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Sample records for bioactivated microfluidic channels

  1. Microfluidic channel fabrication method

    DOEpatents

    Arnold, Don W.; Schoeniger, Joseph S.; Cardinale, Gregory F.

    2001-01-01

    A new channel structure for microfluidic systems and process for fabricating this structure. In contrast to the conventional practice of fabricating fluid channels as trenches or grooves in a substrate, fluid channels are fabricated as thin walled raised structures on a substrate. Microfluidic devices produced in accordance with the invention are a hybrid assembly generally consisting of three layers: 1) a substrate that can or cannot be an electrical insulator; 2) a middle layer, that is an electrically conducting material and preferably silicon, forms the channel walls whose height defines the channel height, joined to and extending from the substrate; and 3) a top layer, joined to the top of the channels, that forms a cover for the channels. The channels can be defined by photolithographic techniques and are produced by etching away the material around the channel walls.

  2. MEMS in microfluidic channels.

    SciTech Connect

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.

    2004-03-01

    Microelectromechanical systems (MEMS) comprise a new class of devices that include various forms of sensors and actuators. Recent studies have shown that microscale cantilever structures are able to detect a wide range of chemicals, biomolecules or even single bacterial cells. In this approach, cantilever deflection replaces optical fluorescence detection thereby eliminating complex chemical tagging steps that are difficult to achieve with chip-based architectures. A key challenge to utilizing this new detection scheme is the incorporation of functionalized MEMS structures within complex microfluidic channel architectures. The ability to accomplish this integration is currently limited by the processing approaches used to seal lids on pre-etched microfluidic channels. This report describes Sandia's first construction of MEMS instrumented microfluidic chips, which were fabricated by combining our leading capabilities in MEMS processing with our low-temperature photolithographic method for fabricating microfluidic channels. We have explored in-situ cantilevers and other similar passive MEMS devices as a new approach to directly sense fluid transport, and have successfully monitored local flow rates and viscosities within microfluidic channels. Actuated MEMS structures have also been incorporated into microfluidic channels, and the electrical requirements for actuation in liquids have been quantified with an elegant theory. Electrostatic actuation in water has been accomplished, and a novel technique for monitoring local electrical conductivities has been invented.

  3. Chemistry in Microfluidic Channels

    ERIC Educational Resources Information Center

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

    2011-01-01

    General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

  4. Chemistry in Microfluidic Channels

    ERIC Educational Resources Information Center

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

    2011-01-01

    General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

  5. Synthesis of Bioactive Microcapsules Using a Microfluidic Device

    PubMed Central

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

    2012-01-01

    Bioactive microcapsules containing Bacillus thuringiensis (BT) spores were generated by a combination of a hydro gel, microfluidic device and chemical polymerization method. As a proof-of-principle, we used BT spores displaying enhanced green fluorescent protein (EGFP) on the spore surface to spatially direct the EGFP-presenting spores within microcapsules. BT spore-encapsulated microdroplets of uniform size and shape are prepared through a flow-focusing method in a microfluidic device and converted into microcapsules through hydrogel polymerization. The size of microdroplets can be controlled by changing both the dispersion and continuous flow rate. Poly(N-isoproplyacrylamide) (PNIPAM), known as a hydrogel material, was employed as a biocompatible material for the encapsulation of BT spores and long-term storage and outstanding stability. Due to these unique properties of PNIPAM, the nutrients from Luria-Bertani complex medium diffused into the microcapsules and the microencapsulated spores germinated into vegetative cells under adequate environmental conditions. These results suggest that there is no limitation of transferring low-molecular-weight-substrates through the PNIPAM structures, and the viability of microencapsulated spores was confirmed by the culture of vegetative cells after the germinations. This microfluidic-based microencapsulation methodology provides a unique way of synthesizing bioactive microcapsules in a one-step process. This microfluidic-based strategy would be potentially suitable to produce microcapsules of various microbial spores for on-site biosensor analysis. PMID:23112592

  6. Understanding cell passage through constricted microfluidic channels

    NASA Astrophysics Data System (ADS)

    Cartas-Ayala, Marco A.; Karnik, Rohit

    2012-11-01

    Recently, several microfluidic platforms have been proposed to characterize cells based on their behaviour during cell passage through constricted channels. Variables like transit time have been analyzed in disease states like sickle cell anemia, malaria and sepsis. Nevertheless, it is hard to make direct comparisons between different platforms and cell types. We present experimental results of the relationship between solid deformable particle properties, i.e. stiffness and relative particle size, and flow properties, i.e. particle's velocity. We measured the hydrodynamic variables during the flow of HL-60 cells, a white myeloid cell type, in narrow microfluidic square channels using a microfluidic differential manometer. We measured the flow force required to move cells of different sizes through microchannels and quantified friction forces opposing cell passage. We determined the non-dimensional parameters that influence the flow of cells and we used them to obtain a non dimensional expression that can be used to predict the forces needed to drive cells through microchannels. We found that the friction force needed to flow HL-60 through a microfluidic channel is the sum of two parts. The first part is a static friction force that is proportional to the force needed to keep the force compressed. The second part is a factor that is proportional to the cell velocity, hence a dynamic term, and slightly sensitive to the compressive force. We thank CONACYT (Mexican Science and Technology Council) for supporting this project, grant 205899.

  7. Evaporative Lithography in Open Microfluidic Channel Networks.

    PubMed

    Lone, Saifullah; Zhang, Jia Ming; Vakarelski, Ivan U; Li, Er Qiang; Thoroddsen, Sigurdur T

    2017-03-13

    We demonstrate a direct capillary-driven method based on wetting and evaporation of various suspensions to fabricate regular two-dimensional wires in an open microfluidic channel through continuous deposition of micro- or nanoparticles under evaporative lithography, akin to the coffee-ring effect. The suspension is gently placed in a loading reservoir connected to the main open microchannel groove on a PDMS substrate. Hydrophilic conditions ensure rapid spreading of the suspension from the loading reservoir to fill the entire channel length. Evaporation during the spreading and after the channel is full increases the particle concentration toward the end of the channel. This evaporation-induced convective transport brings particles from the loading reservoir toward the channel end where this flow deposits a continuous multilayered particle structure. The particle deposition front propagates backward over the entire channel length. The final dry deposit of the particles is thereby much thicker than the initial volume fraction of the suspension. The deposition depth is characterized using a 3D imaging profiler, whereas the deposition topography is revealed using a scanning electron microscope. The patterning technology described here is robust and passive and hence operates without an external field. This work may well become a launching pad to construct low-cost and large-scale thin optoelectronic films with variable thicknesses and interspacing distances.

  8. Surface patterning of bonded microfluidic channels

    PubMed Central

    Priest, Craig

    2010-01-01

    Microfluidic channels in which multiple chemical and biological processes can be integrated into a single chip have provided a suitable platform for high throughput screening, chemical synthesis, detection, and alike. These microchips generally exhibit a homogeneous surface chemistry, which limits their functionality. Localized surface modification of microchannels can be challenging due to the nonplanar geometries involved. However, chip bonding remains the main hurdle, with many methods involving thermal or plasma treatment that, in most cases, neutralizes the desired chemical functionality. Postbonding modification of microchannels is subject to many limitations, some of which have been recently overcome. Novel techniques include solution-based modification using laminar or capillary flow, while conventional techniques such as photolithography remain popular. Nonetheless, new methods, including localized microplasma treatment, are emerging as effective postbonding alternatives. This Review focuses on postbonding methods for surface patterning of microchannels. PMID:21045927

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

    PubMed

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

    2016-04-21

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

  10. Sealing SU-8 microfluidic channels using PDMS.

    PubMed

    Zhang, Zhiyi; Zhao, Ping; Xiao, Gaozhi; Watts, Benjamin R; Xu, Changqing

    2011-12-01

    A simple method of irreversibly sealing SU-8 microfluidic channels using PDMS is reported in this paper. The method is based on inducing a chemical reaction between PDMS and SU-8 by first generating amino groups on PDMS surface using N(2) plasma treatment, then allowing the amino groups to react with the residual epoxy groups on SU-8 surface at an elevated temperature. The N(2) plasma treatment of PDMS can be conducted using an ordinary plasma chamber and high purity N(2), while the residual epoxy groups on SU-8 surface can be preserved by post-exposure baking SU-8 at a temperature no higher than 95 °C. The resultant chemical bonding between PDMS and SU-8 using the method create an interface that can withstand a stress that is greater than the bulk strength of PDMS. The bond is permanent and is long-term resistant to water. The method was applied in fabricating SU-8 microfluidi-photonic integrated devices, and the obtained devices were tested to show desirable performance.

  11. Slopes To Prevent Trapping of Bubbles in Microfluidic Channels

    NASA Technical Reports Server (NTRS)

    Greer, Harold E.; Lee, Michael C.; Smith, J. Anthony; Willis, Peter A.

    2010-01-01

    The idea of designing a microfluidic channel to slope upward along the direction of flow of the liquid in the channel has been conceived to help prevent trapping of gas bubbles in the channel. In the original application that gave rise to this idea, the microfluidic channels are parts of micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. It is necessary to prevent trapping of gas bubbles in these devices because uninterrupted liquid pathways are essential for sustaining the electrical conduction and flows that are essential for CE. The idea is also applicable to microfluidic devices that may be developed for similar terrestrial microCE biotechnological applications or other terrestrial applications in which trapping of bubbles in microfluidic channels cannot be tolerated. A typical microCE device in the original application includes, among other things, multiple layers of borosilicate float glass wafers. Microfluidic channels are formed in the wafers, typically by use of wet chemical etching. The figure presents a simplified cross section of part of such a device in which the CE channel is formed in the lowermost wafer (denoted the channel wafer) and, according to the present innovation, slopes upward into a via hole in another wafer (denoted the manifold wafer) lying immediately above the channel wafer. Another feature of the present innovation is that the via hole in the manifold wafer is made to taper to a wider opening at the top to further reduce the tendency to trap bubbles. At the time of reporting the information for this article, an effort to identify an optimum technique for forming the slope and the taper was in progress. Of the techniques considered thus far, the one considered to be most promising is precision milling by use of femtosecond laser pulses. Other similar techniques that may work equally well are precision milling using a focused ion beam, or a small diamond

  12. Evaluation of microfluidic channels with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Czajkowski, J.; Prykäri, T.; Alarousu, E.; Lauri, J.; Myllylä, R.

    2010-11-01

    Application of time domain, ultra high resolution optical coherence tomography (UHR-OCT) in evaluation of microfluidic channels is demonstrated. Presented study was done using experimental UHR-OCT device based on a Kerr-lens mode locked Ti:sapphire femtosecond laser, a photonic crystal fibre and modified, free-space Michelson interferometer. To show potential of the technique, microfluidic chip fabricated by VTT Center for Printed Intelligence (Oulu, Finland) was measured. Ability for full volumetric reconstruction in non-contact manner enabled complete characterization of closed entity of a microfluidic channel without contamination and harm for the sample. Measurement, occurring problems, and methods of postprocessing for raw data are described. Results present completely resolved physical structure of the channel, its spatial dimensions, draft angles and evaluation of lamination quality.

  13. Fabrication of polyimide based microfluidic channels for biosensor devices

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

  14. Collective sub-diffusive dynamics in bacterial carpet microfluidic channel

    NASA Astrophysics Data System (ADS)

    Hsiao, Yi-Teng; Wang, Jing-Hui; Hsu, Yi-Chun; Chiu, Chien-Chun; Lo, Chien-Jung; Tsao, Chia-Wen; Yen Woon, Wei

    2012-05-01

    We experimentally investigate the collective dynamics in bacterial carpet microfluidic channel. The microfluidic channel is composed of single polar flagellated Vibrio alginolyticus deposited glass substrates. The individual flagellum swimming speed is tuned by varying buffer sodium concentration. Hydrodynamic coupling strength is tuned by varying buffer viscosity. The attached bacteria constantly perform two major modes in flagellum motion, namely, the local rotation and large angle flick. Particle tracking statistics shows high flagellum rotational rate and strong hydrodynamic coupling strength lead to collective sub-diffusive dynamics. The observed effect is strongly correlated to hydrodynamic coupling of flick motions between nearby bacteria.

  15. Co-molding of nanoscale photonic crystals and microfluidic channel

    NASA Astrophysics Data System (ADS)

    Snyder, Chloe E.; Kadiyala, Anand; Srungarapu, Maurya; Liu, Yuxin; Dawson, Jeremy M.

    2014-03-01

    Photonic crystals are nanofabricated structures that enhance light as it is passed through the constructed design. These structures are normally fabricated out of silicon but have shown to be an improvement if fabricated from a more cost effective material. Photonic crystals have uses within biosensing as they may be used to analyze DNA and other analytes. Microfluidic channels are used to transport different analytes and other samples from one end to another. Microfluidics are used in biosensing as a means of transport and are typically fabricated from biocompatible polymers. Integrated together, the photonic crystals and microfluidic channels would be able to achieve better sensing capabilities and cost effective methods for large scale production. Results will be shown from the co-molding.

  16. Simple approach to study biomolecule adsorption in polymeric microfluidic channels.

    PubMed

    Gubala, Vladimir; Siegrist, Jonathan; Monaghan, Ruairi; O'Reilly, Brian; Gandhiraman, Ram Prasad; Daniels, Stephen; Williams, David E; Ducrée, Jens

    2013-01-14

    Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor(®)) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor(®) substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor(®), and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and neutral, hydrogel-like film with polyethylene glycol (PEG) characteristics. This simple analytical approach adds to the fundamental understanding of the interaction forces in real, microfluidic systems. This method provides a straightforward and rapid way to screen surface compositions and chemistry, and relate these to their effects on the sensitivity and resistance to non-specific binding of bioassays using them. In an additional set of experiments, the surface area of the channels in this universal microfluidic chip was increased by precision milling of microscale

  17. Microfluidic vascular channels in gels using commercial 3D printers

    NASA Astrophysics Data System (ADS)

    Selvaganapathy, P. Ravi; Attalla, Rana

    2016-03-01

    This paper details the development of a three dimensional (3D) printing system with a modified microfluidic printhead used for the generation of complex vascular tissue scaffolds. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can easily be patterned using 3Dbioprinting techniques. This microfluidic design allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

  18. Enhancing defect tolerance in periodic post microfluidic channels

    NASA Astrophysics Data System (ADS)

    Chapman, Glenn H.; Gray, Bonnie L.

    2016-03-01

    Biomedical sensors using microfluidic channels are prone to blockage due to particles and bubbles in the fluid. Wider channels may be used, but wide polymer channels may suffer from structural instability (e.g., sagging channel covers). A common design uses many parallel flow channels separated by structural support walls, but these can be rapidly blocked by particulates. We have been studying an alternative "Cathedral Chamber" design where the channel "roof" (cover) is support by periodic posts which creates many possible flow paths to bypass blockages. We use Monte Carlo modelling with iterative COMSOL fluid dynamics simulations to establish the stream lines, and particle velocities. Then a rules based methodology iteratively places trapped particles based on the fluid paths created by the existing blockages, until the system become fully blocked. Previous work has shown that the periodic post design increases lifetime by allowing 6 to 7 times more blockages than can a parallel channel design. In this paper, we simulate and analyze why expanding the number of channels increases almost linearly the number of particles required for blockages. Lifetime increase is still 4.5-5.5 times even for the limiting case of a 2 channel cathedral chamber. This shows the sideways flow created by the periodic posts creates many advantages for the microfluidic chambers.

  19. Hydrogel-coated microfluidic channels for cardiomyocyte culture

    PubMed Central

    Annabi, Nasim; Selimović, Šeila; Cox, Juan Pablo Acevedo; Ribas, João; Bakooshli, Mohsen Afshar; Heintze, Déborah; Weiss, Anthony S.; Cropek, Donald; Khademhosseini, Ali

    2013-01-01

    The research areas of tissue engineering and drug development have displayed increased interest in organ-on-a-chip studies, in which physiologically or pathologically relevant tissues can be engineered to test pharmaceutical candidates. Microfluidic technologies enable the control of the cellular microenvironment for these applications through the topography, size, and elastic properties of the microscale cell culture environment, while delivering nutrients and chemical cues to the cells through continuous media perfusion. Traditional materials used in the fabrication of microfluidic devices, such as poly(dimethylsiloxane) (PDMS), offer high fidelity and high feature resolution, but do not facilitate cell attachment. To overcome this challenge, we have developed a method for coating microfluidic channels inside a closed PDMS device with a cell-compatible hydrogel layer. We have synthesized photocrosslinkable gelatin and tropoelastin-based hydrogel solutions that were used to coat the surfaces under continuous flow inside 50 μm wide, straight microfluidic channels to generate a hydrogel layer on the channel walls. Our observation of primary cardiomyocytes seeded on these hydrogel layers showed preferred attachment as well as higher spontaneous beating rates on tropoelastin coatings compared to gelatin. In addition, cellular attachment, alignment and beating were stronger on 5 % (w/v) hydrogel-coated devices than on 10 % (w/v) gel-coated channels. Our results demonstrate that cardiomyocytes respond favorably to the elastic, soft tropoelastin culture substrates, indicating that tropoelastin-based hydrogels may be a suitable coating choice for some organ-on-a-chip applications. We anticipate that the proposed hydrogel coating method and tropoelastin as a cell culture substrate may be useful for the generation of elastic tissues, e.g. blood vessels, using microfluidic approaches. PMID:23728018

  20. Retinal synaptic regeneration via microfluidic guiding channels

    PubMed Central

    Su, Ping-Jung; Liu, Zongbin; Zhang, Kai; Han, Xin; Saito, Yuki; Xia, Xiaojun; Yokoi, Kenji; Shen, Haifa; Qin, Lidong

    2015-01-01

    In vitro culture of dissociated retinal neurons is an important model for investigating retinal synaptic regeneration (RSR) and exploring potentials in artificial retina. Here, retinal precursor cells were cultured in a microfluidic chip with multiple arrays of microchannels in order to reconstruct the retinal neuronal synapse. The cultured retinal cells were physically connected through microchannels. Activation of electric signal transduction by the cells through the microchannels was demonstrated by administration of glycinergic factors. In addition, an image-based analytical method was used to quantify the synaptic connections and to assess the kinetics of synaptic regeneration. The rate of RSR decreased significantly below 100 μM of inhibitor glycine and then approached to a relatively constant level at higher concentrations. Furthermore, RSR was enhanced by chemical stimulation with potassium chloride. Collectively, the microfluidic synaptic regeneration chip provides a novel tool for high-throughput investigation of RSR at the cellular level and may be useful in quality control of retinal precursor cell transplantation. PMID:26314276

  1. A microfluidic abacus channel for controlling the addition of droplets.

    PubMed

    Um, Eujin; Park, Je-Kyun

    2009-01-21

    This paper reports the first use of the abacus-groove structure to handle droplets in a wide microchannel, with no external forces integrated to the system other than the pumps. Microfluidic abacus channels are demonstrated for the sequential addition of droplets at the desired location. A control channel which is analogous to biasing in electronics can also be used to precisely determine the number of added droplets, when all other experimental conditions are fixed including the size of the droplets and the frequency of droplet-generation. The device allows programmable and autonomous operations of complex two-phase microfluidics as well as new applications for the method of analysis and computations in lab-on-a-chip devices.

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

    DOEpatents

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

    2011-08-09

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

  3. Microfluidic channel-assisted screening of hematopoietic malignancies.

    PubMed

    Mughal, Farah; Baldock, Sara J; Karimiani, Ehsan Ghayoor; Telford, Nick; Goddard, Nicholas J; Day, Philip J R

    2014-03-01

    A simple microfluidic fluorescence in situ hybridization (FISH) device allowing accurate analysis of interphase nuclei in 1 hr in narrow channels is presented. Photolithography and fluorosilicic acid etching were used to fabricate microfluidic channels (referred to as FISHing lines) that allowed analysis of 10 samples on a glass microscope slide 0.2 µl of sample volume was used to fill a micro-channel, which resembled a 250-fold reduction compared to conventional FISH. FISH signals were comparable to conventional FISH, with 50-fold less probe consumption and 10-fold less time. Cells were immobilized in single file in channels just exceeding the diameter of the cells, and were used for minimal residual disease (MRD) analysis. To test the micro-channels for application in FISH, MRD was simulated by mixing K562 cells (an established chronic myeloid leukemia cell line) carrying the BCR/ABL fusion gene across 1:1 to 1:1,000 Jurkat cells (an established acute lymphoblastic leukemia cell line). The limit of detection was seen to be 1:100 cells and 1:1,000 cells for FISHing lines and conventional FISH, respectively; however, the conventional method seemed to over-score the presence of K562 cells. This may in part be attributed to FISHing lines practically eliminating the chance of duplicate screening of cells and hastened the time of screening, enhancing scoring of all cells within the channels. This was compared to 1 in 500 cells on the slide being analyzed with the conventional FISH.

  4. Structural design of microfluidic channels for blood plasma separation.

    PubMed

    Zhang, Jingjing; Wei, Xueyong; Xue, Xiangdong; Jiang, Zhuangde

    2014-10-01

    Microfluidics devices for separation of plasma from whole blood can be applied to numerous clinical laboratory and point-of-care diagnostics, since over 90% of blood diagnosis tests are conducted using plasma. This paper proposed a structural design of microfluidic channels for blood plasma separation. The Euler-Euler Laminar Flow Model in COMSOL Multiphysics has been utilized to simulate the blood flow behavior in microchannels. Micro chips with separating microchannels of different designs were fabricated and tested. The geometrical effect of microchannels on plasma separation was investigated. Simulation results show that curved channel contributes little in lateral migration of cells in low flow rate and becomes a difficult choice in the case of high flow rate due to the coupling of centrifugal migration and Dean Vortex. Studies on the bifurcation corner radius and the angle between main channel and side channel show that an abrupt change in flow direction of cell free layer helps to get more plasma with higher purity. An optimal design of multi-bifurcation separator has been achieved by balancing the flow resistances of the side channels and the main channels.

  5. Stop flow lithography in perfluoropolyether (PFPE) microfluidic channels.

    PubMed

    Bong, Ki Wan; Lee, Jiseok; Doyle, Patrick S

    2014-12-21

    Stop Flow Lithography (SFL) is a microfluidic-based particle synthesis method for creating anisotropic multifunctional particles with applications that range from MEMS to biomedical engineering. Polydimethylsiloxane (PDMS) has been typically used to construct SFL devices as the material enables rapid prototyping of channels with complex geometries, optical transparency, and oxygen permeability. However, PDMS is not compatible with most organic solvents which limit the current range of materials that can be synthesized with SFL. Here, we demonstrate that a fluorinated elastomer, called perfluoropolyether (PFPE), can be an alternative oxygen permeable elastomer for SFL microfluidic flow channels. We fabricate PFPE microfluidic devices with soft lithography and synthesize anisotropic multifunctional particles in the devices via the SFL process--this is the first demonstration of SFL with oxygen lubrication layers in a non-PDMS channel. We benchmark the SFL performance of the PFPE devices by comparing them to PDMS devices. We synthesized particles in both PFPE and PDMS devices under the same SFL conditions and found the difference of particle dimensions was less than a micron. PFPE devices can greatly expand the range of precursor materials that can be processed in SFL because the fluorinated devices are chemically resistant to most organic solvents, an inaccessible class of reagents in PDMS-based devices due to swelling.

  6. Microfluidic channel for characterizing normal and breast cancer cells

    NASA Astrophysics Data System (ADS)

    TruongVo, T. N.; Kennedy, R. M.; Chen, H.; Chen, A.; Berndt, A.; Agarwal, M.; Zhu, L.; Nakshatri, H.; Wallace, J.; Na, S.; Yokota, H.; Ryu, J. E.

    2017-03-01

    A microfluidic channel was designed and fabricated for the investigation of behaviors of normal and cancer cells in a narrow channel. A specific question addressed in this study was whether it is possible to distinguish normal versus cancer cells by detecting their stationary and passing behaviors through a narrow channel. We hypothesized that due to higher deformability, softer cancer cells will pass through the channel further and quicker than normal cells. Two cell lines, employed herein, were non-tumor breast epithelial cells (MCF-10A; 11.2  ±  2.4 µm in diameter) and triple negative breast cancer cells (MDA-MB-231; 12.4  ±  2.1 µm in diameter). The microfluidic channel was 300 µm long and linearly tapered with a width of 30 µm at an inlet to 5 µm at an outlet. The result revealed that MDA-MB-231 cells entered and stuck further toward the outlet than MCF-10A cells in response to a slow flow (2 µl min‑1). Further, in response to a fast flow (5 µl min‑1), the passage time (mean  ±  s.d.) was 26.6  ±  43.9 s for normal cells (N  =  158), and 1.9  ±  1.4 s for cancer cells (N  =  128). The measurement of stiffness by atomic force microscopy as well as model-based predictions pointed out that MDA-MB-231 cells are significantly softer than MCF-10A cells. Collectively, the result in this study suggests that analysis of an individual cell’s behavior through a narrow channel can characterize deformable cancer cells from normal ones, supporting the possibility of enriching circulating tumor cells using novel microfluidics-based analysis.

  7. Optofluidic Waveguides in Teflon AF-Coated PDMS Microfluidic Channels

    PubMed Central

    Cho, Sung Hwan; Godin, Jessica; Lo, Yu-Hwa

    2010-01-01

    We report a new method for fabricating an optofluidic waveguide that is compatible with polydimethylsiloxane (PDMS). The light path follows the microfluidic channels, an architecture that can maximize detection efficiency and make the most economic use of chip area in many lab-on-chip applications. The PDMS-based microfluidic channels are coated with Teflon amorphous fluoropolymers (Teflon AF) which has a lower refractive index (n = 1.31) than water (n = 1.33) to form a water/Teflon AF optical waveguide. Driven by a vacuum pump, the Teflon AF solution was flowed through the channels, leaving a thin (5–15 µm) layer of coating on the channel wall as the cladding layer of optical waveguides. This coating process resolves the limitations of spin-coating processes by reducing the elasticity mismatch between the Teflon AF cladding layer and the PDMS device body. We demonstrate that the resulting optofluidic waveguide confines and guides the laser light through the liquid core channel. Furthermore, the light in such a waveguide can be split when the fluid flow is split. This new method enables highly integrated biosensors such as lab-on-chip flow cytometers and micro-fabricated fluorescence-activated cell sorter with on-chip excitation. PMID:20729984

  8. Optofluidic Waveguides in Teflon AF-Coated PDMS Microfluidic Channels.

    PubMed

    Cho, Sung Hwan; Godin, Jessica; Lo, Yu-Hwa

    2009-08-01

    We report a new method for fabricating an optofluidic waveguide that is compatible with polydimethylsiloxane (PDMS). The light path follows the microfluidic channels, an architecture that can maximize detection efficiency and make the most economic use of chip area in many lab-on-chip applications. The PDMS-based microfluidic channels are coated with Teflon amorphous fluoropolymers (Teflon AF) which has a lower refractive index (n = 1.31) than water (n = 1.33) to form a water/Teflon AF optical waveguide. Driven by a vacuum pump, the Teflon AF solution was flowed through the channels, leaving a thin (5-15 µm) layer of coating on the channel wall as the cladding layer of optical waveguides. This coating process resolves the limitations of spin-coating processes by reducing the elasticity mismatch between the Teflon AF cladding layer and the PDMS device body. We demonstrate that the resulting optofluidic waveguide confines and guides the laser light through the liquid core channel. Furthermore, the light in such a waveguide can be split when the fluid flow is split. This new method enables highly integrated biosensors such as lab-on-chip flow cytometers and micro-fabricated fluorescence-activated cell sorter with on-chip excitation.

