 1. Vrionis, H. A. et al. Microbiological and geochemical heterogeneity in an in situ uranium bioremediation field site. Appl. Environ. Microbiol. 71, 6308-6318 (2005). 2. Pearce, C. I. et al. Pore-scale characterization of biogeochemical controls on iron and uranium speciation under flow conditions. Environ. Sci. Technol. 46, 7992-8000 (2012). 3. Zhang, C., Liu, C. & Shi, Z. Micromodel investigation of transport effect on the kinetics of reductive dissolution of hematite. Environ. Sci. Technol. 47, 4131-4139 (2013). 4. Ginn, T. R. et al. Processes in microbial transport in the natural subsurface. Adv. Water Resour. 25, 1017-1042 (2002). 5. Scheibe, T. D. et al. Coupling a genome-scale metabolic model with a reactive transport model to describe in situ uranium bioremediation. Microb. Biotechnol. 2, 274-286 (2009).

Culturing of PC12 Cells, Neuronal Cells, Astrocytes Cultures and Brain Slices in an Open Microfluidic System

DEFF Research Database (Denmark)

Al Atraktchi, Fatima Al-Zahraa; Bakmand, Tanya; Rømer Sørensen, Ane

The brain is the center of the nervous system, where serious neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s are products of functional loss in the neural cells (1). Typical techniques used to investigate these diseases lack precise control of the cellular surroundings......, in addition to isolating the neural tissue from nutrient delivery and to creating unwanted gradients (2). This means that typical techniques used to investigate neurodegenerative diseases cannot mimic in vivo conditions, as closely as desired. We have developed a novel microfluidic system for culturing PC12...... cells, neuronal cells, astrocytes cultures and brain slices. The microfluidic system provides efficient nutrient delivery, waste removal, access to oxygen, fine control over the neurochemical environment and access to modern microscopy. Additionally, the setup consists of an in vitro culturing...

Spintronic microfluidic platform for biomedical and environmental applications

Science.gov (United States)

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

2010-09-01

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

Microfluidic desalination : capacitive deionization on chip for microfluidic sample preparation

NARCIS (Netherlands)

Roelofs, Susan Helena

2015-01-01

The main aim of the work described in this thesis is to implement the desalination technique capacitive deionization (CDI) on a microfluidic chip to improve the reproducibility in the analysis of biological samples for drug development. Secondly, microfluidic CDI allows for the in situ study of ion

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

Science.gov (United States)

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

2008-10-01

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

Dose-on-demand production of diverse 18F-radiotracers for preclinical applications using a continuous flow microfluidic system.

Science.gov (United States)

Matesic, Lidia; Kallinen, Annukka; Greguric, Ivan; Pascali, Giancarlo

2017-09-01

The production of 18 F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse 18 F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [ 18 F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield. [ 18 F]MEL050, [ 18 F]Fallypride and [ 18 F]PBR111 were radiolabeled with [ 18 F]fluoride using the Advion NanoTek Microfluidic Synthesis System. The outlet of the microreactor was connected to an automated HPLC injector and following the collection of the product, SPE reformulation produced the 18 F-radiotracer in productions for [ 18 F]MEL050 and [ 18 F]Fallypride were performed at total flow rates of 20μL/min, resulting in 40±13% and 25±13% RCY respectively. [ 18 F]PBR111 was performed at 200μL/min to obtain 27±8% RCY. Molar activities for each 18 F-radiotracer were >100GBq/μmol and radiochemical purities were >97%, implying that the cleaning procedure was effective. Using the same initial solution of [ 18 F]fluoride, microreactor, HPLC column and SPE cartridge, three diverse 18 F-radiotracers could be produced in yields sufficient for preclinical studies in a back-to-back fashion using a microfluidic system with no detectable cross-contamination. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Electrogates for stop-and-go control of liquid flow in microfluidics

Science.gov (United States)

Arango, Y.; Temiz, Y.; Gökçe, O.; Delamarche, E.

2018-04-01

Diagnostics based on microfluidic devices necessitate specific reagents, flow conditions, and kinetics for optimal performance. Such an optimization is often achieved using assay-specific microfluidic chip designs or systems with external liquid pumps. Here, we present "electrogates" for stop-and-go control of flow of liquids in capillary-driven microfluidic chips by combining liquid pinning and electrowetting. Electrogates are simple to fabricate and efficient: a sample pipetted to a microfluidic chip flows autonomously in 15-μm-deep hydrophilic channels until the liquid meniscus is pinned at the edge of a 1.5-μm-deep trench patterned at the bottom of a rectangular microchannel. The flow can then be resumed by applying a DC voltage between the liquid and the trench via integrated electrodes. Using a trench geometry with a semicircular shape, we show that retention times longer than 30 min are achieved for various aqueous solutions such as biological buffers, artificial urine, and human serum. We studied the activation voltage and activation delay of electrogates using a chip architecture having 6 independent flow paths and experimentally showed that the flow can be resumed in less than 1 s for voltages smaller than 10 V, making this technique compatible with low-power and portable microfluidic systems. Electrogates therefore can make capillary-driven microfluidic chips very versatile by adding flow control in microfluidic channels in a flexible manner.

Magnetic particle mixing with magnetic micro-convection for microfluidics

International Nuclear Information System (INIS)

Kitenbergs, Guntars; Erglis, Kaspars; Perzynski, Régine; Cēbers, Andrejs

2015-01-01

In this paper we discuss the magnetic micro-convection phenomenon as a tool for mixing enhancement in microfluidics systems in cases when one of the miscible fluids is a magnetic particle colloid. A system of a water-based magnetic fluid and water is investigated experimentally under homogeneous magnetic field in a Hele–Shaw cell. Subsequent image analysis both qualitatively and quantitatively reveals the high enhancement of mixing efficiency provided by this method. The mixing efficiency dependence on the magnetic field and the physical limits is discussed. A suitable model for a continuous-flow microfluidics setup for mixing with magnetic micro-convection is also proposed and justified with an experiment. In addition, possible applications in improving the speed of ferrohydrodynamic sorting and magnetic label or selected tracer mixing in lab on a chip systems are noted. - Highlights: • We study the magnetic micro-convection as a mixing method in microfluidics. • We show that the method enhances mixing with magnetic field squared dependency. • We propose a flow cell setup for mixing and justify it with a sample experiment. • The mixing method can be easily implemented in an existing microfluidics setup

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

KAUST Repository

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

2013-01-01

This paper reports a new technique of fabricating polystyrene microlenses with both convex and concave profiles that are integrated in polymer-based microfluidic system. The polystyrene microlenses, or microlens array, are fabricated using the free

Various on-chip sensors with microfluidics for biological applications.

Science.gov (United States)

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

2014-09-12

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

Review of Recent Metamaterial Microfluidic Sensors.

Science.gov (United States)

Salim, Ahmed; Lim, Sungjoon

2018-01-15

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

Aldolase catalyzed L-phenylserine synthesis in a slug-flow microfluidic system - Performance and diastereoselectivity studies

NARCIS (Netherlands)

Čech, J.; Hessel, V.; Přibyl, M.

2017-01-01

We study synthesis of . L-phenylserine catalyzed by the enzyme . L-threonine aldolase in a slug-flow microfluidic system. Slug-flow arrangement allows for the continuous refilling of sparingly soluble substrate (benzaldehyde) into an aqueous reaction mixture. We identified suitable composition of an

Selective distribution of enzymes in a microfluidic reactor

DEFF Research Database (Denmark)

Daugaard, Anders Egede; Pereira Rosinha Grundtvig, Ines; Krühne, Ulrich

Off stoichiometric thiol-ene mixtures are well suited for preparation of microfluidic devices with highly functional surfaces. Here a two stage process employing first thiol-ene chemistry (TEC) to prepare two opposite parts of a microfluidic system with a 30x30 mm reactor and subsequently a thiol......-epoxy bonding was used to prepare a fully sealed microfluidic system. The reactor was surface functionalized in-situ with allyl glycidyl ether in different patterns (half-reactor, full-reactor, checkerboard structures) on the surface to provide a controlled distribution of epoxides. The method additionally...... enables the selective immobilization on either top-side or bottom-side or both sides of the reactor. Thereafter horseradish peroxidase was immobilized on the surface and activity tests illustrated how this distribution of the enzyme on the surface could be used to optimize the activity of the enzyme...

Tutorial: Digital microfluidic biochips: Towards hardware/software co-design and cyber-physical system integration

DEFF Research Database (Denmark)

Ho, Tsung-Yi; Huang, Juinn-Dar; Pop, Paul

2013-01-01

This tutorial will first provide an overview of typical bio-molecular applications (market drivers) such as immunoassays, DNA sequencing, clinical chemistry, etc. Next, microarrays and various microfluidic platforms will be discussed. The next part of the tutorial will focus on electro-wetting-ba......This tutorial will first provide an overview of typical bio-molecular applications (market drivers) such as immunoassays, DNA sequencing, clinical chemistry, etc. Next, microarrays and various microfluidic platforms will be discussed. The next part of the tutorial will focus on electro......-wetting-based digital micro-fluidic biochips. The key idea here is to manipulate liquids as discrete droplets. A number of case studies based on representative assays and laboratory procedures will be interspersed in appropriate places throughout the tutorial. Basic concepts in micro-fabrication techniques will also...... be discussed. Attendees will next learn about CAD and reconfiguration aspects of digital microfluidic biochips. Synthesis tools will be described to map assay protocols from the lab bench to a droplet-based microfluidic platform and generate an optimized schedule of bioassay operations, the binding of assay...

Engineering Porous Polymer Hollow Fiber Microfluidic Reactors for Sustainable C-H Functionalization.

Science.gov (United States)

He, Yingxin; Rezaei, Fateme; Kapila, Shubhender; Rownaghi, Ali A

2017-05-17

Highly hydrophilic and solvent-stable porous polyamide-imide (PAI) hollow fibers were created by cross-linking of bare PAI hollow fibers with 3-aminopropyl trimethoxysilane (APS). The APS-grafted PAI hollow fibers were then functionalized with salicylic aldehyde for binding catalytically active Pd(II) ions through a covalent postmodification method. The catalytic activity of the composite hollow fiber microfluidic reactors (Pd(II) immobilized APS-grafted PAI hollow fibers) was tested via heterogeneous Heck coupling reaction of aryl halides under both batch and continuous-flow reactions in polar aprotic solvents at high temperature (120 °C) and low operating pressure. X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma (ICP) analyses of the starting and recycled composite hollow fibers indicated that the fibers contain very similar loadings of Pd(II), implying no degree of catalyst leaching from the hollow fibers during reaction. The composite hollow fiber microfluidic reactors showed long-term stability and strong control over the leaching of Pd species.

Exploiting an automated microfluidic hydrodynamic sequential injection system for determination of phosphate.

Science.gov (United States)

Khongpet, Wanpen; Pencharee, Somkid; Puangpila, Chanida; Kradtap Hartwell, Supaporn; Lapanantnoppakhun, Somchai; Jakmunee, Jaroon

2018-01-15

A microfluidic hydrodynamic sequential injection (μHSI) spectrophotometric system was designed and fabricated. The system was built by laser engraving a manifold pattern on an acrylic block and sealing with another flat acrylic plate to form a microfluidic channel platform. The platform was incorporated with small solenoid valves to obtain a portable setup for programmable control of the liquid flow into the channel according to the HSI principle. The system was demonstrated for the determination of phosphate using a molybdenum blue method. An ascorbic acid, standard or sample, and acidic molybdate solutions were sequentially aspirated to fill the channel forming a stack zone before flowing to the detector. Under the optimum condition, a linear calibration graph in the range of 0.1-6mg P L -1 was obtained. The detection limit was 0.1mgL -1 . The system is compact (5.0mm thick, 80mm wide × 140mm long), durable, portable, cost-effective, and consumes little amount of chemicals (83μL each of molybdate and ascorbic acid, 133μL of the sample solution and 1.7mL of water carrier/run). It was applied for the determination of phosphate content in extracted soil samples. The percent recoveries of the analysis were obtained in the range of 91.2-107.3. The results obtained agreed well with those of the batch spectrophotometric method. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic systems for the analysis of viscoelastic fluid flow phenomena in porous media

NARCIS (Netherlands)

Galindo-Rosales, F.J.; Campo-Deano, L.; Pinho, F.T.; Van Bokhorst, E.; Hamersma, P.J.; Oliveira, M.S.N.; Alves, M.A.

2011-01-01

In this study, two microfluidic devices are proposed as simplified 1-D microfluidic analogues of a porous medium. The objectives are twofold: firstly to assess the usefulness of the microchannels to mimic the porous medium in a controlled and simplified manner, and secondly to obtain a better

Field effect control of electro-osmotic flow in microfluidic networks

NARCIS (Netherlands)

van der Wouden, E.J.

2006-01-01

This thesis describes the development of a Field Effect Flow Control (FEFC) system for the control of Electro Osmotic Flow (EOF) in microfluidic networks. For this several aspects of FEFC have been reviewed and a process to fabricate microfluidic channels with integrated electrodes has been

Microfluidic biolector-microfluidic bioprocess control in microtiter plates.

Science.gov (United States)

Funke, Matthias; Buchenauer, Andreas; Schnakenberg, Uwe; Mokwa, Wilfried; Diederichs, Sylvia; Mertens, Alan; Müller, Carsten; Kensy, Frank; Büchs, Jochen

2010-10-15

In industrial-scale biotechnological processes, the active control of the pH-value combined with the controlled feeding of substrate solutions (fed-batch) is the standard strategy to cultivate both prokaryotic and eukaryotic cells. On the contrary, for small-scale cultivations, much simpler batch experiments with no process control are performed. This lack of process control often hinders researchers to scale-up and scale-down fermentation experiments, because the microbial metabolism and thereby the growth and production kinetics drastically changes depending on the cultivation strategy applied. While small-scale batches are typically performed highly parallel and in high throughput, large-scale cultivations demand sophisticated equipment for process control which is in most cases costly and difficult to handle. Currently, there is no technical system on the market that realizes simple process control in high throughput. The novel concept of a microfermentation system described in this work combines a fiber-optic online-monitoring device for microtiter plates (MTPs)--the BioLector technology--together with microfluidic control of cultivation processes in volumes below 1 mL. In the microfluidic chip, a micropump is integrated to realize distinct substrate flow rates during fed-batch cultivation in microscale. Hence, a cultivation system with several distinct advantages could be established: (1) high information output on a microscale; (2) many experiments can be performed in parallel and be automated using MTPs; (3) this system is user-friendly and can easily be transferred to a disposable single-use system. This article elucidates this new concept and illustrates applications in fermentations of Escherichia coli under pH-controlled and fed-batch conditions in shaken MTPs. Copyright 2010 Wiley Periodicals, Inc.

Direct current insulator based dielectrophoresis (DC-iDEP) microfluidic chip for blood plasma separation

OpenAIRE

Mohammadi, Mahdi

2015-01-01

Lab-on-a-Chip (LOC) integrated microfluidics has been a powerful tool for new developments in analytical chemistry. These microfluidic systems enable the miniaturization, integration and automation of complex biochemical assays through the reduction of reagent use and enabling portability.Cell and particle separation in microfluidic systems has recently gained significant attention in many sample preparations for clinical procedures. Direct-current insulator-based dielectrophoresis (DC-iDEP) ...

Pneumatic oscillator circuits for timing and control of integrated microfluidics.

Science.gov (United States)

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

2013-11-05

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

The upcoming 3D-printing revolution in microfluidics

Science.gov (United States)

Bhattacharjee, Nirveek; Urrios, Arturo; Kang, Shawn; Folch, Albert

2016-01-01

In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS micromolding. A long list of key PDMS properties have contributed to the success of soft lithography: PDMS is biocompatible, elastomeric, transparent, gas-permeable, water-impermeable, fairly inexpensive, copyright-free, and rapidly prototyped with high precision using simple procedures. However, the fabrication process typically involves substantial human labor, which tends to make PDMS devices difficult to disseminate outside of research labs, and the layered molding limits the 3D complexity of the devices that can be produced. 3D-printing has recently attracted attention as a way to fabricate microfluidic systems due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. Resins with properties approaching those of PDMS are being developed. Here we review past and recent efforts in 3D-printing of microfluidic systems. We compare the salient features of PDMS molding with those of 3D-printing and we give an overview of the critical barriers that have prevented the adoption of 3D-printing by microfluidic developers, namely resolution, throughput, and resin biocompatibility. We also evaluate the various forces that are persuading researchers to abandon PDMS molding in favor of 3D-printing in growing numbers. PMID:27101171

Molecular Imaging Probe Development using Microfluidics

Science.gov (United States)

Liu, Kan; Wang, Ming-Wei; Lin, Wei-Yu; Phung, Duy Linh; Girgis, Mark D.; Wu, Anna M.; Tomlinson, James S.; Shen, Clifton K.-F.

2012-01-01

In this manuscript, we review the latest advancement of microfluidics in molecular imaging probe development. Due to increasing needs for medical imaging, high demand for many types of molecular imaging probes will have to be met by exploiting novel chemistry/radiochemistry and engineering technologies to improve the production and development of suitable probes. The microfluidic-based probe synthesis is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional systems. Numerous chemical reactions have been successfully performed in micro-reactors and the results convincingly demonstrate with great benefits to aid synthetic procedures, such as purer products, higher yields, shorter reaction times compared to the corresponding batch/macroscale reactions, and more benign reaction conditions. Several ‘proof-of-principle’ examples of molecular imaging probe syntheses using microfluidics, along with basics of device architecture and operation, and their potential limitations are discussed here. PMID:22977436

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.

Polymer dual ring resonators for label-free optical biosensing using microfluidics.

Science.gov (United States)

Salleh, Muhammad H M; Glidle, Andrew; Sorel, Marc; Reboud, Julien; Cooper, Jonathan M

2013-04-18

We demonstrate a polymer resonator microfluidic biosensor that overcomes the complex manufacturing procedures required to fabricate traditional devices. In this new format, we show that a gapless light coupling photonic configuration, fabricated in SU8 polymer, can achieve high sensitivity, label-free chemical sensing in solution and high sensitivity biological sensing, at visible wavelengths.

Various On-Chip Sensors with Microfluidics for Biological Applications

Directory of Open Access Journals (Sweden)

Hun Lee

2014-09-01

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

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.

Route to one-step microstructure mold fabrication for PDMS microfluidic chip

Science.gov (United States)

Lv, Xiaoqing; Geng, Zhaoxin; Fan, Zhiyuan; Wang, Shicai; Su, Yue; Fang, Weihao; Pei, Weihua; Chen, Hongda

2018-04-01

The microstructure mold fabrication for PDMS microfluidic chip remains complex and time-consuming process requiring special equipment and protocols: photolithography and etching. Thus, a rapid and cost-effective method is highly needed. Comparing with the traditional microfluidic chip fabricating process based on the micro-electromechanical system (MEMS), this method is simple and easy to implement, and the whole fabrication process only requires 1-2 h. Different size of microstructure from 100 to 1000 μm was fabricated, and used to culture four kinds of breast cancer cell lines. Cell viability and morphology was assessed when they were cultured in the micro straight channels, micro square holes and the bonding PDMS-glass microfluidic chip. The experimental results indicate that the microfluidic chip is good and meet the experimental requirements. This method can greatly reduce the process time and cost of the microfluidic chip, and provide a simple and effective way for the structure design and in the field of biological microfabrications and microfluidic chips.

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.

Disposable world-to-chip interface for digital microfluidics

Science.gov (United States)

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

2017-05-16

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

The microfluidic probe: operation and use for localized surface processing.