  9. Droplet sorting in a loop of flat microfluidic channels.

    PubMed

    Kadivar, Erfan; Herminghaus, Stephan; Brinkmann, Martin

    2013-07-17

    Motivated by recent experiments, we numerically study the droplet traffic in microfluidic channels forming an asymmetric loop with a long and a short arm. The loop is connected to an inlet and an outlet channel by two right angled T-junctions. Assuming flat channels, we employ the boundary element method (BEM) to numerically solve the two-dimensional Darcy equation that governs two phase flow in the Hele-Shaw limit. The occurrence of different sorting regimes is summarized in sorting diagrams in terms of droplet size, distance between consecutive droplets in the inlet channel, and loop asymmetry for mobility ratios of the liquid phases larger and smaller than one. For large droplet distances, the traffic is regulated by the ratio of the total hydraulic resistances of the long and short arms. At high droplet densities and below a critical droplet size, droplet-droplet collisions are observed for both mobility ratios.

  10. Droplet sorting in a loop of flat microfluidic channels

    NASA Astrophysics Data System (ADS)

    Kadivar, Erfan; Herminghaus, Stephan; Brinkmann, Martin

    2013-07-01

    Motivated by recent experiments, we numerically study the droplet traffic in microfluidic channels forming an asymmetric loop with a long and a short arm. The loop is connected to an inlet and an outlet channel by two right angled T-junctions. Assuming flat channels, we employ the boundary element method (BEM) to numerically solve the two-dimensional Darcy equation that governs two phase flow in the Hele-Shaw limit. The occurrence of different sorting regimes is summarized in sorting diagrams in terms of droplet size, distance between consecutive droplets in the inlet channel, and loop asymmetry for mobility ratios of the liquid phases larger and smaller than one. For large droplet distances, the traffic is regulated by the ratio of the total hydraulic resistances of the long and short arms. At high droplet densities and below a critical droplet size, droplet-droplet collisions are observed for both mobility ratios.

  11. Biopolymers Confined in Surface-Modified Silicon Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Li, Y.; Pfohl, T.; Yasa, M.; Safinya, C. R.; Kim, J. H.; Kim, M. W.; Wen, Z.

    2001-03-01

    We have developed surface modification techniques for control of wettability and surface charge in lithographically fabricated Si microfluidic channels. Surface microstructures (patterns) with contrasting wetting properties were created using a combination of microcontact printing and polyelectrolyte adsorption. The selective control of the surface property enabled us to devise various techniques for loading and processing biomaterials in the channels. Using fluorescence and laser scanning confocal microscopy, we studied the structure of biopolymers including DNA, F-Actin and microtubules confined in the surface-modified microchannels. The polymers were observed to align linearly along the channels, which suggests that the channel arrays can be used as effective substrates for aligning filamentous proteins for structural characterization by x-ray diffraction. (Work supported by NSF-DMR-9972246, NSF-DMR-0076357, ONR-N00014-00-1-0214, UC-Biotech 99-14, and CULAR 99-216)

  12. Particle manipulation in a microfluidic channel using acoustic trap

    PubMed Central

    Lee, Jung Woo; Lee, Chang Yang; Teh, Shia Yen; Lee, Abraham; Shung, K. Kirk

    2011-01-01

    A high frequency sound beam was employed to explore an experimental method that could control particle motions in a microfluidic device. A 24 MHz single element lead zirconate titanate (PZT) transducer was built to transmit a focused ultrasound of variable duty factors (pulse duration/pulse repetition time), and its 1–3 piezo-composite structure established a tight focusing with f-number (focal depth/aperture size) of one. The transducer was excited by the Chebyshev windowed chirp signal sweeping from 18 MHz to 30 MHz with a 50% of duty factor, in order to ensure that enough sound beams were penetrated into the microfluidic device. The device was fabricated from a polydimethylsiloxane (PDMS) mold, and had a main channel composed of three subchannels among which particles flowed in the middle. A 60~70 μm diameter single droplet in the flow could be trapped near the channel bifurcation, and subsequently diverted into the sheath flow by releasing or shifting the acoustic trap. Hence, the results showed the potential use of a focused sound beam in microfluidic devices, and further suggested that this method could be exploited in the development of ultrasound-based flow cytometry and cell sorting devices. PMID:21603963

  13. Effect of channel geometry on cell adhesion in microfluidic devices.

    PubMed

    Green, James V; Kniazeva, Tatiana; Abedi, Mehdi; Sokhey, Darshan S; Taslim, Mohammad E; Murthy, Shashi K

    2009-03-07

    Microfluidic channels coated with ligands are a versatile platform for the separation or enrichment of cells from small sample volumes. This adhesion-based mode of separation is mediated by ligand-receptor bonds between the cells and channel surface and also by fluid shear stress. This paper demonstrates how aspects of microchannel geometry can play an additional role in controlling cell adhesion. With a combination of computational fluid dynamics modeling and cell adhesion experiments, channels with sharp turns are shown to have regions with near-zero velocity at the turn regions where large numbers of cells adhere or become collected. The lack of uniform adhesion in the turn regions compared to other regions of these channels, together with the large variability in observed cell adhesion indicates that channels with sharp turns are not optimal for cell-capture applications where predictable cell adhesion is desired. Channels with curved turns, on the other hand are shown to provide more uniform and predictable cell adhesion provided the gap between parallel arms of the channels is sufficiently wide. The magnitude of cell adhesion in these curved channels is comparable to that in straight channels with no turns.

  14. Photothermal generation of microbubbles on plasmonic nanostructures inside microfluidic channels

    NASA Astrophysics Data System (ADS)

    Li, Jingting; Li, Ming; Santos, Greggy M.; Zhao, Fusheng; Shih, Wei-Chuan

    2016-03-01

    Microbubbles have been utilized as micro-pumps, micro-mixers, micro-valves, micro-robots and surface cleaners. Various generation techniques can be found in the literature, including resistive heating, hydrodynamic methods, illuminating patterned metal films and noble metal nanoparticles of Au or Ag. We present photothermal microbubble generation by irradiating nanoporous gold disk covered microfluidic channels. The size of the microbubble can be controlled by adjusting the laser power. The dynamics of both bubble growth and shrinkage are studied. The advantages of this technique are flexible bubble generation locations, long bubble lifetimes, no need for light-adsorbing dyes, high controllability over bubble size, low power consumption, etc. This technique has the potential to provide new flow control functions in microfluidic devices.

  15. Computerized microfluidic cell culture using elastomeric channels and Braille displays.

    PubMed

    Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S; Takayama, Shuichi

    2004-11-09

    Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.

  16. Computerized microfluidic cell culture using elastomeric channels and Braille displays

    PubMed Central

    Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S.; Takayama, Shuichi

    2004-01-01

    Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use. PMID:15514025

  17. Particle diffusion in a field-guided microfluidic channel

    NASA Astrophysics Data System (ADS)

    Helseth, L. E.; Wen, H. Z.; Fischer, T. M.

    2006-01-01

    If an ensemble of particles is squeezed together in a trap that is suddenly removed, one may anticipate that they obey the normal Fickian diffusion equation, which predicts that the width of the system increases proportionally to the square root of the elapsed time t. Here we show that for a finite one-dimensional system composed of particles which interact via dipolar forces, this is no longer correct. Instead, our measurements using colloidal particles in a removable magnetic trap suggest that the system size increases as t1/5, which may be of importance for the transport of interacting particles in microfluidic channels.

  18. Quasistatic packings of droplets in flat microfluidic channels

    NASA Astrophysics Data System (ADS)

    Kadivar, Erfan

    2016-02-01

    As observed in recent experiments, monodisperse droplets self-assemble spontaneously in different ordered packings. In this work, we present a numerical study of the droplet packings in the flat rectangular microfluidic channels. Employing the boundary element method, we numerically solve the Stokes equation in two-dimension and investigate the appearance of droplet packing and transition between one and two-row packings of monodisperse emulsion droplets. By calculating packing force applied on the droplet interface, we investigate the effect of flow rate, droplet size, and surface tension on the packing configurations of droplets and transition between different topological packings.

  19. Dynamics of tandem bubble interaction in a microfluidic channel

    PubMed Central

    Yuan, Fang; Sankin, Georgy; Zhong, Pei

    2011-01-01

    The dynamics of tandem bubble interaction in a microfluidic channel (800 × 21 μm, W × H) have been investigated using high-speed photography, with resultant fluid motion characterized by particle imaging velocimetry. A single or tandem bubble is produced reliably via laser absorption by micron-sized gold dots (6 μm in diameter with 40 μm in separation distance) coated on a glass surface of the microfluidic channel. Using two pulsed Nd:YAG lasers at λ = 1064 nm and ∼10 μJ/pulse, the dynamics of tandem bubble interaction (individual maximum bubble diameter of 50 μm with a corresponding collapse time of 5.7 μs) are examined at different phase delays. In close proximity (i.e., interbubble distance = 40 μm or γ = 0.8), the tandem bubbles interact strongly with each other, leading to asymmetric deformation of the bubble walls and jet formation, as well as the production of two pairs of vortices in the surrounding fluid rotating in opposite directions. The direction and speed of the jet (up to 95 m/s), as well as the orientation and strength of the vortices can be varied by adjusting the phase delay. PMID:22088007

  20. Dynamics of tandem bubble interaction in a microfluidic channel.

    PubMed

    Yuan, Fang; Sankin, Georgy; Zhong, Pei

    2011-11-01

    The dynamics of tandem bubble interaction in a microfluidic channel (800  ×  21 μm, W × H) have been investigated using high-speed photography, with resultant fluid motion characterized by particle imaging velocimetry. A single or tandem bubble is produced reliably via laser absorption by micron-sized gold dots (6 μm in diameter with 40 μm in separation distance) coated on a glass surface of the microfluidic channel. Using two pulsed Nd:YAG lasers at λ = 1064 nm and ∼10 μJ/pulse, the dynamics of tandem bubble interaction (individual maximum bubble diameter of 50 μm with a corresponding collapse time of 5.7 μs) are examined at different phase delays. In close proximity (i.e., interbubble distance = 40 μm or γ = 0.8), the tandem bubbles interact strongly with each other, leading to asymmetric deformation of the bubble walls and jet formation, as well as the production of two pairs of vortices in the surrounding fluid rotating in opposite directions. The direction and speed of the jet (up to 95 m/s), as well as the orientation and strength of the vortices can be varied by adjusting the phase delay.

  1. Rapid detection of hemagglutination using restrictive microfluidic channels equipped with waveguide-mode sensors

    NASA Astrophysics Data System (ADS)

    Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Fu, Mengying; Ohki, Yoshimichi; Tanaka, Torahiko; Makishima, Makoto

    2016-02-01

    Hemagglutination is utilized for various immunological assays, including blood typing and virus detection. Herein, we describe a method of rapid hemagglutination detection based on a microfluidic channel installed on an optical waveguide-mode sensor. Human blood samples mixed with hemagglutinating antibodies associated with different blood groups were injected into the microfluidic channel, and reflectance spectra of the samples were measured after stopping the flow. The agglutinated and nonagglutinated samples were distinguishable by the alterations in their reflectance spectra with time; the microfluidic channels worked as spatial restraints for agglutinated red blood cells. The demonstrated system allowed rapid hemagglutination detection within 1 min. The suitable height of the channels was also discussed.

  2. Dynamics of Ceramide Channels Detected Using a Microfluidic System

    PubMed Central

    DeVoe, Don L.; Colombini, Marco

    2012-01-01

    Ceramide, a proapoptotic sphingolipid, has been shown to form channels, in mitochondrial outer membranes, large enough to translocate proteins. In phospholipid membranes, electrophysiological studies and electron microscopic visualization both report that these channels form in a range of sizes with a modal value of 10 nm in diameter. A hydrogen bonded barrel-like structure consisting of hundreds of ceramide molecules has been proposed for the structure of the channel and this is supported by electrophysiological studies and molecular dynamic simulations. To our knowledge, the mechanical strength and deformability of such a large diameter but extremely thin cylindrical structure has never been reported. Here we present evidence for a reversible mechanical distortion of the cylinder following the addition of La3+. A microfluidic system was used to repeatedly lower and then restore the conductance by alternatively perfusing La3+ and EDTA. Although aspects of the kinetics of conductance drop and recovery are consistent with a disassembly/diffusion/reassembly model, others are inconsistent with the expected time scale of lateral diffusion of disassembled channel fragments in the membrane. The presence of a residual conductance following La3+ treatment and the relationship between the residual conductance and the initial conductance were both indicative of a distortion/recovery process in analogy with a pressure-induced distortion of a flexible cylinder. PMID:22984432

  3. Exploring the Mode of Action of Bioactive Compounds by Microfluidic Transcriptional Profiling in Mycobacteria

    PubMed Central

    Lim, Vivian; Naim, Ahmad Nazri Mohamed; Bifani, Pablo; Boshoff, Helena I. M.; Sambandamurthy, Vasan K.; Dick, Thomas; Hibberd, Martin L.; Schreiber, Mark; Rao, Srinivasa P. S.

    2013-01-01

    Most candidate anti-bacterials are identified on the basis of their whole cell anti-bacterial activity. A critical bottleneck in the early discovery of novel anti-bacterials is tracking the structure activity relationship (SAR) of the novel compounds synthesized during the hit to lead and lead optimization stage. It is often very difficult for medicinal chemists to visualize if the novel compounds synthesized for understanding SAR of a particular scaffold have similar molecular mechanism of action (MoA) as that of the initial hit. The elucidation of the molecular MoA of bioactive inhibitors is critical. Here, a new strategy and routine assay for MoA de-convolution, using a microfluidic platform for transcriptional profiling of bacterial response to inhibitors with whole cell activity has been presented. First a reference transcriptome compendium of Mycobacterial response to various clinical and investigational drugs was built. Using feature reduction, it was demonstrated that subsets of biomarker genes representative of the whole genome are sufficient for MoA classification and deconvolution in a medium-throughput microfluidic format ultimately leading to a cost effective and rapid tool for routine antibacterial drug-discovery programs. PMID:23935951

  4. Liposomes as signal amplification reagents for bioassays in microfluidic channels.

    PubMed

    Locascio, Laurie E; Hong, Jennifer S; Gaitan, Michael

    2002-03-01

    Liposomes with encapsulated carboxyfluorescein were used in an affinity-based assay to provide signal amplification for small-volume fluorescence measurements. Microfluidic channels were fabricated by imprinting in a plastic substrate material, poly(ethylene terephthalate glycol) (PETG), using a silicon template imprinting tool. Streptavidin was linked to the surface through biotinylated-protein for effective immobilization with minimal nonspecific adsorption of the liposome reagent. Lipids derivatized with biotin were incorporated into the liposome membrane to make the liposomes reactive for affinity assays. Specific binding of the liposomes to microchannel walls, dependence of binding on incubation time, and nonspecific adsorption of the liposome reagent were evaluated. The results of a competitive assay employing liposomes in the microchannels are presented.

  5. Non-planar PDMS microfluidic channels and actuators: a review.

    PubMed

    Hwang, Yongha; Candler, Rob N

    2017-09-01

    This review examines the state of the art for manufacturing non-planar miniature channels and actuators from PDMS, where non-planar structures are defined here as those beyond simple extrusions of 2D designs, either with rounded or variable cross sections or with an emergence of the channel trajectory out-of-plane. The motivation for 3D PDMS structures and advances in their fabrication are described, focusing on geometries that were previously unachievable through conventional microfabrication. The motivation for non-planar microfluidic channels and actuators is first discussed and the existing literature is grouped into general fabrication themes and described. The structures are organized by their method of fabrication and evaluated based on their relevant properties, including the capability of producing structures with complex geometry, automation of the fabrication process, and minimum feature size. Additional properties are included for work in the more recently emerging field of non-planar PDMS actuators, where the feature size, actuation stroke, and actuation method are the key parameters of interest. In particular, this review considers the impact from recent advances in additive manufacturing, which now allow creation of truly arbitrary 3D structures down to ∼100 μm size scales.

  6. Electroosmotic properties of microfluidic channels composed of poly(dimethylsiloxane).

    PubMed

    Ren, X; Bachman, M; Sims, C; Li, G P; Allbritton, N

    2001-10-25

    Microfluidic devices fabricated from polymers exhibit great potential in biological analyses. Poly(dimethylsiloxane) (PDMS) has shown promise as a substrate for rapid prototyping of devices. Despite this, disagreement exists in the literature as to the ability of PDMS to support electroosmotic (EO) flow and the stability of that flow over time. We demonstrate that in low ionic strength solutions near neutral in pH. oxidized PDMS had a four-fold greater EO mobility (mu(eo)) compared to native PDMS. The greater mu(eo) was maintained irrespective of whether glass or PDMS was used as a support forming one side of the channel. This enhanced mu(eo) was preserved as long as the channels were filled with an aqueous solution. Upon exposure of the channels to air, the mobility decreased by a factor of two with a half-life of 9 h. The EO properties of the air-exposed, oxidized PDMS were regenerated by exposure to strong base. High ionic strength, neutral in pH buffers compatible with living eukaryotic cells diminished the EO flow in the oxidized PDMS devices to a much greater extent than in the native PDMS devices. For analyses utilizing intact and living cells, oxidation of PDMS may not be an effective strategy to substantially increase the mu(eo).

  7. Low density cell culture of locust neurons in closed-channel microfluidic devices.

    PubMed

    Göbbels, Katrin; Thiebes, Anja Lena; van Ooyen, André; Schnakenberg, Uwe; Bräunig, Peter

    2010-08-01

    Microfluidic channel systems were fabricated out of polydimethylsiloxane (PDMS) and used as culture vessels for primary culture of neurons from locust thoracic ganglia. In a biocompatibility study it was shown that cell adhesion and neuronal cell growth of locust neurons on uncoated PDMS was restricted. Coating with concanavalin A improved cell adhesion. In closed-channel microfluidic devices neurons were grown in static-bath culture conditions for more than 15 days. Cell densities of up to 20 cells/channel were not exceeded in low-density cultures but we also found optimal cell growth of single neurons inside individual channels. The first successful cultivation of insect neurons in closed-channel microfluidic devices provides a prerequisite for the development of low density neuronal networks on multi electrode arrays combined with microfluidic devices.

  8. Salmonella detection in a microfluidic channel using orbiting magnetic beads

    NASA Astrophysics Data System (ADS)

    Ballard, Matt; Mills, Zachary; Owen, Drew; Hanasoge, Srinivas; Hesketh, Peter; Alexeev, Alexander

    2015-03-01

    We use three-dimensional simulations to model the detection of salmonella in a complex fluid sample in a microfluidic channel. Salmonella is captured using magnetic microbeads orbiting around soft ferromagnetic discs at the microchannel bottom subjected to a rotating external magnetic field. Numerical simulations are used to model the dynamics of salmonella and microbeads throughout the detection process. We examine the effect of the channel geometry on the salmonella capture, and the forces applied to the salmonella as it is dragged through the fluid after capture. Our findings guide the design of a lab-on-a-chip device to be used for detection of salmonella in food samples in a way that ensures that salmonella captured by orbiting microbeads are preserved until they can be extracted from the system for testing, and are not washed away by the fluid flow or damaged due to the experience of excessive stresses. Such a device is needed to detect bacteria at the food source and prevention of consumption of contaminated food, and also can be used for the detection of a variety of biomaterials of interest from complex fluid samples. Support from USDA and NSF is gratefully acknowledged.

  9. Novel nanoplasmonic biosensor integrated in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Solis-Tinoco, V.; Sepulveda, B.; Lechuga, L. M.

    2015-06-01

    An important motivation of the actual biosensor research is to develop a multiplexed sensing platform of high sensitivity fabricated with large-scale and low-cost technologies for applications such as diagnosis and monitoring of diseases, drug discovery and environmental control. Biosensors based on localized plasmon resonance (LSPR) have demonstrated to be a novel and effective platform for quantitative detection of biological and chemical analytes. Here, we describe a novel label-free nanobiosensor consisting of an array of closely spaced, vertical, elastomeric nanopillars capped with plasmonic gold nanodisks in a SU-8 channel. The principle is based on the refractive index sensing using the LSPR of gold nanodisks. The fabrication of the nanobiosensor is based on replica molding technique and gold nanodisks are incorporated on the polymer structures by e-beam evaporation. In this work, we provide the strategies for controlling the silicon nanostructure replication using thermal polymers and photopolymers with different Young's modulus, in order to minimize the common distortions in the process and to obtain a reliable replica of the Si master. The master mold of the biosensor consists of a hexagonal array of silicon nanopillars, whose diameter is ~200 nm, and whose height can range from 250 nm to 1.300 μm, separated 400 nm from the center to center, integrated in a SU-8 microfluidic channel.

  10. Single-File Escape of Colloidal Particles from Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Locatelli, Emanuele; Pierno, Matteo; Baldovin, Fulvio; Orlandini, Enzo; Tan, Yizhou; Pagliara, Stefano

    2016-07-01

    Single-file diffusion is a ubiquitous physical process exploited by living and synthetic systems to exchange molecules with their environment. It is paramount to quantify the escape time needed for single files of particles to exit from constraining synthetic channels and biological pores. This quantity depends on complex cooperative effects, whose predominance can only be established through a strict comparison between theory and experiments. By using colloidal particles, optical manipulation, microfluidics, digital microscopy, and theoretical analysis we uncover the self-similar character of the escape process and provide closed-formula evaluations of the escape time. We find that the escape time scales inversely with the diffusion coefficient of the last particle to leave the channel. Importantly, we find that at the investigated microscale, bias forces as tiny as 10-15 N determine the magnitude of the escape time by drastically reducing interparticle collisions. Our findings provide crucial guidelines to optimize the design of micro- and nanodevices for a variety of applications including drug delivery, particle filtering, and transport in geometrical constrictions.

  11. Single-File Escape of Colloidal Particles from Microfluidic Channels.

    PubMed

    Locatelli, Emanuele; Pierno, Matteo; Baldovin, Fulvio; Orlandini, Enzo; Tan, Yizhou; Pagliara, Stefano

    2016-07-15

    Single-file diffusion is a ubiquitous physical process exploited by living and synthetic systems to exchange molecules with their environment. It is paramount to quantify the escape time needed for single files of particles to exit from constraining synthetic channels and biological pores. This quantity depends on complex cooperative effects, whose predominance can only be established through a strict comparison between theory and experiments. By using colloidal particles, optical manipulation, microfluidics, digital microscopy, and theoretical analysis we uncover the self-similar character of the escape process and provide closed-formula evaluations of the escape time. We find that the escape time scales inversely with the diffusion coefficient of the last particle to leave the channel. Importantly, we find that at the investigated microscale, bias forces as tiny as 10^{-15}  N determine the magnitude of the escape time by drastically reducing interparticle collisions. Our findings provide crucial guidelines to optimize the design of micro- and nanodevices for a variety of applications including drug delivery, particle filtering, and transport in geometrical constrictions.

  12. Enhancing the biocompatibility of microfluidics-assisted fabrication of cell-laden microgels with channel geometry.

    PubMed

    Kim, Suntae; Oh, Jonghyun; Cha, Chaenyung

    2016-11-01

    Microfluidic flow-focusing devices (FFD) are widely used to generate monodisperse droplets and microgels with controllable size, shape and composition for various biomedical applications. However, highly inconsistent and often low viability of cells encapsulated within the microgels prepared via microfluidic FFD has been a major concern, and yet this aspect has not been systematically explored. In this study, we demonstrate that the biocompatibility of microfluidic FFD to fabricate cell-laden microgels can be significantly enhanced by controlling the channel geometry. When a single emulsion ("single") microfluidic FFD is used to fabricate cell-laden microgels, there is a significant decrease and batch-to-batch variability in the cell viability, regardless of their size and composition. It is determined that during droplet generation, some of the cells are exposed to the oil phase which is shown to have a cytotoxic effect. Therefore, a microfluidic device with a sequential ('double') flow-focusing channels is employed instead, in which a secondary aqueous phase containing cells enters the primary aqueous phase, so the cells' exposure to the oil phase is minimized by directing them to the center of droplets. This microfluidic channel geometry significantly enhances the biocompatibility of cell-laden microgels, while maintaining the benefits of a typical microfluidic process. This study therefore provides a simple and yet highly effective strategy to improve the biocompatibility of microfluidic fabrication of cell-laden microgels.

  13. Fabrication of three-dimensional microfluidic channels inside glass using nanosecond laser direct writing.

    PubMed

    Liu, Changning; Liao, Yang; He, Fei; Shen, Yinglong; Chen, Danping; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

    2012-02-13

    We show that fabrication of three-dimensional microfluidic channels embedded in glass can be achieved by using a Q-switched, frequency-doubled Nd:YAG laser. The processing mainly consists of two steps: (1) formation of hollow microfluidic channels in porous glass immersed in Rhodamine 6G dissolved in water by nanosecond laser ablation; and (2) postannealing of the fabricated porous glass sample at 1120 °C for consolidation of the sample. In particular, a bilayer microfluidic structure is created in glass substrate using this technique for showcasing its capability of three-dimensional structuring.

  14. Tunable mode coupler in the microfluidic channel for the fiber optics refractive index sensor

    NASA Astrophysics Data System (ADS)

    Gao, R.; Li, G.; Zhou, Y.; Jiang, Y.

    2014-11-01

    We propose and demonstrate a highly sensitive optical fiber microfluidic refractometer. A microhole is fabricated in the photonic crystal fiber (PCF) by using femtosecond laser beam, which combines the tunable mode coupler and microfluidic channel. The mode field diameter of the guided light is changed with the refractive index in the microfluidic channel, which results in the tunable coupling ratio between the core and the cladding in the PCF. Therefore, the refractive index of the liquid in the microfluidic channel is detected by interrogating the fringe visibility of the reflection spectrum. These experiments results demonstrate that the sensor is insensitive with the temperature and strain, and a RI sensitivity of up to 150.7 dB/RIU is achieved, establishing the tunable mode coupler as a sensitive and versatile sensor.

  15. Noninvasive fluid flow measurements in microfluidic channels with backscatter interferometry.

    PubMed

    Markov, Dmitry A; Dotson, Stephen; Wood, Scott; Bornhop, Darryl J

    2004-11-01

    The ability to measure fluid velocity within picoliter volumes or on-chip noninvasively, is important toward fully realizing the potential of microfluidics and micrototal analysis systems, particularly in applications such as micro-high-performance liquid chromatography (HPLC) or in metering mixing where the flow rate must be quantified. Additionally, these measurements need to be performed directly on moving fluids in a noninvasive fashion. We presented here the proof of principle experiments showing nonintrusive fluid flow measurements can be accomplished on-chip using a pump and probe configuration with backscattering interferometry. The on-chip interferometric backscatter detector (OCIBD) is based on a fiber-coupled HeNe laser that illuminates a portion of an isotropically etched 40 microm radius channel and a position sensitive transducer to measure fringe pattern shifts. An infrared laser with a mechanical shutter is used to heat a section of a flowing volume and the resulting refractive index (RI) change is detected with the OCIBD downstream as a time-dependent RI perturbation. Fluid velocity is quantified as changes in the phase difference between the shutter signal and the OCIBD detected signal in the Fourier domain. The experiments are performed in the range of 3-6 microL/h with 3sigma detection limits determined to be 0.127 nL/s. Additionally, the RI response of the system is calibrated using temperature changes as well as glycerol solutions.

  16. Etched core fiber Bragg grating sensor integrated with microfluidic channel

    NASA Astrophysics Data System (ADS)

    Lee, Sang-Mae; Jeong, Myung-Yung; Saini, Simarjeet S.

    2011-05-01

    We demonstrate an etched-core fiber Bragg grating sensor for detection of bio-chemical agents. The fiber Bragg grating of the sensor is etched to a diameter of 7 μm. The transition between the etched and the unetched core consists of an asymmetric taper resulting in excitation of multiple modes. The different excited modes respond differently to change in refractive index, temperature and strain. This allows for measurements for changes in these three parameters in a single measurement by simultaneous measurement of reflections in Bragg wavelengths for different modes. This parametric discrimination is confirmed experimentally by measuring the refractive index of water as temperature is increased. The sensor is then integrated in a micro-fluidic channel fabricated using Polydimethylsiloxane (PDMS) substrate and tested by introducing different chemicals. The sensitivity of the sensor to refractive index change is 92 nm/riu close to the refractive index of water. Assuming a wavelength resolution of 1 pm, index resolution of 1x10-5, a strain resolution of 1 microstrain, and a temperature resolution of 0.032 ºC is achieved by the sensor.

  17. Microfluidic Mixing Using Pulsing in Simple Geometry Channels

    NASA Astrophysics Data System (ADS)

    Glasgow, Ian; Lieber, Samuel; Aubry, Nadine

    2003-11-01

    Mixing at the microscale, a necessary step for practically every integrated microfluidic device, has been a challenge to researchers for years. The method we present consists of superimposing out-of-phase pulsing over the base flow. Studies of the effects of the salient parameters were conducted by computational fluid dynamics and by the physical mixing of two aqueous reagents at room temperature. All channel segments, upstream and downstream of the confluence, are 200 μm wide by 120 μm deep --- a practical scale for mass-produced disposable devices. The flow rate and average velocity after the confluence of the two reagents are in the range of 10-200 nl s-1 and 0.5-8.0mm s-1, respectively (Reynolds number ranges from 0.07 to 1.2). We use a mass diffusion constant of 10-10m^2s-1, typical of many BioMEMS applications. This simple solution provides complete and reliable mixing at the confluence of most practical devices. Because the mixing does not require fancy geometry, additional parts, nor extra volume, this method will be useful for microreactors and micro total analysis systems, for applications including genetic screening, point-of-care diagnostics, pharmaceutical development, and environmental monitoring.

  18. Method of measuring nitric oxide release by vascular endothelial cells grown in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Hosseinpour, S.; Liu, A. C.; Barakat, A. I.; Choy, J. C.; Gray, B. L.

    2014-03-01

    In this paper, a simple and versatile method is presented which enables detection of nitric oxide (NO) released from vascular endothelial cells (ECs) cultured in microfluidic structures. The culturing system and NO measurement method allow cell shape to be controlled in a non-invasive manner using microfluidic structures while NO release is monitored for cell shape versus function studies. The culturing system consists of arrays of polydimethylsiloxane (PDMS) fluidic channels 120 micrometers in depth and ranging from 100 micrometers to 3 mm in width. The number of channels in each array is varied to yield a constant cell culture surface area (75 mm2) independent of channel width. The channel surfaces are collagen-coated and ECs are cultured to confluence within the channels. A cell scraper is then used to scrape extraneous cells cultured between channels, and NO measurements are made 18 to 24 hours later. A chemiluminescence-based sensor system (NOA 280i, Sievers NO Analyzer) is utilized to measure sample NO. Initial results indicate that NO concentrations can be measured from different microfluidic channel-containing samples using this method. It is shown that there is no significant difference in NO concentration derived from channels of different widths even though the degree of cell elongation varies due to physical constraint by microfluidic channel walls. However, cells treated with TNFα release more NO than untreated cells in fluidic channels, which is comparable to the function of ECs cultured in conventional culturing systems such as culturing dishes.

  19. Light-sheet based lithography technique for patterning an array of microfluidic channels.

    PubMed

    Mohan, Kavya; Mondal, Partha Pratim

    2017-02-08

    We propose a Light-sheet laser interference lithography technique for fabricating periodic microfluidic channels. This technique uses multiple light-sheet illumination pattern that is generated using a spatial filter at the back-aperture of the cylindrical lens. Specially designed spatial filter is used that give rise to a periodic pattern at the focal plane which is essentially a 1D Fourier transform of the spatial filter transfer function. One-dimensional focusing property of the cylindrical lens result in the generation of line shaped channel geometry. To design microfluidic channels, the illumination pattern is exposed to the glass substrate coated with a photopolymer sensitized to 532 nm and subsequently developed using standard chemical protocols. Experimentally, the 1D periodic channel structure has an approximate width and periodicity of approximately 11.25 microns. Light-sheets based lithography technique offer a fast and single-shot process to generate microfluidic channels. © 2016 Wiley Periodicals, Inc.

  20. Single-step fabrication of microfluidic channels filled with nanofibrous membrane using femtosecond laser irradiation

    NASA Astrophysics Data System (ADS)

    Tavangar, Amirhossein; Tan, Bo; Venkatakrishnan, K.

    2010-08-01

    In this paper, we demonstrate a new method of fabricating silicon microfluidic channels filled with a porous nanofibrous structure utilizing a femtosecond laser. The nanofibrous structure can act as a membrane used for microfiltration. This method allows us to generate both the microfluidic channel and the fibrous nanostructure in a single step under ambient conditions. Due to laser irradiation, a large number of nanoparticles ablate from the channel surface, and then aggregate and grow into porous nanofibrous structures and fill the channels. Energy dispersive x-ray spectroscopy (EDS) analysis was conducted to examine the oxygen concentration in the membrane structure. Our results demonstrated that by controlling the laser parameters including pulse repetition, pulse width and scanning speed, different microfluidic channels with a variety of porosity could be obtained.

  1. Deformation of a single mouse oocyte in a constricted microfluidic channel

    PubMed Central

    Luo, ZhengYuan; Guven, Sinan; Gozen, Irep; Chen, Pu; Tasoglu, Savas; Anchan, Raymond M; Bai, BoFeng; Demirci, Utkan

    2015-01-01

    Single oocyte manipulation in microfluidic channels via precisely controlled flow is critical in microfluidic-based in vitro fertilization. Such systems can potentially minimize the number of transfer steps among containers for rinsing as often performed during conventional in vitro fertilization and can standardize protocols by minimizing manual handling steps. To study shape deformation of oocytes under shear flow and its subsequent impact on their spindle structure is essential for designing microfluidics for in vitro fertilization. Here, we developed a simple yet powerful approach to (i) trap a single oocyte and induce its deformation through a constricted microfluidic channel, (ii) quantify oocyte deformation in real-time using a conventional microscope, and (iii) retrieve the oocyte from the microfluidic device to evaluate changes in their spindle structures. We found that oocytes can be significantly deformed under high flow rates, e.g., 10 μl/min in a constricted channel with a width and height of 50 and 150 μm, respectively. Oocyte spindles can be severely damaged, as shown here by immunocytochemistry staining of the microtubules and chromosomes. The present approach can be useful to investigate underlying mechanisms of oocyte deformation exposed to well-controlled shear stresses in microfluidic channels, which enables a broad range of applications for reproductive medicine. PMID:26696793

  2. The Deformation of Polydimethylsiloxane (PDMS) Microfluidic Channels Filled with Embedded Circular Obstacles under Certain Circumstances.

    PubMed

    Roh, Changhyun; Lee, Jaewoong; Kang, Chankyu

    2016-06-18

    Experimental investigations were conducted to determine the influence of polydimethylsiloxane (PDMS) microfluidic channels containing aligned circular obstacles (with diameters of 172 µm and 132 µm) on the flow velocity and pressure drop under steady-state flow conditions. A significant PDMS bulging was observed when the fluid flow initially contacted the obstacles, but this phenomenon decreased in the 1 mm length of the microfluidic channels when the flow reached a steady-state. This implies that a microfluidic device operating with steady-state flows does not provide fully reliable information, even though less PDMS bulging is observed compared to quasi steady-state flow. Numerical analysis of PDMS bulging using ANSYS Workbench showed a relatively good agreement with the measured data. To verify the influence of PDMS bulging on the pressure drop and flow velocity, theoretical analyses were performed and the results were compared with the experimental results. The measured flow velocity and pressure drop data relatively matched well with the classical prediction under certain circumstances. However, discrepancies were generated and became worse as the microfluidic devices were operated under the following conditions: (1) restricted geometry of the microfluidic channels (i.e., shallow channel height, large diameter of obstacles and a short microchannel length); (2) operation in quasi-steady state flow; (3) increasing flow rates; and (4) decreasing amount of curing agent in the PDMS mixture. Therefore, in order to obtain reliable data a microfluidic device must be operated under appropriate conditions.

  3. Deformation of a single mouse oocyte in a constricted microfluidic channel.

    PubMed

    Luo, ZhengYuan; Guven, Sinan; Gozen, Irep; Chen, Pu; Tasoglu, Savas; Anchan, Raymond M; Bai, BoFeng; Demirci, Utkan

    2015-10-01

    Single oocyte manipulation in microfluidic channels via precisely controlled flow is critical in microfluidic-based in vitro fertilization. Such systems can potentially minimize the number of transfer steps among containers for rinsing as often performed during conventional in vitro fertilization and can standardize protocols by minimizing manual handling steps. To study shape deformation of oocytes under shear flow and its subsequent impact on their spindle structure is essential for designing microfluidics for in vitro fertilization. Here, we developed a simple yet powerful approach to (i) trap a single oocyte and induce its deformation through a constricted microfluidic channel, (ii) quantify oocyte deformation in real-time using a conventional microscope, and (iii) retrieve the oocyte from the microfluidic device to evaluate changes in their spindle structures. We found that oocytes can be significantly deformed under high flow rates, e.g., 10 μl/min in a constricted channel with a width and height of 50 and 150 μm, respectively. Oocyte spindles can be severely damaged, as shown here by immunocytochemistry staining of the microtubules and chromosomes. The present approach can be useful to investigate underlying mechanisms of oocyte deformation exposed to well-controlled shear stresses in microfluidic channels, which enables a broad range of applications for reproductive medicine.

  4. Motion of an elastic capsule in a square microfluidic channel.

    PubMed

    Kuriakose, S; Dimitrakopoulos, P

    2011-07-01

    In the present study we investigate computationally the steady-state motion of an elastic capsule along the centerline of a square microfluidic channel and compare it with that in a cylindrical tube. In particular, we consider a slightly over-inflated elastic capsule made of a strain-hardening membrane with comparable shearing and area-dilatation resistance. Under the conditions studied in this paper (i.e., small, moderate, and large capsules at low and moderate flow rates), the capsule motion in a square channel is similar to and thus governed by the same scaling laws with the capsule motion in a cylindrical tube, even though in the channel the cross section in the upstream portion of large capsules is nonaxisymmetric (i.e., square-like with rounded corners). When the hydrodynamic forces on the membrane increase, the capsule develops a pointed downstream edge and a flattened rear (possibly with a negative curvature) so that the restoring tension forces are increased as also happens with droplets. Membrane tensions increase significantly with the capsule size while the area near the downstream tip is the most probable to rupture when a capsule flows in a microchannel. Because the membrane tensions increase with the interfacial deformation, a suitable Landau-Levich-Derjaguin-Bretherton analysis reveals that the lubrication film thickness h for large capsules depends on both the capillary number Ca and the capsule size a; our computations determine the latter dependence to be (in dimensionless form) h ~ a(-2) for the large capsules studied in this work. For small and moderate capsule sizes a, the capsule velocity Ux and additional pressure drop ΔP+ are governed by the same scaling laws as for high-viscosity droplets. The velocity and additional pressure drop of large thick capsules also follow the dynamics of high-viscosity droplets, and are affected by the lubrication film thickness. The motion of our large thick capsules is characterized by a Ux-U ~ h ~ a(-2

  5. Motion of an elastic capsule in a square microfluidic channel

    PubMed Central

    Kuriakose, S.; Dimitrakopoulos, P.

    2013-01-01

    In the present study we investigate computationally the steady-state motion of an elastic capsule along the centerline of a square microfluidic channel and compare it with that in a cylindrical tube. In particular, we consider a slightly over-inflated elastic capsule made of a strain-hardening membrane with comparable shearing and area-dilatation resistance. Under the conditions studied in this paper (i.e. small, moderate and large capsules at low and moderate flow rates), the capsule motion in a square channel is similar to, and thus governed by the same scaling laws with the capsule motion in a cylindrical tube, even though in the channel the cross-section in the upstream portion of large capsules is non-axisymmetric (i.e. square-like with rounded corners). When the hydrodynamic forces on the membrane increase, the capsule develops a pointed downstream edge and a flattened rear (possibly with a negative curvature) so that the restoring tension forces are increased as also happens with droplets. Membrane tensions increase significantly with the capsule size while the area near the downstream tip is the most probable to rupture when a capsule flows in a microchannel. Because the membrane tensions increase with the interfacial deformation, a suitable Landau-Levich-Derjaguin-Bretherton analysis reveals that the lubrication film thickness h for large capsules depends on both the capillary number Ca and the capsule size a; our computations determine the latter dependence to be (in dimensionless form) h ~ a−2 for the large capsules studied in this work. For small and moderate capsule sizes a, the capsule velocity Ux and additional pressure drop ΔP+ are governed by the same scaling laws as for high-viscosity droplets. The velocity and additional pressure drop of large thick capsules also follow the dynamics of high-viscosity droplets, and are affected by the lubrication film thickness. The motion of our large thick capsules is characterized by a Ux−u~h~a−2

  6. Femtosecond laser written optofluidic sensor: Bragg Grating Waveguide evanescent probing of microfluidic channel.

    PubMed

    Maselli, Valeria; Grenier, Jason R; Ho, Stephen; Herman, Peter R

    2009-07-06

    Microfluidic channels and Bragg Grating Waveguides (BGWs) were simultaneously fabricated inside fused silica glass by means of femtosecond laser exposure followed by chemical etching. Evanescent field penetration of the waveguide mode into the parallel microfluidic channel induced Bragg resonant wavelength shifts to enable refractive index characterization of the fluidic medium in the 1 to 1.452 range. Laser exposure was optimized to fabricate devices with optically smooth channel walls and narrow Bragg resonances for high sensing response at 1560 nm wavelength. Reference gratings were also employed in the optical circuit for temperature and strain compensation. These devices open new directions for optical sensing in three-dimensional optofluidic and reactor microsystems.

  7. On-demand magnetic manipulation of liquid metal in microfluidic channels for electrical switching applications.

    PubMed

    Jeon, Jinpyo; Lee, Jeong-Bong; Chung, Sang Kug; Kim, Daeyoung

    2016-12-20

    We report magnetic-field-driven on-demand manipulation of liquid metal in microfluidic channels filled with base or acid. The liquid metal was coated with iron (Fe) particles and treated with hydrochloric acid to have strong bonding strength with the Fe particles. The magnetic liquid metal slug inserted in the microchannel is manipulated, merged, and separated. In addition, corresponding to the repositioning of an external magnet, the liquid metal slug can be readily moved in microfluidic channels with different angles (>90°) and cross-linked channels in any direction. We demonstrated the functionality of the liquid metal in the microfluidic channel for electrical switching applications by manipulation of the liquid metal, resulting in the sequential turning on of light emitting diodes (LEDs).

  8. Coated and uncoated cellophane as materials for microplates and open-channel microfluidics devices.

    PubMed

    Hamedi, Mahiar M; Ünal, Barış; Kerr, Emily; Glavan, Ana C; Fernandez-Abedul, M Teresa; Whitesides, George M

    2016-10-05

    This communication describes the use of uncoated cellophane (regenerated cellulose films) for the fabrication of microplates, and the use of coated cellophane for the fabrication of open-channel microfluidic devices. The microplates based on uncoated cellophane are particularly interesting for applications that require high transparency in the ultraviolet (UV) regime, and offer a low-cost alternative to expensive quartz-well plates. Uncoated cellophane is also resistant to damage by various solvents. The microfluidic devices, based on coated cellophane, can have features with dimensions as small as 500 μm, and complex, non-planar geometries. Electrodes can be printed on the surface of the coated cellophane, and embedded in microfluidic devices, to develop resistive heaters and electroanalytical devices for flow injection analysis, and continuous flow electrochemiluminescence (ECL) applications. These open-channel devices are appropriate for applications where optical transparency (especially in the visible regime), resistance to damage by water, biocompatibility and biodegradability are important. Cellophane microfluidic systems complement existing cellulose-based paper microfluidic systems, and provide an alternative to other materials used in microfluidics, such as synthetic polymers or glass. Cellulose films are plausible materials for uses in integrated microfluidic systems for diagnostics, analyses, cell-culture, and MEMS.

  9. Fabrication of circular microfluidic channels by combining mechanical micromilling and soft lithography.

    PubMed

    Wilson, Mary E; Kota, Nithyanand; Kim, YongTae; Wang, Yadong; Stolz, Donna B; LeDuc, Philip R; Ozdoganlar, O Burak

    2011-04-21

    The fabrication of microfluidic channels with complex three-dimensional (3D) geometries presents a major challenge to the field of microfluidics, because conventional lithography methods are mainly limited to rectangular cross-sections. In this paper, we demonstrate the use of mechanical micromachining to fabricate microfluidic channels with complex cross-sectional geometries. Micro-scale milling tools are first used to fabricate semi-circular patterns on planar metallic surfaces to create a master mold. The micromilled pattern is then transferred to polydimethylsiloxane (PDMS) through a two-step reverse molding process. Using these semi-circular PDMS channels, circular cross-sectioned microchannels are created by aligning and adhering two channels face-to-face. Straight and serpentine-shaped microchannels were fabricated, and the channel geometry and precision of the metallic master and PDMS molds were assessed through scanning electron microscopy and non-contact profilometry. Channel functionality was tested by perfusion of liquid through the channels. This work demonstrates that micromachining enabled soft lithography is capable of fabricating non-rectangular cross-section channels for microfluidic applications. We believe that this approach will be important for many fields from biomimetics and vascular engineering to microfabrication and microreactor technologies.

  10. Rollable Microfluidic Systems with Microscale Bending Radius and Tuning of Device Function with Reconfigurable 3D Channel Geometry.

    PubMed

    Kim, Jihye; You, Jae Bem; Nam, Sung Min; Seo, Sumin; Im, Sung Gap; Lee, Wonhee

    2017-03-29

    Flexible microfluidic system is an essential component of wearable biosensors to handle body fluids. A parylene-based, thin-film microfluidic system is developed to achieve flexible microfluidics with microscale bending radius. A new molding and bonding technique is developed for parylene microchannel fabrication. Bonding with nanoadhesive layers deposited by initiated chemical vapor deposition (iCVD) enables the construction of microfluidic channels with short fabrication time and high bonding strength. The high mechanical strength of parylene allows less channel deformation from the internal pressure for the thin-film parylene channel than bulk PDMS channel. At the same time, negligible channel sagging or collapse is observed during channel bending down to a few hundreds of micrometers due to stress relaxation by prestretch structure. The flexible parylene channels are also developed into a rollable microfluidic system. In a rollable microfluidics format, 2D parylene channels can be rolled around a capillary tubing working as inlets to minimize the device footprint. In addition, we show that creating reconfigurable 3D channel geometry with microscale bending radius can lead to tunable device function: tunable Dean-flow mixer is demonstrated using reconfigurable microscale 3D curved channel. Flexible parylene microfluidics with microscale bending radius is expected to provide an important breakthrough for many fields including wearable biosensors and tunable 3D microfluidics.

  11. Simulation of malaria-infected red blood cells in microfluidic channels: Passage and blockage

    PubMed Central

    Wu, Tenghu; Feng, James J.

    2013-01-01

    Malaria-infected red blood cells (iRBCs) become less deformable with the progression of infection and tend to occlude microcapillaries. This process has been investigated in vitro using microfluidic channels. The objective of this paper is to provide a quantitative basis for interpreting the experimental observations of iRBC occlusion of microfluidic channels. Using a particle-based model for the iRBC, we simulate the traverse of iRBCs through a converging microfluidic channel and explore the progressive loss of cell deformability due to three factors: the stiffening of the membrane, the reduction of the cell's surface-volume ratio, and the growing solid parasites inside the cell. When examined individually, each factor tends to hinder the passage of the iRBC and lengthen the transit time. Moreover, at sufficient magnitude, each may lead to obstruction of narrow microfluidic channels. We then integrate the three factors into a series of simulations that mimic the development of malaria infection through the ring, trophozoite, and schizont stages. These simulations successfully reproduce the experimental observation that with progression of infection, the iRBC transitions from passage to blockage in larger and larger channels. The numerical results suggest a scheme for quantifying iRBC rigidification through microfluidic measurements of the critical pressure required for passage. PMID:24404048

  12. Integration of microfluidics with a four-channel integrated optical Young interferometer immunosensor.

    PubMed

    Ymeti, A; Kanger, J S; Greve, J; Besselink, G A J; Lambeck, P V; Wijn, R; Heideman, R G

    2005-01-15

    This report describes an optical sensing hybrid system obtained by bonding a microfluidic system to an integrated optical (IO) four-channel Young interferometer (YI) chip. The microfluidic system implemented into a glass plate consists of four microchannels with cross-sectional dimensions of 200 microm x 15 microm. The microfluidic system is structured in such a way that after bonding to the IO chip, each microchannel addresses one sensing window in the four-channel YI sensor. Experimental tests show that the implementation of the microfluidics reduces the response time of the sensor from 100s, as achieved with a bulky cuvette, to 4s. Monitoring the anti-human serum albumine/human serum albumine (alpha-HSA/HSA) immunoreaction demonstrates the feasibility to use the microfluidic sensing system for immunosensing applications. In this case, a better discrimination between the bulk refractive index change and the layer formation can be made, resulting into higher accuracy and offering the prospect of being able to use the kinetics of the immunoreaction. The microfluidic sensing system shows an average phase resolution of 7 x 10(-5) x 2pi for different pairs of channels, which at the given interaction length of 4 mm corresponds to a refractive index resolution of 6 x 10(-8), being equivalent to a protein mass coverage resolution of 20 fg/mm2.

  13. Cell mechanics through analysis of cell trajectories in microfluidic channel

    NASA Astrophysics Data System (ADS)

    Bowie, Samuel; Alexeev, Alexander; Sulchek, Todd

    The understanding of dynamic cell behavior can aid in research ranging from the mechanistic causes of diseases to the development of microfluidic devices for cancer detection. Through analysis of trajectories captured from video of the cells moving in a specially designed microfluidic device, insight into the dynamic viscoelastic nature of cells can be found. The microfluidic device distinguishes cells viscoelastic properties through the use of angled ridges causing a series of compressions, resulting in differences in trajectories based on cell stiffness. Trajectories of cell passing through the device are collected using image processing methods and data mining techniques are used to relate the trajectories to cell properties obtained from experiments. Furthermore, numerical simulation of the cell and microfluidic device are used to match the experimental results from the trajectory analysis. Combination of the modeling and experimental data help to uncover how changes in cellular structures result in changes in mechanical properties.

  14. Open-channel, water-in-oil emulsification in paper-based microfluidic devices.

    PubMed

    Li, C; Boban, M; Tuteja, A

    2017-04-11

    Open-channel microfluidic devices have shown great potential in achieving a high degree of fluid control, at relatively low-cost, while enabling the opportunity for rapid fabrication. However, thus far, work in open channel microfluidics has largely focused on controlling the flow of water or other aqueous solutions. In this work we present new open channel microfluidic devices based on surfaces with patterned wettabilty that are capable of controlling the flow of virtually all high and low surface tension liquids. The fabricated open channel devices are capable of constraining a variety of low surface tension oils at high enough flow rates to enable, for the first time, water-in-oil microfluidic emulsification in an open channel device. By changing the flow rates for both the aqueous (dispersed) and organic (continuous) phases, we show that it is possible to vary the size of the emulsified droplets produced in the open channel device. Finally, we utilized the fabricated devices to synthesize relatively monodisperse, hydrogel microparticles that could incorporate a drug molecule. We also investigated the drug release characteristics of the fabricated particles.

  15. Improving agglutination tests by working in microfluidic channels.

    PubMed

    Degré, G; Brunet, E; Dodge, A; Tabeling, P

    2005-06-01

    Latex agglutination tests are used for the diagnosis of diseases in man and animals. They are generally simple, cheap, and do not require sophisticated equipment, nor highly specialized skills. In this Technical Note, we put latex agglutination tests in a microfluidic format. The experiment is performed in PDMS (polydimethylsiloxane) microchannels, using streptavidin-coated superparamagnetic beads and a magnetic field. The target molecule is biotinylated protein A. By taking full advantage of the microfluidic conditions (scaling down of the detection volume and controlled action of the shear flow), we achieved an analytical sensitivity of 10 fmol l(-1)(several hundreds of fg ml(-1)) and a fast response (a few minutes) ; the test is also quantitative. Performances of agglutination tests can thus be improved by orders of magnitude by adapting them to a microfluidic format; this comes in addition to the usual advantages offered by this technology (integration, high throughput etc.).

  16. Monolithic integration of microfluidic channels and optical waveguides in silica on silicon.

    PubMed

    Friis, P; Hoppe, K; Leistiko, O; Mogensen, K B; Hübner, J; Kutter, J P

    2001-12-01

    Sealing of the flow channel is an important aspect during integration of microfluidic channels and optical waveguides. The uneven topography of many waveguide-fabrication techniques will lead to leakage of the fluid channels. Planarization methods such as chemical mechanical polishing or the etch-back technique are possible, but troublesome. We present a simple but efficient alternative: By means of changing the waveguide layout, bonding pads are formed along the microfluidic channels. With the same height as the waveguide, they effectively prevent leakage and hermetically seal the channels during bonding. Negligible influence on light propagation is found when 10-mum-wide bonding pads are used. Fabricated microsystems with application in absorbance measurements and flow cytometry are presented.

  17. Microfluidic channel structures speed up mixing of multiple emulsions by a factor of ten

    PubMed Central

    Mbanjwa, Mesuli; Korvink, Jan G.

    2014-01-01

    We present a novel use for channel structures in microfluidic devices, whereby two two-phase emulsions, one created on-chip, the other off-chip, are rapidly mixed with each other in order to allow for the coalescence of one emulsion with the other. This approach has been motivated by the difficulty in introducing aqueous cross linking agents into droplets by utilising conventional approaches. These conventional approaches include continuous introduction of the different aqueous reagents before droplet formation or alternatively formation of individual droplets of each reagent and subsequent droplet merging later in the microfluidic device. We show that our approach can decrease the mixing time for these fluidic systems by a factor greater than 10 times when compared to a standard microfluidic channel without structures, thereby also allowing for additional reaction time within the microfluidic device. This method shows an application for microfluidic channel structures not before demonstrated, also demonstrating an alternative method for introducing reagents such as cross linkers which link polymer chains to form particles, and provides an example where enzymes are immobilized in monodisperse particles. PMID:25332738

  18. Metal-coated microfluidic channels: An approach to eliminate streaming potential effects in nano biosensors.

    PubMed

    Lee, Jieun; Wipf, Mathias; Mu, Luye; Adams, Chris; Hannant, Jennifer; Reed, Mark A

    2017-01-15

    We report a method to suppress streaming potential using an Ag-coated microfluidic channel on a p-type silicon nanowire (SiNW) array measured by a multiplexed electrical readout. The metal layer sets a constant electrical potential along the microfluidic channel for a given reference electrode voltage regardless of the flow velocity. Without the Ag layer, the magnitude and sign of the surface potential change on the SiNW depends on the flow velocity, width of the microfluidic channel and the device's location inside the microfluidic channel with respect to the reference electrode. Noise analysis of the SiNW array with and without the Ag coating in the fluidic channel shows that noise frequency peaks, resulting from the operation of a piezoelectric micropump, are eliminated using the Ag layer with two reference electrodes located at inlet and outlet. This strategy presents a simple platform to eliminate the streaming potential and can become a powerful tool for nanoscale potentiometric biosensors.