Science.gov (United States)

Perrault, Cecile M; Qasaimeh, Mohammad A; Juncker, David

2009-06-04

Microfluidic devices allow assays to be performed using minute amounts of sample and have recently been used to control the microenvironment of cells. Microfluidics is commonly associated with closed microchannels which limit their use to samples that can be introduced, and cultured in the case of cells, within a confined volume. On the other hand, micropipetting system have been used to locally perfuse cells and surfaces, notably using push-pull setups where one pipette acts as source and the other one as sink, but the confinement of the flow is difficult in three dimensions. Furthermore, pipettes are fragile and difficult to position and hence are used in static configuration only. The microfluidic probe (MFP) circumvents the constraints imposed by the construction of closed microfluidic channels and instead of enclosing the sample into the microfluidic system, the microfluidic flow can be directly delivered onto the sample, and scanned across the sample, using the MFP. . The injection and aspiration openings are located within a few tens of micrometers of one another so that a microjet injected into the gap is confined by the hydrodynamic forces of the surrounding liquid and entirely aspirated back into the other opening. The microjet can be flushed across the substrate surface and provides a precise tool for localized deposition/delivery of reagents which can be used over large areas by scanning the probe across the surface. In this video we present the microfluidic probe (MFP). We explain in detail how to assemble the MFP, mount it atop an inverted microscope, and align it relative to the substrate surface, and finally show how to use it to process a substrate surface immersed in a buffer.

Real-time monitoring of cellular dynamics using a microfluidic cell culture system with integrated electrode array and potentiostat

DEFF Research Database (Denmark)

Zor, Kinga; Vergani, M.; Heiskanen, Arto

2011-01-01

A versatile microfluidic, multichamber cell culture and analysis system with an integrated electrode array and potentiostat suitable for electrochemical detection and microscopic imaging is presented in this paper. The system, which allows on-line electrode cleaning and modification, was develope...

Review of Recent Metamaterial Microfluidic Sensors

Directory of Open Access Journals (Sweden)

Ahmed Salim

2018-01-01

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

Microfluidic sensor for ultra high redox cycling amplification for highly selective electrochemical measurements

NARCIS (Netherlands)

Odijk, Mathieu; Straver, Martin; Olthuis, Wouter; van den Berg, Albert

2011-01-01

In this contribution a SU8/glass-based microfluidic sensor is described with two closely spaced parallel electrodes for highly selective measurements using the redox cycling (RC) effect. Using this sensor, a RC amplification of ~2000x is measured using the ferrocyanide redox couple, which is much

Fluorescence Detection 400–480 nm Using Microfluidic System Integrated GaP Photodiodes

Directory of Open Access Journals (Sweden)

Dion McIntosh

2011-01-01

Full Text Available Ciprofloxacin is a commonly used antibiotic and the active ingredient in a veterinary antibiotic. Detecting its presence allows us to understand its absorption process in blood as well as tissue. A portable microfluidic system has been fabricated. It operates at low bias voltage and shows a linear relationship between concentration levels and system response. Detection of concentrations down to 1 ppb of ciprofloxacin in microliters of solution was achieved.

Monolithic integration of microfluidic channels and semiconductor lasers

Science.gov (United States)

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

2006-08-01

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

Microfluidic 3D cell culture: potential application for tissue-based bioassays

Science.gov (United States)

Li, XiuJun (James); Valadez, Alejandra V.; Zuo, Peng; Nie, Zhihong

2014-01-01

Current fundamental investigations of human biology and the development of therapeutic drugs, commonly rely on two-dimensional (2D) monolayer cell culture systems. However, 2D cell culture systems do not accurately recapitulate the structure, function, physiology of living tissues, as well as highly complex and dynamic three-dimensional (3D) environments in vivo. The microfluidic technology can provide micro-scale complex structures and well-controlled parameters to mimic the in vivo environment of cells. The combination of microfluidic technology with 3D cell culture offers great potential for in vivo-like tissue-based applications, such as the emerging organ-on-a-chip system. This article will review recent advances in microfluidic technology for 3D cell culture and their biological applications. PMID:22793034

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.

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...

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.

A multiplexed microfluidic toolbox for the rapid optimization of affinity-driven partition in aqueous two phase systems.

Science.gov (United States)

Bras, Eduardo J S; Soares, Ruben R G; Azevedo, Ana M; Fernandes, Pedro; Arévalo-Rodríguez, Miguel; Chu, Virginia; Conde, João P; Aires-Barros, M Raquel

2017-09-15

Antibodies and other protein products such as interferons and cytokines are biopharmaceuticals of critical importance which, in order to be safely administered, have to be thoroughly purified in a cost effective and efficient manner. The use of aqueous two-phase extraction (ATPE) is a viable option for this purification, but these systems are difficult to model and optimization procedures require lengthy and expensive screening processes. Here, a methodology for the rapid screening of antibody extraction conditions using a microfluidic channel-based toolbox is presented. A first microfluidic structure allows a simple negative-pressure driven rapid screening of up to 8 extraction conditions simultaneously, using less than 20μL of each phase-forming solution per experiment, while a second microfluidic structure allows the integration of multi-step extraction protocols based on the results obtained with the first device. In this paper, this microfluidic toolbox was used to demonstrate the potential of LYTAG fusion proteins used as affinity tags to optimize the partitioning of antibodies in ATPE processes, where a maximum partition coefficient (K) of 9.2 in a PEG 3350/phosphate system was obtained for the antibody extraction in the presence of the LYTAG-Z dual ligand. This represents an increase of approx. 3.7 fold when compared with the same conditions without the affinity molecule (K=2.5). Overall, this miniaturized and versatile approach allowed the rapid optimization of molecule partition followed by a proof-of-concept demonstration of an integrated back extraction procedure, both of which are critical procedures towards obtaining high purity biopharmaceuticals using ATPE. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum-Pressure Accelerated Movement (V-PAM).

Science.gov (United States)

Yu, Zeta Tak For; Cheung, Mei Ki; Liu, Shirley Xiaosu; Fu, Jianping

2016-09-01

Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum-Pressure Accelerated Movement (V-PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead-end channels and closed chambers. Operation of the V-PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas-permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V-PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V-PAM for rapid filling of temperature-sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V-PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs-on-chips, and biomimetic studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.

Science.gov (United States)

Tran, Reginald; Myers, David R; Denning, Gabriela; Shields, Jordan E; Lytle, Allison M; Alrowais, Hommood; Qiu, Yongzhi; Sakurai, Yumiko; Li, William C; Brand, Oliver; Le Doux, Joseph M; Spencer, H Trent; Doering, Christopher B; Lam, Wilbur A

2017-10-04

Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency. This novel ex vivo LV transduction platform is flexible in design, easy to use, scalable, and compatible with standard cell transduction reagents and LV preparations. Using hematopoietic cell lines, primary human T cells, primary hematopoietic stem and progenitor cells (HSPCs) of both murine (Sca-1 + ) and human (CD34 + ) origin, microfluidic transduction using clinically processed LVs occurs up to 5-fold faster and requires as little as one-twentieth of LV. As an in vivo validation of the microfluidic-based transduction technology, HSPC gene therapy was performed in hemophilia A mice using limiting amounts of LV. Compared to the standard static well-based transduction protocols, only animals transplanted with microfluidic-transduced cells displayed clotting levels restored to normal. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

Laser micromachined wax-covered plastic paper as both sputter deposition shadow masks and deep-ultraviolet patterning masks for polymethylmethacrylate-based microfluidic systems

KAUST Repository

Fan, Yiqiang

2013-12-16

We report a technically innovative method of fabricating masks for both deep-ultraviolet (UV) patterning and metal sputtering on polymethylmethacrylate (PMMA) for microfluidic systems. We used a CO2 laser system to cut the required patterns on wax-covered plastic paper; the laser-patterned wax paper will either work as a mask for deep-UV patterning or as a mask for metal sputtering. A microfluidic device was also fabricated to demonstrate the feasibility of this method. The device has two layers: the first layer is a 1-mm thick PMMA substrate that was patterned by deep-UV exposure to create microchannels. The mask used in this process was the laser-cut wax paper. The second layer, also a 1-mm thick PMMA layer, was gold sputtered with patterned wax paper as the shadow mask. These two pieces of PMMA were then bonded to form microchannels with exposed electrodes. This process is a simple and rapid method for creating integrated microfluidic systems that do not require cleanroom facilities.

Development of a Microfluidic Platform to Analyze Evolution of Programmed Bacterial Death

Science.gov (United States)

2015-12-20

droplet-based microfluidic technology to generate population ‘bottleneck’. This platform will serve as a critical foundation for our long-term goal to...Final Report: Development of a Microfluidic Platform to Analyze Evolution of Programmed Bacterial Death The views, opinions and/or findings contained...Triangle Park, NC 27709-2211 Microfluidics , systems biology REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 10. SPONSOR/MONITOR’S ACRONYM

Microfluidics to Mimic Blood Flow in Health and Disease

Science.gov (United States)

Sebastian, Bernhard; Dittrich, Petra S.

2018-01-01

Throughout history, capillary systems have aided the establishment of the fundamental laws of blood flow and its non-Newtonian properties. The advent of microfluidics technology in the 1990s propelled the development of highly integrated lab-on-a-chip platforms that allow highly accurate replication of vascular systems' dimensions, mechanical properties, and biological complexity. Applications include the detection of pathological changes to red blood cells, white blood cells, and platelets at unparalleled sensitivity and the efficacy assessment of drug treatment. Recent efforts have aimed at the development of microfluidics-based tests usable in a clinial environment or the replication of more complex diseases such as thrombosis. These microfluidic disease models enable the study of onset and progression of disease as well as the identification of key players and risk factors, which have led to a spectrum of clinically relevant findings.

Microfluidic biofunctionalisation protocols to form multi-valent interactions for cell rolling and phenotype modification investigations

KAUST Repository

Perozziello, Gerardo; Simone, Giuseppina; Malara, Natalia Maria; La Rocca, Rosanna; Tallerico, Rossana; Catalano, Rossella; Pardeo, Francesca; Candeloro, Patrizio; Cuda, Giovanni; Carbone, Ennio; Di Fabrizio, Enzo M.

2013-01-01

for cellomic studies. Based on this principle, we exploit the streptavidin-biotin interaction to couple antibodies to the biofunctionalised microfluidic environment within 5 h using 200 μL of reagents and biomolecules. We selected the antibodies able to form

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.

Reversible thermo-pneumatic valves on centrifugal microfluidic platforms.

Science.gov (United States)

Aeinehvand, Mohammad Mahdi; Ibrahim, Fatimah; Harun, Sulaiman Wadi; Kazemzadeh, Amin; Rothan, Hussin A; Yusof, Rohana; Madou, Marc

2015-08-21

Centrifugal microfluidic systems utilize a conventional spindle motor to automate parallel biochemical assays on a single microfluidic disk. The integration of complex, sequential microfluidic procedures on these platforms relies on robust valving techniques that allow for the precise control and manipulation of fluid flow. The ability of valves to consistently return to their former conditions after each actuation plays a significant role in the real-time manipulation of fluidic operations. In this paper, we introduce an active valving technique that operates based on the deflection of a latex film with the potential for real-time flow manipulation in a wide range of operational spinning speeds. The reversible thermo-pneumatic valve (RTPV) seals or reopens an inlet when a trapped air volume is heated or cooled, respectively. The RTPV is a gas-impermeable valve composed of an air chamber enclosed by a latex membrane and a specially designed liquid transition chamber that enables the efficient usage of the applied thermal energy. Inputting thermo-pneumatic (TP) energy into the air chamber deflects the membrane into the liquid transition chamber against an inlet, sealing it and thus preventing fluid flow. From this point, a centrifugal pressure higher than the induced TP pressure in the air chamber reopens the fluid pathway. The behaviour of this newly introduced reversible valving system on a microfluidic disk is studied experimentally and theoretically over a range of rotational frequencies from 700 RPM to 2500 RPM. Furthermore, adding a physical component (e.g., a hemispherical rubber element) to induce initial flow resistance shifts the operational range of rotational frequencies of the RTPV to more than 6000 RPM. An analytical solution for the cooling of a heated RTPV on a spinning disk is also presented, which highlights the need for the future development of time-programmable RTPVs. Moreover, the reversibility and gas impermeability of the RTPV in the

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

Microfluidic System Simulation Including the Electro-Viscous Effect

Science.gov (United States)

Rojas, Eileen; Chen, C. P.; Majumdar, Alok

2007-01-01

This paper describes a practical approach using a general purpose lumped-parameter computer program, GFSSP (Generalized Fluid System Simulation Program) for calculating flow distribution in a network of micro-channels including electro-viscous effects due to the existence of electrical double layer (EDL). In this study, an empirical formulation for calculating an effective viscosity of ionic solutions based on dimensional analysis is described to account for surface charge and bulk fluid conductivity, which give rise to electro-viscous effect in microfluidics network. Two dimensional slit micro flow data was used to determine the model coefficients. Geometry effect is then included through a Poiseuille number correlation in GFSSP. The bi-power model was used to calculate flow distribution of isotropically etched straight channel and T-junction microflows involving ionic solutions. Performance of the proposed model is assessed against experimental test data.

Centrifugal microfluidic platforms: advanced unit operations and applications.

Science.gov (United States)

Strohmeier, O; Keller, M; Schwemmer, F; Zehnle, S; Mark, D; von Stetten, F; Zengerle, R; Paust, N

2015-10-07

Centrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term "process chain" to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as

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.

A microfluidic galvanic cell on a single layer of paper

Science.gov (United States)

Purohit, Krutarth H.; Emrani, Saina; Rodriguez, Sandra; Liaw, Shi-Shen; Pham, Linda; Galvan, Vicente; Domalaon, Kryls; Gomez, Frank A.; Haan, John L.

2016-06-01

Paper microfluidics is used to produce single layer galvanic and hybrid cells to produce energy that could power paper-based analytical sensors. When two aqueous streams are absorbed onto paper to establish co-laminar flow, the streams stay in contact with each other with limited mixing. The interface at which mixing occurs acts as a charge-transfer region, eliminating the need for a salt bridge. We designed a Cusbnd Zn galvanic cell that powers an LED when two are placed in series. We also used more powerful redox couples (formate and silver, formate and permanganate) to produce higher power density (18 and 3.1 mW mg-1 Pd). These power densities are greater than previously reported paper microfluidic fuel cells using formate or methanol. The single layer design is much more simplified than previous reports of multi-layer galvanic cells on paper.

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.

Evaluation of photodynamic therapy (PDT) procedures using microfluidic system

Energy Technology Data Exchange (ETDEWEB)

Jedrych, Elzbieta, E-mail: ejedrych@ch.pw.edu.pl [Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 300-664 Warsaw (Poland); Pawlicka, Zuzanna; Chudy, Michal; Dybko, Artur; Brzozka, Zbigniew [Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 300-664 Warsaw (Poland)

2011-01-10

A hybrid PDMS/glass microfluidic system for evaluation of the efficiency of photodynamic therapy is presented. 5-aminolevulinic acid (ALA) was used as a precursor of photosensitizer. The geometry of the microdevice presented in this paper enables to test different concentrations of the photosensitizer in a single assay. The viability of the A549 cells was determined 24 h after PDT procedure (irradiation with light which induced a photosensitizer accumulated in carcinoma cells, {lambda} = 625 nm). The presented results confirmed the possibility to perform the photodynamic therapy process in vitro in microscale and the possibility to assess its effectiveness. Moreover, because two identical microstructures on a single chip were performed, the microchip can be used for examination simultaneously various cell lines (carcinoma and normal) or various photosensitizers.

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

Fabrication and optimisation of a fused filament 3D-printed microfluidic platform

International Nuclear Information System (INIS)

Tothill, A M; Partridge, M; James, S W; Tatam, R P

2017-01-01

A 3D-printed microfluidic device was designed and manufactured using a low cost ($2000) consumer grade fusion deposition modelling (FDM) 3D printer. FDM printers are not typically used, or are capable, of producing the fine detailed structures required for microfluidic fabrication. However, in this work, the optical transparency of the device was improved through manufacture optimisation to such a point that optical colorimetric assays can be performed in a 50 µ l device. A colorimetric enzymatic cascade assay was optimised using glucose oxidase and horseradish peroxidase for the oxidative coupling of aminoantipyrine and chromotropic acid to produce a blue quinoneimine dye with a broad absorbance peaking at 590 nm for the quantification of glucose in solution. For comparison the assay was run in standard 96 well plates with a commercial plate reader. The results show the accurate and reproducible quantification of 0–10 mM glucose solution using a 3D-printed microfluidic optical device with performance comparable to that of a plate reader assay. (paper)

Detection of Plasmodium Aldolase Using a Smartphone and Microfluidic Enzyme Linked Immunosorbent Assay

Directory of Open Access Journals (Sweden)

Nikhil S. Gopal

2017-01-01

Full Text Available Background. Malaria control efforts are limited in rural areas. A low-cost system to monitor response without the use of electricity is needed. Plasmodium aldolase is a malaria biomarker measured using enzyme linked immunosorbent assay (ELISA techniques. A three-part system using ELISA was developed consisting of a microfluidic chip, hand crank centrifuge, and a smartphone. Methods. A circular microfluidic chip was fabricated using clear acrylic and a CO2 laser. A series of passive valves released reagents at precise times based upon centrifugal force. Color change was measured via smartphone camera using an application programmed in Java. The microchip was compared to a standard 96-well sandwich ELISA. Results. Results from standard ELISA were compared to microchip at varying concentrations (1–10 ng/mL. Over 15 different microfluidic patterns were tested, and a final prototype of the chip was created. The prototype microchip was compared to standard sandwich ELISA (n=20 using samples of recombinant aldolase. Color readings of standard ELISA and microfluidic microchip showed similar results. Conclusion. A low-cost microfluidic system could detect and follow therapeutic outcomes in rural areas and identify resistant strains.

Binary particle separation in droplet microfluidics using acoustophoresis

Science.gov (United States)

Fornell, Anna; Cushing, Kevin; Nilsson, Johan; Tenje, Maria

2018-02-01

We show a method for separation of two particle species with different acoustic contrasts originally encapsulated in the same droplet in a continuous two-phase system. This was realized by using bulk acoustic standing waves in a 380 μm wide silicon-glass microfluidic channel. Polystyrene particles (positive acoustic contrast particles) and in-house synthesized polydimethylsiloxane (PDMS) particles (negative acoustic contrast particles) were encapsulated inside water-in-oil droplets either individually or in a mixture. At acoustic actuation of the system at the fundamental resonance frequency, the polystyrene particles were moved to the center of the droplet (pressure node), while the PDMS particles were moved to the sides of the droplet (pressure anti-nodes). The acoustic particle manipulation step was combined in series with a trifurcation droplet splitter, and as the original droplet passed through the splitter and was divided into three daughter droplets, the polystyrene particles were directed into the center daughter droplet, while the PDMS particles were directed into the two side daughter droplets. The presented method expands the droplet microfluidics tool-box and offers new possibilities to perform binary particle separation in droplet microfluidic systems.

A self-contained, programmable microfluidic cell culture system with real-time microscopy access

DEFF Research Database (Denmark)

Skafte-Pedersen, Peder; Hemmingsen, Mette; Sabourin, David

2011-01-01

Utilizing microfluidics is a promising way for increasing the throughput and automation of cell biology research. We present a complete self-contained system for automated cell culture and experiments with real-time optical read-out. The system offers a high degree of user-friendliness, stability...... enables the system to perform parallel, programmable and multiconditional assays on a single chip. A modular approach provides system versatility and allows many different chips to be used dependent upon application. We validate the system's performance by demonstrating on-chip passive switching...... and mixing by peristaltically driven flows. Applicability for biological assays is demonstrated by on-chip cell culture including on-chip transfection and temporally programmable gene expression....