  19. Multipoint viscosity measurements in microfluidic channels using optical tweezers.

    PubMed

    Keen, Stephen; Yao, Alison; Leach, Jonathan; Di Leonardo, Roberto; Saunter, Chris; Love, Gordon; Cooper, Jonathan; Padgett, Miles

    2009-07-21

    We demonstrate the technique of multipoint viscosity measurements incorporating the accurate calibration of micron sized particles. We describe the use of a high-speed camera to measure the residual motion of particles trapped in holographic optical tweezers, enabling us to calculate the fluid viscosity at multiple points across the field-of-view of the microscope within a microfluidic system.

  20. Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems

    PubMed Central

    Lv, Chao; Xia, Hong; Guan, Wei; Sun, Yun-Lu; Tian, Zhen-Nan; Jiang, Tong; Wang, Ying-Shuai; Zhang, Yong-Lai; Chen, Qi-Dai; Ariga, Katsuhiko; Yu, Yu-De; Sun, Hong-Bo

    2016-01-01

    Optofluidics, which integrates microfluidics and micro-optical components, is crucial for optical sensing, fluorescence analysis, and cell detection. However, the realization of an integrated system from optofluidic manipulation and a microfluidic channel is often hampered by the lack of a universal substrate for achieving monolithic integration. In this study, we report on an integrated optofluidic-microfluidic twin channels chip fabricated by one-time exposure photolithography, in which the twin microchannels on both surfaces of the substrate were exactly aligned in the vertical direction. The twin microchannels can be controlled independently, meaning that fluids could flow through both microchannels simultaneously without interfering with each other. As representative examples, a tunable hydrogel microlens was integrated into the optofluidic channel by femtosecond laser direct writing, which responds to the salt solution concentration and could be used to detect the microstructure at different depths. The integration of such optofluidic and microfluidic channels provides an opportunity to apply optofluidic detection practically and may lead to great promise for the integration and miniaturization of Lab-on-a-Chip systems. PMID:26823292

  1. Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems

    NASA Astrophysics Data System (ADS)

    Lv, Chao; Xia, Hong; Guan, Wei; Sun, Yun-Lu; Tian, Zhen-Nan; Jiang, Tong; Wang, Ying-Shuai; Zhang, Yong-Lai; Chen, Qi-Dai; Ariga, Katsuhiko; Yu, Yu-De; Sun, Hong-Bo

    2016-01-01

    Optofluidics, which integrates microfluidics and micro-optical components, is crucial for optical sensing, fluorescence analysis, and cell detection. However, the realization of an integrated system from optofluidic manipulation and a microfluidic channel is often hampered by the lack of a universal substrate for achieving monolithic integration. In this study, we report on an integrated optofluidic-microfluidic twin channels chip fabricated by one-time exposure photolithography, in which the twin microchannels on both surfaces of the substrate were exactly aligned in the vertical direction. The twin microchannels can be controlled independently, meaning that fluids could flow through both microchannels simultaneously without interfering with each other. As representative examples, a tunable hydrogel microlens was integrated into the optofluidic channel by femtosecond laser direct writing, which responds to the salt solution concentration and could be used to detect the microstructure at different depths. The integration of such optofluidic and microfluidic channels provides an opportunity to apply optofluidic detection practically and may lead to great promise for the integration and miniaturization of Lab-on-a-Chip systems.

  2. Characterization of Printable Cellular Micro-fluidic Channels for Tissue Engineering

    PubMed Central

    Zhang, Yahui; Yu, Yin; Chen, Howard; Ozbolat, Ibrahim T.

    2014-01-01

    Tissue engineering has been a promising field of research, offering hope of bridging the gap between organ shortage and transplantation needs. However, building three-dimensional (3D) vascularized organs remains the main technological barrier to be overcome. One of the major challenges is the inclusion of a vascular network to support cell viability in terms of nutrients and oxygen perfusion. This paper introduces a new approach to fabrication of vessel-like microfluidic channels that has the potential to be used in thick tissue or organ fabrication in the future. In this research, we investigate the manufacturability of printable micro-fluidic channels, where micro-fluidic channels support mechanical integrity as well as enable fluid transport in 3D. A pressure-assisted solid freeform fabrication platform is developed with a coaxial needle dispenser unit to print hollow hydrogel filaments. The dispensing rheology is studied, and effects of material properties on structural formation of hollow filaments are analyzed. Sample structures are printed through the developed computer-controlled system. In addition, cell viability and gene expression studies are presented in this paper. Cell viability shows that cartilage progenitor cells (CPCs) maintained their viability right after bioprinting and during prolonged in vitro culture. Real-time PCR analysis yielded relatively higher expression of cartilage-specific genes in alginate hollow filament encapsulating CPCs, compared with monolayer cultured CPCs, which revealed that printable semi-permeable micro-fluidic channels provided an ideal environment for cell growth and function. PMID:23458889

  3. Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems.

    PubMed

    Lv, Chao; Xia, Hong; Guan, Wei; Sun, Yun-Lu; Tian, Zhen-Nan; Jiang, Tong; Wang, Ying-Shuai; Zhang, Yong-Lai; Chen, Qi-Dai; Ariga, Katsuhiko; Yu, Yu-De; Sun, Hong-Bo

    2016-01-29

    Optofluidics, which integrates microfluidics and micro-optical components, is crucial for optical sensing, fluorescence analysis, and cell detection. However, the realization of an integrated system from optofluidic manipulation and a microfluidic channel is often hampered by the lack of a universal substrate for achieving monolithic integration. In this study, we report on an integrated optofluidic-microfluidic twin channels chip fabricated by one-time exposure photolithography, in which the twin microchannels on both surfaces of the substrate were exactly aligned in the vertical direction. The twin microchannels can be controlled independently, meaning that fluids could flow through both microchannels simultaneously without interfering with each other. As representative examples, a tunable hydrogel microlens was integrated into the optofluidic channel by femtosecond laser direct writing, which responds to the salt solution concentration and could be used to detect the microstructure at different depths. The integration of such optofluidic and microfluidic channels provides an opportunity to apply optofluidic detection practically and may lead to great promise for the integration and miniaturization of Lab-on-a-Chip systems.

  4. Addressing a vascular endothelium array with blood components using underlying microfluidic channels.

    PubMed

    Genes, Luiza I; V Tolan, Nicole; Hulvey, Matthew K; Martin, R Scott; Spence, Dana M

    2007-10-01

    Here, we show that an array of endothelial cells, addressable by an underlying microfluidic network of channels containing red blood cells, can be employed as an in vitro model of in vivo circulation to monitor cellular communication between different cell types in the drug discovery process.

  5. Controlling flow in microfluidic channels with a manually actuated pin valve.

    PubMed

    Brett, Marie-Elena; Zhao, Shuping; Stoia, Jonathan L; Eddington, David T

    2011-08-01

    There is a need for a simple method to control fluid flow within microfluidic channels. To meet this need, a simple push pin with a polydimethylsiloxane (PDMS) tip has been integrated into microfluidic networks to be placed within the microchannel to obstruct flow. This new valve design can attain on/off control of fluid flow without an external power source using readily-available, low-cost materials. The valve consists of a 14 gauge (1.6 mm) one inch piece of metal tubing with a PDMS pad at the tip to achieve a fluidic seal when pressed against a microfluidic channel's substrate. The metal tubing or pin is then either manually pushed down to block or pulled up to allow fluid flow. The valve was validated using a pressure transducer and fluorescent dye to determine the breakthrough pressure the valve can withstand over multiple cycles. In the first cycle, the median value for pressure withstood by the valve was 8.8 psi with a range of 17.5-2.7 psi. The pressure the valves were able to withstand during each successive trial was lower suggesting they may be most valuable as a method to control the initial introduction of fluids into a microfluidic device. These valves can achieve flow regulation within microfluidic devices, have a small dead volume, and are simple to fabricate and use, making this technique widely suitable for a range of applications.

  6. Microfluidic converging/diverging channels optimised for homogeneous extensional deformation.

    PubMed

    Zografos, K; Pimenta, F; Alves, M A; Oliveira, M S N

    2016-07-01

    In this work, we optimise microfluidic converging/diverging geometries in order to produce constant strain-rates along the centreline of the flow, for performing studies under homogeneous extension. The design is examined for both two-dimensional and three-dimensional flows where the effects of aspect ratio and dimensionless contraction length are investigated. Initially, pressure driven flows of Newtonian fluids under creeping flow conditions are considered, which is a reasonable approximation in microfluidics, and the limits of the applicability of the design in terms of Reynolds numbers are investigated. The optimised geometry is then used for studying the flow of viscoelastic fluids and the practical limitations in terms of Weissenberg number are reported. Furthermore, the optimisation strategy is also applied for electro-osmotic driven flows, where the development of a plug-like velocity profile allows for a wider region of homogeneous extensional deformation in the flow field.

  7. Microfluidic converging/diverging channels optimised for homogeneous extensional deformation

    PubMed Central

    Zografos, K.; Oliveira, M. S. N.

    2016-01-01

    In this work, we optimise microfluidic converging/diverging geometries in order to produce constant strain-rates along the centreline of the flow, for performing studies under homogeneous extension. The design is examined for both two-dimensional and three-dimensional flows where the effects of aspect ratio and dimensionless contraction length are investigated. Initially, pressure driven flows of Newtonian fluids under creeping flow conditions are considered, which is a reasonable approximation in microfluidics, and the limits of the applicability of the design in terms of Reynolds numbers are investigated. The optimised geometry is then used for studying the flow of viscoelastic fluids and the practical limitations in terms of Weissenberg number are reported. Furthermore, the optimisation strategy is also applied for electro-osmotic driven flows, where the development of a plug-like velocity profile allows for a wider region of homogeneous extensional deformation in the flow field. PMID:27478523

  8. Preliminary assessment for DNA extraction on microfluidic channel

    NASA Astrophysics Data System (ADS)

    Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

    2017-03-01

    The aim of this research is to extract, purify and yield DNA in mushroom from solid state mushroom sample by using fabricated continuous high-capacity sample delivery microfluidic through integrated solid state extraction based amino-coated silica bead. This device is made to specifically extract DNA in mushroom sample in continuous inflow process with energy and cost consumption. In this project, we present two methods of DNA extraction and purification which are by using centrifuge (complex and conventional method) and by using microfluidic biosensor (new and fast method). DNA extracted can be determined by using ultraviolet-visible spectroscopy (UV-VIS). The peak obtained at wavelength 260nm after measuring the absorbance of sample proves that DNA is successfully extracted from the mushroom.

  9. Absolute 3D reconstruction of thin films topography in microfluidic channels by interference reflection microscopy.

    PubMed

    Huerre, A; Jullien, M-C; Theodoly, O; Valignat, M-P

    2016-03-07

    The travel of droplets, bubbles, vesicles, capsules, living cells or small organisms in microchannels is a hallmark in microfluidics applications. A full description of the dynamics of such objects requires a quantitative understanding of the complex hydrodynamic and interfacial interactions between objects and channel walls. In this paper, we present an interferometric method that allows absolute topographic reconstruction of the interspace between an object and channel walls for objects confined in microfluidic channels. Wide field microscopic imaging in reflection interference contrast mode (RICM) is directly performed at the bottom wall of microfluidic chips. Importantly, we show that the reflections at both the lower and upper surface of the microchannel have to be considered in the quantitative analysis of the optical signal. More precisely, the contribution of the reflection at the upper surface is weighted depending on the light coherence length and channel height. Using several wavelengths and illumination apertures, our method allows reconstructing the topography of thin films on channel walls in a range of 0-500 nm, with a precision as accurate as 2 nm for the thinnest films. A complete description of the protocol is exemplified for oil in water droplets travelling in channels of height 10-400 μm at a speed up to 5 mm s(-1).

  10. Microscopy imaging and quantitative phase contrast mapping in turbid microfluidic channels by digital holography.

    PubMed

    Paturzo, Melania; Finizio, Andrea; Memmolo, Pasquale; Puglisi, Roberto; Balduzzi, Donatella; Galli, Andrea; Ferraro, Pietro

    2012-09-07

    We show that sharp imaging and quantitative phase-contrast microcopy is possible in microfluidics in flowing turbid media by digital holography. In fact, in flowing liquids with suspended colloidal particles, clear vision is hindered and cannot be recovered by any other microscopic imaging technique. On the contrary, using digital holography, clear imaging is possible thanks to the Doppler frequency shift experienced by the photons scattered by the flowing colloidal particles, which do not contribute to the interference process, i.e. the recorded hologram. The method is illustrated and imaging results are demonstrated for pure phase objects, i.e. biological cells in microfluidic channels.

  11. Modelling of capillary-driven flow for closed paper-based microfluidic channels

    NASA Astrophysics Data System (ADS)

    Songok, Joel; Toivakka, Martti

    2017-06-01

    Paper-based microfluidics is an emerging field focused on creating inexpensive devices, with simple fabrication methods for applications in various fields including healthcare, environmental monitoring and veterinary medicine. Understanding the flow of liquid is important in achieving consistent operation of the devices. This paper proposes capillary models to predict flow in paper-based microfluidic channels, which include a flow accelerating hydrophobic top cover. The models, which consider both non-absorbing and absorbing substrates, are in good agreement with the experimental results.

  12. Design, fabrication and characterization of nano-filters in silicon microfluidic channels based on MEMS technology.

    PubMed

    Chen, Xing; Cui, Dafu; Chen, Jian

    2009-09-01

    Since most clinical assays are performed on cell-free serum or plasma, micro-analytical systems for blood tests require integrated on-chip microfluidics for the isolation of plasma or serum from crude blood samples. In this paper, we present a crossflow filtration method using novel silicon nano-filters for plasma separation. The microfluidic chip is made of a silicon substrate containing micropillar arrays, feed channels, side channels and nano-gap structures, sealed with a PDMS-glass compound cover. The design of the silicon filtration structures were optimized using numerical analysis and the optimal MEMS fabrication procedures were obtained. The filtration structures including nano-filters were characterized using SEM and subsequently used to isolate plasma from whole blood in a continuous manner. Compared with micro-gap structures in silicon microfluidic channels, the nano-gap structures have been used to separate plasma from whole blood samples with higher selectivity, where a maximum plasma selectivity of 97.7% has been obtained. Common problems of clogging and jamming in filtration applications have seldom been noticed in our device. The presented microfluidic filtration device for plasma isolation could be integrated into microTAS for point-of-care diagnostics in the near future.

  13. The Mechanical Analysis of the Biofilm Streamer Nucleation and Geometry Characterization in Microfluidic Channels

    PubMed Central

    Wang, Xiaoling; Hao, Mudong; Du, Xin; Wang, Guoqing; Matsushita, Jun-ichi

    2016-01-01

    Bacteria can form biofilm streamers in microfluidic channels with various geometries. Experiments show that the streamer geometry, such as its shape or thickness, depends on the fluid velocity and the geometry and curvature of the microfluidic channel. In the paper, a mechanical analysis of the flow field is made in different channels, which shows that the secondary flow in the channel is the reason for streamer nucleation and that the shear stress distribution decides the streamer geometry including shape and thickness. Through a finite elements simulation, we obtain the secondary flow forming positions in both static and rotating channels: positions that are the location of nucleation of the streamer. Thick or wide biofilm streamers occur at the points of minimum shear stress in static channels. Furthermore, in rotating channels, spiral-like streamers form, due to the helical shape of the minimum shear stress distribution. The findings may allow the prevention of biofilm formation and also the removal of bacteria adhered onto certain surfaces in channels with small cross sections. The analysis also indicates how one can obtain desirable biofilm streamers by control of the channel geometry and the loading conditions. PMID:27313658

  14. A numerical procedure for scaling droplet deformation in a microfluidic expansion channel

    NASA Astrophysics Data System (ADS)

    Kadivar, Erfan; Farrokhbin, Mojtaba

    2017-08-01

    Motivated by recent experiments, deformation and relaxation of a droplet flowing through a narrow channel opening to a planar sudden expansion are studied. Using the boundary element method (BEM), we numerically solve the Darcy equation in the two-dimensional microfluidic channel and investigate droplet motion as the droplet enters the sudden expansion channel. We find two regimes of deformation with a dependency on relative droplet size compared to narrow channel width. A first regime, for droplet smaller than the narrow channel width, is characterized by a deformation affected by the droplet size and capillary number. The second regime, in which droplet larger than the narrow channel width, deformation is characterized by dependence on the capillary number and the width ratio of two channels. Our numerical scalings are in good agreement with reported experimental scalings. Finally, by employing the Fourier analysis method, the relation between the Fourier coefficients and droplet shape is investigated.

  15. Microfluidic channels with ultralow-loss waveguide crossings for various chip-integrated photonic sensors.

    PubMed

    Wang, Zheng; Yan, Hai; Chakravarty, Swapnajit; Subbaraman, Harish; Xu, Xiaochuan; Fan, D L; Wang, Alan X; Chen, Ray T

    2015-04-01

    Traditional silicon waveguides are defined by waveguide trenches on either side of the high-index silicon core that leads to fluid leakage orifices for over-layed microfluidic channels. Closing the orifices needs additional fabrication steps which may include oxide deposition and planarization. We experimentally demonstrated a new type of microfluidic channel design with ultralow-loss waveguide crossings (0.00248 dB per crossings). The waveguide crossings and all other on-chip passive-waveguide components are fabricated in one step with no additional planarization steps which eliminates any orifices and leads to leak-free fluid flow. Such designs are applicable in all optical-waveguide-based sensing applications where the analyte must be flowed over the sensor. The new channel design was demonstrated in a L55 photonic crystal sensor operating between 1540 and 1580 nm.

  16. Microfluidic in-channel multi-electrode platform for neurotransmitter sensing

    NASA Astrophysics Data System (ADS)

    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.

  17. Spatial control over cell attachment by partial solvent entrapment of poly lysine in microfluidic channels

    PubMed Central

    Baman, Nicki K; Schneider, Galen B; Terry, Treniece L; Zaharias, Rebecca; Salem, Aliasger K

    2006-01-01

    We demonstrate spatial control over cell attachment on biodegradable surfaces by flowing cell adhesive poly (D-lysine) (PDL) in a trifluoroethanol (TFE)–water mixture through microfluidic channels placed on a biodegradable poly (lactic acid)–poly (ethylene glycol) (PLA–PEG) substrate. The partial solvent mixture swells the PLA–PEG within the confines of the microfluidic channels allowing PDL to diffuse on to the surface gel layer. When excess water is flowed through the channels substituting the TFE–water mixture, the swollen PLA surface collapses, entrapping PDL polymer. Results using preosteoblast human palatal mesenchymal cells (HEPM) indicate that this new procedure can be used for facile attachment of cells in localized regions. The PEG component of the PLA–PEG copolymer prevents cells from binding to the nonpatterned regions. PMID:17722538

  18. Integrated acoustic and magnetic separation in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Adams, Jonathan D.; Thévoz, Patrick; Bruus, Henrik; Soh, H. Tom

    2009-12-01

    With a growing number of cell-based biotechnological applications, there is a need for particle separation systems capable of multiparameter separations at high purity and throughput, beyond what is presently offered by traditional methods including fluorescence activated cell sorting and column-based magnetic separation. Toward this aim, we report on the integration of microfluidic acoustic and magnetic separation in a monolithic device for multiparameter particle separation. Using our device, we demonstrate high-purity separation of a multicomponent particle mixture at a throughput of up to 108 particles/hr.

  19. Three-dimensional closed microfluidic channel fabrication by stepper projection single step lithography: the diabolo effect.

    PubMed

    Larramendy, F; Mazenq, L; Temple-Boyer, P; Nicu, L

    2012-01-21

    Microfluidic devices are currently being used in many types of biochemical microsystems for liquid phase analysis in the frame of medical applications. This paper presents a new technique for the realization of microfluidic channels using SU-8, a commonly used epoxy-based negative photo-resist. These microchannels were fabricated by a single stepper UV-photolithography process. By changing the process parameters, e.g. the optical focus depth and the UV exposure dose, well-defined, covered microchannels with various dimensions and aspect ratios were realized and proven to be effective for the fluid transport by capillarity. This technique can easily be used for the fabrication of microfluidic devices in the microanalysis and lab-on-chip applications realm.

  20. Fundamentals of elasto-inertial particle focusing in curved microfluidic channels.

    PubMed

    Xiang, Nan; Zhang, Xinjie; Dai, Qing; Cheng, Jie; Chen, Ke; Ni, Zhonghua

    2016-07-05

    Elasto-inertial focusing in viscoelastic fluids has attracted increasing interest in recent years due to its potential applications in particle counting and sorting. However, current investigations of the elasto-inertial focusing mechanisms have mainly been focused on simple straight channels with little attention being paid to curved channels. Herein, we experimentally explore the elasto-inertial focusing behaviors of particles in spiral microfluidic channels over a wide range of flow rates, channel aspect ratios and channel radii. As compared with those observed in inertial microfluidics without viscoelasticity, the particle focusing pattern in our spiral elasto-inertial microfluidic system appears in a more interesting manner due to the complex coupling of elasticity, inertia and Dean flow effects. On the basis of the obtained data, the underlying mechanics and force competition behind the focusing behaviors are analyzed. In addition, for the first time, we propose a six-stage process model illustrating the particle focusing process in Dean-coupled elasto-inertial flows with increasing flow rate. It is interesting to find that the Dean drag force makes a significant contribution to particle focusing only at high flow rates and finally shifts the particle focusing positions into the outer channel region. Through carefully balancing the forces acting on particles, single-line 3D focusing can also be achieved at a throughput level of ∼100 μl min(-1), which is much higher than those in most existing studies. We envision that this improved understanding of the particle focusing mechanisms would provide helpful insights into the design and operation of spiral elasto-inertial microfluidic systems.

  1. K-Channel: A Multifunctional Architecture for Dynamically Reconfigurable Sample Processing in Droplet Microfluidics.

    PubMed

    Doonan, Steven R; Bailey, Ryan C

    2017-03-13

    By rapidly creating libraries of thousands of unique, miniaturized reactors, droplet microfluidics provides a powerful method for automating high-throughput chemical analysis. In order to engineer in-droplet assays, microfluidic devices must add reagents into droplets, remove fluid from droplets, and perform other necessary operations, each typically provided by a unique, specialized geometry. Unfortunately, modifying device performance or changing operations usually requires re-engineering the device among these specialized geometries, a time-consuming and costly process when optimizing in-droplet assays. To address this challenge in implementing droplet chemistry, we have developed the "K-channel," which couples a cross-channel flow to the segmented droplet flow to enable a range of operations on passing droplets. K-channels perform reagent injection (0-100% of droplet volume), fluid extraction (0-50% of droplet volume), and droplet splitting (1:1-1:5 daughter droplet ratio). Instead of modifying device dimensions or channel configuration, adjusting external conditions, such as applied pressure and electric field, selects the K-channel process and tunes its magnitude. Finally, interfacing a device-embedded magnet allows selective capture of 96% of droplet-encapsulated superparamagnetic beads during 1:1 droplet splitting events at ∼400 Hz. Addition of a second K-channel for injection (after the droplet splitting K-channel) enables integrated washing of magnetic beads within rapidly moving droplets. Ultimately, the K-channel provides an exciting opportunity to perform many useful droplet operations across a range of magnitudes without requiring architectural modifications. Therefore, we envision the K-channel as a versatile, easy to use microfluidic component enabling diverse, in-droplet (bio)chemical manipulations.

  2. In situ analysis of bacterial capture in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Balasubramanian, Ashwin K.; Beskok, Ali; Pillai, Suresh D.

    2007-08-01

    We present a microfluidic approach for the continuous capture of Salmonella Newport cells suspended in a phosphate buffer using externally applied electric fields. The effects of flow rate, applied electric field and wall shear stress on cell capture in the device are analyzed using particle tracking via fluorescent microscopy techniques. Analyzing capture across multiple locations on the electrode surface enabled the estimation of average capture over the entire electrode area as a function of time. The device exhibits approximately a constant capture rate over an extended time frame, which is verified independently using the cell culture methods. An increased capture rate with an increased electric field is observed. The capture rate dependence on the flow rate and capture rate at various locations with different wall shear stress magnitudes does not exhibit statistically significant variations. The capture trends presented in this study can be utilized for designing microfluidic systems for biosensors, designed bacterial bio-films and devices for bacterial sample concentration from large volumes.

  3. Stimulus-responsive polymers and other functional polymer surfaces as components in glass microfluidic channels.

    PubMed

    Kieviet, Bernard D; Schön, Peter M; Vancso, G Julius

    2014-11-07

    The integration of smart stimulus-responsive polymers as functional elements within microfluidic devices has greatly improved the performance capabilities of controlled fluid delivery. For their use as actuators in microfluidic systems, reversible expansion and shrinking are unique mechanisms which can be utilized as both passive and active fluid control elements to establish gate and valve functions (passive) and pumping elements (active). Various constituents in microfluidic glass channels based on stimulus-responsive elements have been reported based on pH-responsive, thermoresponsive and photoresponsive coatings. Fluid control and robust performance have been demonstrated in microfluidic devices in a number of studies. Here we give a brief overview of selected examples from the literature reporting on the use of stimulus response polymers as active or passive elements for fluid control in microfluidic devices, with specific emphasis on glass-based devices. The remaining challenges include improving switching times and achieving local addressability of the responsive constituent. We envisage tackling these challenges by utilizing redox-responsive polymers which offer fast and reversible switching and local addressability in combination with nanofabricated electrodes.

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

    PubMed

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

    2014-08-01

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

  5. Paramagnetic Structures within a Microfluidic Channel for Enhanced Immunomagnetic Isolation and Surface Patterning of Cells

    PubMed Central

    Sun, Chen; Hassanisaber, Hamid; Yu, Richard; Ma, Sai; Verbridge, Scott S.; Lu, Chang

    2016-01-01

    In this report, we demonstrate a unique method for embedding magnetic structures inside a microfluidic channel for cell isolation. We used a molding process to fabricate these structures out of a ferrofluid of cobalt ferrite nanoparticles. We show that the embedded magnetic structures significantly increased the magnetic field in the channel, resulting in up to 4-fold enhancement in immunomagnetic capture as compared with a channel without these embedded magnetic structures. We also studied the spatial distribution of trapped cells both experimentally and computationally. We determined that the surface pattern of these trapped cells was determined by both location of the magnet and layout of the in-channel magnetic structures. Our magnetic structure embedded microfluidic device achieved over 90% capture efficiency at a flow velocity of 4 mm/s, a speed that was roughly two orders of magnitude faster than previous microfluidic systems used for a similar purpose. We envision that our technology will provide a powerful tool for detection and enrichment of rare cells from biological samples. PMID:27388549

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

    PubMed

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

    2014-08-01

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

  7. Modeling defect tolerance sensitivity to periodic post parameters in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Mehran, Mahyar; Gray, Bonnie L.; Chapman, Glenn H.

    2015-03-01

    Previously we modeled the theoretical benefits of using microfluidic channels that utilize a "Cathedral Chamber" design, in which the ceiling is supported by an array of periodic posts, compared to an array of parallel microfluidic channels. We developed a semi-automated technique that combines a rule-base defect placement system with a Monte Carlo method for modeling the fluid dynamics and blockage formation based on the likelihood of blockages forming in areas of high particle traffic and low flow rate. Earlier results indicate that Cathedral Chambers, that are supported by an array of 10 by 11 periodic posts with the same size as the spacing have six times higher lifetime expectancy compared to an array of 10 parallel channels, likely due to the provision of multiple paths during localized blockage formation in the Cathedral Chamber. In this paper, we have expanded our investigations by considering the defect tolerance sensitivity to scale by altering parameters such as the number and size of the posts and overall size of the chamber. For one set of simulations, we used the same number of posts in the chamber and the same starting position for the first 10 blockages as in our previous work. However, we shrank the size of the posts to 66% of their former size so that the new channels (flow pathways) are twice the size of the modified posts. In addition, we have also performed initial simulations based on wider microfluidic channels supported by an array of 20 by 11 periodic posts in order to explore their microfluidic behavior and lifetime.