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells.

Science.gov (United States)

Cole, Russell H; Tang, Shi-Yang; Siltanen, Christian A; Shahi, Payam; Zhang, Jesse Q; Poust, Sean; Gartner, Zev J; Abate, Adam R

2017-08-15

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.

Solenoid Driven Pressure Valve System: Toward Versatile Fluidic Control in Paper Microfluidics.

Science.gov (United States)

Kim, Taehoon H; Hahn, Young Ki; Lee, Jungmin; van Noort, Danny; Kim, Minseok S

2018-02-20

As paper-based diagnostics has become predominantly driven by more advanced microfluidic technology, many of the research efforts are still focused on developing reliable and versatile fluidic control devices, apart from improving sensitivity and reproducibility. In this work, we introduce a novel and robust paper fluidic control system enabling versatile fluidic control. The system comprises a linear push-pull solenoid and an Arduino Uno microcontroller. The precisely controlled pressure exerted on the paper stops the flow. We first determined the stroke distance of the solenoid to obtain a constant pressure while examining the fluidic time delay as a function of the pressure. Results showed that strips of grade 1 chromatography paper had superior reproducibility in fluid transport. Next, we characterized the reproducibility of the fluidic velocity which depends on the type and grade of paper used. As such, we were able to control the flow velocity on the paper and also achieve a complete stop of flow with a pressure over 2.0 MPa. Notably, after the actuation of the pressure driven valve (PDV), the previously pressed area regained its original flow properties. This means that, even on a previously pressed area, multiple valve operations can be successfully conducted. To the best of our knowledge, this is the first demonstration of an active and repetitive valve operation in paper microfluidics. As a proof of concept, we have chosen to perform a multistep detection system in the form of an enzyme-linked immunosorbent assay with mouse IgG as the target analyte.

Applications of Microfluidics in Quantitative Biology.

Science.gov (United States)

Bai, Yang; Gao, Meng; Wen, Lingling; He, Caiyun; Chen, Yuan; Liu, Chenli; Fu, Xiongfei; Huang, Shuqiang

2018-05-01

Quantitative biology is dedicated to taking advantage of quantitative reasoning and advanced engineering technologies to make biology more predictable. Microfluidics, as an emerging technique, provides new approaches to precisely control fluidic conditions on small scales and collect data in high-throughput and quantitative manners. In this review, the authors present the relevant applications of microfluidics to quantitative biology based on two major categories (channel-based microfluidics and droplet-based microfluidics), and their typical features. We also envision some other microfluidic techniques that may not be employed in quantitative biology right now, but have great potential in the near future. © 2017 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Intensely oscillating cavitation bubble in microfluidics

International Nuclear Information System (INIS)

Siew-Wan, Ohl; Tandiono; Klaseboer, Evert; Dave, Ow; Choo, Andre; Claus-Dieter, Ohl

2015-01-01

This study reports the technical breakthrough in generating intense ultrasonic cavitation in the confinement of a microfluidics channel [1], and applications that has been developed on this platform for the past few years [2,3,4,5]. Our system consists of circular disc transducers (10-20 mm in diameter), the microfluidics channels on PDMS (polydimethylsiloxane), and a driving circuitry. The cavitation bubbles are created at the gas- water interface due to strong capillary waves which are generated when the system is driven at its natural frequency (around 100 kHz) [1]. These bubbles oscillate and collapse within the channel. The bubbles are useful for sonochemistry and the generation of sonoluminescence [2]. When we add bacteria (Escherichia coli), and yeast cells (Pichia pastoris) into the microfluidics channels, the oscillating and collapsing bubbles stretch and lyse these cells [3]. Furthermore, the system is effective (DNA of the harvested intracellular content remains largely intact), and efficient (yield reaches saturation in less than 1 second). In another application, human red blood cells are added to a microchamber. Cell stretching and rapture are observed when a laser generated cavitation bubble expands and collapses next to the cell [4]. A numerical model of a liquid pocket surrounded by a membrane with surface tension which was placed next to an oscillating bubble was developed using the Boundary Element Method. The simulation results showed that the stretching of the liquid pocket occurs only when the surface tension is within a certain range. (paper)

A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions

KAUST Repository

Fan, Qihui

2017-07-10

A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tuneable biochemical gradients that mimics the tumour microenvironment of mammary glands was constructed for the investigation on the interactions between invasive breast cancer cells and stromal cells. The hollow microchambers in collagen provide a very similar 3-D environment to that in vivo that regulates collective cellular dynamics and behaviour, while the microfluidic channels surrounding the collagen microchamber arrays allow one to impose complex concentration gradients of specific biological molecules or drugs. We found that breast epithelial cells (MCF-10A) seeded in the microchambers formed lumen-like structures similar to those in epithelial layers. When MCF-10A cells were co-cultured with invasive breast cancer cells (MDA-MB-231), the formation of lumen-like structures in the microchambers was inhibited, indicating the capability of cancer cells to disrupt the structures formed by surrounding cells for further invasion and metastasis. Subsequent mechanism studies showed that down regulation of E-cad expression due to MMPs produced by the cancer cells plays a dominant role in determining the cellular behaviour. Our microfluidic system offers a robust platform for high throughput studies that aim to understand combinatorial effects of multiple biochemical and microenvironmental factors.

A zero-flow microfluidics for long-term cell culture and detection

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Shengbo Sang

2015-04-01

Full Text Available A zero-flow microfluidic design is proposed in this paper, which can be used for long-term cell culture and detection, especially for a lab-on-chip integrated with a biosensor. It consists of two parts: a main microchannel; and a circle microchamber. The Finite Element Method (FEM was employed to predict the fluid transport properties for a minimum fluid flow disturbance. Some commonly used microfluidic structures were also analysed systematically to prove the designed structure. Then the designed microfluidics was fabricated. Based on the simulations and experiments, this design provides a continuous flow environment, with a relatively stable and low shear stress atmosphere, similar to a zero-flow environment. Furthermore, the nutrients maintaining cells’ normal growth can be taken into the chamber through the diffusion effect. It also proves that the microfluidics can realize long-term cell culture and detection. The application of the structure in the field of biological microelectromechenical systems (BioMEMS will provide a research foundation for microfluidic technology.

Nucleic Acid-based Detection of Bacterial Pathogens Using Integrated Microfluidic Platform Systems

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Carl A. Batt

2009-05-01

Full Text Available The advent of nucleic acid-based pathogen detection methods offers increased sensitivity and specificity over traditional microbiological techniques, driving the development of portable, integrated biosensors. The miniaturization and automation of integrated detection systems presents a significant advantage for rapid, portable field-based testing. In this review, we highlight current developments and directions in nucleic acid-based micro total analysis systems for the detection of bacterial pathogens. Recent progress in the miniaturization of microfluidic processing steps for cell capture, DNA extraction and purification, polymerase chain reaction, and product detection are detailed. Discussions include strategies and challenges for implementation of an integrated portable platform.

Towards rapid prototyped convective microfluidic DNA amplification platform

Science.gov (United States)

Ajit, Smrithi; Praveen, Hemanth Mithun; Puneeth, S. B.; Dave, Abhishek; Sesham, Bharat; Mohan, K. N.; Goel, Sanket

2017-02-01

Today, Polymerase Chain Reaction (PCR) based DNA amplification plays an indispensable role in the field of biomedical research. Its inherent ability to exponentially amplify sample DNA has proven useful for the identification of virulent pathogens like those causing Multiple Drug-Resistant Tuberculosis (MDR-TB). The intervention of Microfluidics technology has revolutionized the concept of PCR from being a laborious and time consuming process into one that is faster, easily portable and capable of being multifunctional. The Microfluidics based PCR outweighs its traditional counterpart in terms of flexibility of varying reaction rate, operation simplicity, need of a fraction of volume and capability of being integrated with other functional elements. The scope of the present work involves the development of a real-time continuous flow microfluidic device, fabricated by 3D printing-governed rapid prototyping method, eventually leading to an automated and robust platform to process multiple DNA samples for detection of MDRTB-associated mutations. The thermal gradient characteristic to the PCR process is produced using peltier units appropriate to the microfluidic environment fully monitored and controlled by a low cost controller driven by a Data Acquisition System. The process efficiency achieved in the microfluidic environment in terms of output per cycle is expected to be on par with the traditional PCR and capable of earning the additional advantages of being faster and minimizing the handling.

Microfluidic device, and related methods

Science.gov (United States)

Wong, Eric W. (Inventor)

2010-01-01

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

A single microfluidic chip with dual surface properties for protein drug delivery.

Science.gov (United States)

Bokharaei, Mehrdad; Saatchi, Katayoun; Häfeli, Urs O

2017-04-15

Principles of double emulsion generation were incorporated in a glass microfluidic chip fabricated with two different surface properties in order to produce protein loaded polymer microspheres. The microspheres were produced by integrating two microfluidic flow focusing systems and a multi-step droplet splitting and mixing system into one chip. The chip consists of a hydrophobic and a hydrophilic section with two different heights, 12μm and 45μm, respectively. As a result, the protein is homogenously distributed throughout the polymer microsphere matrix, not just in its center (which has been studied before). In our work, the inner phase was bovine serum albumin (BSA) in phosphate buffered saline, the disperse phase was poly (lactic acid) in chloroform and the continuous phase was an aqueous solution of poly(vinyl alcohol). After solvent removal, BSA loaded microspheres with an encapsulation efficiency of up to 96% were obtained. Our results show the feasibility of producing microspheres loaded with a hydrophilic drug in a microfluidic system that integrates different microfluidic units into one chip. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic Apps for off-the-shelf instruments.

Science.gov (United States)

Mark, Daniel; von Stetten, Felix; Zengerle, Roland

2012-07-21

Within the last decade a huge increase in research activity in microfluidics could be observed. However, despite several commercial success stories, microfluidic chips are still not sold in high numbers in mass markets so far. Here we promote a new concept that could be an alternative approach to commercialization: designing microfluidic chips for existing off-the-shelf instruments. Such "Microfluidic Apps" could significantly lower market entry barriers and provide many advantages: developers of microfluidic chips make use of existing equipment or platforms and do not have to develop instruments from scratch; end-users can profit from microfluidics without the need to invest in new equipment; instrument manufacturers benefit from an expanded customer base due to the new applications that can be implemented in their instruments. Microfluidic Apps could be considered as low-cost disposables which can easily be distributed globally via web-shops. Therefore they could be a door-opener for high-volume mass markets.

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…

Cell manipulation in microfluidics

International Nuclear Information System (INIS)

Yun, Hoyoung; Kim, Kisoo; Lee, Won Gu

2013-01-01

Recent advances in the lab-on-a-chip field in association with nano/microfluidics have been made for new applications and functionalities to the fields of molecular biology, genetic analysis and proteomics, enabling the expansion of the cell biology field. Specifically, microfluidics has provided promising tools for enhancing cell biological research, since it has the ability to precisely control the cellular environment, to easily mimic heterogeneous cellular environment by multiplexing, and to analyze sub-cellular information by high-contents screening assays at the single-cell level. Various cell manipulation techniques in microfluidics have been developed in accordance with specific objectives and applications. In this review, we examine the latest achievements of cell manipulation techniques in microfluidics by categorizing externally applied forces for manipulation: (i) optical, (ii) magnetic, (iii) electrical, (iv) mechanical and (v) other manipulations. We furthermore focus on history where the manipulation techniques originate and also discuss future perspectives with key examples where available. (topical review)

Microfluidics for Antibiotic Susceptibility and Toxicity Testing

Directory of Open Access Journals (Sweden)

Jing Dai

2016-10-01

Full Text Available The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

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.

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

International Nuclear Information System (INIS)

Chung, Daehan; Gray, Bonnie L

2017-01-01

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

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

Science.gov (United States)

Chung, Daehan; Gray, Bonnie L.

2017-11-01

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

IR thermocycler for centrifugal microfluidic platform with direct on-disk wireless temperature measurement system

Science.gov (United States)

Burger, J.; Gross, A.; Mark, D.; Roth, G.; von Stetten, F.; Zengerle, R.

2011-06-01

The direct on-disk wireless temperature measurement system [1,2] presented at μTAS 2010 was further improved in its robustness. We apply it to an IR thermocycler as part of a centrifugal microfluidic analyzer for polymerase chain reactions (PCR). This IR thermocycler allows the very efficient direct heating of aqueous liquids in microfluidic cavities by an IR radiation source. The efficiency factor of this IR heating system depends on several parameters. First there is the efficiency of the IR radiator considering the transformation of electrical energy into radiation energy. This radiation energy needs to be focused by a reflector to the center of the cavity. Both, the reflectors shape and the quality of the reflecting layer affect the efficiency. On the way to the center of the cavity the radiation energy will be diminished by absorption in the surrounding air/humidity and especially in the cavity lid of the microfluidic disk. The transmission spectrum of the lid material and its thickness is of significant impact. We chose a COC polymer film with a thickness of 150 μm. At a peak frequency of the IR radiator of ~2 μm approximately 85 % of the incoming radiation energy passes the lid and is absorbed within the first 1.5 mm depth of liquid in the cavity. As we perform the thermocycling for a PCR, after heating to the denaturation temperature of ~ 92 °C we need to cool down rapidly to the primer annealing temperature of ~ 55 °C. Cooling is realized by 3 ventilators venting air of room temperature into the disk chamber. Due to the air flow itself and an additional rotation of the centrifugal microfluidic disk the PCR reagents in the cavities are cooled by forced air convection. Simulation studies based upon analogous electrical models enable to optimize the disk geometry and the optical path. Both the IR heater and the ventilators are controlled by the digital PID controller HAPRO 0135 [3]. The sampling frequency is set to 2 Hz. It could be further increased up

PREFACE: Nano- and microfluidics Nano- and microfluidics

Science.gov (United States)

Jacobs, Karin

2011-05-01

The field of nano- and microfluidics emerged at the end of the 1990s parallel to the demand for smaller and smaller containers and channels for chemical, biochemical and medical applications such as blood and DNS analysis [1], gene sequencing or proteomics [2, 3]. Since then, new journals and conferences have been launched and meanwhile, about two decades later, a variety of microfluidic applications are on the market. Briefly, 'the small flow becomes mainstream' [4]. Nevertheless, research in nano- and microfluidics is more than downsizing the spatial dimensions. For liquids on the nanoscale, surface and interface phenomena grow in importance and may even dominate the behavior in some systems. The studies collected in this special issue all concentrate on these type of systems and were part ot the priority programme SPP1164 'Nano- and Microfluidics' of the German Science Foundation (Deutsche Forschungsgemeinschaft, DFG). The priority programme was initiated in 2002 by Hendrik Kuhlmann and myself and was launched in 2004. Friction between a moving liquid and a solid wall may, for instance, play an important role so that the usual assumption of a no-slip boundary condition is no longer valid. Likewise, the dynamic deformations of soft objects like polymers, vesicles or capsules in flow arise from the subtle interplay between the (visco-)elasticity of the object and the viscous stresses in the surrounding fluid and, potentially, the presence of structures confining the flow like channels. Consequently, new theories were developed ( see articles in this issue by Münch and Wagner, Falk and Mecke, Bonthuis et al, Finken et al, Almenar and Rauscher, Straube) and experiments were set up to unambiguously demonstrate deviations from bulk, or 'macro', behavior (see articles in this issue by Wolff et al, Vinogradova and Belyaev, Hahn et al, Seemann et al, Grüner and Huber, Müller-Buschbaum et al, Gutsche et al, Braunmüller et al, Laube et al, Brücker, Nottebrock et al

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.

Using the Model Coupling Toolkit to couple earth system models

Science.gov (United States)

Warner, J.C.; Perlin, N.; Skyllingstad, E.D.

2008-01-01

Continued advances in computational resources are providing the opportunity to operate more sophisticated numerical models. Additionally, there is an increasing demand for multidisciplinary studies that include interactions between different physical processes. Therefore there is a strong desire to develop coupled modeling systems that utilize existing models and allow efficient data exchange and model control. The basic system would entail model "1" running on "M" processors and model "2" running on "N" processors, with efficient exchange of model fields at predetermined synchronization intervals. Here we demonstrate two coupled systems: the coupling of the ocean circulation model Regional Ocean Modeling System (ROMS) to the surface wave model Simulating WAves Nearshore (SWAN), and the coupling of ROMS to the atmospheric model Coupled Ocean Atmosphere Prediction System (COAMPS). Both coupled systems use the Model Coupling Toolkit (MCT) as a mechanism for operation control and inter-model distributed memory transfer of model variables. In this paper we describe requirements and other options for model coupling, explain the MCT library, ROMS, SWAN and COAMPS models, methods for grid decomposition and sparse matrix interpolation, and provide an example from each coupled system. Methods presented in this paper are clearly applicable for coupling of other types of models. ?? 2008 Elsevier Ltd. All rights reserved.

Paper-based microfluidics with high resolution, cut on a glass fiber membrane for bioassays.

Science.gov (United States)

Fang, Xueen; Wei, Shasha; Kong, Jilie

2014-03-07

In this report, we describe a simple, low-cost, straight forward and highly reproducible fabrication method of microfluidic systems. This system was cut on a glass fiber membrane by a common cutter without using any other sophisticated equipment or organic solvents. This format represents a novel type of paper-based microfluidics with high resolution of the microchannel down to ~137 μm, comparable to those made by conventional photolithography. We successfully applied this method to microfluidics to create a star micro-array format of multiplexed urine tests in this study.

Automated quantitative cytological analysis using portable microfluidic microscopy.

Science.gov (United States)

Jagannadh, Veerendra Kalyan; Murthy, Rashmi Sreeramachandra; Srinivasan, Rajesh; Gorthi, Sai Siva

2016-06-01

In this article, a portable microfluidic microscopy based approach for automated cytological investigations is presented. Inexpensive optical and electronic components have been used to construct a simple microfluidic microscopy system. In contrast to the conventional slide-based methods, the presented method employs microfluidics to enable automated sample handling and image acquisition. The approach involves the use of simple in-suspension staining and automated image acquisition to enable quantitative cytological analysis of samples. The applicability of the presented approach to research in cellular biology is shown by performing an automated cell viability assessment on a given population of yeast cells. Further, the relevance of the presented approach to clinical diagnosis and prognosis has been demonstrated by performing detection and differential assessment of malaria infection in a given sample. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Microfluidic fuel cells and batteries

CERN Document Server

Kjeang, Erik

2014-01-01

Microfluidic fuel cells and batteries represent a special type of electrochemical power generators that can be miniaturized and integrated in a microfluidic chip. Summarizing the initial ten years of research and development in this emerging field, this SpringerBrief is the first book dedicated to microfluidic fuel cell and battery technology for electrochemical energy conversion and storage. Written at a critical juncture, where strategically applied research is urgently required to seize impending technology opportunities for commercial, analytical, and educational utility, the intention is

Radio frequency feedback method for parallelized droplet microfluidics

KAUST Repository

Conchouso Gonzalez, David

2016-12-19

This paper reports on a radio frequency micro-strip T-resonator that is integrated to a parallel droplet microfluidic system. The T-resonator works as a feedback system to monitor uniform droplet production and to detect, in real-time, any malfunctions due to channel fouling or clogging. Emulsions at different W/O flow-rate ratios are generated in a microfluidic device containing 8 parallelized generators. These emulsions are then guided towards the RF sensor, which is then read using a Network Analyzer to obtain the frequency response of the system. The proposed T-resonator shows frequency shifts of 45MHz for only 5% change in the emulsion\\'s water in oil content. These shifts can then be used as a feedback system to trigger alarms and notify production and quality control engineers about problems in the droplet generation process.