  8. A microfluidic-based enzymatic assay for bioactivity screening combined with capillary liquid chromatography and mass spectrometry.

    PubMed

    de Boer, Arjen R; Bruyneel, Ben; Krabbe, Johannes G; Lingeman, Henk; Niessen, Wilfried M A; Irth, Hubertus

    2005-11-01

    The design and implementation of a continuous-flow microfluidic assay for the screening of (complex) mixtures for bioactive compounds is described. The microfluidic chip featured two microreactors (1.6 and 2.4 microL) in which an enzyme inhibition and a substrate conversion reaction were performed, respectively. Enzyme inhibition was detected by continuously monitoring the products formed in the enzyme-substrate reaction by electrospray ionization mass spectrometry (ESI-MS). In order to enable the screening of mixtures of compounds, the chip-based assay was coupled on-line to capillary reversed-phase high-performance liquid chromatography (HPLC) with the HPLC column being operated either in isocratic or gradient elution mode. In order to improve the detection limits of the current method, sample preconcentration based on a micro on-line solid-phase extraction column was employed. The use of electrospray MS allowed the simultaneous detection of chemical (MS spectra) and biological parameters (enzyme inhibition) of ligands eluting from the HPLC column. The present system was optimized and validated using the protease cathepsin B as enzyme of choice. Inhibition of cathepsin B is detected by monitoring three product traces, obtained by cleavage of the substrate. The two microreactors provided 32 and 36 s reaction time, respectively, which resulted in sufficient assay dynamics to enable the screening of bioactive compounds. The total flow rate was 4 microL min-1, which a 25-fold decrease was compared with a macro-scale system described earlier. Detection limits of 0.17-2.6 micromol L-1 were obtained for the screening of inhibitors, which is comparable to either microtiter plate assays or continuous-flow assays described in the literature.

  9. Osmosis and pervaporation in polyimide submicron microfluidic channel structures

    NASA Astrophysics Data System (ADS)

    Eijkel, Jan C. T.; Bomer, Johan G.; van den Berg, Albert

    2005-09-01

    Osmosis and pervaporation of water through the roof of all-polyimide channels of 500nm height is described. The phenomena cause both a liquid flow in the channels and a concentration change of dissolved salt. Both effects are amplified due to the thin channel roof and the small channel height. Osmotic movement of demineralized water was observed towards a salt solution and towards ethanol and isopropanol. Water movement by pervaporation was observed from a salt solution towards the atmosphere. Flow velocities of up to 70μm/s were generated in the channels. The results are in accordance with predictions from the solution-diffusion model for membrane transport. The observed phenomena can be applied in a nanofluidic osmotic pump or for an osmotic or pervaporative concentrator.

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

    NASA Astrophysics Data System (ADS)

    Tu, Jing; Qiao, Yi; Xu, Minghua; Li, Junji; Liang, Fupeng; Duan, Mengqin; Ju, An; Lu, Zuhong

    2016-12-01

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

  11. Generating multiplex gradients of biomolecules for controlling cellular adhesion in parallel microfluidic channels.

    PubMed

    Didar, Tohid Fatanat; Tabrizian, Maryam

    2012-11-07

    Here we present a microfluidic platform to generate multiplex gradients of biomolecules within parallel microfluidic channels, in which a range of multiplex concentration gradients with different profile shapes are simultaneously produced. Nonlinear polynomial gradients were also generated using this device. The gradient generation principle is based on implementing parrallel channels with each providing a different hydrodynamic resistance. The generated biomolecule gradients were then covalently functionalized onto the microchannel surfaces. Surface gradients along the channel width were a result of covalent attachments of biomolecules to the surface, which remained functional under high shear stresses (50 dyn/cm(2)). An IgG antibody conjugated to three different fluorescence dyes (FITC, Cy5 and Cy3) was used to demonstrate the resulting multiplex concentration gradients of biomolecules. The device enabled generation of gradients with up to three different biomolecules in each channel with varying concentration profiles. We were also able to produce 2-dimensional gradients in which biomolecules were distributed along the length and width of the channel. To demonstrate the applicability of the developed design, three different multiplex concentration gradients of REDV and KRSR peptides were patterned along the width of three parallel channels and adhesion of primary human umbilical vein endothelial cell (HUVEC) in each channel was subsequently investigated using a single chip.

  12. Unstable flow of worm-like micelles in rectangular microfluidic channels

    NASA Astrophysics Data System (ADS)

    Salipante, Paul; Hudson, Steven

    2016-11-01

    We investigate a jetting instability of shear banding worm-like micelle (WLM) solutions in microfluidic channels with rectangular cross-sections. The flow is tracked using both 3-D and 2-D particle tracking methods in channels of different aspect ratio, size, and wall materials. We observe that the instability forms in high aspect ratio channels within an intermediate range of volumetric flows. The location of the high velocity jet in the channel appears to be sensitive to stress localizations induced by channel defects and wall roughness. A lower concentration WLM solution, with a monotonic stress curve, does not show the banding instability but displays non-negligible velocity gradients across the channel width. The transient development of the instability at the entrance of the microfluidic channel is observed in various geometries. The experimental measurements are compared to finite volume simulations using the Johnson-Segalman viscoelastic model. The simulations show a qualitatively similar behavior to our experimental observations and indicate that normal stresses in the cross stream directions lead to the development of the jetting flow.

  13. Femtosecond laser fabrication of microfluidic channels for organic photonic devices.

    PubMed

    Chaitanya Vishnubhatla, Krishna; Clark, Jenny; Lanzani, Guglielmo; Ramponi, Roberta; Osellame, Roberto; Virgili, Tersilla

    2009-11-01

    We report on innovative application of microchannels with access holes fabricated by femtosecond laser irradiation followed by chemical etching. This technique allows us to demonstrate a novel approach to the achievement of organic photonic devices in which the properties of a conjugated polymer in solution are exploited in a microfluidic configuration to produce an easy-to-integrate photonic device. Filling the microchannel with a diluted polyfluorene solution, we exploit the unique properties of isolated polymeric chains such as ultrafast gain switching (switching response time of 150 fs) with a 100% on-off ratio. In addition, by dispersing nanoparticles in the polymeric solution we are able to achieve random lasing in the microchannel.

  14. Two-dimensional optical feedback control of Euglena confined in closed-type microfluidic channels.

    PubMed

    Ozasa, Kazunari; Lee, Jeesoo; Song, Simon; Hara, Masahiko; Maeda, Mizuo

    2011-06-07

    We examined two-dimensional (2D) optical feedback control of phototaxis flagellate Euglena cells confined in closed-type microfluidic channels (microaquariums), and demonstrated that the 2D optical feedback enables the control of the density and position of Euglena cells in microaquariums externally, flexibly, and dynamically. Using three types of feedback algorithms, the density of Euglena cells in a specified area can be controlled arbitrarily and dynamically, and more than 70% of the cells can be concentrated into a specified area. Separation of photo-sensitive/insensitive Euglena cells was also demonstrated. Moreover, Euglena-based neuro-computing has been achieved, where 16 imaginary neurons were defined as Euglena-activity levels in 16 individual areas in microaquariums. The study proves that 2D optical feedback control of photoreactive flagellate microbes is promising for microbial biology studies as well as applications such as microbe-based particle transportation in microfluidic channels or separation of photo-sensitive/insensitive microbes.

  15. Preparation of monodisperse PEG hydrogel composite microspheres via microfluidic chip with rounded channels

    NASA Astrophysics Data System (ADS)

    Yu, Bing; Cong, Hailin; Liu, Xuesong; Ren, Yumin; Wang, Jilei; Zhang, Lixin; Tang, Jianguo; Ma, Yurong; Akasaka, Takeshi

    2013-09-01

    An effective microfluidic method to fabricate monodisperse polyethylene glycol (PEG) hydrogel composite microspheres with tunable dimensions and properties is reported in this paper. A T-junction microfluidic chip equipped with rounded channels and online photopolymerization system is applied for the microsphere microfabrication. The shape and size of the microspheres are well controlled by the rounded channels and PEG prepolymer/silicon oil flow rate ratios. The obtained PEG/aspirin composite microspheres exhibit a sustained release of aspirin for a wide time range; the obtained PEG/Fe3O4 nanocomposite microspheres exhibit excellent magnetic properties; and the obtained binary PEG/dye composite microspheres show the ability to synchronously load two functional components in the same peanut-shaped or Janus hydrogel particles.

  16. Generation of femtoliter reactor arrays within a microfluidic channel for biochemical analysis.

    PubMed

    Ota, Sadao; Kitagawa, Hiroaki; Takeuchi, Shoji

    2012-08-07

    We present a simple microfluidic method to generate high-density femotoliter-sized microreactor arrays within microfluidic channels. In general, we designed a main channel with many small chambers built into its walls. After sequentially infusing aqueous solution and organic solvent from a single tube into the device, aqueous droplets are confined in the chambers by the solvent flow. The generated reactors are small and stable enough for carrying out ultrasensitive biochemical assays at single molecule levels. As a demonstration, in this paper, we optically observed hydrolysis activity of β-galactosidase enzymatic molecules in the reactor arrays at single molecule levels. Further, this method has the following advantages: (1) the droplets are observable immediately after formation and (2) its simple procedure is sufficiently robust such that even handy infusion of the preloaded solutions is reproducible. We believe our method provides a platform attractive to a variety of single molecule studies and sensing applications such as clinical diagnostics.

  17. Analysis of remote detection travel time curves measured from microfluidic channels.

    PubMed

    Telkki, Ville-Veikko; Zhivonitko, Vladimir V

    2011-06-01

    Remote detection technique can increase sensitivity of an NMR experiment by several orders of magnitude in microfluidic applications. Travel time experiment is a basic remote detection NMR experiment, which reveals the travel time distribution of the molecules flowing from the encoding coil region to the detector. In this article, we focus on analyzing how flow type (Poiseuille or plug flow), diffusion, dispersion and geometry of the flow channels are manifested in the travel time curves measured from microfluidic channels. We demonstrate that remote detection travel time experiment could be used even as an alternative NMR method for measuring self-diffusion coefficient of a fluid without magnetic field gradients. In addition, we introduce a modified travel time pulse sequence, which removes the signal of unencoded fluid spins as well as the background signal arising from the material inside or close to the detector. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. World-to-chip interconnects for efficient loading of genomic DNA into microfluidic channels

    NASA Astrophysics Data System (ADS)

    Humphreys, Tim; Andersson, Johan; Södervall, Ulf; Melvin, Tracy

    2009-10-01

    A novel sloped interconnect for the efficient delivery of long genomic DNA fragments into a microfluidic channel is designed, fabricated and tested. Out-of-plane slopes are fabricated in silicon wafers using the deep reactive-ion etch lag phenomenon and a combination of anisotropic and isotropic etching. The final structure is capped with anodically bonded glass. Based upon a series of etch-lag calibration studies, the interconnect was designed using finite element analysis to provide a channel with flow acceleration properties appropriate to straighten DNA molecules. The efficiency of transit of the 48.5 kb DNA fragments (~16.5 µm long when fully extended) through the microfluidic device, established using quantitative real-time polymerase chain reaction, is 95 ± 7.3%.

  19. Prediction and validation of concentration gradient generation in a paper-based microfluidic channel

    NASA Astrophysics Data System (ADS)

    Jang, Ilhoon; Kim, Gang-June; Song, Simon

    2016-11-01

    A paper-based microfluidic channel has obtained attention as a diagnosis device that can implement various chemical or biological reactions. With benefits of thin, flexible, and strong features of paper devices, for example, it is often utilized for cell culture where controlling oxygen, nutrients, metabolism, and signaling molecules gradient affects the growth and movement of the cells. Among various features of paper-based microfluidic devices, we focus on establishment of concentration gradient in a paper channel. The flow is subject to dispersion and capillary effects because a paper is a porous media. In this presentation, we describe facile, fast and accurate method of generating a concentration gradient by using flow mixing of different concentrations. Both theoretical prediction and experimental validation are discussed along with inter-diffusion characteristics of porous flows. This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

  20. Deoxyribonucleic acid modified poly(dimethylsiloxane) microfluidic channels for the enhancement of microchip electrophoresis.

    PubMed

    Liang, Ruping; Hu, Pengfei; Gan, Guihua; Qiu, Jianding

    2009-03-15

    In this paper, deoxyribonucleic acid (DNA) was employed to construct a functional film on the PDMS microfluidic channel surface and apply to perform electrophoresis coupled with electrochemical detection. The functional film was formed by sequentially immobilizing chitosan and DNA to the PDMS microfluidic channel surface using the layer-by-layer assembly. The polysaccharide backbone of chitosan can be strongly adsorbed onto the hydrophobic PDMS surface through electrostatic interaction in the acidic media, meanwhile, chitosan contains one protonatable functional moiety resulting in a strong electrostatic interactions between the surface amine group of chitosan and the charged phosphate backbone of DNA at low pH, which generates a hydrophilic microchannel surface and reveals perfect resistance to nonspecific adsorption of analytes. Aminophenol isomers (p-, o-, and m-aminophenol) served as a separation model to evaluate the effect of the functional PDMS microfluidic chips. The results clearly showed that these analytes were efficiently separated within 60s in a 3.7 cm long separation channel and successfully detected on the modified microchip coupled with in-channel amperometric detection mode at a single carbon fiber electrode. The theoretical plate numbers were 74,021, 92,658 and 60,552 Nm(-1) at the separation voltage of 900 V with the detection limits of 1.6, 4.7 and 2.5 microM (S/N=3) for p-, o-, and m-aminophenol, respectively. In addition, this report offered an effective means for preparing hydrophilic and biocompatible PDMS microchannel surface, which would facilitate the use of microfluidic devices for more widespread applications.

  1. On the role of oxygen in fabricating microfluidic channels with ultraviolet curable materials.

    PubMed

    Jeong, Hoon Eui; Suh, Kahp Y

    2008-11-01

    We present the effects of oxygen on the irreversible bonding of a microchannel using an ultraviolet (UV) curable material of polyurethane acrylate (PUA). Microchannels were fabricated by bonding a top layer with impressions of a microfluidic channel and a bottom layer consisting of a PUA coating on a glass or a polyethylene terephthalate (PET) film substrate. The resulting channel is a homogeneous conduit of the PUA material. To find optimal bonding conditions, the bottom layer was cured under different oxygen concentration and UV exposure time at a constant UV intensity (10 mW cm(-2)). Our experimental and theoretical studies revealed that the channel bonding is severely affected by the concentration of oxygen either in the form of trapped air or permeated air out of the channel. In addition, an optimal UV exposure time is needed to prevent clogging or non-bonding of the channel.

  2. Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels.

    PubMed

    Wang, Xiaolin; Phan, Duc T T; Sobrino, Agua; George, Steven C; Hughes, Christopher C W; Lee, Abraham P

    2016-01-21

    This paper reports a method for generating an intact and perfusable microvascular network that connects to microfluidic channels without appreciable leakage. This platform incorporates different stages of vascular development including vasculogenesis, endothelial cell (EC) lining, sprouting angiogenesis, and anastomosis in sequential order. After formation of a capillary network inside the tissue chamber via vasculogenesis, the adjacent microfluidic channels are lined with a monolayer of ECs, which then serve as the high-pressure input ("artery") and low pressure output ("vein") conduits. To promote a tight interconnection between the artery/vein and the capillary network, sprouting angiogenesis is induced, which promotes anastomosis of the vasculature inside the tissue chamber with the EC lining along the microfluidic channels. Flow of fluorescent microparticles confirms the perfusability of the lumenized microvascular network, and minimal leakage of 70 kDa FITC-dextran confirms physiologic tightness of the EC junctions and completeness of the interconnections between artery/vein and the capillary network. This versatile device design and its robust construction methodology establish a physiological transport model of interconnected perfused vessels from artery to vascularized tissue to vein. The system has utility in a wide range of organ-on-a-chip applications as it enables the physiological vascular interconnection of multiple on-chip tissue constructs that can serve as disease models for drug screening.

  3. A new floating electrode structure for generating homogeneous electrical fields in microfluidic channels.

    PubMed

    Segerink, Loes I; Sprenkels, Ad J; Bomer, Johan G; Vermes, Istvan; van den Berg, Albert

    2011-06-21

    In this article a new parallel electrode structure in a microfluidic channel is described that makes use of a floating electrode to get a homogeneous electrical field. Compared to existing parallel electrode structures, the new structure has an easier production process and there is no need for an electrical connection to both sides of the microfluidic chip. With the new chip design, polystyrene beads suspended in background electrolyte have been detected using electrical impedance measurements. The results of electrical impedance changes caused by beads passing the electrodes are compared with results in a similar planar electrode configuration. It is shown that in the new configuration the coefficient of variation of the impedance changes is lower compared to the planar configuration (0.39 versus 0.56) and less dependent on the position of the beads passage in the channel as a result of the homogeneous electrical field. To our knowledge this is the first time that a floating electrode is used for the realization of a parallel electrode structure. The proposed production method for parallel electrodes in microfluidic channels can easily be applied to other applications.

  4. Computational Fluid Dynamics Modelling of Microfluidic Channel for Dielectrophoretic BioMEMS Application

    PubMed Central

    Low, Wan Shi; Kadri, Nahrizul Adib; Wan Abas, Wan Abu Bakar bin

    2014-01-01

    We propose a strategy for optimizing distribution of flow in a typical benchtop microfluidic chamber for dielectrophoretic application. It is aimed at encouraging uniform flow velocity along the whole analysis chamber in order to ensure DEP force is evenly applied to biological particle. Via the study, we have come up with a constructive strategy in improving the design of microfluidic channel which will greatly facilitate the use of DEP system in laboratory and primarily focus on the relationship between architecture and cell distribution, by resorting to the tubular structure of blood vessels. The design was validated by hydrodynamic flow simulation using COMSOL Multiphysics v4.2a software. Simulations show that the presence of 2-level bifurcation has developed portioning of volumetric flow which produced uniform flow across the channel. However, further bifurcation will reduce the volumetric flow rate, thus causing undesirable deposition of cell suspension around the chamber. Finally, an improvement of microfluidic design with rounded corner is proposed to encourage a uniform cell adhesion within the channel. PMID:25136701

  5. Computational fluid dynamics modelling of microfluidic channel for dielectrophoretic BioMEMS application.

    PubMed

    Low, Wan Shi; Kadri, Nahrizul Adib; Abas, Wan Abu Bakar bin Wan

    2014-01-01

    We propose a strategy for optimizing distribution of flow in a typical benchtop microfluidic chamber for dielectrophoretic application. It is aimed at encouraging uniform flow velocity along the whole analysis chamber in order to ensure DEP force is evenly applied to biological particle. Via the study, we have come up with a constructive strategy in improving the design of microfluidic channel which will greatly facilitate the use of DEP system in laboratory and primarily focus on the relationship between architecture and cell distribution, by resorting to the tubular structure of blood vessels. The design was validated by hydrodynamic flow simulation using COMSOL Multiphysics v4.2a software. Simulations show that the presence of 2-level bifurcation has developed portioning of volumetric flow which produced uniform flow across the channel. However, further bifurcation will reduce the volumetric flow rate, thus causing undesirable deposition of cell suspension around the chamber. Finally, an improvement of microfluidic design with rounded corner is proposed to encourage a uniform cell adhesion within the channel.

  6. Blood plasma separation in microfluidic channels using flow rate control.

    PubMed

    Yang, Sung; Undar, Akif; Zahn, Jeffrey D

    2005-01-01

    Several studies have clearly shown that cardiac surgery induces systemic inflammatory responses, particularly when cardiopulmonary bypass (CPB) is used. CPB induces complex inflammatory responses. Considerable evidence suggests that systemic inflammation causes many postoperative complications. Currently, there is no effective method to prevent this systemic inflammatory response syndrome in patients undergoing CPB. The ability to clinically intervene in inflammation, or even study the inflammatory response to CPB, is limited by the lack of timely measurements of inflammatory responses. In this study, a microfluidic device for continuous, real-time blood plasma separation, which may be integrated with downstream plasma analysis device, is introduced. This device is designed to have a whole blood inlet, a purified plasma outlet, and a concentrated blood cell outlet. The device is designed to separate plasma with up to 45% hematocrit of the inlet blood and is analyzed using computational fluid dynamics simulation. The simulation results show that 27% and 25% of plasma can be collected from the total inlet blood volume for 45% and 39% hematocrit, respectively. The device's functionality was demonstrated using defibrinated sheep blood (hematocrit=39%). During the experiment, all the blood cells traveled through the device toward the concentrated blood outlet while only the plasma flowed towards the plasma outlet without any clogging or lysis of cells. Because of its simple structure and control mechanism, this microdevice is expected to be used for highly efficient, realtime, continuous cell-free plasma separation.

  7. Regeneration-Type Nerve Electrode Using Bundled Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Suzuki, Takafumi; Kotake, Naoki; Mabuchi, Kunihiko; Takeuchi, Shoji

    Neural interface devices that will allow signals from the human nervous system to control external equipment are extremely important for the next generation of prosthetic systems. A novel multichannel regeneration-type nerve electrode designed to record from and stimulate peripheral nerves has been developed to allow the control of artificial hands and to generate artificial sensations. In this study a novel flexible regeneration microelectrode based on the nerve regeneration principle was designed and fabricated using MEMS technologies. The electrode, which was fabricated on a 25-μm-thick Parylene C substrate, has multiple fluidic channels. Each fluidic channel was 100 μm wide × 30 μm high × 1500 μm long and featured multiple electrodes inside them as recording and stimulating sites. They also served as guidance channels for the regenerating axons.

  8. Method and apparatus for controlling cross contamination of microfluid channels

    DOEpatents

    Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Paul, Phillip H.; Arnold, Don W.

    2006-02-07

    A method for controlling fluid flow at junctions in microchannel systems. Control of fluid flow is accomplished generally by providing increased resistance to electric-field and pressure-driven flow in the form of regions of reduced effective cross-sectional area within the microchannels and proximate a channel junction. By controlling these flows in the region of a microchannel junction it is possible to eliminate sample dispersion and cross contamination and inject well-defined volumes of fluid from one channel to another.

  9. Inertial and viscoelastic forces on rigid colloids in microfluidic channels.

    PubMed

    Howard, Michael P; Panagiotopoulos, Athanassios Z; Nikoubashman, Arash

    2015-06-14

    We perform hybrid molecular dynamics simulations to study the flow behavior of rigid colloids dispersed in a dilute polymer solution. The underlying Newtonian solvent and the ensuing hydrodynamic interactions are incorporated through multiparticle collision dynamics, while the constituent polymers are modeled as bead-spring chains, maintaining a description consistent with the colloidal nature of our system. We study the cross-stream migration of the solute particles in slit-like channels for various polymer lengths and colloid sizes and find a distinct focusing onto the channel center under specific solvent and flow conditions. To better understand this phenomenon, we systematically measure the effective forces exerted on the colloids. We find that the migration originates from a competition between viscoelastic forces from the polymer solution and hydrodynamically induced inertial forces. Our simulations reveal a significantly stronger fluctuation of the lateral colloid position than expected from thermal motion alone, which originates from the complex interplay between the colloid and polymer chains.

  10. ATOMIC FORCE LITHOGRAPHY OF NANO/MICROFLUIDIC CHANNELS FOR VERIFICATION AND MONITORING OF AQUEOUS SOLUTIONS

    SciTech Connect

    Mendez-Torres, A.; Torres, R.; Lam, P.

    2011-07-15

    The growing interest in the physics of fluidic flow in nanoscale channels, as well as the possibility for high sensitive detection of ions and single molecules is driving the development of nanofluidic channels. The enrichment of charged analytes due to electric field-controlled flow and surface charge/dipole interactions along the channel can lead to enhancement of sensitivity and limits-of-detection in sensor instruments. Nuclear material processing, waste remediation, and nuclear non-proliferation applications can greatly benefit from this capability. Atomic force microscopy (AFM) provides a low-cost alternative for the machining of disposable nanochannels. The small AFM tip diameter (< 10 nm) can provide for features at scales restricted in conventional optical and electron-beam lithography. This work presents preliminary results on the fabrication of nano/microfluidic channels on polymer films deposited on quartz substrates by AFM lithography.

  11. ATOMIC FORCE LITHOGRAPHY OF NANO MICROFLUIDIC CHANNELS FOR VERIFICATION AND MONITORING IN AQUEOUS SOLUTIONS

    SciTech Connect

    Torres, R.; Mendez-Torres, A.; Lam, P.

    2011-06-09

    The growing interest in the physics of fluidic flow in nanoscale channels, as well as the possibility for high sensitive detection of ions and single molecules is driving the development of nanofluidic channels. The enrichment of charged analytes due to electric field-controlled flow and surface charge/dipole interactions along the channel can lead to enhancement of sensitivity and limits-of-detection in sensor instruments. Nuclear material processing, waste remediation, and nuclear non-proliferation applications can greatly benefit from this capability. Atomic force microscopy (AFM) provides a low-cost alternative for the machining of disposable nanochannels. The small AFM tip diameter (< 10 nm) can provide for features at scales restricted in conventional optical and electron-beam lithography. This work presents preliminary results on the fabrication of nano/microfluidic channels on polymer films deposited on quartz substrates by AFM lithography.

  12. Probing structure and function of ion channels using limited proteolysis and microfluidics.

    PubMed

    Trkulja, Carolina L; Jansson, Erik T; Jardemark, Kent; Orwar, Owe

    2014-10-22

    Even though gain, loss, or modulation of ion channel function is implicated in many diseases, both rare and common, the development of new pharmaceuticals targeting this class has been disappointing, where it has been a major problem to obtain correlated structural and functional information. Here, we present a microfluidic method in which the ion channel TRPV1, contained in proteoliposomes or in excised patches, was exposed to limited trypsin proteolysis. Cleaved-off peptides were identified by MS, and electrophysiological properties were recorded by patch clamp. Thus, the structure-function relationship was evaluated by correlating changes in function with removal of structural elements. Using this approach, we pinpointed regions of TRPV1 that affect channel properties upon their removal, causing changes in current amplitude, single-channel conductance, and EC50 value toward its agonist, capsaicin. We have provided a fast "shotgun" method for chemical truncation of a membrane protein, which allows for functional assessments of various peptide regions.

  13. Patterned Immobilization of Antibodies within Roll-to-Roll Hot Embossed Polymeric Microfluidic Channels

    PubMed Central

    Feyssa, Belachew; Liedert, Christina; Kivimaki, Liisa; Johansson, Leena-Sisko; Jantunen, Heli; Hakalahti, Leena

    2013-01-01

    This paper describes a method for the patterned immobilization of capture antibodies into a microfluidic platform fabricated by roll-to-roll (R2R) hot embossing on poly (methyl methacrylate) (PMMA). Covalent attachment of antibodies was achieved by two sequential inkjet printing steps. First, a polyethyleneimine (PEI) layer was deposited onto oxygen plasma activated PMMA foil and further cross-linked with glutaraldehyde (GA) to provide an amine-reactive aldehyde surface (PEI-GA). This step was followed by a second deposition of antibody by overprinting on the PEI-GA patterned PMMA foil. The PEI polymer ink was first formulated to ensure stable drop formation in inkjet printing and the printed films were characterized using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Anti-CRP antibody was patterned on PMMA foil by the developed method and bonded permanently with R2R hot embossed PMMA microchannels by solvent bonding lamination. The functionality of the immobilized antibody inside the microfluidic channel was evaluated by fluorescence-based sandwich immunoassay for detection of C-reactive protein (CRP). The antibody-antigen assay exhibited a good level of linearity over the range of 10 ng/ml to 500 ng/ml (R2 = 0.991) with a calculated detection limit of 5.2 ng/ml. The developed patterning method is straightforward, rapid and provides a versatile approach for creating multiple protein patterns in a single microfluidic channel for multiplexed immunoassays. PMID:23874811

  14. Fabrication of monolithic microfluidic channels in diamond with ion beam lithography

    NASA Astrophysics Data System (ADS)

    Picollo, F.; Battiato, A.; Boarino, L.; Ditalia Tchernij, S.; Enrico, E.; Forneris, J.; Gilardino, A.; Jakšić, M.; Sardi, F.; Skukan, N.; Tengattini, A.; Olivero, P.; Re, A.; Vittone, E.

    2017-08-01

    In the present work, we report on the monolithic fabrication by means of ion beam lithography of hollow micro-channels within a diamond substrate, to be employed for microfluidic applications. The fabrication strategy takes advantage of ion beam induced damage to convert diamond into graphite, which is characterized by a higher reactivity to oxidative etching with respect to the chemically inert pristine structure. This phase transition occurs in sub-superficial layers thanks to the peculiar damage profile of MeV ions, which mostly damage the target material at their end of range. The structures were obtained by irradiating commercial CVD diamond samples with a micrometric collimated C+ ion beam at three different energies (4 MeV, 3.5 MeV and 3 MeV) at a total fluence of 2 × 1016 cm-2. The chosen multiple-energy implantation strategy allows to obtain a thick box-like highly damaged region ranging from 1.6 μm to 2.1 μm below the sample surface. High-temperature annealing was performed to both promote the graphitization of the ion-induced amorphous layer and to recover the pristine crystalline structure in the cap layer. Finally, the graphite was removed by ozone etching, obtaining monolithic microfluidic structures. These prototypal microfluidic devices were tested injecting aqueous solutions and the evidence of the passage of fluids through the channels was confirmed by confocal fluorescent microscopy.

  15. Numerical simulations of interacting surfactant-laden jets in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Goel, Garvit; Yang, Junfeng; Cabral, Joao; Matar, Omar

    2014-11-01

    We consider the dynamics of jets of surfactant solution in oil under microfluidic confinement. Previous experimental work has demonstrated the occurrence of ``jetting'' and ``dripping'' flow regimes depending on the choice of oil and water flow rates, viscosity ratio, and surfactant concentration. To take into account the influence of soluble surfactant on the behaviour of the jets, we present a computational fluid dynamics (CFD) approach which uses the Volume-of-Fluid method capturing the interface topology accurately with minimal mass loss. This approach accounts for sorption kinetics, Marangoni stresses, diffusion, and surface dilation. This method is incorporated into a CFD code to study the jetting and dripping regimes in a microfluidics channel. The modelling results are validated against experimental measurements. EPSRC Programme Grant, MEMPHIS, EP/K0039761/1, and Grant Number EP/J010502/1.

  16. Flow-induced demixing of polymer-colloid mixtures in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Nikoubashman, Arash; Mahynski, Nathan A.; Pirayandeh, Amir H.; Panagiotopoulos, Athanassios Z.

    2014-03-01

    We employ extensive computer simulations to study the flow behavior of spherical, nanoscale colloids in a viscoelastic solvent under Poiseuille flow. The systems are confined in a slit-like microfluidic channel, and viscoelasticity is introduced explicitly through the inclusion of polymer chains on the same length scale as the dispersed solute particles. We systematically study the effects of flow strength and polymer concentration, and identify a regime in which the colloids migrate to the centerline of the microchannel, expelling the polymer chains to the sides. This behavior was recently identified in experiments, but a detailed understanding of the underlying physics was lacking. To this end, we provide a detailed analysis of this phenomenon and discuss ways to maximize its effectiveness. The focusing mechanism can be exploited to separate and capture particles at the sub-micrometer scale using simple microfluidic devices, which is a crucial task for many biomedical applications, such as cell counting and genomic mapping.

  17. Control of microparticles packing density in a microfluidic channel for bead based immunoassays applications

    NASA Astrophysics Data System (ADS)

    Caballero-Robledo, Gabriel; Guevara-Pantoja, Pablo

    2014-11-01

    Bead based immunoassays in microfluidic devices have shown to greatly outperform conventional methods. But if functional point-of-care devices are to be developed, precise and reproducible control over the granulate packings inside microchannels is needed. In this work we study the efficiency of a nanoparticles magnetic trap previously developed by B. Teste et al. [Lab Chip 11, 4207 (2011)] when we vary the compaction of micrometric iron beads packed against a restriction inside a microfluidic channel. The packing density of the beads is finely and reproducibly changed by applying a vibrational protocol originally developed for macroscopic, dry granular systems. We find, counterintuitively, that the most compact and stable packings are up to four times less efficient in trapping nano particles than the loosest packings. This work has been supported by Conacyt, Mexico, under Grant No. 180873.

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

    PubMed

    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.

  19. Specific transport of target molecules by motor proteins in microfluidic channels.

    PubMed

    Tarhan, Mehmet C; Yokokawa, Ryuji; Morin, Fabrice O; Fujita, Hiroyuki

    2013-06-03

    Direct transport powered by motor proteins can alleviate the challenges presented by miniaturization of microfluidic systems. There have been several recent attempts to build motor-protein-driven transport systems based on simple capturing or transport mechanisms. However, to achieve a multifunctional device for practical applications, a more complex sorting/transport system should be realized. Herein, the proof of concept of a sorting device employing selective capture of distinct target molecules and transport of the sorted molecules to different predefined directions is presented. By combining the bottom-up functionality of biological systems with the top-down handling capabilities of micro-electromechanical systems technology, highly selective molecular recognition and motor-protein-based transport is integrated in a microfluidic channel network.

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

    PubMed Central

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

    2009-01-01

    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. PMID:20216959

  1. Enhancing Capillary-Driven Flow for Paper-Based Microfluidic Channels.

    PubMed

    Songok, Joel; Toivakka, Martti

    2016-11-09

    Paper-based microfluidic devices have received considerable interest due to their benefits with regards to low manufacturing costs, simplicity, and the wide scope of applications. However, limitations including sample retention in paper matrix and evaporation as well as low liquid flow rates have often been overlooked. This paper presents a paper-based capillary-driven flow system that speeds up flow rates by utilizing narrow gap geometry between two parallel surfaces separated by a spacer. The top surface is hydrophobic, while the bottom surface is a hydrophobic paper substrate with a microfluidic channel defined by a hydrophilic pathway, leaving sides of the channel open to air. The liquid flows on the hydrophilic path in the gap without spreading onto the hydrophobic regions. The closed-channel flow system showed higher spreading distances and accelerated liquid flow. An average flow rate increases of 200 and 100% were obtained for the nanoparticle-coated paperboard and the blotting papers used, respectively. Fast liquid delivery to detection zones or reaction implies rapid results from analytical devices. In addition, liquid drying and evaporation can be reduced in the proposed closed-channel system.

  2. CO2 laser polishing of microfluidic channels fabricated by femtosecond laser assisted carving

    NASA Astrophysics Data System (ADS)

    Serhatlioglu, Murat; Ortaç, Bülend; Elbuken, Caglar; Biyikli, Necmi; Solmaz, Mehmet E.

    2016-11-01

    In this study, we investigate the effects of CO2 laser polishing on microscopic structures fabricated by femtosecond laser assisted carving (FLAC). FLAC is the peripheral laser irradiation of 2.5D structures suitable for low repetition rate lasers and is first used to define the microwell structures in fused silica followed by chemical etching. Subsequently, the bottom surface of patterned microwells is irradiated with a pulsed CO2 laser. The surfaces were characterized using an atomic force microscope (AFM) and scanning electron microscope (SEM) in terms of roughness and high quality optical imaging before and after the CO2 laser treatment. The AFM measurements show that the surface roughness improves more than threefold after CO2 laser polishing, which promises good channel quality for applications that require optical imaging. In order to demonstrate the ability of this method to produce low surface roughness systems, we have fabricated a microfluidic channel. The channel is filled with polystyrene bead-laden fluid and imaged with transmission mode microscopy. The high quality optical images prove CO2 laser processing as a practical method to reduce the surface roughness of microfluidic channels fabricated by femtosecond laser irradiation. We further compared the traditional and laser-based glass micromachining approaches, which includes FLAC followed by the CO2 polishing technique.

  3. Experimental evaluation of chromatographic performance of capillary and microfluidic columns with linear or curved channels.

    PubMed

    Gilar, Martin; McDonald, Thomas S; Gritti, Fabrice

    2016-10-28

    We prepared 0.3 or 0.15mm i.d. columns from both fused silica capillaries and planar titanium wafers with machined grooves. Both types of devices were packed with sub-two micron C18 sorbent. Chromatographic efficiency and peak capacity were tested using LC instruments with low extra column dispersion (300nL(2) or 30nL(2) for 0.3 or 0.15mm i.d. columns, respectively). Micro column testing in gradient mode was less affected by extra column (pre-column) dispersion. To exploit this feature we developed a method for estimation of column efficiency from gradient analysis using the theoretical relationship (Pc-1)=N(0.5)×const. The validity of this relationship was experimentally verified using 2.1mm i.d. and 0.3mm i.d. columns. The (Pc-1) versus N relationship was experimentally determined with straight columns, which in turn was employed for the estimation of microfluidic column efficiency. Microfluidic devices with serpentine channels exhibited lower isocratic efficiency than straight capillary columns, but the loss of peak capacity was less significant. The loss chromatographic efficiency due to zone dispersion in serpentine microfluidic channels was more apparent for 0.3 than 0.15mm i.d. devices. Gradient performance of 0.15×100mm microfluidic columns was comparable to state-of-the-art 2.1×100mm columns packed with the same sorbent. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Monolithic column plastic microfluidic device for peptide analysis using electrospray from a channel opening on the edge of the device

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Ro, Kyung-Won; Nayak, Ranu; Knapp, Daniel R.

    2007-01-01

    Electrospray from a channel exit at the edge of a fluorocarbon coated cycloolefin copolymer microfluidic device has been investigated. The fluorocarbon coating facilitated generation of a stable electrospray, thereby enhancing the detectability of electrospray ionization (ESI) mass spectrometry (MS). A microfluidic device of integrated ESI emitters and monolithic liquid chromatography columns has been fabricated on a cycloolefin copolymer chip. The monolithic columns were polymerized in situ using UV irradiation with a photomask to confine the porous polymer monolith to the desired regions of the channels. The monolithic stationary phase was homogenous and well bonded to the channel surfaces, which had been functionalized by graft polymerization. The ESI potential was applied within the channel via a carbon ink line. The performance of this microfluidic device was demonstrated by analysis of a tryptic digest of bovine serum albumin on an ion trap MS instrument.

  5. Concentration distributions of arbitrary shaped particles in microfluidic channel flows

    NASA Astrophysics Data System (ADS)

    Saibaba, Arvind; Shaqfeh, Eric; Darve, Eric

    2009-11-01

    We are interested in the study of the transient and steady state concentration distribution of orientable Brownian particles across channels at low Reynolds numbers. This is important in understanding margination of blood ``particles'' including platelets as well as new drug delivery and cancer nanotechnology particles which are involved in hemostasis as well as delivering drugs to the vascular endothelial cells. Although our formulation is general, the particles we consider are rigid Brownian ``surfboards'' which have been found to be effective in drug delivery since they are resistant to leukocyte attack [1]. The Stokes flow in the channel around the particles, driven by a mean pressure gradient, is computed using the Boundary Element method within the single layer formulation. The particle motion is calculated using rigid body dynamics with a contribution due to Brownian motion that satisfies the Fluctuation-Dissipation theorem. Finite concentrations are considered, and all hydrodynamic interactions are included. The concentration distribution is computed and interpreted as a balance between the concentration dependent variation in the non-equilibrium particle osmotic pressure and the cross stream particle normal stresses. [4pt] [1] J. A. Champion, S. Mitragotri, ``Role of target geometry in phagocytosis'', PNAS 103, 4930-4934, (2006)

  6. Electroosmosis-modulated peristaltic transport in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Bandopadhyay, Aditya; Tripathi, Dharmendra; Chakraborty, Suman

    2016-05-01

    We analyze the peristaltic motion of aqueous electrolytes altered by means of applied electric fields. Handling electrolytes in typical peristaltic channel material such as polyvinyl chloride and Teflon leads to the generation of a net surface charge on the channel walls, which attracts counter-ions and repels co-ions from the aqueous solution, thus leading to the formation of an electrical double layer—a region of net charges near the wall. We analyze the spatial distribution of pressure and wall shear stress for a continuous wave train and single pulse peristaltic wave in the presence of an electrical (electroosmotic) body force, which acts on the net charges in the electrical double layer. We then analyze the effect of the electroosmotic body force on the particle reflux as elucidated through the net displacement of neutrally buoyant particles in the flow as the peristaltic waves progress. The impact of combined electroosmosis and peristalsis on trapping of a fluid volume (e.g., bolus) inside the travelling wave is also discussed. The present analysis goes beyond the traditional analysis, which neglects the possibility of coupling the net pumping of fluids due to peristalsis and allows us to derive general expressions for the pressure drop and flow rate in order to set up a general framework for incorporating flow control and actuation by simultaneous peristalsis and application of electric fields to aqueous solutions. It is envisaged that the results presented here may act as a model for the design of lab-on-a-chip devices.

  7. Ion channel pharmacology under flow: automation via well-plate microfluidics.

    PubMed

    Spencer, C Ian; Li, Nianzhen; Chen, Qin; Johnson, Juliette; Nevill, Tanner; Kammonen, Juha; Ionescu-Zanetti, Cristian

    2012-08-01

    Automated patch clamping addresses the need for high-throughput screening of chemical entities that alter ion channel function. As a result, there is considerable utility in the pharmaceutical screening arena for novel platforms that can produce relevant data both rapidly and consistently. Here we present results that were obtained with an innovative microfluidic automated patch clamp system utilizing a well-plate that eliminates the necessity of internal robotic liquid handling. Continuous recording from cell ensembles, rapid solution switching, and a bench-top footprint enable a number of assay formats previously inaccessible to automated systems. An electro-pneumatic interface was employed to drive the laminar flow of solutions in a microfluidic network that delivered cells in suspension to ensemble recording sites. Whole-cell voltage clamp was applied to linear arrays of 20 cells in parallel utilizing a 64-channel voltage clamp amplifier. A number of unique assays requiring sequential compound applications separated by a second or less, such as rapid determination of the agonist EC(50) for a ligand-gated ion channel or the kinetics of desensitization recovery, are enabled by the system. In addition, the system was validated via electrophysiological characterizations of both voltage-gated and ligand-gated ion channel targets: hK(V)2.1 and human Ether-à-go-go-related gene potassium channels, hNa(V)1.7 and 1.8 sodium channels, and (α1) hGABA(A) and (α1) human nicotinic acetylcholine receptor receptors. Our results show that the voltage dependence, kinetics, and interactions of these channels with pharmacological agents were matched to reference data. The results from these IonFlux™ experiments demonstrate that the system provides high-throughput automated electrophysiology with enhanced reliability and consistency, in a user-friendly format.

  8. Single channel layer, single sheath-flow inlet microfluidic flow cytometer with three-dimensional hydrodynamic focusing.

    PubMed

    Lin, Shiang-Chi; Yen, Pei-Wen; Peng, Chien-Chung; Tung, Yi-Chung

    2012-09-07

    Flow cytometry is a technique capable of optically characterizing biological particles in a high-throughput manner. In flow cytometry, three dimensional (3D) hydrodynamic focusing is critical for accurate and consistent measurements. Due to the advantages of microfluidic techniques, a number of microfluidic flow cytometers with 3D hydrodynamic focusing have been developed in recent decades. However, the existing devices consist of multiple layers of microfluidic channels and tedious fluidic interconnections. As a result, these devices often require complicated fabrication and professional operation. Consequently, the development of a robust and reliable microfluidic flow cytometer for practical biological applications is desired. This paper develops a microfluidic device with a single channel layer and single sheath-flow inlet capable of achieving 3D hydrodynamic focusing for flow cytometry. The sheath-flow stream is introduced perpendicular to the microfluidic channel to encircle the sample flow. In this paper, the flow fields are simulated using a computational fluidic dynamic (CFD) software, and the results show that the 3D hydrodynamic focusing can be successfully formed in the designed microfluidic device under proper flow conditions. The developed device is further characterized experimentally. First, confocal microscopy is exploited to investigate the flow fields. The resultant Z-stack confocal images show the cross-sectional view of 3D hydrodynamic with flow conditions that agree with the simulated ones. Furthermore, the flow cytometric detections of fluorescence beads are performed using the developed device with various flow rate combinations. The measurement results demonstrate that the device can achieve great detection performances, which are comparable to the conventional flow cytometer. In addition, the enumeration of fluorescence-labelled cells is also performed to show its practicality for biological applications. Consequently, the microfluidic

  9. DNA Extraction by Isotachophoresis in a Microfluidic Channel

    SciTech Connect

    Stephenson, S J

    2011-08-10

    electrolyte ions. Conversely, the trailing electrolyte ions have a slow electrophoretic mobility, so they lag behind the sample, thus trapping the species of interest between the LE and TE streams. In a typical isotachophoresis configuration, the electric field is applied in a direction parallel to the direction of flow. The species then form bands that stretch across the width of the channel. A major limitation of that approach is that only a finite amount of sample can be processed at once, and the sample must be processed in batches. For our purposes, a form of free-flow isotachophoresis is more convenient, where the DNA forms a band parallel to the edges of the channel. To achieve this, in our chip, the electric field is applied transversely. This creates a force perpendicular to the direction of flow, which causes the different ions to migrate across the flow direction. Because the mobility of the DNA is between the mobility of the leading and the trailing electrolyte, the DNA is focused in a tight band near the center of the channel. The stream of DNA can then be directed to a different output to produce a highly concentrated outlet stream without batch processing. One hurdle that must be overcome for successful ITP is isolating the electrochemical reactions that result from the application of high voltage for the actual process of isotachophoresis. The electrochemical reactions that occur around metal electrodes produce bubbles and pH changes that are detrimental to successful ITP. The design of the chips we use incorporates polyacrylamide gels to serve as electrodes along the central channel. For our design, the metal electrodes are located away from the chip, and high conductivity buffer streams carry the potential to the chip, functioning as a 'liquid electrode.' The stream then runs alongside a gel barrier. The gel electrode permits ion transfer while simultaneously isolating the separation chamber from any contaminants in the outer, 'liquid electrode' streams. The

  10. Multi-channel PMMA microfluidic biosensor with integrated IDUAs for electrochemical detection

    PubMed Central

    Wongkaew, Nongnoot; He, Peng; Kurth, Vanessa; Surareungchai, Werasak; Baeumner, Antje J.

    2013-01-01

    A novel multi-channel poly(methyl methacrylate) (PMMA) microfluidic biosensor with interdigitated ultramicroelectrode arrays (IDUAs) for electrochemical detection was developed. The focus of the development was a simple fabrication procedure and the realization of a reliable large IDUA that can provide detection simultaneously to several microchannels. As proof of concept, five microchannels are positioned over a large single IDUA where the channels are parallel with the length of electrode finger. The IDUAs were fabricated on the PMMA cover piece and bonded to a PMMA substrate containing the microfluidic channels using UV/ozone-assisted thermal bonding. Conditions of device fabrication were optimized realizing a rugged large IDUA within a bonded PMMA device. Gold adhesion to the PMMA, protective coatings and pressure during bonding were optimized. Its electrochemical performance was studied using amperometric detection of potassium ferri and ferro hexacyanide. Cumulative signals within the same chip showed very good linearity over a range of 0 - 38 μM (R2 = 0.98) and a limit of detection of 3.48 μM. The bonding of the device was optimized so that no cross-talk between the channels was observed which otherwise would have resulted in unreliable electrochemical responses. The highly reproducible signals achieved were comparable to those obtained with separate single-channel devices. Subsequently, the multi-channel microfluidic chip was applied to a model bioanalytical detection strategy, i.e. the quantification of specific nucleic acid sequences using a sandwich approach. Here probe-coated paramagnetic beads and probe-tagged liposomes entrapping ferri/ferro hexacyanide as the redox marker were used to bind to a single stranded DNA sequence. Flow rates of the non-ionic detergent n-octyl-β-D-glucopyranoside (OG) for liposome lysis were optimized and the detection of the target sequences was carried out coulometrically within 250 s and with a limit of detection of 12

  11. Imaging through scattering microfluidic channels by digital holography for information recovery in lab on chip.

    PubMed

    Bianco, V; Paturzo, M; Gennari, O; Finizio, A; Ferraro, P

    2013-10-07

    We tackle the problem of information recovery and imaging through scattering microfluidic chips by means of digital holography (DH). In many cases the chip can become opalescent due to residual deposits settling down the inner channel faces, biofilm formation, scattering particle uptake by the channel cladding or its damaging by corrosive substances, or even by condensing effect on the exterior channels walls. In these cases white-light imaging is severely degraded and no information is obtainable at all about the flowing samples. Here we investigate the problem of counting and estimating velocity of cells flowing inside a scattering chip. Moreover we propose and test a method based on the recording of multiple digital holograms to retrieve improved phase-contrast images despite the strong scattering effect. This method helps, thanks to DH, to recover information which, otherwise, would be completely lost.

  12. Simultaneous dielectric monitoring of microfluidic channels at microwaves utilizing a metamaterial transmission line structure.

    PubMed

    Schüßler, M; Puentes, M; Dubuc, D; Grenier, K; Jakoby, R

    2012-01-01

    The paper presents a technique that allows the simultaneous monitoring of the dielectric properties of liquids in microfluidic channels at microwave frequencies. It is capable of being integrated within the lab-on-a-chip concept and uses a composite right/left-handed transmission line resonator which is detuned by the dielectric loading of the liquids in the channels. By monitoring the change in the resonance spectrum of the resonator the loading profile can be derived with the multi-resonant perturbation method. From the value of the dielectric constant inference on the substances like cells or chemicals in the channels can be drawn. The paper presents concept, design, fabrication and characterization of prototype sensors. The sensors have been designed to operate between 20 and 30 GHz and were tested with water and water ethanol mixtures.

  13. Hydrodynamic resistance and mobility of deformable objects in microfluidic channels

    PubMed Central

    Sajeesh, P.; Doble, M.; Sen, A. K.

    2014-01-01

    This work reports experimental and theoretical studies of hydrodynamic behaviour of deformable objects such as droplets and cells in a microchannel. Effects of mechanical properties including size and viscosity of these objects on their deformability, mobility, and induced hydrodynamic resistance are investigated. The experimental results revealed that the deformability of droplets, which is quantified in terms of deformability index (D.I.), depends on the droplet-to-channel size ratio ρ and droplet-to-medium viscosity ratio λ. Using a large set of experimental data, for the first time, we provide a mathematical formula that correlates induced hydrodynamic resistance of a single droplet ΔRd with the droplet size ρ and viscosity λ. A simple theoretical model is developed to obtain closed form expressions for droplet mobility ϕ and ΔRd. The predictions of the theoretical model successfully confront the experimental results in terms of the droplet mobility ϕ and induced hydrodynamic resistance ΔRd. Numerical simulations are carried out using volume-of-fluid model to predict droplet generation and deformation of droplets of different size ratio ρ and viscosity ratio λ, which compare well with that obtained from the experiments. In a novel effort, we performed experiments to measure the bulk induced hydrodynamic resistance ΔR of different biological cells (yeast, L6, and HEK 293). The results reveal that the bulk induced hydrodynamic resistance ΔR is related to the cell concentration and apparent viscosity of the cells. PMID:25538806

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Circumferential alignment of vascular smooth muscle cells in a circular microfluidic channel.

    PubMed

    Choi, Jong Seob; Piao, Yunxian; Seo, Tae Seok

    2014-01-01

    The circumferential alignment of human aortic smooth muscle cells (HASMCs) in an orthogonally micropatterned circular microfluidic channel is reported to form an in vivo-like smooth muscle cell layer. To construct a biomimetic smooth muscle cell layer which is aligned perpendicular to the axis of blood vessel, a half-circular polydimethylsiloxane (PDMS) microchannel is first fabricated by soft lithography using a convex PDMS mold. Then, the orthogonally microwrinkle patterns are generated inside the half-circular microchannel by a strain responsive wrinkling method. During the UV treatment on a PDMS substrate with uniaxial 40% stretch and a subsequent strain releasing step, the microwrinkle patterns perpendicular to the axial direction of the circular microchannel are generated, which can guide the circumferential alignment of HASMCs during cultivation. The analysis of orientation angle, shape index, and contractile protein marker expression indicates that the cultured HASMCs reveal the in vivo-like cell phenotype. Finally, a fully circular microchannel is produced by bonding two half-circular microchannels, and the HASMCs are cultured circumferentially inside the channels with high alignment and viability for 5 days. These results demonstrated the creation of an in vivo-like 3D smooth muscle cell layer in the circular microfluidic channel which can provide a bioassay platforms for in-depth study of HASMC biology and vascular function.

  16. Wirelessly powered micro-tracer enabled by miniaturized antenna and microfluidic channel

    NASA Astrophysics Data System (ADS)

    Duan, G.; Zhao, X.; Seren, H. R.; Chen, C.; Zhang, X.

    2015-12-01

    A miniaturized antenna, 380μm by 380μm in size, was fabricated and integrated with a commercialized passive RFID chip to form a micro-tracer, whose size was 2mm by 1mm in total. The micro-tracer was wirelessly powered and interrogated by a single layer spiral reader antenna through near field coupling. To maximize the working distance, the resonant frequency of micro-tracer and reader antenna were matched at 840MHz. Due to the ultra small size of the tracer antenna, power transfer efficiency decreased dramatically as the distance between tracer antenna and reader antenna increased, thus the working distance of the microtracer was limited within 1mm. To achieve massive operation of the micro-tracer, a microfluidic platform was fabricated with in channel focusing and separation. Acrylic sheets were laser cut to define the channel and cover structure, then bonded together layer by layer with a glass substrate, on which reader antenna was integrated. Pump oil was used as the fluidic media carrying the micro-tracer flowing inside the microfluidic channel. The wireless power transfer and real-time communication was demonstrated with the micro-tracer flowing above the reader antenna, as the ID of the micro-tracer was retrieved and displayed on a computer screen.

  17. Mode Transition of RNA Trap by Electric and Hydraulic Force Field in Microfluidic Taper Shape Channel

    NASA Astrophysics Data System (ADS)

    Takamura, Yuzuru; Ueno, Kunimitsu; Nagasaka, Wako; Tomizawa, Yuichi; Tamiya, Eiichi

    2007-03-01

    We have discovered a phenomenon of accumulation of DNA near the constricted position of a microfluidic chip with taper shaped channel when both hydro pressure and electric field are applied in opposite directions. However, RNA has not been able to trap so far, unlike huge and uniformly double stranded DNA molecules, RNAs are smaller in size and single stranded with complicated conformation like blocks in lysed cell solution. In this paper, we will report not only large but also small RNA (100˜10b) are successfully trapped in relatively large microfluidic taper shape channel (width >10um). RNA are trapped in circular motion near the constricted position of taper shape channel, and the position and shape of the trapped RNA are controlled and make mode transition by changing the hydraulic and the electric force. Using this technique, smaller size molecule can be trapped in larger micro fluidic structure compared to the trap using dielectrophoresis. This technique is expected to establish easy and practical device as a direct total RNA extraction tool from living cells or tissues.

  18. Toward a hybridization assay using fluorescence resonance energy transfer and quantum dots immobilized in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Tavares, Anthony J.; Petryayeva, Eleonora; Algar, W. Russ; Chen, Lu; Krull, Ulrich J.