Radio frequency feedback method for parallelized droplet microfluidics

KAUST Repository

Conchouso Gonzalez, David; Carreno, Armando Arpys Arevalo; McKerricher, Garret; Castro, David; Foulds, Ian G.

2016-01-01

This paper reports on a radio frequency micro-strip T-resonator that is integrated to a parallel droplet microfluidic system. The T-resonator works as a feedback system to monitor uniform droplet production and to detect, in real-time, any malfunctions due to channel fouling or clogging. Emulsions at different W/O flow-rate ratios are generated in a microfluidic device containing 8 parallelized generators. These emulsions are then guided towards the RF sensor, which is then read using a Network Analyzer to obtain the frequency response of the system. The proposed T-resonator shows frequency shifts of 45MHz for only 5% change in the emulsion's water in oil content. These shifts can then be used as a feedback system to trigger alarms and notify production and quality control engineers about problems in the droplet generation process.

Development of Plate Reader and On-Line Microfluidic Screening to Identify Ligands of the 5-Hydroxytryptamine Binding Protein in Venoms

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Reka A. Otvos

2015-06-01

Full Text Available The 5-HT3 receptor is a ligand-gated ion channel, which is expressed in the nervous system. Its antagonists are used clinically for treatment of postoperative- and radiotherapy-induced emesis and irritable bowel syndrome. In order to better understand the structure and function of the 5-HT3 receptor, and to allow for compound screening at this receptor, recently a serotonin binding protein (5HTBP was engineered with the Acetylcholine Binding Protein as template. In this study, a fluorescence enhancement assay for 5HTBP ligands was developed in plate-reader format and subsequently used in an on-line microfluidic format. Both assay types were validated using an existing radioligand binding assay. The on-line microfluidic assay was coupled to HPLC via a post-column split which allowed parallel coupling to a mass spectrometer to collect MS data. This high-resolution screening (HRS system is well suitable for compound mixture analysis. As a proof of principle, the venoms of Dendroapsis polylepis, Pseudonaja affinis and Pseudonaja inframacula snakes were screened and the accurate masses of the found bioactives were established. To demonstrate the subsequent workflow towards structural identification of bioactive proteins and peptides, the partial amino acid sequence of one of the bioactives from the Pseudonaja affinis venom was determined using a bottom-up proteomics approach.

Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection

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André Darveau

2007-09-01

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

A light writable microfluidic "flash memory": optically addressed actuator array with latched operation for microfluidic applications.

Science.gov (United States)

Hua, Zhishan; Pal, Rohit; Srivannavit, Onnop; Burns, Mark A; Gulari, Erdogan

2008-03-01

This paper presents a novel optically addressed microactuator array (microfluidic "flash memory") with latched operation. Analogous to the address-data bus mediated memory address protocol in electronics, the microactuator array consists of individual phase-change based actuators addressed by localized heating through focused light patterns (address bus), which can be provided by a modified projector or high power laser pointer. A common pressure manifold (data bus) for the entire array is used to generate large deflections of the phase change actuators in the molten phase. The use of phase change material as the working media enables latched operation of the actuator array. After the initial light "writing" during which the phase is temporarily changed to molten, the actuated status is self-maintained by the solid phase of the actuator without power and pressure inputs. The microfluidic flash memory can be re-configured by a new light illumination pattern and common pressure signal. The proposed approach can achieve actuation of arbitrary units in a large-scale array without the need for complex external equipment such as solenoid valves and electrical modules, which leads to significantly simplified system implementation and compact system size. The proposed work therefore provides a flexible, energy-efficient, and low cost multiplexing solution for microfluidic applications based on physical displacements. As an example, the use of the latched microactuator array as "normally closed" or "normally open" microvalves is demonstrated. The phase-change wax is fully encapsulated and thus immune from contamination issues in fluidic environments.

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.

Microfluidic Organ-on-a-Chip Models of Human IntestineSummary

Directory of Open Access Journals (Sweden)

Amir Bein

Full Text Available Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine. Keywords: Organs-on-Chips, Gut-on-a-Chip, Intestine-on-a-Chip, Microfluidic

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

Science.gov (United States)

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

2012-10-21

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

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)

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.

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

DEFF Research Database (Denmark)

Perozziello, Gerardo; Bundgaard, Frederik; Geschke, Oliver

2008-01-01

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

Recent results of the investigation of a micro-fluidic sampling chip and sampling system for hot cell aqueous processing streams

International Nuclear Information System (INIS)

Tripp, J.; Smith, T.; Law, J.

2013-01-01

A Fuel Cycle Research and Development project has investigated an innovative sampling method that could evolve into the next generation sampling and analysis system for metallic elements present in aqueous processing streams. Initially sampling technologies were evaluated and micro-fluidic sampling chip technology was selected and tested. A conceptual design for a fully automated microcapillary-based system was completed and a robotic automated sampling system was fabricated. The mechanical and sampling operation of the completed sampling system was investigated. Different sampling volumes have been tested. It appears that the 10 μl volume has produced data that had much smaller relative standard deviations than the 2 μl volume. In addition, the production of a less expensive, mass produced sampling chip was investigated to avoid chip reuse thus increasing sampling reproducibility/accuracy. The micro-fluidic-based robotic sampling system's mechanical elements were tested to ensure analytical reproducibility and the optimum robotic handling of micro-fluidic sampling chips. (authors)

Pulsed laser triggered high speed microfluidic switch

Science.gov (United States)

Wu, Ting-Hsiang; Gao, Lanyu; Chen, Yue; Wei, Kenneth; Chiou, Pei-Yu

2008-10-01

We report a high-speed microfluidic switch capable of achieving a switching time of 10 μs. The switching mechanism is realized by exciting dynamic vapor bubbles with focused laser pulses in a microfluidic polydimethylsiloxane (PDMS) channel. The bubble expansion deforms the elastic PDMS channel wall and squeezes the adjacent sample channel to control its fluid and particle flows as captured by the time-resolved imaging system. A switching of polystyrene microspheres in a Y-shaped channel has also been demonstrated. This ultrafast laser triggered switching mechanism has the potential to advance the sorting speed of state-of-the-art microscale fluorescence activated cell sorting devices.

Operation placement for application-specific digital microfluidic biochips

DEFF Research Database (Denmark)

Alistar, Mirela; Pop, Paul; Madsen, Jan

2013-01-01

Microfluidic-based biochips are replacing the conventional biochemical analyzers, and are able to integrate onchip all the necessary functions for biochemical analysis using microfluidics. The digital microfluidic biochips are based on the manipulation of liquids not as a continuous flow......, but as discrete droplets on an array of electrodes. Microfluidic operations, such as transport, mixing, split, are performed on this array by routing the corresponding droplets on a series of electrodes. Researchers have proposed several approaches for the synthesis of digital microfluidic biochips. All previous...

Automated Microfluidic Platform for Serial Polymerase Chain Reaction and High-Resolution Melting Analysis.

Science.gov (United States)

Cao, Weidong; Bean, Brian; Corey, Scott; Coursey, Johnathan S; Hasson, Kenton C; Inoue, Hiroshi; Isano, Taisuke; Kanderian, Sami; Lane, Ben; Liang, Hongye; Murphy, Brian; Owen, Greg; Shinoda, Nobuhiko; Zeng, Shulin; Knight, Ivor T

2016-06-01

We report the development of an automated genetic analyzer for human sample testing based on microfluidic rapid polymerase chain reaction (PCR) with high-resolution melting analysis (HRMA). The integrated DNA microfluidic cartridge was used on a platform designed with a robotic pipettor system that works by sequentially picking up different test solutions from a 384-well plate, mixing them in the tips, and delivering mixed fluids to the DNA cartridge. A novel image feedback flow control system based on a Canon 5D Mark II digital camera was developed for controlling fluid movement through a complex microfluidic branching network without the use of valves. The same camera was used for measuring the high-resolution melt curve of DNA amplicons that were generated in the microfluidic chip. Owing to fast heating and cooling as well as sensitive temperature measurement in the microfluidic channels, the time frame for PCR and HRMA was dramatically reduced from hours to minutes. Preliminary testing results demonstrated that rapid serial PCR and HRMA are possible while still achieving high data quality that is suitable for human sample testing. © 2015 Society for Laboratory Automation and Screening.

Open-source, community-driven microfluidics with Metafluidics.

Science.gov (United States)

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

2017-06-07

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

Microfluidic mixing through oscillatory transverse perturbations

Science.gov (United States)

Wu, J. W.; Xia, H. M.; Zhang, Y. Y.; Zhu, P.

2018-05-01

Fluid mixing in miniaturized fluidic devices is a challenging task. In this work, the mixing enhancement through oscillatory transverse perturbations coupling with divergent circular chambers is studied. To simplify the design, an autonomous microfluidic oscillator is used to produce the oscillatory flow. It is then applied to four side-channels that intersect with a central channel of constant flow. The mixing performance is tested at high fluid viscosities of up to 16 cP. Results show that the oscillatory flow can cause strong transverse perturbations which effectively enhance the mixing. The influence of a fluidic capacitor in the central channel is also examined, which at low viscosities can intensify the perturbations and further improve the mixing.

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

Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations.

Science.gov (United States)

Waldbaur, Ansgar; Kittelmann, Jörg; Radtke, Carsten P; Hubbuch, Jürgen; Rapp, Bastian E

2013-06-21

We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS). A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS. The concept allows complete freedom of design for the microfluidic chip itself. In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS. Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer. Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry.

Microfluidic systems with ion-selective membranes.

Science.gov (United States)

Slouka, Zdenek; Senapati, Satyajyoti; Chang, Hsueh-Chia

2014-01-01

When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.

Microfluidics: an enabling screening technology for enhanced oil recovery (EOR).

Science.gov (United States)

Lifton, Victor A

2016-05-21

Oil production is a critical industrial process that affects the entire world population and any improvements in its efficiency while reducing its environmental impact are of utmost societal importance. The paper reviews recent applications of microfluidics and microtechnology to study processes of oil extraction and recovery. It shows that microfluidic devices can be useful tools in investigation and visualization of such processes used in the oil & gas industry as fluid propagation, flooding, fracturing, emulsification and many others. Critical macro-scale processes that define oil extraction and recovery are controlled by the micro-scale processes based on wetting, adhesion, surface tension, colloids and other concepts of microfluidics. A growing number of research efforts demonstrates that microfluidics is becoming, albeit slowly, an accepted methodology in this area. We propose several areas of development where implementation of microfluidics may bring about deeper understanding and hence better control over the processes of oil recovery based on fluid propagation, droplet generation, wettability control. Studies of processes such as hydraulic fracturing, sand particle propagation in porous networks, high throughput screening of chemicals (for example, emulsifiers and surfactants) in microfluidic devices that simulate oil reservoirs are proposed to improve our understanding of these complicated physico-chemical systems. We also discuss why methods of additive manufacturing (3D printing) should be evaluated for quick prototyping and modification of the three-dimensional structures replicating natural oil-bearing rock formations for studies accessible to a wider audience of researchers.

Microfluidic and nanofluidic phase behaviour characterization for industrial CO2, oil and gas.

Science.gov (United States)

Bao, Bo; Riordon, Jason; Mostowfi, Farshid; Sinton, David

2017-08-08

Microfluidic systems that leverage unique micro-scale phenomena have been developed to provide rapid, accurate and robust analysis, predominantly for biomedical applications. These attributes, in addition to the ability to access high temperatures and pressures, have motivated recent expanded applications in phase measurements relevant to industrial CO 2 , oil and gas applications. We here present a comprehensive review of this exciting new field, separating microfluidic and nanofluidic approaches. Microfluidics is practical, and provides similar phase properties analysis to established bulk methods with advantages in speed, control and sample size. Nanofluidic phase behaviour can deviate from bulk measurements, which is of particular relevance to emerging unconventional oil and gas production from nanoporous shale. In short, microfluidics offers a practical, compelling replacement of current bulk phase measurement systems, whereas nanofluidics is not practical, but uniquely provides insight into phase change phenomena at nanoscales. Challenges, trends and opportunities for phase measurements at both scales are highlighted.

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

Science.gov (United States)

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

2015-11-09

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

A microfluidic timer for timed valving and pumping in centrifugal microfluidics.

Science.gov (United States)

Schwemmer, F; Zehnle, S; Mark, D; von Stetten, F; Zengerle, R; Paust, N

2015-03-21

Accurate timing of microfluidic operations is essential for the automation of complex laboratory workflows, in particular for the supply of sample and reagents. Here we present a new unit operation for timed valving and pumping in centrifugal microfluidics. It is based on temporary storage of pneumatic energy and time delayed sudden release of said energy. The timer is loaded at a relatively higher spinning frequency. The countdown is started by reducing to a relatively lower release frequency, at which the timer is released after a pre-defined delay time. We demonstrate timing for 1) the sequential release of 4 liquids at times of 2.7 s ± 0.2 s, 14.0 s ± 0.5 s, 43.4 s ± 1.0 s and 133.8 s ± 2.3 s, 2) timed valving of typical assay reagents (contact angles 36-78°, viscosities 0.9-5.6 mPa s) and 3) on demand valving of liquids from 4 inlet chambers in any user defined sequence controlled by the spinning protocol. The microfluidic timer is compatible to all wetting properties and viscosities of common assay reagents and does neither require assistive equipment, nor coatings. It can be monolithically integrated into a microfluidic test carrier and is compatible to scalable fabrication technologies such as thermoforming or injection molding.

Materials for Microfluidic Immunoassays: A Review.

Science.gov (United States)

Mou, Lei; Jiang, Xingyu

2017-08-01

Conventional immunoassays suffer from at least one of these following limitations: long processing time, high costs, poor user-friendliness, technical complexity, poor sensitivity and specificity. Microfluidics, a technology characterized by the engineered manipulation of fluids in channels with characteristic lengthscale of tens of micrometers, has shown considerable promise for improving immunoassays that could overcome these limitations in medical diagnostics and biology research. The combination of microfluidics and immunoassay can detect biomarkers with faster assay time, reduced volumes of reagents, lower power requirements, and higher levels of integration and automation compared to traditional approaches. This review focuses on the materials-related aspects of the recent advances in microfluidics-based immunoassays for point-of-care (POC) diagnostics of biomarkers. We compare the materials for microfluidic chips fabrication in five aspects: fabrication, integration, function, modification and cost, and describe their advantages and drawbacks. In addition, we review materials for modifying antibodies to improve the performance of the reaction of immunoassay. We also review the state of the art in microfluidic immunoassays POC platforms, from the laboratory to routine clinical practice, and also commercial products in the market. Finally, we discuss the current challenges and future developments in microfluidic immunoassays. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Stack air-breathing membraneless glucose microfluidic biofuel cell

International Nuclear Information System (INIS)

Galindo-de-la-Rosa, J; Moreno-Zuria, A; Vallejo-Becerra, V; Guerra-Balcázar, M; Ledesma-García, J; Arjona, N; Arriaga, L G

2016-01-01

A novel stacked microfluidic fuel cell design comprising re-utilization of the anodic and cathodic solutions on the secondary cell is presented. This membraneless microfluidic fuel cell employs porous flow-through electrodes in a “V”-shape cell architecture. Enzymatic bioanodic arrays based on glucose oxidase were prepared by immobilizing the enzyme onto Toray carbon paper electrodes using tetrabutylammonium bromide, Nafion and glutaraldehyde. These electrodes were characterized through the scanning electrochemical microscope technique, evidencing a good electrochemical response due to the electronic transference observed with the presence of glucose over the entire of the electrode. Moreover, the evaluation of this microfluidic fuel cell with an air-breathing system in a double-cell mode showed a performance of 0.8951 mWcm -2 in a series connection (2.2822mAcm -2 , 1.3607V), and 0.8427 mWcm -2 in a parallel connection (3.5786mAcm -2 , 0.8164V). (paper)

A simple method for preparation of macroporous polydimethylsiloxane membrane for microfluidic chip-based isoelectric focusing applications

Energy Technology Data Exchange (ETDEWEB)

Ou Junjie [Department of Mechanical and Mechatronics Engineering, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada); Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada); Ren, Carolyn L., E-mail: c3ren@mecheng1.uwaterloo.ca [Department of Mechanical and Mechatronics Engineering, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada); Pawliszyn, Janusz [Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada)

2010-03-10

A new, simple method was reported to prepare PDMS membranes with micrometer size pores for microfluidic chip applications. The pores were formed by adding polystyrene and toluene into PDMS prepolymer solution prior to spin-coating and curing. The resulting PDMS membrane has a thickness of around 10 {mu}m and macropores with a diameter ranging from 1 to 2 {mu}m measured using scanning electron microscope (SEM) imaging. This PDMS membrane was validated by integrating it with PDMS microfluidic chips for protein separation using isoelectric focusing mechanism coupled with whole channel imaging detection (IEF-WCID). It has been shown that five standard pI markers and a mixture of two proteins, myoglobin and {beta}-lactoglobulin, can be separated using these chips. The results indicated that this macroporous PDMS membrane can replace the dialysis membrane in PDMS chips for the IEF-WCID technique. The preparation method of macroporous PDMS membrane may be potentially applied in other fields of microfluidic chips.

CD-Based Microfluidics for Primary Care in Extreme Point-of-Care Settings

Directory of Open Access Journals (Sweden)

Suzanne Smith

2016-01-01

Full Text Available We review the utility of centrifugal microfluidic technologies applied to point-of-care diagnosis in extremely under-resourced environments. The various challenges faced in these settings are showcased, using areas in India and Africa as examples. Measures for the ability of integrated devices to effectively address point-of-care challenges are highlighted, and centrifugal, often termed CD-based microfluidic technologies, technologies are presented as a promising platform to address these challenges. We describe the advantages of centrifugal liquid handling, as well as the ability of a standard CD player to perform a number of common laboratory tests, fulfilling the role of an integrated lab-on-a-CD. Innovative centrifugal approaches for point-of-care in extremely resource-poor settings are highlighted, including sensing and detection strategies, smart power sources and biomimetic inspiration for environmental control. The evolution of centrifugal microfluidics, along with examples of commercial and advanced prototype centrifugal microfluidic systems, is presented, illustrating the success of deployment at the point-of-care. A close fit of emerging centrifugal systems to address a critical panel of tests for under-resourced clinic settings, formulated by medical experts, is demonstrated. This emphasizes the potential of centrifugal microfluidic technologies to be applied effectively to extremely challenging point-of-care scenarios and in playing a role in improving primary care in resource-limited settings across the developing world.