    2010-06-01

    Quantum dots (QDs) have been widely adopted as integrated components of bioassays and biosensors. In particular, solid phase nucleic acid hybridization assays have been demonstrated to have several advantages and permit the detection of up to four DNA targets simultaneously using fluorescence resonance energy transfer (FRET). This work explores the potential for miniaturization of a solid-phase nucleic acid hybridization assay using QDs and FRET on a microfluidics platform. A method was developed for the immobilization of Streptavidin coated QDs and the preparation of QD-probe oligonucleotide conjugates within microfluidic channels using electrokinetic delivery. Proof-of-concept was demonstrated for the selective detection of target DNA using FRET-sensitized emission from a Cy3 acceptor paired with a green emitting QD donor. The microfluidic platform offered the advantages of smaller sample volumes, nearly undetectable non-specific adsorption, and hybridization within minutes. This work is an important first step toward the development of biochips that enable the multiplexed detection of nucleic acid targets.

  19. A microfluidic pipette array for mechanophenotyping of cancer cells and mechanical gating of mechanosensitive channels.

    PubMed

    Lee, Lap Man; Liu, Allen P

    2015-01-07

    Micropipette aspiration measures the mechanical properties of single cells. A traditional micropipette aspiration system requires a bulky infrastructure and has a low throughput and limited potential for automation. We have developed a simple microfluidic device which is able to trap and apply pressure to single cells in designated aspiration arrays. By changing the volume flow rate using a syringe pump, we can accurately exert a pressure difference across the trapped cells for pipette aspiration. By examining cell deformation and protrusion length into the pipette under an optical microscope, several important cell mechanical properties, such as the cortical tension and the Young's modulus, can be measured quantitatively using automated image analysis. Using the microfluidic pipette array, the stiffness of breast cancer cells and healthy breast epithelial cells was measured and compared. Finally, we applied our device to examine the gating threshold of the mechanosensitive channel MscL expressed in mammalian cells. Together, the development of a microfluidic pipette array could enable rapid mechanophenotyping of individual cells and for mechanotransduction studies.

  20. Biodegradable microsphere-mediated cell perforation in microfluidic channel using femtosecond laser

    NASA Astrophysics Data System (ADS)

    Ishii, Atsuhiro; Ariyasu, Kazumasa; Mitsuhashi, Tatsuki; Heinemann, Dag; Heisterkamp, Alexander; Terakawa, Mitsuhiro

    2016-05-01

    The use of small particles has expanded the capability of ultrashort pulsed laser optoinjection technology toward simultaneous treatment of multiple cells. The microfluidic platform is one of the attractive systems that has obtained synergy with laser-based technology for cell manipulation, including optoinjection. We have demonstrated the delivery of molecules into suspended-flowing cells in a microfluidic channel by using biodegradable polymer microspheres and a near-infrared femtosecond laser pulse. The use of polylactic-co-glycolic acid microspheres realized not only a higher optoinjection ratio compared to that with polylactic acid microspheres but also avoids optical damage to the microfluidic chip, which is attributable to its higher optical intensity enhancement at the localized spot under a microsphere. Interestingly, optoinjection ratios to nucleus showed a difference for adhered cells and suspended cells. The use of biodegradable polymer microspheres provides high throughput optoinjection; i.e., multiple cells can be treated in a short time, which is promising for various applications in cell analysis, drug delivery, and ex vivo gene transfection to bone marrow cells and stem cells without concerns about residual microspheres.

  1. Enhancing depth of focus in tilted microfluidics channels by digital holography.

    PubMed

    Matrecano, Marcella; Paturzo, Melania; Finizio, Andrea; Ferraro, Pietro

    2013-03-15

    In this Letter we propose a method to enhance the limited depth of field (DOF) in optical imaging systems, through digital holography. The proposed approach is based on the introduction of a cubic phase plate into the diffraction integral, analogous to what occurs in white-light imaging systems. By this approach we show that it is possible to improve the DOF and to recover the extended focus image of a tilted object in a single reconstruction step. Moreover, we demonstrate the possibility of obtaining well-focused biological cells flowing into a tilted microfluidic channel.

  2. Label-free biosensing using cascaded double-microring resonators integrated with microfluidic channels

    NASA Astrophysics Data System (ADS)

    Chen, Yangqing; Yu, Fang; Yang, Chang; Song, Jinyan; Tang, Longhua; Li, Mingyu; He, Jian-Jun

    2015-06-01

    Fast and accurate quantitative measurement of biologically relevant molecules has been demonstrated for medical diagnostics and drug applications in photonic integrated circuits. Herein, we reported a highly-sensitive optical biosensor based on cascaded double-microring resonators. The sensor was integrated with microfluidic channels and investigated with its label-free detection capability. With a wavelength resolution of 0.47 nm, the measured binding capacity of the antibody on the surface exhibits reliable detection limit down to 7.10 μg/mL using human immunoglobulin G (hIgG).

  3. A radio frequency device for measurement of minute dielectric property changes in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Song, Chunrong; Wang, Pingshan

    2009-01-01

    We demonstrate a sensitive radio frequency (rf) device to detect small dielectric property changes in microfluidic channel. The device consists of an on-chip Wilkinson power divider and a rat-race hybrid, which are built with planar microstrip lines and thin film chip resistors. Interference is used to cancel parasitic background signals. As a result, the measurement sensitivity is improved by more than 20 dB compared with conventional transmission lines. Compared with an ultrasensitive slot antenna/cuvette assembly [K. M. Taylor and D. W. van der Weide, IEEE Trans. Microwave Theory Tech. 53, 1576 (2005)], the proposed rf device is two times more sensitive.

  4. Influence of outlet channel width to the flow velocity and pressure of a flow focusing microfluidic device

    NASA Astrophysics Data System (ADS)

    Fhong Soon, Chin; Hiung Yin, Yap; Sek Tee, Kian; Khairul Ahmad, Mohd; Zainizan Sahdan, Mohd; Nayan, Nafarizal

    2016-11-01

    Microencapsulation using flow focusing microfluidic devices attract great interest because of the simple fabrication technique using polymeric material. Simulation of the microfluidic device provides the advantage of reducing the waste of material before actual implementation of the fabrication. This paper reports the design of a flow focusing microfluidic device based on emulsification of two immiscible fluids. The system was build and simulated in COMSOL Multiphysics software by varying the outlet width in examining the effects of the flow and pressure at the outlet. The simulation results reveal that both the flow rate and the pressure decreased dramatically when the ratio of outlet channel to inlet channel (R) is greater than 2. The width of the outlet is critical in ensuring the flow of microcapsules without accumulation of microcapsules at the output pool due to the poor flow rate at the outlet channel and avoidance of leakage problem. The recommended R to achieve the objective of microencapsulation is between 2 and 4.

  5. Effect of a dual inlet channel on cell loading in microfluidics

    PubMed Central

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

    2014-01-01

    Unwanted sedimentation and attachment of a number of cells onto the bottom channel often occur on relatively large-scale inlets of conventional microfluidic channels as a result of gravity and fluid shear. Phenomena such as sedimentation have become recognized problems that can be overcome by performing microfluidic experiments properly, such as by calculating a meaningful output efficiency with respect to real input. Here, we present a dual-inlet design method for reducing cell loss at the inlet of channels by adding a new “ upstream inlet ” to a single main inlet design. The simple addition of an upstream inlet can create a vertically layered sheath flow prior to the main inlet for cell loading. The bottom layer flow plays a critical role in preventing the cells from attaching to the bottom of the channel entrance, resulting in a low possibility of cell sedimentation at the main channel entrance. To provide proof-of-concept validation, we applied our design to a microfabricated flow cytometer system (μFCS) and compared the cell counting efficiency of the proposed μFCS with that of the previous single-inlet μFCS and conventional FCS. We used human white blood cells and fluorescent microspheres to quantitatively evaluate the rate of cell sedimentation in the main inlet and to measure fluorescence sensitivity at the detection zone of the flow cytometer microchip. Generating a sheath flow as the bottom layer was meaningfully used to reduce the depth of field as well as the relative deviation of targets in the z-direction (compared to the x-y flow plane), leading to an increased counting sensitivity of fluorescent detection signals. Counting results using fluorescent microspheres showed both a 40% reduction in the rate of sedimentation and a 2-fold higher sensitivity in comparison with the single-inlet μFCS. The results of CD4+ T-cell counting also showed that the proposed design results in a 25% decrease in the rate of cell sedimentation and a 28% increase in

  6. Plasticity of primary microglia on micropatterned geometries and spontaneous long-distance migration in microfluidic channels

    PubMed Central

    2013-01-01

    Background Microglia possess an elevated grade of plasticity, undergoing several structural changes based on their location and state of activation. The first step towards the comprehension of microglia’s biology and functional responses to an extremely mutable extracellular milieu, consists in discriminating the morphological features acquired by cells maintained in vitro under diverse environmental conditions. Previous work described neither primary microglia grown on artificially patterned environments which impose physical cues and constraints, nor long distance migration of microglia in vitro. To this aim, the present work exploits artificial bio-mimetic microstructured substrates with pillar-shaped or line-grating geometries fabricated on poly(dimethylsiloxane) by soft lithography, in addition to microfluidic devices, and highlights some morphological/functional characteristics of microglia which were underestimated or unknown so far. Results We report that primary microglia selectively adapt to diverse microstructured substrates modifying accordingly their morphological features and behavior. On micropatterned pillar-shaped geometries, microglia appear multipolar, extend several protrusions in all directions and form distinct pseudopodia. On both micropatterned line-grating geometries and microfluidic channels, microglia extend the cytoplasm from a roundish to a stretched, flattened morphology and assume a filopodia-bearing bipolar structure. Finally, we show that in the absence of any applied chemical gradient, primary microglia spontaneously moves through microfluidic channels for a distance of up to 500 μm in approximately 12 hours, with an average speed of 0.66 μm/min. Conclusions We demonstrate an elevated grade of microglia plasticity in response to a mutable extracellular environment, thus making these cells an appealing population to be further exploited for lab on chip technologies. The development of microglia-based microstructured

  7. Mass Transport Effects in Suspended Waveguide Biosensors Integrated in Microfluidic Channels

    PubMed Central

    Murthy, Chaitanya R.; Armani, Andrea M.

    2012-01-01

    Label-free optical biosensors based on integrated photonic devices have demonstrated sensitive and selective detection of biological analytes. Integrating these sensor platforms into microfluidic devices reduces the required sample volume and enables rapid delivery of sample to the sensor surface, thereby improving response times. Conventionally, these devices are embedded in or adjacent to the substrate; therefore, the effective sensing area lies within the slow-flow region at the floor of the channel, reducing the efficiency of sample delivery. Recently, a suspended waveguide sensor was developed in which the device is elevated off of the substrate and the sensing region does not rest on the substrate. This geometry places the sensing region in the middle of the parabolic velocity profile, reduces the distance that a particle must travel by diffusion to be detected, and allows binding to both surfaces of the sensor. We use a finite element model to simulate advection, diffusion, and specific binding of interleukin 6, a signaling protein, to this waveguide-based biosensor at a range of elevations within a microfluidic channel. We compare the transient performance of these suspended waveguide sensors with that of traditional planar devices, studying both the detection threshold response time and the time to reach equilibrium. We also develop a theoretical framework for predicting the behavior of these suspended sensors. These simulation and theoretical results provide a roadmap for improving sensor performance and minimizing the amount of sample required to make measurements. PMID:23202163

  8. Multi-channeled single chain variable fragment (scFv) based microfluidic device for explosives detection.

    PubMed

    Charles, Paul T; Davis, Jasmine; Adams, André A; Anderson, George P; Liu, Jinny L; Deschamps, Jeffrey R; Kusterbeck, Anne W

    2015-11-01

    The development of explosives detection technologies has increased significantly over the years as environmental and national security agencies implement tighter pollution control measures and methods for improving homeland security. 2, 4, 6-Trinitrotoluene (TNT), known primarily as a component in munitions, has been targeted for both its toxicity and carcinogenic properties that if present at high concentrations can be a detriment to both humans, marine and plant ecosystems. Enabling end users with environmental detection and monitoring systems capable of providing real-time, qualitative and quantitative chemical analysis of these toxic compounds would be extremely beneficial. Reported herein is the development of a multi-channeled microfluidic device immobilized with single chain fragment variable (scFv) recombinant proteins specific for the explosive, TNT. Fluorescence displacement immunoassays performed under constant flow demonstrated trace level sensitivity and specificity for TNT. The utility of three multi-channeled devices immobilized with either (1) scFv recombinant protein, (2) biotinylated-scFv (bt-scFv) and (3) monoclonal anti-TNT (whole IgG molecule) were investigated and compared. Fluorescence dose response curves, crossreactivity measurements and limits of detection (LOD) for TNT were determined. Fluorescence displacement immunoassays for TNT in natural seawater demonstrated detection limits at sub-parts-per-billion levels (0.5 ppb) utilizing the microfluidic device with immobilized bt-scFv. Published by Elsevier B.V.

  9. Crystallization of the Large Membrane Protein Complex Photosystem I in a Microfluidic Channel

    PubMed Central

    Abdallah, Bahige G.; Kupitz, Christopher; Fromme, Petra; Ros, Alexandra

    2014-01-01

    Traditional macroscale protein crystallization is accomplished non-trivially by exploring a range of protein concentrations and buffers in solution until a suitable combination is attained. This methodology is time consuming and resource intensive, hindering protein structure determination. Even more difficulties arise when crystallizing large membrane protein complexes such as photosystem I (PSI) due to their large unit cells dominated by solvent and complex characteristics that call for even stricter buffer requirements. Structure determination techniques tailored for these ‘difficult to crystallize’ proteins such as femtosecond nanocrystallography are being developed, yet still need specific crystal characteristics. Here, we demonstrate a simple and robust method to screen protein crystallization conditions at low ionic strength in a microfluidic device. This is realized in one microfluidic experiment using low sample amounts, unlike traditional methods where each solution condition is set up separately. Second harmonic generation microscopy via Second Order Nonlinear Imaging of Chiral Crystals (SONICC) was applied for the detection of nanometer and micrometer sized PSI crystals within microchannels. To develop a crystallization phase diagram, crystals imaged with SONICC at specific channel locations were correlated to protein and salt concentrations determined by numerical simulations of the time-dependent diffusion process along the channel. Our method demonstrated that a portion of the PSI crystallization phase diagram could be reconstructed in excellent agreement with crystallization conditions determined by traditional methods. We postulate that this approach could be utilized to efficiently study and optimize crystallization conditions for a wide range of proteins that are poorly understood to date. PMID:24191698

  10. Fabrication and validation of a multi-channel type microfluidic chip for electrokinetic streaming potential devices.

    PubMed

    Chun, Myung-Suk; Shim, Min Suk; Choi, Nak Won

    2006-02-01

    To elaborate on the applicability of the electrokinetic micro power generation, we designed and fabricated the silicon-glass as well as the PDMS-glass microfluidic chips with the unique features of a multi-channel. Besides miniaturizing the device, the key advantage of our microfluidic chip utilization lies in the reduction in water flow rate. Both a distributor and a collector taking the tapered duct geometry are positioned aiming the uniform distribution of water flow into all individual channels of the chip, in which several hundreds of single microchannels are assembled in parallel. A proper methodology is developed accompanying the deep reactive ion etching as well as the anodic bonding, and optimum process conditions necessary for hard and soft micromachining are presented. It has been shown experimentally and theoretically that the silicon-based microchannel leads to increasing streaming potential and higher external current compared to those of the PDMS-based one. A proper comparison between experimental results and theoretical computations allows justification of the validity of our novel devices. It is useful to recognize that a material inducing a higher magnitude of zeta potential has an advantage for obtaining higher power density under the same external resistance.

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

    NASA Astrophysics Data System (ADS)

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

    2017-06-01

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

  12. A microfluidic mixer with grooves placed on the top and bottom of the channel.

    PubMed

    Howell, Peter B; Mott, David R; Fertig, Stephanie; Kaplan, Carolyn R; Golden, Joel P; Oran, Elaine S; Ligler, Frances S

    2005-05-01

    A new microfluidic mixer is presented consisting of a rectangular channel with grooves placed in the top and bottom. This not only increases the driving force behind the lateral flow, but allows for the formation of advection patterns that cannot be created with structures on the bottom alone. Chevrons, pointing in opposite directions on the top and bottom, are used to create a pair of vortices positioned side by side. Stripes running the width of the channel generate a pair of vertically stacked vortices. Computational fluid dynamics (CFD) simulations are used to model the behavior of the systems and provide velocity maps at cross-sections within the mixer. Experiments demonstrate the mixing that results when two segregated species enter the mixer side-by-side and pass through two cycles of the mixer (i.e., two alternating sets of four stripes and four chevrons).

  13. Fabrication of self-sealed circular nano/microfluidic channels in glass substrates.

    PubMed

    Wong, Chee Chung; Agarwal, Ajay; Balasubramanian, N; Kwong, Dim Lee

    2007-04-04

    We realized self-sealing fluidics channels with circular cross-sections having diameters ranging between 30 and 2000 nm on a 200 mm glass wafer through CMOS compatible processes. Lateral voids were narrowed and sealed with non-conformal plasma enhanced chemical vapour deposition (PECVD) of phospho silicate glass (PSG) along silicon oxide trenches on silicon wafers. Leveraging on the reflow properties of PSG, circular profiled-channels were formed after undergoing high temperature annealing. These devices were subsequently transferred onto a borosilicate glass substrate through anodic bonding, and a fully transparent microfluidic device was achieved with the complete removal of the handle silicon substrate. The process offers a means of integrating electrochemical and optical sensing on the same platform, for biological research.

  14. DNA probe attachment on plastic surfaces and microfluidic hybridization array channel devices with sample oscillation.

    PubMed

    Liu, Yingjie; Rauch, Cory B

    2003-06-01

    DNA probe immobilization on plastic surfaces and device assembly are both critical to the fabrication of microfluidic hybridization array channel (MHAC) devices. Three oligonucleotide (oligo) probe immobilization procedures were investigated for attaching oligo probes on four different types of plastic surfaces (polystyrene, polycarbonate, poly(methylmethacrylate), and polypropylene). These procedures are the Surmodics procedure, the cetyltrimethylammonium bromide (CTAB) procedure, and the Reacti-Bind procedure. To determine the optimal plastic substrate and attachment chemistry for array fabrication, we investigated plastic hydrophobicity, intrinsic fluorescence, and oligo attachment efficiency. The Reacti-Bind procedure is least effective for attaching oligo probes in the microarray format. The CTAB procedure performs well enough to use in array fabrication, and the concentration of CTAB has a significant effect on oligo immobilization efficiency. We also found that use of amine-modified oligo probes resulted in better immobilization efficiency than use of unmodified oligos with the CTAB procedure. The oligo probe immobilization on plastic surfaces by the Surmodics procedure is the most effective with regard to probe spot quality and hybridization sensitivity. A DNA hybridization assay on such a device results in a limit of detection of 12pM. Utilizing a CO(2) IR laser machining and adhesive layer approach, we have developed an improved procedure for realizing a DNA microarray inside a microfluidic channel. This device fabrication procedure allows for more feasible spot placement in the channel and reduced sample adsorption by adhesive tapes used in the fabrication procedure. We also demonstrated improved hybridization kinetics and increased detection sensitivity in MHAC devices by implementing sample oscillation inside the channel. A limit of detection of 5pM has been achieved in MHAC devices with sample oscillation.

  15. Droplet-based lipid bilayer system integrated with microfluidic channels for solution exchange.

    PubMed

    Tsuji, Yutaro; Kawano, Ryuji; Osaki, Toshihisa; Kamiya, Koki; Miki, Norihisa; Takeuchi, Shoji

    2013-04-21

    This paper proposes a solution exchange of a droplet-based lipid bilayer system, in which the inner solution of a droplet is replaced for the purpose of efficient ion channel analyses. In our previous report, we successfully recorded the channel conductance of alpha-hemolysin in a bilayer lipid membrane using a droplet contact method that can create a spontaneous lipid bilayer at the interface of contacting droplets; this method is widely used as highly efficient method for preparing planar lipid membranes. When only pipetting droplets of the solution, this method is highly efficient for preparing lipid membranes. However, the drawback of droplet-based systems is their inability to exchange the solution within the droplets. To study the effect of inhibitors and promoters of ion channels in drug discovery, it would be beneficial to conduct a solution exchange of droplets to introduce membrane proteins and to apply or wash-out the chemicals. In this study, we propose a droplet contact method that allows for the solution exchange of droplets via microfluidic channels. We experimentally and numerically investigated the bilayer stability with respect to exchanging flow rates, and then demonstrated a binding assay of an alpha-hemolysin using one of its blockers. The solution exchange in this system was conducted in less than 20 s without rupturing the membrane. We believe that the proposed system will enhance the efficiency of ion channel analyses.

  16. Low-Reynolds-number droplet motion in a square microfluidic channel

    NASA Astrophysics Data System (ADS)

    Wang, Yechun; Dimitrakopoulos, Panagiotis

    2012-01-01

    In this study, we investigate computationally the low-Reynolds-number droplet motion in a square micro-channel, a problem frequently encountered in microfluidic devices, enhanced oil recovery and coating processes. The droplet deformation and motion are determined via a three-dimensional spectral boundary element method for wall-bounded flows. The effects of the flow rate, viscosity ratio and droplet size on the interfacial dynamics are identified for droplets smaller and larger than the channel size and for a wide range of viscosity ratio. Owing to the stronger hydrodynamic forces in the thin lubrication film between the droplet interface and the solid walls, large droplets exhibit larger deformation and smaller velocity. Under the same average velocity, a droplet in a channel shows a significantly smaller deformation and higher velocity than in a cylindrical tube with the same size, owing to the existence of the corners' area in the channel which permits flow of the surrounding fluid. A suitable periodic boundary implementation for our spectral element method is developed to study the dynamics of an array of identical droplets moving in the channel. In this case, the droplet deformation and velocity are reduced as their separation decreases; the reduction is influenced by the flow rate, viscosity ratio and more significantly the droplet size.

  17. Screening reactive metabolites bioactivated by multiple enzyme pathways using a multiplexed microfluidic system.

    PubMed

    Wasalathanthri, Dhanuka P; Faria, Ronaldo C; Malla, Spundana; Joshi, Amit A; Schenkman, John B; Rusling, James F

    2013-01-07

    A multiplexed, microfluidic platform to detect reactive metabolites is described, and its performance is illustrated for compounds metabolized by oxidative and bioconjugation enzymes in multi-enzyme pathways to mimic natural human drug metabolism. The device features four 8-electrode screen printed carbon arrays coated with thin films of DNA, a ruthenium-polyvinylpyridine (RuPVP) catalyst, and multiple enzyme sources including human liver microsomes (HLM), cytochrome P450 (cyt P450) 1B1 supersomes, microsomal epoxide hydrolase (EH), human S9 liver fractions (Hs9) and N-acetyltransferase (NAT). Arrays are arranged in parallel to facilitate multiple compound screening, enabling up to 32 enzyme reactions and measurements in 20-30 min. In the first step of the assay, metabolic reactions are achieved under constant flow of oxygenated reactant solutions by electrode driven natural catalytic cycles of cyt P450s and cofactor-supported bioconjugation enzymes. Reactive metabolites formed in the enzyme reactions can react with DNA. Relative DNA damage is measured in the second assay step using square wave voltammetry (SWV) with RuPVP as catalyst. Studies were done on chemicals known to require metabolic activation to induce genotoxicity, and results reproduced known features of metabolite DNA-reactivity for the test compounds. Metabolism of benzo[a]pyrene (B[a]P) by cyt P450s and epoxide hydrolase showed an enhanced relative DNA damage rate for DNA compared to cyt P450s alone. DNA damage rates for arylamines by pathways featuring both oxidative and conjugative enzymes at pH 7.4 gave better correlation with rodent genotoxicity metric TD(50). Results illustrate the broad utility of the reactive metabolite screening device.

  18. A Microfluidic Channel Method for Rapid Drug-Susceptibility Testing of Pseudomonas aeruginosa.

    PubMed

    Matsumoto, Yoshimi; Sakakihara, Shouichi; Grushnikov, Andrey; Kikuchi, Kazuma; Noji, Hiroyuki; Yamaguchi, Akihito; Iino, Ryota; Yagi, Yasushi; Nishino, Kunihiko

    2016-01-01

    The recent global increase in the prevalence of antibiotic-resistant bacteria and lack of development of new therapeutic agents emphasize the importance of selecting appropriate antimicrobials for the treatment of infections. However, to date, the development of completely accelerated drug susceptibility testing methods has not been achieved despite the availability of a rapid identification method. We proposed an innovative rapid method for drug susceptibility testing for Pseudomonas aeruginosa that provides results within 3 h. The drug susceptibility testing microfluidic (DSTM) device was prepared using soft lithography. It consisted of five sets of four microfluidic channels sharing one inlet slot, and the four channels are gathered in a small area, permitting simultaneous microscopic observation. Antimicrobials were pre-introduced into each channel and dried before use. Bacterial suspensions in cation-adjusted Mueller-Hinton broth were introduced from the inlet slot and incubated for 3 h. Susceptibilities were microscopically evaluated on the basis of differences in cell numbers and shapes between drug-treated and control cells, using dedicated software. The results of 101 clinically isolated strains of P. aeruginosa obtained using the DSTM method strongly correlated with results obtained using the ordinary microbroth dilution method. Ciprofloxacin, meropenem, ceftazidime, and piperacillin caused elongation in susceptible cells, while meropenem also induced spheroplast and bulge formation. Morphological observation could alternatively be used to determine the susceptibility of P. aeruginosa to these drugs, although amikacin had little effect on cell shape. The rapid determination of bacterial drug susceptibility using the DSTM method could also be applicable to other pathogenic species, and it could easily be introduced into clinical laboratories without the need for expensive instrumentation.

  19. Modeling RedOx-based magnetohydrodynamics in three-dimensional microfluidic channels

    NASA Astrophysics Data System (ADS)

    Kabbani, Hussameddine; Wang, Aihua; Luo, Xiaobing; Qian, Shizhi

    2007-08-01

    RedOx-based magnetohydrodynamic (MHD) flows in three-dimensional microfluidic channels are investigated theoretically with a coupled mathematical model consisting of the Nernst-Planck equations for the concentrations of ionic species, the local electroneutrality condition for the electric potential, and the Navier-Stokes equations for the flow field. A potential difference is externally applied across two planar electrodes positioned along the opposing walls of a microchannel that is filled with a dilute RedOx electrolyte solution, and a Faradaic current transmitted through the solution results. The entire device is positioned under a magnetic field which can be provided by either a permanent magnet or an electromagnet. The interaction between the current density and the magnetic field induces Lorentz forces, which can be used to pump and/or stir fluids for microfluidic applications. The induced currents and flow rates in three-dimensional (3D) planar channels obtained from the full 3D model are compared with the experimental data obtained from the literature and those obtained from our previous two-dimensional mathematical model. A closed form approximation for the average velocity (flow rate) in 3D planar microchannels is derived and validated by comparing its predictions with the results obtained from the full 3D model and the experimental data obtained from the literature. The closed form approximation can be used to optimize the dimensions of the channel and to determine the magnitudes and polarities of the prescribed currents in MHD networks so as to achieve the desired flow patterns and flow rates.

  20. Microfluidic channel-based wireless charging and communication platform for microsensors with miniaturized onboard antenna

    NASA Astrophysics Data System (ADS)

    Duan, G.; Zhao, X.; Seren, H. R.; Chen, C.; Li, A.; Zhang, X.