Lab-on-chip system combining a microfluidic-ELISA with an array of amorphous silicon photosensors for the detection of celiac disease epitopes

Directory of Open Access Journals (Sweden)

Francesca Costantini

2015-12-01

Full Text Available This work presents a lab-on-chip system, which combines a glass-polydimethilsiloxane microfluidic network and an array of amorphous silicon photosensors for the diagnosis and follow-up of Celiac disease. The microfluidic chip implements an on-chip enzyme-linked immunosorbent assay (ELISA, relying on a sandwich immunoassay between antibodies against gliadin peptides (GPs and a secondary antibody marked with horseradish peroxidase (Ig-HRP. This enzyme catalyzes a chemiluminescent reaction, whose light intensity is detected by the amorphous silicon photosensors and transduced into an electrical signal that can be processed to recognize the presence of antibodies against GPs in the serum of people affected by Celiac syndrome.The correct operation of the developed lab-on-chip has been demonstrated using rabbit serum in the microfluidic ELISA. In particular, optimizing the dilution factors of both sera and Ig-HRP samples in the flowing solutions, the specific and non-specific antibodies against GPs can be successfully distinguished, showing the suitability of the presented device to effectively screen celiac disease epitopes. Keywords: Lab-on-chip, Celiac disease, Microfluidics, On-chip detection, ELISA, Amorphous silicon photosensors

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.

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

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

Laser micromachined wax-covered plastic paper as both sputter deposition shadow masks and deep-ultraviolet patterning masks for polymethylmethacrylate-based microfluidic systems

KAUST Repository

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

2013-01-01

We report a technically innovative method of fabricating masks for both deep-ultraviolet (UV) patterning and metal sputtering on polymethylmethacrylate (PMMA) for microfluidic systems. We used a CO2 laser system to cut the required patterns on wax

DNA microarrays immobilized on unmodified plastics in a microfluidic biochip for rapid typing of Avian Influenza Virus

DEFF Research Database (Denmark)

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

2011-01-01

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 that UV irradiation can be used to d...

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.

Translation-coupling systems

Science.gov (United States)

Pfleger, Brian; Mendez-Perez, Daniel

2013-11-05

Disclosed are systems and methods for coupling translation of a target gene to a detectable response gene. A version of the invention includes a translation-coupling cassette. The translation-coupling cassette includes a target gene, a response gene, a response-gene translation control element, and a secondary structure-forming sequence that reversibly forms a secondary structure masking the response-gene translation control element. Masking of the response-gene translation control element inhibits translation of the response gene. Full translation of the target gene results in unfolding of the secondary structure and consequent translation of the response gene. Translation of the target gene is determined by detecting presence of the response-gene protein product. The invention further includes RNA transcripts of the translation-coupling cassettes, vectors comprising the translation-coupling cassettes, hosts comprising the translation-coupling cassettes, methods of using the translation-coupling cassettes, and gene products produced with the translation-coupling cassettes.

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

Directory of Open Access Journals (Sweden)

Mohamed Yafia

2015-09-01

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

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.

Investigation of endothelial growth using a sensors-integrated microfluidic system to simulate physiological barriers

Directory of Open Access Journals (Sweden)

Rajabi Taleieh

2015-09-01

Full Text Available In this paper we present a microfluidic system based on transparent biocompatible polymers with a porous membrane as substrate for various cell types which allows the simulation of various physiological barriers under continuous laminar flow conditions at distinct tunable shear rates. Besides live cell and fluorescence microscopy, integrated electrodes enable the investigation of the permeability and barrier function of the cell layer as well as their interaction with external manipulations using the Electric Cell-substrate Impedance Sensing (ECIS method.

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.

Towards Biofilm Spectroscopy - A Novel Microfluidic Approach for Characterizing Biofilm Subpopulation by Microwave-Based Electrical Impedance Spectroscopy

Science.gov (United States)

Richter, Christiane; Schneider, Stefan; Rapp, Bastian E.; Schmidt, Sönke; Schüßler, Martin; Jakoby, Rolf; Bruchmann, Julia; Bischer, Moritz; Schwartz, Thomas

2018-03-01

In this work three disciplines - microfluidics, microbiology and microwave engineering - are utilized to develop a system for analyzing subpopulations of biofilms and their reaction to antibiotic treatment. We present handling strategies to destabilize a biofilm inside a microfluidic system down to aggregate sizes ofbiofilm effects.

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

Science.gov (United States)

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

2013-11-07

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

Electrochemistry, biosensors and microfluidics: a convergence of fields.

Science.gov (United States)

Rackus, Darius G; Shamsi, Mohtashim H; Wheeler, Aaron R

2015-08-07

Electrochemistry, biosensors and microfluidics are popular research topics that have attracted widespread attention from chemists, biologists, physicists, and engineers. Here, we introduce the basic concepts and recent histories of electrochemistry, biosensors, and microfluidics, and describe how they are combining to form new application-areas, including so-called "point-of-care" systems in which measurements traditionally performed in a laboratory are moved into the field. We propose that this review can serve both as a useful starting-point for researchers who are new to these topics, as well as being a compendium of the current state-of-the art for experts in these evolving areas.

Shannon Meets Fick on the Microfluidic Channel: Diffusion Limit to Sum Broadcast Capacity for Molecular Communication.

Science.gov (United States)

Bicen, A Ozan; Lehtomaki, Janne J; Akyildiz, Ian F

2018-03-01

Molecular communication (MC) over a microfluidic channel with flow is investigated based on Shannon's channel capacity theorem and Fick's laws of diffusion. Specifically, the sum capacity for MC between a single transmitter and multiple receivers (broadcast MC) is studied. The transmitter communicates by using different types of signaling molecules with each receiver over the microfluidic channel. The transmitted molecules propagate through microfluidic channel until reaching the corresponding receiver. Although the use of different types of molecules provides orthogonal signaling, the sum broadcast capacity may not scale with the number of the receivers due to physics of the propagation (interplay between convection and diffusion based on distance). In this paper, the performance of broadcast MC on a microfluidic chip is characterized by studying the physical geometry of the microfluidic channel and leveraging the information theory. The convergence of the sum capacity for microfluidic broadcast channel is analytically investigated based on the physical system parameters with respect to the increasing number of molecular receivers. The analysis presented here can be useful to predict the achievable information rate in microfluidic interconnects for the biochemical computation and microfluidic multi-sample assays.

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.

Microfluidic Cytometer for Complete Blood Count Analysis, Phase II

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National Aeronautics and Space Administration — We will fabricate and test microfluidic designs for a micro-electromechanical system based complete blood count (CBC) analysis in separate modules and integrate them...

Design and development of a microfluidic platform for use with colorimetric gold nanoprobe assays

Science.gov (United States)

Bernacka-Wojcik, Iwona

Due to the importance and wide applications of the DNA analysis, there is a need to make genetic analysis more available and more affordable. As such, the aim of this PhD thesis is to optimize a colorimetric DNA biosensor based on gold nanoprobes developed in CEMOP by reducing its price and the needed volume of solution without compromising the device sensitivity and reliability, towards the point of care use. Firstly, the price of the biosensor was decreased by replacing the silicon photodetector by a low cost, solution processed TiO2 photodetector. To further reduce the photodetector price, a novel fabrication method was developed: a cost-effective inkjet printing technology that enabled to increase TiO2 surface area. Secondly, the DNA biosensor was optimized by means of microfluidics that offer advantages of miniaturization, much lower sample/reagents consumption, enhanced system performance and functionality by integrating different components. In the developed microfluidic platform, the optical path length was extended by detecting along the channel and the light was transmitted by optical fibres enabling to guide the light very close to the analysed solution. Microfluidic chip of high aspect ratio ( 13), smooth and nearly vertical sidewalls was fabricated in PDMS using a SU-8 mould for patterning. The platform coupled to the gold nanoprobe assay enabled detection of Mycobacterium tuberculosis using 3 mul on DNA solution, i.e. 20 times less than in the previous state-of-the-art. Subsequently, the bio-microfluidic platform was optimized in terms of cost, electrical signal processing and sensitivity to colour variation, yielding 160% improvement of colorimetric AuNPs analysis. Planar microlenses were incorporated to converge light into the sample and then to the output fibre core increasing 6 times the signal-to-losses ratio. The optimized platform enabled detection of single nucleotide polymorphism related with obesity risk (FTO) using target DNA concentration

Wirelessly powered microfluidic dielectrophoresis devices using printable RF circuits.

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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

Patterned Fibers Embedded Microfluidic Chips Based on PLA and PDMS for Ag Nanoparticle Safety Testing

Directory of Open Access Journals (Sweden)

Yaowen Liu

2016-11-01

Full Text Available A new method to integrate poly-dl-lactide (PLA patterned electrospun fibers with a polydimethylsiloxane (PDMS microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP. In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles.

Design and Simulation of a T-Type Lymphocyte Cells Filter on a Microfluidic System

Directory of Open Access Journals (Sweden)

Daniel A. Quiroga T.

2016-01-01

Full Text Available This work consisted in designing and validating, by experimental computational simulation, a T-Lymphocites filtering system based on microfluidics for hiv virus detection. Material and methods: It was used AutoDesk® Inventor simulation tool was used with which the microflui­dic system design was performed. The filter system was tested by a computer simulation in the AutoDesk® Simulation cfd (computational fluid dynamics software, simulation tool in which different particles with different diameters (5 μm, 10 μm, 15 μm flow through the system to test. Results and conclusions: Results showed that this system allowed to pass the expected particles, however, it also was observed that it allows bigger particles than desired, for this reason it is neces­sary to keep on working on system perfectioning. Filtering system efficiency was of a 33.33 %.

A microfluidic platform for generating large-scale nearly identical human microphysiological system arrays

Science.gov (United States)

Hsu, Yu-Hsiang; Moya, Monica L.; Hughes, Christopher C.W.; Georgea, Steven C.; Lee, Abraham P.

2013-01-01

This paper reports a polydimethylsiloxane microfluidic model system that can develop an array of nearly identical human microtissues with interconnected vascular networks. The microfluidic system design is based on an analogy with an electric circuit, applying resistive circuit concepts to design pressure dividers in serially-connected microtissue chambers. A long microchannel (550, 620 and 775 mm) creates a resistive circuit with a large hydraulic resistance. Two media reservoirs with a large cross-sectional area and of different heights are connected to the entrance and exit of the long microchannel to serve as a pressure source, and create a near constant pressure drop along the long microchannel. Microtissue chambers (0.12 μl) serve as a two-terminal resistive component with an input impedance > 50-fold larger than the long microchannel. Connecting each microtissue chamber to two different positions along the long microchannel creates a series of pressure dividers. Each microtissue chamber enables a controlled pressure drop of a segment of the microchannel without altering the hydrodynamic behaviour of the microchannel. The result is a controlled and predictable microphysiological environment within the microchamber. Interstitial flow, a mechanical cue for stimulating vasculogenesis, was verified by finite element simulation and experiments. The simplicity of this design enabled the development of multiple microtissue arrays (5, 12, and 30 microtissues) by co-culturing endothelial cells, stromal cells, and fibrin within the microchambers over two and three week periods. This methodology enables the culturing of a large array of microtissues with interconnected vascular networks for biological studies and applications such as drug development. PMID:23723013

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.

Screening applications in drug discovery based on microfluidic technology

Science.gov (United States)

Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

Science.gov (United States)

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Fabrication of circular microfluidic network in enzymatically-crosslinked gelatin hydrogel

Energy Technology Data Exchange (ETDEWEB)

He, Jiankang, E-mail: jiankanghe@mail.xjtu.edu.cn; Chen, Ruomeng; Lu, Yongjie; Zhan, Li; Liu, Yaxiong; Li, Dichen; Jin, Zhongmin

2016-02-01

It is a huge challenge to engineer vascular networks in vital organ tissue engineering. Although the incorporation of artificial microfluidic network into thick tissue-engineered constructs has shown great promise, most of the existing microfluidic strategies are limited to generate rectangle cross-sectional channels rather than circular vessels in soft hydrogels. Here we present a facile approach to fabricate branched microfluidic network with circular cross-sections in gelatin hydrogels by combining micromolding and enzymatically-crosslinking mechanism. Partially crosslinked hydrogel slides with predefined semi-circular channels were molded, assembled and in situ fully crosslinked to form a seamless and circular microfluidic network. The bonding strength of the resultant gelatin hydrogels was investigated. The morphology and the dimension of the resultant circular channels were characterized using scanning electron microscopy (SEM) and micro-computerized tomography (μCT). Computational fluid dynamic simulation shows that the fabrication error had little effect on the distribution of flow field but affected the maximum velocity in comparison with designed models. The microfluidic gelatin hydrogel facilitates the attachment and spreading of human umbilical endothelial cells (HUVECs) to form a uniform endothelialized layer around the circular channel surface, which successfully exhibited barrier functions. The presented method might provide a simple way to fabricate circular microfluidic networks in biologically-relevant hydrogels to advance various applications of in vitro tissue models, organ-on-a-chip systems and tissue engineering. - Highlights: • A facile method was proposed to build a circular fluidic network in gelatin hydrogel. • The fluidic network is mechanically robust and supports physiological flow. • HUVECs formed endothelialized layer around the channel to express barrier function.

Multi-depth valved microfluidics for biofilm segmentation

International Nuclear Information System (INIS)

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

2015-01-01

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

Multi-depth valved microfluidics for biofilm segmentation

Science.gov (United States)

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

2015-09-01

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

Differential white cell count by centrifugal microfluidics.

Energy Technology Data Exchange (ETDEWEB)

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

2010-07-01

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

Quantum dot-based microfluidic biosensor for cancer detection

Science.gov (United States)

Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

2015-05-01

We report results of the studies relating to fabrication of an impedimetric microfluidic-based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium-tin-oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir-Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10-15 M to 10-11 M.

Merging microfluidics and sonochemistry: towards greener and more efficient micro-sono-reactors.

Science.gov (United States)

Fernandez Rivas, David; Cintas, Pedro; Gardeniers, Han J G E

2012-11-18

Microfluidics enable the manipulation of chemical reactions using very small amounts of fluid, in channels with dimensions of tens to hundreds of micrometers; so-called microstructured devices, from which the iconic image of chips emerges. The immediate attraction of microfluidics lies in its greenness: use of small quantities of reagents and solvents, and hence less waste, a precise control of reaction conditions, integration of functionality for process intensification, safer and often faster protocols, reliable scale-up, and possibility of performing multiphase reactions. Among the limitations found in microfluidics the facile formation of precipitating products should be highlighted, and in this context, the search for efficient mass and energy transfers is a must. Such limitations have been partially overcome with the aid of ultrasound in conventional flow systems, and can now be successfully used in microreactors, which provide new capabilities. Novel applications and a better understanding of the physical and chemical aspects of sonochemistry can certainly be achieved by combining microfluidics and ultrasound. We will review this nascent area of research, paying attention to the latest developments and showing future directions, which benefit both from the existing microfluidic technology and sonochemistry itself.

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

Science.gov (United States)

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

2013-10-07

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

Long-term brain slice culturing in a microfluidic platform

DEFF Research Database (Denmark)

Vedarethinam, Indumathi; Avaliani, N.; Tønnesen, J.

2011-01-01

In this work, we present the development of a transparent poly(methyl methacrylate) (PMMA) based microfluidic culture system for handling long-term brain slice cultures independent of an incubator. The different stages of system development have been validated by culturing GFP producing brain sli...

Complex Dynamics of Droplet Traffic in a Bifurcating Microfluidic Channel: Periodicity, Multistability, and Selection Rules

Science.gov (United States)

Sessoms, D. A.; Amon, A.; Courbin, L.; Panizza, P.

2010-10-01

The binary path selection of droplets reaching a T junction is regulated by time-delayed feedback and nonlinear couplings. Such mechanisms result in complex dynamics of droplet partitioning: numerous discrete bifurcations between periodic regimes are observed. We introduce a model based on an approximation that makes this problem tractable. This allows us to derive analytical formulae that predict the occurrence of the bifurcations between consecutive regimes, establish selection rules for the period of a regime, and describe the evolutions of the period and complexity of droplet pattern in a cycle with the key parameters of the system. We discuss the validity and limitations of our model which describes semiquantitatively both numerical simulations and microfluidic experiments.

Making the invisible visible: a microfluidic chip using a low refractive index polymer.

Science.gov (United States)

Hanada, Yasutaka; Ogawa, Tatsuya; Koike, Kazuhiko; Sugioka, Koji

2016-07-07

Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries.

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.

Paper-Based Digital Microfluidic Chip for Multiple Electrochemical Assay Operated by a Wireless Portable Control System

DEFF Research Database (Denmark)

Ruecha, Nipapan; Lee, Jumi; Chae, Heedo

2017-01-01

for multiple analysis assays are fabricated by affordable printing techniques. For enhanced sensitivity of the sensor, the working electrode is modified through the electrochemical method, namely by reducing graphene with voltammetry and coating gold nanoparticles by amperometry. Detachable sensor and absorber...... designed portable power supply and wireless control system, the active paper-based chip platform can be utilized as an advanced point-of-care device for multiple assays in digital microfluidics....

Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

International Nuclear Information System (INIS)

Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y.S.

2016-01-01

Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe 3 O 4 ) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY’S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis. - Highlights: • Homogeneous field yields an aggregation of particles along the lines of the field. • Additional electromagnet field rotates the

Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

Energy Technology Data Exchange (ETDEWEB)

Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y.S.

2016-03-01

Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe{sub 3}O{sub 4}) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY’S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis. - Highlights: • Homogeneous field yields an aggregation of particles along the lines of the field. • Additional electromagnet field rotates the

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.

Material Biocompatibility for PCR Microfluidic Chips

KAUST Repository

Kodzius, Rimantas

2010-04-23

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

Material Biocompatibility for PCR Microfluidic Chips

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.

Microfluidic Flame Barrier

Science.gov (United States)

Mungas, Gregory S. (Inventor); Fisher, David J. (Inventor); Mungas, Christopher (Inventor)

2013-01-01

Propellants flow through specialized mechanical hardware that is designed for effective and safe ignition and sustained combustion of the propellants. By integrating a micro-fluidic porous media element between a propellant feed source and the combustion chamber, an effective and reliable propellant injector head may be implemented that is capable of withstanding transient combustion and detonation waves that commonly occur during an ignition event. The micro-fluidic porous media element is of specified porosity or porosity gradient selected to be appropriate for a given propellant. Additionally the propellant injector head design integrates a spark ignition mechanism that withstands extremely hot running conditions without noticeable spark mechanism degradation.

Routing-based synthesis of digital microfluidic biochips

DEFF Research Database (Denmark)

Maftei, Elena; Pop, Paul; Madsen, Jan

2012-01-01

Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the necessary functions for biochemical analysis. The “digital” biochips are manipulating liquids as discrete droplets on a two-dimensional array of electrodes. Basic microfluidic...... electrodes are considered occupied during the operation execution, although the droplet uses only one electrode at a time. Moreover, the operations can actually be performed by routing the droplets on any sequence of electrodes on the microfluidic array. Hence, in this paper, we eliminate the concept...... on the surface of the microfluidic array. We have extended the GRASP-based algorithm to consider contamination avoidance during routing-based synthesis. Several real-life examples and synthetic benchmarks are used to evaluate the proposed approaches....

Power Generation from Concentration Gradient by Reverse Electrodialysis in Dense Silica Membranes for Microfluidic and Nanofluidic Systems

Directory of Open Access Journals (Sweden)

Sang Woo Lee

2016-01-01

Full Text Available In this study, we investigate power generation by reverse electrodialysis in a dense silica membrane that is between two NaCl solutions with various combinations of concentrations. Each silica membrane is fabricated by depositing a silica layer on a porous alumina substrate via chemical vapor deposition. The measured potential-current (V-I characteristics of the silica membrane are used to obtain the transference number, diffusion potential, and electrical resistance. We develop empirical correlations for the transference number and the area-specific resistance, and present the results of power generation by reverse electrodialysis using the fabricated silica membranes. The highest measured power density is 0.98 mW/m2. In addition, we develop a contour map of the power density as a function of NaCl concentrations on the basis of the empirical correlations. The contour map shows that a power output density of 1.2 mW/m2 is achievable with the use of silica membranes and is sufficient to drive nanofluidic and microfluidic systems. The dense silica membrane has the potential for use in micro power generators in nanofluidic and microfluidic systems.

Microfluidic acoustophoretic force based low-concentration oil separation and detection from the environment.

Science.gov (United States)

Wang, Han; Liu, Zhongzheng; Kim, Sungman; Koo, Chiwan; Cho, Younghak; Jang, Dong-Young; Kim, Yong-Joe; Han, Arum

2014-03-07

Detecting and quantifying extremely low concentrations of oil from the environment have broad applications in oil spill monitoring in ocean and coastal areas as well as in oil leakage monitoring on land. Currently available methods for low-concentration oil detection are bulky or costly with limited sensitivities. Thus they are difficult to be used as portable and field-deployable detectors in the case of oil spills or for monitoring the long-term effects of dispersed oil on marine and coastal ecosystems. Here, we present a low-concentration oil droplet trapping and detection microfluidic system based on the acoustophoresis phenomenon where oil droplets in water having a negative acoustic contrast factor move towards acoustic pressure anti-nodes. By trapping oil droplets from water samples flowing through a microfluidic channel, even very low concentrations of oil droplets can be concentrated to a detectable level for further analyses, which is a significant improvement over currently available oil detection systems. Oil droplets in water were successfully trapped and accumulated in a circular acoustophoretic trapping chamber of the microfluidic device and detected using a custom-built compact fluorescent detector based on the natural fluorescence of the trapped crude oil droplets. After the on-line detection, crude oil droplets released from the trapping chamber were successfully separated into a collection outlet by acoustophoretic force for further off-chip analyses. The developed microfluidic system provides a new way of trapping, detecting, and separating low-concentration crude oil from environmental water samples and holds promise as a low-cost field-deployable oil detector with extremely high sensitivity. The microfluidic system and operation principle are expected to be utilized in a wide range of applications where separating, concentrating, and detecting small particles having a negative acoustic contrast factor are required.

Preface book Microfluidics for medical applications

NARCIS (Netherlands)

van den Berg, Albert; Segerink, Loes Irene

2015-01-01

This book presents an overview of the major microfluidics techniques and platforms used for medicine and medical applications, providing the reader with an overview of the recent developments in this field. It is divided in three parts: (1) tissue and organs on-chip, (2) microfluidics for medicine

Research highlights: microfluidics meets big data.

Science.gov (United States)

Tseng, Peter; Weaver, Westbrook M; Masaeli, Mahdokht; Owsley, Keegan; Di Carlo, Dino

2014-03-07

In this issue we highlight a collection of recent work in which microfluidic parallelization and automation have been employed to address the increasing need for large amounts of quantitative data concerning cellular function--from correlating microRNA levels to protein expression, increasing the throughput and reducing the noise when studying protein dynamics in single-cells, and understanding how signal dynamics encodes information. The painstaking dissection of cellular pathways one protein at a time appears to be coming to an end, leading to more rapid discoveries which will inevitably translate to better cellular control--in producing useful gene products and treating disease at the individual cell level. From these studies it is also clear that development of large scale mutant or fusion libraries, automation of microscopy, image analysis, and data extraction will be key components as microfluidics contributes its strengths to aid systems biology moving forward.

Microfluidic in-channel multi-electrode platform for neurotransmitter sensing

Science.gov (United States)

Kara, A.; Mathault, J.; Reitz, A.; Boisvert, M.; Tessier, F.; Greener, J.; Miled, A.

2016-03-01

In this project we present a microfluidic platform with in-channel micro-electrodes for in situ screening of bio/chemical samples through a lab-on-chip system. We used a novel method to incorporate electrochemical sensors array (16x20) connected to a PCB, which opens the way for imaging applications. A 200 μm height microfluidic channel was bonded to electrochemical sensors. The micro-channel contains 3 inlets used to introduce phosphate buffer saline (PBS), ferrocynide and neurotransmitters. The flow rate was controlled through automated micro-pumps. A multiplexer was used to scan electrodes and perform individual cyclic voltammograms by a custom potentiostat. The behavior of the system was linear in terms of variation of current versus concentration. It was used to detect the neurotransmitters serotonin, dopamine and glutamate.

Microfluidic PMMA interfaces for rectangular glass capillaries

International Nuclear Information System (INIS)

Evander, Mikael; Tenje, Maria

2014-01-01

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

Accumulation of BSA in Packed-bed Microfluidics

Science.gov (United States)

Summers, Samantha; Hu, Chuntian; Hartman, Ryan

2012-11-01

Alzheimers and Parkinsons are two diseases that are associated with protein deposition in the brain, causing loss of either cognitive or muscle functioning. Protein deposition diseases are considered progressive diseases since the continual aggregation of protein causes the patient's symptoms to slowly worsen over time. There are currently no known means of treatment for protein deposition diseases. Our goal is to understand the potential for packed-bed microfluidics to study protein accumulation. Measurement of the resistance to flow through micro-scale packed-beds is critical to understanding the process of protein accumulation. Aggregation in bulk is fundamentally different from accumulation on surfaces. Our study attempts to distinguish between either mechanism. The results from our experiments involving protein injection through a microfluidic system will be presented and discussed. Funding received by NSF REU Grant 1062611.

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

A Microfluidic Chip Based on Localized Surface Plasmon Resonance for Real-Time Monitoring of Antigen-Antibody Reactions

Science.gov (United States)

Hiep, Ha Minh; Nakayama, Tsuyoshi; Saito, Masato; Yamamura, Shohei; Takamura, Yuzuru; Tamiya, Eiichi

2008-02-01

Localized surface plasmon resonance (LSPR) connecting to noble metal nanoparticles is an important issue for many analytical and biological applications. Therefore, the development of microfluidic LSPR chip that allows studying biomolecular interactions becomes an essential requirement for micro total analysis systems (µTAS) integration. However, miniaturized process of the conventional surface plasmon resonance system has been faced with some limitations, especially with the usage of Kretschmann configuration in total internal reflection mode. In this study, we have tried to solve this problem by proposing a novel microfluidic LSPR chip operated with a simple collinear optical system. The poly(dimethylsiloxane) (PDMS) based microfluidic chip was fabricated by soft-lithography technique and enables to interrogate specific insulin and anti-insulin antibody reaction in real-time after immobilizing antibody on its surface. Moreover, the sensing ability of microfluidic LSPR chip was also evaluated with various glucose concentrations. The kinetic constant of insulin and anti-insulin antibody was determined and the detection limit of 100 ng/mL insulin was archived.

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

Science.gov (United States)

Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

2017-09-01

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Hardware/software co-design and optimization for cyberphysical integration in digital microfluidic biochips

CERN Document Server

Luo, Yan; Ho, Tsung-Yi

2015-01-01

This book describes a comprehensive framework for hardware/software co-design, optimization, and use of robust, low-cost, and cyberphysical digital microfluidic systems. Readers with a background in electronic design automation will find this book to be a valuable reference for leveraging conventional VLSI CAD techniques for emerging technologies, e.g., biochips or bioMEMS. Readers from the circuit/system design community will benefit from methods presented to extend design and testing techniques from microelectronics to mixed-technology microsystems. For readers from the microfluidics domain,

Manipulation of microfluidic droplets by electrorheological fluid

KAUST Repository

Zhang, Menying; Gong, Xiuqing; Wen, Weijia

2009-01-01

Microfluidics, especially droplet microfluidics, attracts more and more researchers from diverse fields, because it requires fewer materials and less time, produces less waste and has the potential of highly integrated and computer

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...

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.

Microfluidics for investigating vaso-occlusions in sickle cell disease.

Science.gov (United States)

Horton, Renita E

2017-07-01

SCD stems from amutation in the beta globin gene. Upon deoxygenation, hemoglobin polymerizes and triggers RBC remodeling. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications; unfortunately, the complex mechanisms that contribute to vaso-occlusions are not well understood. Vaso-occlusions can occur in post-capillary venules; hence, the microvasculature is a prime target for SCD therapies. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivo systems. However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and ECM presentation. This review, although not comprehensive, highlights microfluidic approaches that aim to improve our current understanding of the pathophysiological mechanisms surrounding SCD. Microfluidic platforms can aid in identifying factors that may contribute to disease severity and can serve as suitable test beds for novel treatment strategies which may improve patient outcomes. © 2017 John Wiley & Sons Ltd.

Development of droplets‐based microfluidic systems for single­‐cell high‐throughput screening

DEFF Research Database (Denmark)

Chen, Jun; Jensen, Thomas Glasdam; Godina, Alexei

2014-01-01

High-throughput screening (HTS) plays an important role in the development of microbial cell factories. One of the most popular approaches is to use microplates combined with the application of robotics, liquid handling and sophisticated detection methods. However, these workstations require large...... investment, and a logarithmic increase to screen large combinatorial libraries over the decades also makes it gradually out of depth. Here, we are trying to develop a feasible high‐throughput system that uses microfluidics to compartmentalize a single cell for propagation and analysis in monodisperse...... picoliter aqueous droplets surround by an immiscible fluorinated oil phase. Our aim is to use this system to facilitate the screening process for both the biotechnology and food industry....

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

Science.gov (United States)

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

2014-11-21

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

A micro-pillar array to trap magnetic beads in microfluidic systems

KAUST Repository

Gooneratne, Chinthaka Pasan

2012-12-01

A micro-pillar array (MPA) is proposed in this paper to trap and separate magnetic beads (MBs) in microfluidic systems. MBs are used in many biomedical applications due to being compatible in dimension to biomolecules, the large surface area available to attach biomolecules, and the fact that they can be controlled by a magnetic field. Trapping and separating these labeled biomolecules is an important step toward achieving reliable and accurate quantification for disease diagnostics. Nickel Iron (Ni50Fe 50) micro-pillars were fabricated on a Silicon (Si) substrate by standard microfabrication techniques. Experimental results showed that MBs could be trapped on the MPA at the single bead level and separated from other non-target particles. This principle can easily be extended to trap and separate target biomolecules in heterogeneous biological samples. © 2012 IEEE.

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

Real-time control of a microfluidic channel for size-independent deformability cytometry

International Nuclear Information System (INIS)

Guan, Guofeng; Chen, Peter C Y; Ong, Chong Jin; Peng, Weng Kung; Bhagat, Ali Asgar; Han, Jongyoon

2012-01-01

Mechanical properties of cells can be correlated with various cell states and are now considered as an important class of biophysical markers. Effectiveness of existing high-throughput microfluidic techniques for investigating cell mechanical properties is adversely affected by cell-size variation in a given cell population. In this work, we introduce a new microfluidic system with real-time feedback control to evaluate single-cell deformability while minimizing cell-size dependence of the measurement. Using breast cancer cells (MCF-7), we demonstrate the potential of this system for stiffness profiling of cells in complex, diverse cell populations. (paper)

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

Science.gov (United States)

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

2013-11-01

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

Enhanced performance of microfluidic soft pressure sensors with embedded solid microspheres

Science.gov (United States)

Shin, Hee-Sup; Ryu, Jaiyoung; Majidi, Carmel; Park, Yong-Lae

2016-02-01

The cross-sectional geometry of an embedded microchannel influences the electromechanical response of a soft microfluidic sensor to applied surface pressure. When a pressure is exerted on the surface of the sensor deforming the soft structure, the cross-sectional area of the embedded channel filled with a conductive fluid decreases, increasing the channel’s electrical resistance. This electromechanical coupling can be tuned by adding solid microspheres into the channel. In order to determine the influence of microspheres, we use both analytic and computational methods to predict the pressure responses of soft microfluidic sensors with two different channel cross-sections: a square and an equilateral triangular. The analytical models were derived from contact mechanics in which microspheres were regarded as spherical indenters, and finite element analysis (FEA) was used for simulation. For experimental validation, sensor samples with the two different channel cross-sections were prepared and tested. For comparison, the sensor samples were tested both with and without microspheres. All three results from the analytical models, the FEA simulations, and the experiments showed reasonable agreement confirming that the multi-material soft structure significantly improved its pressure response in terms of both linearity and sensitivity. The embedded solid particles enhanced the performance of soft sensors while maintaining their flexible and stretchable mechanical characteristic. We also provide analytical and experimental analyses of hysteresis of microfluidic soft sensors considering a resistive force to the shape recovery of the polymer structure by the embedded viscous fluid.

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...

Microfluidic perfusion culture of human induced pluripotent stem cells under fully defined culture conditions.

Science.gov (United States)

Yoshimitsu, Ryosuke; Hattori, Koji; Sugiura, Shinji; Kondo, Yuki; Yamada, Rotaro; Tachikawa, Saoko; Satoh, Taku; Kurisaki, Akira; Ohnuma, Kiyoshi; Asashima, Makoto; Kanamori, Toshiyuki

2014-05-01

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for drug screening. For this application, self-renewal or differentiation of the cells is required, and undefined factors in the culture conditions are not desirable. Microfluidic perfusion culture allows the production of small volume cultures with precisely controlled microenvironments, and is applicable to high-throughput cellular environment screening. Here, we developed a microfluidic perfusion culture system for hiPSCs that uses a microchamber array chip under defined extracellular matrix (ECM) and culture medium conditions. By screening various ECMs we determined that fibronectin and laminin are appropriate for microfluidic devices made out of the most popular material, polydimethylsiloxane (PDMS). We found that the growth rate of hiPSCs under pressure-driven perfusion culture conditions was higher than under static culture conditions in the microchamber array. We applied our new system to self-renewal and differentiation cultures of hiPSCs, and immunocytochemical analysis showed that the state of the hiPSCs was successfully controlled. The effects of three antitumor drugs on hiPSCs were comparable between microchamber array and 96-well plates. We believe that our system will be a platform technology for future large-scale screening of fully defined conditions for differentiation cultures on integrated microfluidic devices. © 2013 Wiley Periodicals, Inc.

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.

Coding/decoding and reversibility of droplet trains in microfluidic networks.

Science.gov (United States)

Fuerstman, Michael J; Garstecki, Piotr; Whitesides, George M

2007-02-09

Droplets of one liquid suspended in a second, immiscible liquid move through a microfluidic device in which a channel splits into two branches that reconnect downstream. The droplets choose a path based on the number of droplets that occupy each branch. The interaction among droplets in the channels results in complex sequences of path selection. The linearity of the flow through the microchannels, however, ensures that the behavior of the system can be reversed. This reversibility makes it possible to encrypt and decrypt signals coded in the intervals between droplets. The encoding/decoding device is a functional microfluidic system that requires droplets to navigate a network in a precise manner without the use of valves, switches, or other means of external control.

Fabrication of Microfluidic Valves Using a Hydrogel Molding Method.

Science.gov (United States)

Sugiura, Yusuke; Hirama, Hirotada; Torii, Toru

2015-08-24

In this paper, a method for fabricating a microfluidic valve made of polydimethylsiloxane (PDMS) using a rapid prototyping method for microchannels through hydrogel cast molding is discussed. Currently, the valves in microchannels play an important role in various microfluidic devices. The technology to prototype microfluidic valves rapidly is actively being developed. For the rapid prototyping of PDMS microchannels, a method that uses a hydrogel as the casting mold has been recently developed. This technique can be used to prepare a three-dimensional structure through simple and uncomplicated methods. In this study, we were able to fabricate microfluidic valves easily using this rapid prototyping method that utilizes hydrogel cast molding. In addition, we confirmed that the valve displacement could be predicted within a range of constant pressures. Moreover, because microfluidic valves fabricated using this method can be directly observed from a cross-sectional direction, we anticipate that this technology will significantly contribute to clarifying fluid behavior and other phenomena in microchannels and microfluidic valves with complex structures.

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.

Routing-based Synthesis of Digital Microfluidic Biochips

DEFF Research Database (Denmark)

Maftei, Elena; Pop, Paul; Madsen, Jan

2010-01-01

Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the basic functsions for biochemical analysis. The "digital" microfluidic biochips are manipulating liquids not as a continuous flow, but as discrete droplets on a two-dimensional array...... of electrodes. Basic microfluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. So far, researchers have assumed that these operations are executed on rectangular virtual devices, formed by grouping several adjacent...

Microfluidic Extraction of Biomarkers using Water as Solvent

Science.gov (United States)

Amashukeli, Xenia; Manohara, Harish; Chattopadhyay, Goutam; Mehdi, Imran

2009-01-01

A proposed device, denoted a miniature microfluidic biomarker extractor (mu-EX), would extract trace amounts of chemicals of interest from samples, such as soils and rocks. Traditionally, such extractions are performed on a large scale with hazardous organic solvents; each solvent capable of dissolving only those molecules lying within narrow ranges of specific chemical and physical characteristics that notably include volatility, electric charge, and polarity. In contrast, in the mu-EX, extractions could be performed by use of small amounts (typically between 0.1 and 100 L) of water as a universal solvent. As a rule of thumb, in order to enable solvation and extraction of molecules, it is necessary to use solvents that have polarity sufficiently close to the polarity of the target molecules. The mu-EX would make selection of specific organic solvents unnecessary, because mu-EX would exploit a unique property of liquid water: the possibility of tuning its polarity to match the polarity of organic solvents appropriate for extraction of molecules of interest. The change of the permittivity of water would be achieved by exploiting interactions between the translational states of water molecules and an imposed electromagnetic field in the frequency range of 300 to 600 GHz. On a molecular level, these interactions would result in disruption of the three-dimensional hydrogen-bonding network among liquid-water molecules and subsequent solvation and hydrolysis of target molecules. The mu-EX is expected to be an efficient means of hydrolyzing chemical bonds in complex macromolecules as well and, thus, enabling analysis of the building blocks of these complex chemical systems. The mu-EX device would include a microfluidic channel, part of which would lie within a waveguide coupled to an electronically tuned source of broad-band electromagnetic radiation in the frequency range from 300 to 600 GHz (see figure). The part of the microfluidic channel lying in the waveguide would

Design, fabrication and characterisation of a microfluidic time-temperature indicator

Science.gov (United States)

Schmitt, P.; Wedrich, K.; Müller, L.; Mehner, H.; Hoffmann, M.

2017-11-01

This paper describes a concept for a passive microfluidic time-temperature indicator (TTI) intended for intelligent food packaging. A microfluidic system is presented that makes use of the temperature-dependent flow of suitable food ingredients in a microcapillary. Based on the creeping distance inside the capillary, the time-temperature integral can be determined. A demonstrator of the microsystem has been designed, fabricated and characterised using liquid sugar alcohols as indicator fluids. To enable a first wireless read-out of the passive TTI, the sensor was read out using a commercial RFID equipment, and capacitive measurements have been carried out.

Reagent-loaded plastic microfluidic chips for detecting homocysteine

International Nuclear Information System (INIS)

Suk, Ji Won; Jang, Jae-Young; Cho, Jun-Hyeong

2008-01-01

This report describes the preliminary study on plastic microfluidic chips with pre-loaded reagents for detecting homocysteine (Hcy). All reagents needed in an Hcy immunoassay were included in a microfluidic chip to remove tedious assay steps. A simple and cost-effective bonding method was developed to realize reagent-loaded microfluidic chips. This technique uses an intermediate layer between two plastic substrates by selectively patterning polydimethylsiloxane (PDMS) on the embossed surface of microchannels and fixing the substrates under pressure. Using this bonding method, the competitive immunoassay for SAH, a converted form of Hcy, was performed without any damage to reagents in chips, and the results showed that the fluorescent signal from antibody antigen binding decreased as the SAH concentration increased. Based on the SAH immunoassay, whole immunoassay steps for Hcy detection were carried out in plastic microfluidic chips with all necessary reagents. These experiments demonstrated the feasibility of the Hcy immunoassay in microfluidic devices

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

KAUST Repository

Chen, Yu-Chih

2013-01-01

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

From Single Microparticles to Microfluidic Emulsification

DEFF Research Database (Denmark)

Kinoshita, K.; Ortiz, Elisa Parra; Hussein, Abdirazak

2016-01-01

The micropipette manipulation technique is capable of making fundamental single particle measurements and analyses. This information is critical for establishing processing parameters in systems such as microfluidics and homogenization. To demonstrate what can be achieved at the single particle l...... a very useful tool for understanding microsphere-processes and hence can help to establish process conditions without resorting to expensive and material-consuming bulk particle runs....

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

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.

Development of micropump-actuated negative pressure pinched injection for parallel electrophoresis on array microfluidic chip.

Science.gov (United States)

Li, Bowei; Jiang, Lei; Xie, Hua; Gao, Yan; Qin, Jianhua; Lin, Bingcheng

2009-09-01

A micropump-actuated negative pressure pinched injection method is developed for parallel electrophoresis on a multi-channel LIF detection system. The system has a home-made device that could individually control 16-port solenoid valves and a high-voltage power supply. The laser beam is excitated and distributes to the array separation channels for detection. The hybrid Glass-PDMS microfluidic chip comprises two common reservoirs, four separation channels coupled to their respective pneumatic micropumps and two reference channels. Due to use of pressure as a driving force, the proposed method has no sample bias effect for separation. There is only one high-voltage supply needed for separation without relying on the number of channels, which is significant for high-throughput analysis, and the time for sample loading is shortened to 1 s. In addition, the integrated micropumps can provide the versatile interface for coupling with other function units to satisfy the complicated demands. The performance is verified by separation of DNA marker and Hepatitis B virus DNA samples. And this method is also expected to show the potential throughput for the DNA analysis in the field of disease diagnosis.

pH-Sensitive Hydrogel for Micro-Fluidic Valve

Directory of Open Access Journals (Sweden)

Zhengzhi Yang

2012-07-01

Full Text Available The deformation behavior of a pH-sensitive hydrogel micro-fluidic valve system is investigated using inhomogeneous gel deformation theory, in which the fluid-structure interaction (FSI of the gel solid and fluid flow in the pipe is considered. We use a finite element method with a well adopted hydrogel constitutive equation, which is coded in commercial software, ABAQUS, to simulate the hydrogel valve swelling deformation, while FLUENT is adopted to model the fluid flow in the pipe of the hydrogel valve system. The study demonstrates that FSI significantly affects the gel swelling deformed shapes, fluid flow pressure and velocity patterns. FSI has to be considered in the study on fluid flow regulated by hydrogel microfluidic valve. The study provides a more accurate and adoptable model for future design of new pH-sensitive hydrogel valves, and also gives a useful guideline for further studies on hydrogel fluidic applications.

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.

Inkjet 3D printing of microfluidic structures—on the selection of the printer towards printing your own microfluidic chips

International Nuclear Information System (INIS)

Walczak, Rafał; Adamski, Krzysztof

2015-01-01

This article reports, for the first time, the results of detailed research on the application of inkjet 3D printing for the fabrication of microfluidic structures. CAD designed test structures were printed with four different printers. Dimensional fidelity, shape conformity, and surface roughness were studied for each printout. It was found that the minimum dimension (width or depth) for a properly printed microfluidic channel was approximately 200 μm. Although the nominal resolution of the printers was one order of magnitude better, smaller structures were significantly deformed or not printed at all. It was also found that a crucial step in one-step fabrication of embedded microchannels is the removal of the support material. We also discuss the source of print error and present a way to evaluate other printers. The printouts obtained from the four different printers were compared, and the optimal printing technique and printer were used to fabricate a microfluidic structure for the spectrophotometric characterisation of beverages. UV/VIS absorbance characteristics were collected using this microfluidic structure, demonstrating that the fabricated spectrophotometric chip operated properly. Thus, a proof-of-concept for using inkjet 3D printing for the fabrication of microfluidic structures was obtained. (paper)

Opportunities for microfluidic technologies in synthetic biology

OpenAIRE

Gulati, Shelly; Rouilly, Vincent; Niu, Xize; Chappell, James; Kitney, Richard I.; Edel, Joshua B.; Freemont, Paul S.; deMello, Andrew J.

2009-01-01

We introduce microfluidics technologies as a key foundational technology for synthetic biology experimentation. Recent advances in the field of microfluidics are reviewed and the potential of such a technological platform to support the rapid development of synthetic biology solutions is discussed.

Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method.

Science.gov (United States)

Gu, Shuqing; Lu, Youlan; Ding, Yaping; Li, Li; Zhang, Fenfen; Wu, Qingsheng

2013-09-24

A simple but robust droplet-based microfluidic system was developed for dose-response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose-response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC50 (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6 min, and the total consumption of reagents was less than 5 μL. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active. Copyright © 2013 Elsevier B.V. All rights reserved.

Microfluidics without channels: highly-flexible synthesis on a digital-microfluidic chip for production of diverse PET tracers

Energy Technology Data Exchange (ETDEWEB)

Van Dam, Robert Michael [Univ. of California, Los Angeles, CA (United States)

2010-09-01

Positron emission tomography (PET) imaging is used for fundamental studies of living biological organisms and microbial ecosystems in applications ranging from biofuel production to environmental remediation to the study, diagnosis, and treatment monitoring of human disease. Routine access to PET imaging, to monitor biochemical reactions in living organisms in real time, could accelerate a broad range of research programs of interest to DOE. Using PET requires access to short-lived radioactive-labeled compounds that specifically probe the desired living processes. The overall aims of this project were to develop a miniature liquid-handling technology platform (called “microfluidics”) that increases the availability of diverse PET probes by reducing the cost and complexity of their production. Based on preliminary experiments showing that microfluidic chips can synthesis such compounds, we aimed to advance this technology to improve its robustness, increase its flexibility for a broad range of probes, and increase its user-friendliness. Through the research activities of this project, numerous advances were made; Tools were developed to enable the visualization of radioactive materials within microfluidic chips; Fundamental advances were made in the microfluidic chip architecture and fabrication process to increase its robustness and reliability; The microfluidic chip technology was shown to produce useful quantities of an example PET probes, and methods to further increase the output were successfully pursued; A “universal” chip was developed that could produce multiple types of PET probes, enabling the possibility of “on demand” synthesis of different probes; and Operation of the chip was automated to ensure minimal radiation exposure to the operator Based on the demonstrations of promising technical feasibility and performance, the microfluidic chip technology is currently being commercialized. It is anticipated that costs of microfluidic chips can be

Detection methods for centrifugal microfluidic platforms

DEFF Research Database (Denmark)

Burger, Robert; Amato, Letizia; Boisen, Anja

2016-01-01

Centrifugal microfluidics has attracted much interest from academia as well as industry, since it potentially offers solutions for affordable, user-friendly and portable biosensing. A wide range of so-called fluidic unit operations, e.g. mixing, metering, liquid routing, and particle separation...... for the centrifugal microfluidics platform and cover optical as well as mechanical and electrical detection principles....

ESPC Coupled Global Prediction System

Science.gov (United States)

2015-09-30

through an improvement to the sea ice albedo . Fig. 3: 2-m Temperature bias (deg C) of 120-h forecasts for the month of May 2014 for the Arctic...forecast system (NAVGEM) and ocean- sea ice forecast system (HYCOM/CICE) have never been coupled at high resolution. The coupled processes will be...winds and currents across the interface. The sea - ice component of this project requires modification of CICE versions 4 and 5 to run in the coupled

Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

International Nuclear Information System (INIS)

Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W; Emami, K; Wu, H

2011-01-01

The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

Energy Technology Data Exchange (ETDEWEB)

Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail: sunwei@drexel.edu, E-mail: weisun@tsinghua.edu.cn [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)

2011-09-15

The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

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...

Development and simulation of microfluidic Wheatstone bridge for high-precision sensor

International Nuclear Information System (INIS)

Shipulya, N D; Konakov, S A; Krzhizhanovskaya, V V

2016-01-01

In this work we present the results of analytical modeling and 3D computer simulation of microfluidic Wheatstone bridge, which is used for high-accuracy measurements and precision instruments. We propose and simulate a new method of a bridge balancing process by changing the microchannel geometry. This process is based on the “etching in microchannel” technology we developed earlier (doi:10.1088/1742-6596/681/1/012035). Our method ensures a precise control of the flow rate and flow direction in the bridge microchannel. The advantage of our approach is the ability to work without any control valves and other active electronic systems, which are usually used for bridge balancing. The geometrical configuration of microchannels was selected based on the analytical estimations. A detailed 3D numerical model was based on Navier-Stokes equations for a laminar fluid flow at low Reynolds numbers. We investigated the behavior of the Wheatstone bridge under different process conditions; found a relation between the channel resistance and flow rate through the bridge; and calculated the pressure drop across the system under different total flow rates and viscosities. Finally, we describe a high-precision microfluidic pressure sensor that employs the Wheatstone bridge and discuss other applications in complex precision microfluidic systems. (paper)

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...

Biosensing utilizing the motion of magnetic microparticles in a microfluidic system

KAUST Repository

Giouroudi, Ioanna

2010-10-23

The study for the design of a compact and inexpensive biosensing device, which can be operated either by primary care personnel or by patients as opposed to skilled operators, is presented. The main parts of the proposed device are a microfluidic channel, permanent magnets and functionalized magnetic microparticles. The innovative aspect of the proposed biosensing method is that it utilizes the volumetric increase of magnetic microparticles when analyte binds to their surface. Their velocity decreases drastically when they are accelerated by an externally applied magnetic force within a microfluidic channel. This effect is utilized to detect the presence of analyte e.g. microbes. Analytical calculations showed that a decrease in velocity of approximately 23% can be achieved due to the volumetric change of a magnetic microparticle of View the MathML source1μm diameter when HIV virions of approximately View the MathML source0,135μm are bound to its surface and by keeping its magnetic properties the same. Preliminary experiments were carried out utilizing superparamagnetic microparticles coated with streptavidin and polystyrene microparticles coated with biotin.

A hemispherical microfluidic channel for the trapping and passive dissipation of microbubbles

International Nuclear Information System (INIS)

Kang, Edward; Lee, Dae Ho; Kim, Chang-Beom; Yoo, Sung Ju; Lee, Sang-Hoon

2010-01-01

In this paper, we present that trapping and dissipating of bubbles in a microfluidic cell culture system can be simultaneously achieved by utilizing curved geometry principles. For this end, a simple and cost-effective method to fabricate a curved hemispherical microfluidic channel is presented. On the basis of an analytical model, the mechanism that the hemispherical well can trap various sizes of bubbles better than the cylindrical well is described, and we present a quantitative comparison of the trapping capabilities of the hemispherical versus conventional cylindrical wells through experiments. The surface tension is another important factor to trap bubbles, which was also verified through the analysis and experiments. In the hemispherical wells, the trapped bubbles were spontaneously dissipated under the flowing condition without using any active source, and we characterized the degassing process by measuring the area of bubbles occupied in the well over time. For an application to a biomedical system, a cell culture chamber was combined with the bubble trapping system, and the performance of the system was verified by culturing HeLa cells with the flowing bubbled culture media. Conclusively, the suggested method demonstrated excellent performance in trapping of microbubbles and dissipation without using any peripheral device, and will be broadly applied in biomedical microfluidic research

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.

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...

Point-of-care, portable microfluidic blood analyzer system

Science.gov (United States)

Maleki, Teimour; Fricke, Todd; Quesenberry, J. T.; Todd, Paul W.; Leary, James F.

2012-03-01

Recent advances in MEMS technology have provided an opportunity to develop microfluidic devices with enormous potential for portable, point-of-care, low-cost medical diagnostic tools. Hand-held flow cytometers will soon be used in disease diagnosis and monitoring. Despite much interest in miniaturizing commercially available cytometers, they remain costly, bulky, and require expert operation. In this article, we report progress on the development of a battery-powered handheld blood analyzer that will quickly and automatically process a drop of whole human blood by real-time, on-chip magnetic separation of white blood cells (WBCs), fluorescence analysis of labeled WBC subsets, and counting a reproducible fraction of the red blood cells (RBCs) by light scattering. The whole blood (WB) analyzer is composed of a micro-mixer, a special branching/separation system, an optical detection system, and electronic readout circuitry. A droplet of un-processed blood is mixed with the reagents, i.e. magnetic beads and fluorescent stain in the micro-mixer. Valve-less sorting is achieved by magnetic deflection of magnetic microparticle-labeled WBC. LED excitation in combination with an avalanche photodiode (APD) detection system is used for counting fluorescent WBC subsets using several colors of immune-Qdots, while counting a reproducible fraction of red blood cells (RBC) is performed using a laser light scatting measurement with a photodiode. Optimized branching/channel width is achieved using Comsol Multi-Physics™ simulation. To accommodate full portability, all required power supplies (40v, +/-10V, and +3V) are provided via step-up voltage converters from one battery. A simple onboard lock-in amplifier is used to increase the sensitivity/resolution of the pulse counting circuitry.

Predictive toxicology using systemic biology and liver microfluidic “on chip” approaches: Application to acetaminophen injury

International Nuclear Information System (INIS)

Prot, Jean-Matthieu; Bunescu, Andrei; Elena-Herrmann, Bénédicte; Aninat, Caroline; Snouber, Leila Choucha; Griscom, Laurent; Razan, Florence; Bois, Frederic Y.; Legallais, Cécile

2012-01-01

We have analyzed transcriptomic, proteomic and metabolomic profiles of hepatoma cells cultivated inside a microfluidic biochip with or without acetaminophen (APAP). Without APAP, the results show an adaptive cellular response to the microfluidic environment, leading to the induction of anti-oxidative stress and cytoprotective pathways. In presence of APAP, calcium homeostasis perturbation, lipid peroxidation and cell death are observed. These effects can be attributed to APAP metabolism into its highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). That toxicity pathway was confirmed by the detection of GSH-APAP, the large production of 2-hydroxybutyrate and 3-hydroxybutyrate, and methionine, cystine, and histidine consumption in the treated biochips. Those metabolites have been reported as specific biomarkers of hepatotoxicity and glutathione depletion in the literature. In addition, the integration of the metabolomic, transcriptomic and proteomic collected profiles allowed a more complete reconstruction of the APAP injury pathways. To our knowledge, this work is the first example of a global integration of microfluidic biochip data in toxicity assessment. Our results demonstrate the potential of that new approach to predictive toxicology. -- Highlights: ► We cultivated liver cells in microfluidic biochips ► We integrated transcriptomic, proteomic and metabolomics profiles ► Pathways reconstructions were proposed in control and acetaminophen treated cultures ► Biomarkers were identified ► Comparisons with in vivo studies were proposed.

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

Fabrication and characterization of injection molded multi level nano and microfluidic systems

DEFF Research Database (Denmark)

Matteucci, Marco; Christiansen, Thomas Lehrmann; Tanzi, Simone

2013-01-01

We here present a method for fabrication of multi-level all-polymer chips by means of silicon dry etching, electroplating and injection molding. This method was used for successful fabrication of microfluidic chips for applications in the fields of electrochemistry, cell trapping and DNA elongati...

[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.

Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays.

Science.gov (United States)

Hansson, Jonas; Yasuga, Hiroki; Haraldsson, Tommy; van der Wijngaart, Wouter

2016-01-21

We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.

Coupling Strength and System Size Induce Firing Activity of Globally Coupled Neural Network

International Nuclear Information System (INIS)

Wei Duqu; Luo Xiaoshu; Zou Yanli

2008-01-01

We investigate how firing activity of globally coupled neural network depends on the coupling strength C and system size N. Network elements are described by space-clamped FitzHugh-Nagumo (SCFHN) neurons with the values of parameters at which no firing activity occurs. It is found that for a given appropriate coupling strength, there is an intermediate range of system size where the firing activity of globally coupled SCFHN neural network is induced and enhanced. On the other hand, for a given intermediate system size level, there exists an optimal value of coupling strength such that the intensity of firing activity reaches its maximum. These phenomena imply that the coupling strength and system size play a vital role in firing activity of neural network

Interface of nanocatalysis and microfluidic reactors for green chemistry methods

CSIR Research Space (South Africa)

Makgwane, PR

2013-10-01

Full Text Available The development of green catalytic methods for chemical synthesis and energy generation based on nanocoated catalyst microfluidic systems is a growing area of innovative research. The interface between heterogeneous catalysis and microchannel...

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.

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.

Centrifugally driven microfluidic disc for detection of chromosomal translocations

DEFF Research Database (Denmark)

Brøgger, Anna Line; Kwasny, Dorota; Bosco, Filippo G.

2012-01-01

and prognosis of patients. In this work we demonstrate a novel, centrifugally-driven microfluidic system for controlled manipulation of oligonucleotides and subsequent detection of chromosomal translocations. The device is fabricated in the form of a disc with capillary burst microvalves employed to control...

Development & Characterization of Multifunctional Microfluidic Materials

Science.gov (United States)

Ucar, Ahmet Burak

The field of microfluidics has been mostly investigated for miniaturized lab on a chip devices for analytical and clinical applications. However, there is an emerging class of "smart" microfluidic materials, combining microfluidics with soft polymers to yield new functionalities. The best inspiration for such materials found in nature is skin, whose functions are maintained and controlled by a vascular "microfluidic" network. We report here the development and characterization of a few new classes of microfluidic materials. First, we introduced microfluidic materials that can change their stiffness on demand. These materials were based on an engineered microchannel network embedded into a matrix of polydimethylsiloxane (PDMS), whose channels were filled with a liquid photoresist (SU- 8). The elastomer filled with the photoresist was initially soft. The materials were shaped into a desired geometry and then exposed to UV-light. Once photocured, the material preserved the defined shape and it could be bent, twisted or stretched with a very high recoverable strain. As soon as the external force was removed the material returned back to its predefined shape. Thus, the polymerized SU-8 acted as the 'endoskeleton' of the microfluidic network, which drastically increased the composite's elastic and bending moduli. Second, we demonstrated a class of simple and versatile soft microfluidic materials that can be turned optically transparent or colored on demand. These materials were made in the form of flexible sheets containing a microchannel network embedded in PDMS, similar to the photocurable materials. However, this time the channels were filled with a glycerolwater mixture, whose refractive index was matched with that of the PDMS matrix. By pumping such dye solutions into the channel network and consecutively replacing the medium, we showed that we can control the material's color and light transmittance in the visible and near-infrared regions, which can be used for

Cyclic olefin homopolymer-based microfluidics for protein crystallization and in situ X-ray diffraction

International Nuclear Information System (INIS)

Emamzadah, Soheila; Petty, Tom J.; De Almeida, Victor; Nishimura, Taisuke; Joly, Jacques; Ferrer, Jean-Luc; Halazonetis, Thanos D.

2009-01-01

A cyclic olefin homopolymer-based microfluidics system has been established for protein crystallization and in situ X-ray diffraction. Microfluidics is a promising technology for the rapid identification of protein crystallization conditions. However, most of the existing systems utilize silicone elastomers as the chip material which, despite its many benefits, is highly permeable to water vapour. This limits the time available for protein crystallization to less than a week. Here, the use of a cyclic olefin homopolymer-based microfluidics system for protein crystallization and in situ X-ray diffraction is described. Liquid handling in this system is performed in 2 mm thin transparent cards which contain 500 chambers, each with a volume of 320 nl. Microbatch, vapour-diffusion and free-interface diffusion protocols for protein crystallization were implemented and crystals were obtained of a number of proteins, including chicken lysozyme, bovine trypsin, a human p53 protein containing both the DNA-binding and oligomerization domains bound to DNA and a functionally important domain of Arabidopsis Morpheus’ molecule 1 (MOM1). The latter two polypeptides have not been crystallized previously. For X-ray diffraction analysis, either the cards were opened to allow mounting of the crystals on loops or the crystals were exposed to X-rays in situ. For lysozyme, an entire X-ray diffraction data set at 1.5 Å resolution was collected without removing the crystal from the card. Thus, cyclic olefin homopolymer-based microfluidics systems have the potential to further automate protein crystallization and structural genomics efforts

Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery

Directory of Open Access Journals (Sweden)

Jiandi Wan

2012-04-01

Full Text Available Encapsulation of cells in hydrogel particles has been demonstrated as an effective approach to deliver therapeutic agents. The properties of hydrogel particles, such as the chemical composition, size, porosity, and number of cells per particle, affect cellular functions and consequently play important roles for the cell-based drug delivery. Microfluidics has shown unparalleled advantages for the synthesis of polymer particles and been utilized to produce hydrogel particles with a well-defined size, shape and morphology. Most importantly, during the encapsulation process, microfluidics can control the number of cells per particle and the overall encapsulation efficiency. Therefore, microfluidics is becoming the powerful approach for cell microencapsulation and construction of cell-based drug delivery systems. In this article, I summarize and discuss microfluidic approaches that have been developed recently for the synthesis of hydrogel particles and encapsulation of cells. I will start by classifying different types of hydrogel material, including natural biopolymers and synthetic polymers that are used for cell encapsulation, and then focus on the current status and challenges of microfluidic-based approaches. Finally, applications of cell-containing hydrogel particles for cell-based drug delivery, particularly for cancer therapy, are discussed.

Raman tweezers in microfluidic systems for analysis and sorting of living cells

Science.gov (United States)

Pilát, Zdeněk.; Ježek, Jan; Kaňka, Jan; Zemánek, Pavel

2014-12-01

We have devised an analytical and sorting system combining optical trapping with Raman spectroscopy in microfluidic environment, dedicated to identification and sorting of biological objects, such as living cells of various unicellular organisms. Our main goal was to create a robust and universal platform for non-destructive and non-contact sorting of micro-objects based on their Raman spectral properties. This approach allowed us to collect spectra containing information about the chemical composition of the objects, such as the presence and composition of pigments, lipids, proteins, or nucleic acids, avoiding artificial chemical probes such as fluorescent markers. The non-destructive nature of this optical analysis and manipulation allowed us to separate individual living cells of our interest in a sterile environment and provided the possibility to cultivate the selected cells for further experiments. We used a mixture of polystyrene micro-particles and algal cells to test and demonstrate the function of our analytical and sorting system. The devised system could find its use in many medical, biotechnological, and biological applications.

Immobilization of pH-sensitive CdTe Quantum Dots in a Poly(acrylate) Hydrogel for Microfluidic Applications

Science.gov (United States)

Franke, M.; Leubner, S.; Dubavik, A.; George, A.; Savchenko, T.; Pini, C.; Frank, P.; Melnikau, D.; Rakovich, Y.; Gaponik, N.; Eychmüller, A.; Richter, A.

2017-04-01

Microfluidic devices present the basis of modern life sciences and chemical information processing. To control the flow and to allow optical readout, a reliable sensor material that can be easily utilized for microfluidic systems is in demand. Here, we present a new optical readout system for pH sensing based on pH sensitive, photoluminescent glutathione capped cadmium telluride quantum dots that are covalently immobilized in a poly(acrylate) hydrogel. For an applicable pH sensing the generated hybrid material is integrated in a microfluidic sensor chip setup. The hybrid material not only allows in situ readout, but also possesses valve properties due to the swelling behavior of the poly(acrylate) hydrogel. In this work, the swelling property of the hybrid material is utilized in a microfluidic valve seat, where a valve opening process is demonstrated by a fluid flow change and in situ monitored by photoluminescence quenching. This discrete photoluminescence detection (ON/OFF) of the fluid flow change (OFF/ON) enables upcoming chemical information processing.

Design of protein-responsive micro-sized hydrogels for self-regulating microfluidic systems

Science.gov (United States)

Hirayama, Mayu; Tsuruta, Kazuhiro; Kawamura, Akifumi; Ohara, Masayuki; Shoji, Kan; Kawano, Ryuji; Miyata, Takashi

2018-03-01

Diagnosis sensors using micro-total analysis systems (µ-TAS) have been developed for detecting target biomolecules such as proteins and saccharides because they are signal biomolecules for monitoring body conditions and diseases. In this study, biomolecularly stimuli-responsive micro-sized hydrogels that exhibited quick shrinkage in response to lectin concanavalinA (ConA) were prepared in a microchannel by photopolymerization using a fluorescence microscope. In preparing the micro-size hydrogels, glycosyloxyethyl methacrylate (GEMA) as a ligand monomer was copolymerized with a crosslinker in the presence of template ConA in molecular imprinting. The ConA-imprinted micro-hydrogel showed greater shrinkage in response to target ConA than nonimprinted micro-hydrogel. When a buffer solution was switched to an aqueous ConA solution in the Y-shaped microchannel, the flow rates changed quickly because of the responsive shrinkage of the micro-hydrogel prepared in the microchannel. These results suggest that the ConA-imprinted micro-hydrogel acted as a self-regulated microvalve in microfluidic systems.

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...

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...

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Science.gov (United States)

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

2015-01-15

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

Microfluidic strategies for design and assembly of microfibers and nanofibers with tissue engineering and regenerative medicine applications.

Science.gov (United States)

Daniele, Michael A; Boyd, Darryl A; Adams, André A; Ligler, Frances S

2015-01-07

Fiber-based materials provide critical capabilities for biomedical applications. Microfluidic fiber fabrication has recently emerged as a very promising route to the synthesis of polymeric fibers at the micro and nanoscale, providing fine control over fiber shape, size, chemical anisotropy, and biological activity. This Progress Report summarizes advanced microfluidic methods for the fabrication of both microscale and nanoscale fibers and illustrates how different methods are enabling new biomedical applications. Microfluidic fabrication methods and resultant materials are explained from the perspective of their microfluidic device principles, including co-flow, cross-flow, and flow-shaping designs. It is then detailed how the microchannel design and flow parameters influence the variety of synthesis chemistries that can be utilized. Finally, the integration of biomaterials and microfluidic strategies is discussed to manufacture unique fiber-based systems, including cell scaffolds, cell encapsulation, and woven tissue matrices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Highly Stretchable and Transparent Microfluidic Strain Sensors for Monitoring Human Body Motions.

Science.gov (United States)

Yoon, Sun Geun; Koo, Hyung-Jun; Chang, Suk Tai

2015-12-16

We report a new class of simple microfluidic strain sensors with high stretchability, transparency, sensitivity, and long-term stability with no considerable hysteresis and a fast response to various deformations by combining the merits of microfluidic techniques and ionic liquids. The high optical transparency of the strain sensors was achieved by introducing refractive-index matched ionic liquids into microfluidic networks or channels embedded in an elastomeric matrix. The microfluidic strain sensors offer the outstanding sensor performance under a variety of deformations induced by stretching, bending, pressing, and twisting of the microfluidic strain sensors. The principle of our microfluidic strain sensor is explained by a theoretical model based on the elastic channel deformation. In order to demonstrate its capability of practical usage, the simple-structured microfluidic strain sensors were performed onto a finger, wrist, and arm. The highly stretchable and transparent microfluidic strain sensors were successfully applied as potential platforms for distinctively monitoring a wide range of human body motions in real time. Our novel microfluidic strain sensors show great promise for making future stretchable electronic devices.

Bead Capture on Magnetic Sensors in a Microfluidic System

DEFF Research Database (Denmark)

Østerberg, Frederik Westergaard; Dalslet, Bjarke Thomas; Damsgaard, Christian Danvad

2009-01-01

The accumulation of magnetic beads by gravitational sedimentation and magnetic capture on a planar Hall-effect sensor integrated in a microfluidic channel is studied systematically as a function of the bead concentration, the fluid flow rate, and the sensor bias current. It is demonstrated...... that the sedimentation flux is proportional to the bead concentration and has a power law relation to the fluid flow rate. The mechanisms for the bead accumulation are investigated and it is found that gravitational sedimentation dominates the bead accumulation, whereas the stability of the sedimented beads against...

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.

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.

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

DEFF Research Database (Denmark)

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

2018-01-01

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

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

KAUST Repository

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

2013-01-01

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

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

KAUST Repository

Wang, Xiang

2013-01-01

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

Continuous monitoring of bisulfide variation in microdialysis effluents by on-line droplet-based microfluidic fluorescent sensor.

Science.gov (United States)

Zhu, Xiaocui; Xu, Lei; Wu, Tongbo; Xu, Anqin; Zhao, Meiping; Liu, Shaorong

2014-05-15

We demonstrate a novel fluorescent sensor for real-time and continuous monitoring of the variation of bisulfide in microdialysis effluents by using a nanoparticle-glutathione-fluorescein isothiocyanate (AuNP-GSH-FITC) probe coupled with on-line droplet-based microfluidic chip. The AuNP-GSH-FITC fluorescent probe was firstly developed and used for bisulfide detection in bulk solution by quantitative real-time PCR, which achieved a linear working range from 0.1 μM to 5.0 μM and a limit of detection of ~50 nM. The response time was less than 2 min. With the aid of co-immobilized thiol-polyethylene glycol, the probe exhibited excellent stability and reproducibility in high salinity solutions, including artificial cerebrospinal fluids (aCSF). By adding 0.1% glyoxal to the probe solution, the assay allowed quantification of bisulfide in the presence of cysteine at the micro-molarity level. Using the AuNP-GSH-FITC probe, a droplet-based microfluidic fluorescent sensor was further constructed for online monitoring of bisulfide variation in the effluent of microdialysis. By using fluorescence microscope-charge-coupled device camera as the detector, the integrated microdialysis/microfluidic chip device achieved a detection limit of 2.0 μM and a linear response from 5.0 μM to 50 μM for bisulfide in the tested sample. The method was successfully applied for the on-line measurement of bisulfide variation in aCSF and serum samples. It will be a very useful tool for tracking the variation of bisulfide or hydrogen sulfide in extracellular fluids. Copyright © 2013 Elsevier B.V. All rights reserved.

Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA

Directory of Open Access Journals (Sweden)

Nathan M Belliveau

2012-01-01

Full Text Available Lipid nanoparticles (LNP are the leading systems for in vivo delivery of small interfering RNA (siRNA for therapeutic applications. Formulation of LNP siRNA systems requires rapid mixing of solutions containing cationic lipid with solutions containing siRNA. Current formulation procedures employ macroscopic mixing processes to produce systems 70-nm diameter or larger that have variable siRNA encapsulation efficiency, homogeneity, and reproducibility. Here, we show that microfluidic mixing techniques, which permit millisecond mixing at the nanoliter scale, can reproducibly generate limit size LNP siRNA systems 20 nm and larger with essentially complete encapsulation of siRNA over a wide range of conditions with polydispersity indexes as low as 0.02. Optimized LNP siRNA systems produced by microfluidic mixing achieved 50% target gene silencing in hepatocytes at a dose level of 10 µg/kg siRNA in mice. We anticipate that microfluidic mixing, a precisely controlled and readily scalable technique, will become the preferred method for formulation of LNP siRNA delivery systems.

A truly Lego®-like modular microfluidics platform

Science.gov (United States)

Vittayarukskul, Kevin; Lee, Abraham Phillip

2017-03-01

Ideally, a modular microfluidics platform should be simple to assemble and support 3D configurations for increased versatility. The modular building blocks should also be mass producible like electrical components. These are fundamental features of world-renowned Legos® and why Legos® inspire many existing modular microfluidics platforms. In this paper, a truly Lego®-like microfluidics platform is introduced, and its basic feasibility is demonstrated. Here, PDMS building blocks resembling 2  ×  2 Lego® bricks are cast from 3D-printed master molds. The blocks are pegged and stacked on a traditional Lego® plate to create simple, 3D microfluidic networks, such as a single basket weave. Characteristics of the platform, including reversible sealing and automatic alignment of channels, are also analyzed and discussed in detail.

A truly Lego®-like modular microfluidics platform

International Nuclear Information System (INIS)

Vittayarukskul, Kevin; Lee, Abraham Phillip

2017-01-01

Ideally, a modular microfluidics platform should be simple to assemble and support 3D configurations for increased versatility. The modular building blocks should also be mass producible like electrical components. These are fundamental features of world-renowned Legos ® and why Legos ® inspire many existing modular microfluidics platforms. In this paper, a truly Lego ® -like microfluidics platform is introduced, and its basic feasibility is demonstrated. Here, PDMS building blocks resembling 2  ×  2 Lego ® bricks are cast from 3D-printed master molds. The blocks are pegged and stacked on a traditional Lego ® plate to create simple, 3D microfluidic networks, such as a single basket weave. Characteristics of the platform, including reversible sealing and automatic alignment of channels, are also analyzed and discussed in detail. (paper)

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

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

Science.gov (United States)

Chaturvedi, Akhil; Gorthi, Sai Siva

2017-02-01

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

Adjoint-consistent formulations of slip models for coupled electroosmotic flow systems

KAUST Repository

Garg, Vikram V

2014-09-27

Background Models based on the Helmholtz `slip\\' approximation are often used for the simulation of electroosmotic flows. The objectives of this paper are to construct adjoint-consistent formulations of such models, and to develop adjoint-based numerical tools for adaptive mesh refinement and parameter sensitivity analysis. Methods We show that the direct formulation of the `slip\\' model is adjoint inconsistent, and leads to an ill-posed adjoint problem. We propose a modified formulation of the coupled `slip\\' model, which is shown to be well-posed, and therefore automatically adjoint-consistent. Results Numerical examples are presented to illustrate the computation and use of the adjoint solution in two-dimensional microfluidics problems. Conclusions An adjoint-consistent formulation for Helmholtz `slip\\' models of electroosmotic flows has been proposed. This formulation provides adjoint solutions that can be reliably used for mesh refinement and sensitivity analysis.

Controllable nonlinearity in a dual-coupling optomechanical system under a weak-coupling regime

Science.gov (United States)

Zhu, Gui-Lei; Lü, Xin-You; Wan, Liang-Liang; Yin, Tai-Shuang; Bin, Qian; Wu, Ying

2018-03-01

Strong quantum nonlinearity gives rise to many interesting quantum effects and has wide applications in quantum physics. Here we investigate the quantum nonlinear effect of an optomechanical system (OMS) consisting of both linear and quadratic coupling. Interestingly, a controllable optomechanical nonlinearity is obtained by applying a driving laser into the cavity. This controllable optomechanical nonlinearity can be enhanced into a strong coupling regime, even if the system is initially in the weak-coupling regime. Moreover, the system dissipation can be suppressed effectively, which allows the appearance of phonon sideband and photon blockade effects in the weak-coupling regime. This work may inspire the exploration of a dual-coupling optomechanical system as well as its applications in modern quantum science.

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

Impact of Nutrient Restriction on the Structure of Listeria monocytogenes Biofilm Grown in a Microfluidic System

Science.gov (United States)

Cherifi, Tamazight; Jacques, Mario; Quessy, Sylvain; Fravalo, Philippe

2017-01-01

Biofilm formation by the pathogen Listeria monocytogenes is a major concern in food industries. The aim of this work was to elucidate the effect of nutrient limitation on both biofilm architecture and on the viability of the bacteria in microfluidic growth conditions. Biofilm formation by two L. monocytogenes strains was performed in a rich medium (BHI) and in a 10-fold diluted BHI (BHI/10) at 30°C for 24 h by using both static conditions and the microfluidic system Bioflux. In dynamic conditions, biofilms grown in rich and poor medium showed significant differences as well in structure and in the resulting biovolume. In BHI/10, biofilm was organized in a knitted network where cells formed long chains, whereas in the rich medium, the observed structure was homogeneous cellular multilayers. Biofilm biovolume production in BHI/10 was significantly higher than in BHI in these dynamic conditions. Interestingly, biovolume of dead cells in biofilms formed under limited nutrient conditions (BHI/10) was significantly higher than in biofilms formed in the BHI medium. In the other hand, in static conditions, biofilm is organized in a multilayer cells and dispersed cells in a rich medium BHI and poor medium BHI/10 respectively. There was significantly more biomass in the rich medium compared to BHI/10 but no difference was noted in the dead/damaged subpopulation showing how L. monocytogenes biofilm could be affected by the growth conditions. This work demonstrated that nutrient concentration affects biofilm structure and the proportion of dead cells in biofilms under microfluidic condition. Our study also showed that limited nutrients play an important role in the structural stability of L. monocytogenes biofilm by enhancing cell death and liberating extracellular DNA. PMID:28567031

Impact of Nutrient Restriction on the Structure of Listeria monocytogenes Biofilm Grown in a Microfluidic System

Directory of Open Access Journals (Sweden)

Tamazight Cherifi

2017-05-01

Full Text Available Biofilm formation by the pathogen Listeria monocytogenes is a major concern in food industries. The aim of this work was to elucidate the effect of nutrient limitation on both biofilm architecture and on the viability of the bacteria in microfluidic growth conditions. Biofilm formation by two L. monocytogenes strains was performed in a rich medium (BHI and in a 10-fold diluted BHI (BHI/10 at 30°C for 24 h by using both static conditions and the microfluidic system Bioflux. In dynamic conditions, biofilms grown in rich and poor medium showed significant differences as well in structure and in the resulting biovolume. In BHI/10, biofilm was organized in a knitted network where cells formed long chains, whereas in the rich medium, the observed structure was homogeneous cellular multilayers. Biofilm biovolume production in BHI/10 was significantly higher than in BHI in these dynamic conditions. Interestingly, biovolume of dead cells in biofilms formed under limited nutrient conditions (BHI/10 was significantly higher than in biofilms formed in the BHI medium. In the other hand, in static conditions, biofilm is organized in a multilayer cells and dispersed cells in a rich medium BHI and poor medium BHI/10 respectively. There was significantly more biomass in the rich medium compared to BHI/10 but no difference was noted in the dead/damaged subpopulation showing how L. monocytogenes biofilm could be affected by the growth conditions. This work demonstrated that nutrient concentration affects biofilm structure and the proportion of dead cells in biofilms under microfluidic condition. Our study also showed that limited nutrients play an important role in the structural stability of L. monocytogenes biofilm by enhancing cell death and liberating extracellular DNA.

Microfluidic monitoring of programmed cell death in living plant seed tissue

DEFF Research Database (Denmark)

Mark, Christina; Heiskanen, Arto; Zor, Kinga

, et al., (2006), BioEssays, 28, p. 1091). Microfluidic cell culture enables in vitro experiments to approach in vivo conditions. Combining microfluidics with the Lab-On-a-Chip concept allows implementing a wide range of assays for real-time monitoring of effects in a biological system of factors...... such as concentration of selected compounds, external pH, oxygen consumption, redox state and cell viability. The aleurone layer of the barley seed is a 2-3 single cell type thick tissue that can be dissected from the embryo and starchy endosperm. During incubation in vitro this mechanically very robust maintains...

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

Science.gov (United States)

Kimura, Hiroshi; Sakai, Yasuyuki; Fujii, Teruo