    2016-12-01

    A double layer spiral antenna with side length of 380 μm was fabricated by a multi-step electroplating process, and integrated with a commercialized passive RFID chip to realize the RF power harvesting and communication functions of a microsensor. To power up and communicate with the microchips, a single layer spiral reader antenna was fabricated on top of a glass substrate with side length of 1 mm. The microchips and the reader antenna were both optimized at the frequency of 915 MHz. Due to the small size of the reader antenna, the strength of the magnetic field decreased dramatically along the axial direction of the reader antenna, which limited the working distance to within 1 mm. To enclose the microchips within the reading range, a three-layer microfluidic channel was designed and fabricated. The channel and cover layers were fabricated by laser cutting of acrylic sheets, and bonded with the glass substrate to form the channel. To operate multiple microchips simultaneously, separation and focusing function units were also designed. Low loss pump oil was used to transport the microchips flowing inside the channel. Within the reading area, the microchips were powered up, and their ID information was retrieved and displayed on the computer interface successfully.

  1. Pulsatile Poiseuille flows in microfluidic channels with back-and-forth mode

    NASA Astrophysics Data System (ADS)

    Kim, Kwang Seok; Chun, Myung-Suk

    2012-06-01

    The numerical solver for the velocity field equation describing laminar pulsatile flows driven by a time-dependent pressure drop in the straight microfluidic channel of square cross-section is developed. In the computational algorithm, an orthogonal collocation on finite element scheme for spatial discretizations is combined with an adaptive Runge-Kutta method for time integration. The algorithm with the 1,521 computational nodes and the accuracy up to O(10-5) is applied to the flow in the back-and-forth standing mode with the channel hydraulic diameter ( D h ) in the range 10-500 μm and the oscillating frequency ( f) of 1 to 100 Hz. As a result, a periodic steady state is defined as the flow condition where there would be no net movement after long time elapses. Following by the retardation phenomena in a cycle, reversal of the axial velocity is observed at the channel center. Major attention is focused on the influences of the size of channel cross-section and the oscillating frequency. Increasing D h and f results in the decrease in the amplitude of mean velocity but the increase in the start-up time. Larger time delay occurs by low-frequency pulsation.

  2. Variation of velocity profile according to blood viscosity in a microfluidic channel

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    The shear-thinning effect of blood flows is known to change blood viscosity. Since blood viscosity and motion of red blood cells (RBCs) are closely related, hemorheological variations have a strong influence on hemodynamic characteristics. Therefore, understanding on the relationship between the hemorheological and hemodynamic properties is importance for getting more detailed information on blood circulation in microvessels. In this study, the blood viscosity and velocity profiles in a microfluidic channel were systematically investigated. Rat blood was delivered in the microfluidic device which can measure blood viscosity by monitoring the flow-switching phenomenon. Velocity profiles of blood flows in the microchannel were measured by using a micro-particle image velocimetry (PIV) technique. Shape of velocity profiles measured at different flow rates was quantified by using a curve-fitting equation. It was observed that the shape of velocity profiles is highly correlated with blood viscosity. The study on the relation between blood viscosity and velocity profile would be helpful to understand the roles of hemorheological and hemodynamic properties in cardiovascular diseases. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (No. 2008-0061991).

  3. Combining optical trapping in a microfluidic channel with simultaneous micro-Raman spectroscopy and motion detection

    NASA Astrophysics Data System (ADS)

    Lawton, Penelope F.; Saunter, Christopher D.; Girkin, John M.

    2014-03-01

    Since their invention by Ashkin optical tweezers have demonstrated their ability and versatility as a non-invasive tool for micromanipulation. One of the most useful additions to the basic optical tweezers system is micro-Raman spectroscopy, which permits highly sensitive analysis of single cells or particles. We report on the development of a dual laser system combining two spatial light modulators to holographically manipulate multiple traps (at 1064nm) whilst undertaking Raman spectroscopy using a 532nm laser. We can thus simultaneously trap multiple particles and record their Raman spectra, without perturbing the trapping system. The dual beam system is built around micro-fluidic channels where crystallisation of calcium carbonate occurs on polymethylmethacrylate (PMMA) beads. The setup is designed to simulate at a microscopic level the reactions that occur on items in a dishwasher, where permanent filming of calcium carbonate on drinking glasses is a problem. Our system allows us to monitor crystal growth on trapped particles in which the Raman spectrum and changes in movement of the bead are recorded. Due to the expected low level of crystallisation on the bead surfaces this allows us to obtain results quickly and with high sensitivity. The long term goal is to study the development of filming on samples in-situ with the microfl.uidic system acting as a model dishwasher.

  4. Laser direct writing 3D structures for microfluidic channels: flow meter and mixer

    NASA Astrophysics Data System (ADS)

    Lin, Chih-Lang; Liu, Yi-Jui; Lin, Zheng-Da; Wu, Bo-Long; Lee, Yi-Hsiung; Shin, Chow-Shing; Baldeck, Patrice L.

    2015-03-01

    The 3D laser direct-writing technology is aimed at the modeling of arbitrary three-dimensional (3D) complex microstructures by scanning a laser-focusing point along predetermined trajectories. Through the perspective technique, the details of designed 3D structures can be properly fabricated in a microchannel. This study introduces a direct reading flow meter and a 3D passive mixer fabricated by laser direct writing for microfluidic applications. The flow meter consists of two rod-shaped springs, a pillar, an anchor, and a wedge-shaped indicator, installed inside a microfluidic channel. The indicator is deflected by the flowing fluid while restrained by the spring to establish an equilibrium indication according to the flow rate. The measurement is readily carried out by optical microscopy observation. The 3D passive Archimedes-screw-shaped mixer is designed to disturb the laminar flow 3D direction for enhancing the mixing efficiency. The simulation results indicate that the screw provides 3D disturbance of streamlines in the microchannel. The mixing demonstration for fluids flowing in the micrchannel approximately agrees with the simulation result. Thanks to the advantage of the laser direct writing technology, this study performs the ingenious applications of 3D structures for microchannels.

  5. Label-free viscosity measurement of complex fluids using reversal flow switching manipulation in a microfluidic channel

    PubMed Central

    Jun Kang, Yang; Ryu, Jeongeun; Lee, Sang-Joon

    2013-01-01

    The accurate viscosity measurement of complex fluids is essential for characterizing fluidic behaviors in blood vessels and in microfluidic channels of lab-on-a-chip devices. A microfluidic platform that accurately identifies biophysical properties of blood can be used as a promising tool for the early detections of cardiovascular and microcirculation diseases. In this study, a flow-switching phenomenon depending on hydrodynamic balancing in a microfluidic channel was adopted to conduct viscosity measurement of complex fluids with label-free operation. A microfluidic device for demonstrating this proposed method was designed to have two inlets for supplying the test and reference fluids, two side channels in parallel, and a junction channel connected to the midpoint of the two side channels. According to this proposed method, viscosities of various fluids with different phases (aqueous, oil, and blood) in relation to that of reference fluid were accurately determined by measuring the switching flow-rate ratio between the test and reference fluids, when a reverse flow of the test or reference fluid occurs in the junction channel. An analytical viscosity formula was derived to measure the viscosity of a test fluid in relation to that of the corresponding reference fluid using a discrete circuit model for the microfluidic device. The experimental analysis for evaluating the effects of various parameters on the performance of the proposed method revealed that the fluidic resistance ratio (RJL/RL, fluidic resistance in the junction channel (RJL) to fluidic resistance in the side channel (RL)) strongly affects the measurement accuracy. The microfluidic device with smaller RJL/RL values is helpful to measure accurately the viscosity of the test fluid. The proposed method accurately measured the viscosities of various fluids, including single-phase (Glycerin and plasma) and oil-water phase (oil vs. deionized water) fluids, compared with conventional methods. The proposed

  6. Label-free viscosity measurement of complex fluids using reversal flow switching manipulation in a microfluidic channel.

    PubMed

    Jun Kang, Yang; Ryu, Jeongeun; Lee, Sang-Joon

    2013-01-01

    The accurate viscosity measurement of complex fluids is essential for characterizing fluidic behaviors in blood vessels and in microfluidic channels of lab-on-a-chip devices. A microfluidic platform that accurately identifies biophysical properties of blood can be used as a promising tool for the early detections of cardiovascular and microcirculation diseases. In this study, a flow-switching phenomenon depending on hydrodynamic balancing in a microfluidic channel was adopted to conduct viscosity measurement of complex fluids with label-free operation. A microfluidic device for demonstrating this proposed method was designed to have two inlets for supplying the test and reference fluids, two side channels in parallel, and a junction channel connected to the midpoint of the two side channels. According to this proposed method, viscosities of various fluids with different phases (aqueous, oil, and blood) in relation to that of reference fluid were accurately determined by measuring the switching flow-rate ratio between the test and reference fluids, when a reverse flow of the test or reference fluid occurs in the junction channel. An analytical viscosity formula was derived to measure the viscosity of a test fluid in relation to that of the corresponding reference fluid using a discrete circuit model for the microfluidic device. The experimental analysis for evaluating the effects of various parameters on the performance of the proposed method revealed that the fluidic resistance ratio ( R J L / R L , fluidic resistance in the junction channel ( R J L ) to fluidic resistance in the side channel ( R L )) strongly affects the measurement accuracy. The microfluidic device with smaller R J L / R L values is helpful to measure accurately the viscosity of the test fluid. The proposed method accurately measured the viscosities of various fluids, including single-phase (Glycerin and plasma) and oil-water phase (oil vs. deionized water) fluids, compared with conventional

  7. Long-range forces affecting equilibrium inertial focusing behavior in straight high aspect ratio microfluidic channels.

    PubMed

    Reece, Amy E; Oakey, John

    2016-04-01

    The controlled and directed focusing of particles within flowing fluids is a problem of fundamental and technological significance. Microfluidic inertial focusing provides passive and precise lateral and longitudinal alignment of small particles without the need for external actuation or sheath fluid. The benefits of inertial focusing have quickly enabled the development of miniaturized flow cytometers, size-selective sorting devices, and other high-throughput particle screening tools. Straight channel inertial focusing device design requires knowledge of fluid properties and particle-channel size ratio. Equilibrium behavior of inertially focused particles has been extensively characterized and the constitutive phenomena described by scaling relationships for straight channels of square and rectangular cross section. In concentrated particle suspensions, however, long-range hydrodynamic repulsions give rise to complex particle ordering that, while interesting and potentially useful, can also dramatically diminish the technique's effectiveness for high-throughput particle handling applications. We have empirically investigated particle focusing behavior within channels of increasing aspect ratio and have identified three scaling regimes that produce varying degrees of geometrical ordering between focused particles. To explore the limits of inertial particle focusing and identify the origins of these long-range interparticle forces, we have explored equilibrium focusing behavior as a function of channel geometry and particle concentration. Experimental results for highly concentrated particle solutions identify equilibrium thresholds for focusing that scale weakly with concentration and strongly with channel geometry. Balancing geometry mediated inertial forces with estimates for interparticle repulsive forces now provide a complete picture of pattern formation among concentrated inertially focused particles and enhance our understanding of the fundamental limits of

  8. Long-range forces affecting equilibrium inertial focusing behavior in straight high aspect ratio microfluidic channels

    NASA Astrophysics Data System (ADS)

    Reece, Amy E.; Oakey, John

    2016-04-01

    The controlled and directed focusing of particles within flowing fluids is a problem of fundamental and technological significance. Microfluidic inertial focusing provides passive and precise lateral and longitudinal alignment of small particles without the need for external actuation or sheath fluid. The benefits of inertial focusing have quickly enabled the development of miniaturized flow cytometers, size-selective sorting devices, and other high-throughput particle screening tools. Straight channel inertial focusing device design requires knowledge of fluid properties and particle-channel size ratio. Equilibrium behavior of inertially focused particles has been extensively characterized and the constitutive phenomena described by scaling relationships for straight channels of square and rectangular cross section. In concentrated particle suspensions, however, long-range hydrodynamic repulsions give rise to complex particle ordering that, while interesting and potentially useful, can also dramatically diminish the technique's effectiveness for high-throughput particle handling applications. We have empirically investigated particle focusing behavior within channels of increasing aspect ratio and have identified three scaling regimes that produce varying degrees of geometrical ordering between focused particles. To explore the limits of inertial particle focusing and identify the origins of these long-range interparticle forces, we have explored equilibrium focusing behavior as a function of channel geometry and particle concentration. Experimental results for highly concentrated particle solutions identify equilibrium thresholds for focusing that scale weakly with concentration and strongly with channel geometry. Balancing geometry mediated inertial forces with estimates for interparticle repulsive forces now provide a complete picture of pattern formation among concentrated inertially focused particles and enhance our understanding of the fundamental limits of

  9. Long-range forces affecting equilibrium inertial focusing behavior in straight high aspect ratio microfluidic channels

    SciTech Connect

    Reece, Amy E.; Oakey, John

    2016-04-15

    The controlled and directed focusing of particles within flowing fluids is a problem of fundamental and technological significance. Microfluidic inertial focusing provides passive and precise lateral and longitudinal alignment of small particles without the need for external actuation or sheath fluid. The benefits of inertial focusing have quickly enabled the development of miniaturized flow cytometers, size-selective sorting devices, and other high-throughput particle screening tools. Straight channel inertial focusing device design requires knowledge of fluid properties and particle-channel size ratio. Equilibrium behavior of inertially focused particles has been extensively characterized and the constitutive phenomena described by scaling relationships for straight channels of square and rectangular cross section. In concentrated particle suspensions, however, long-range hydrodynamic repulsions give rise to complex particle ordering that, while interesting and potentially useful, can also dramatically diminish the technique’s effectiveness for high-throughput particle handling applications. We have empirically investigated particle focusing behavior within channels of increasing aspect ratio and have identified three scaling regimes that produce varying degrees of geometrical ordering between focused particles. To explore the limits of inertial particle focusing and identify the origins of these long-range interparticle forces, we have explored equilibrium focusing behavior as a function of channel geometry and particle concentration. Experimental results for highly concentrated particle solutions identify equilibrium thresholds for focusing that scale weakly with concentration and strongly with channel geometry. Balancing geometry mediated inertial forces with estimates for interparticle repulsive forces now provide a complete picture of pattern formation among concentrated inertially focused particles and enhance our understanding of the fundamental limits

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

    SciTech Connect

    Van Dam, Robert Michael

    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

  11. Effect of surface waves on the secondary Bjerknes force experienced by bubbles in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Doinikov, Alexander A.; Combriat, Thomas; Thibault, Pierre; Marmottant, Philippe

    2016-08-01

    An analytical expression is derived for the secondary Bjerknes force experienced by two cylindrical bubbles in a microfluidic channel with planar elastic walls. The derived expression takes into account that the bubbles generate two types of scattered acoustic waves: bulk waves that propagate in the fluid gap with the speed of sound and Lamb-type surface waves that propagate at the fluid-wall interfaces with a much lower speed than that of the bulk waves. It is shown that the surface waves cause the bubbles to form a bound pair in which the equilibrium interbubble distance is determined by the wavelength of the surface waves, which is much smaller than the acoustic wavelength. Comparison of theoretical and experimental results demonstrates good agreement.

  12. Simultaneous bioassays in a microfluidic channel on plugs of different magnetic particles.

    PubMed

    Bronzeau, Sandrine; Pamme, Nicole

    2008-02-18

    Magnetic particles coated with specific biomolecules are often used as solid supports for bioassays but conventional test tube based techniques are time consuming and labour intensive. An alternative is to work on magnetic particle plugs immobilised inside microfluidic channels. Most research so far has focussed on immobilising one type of particle to perform one type of assay. Here we demonstrate how several assays can be performed simultaneously by flushing a sample solution over several plugs of magnetic particles with different surface coatings. Within a microchannel, three plugs of magnetic particles were immobilised with external magnets. The particles featured surface coatings of glycine, streptavidin and protein A, respectively. Reagents were then flushed through the three plugs. Molecular binding occurred between matching antigens and antibodies in continuous flow and was detected by fluorescence. This first demonstration opens the door to a quicker and easier technique for simultaneous bioassays using magnetic particles.

  13. Development of Macroporous Poly(ethylene glycol) Hydrogel Arrays Within Microfluidic Channels

    PubMed Central

    Lee, Andrew G.; Arena, Christopher P.; Beebe, David J.; Palecek, Sean P.

    2010-01-01

    The mass transport of solutes through hydrogels is an important design consideration in materials used for tissue engineering, drug delivery, and protein arrays used to quantify protein concentration and activity. We investigated the use of poly(ethylene glycol) (PEG) as a porogen to enhance diffusion of macromolecules into the interior of polyacrylamide and PEG hydrogel posts photopatterned within microfluidic channels. The diffusion of GST–GFP and dextran–FITC into hydrogels was monitored and effective diffusion coefficients were determined by fitting to the Fickian diffusion equations. PEG-diacrylate (Mr 700) with porogen formed a macroporous structure and permitted significant penetration of 250 kDa dextran. Proteins copolymerized in these macroporous hydrogels retained activity and were more accessible to antibody binding than proteins copolymerized in nonporous gels. These results suggest that hydrogel macroporosity can be tuned to regulate macromolecular transport in applications such as tissue engineering and protein arrays. PMID:21028794

  14. Effect of analyte adsorption on the electroosmotic flow in microfluidic channels.

    PubMed

    Ghosal, Sandip

    2002-02-15

    The predictability and constancy over time of the electroosmotic flow in microchannels is an important consideration in microfluidic devices. A common cause for alteration of the flow is the adsorption of analytes to channel walls, for example, during capillary electrophoresis of proteins. It is shown that certain experimental data, published by Towns and Regnier (Towns, J. K; Regnier, F. E. Anal. Chem. 1992, 64, 2473-2478.), on the anomalous elution times for proteins in capillary electrophoresis can be explained using a simple model for analyte adsorption that uses a result first reported by Anderson and Idol (Anderson, J. L.; Idol, W. K Chem. Eng. Commun. 1985, 38, 93-106.) on the electroosmotic flux in capillaries with axial variations in zeta-potential. It is suggested that it might be possible to use such a model to dynamically correct for altered elution times in capillary electrophoretic devices.

  15. Separation by nanoparticles plasmonic resonance with low stress in microfluidics channel (analytical and design).

    PubMed

    SalmanOgli, Ahmad; Farhadnia, Farshad; Piskin, Erhan

    2016-08-01

    In this study, nanoparticles near-field plasmonic resonance is used to improve the traditional cell separation main outputs such as viability and efficiency. The live cells viability is severely depend on stresses, which are applied on cells in the microfluidics channel. Hence, for improving the cell viability, the enforced stresses inside of the structure should be declined. The major factors of the enforced stresses are related to the electric field non-uniformity, which are attributed to the hurdles and applied voltage magnitude. Therefore, in this study, a new structure is presented and thereby, the magnitude of the applied stresses on live cells is minimised which is contributed to the decreasing the non-uniformity strength of channel. It should be noted that in the new structure two arrays of nanoparticles were used to produce a short range and localised non-uniform electrical field because of their near-field plasmonic resonance. Hence, the enforced stress on the live cell severely decreased at the far-field and confined at the small section of the channel. It is due to, the near-field plasmonic amplitude is dramatically disappeared by increasing distance, hence, the cells far from the nanoparticles will be endured the low level but effective amount of the optical force.

  16. Blood-plasma separation in Y-shaped bifurcating microfluidic channels: a dissipative particle dynamics simulation study.

    PubMed

    Li, Xuejin; Popel, Aleksander S; Karniadakis, George Em

    2012-04-04

    The motion of a suspension of red blood cells (RBCs) flowing in a Y-shaped bifurcating microfluidic channel is investigated using a validated low-dimensional RBC model based on dissipative particle dynamics. Specifically, the RBC is represented as a closed torus-like ring of ten colloidal particles, which leads to efficient simulations of blood flow in microcirculation over a wide range of hematocrits. Adaptive no-slip wall boundary conditions were implemented to model hydrodynamic flow within a specific wall structure of diverging three-dimensional microfluidic channels, paying attention to controlling density fluctuations. Plasma skimming and the all-or-nothing phenomenon of RBCs in a bifurcating microfluidic channel have been investigated in our simulations for healthy and diseased blood, including the size of a cell-free layer on the daughter branches. The feed hematocrit level in the parent channel has considerable influence on blood-plasma separation. Compared to the blood-plasma separation efficiencies of healthy RBCs, malaria-infected stiff RBCs (iRBCs) have a tendency to travel into the low flow-rate daughter branch because of their different initial distribution in the parent channel. Our simulation results are consistent with previously published experimental results and theoretical predictions.

  17. Blood-plasma separation in Y-shaped bifurcating microfluidic channels: a dissipative particle dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Li, Xuejin; Popel, Aleksander S.; Karniadakis, George Em

    2012-04-01

    The motion of a suspension of red blood cells (RBCs) flowing in a Y-shaped bifurcating microfluidic channel is investigated using a validated low-dimensional RBC model based on dissipative particle dynamics. Specifically, the RBC is represented as a closed torus-like ring of ten colloidal particles, which leads to efficient simulations of blood flow in microcirculation over a wide range of hematocrits. Adaptive no-slip wall boundary conditions were implemented to model hydrodynamic flow within a specific wall structure of diverging three-dimensional microfluidic channels, paying attention to controlling density fluctuations. Plasma skimming and the all-or-nothing phenomenon of RBCs in a bifurcating microfluidic channel have been investigated in our simulations for healthy and diseased blood, including the size of a cell-free layer on the daughter branches. The feed hematocrit level in the parent channel has considerable influence on blood-plasma separation. Compared to the blood-plasma separation efficiencies of healthy RBCs, malaria-infected stiff RBCs (iRBCs) have a tendency to travel into the low flow-rate daughter branch because of their different initial distribution in the parent channel. Our simulation results are consistent with previously published experimental results and theoretical predictions.

  18. Enzymatically-generated fluorescent detection in micro-channels with internal magnetic mixing for the development of parallel microfluidic ELISA.

    PubMed

    Herrmann, M; Veres, T; Tabrizian, M

    2006-04-01

    The Enzyme-Linked Immuno-Sorbent Assay, or ELISA, is commonly utilized to quantify small concentrations of specific proteins for a large variety of purposes, ranging from medical diagnosis to environmental analysis and food safety. However, this technique requires large volumes of costly reagents and long incubation periods. The use of microfluidics permits one to specifically address these drawbacks by decreasing both the volume and the distance of diffusion inside the micro-channels. Existing microfluidic systems are limited by the necessary control of extremely low flow rates to provide sufficient time for the molecules to interact with each other by diffusion only. In this paper, we describe a new microfluidic design for the realization of parallel ELISA in stop-flow conditions. Magnetic beads were used both as a solid phase to support the formation of the reactive immune complex and to achieve a magnetic mixing inside the channels. In order to test the detection procedure, the formation of the immune complex was performed off-chip before the reactive beads were injected into the reaction chamber. Anti-streptavidin antibodies were quantified with low picomolar sensitivity (0.1-6.7 pM), a linear range of 2 orders of magnitude and good reproducibility. This work represents the first step toward a new platform for simple, highly effective and parallel microfluidic ELISA.

  19. Design and fabrication of a screw-driven multi-channel peristaltic pump for portable microfluidic devices

    NASA Astrophysics Data System (ADS)

    Rhie, Wonsei; Higuchi, Toshiro

    2010-08-01

    A novel peristaltic pump for portable microfluidic devices has been recently designed and fabricated. The operation principle is based on the peristaltic motion of eight elastic pumping channels that are occluded by a screw shaft. The screw shaft rotating inside the pumping channel unit has a spirally arranged projection which deforms and closes down the channels as a normally closed valve. While the shaft rotates, the pinched locations in the channels move either way according to the direction of rotation, squeezing out the fluid inside. It features unlimited and quantitative fluid feeding with a wide range of flow rates for one channel from 3.5 µL min-1 at 3 rpm to 280.2 µL min-1 at 180 rpm. It was demonstrated that pulsation can be drastically reduced by merging two anti-phase channels.

  20. Real-time Full-spectral Imaging and Affinity Measurements from 50 Microfluidic Channels using Nanohole Surface Plasmon Resonance†

    PubMed Central

    Lee, Si Hoon; Lindquist, Nathan C.; Wittenberg, Nathan J.; Jordan, Luke R.; Oh, Sang-Hyun

    2012-01-01

    With recent advances in high-throughput proteomics and systems biology, there is a growing demand for new instruments that can precisely quantify a wide range of receptor-ligand binding kinetics in a high-throughput fashion. Here we demonstrate a surface plasmon resonance (SPR) imaging spectroscopy instrument capable of extracting binding kinetics and affinities from 50 parallel microfluidic channels simultaneously. The instrument utilizes large-area (~cm2) metallic nanohole arrays as SPR sensing substrates and combines a broadband light source, a high-resolution imaging spectrometer and a low-noise CCD camera to extract spectral information from every channel in real time with a refractive index resolution of 7.7 × 10−6. To demonstrate the utility of our instrument for quantifying a wide range of biomolecular interactions, each parallel microfluidic channel is coated with a biomimetic supported lipid membrane containing ganglioside (GM1) receptors. The binding kinetics of cholera toxin b (CTX-b) to GM1 are then measured in a single experiment from 50 channels. By combining the highly parallel microfluidic device with large-area periodic nanohole array chips, our SPR imaging spectrometer system enables high-throughput, label-free, real-time SPR biosensing, and its full-spectral imaging capability combined with nanohole arrays could enable integration of SPR imaging with concurrent surface-enhanced Raman spectroscopy. PMID:22895607

  1. Theoretical analysis of molecular diffusion in pressure-driven laminar flow in microfluidic channels.

    PubMed Central

    Kamholz, A E; Yager, P

    2001-01-01

    The T-sensor is a microfluidic analytical device that operates at low Reynolds numbers to ensure entirely laminar flow. Diffusion of molecules between streams flowing side by side may be observed directly. The pressure-driven velocity profile in the duct-shaped device influences diffusive transport in ways that affect the use of the T-sensor to measure molecular properties. The primary effect is a position-dependent variation in the extent of diffusion that occurs due to the distribution of residence time among different fluid laminae. A more detailed characterization reveals that resultant secondary concentration gradients yield variations in the scaling behavior between diffusive displacement and elapsed time in different regions of the channel. In this study, the time-dependent evolution of analyte distribution has been quantified using a combination of one- and two-dimensional models. The results include an accurate portrayal of the shape of the interdiffusion region in a representative T-sensor assay, calculation of the diffusive scaling law across the width of the channel, and quantification of artifacts that occur when making diffusion coefficient measurements in the T-sensor. PMID:11159391

  2. Ultrafast STR Separations on Short-Channel Microfluidic Systems for Forensic Screening and Genotyping.

    PubMed

    Aboud, Maurice J; Gassmann, Marcus; McCord, Bruce

    2015-09-01

    There are situations in which it is important to quickly and positively identify an individual. Examples include suspects detained in the neighborhood of a bombing or terrorist incident, individuals detained attempting to enter or leave the country, and victims of mass disasters. Systems utilized for these purposes must be fast, portable, and easy to maintain. DNA typing methods provide the best biometric information yielding identity, kinship, and geographical origin, but they are not portable and rapid. This study details the development of a portable short-channel microfluidic device based on a modified Agilent 2100 bioanalyzer for applications in forensic genomics. The system utilizes a denaturing polymer matrix with dual-channel laser-induced fluorescence and is capable of producing a genotype in 80 sec. The device was tested for precision and resolution using an allelic ladder created from 6 short tandem repeat (STR) loci and a sex marker (amelogenin). The results demonstrated a precision of 0.09-0.21 bp over the entire size range and resolution values from 2.5 to 4.1 bp. Overall, the results demonstrate the chip provides a portable, rapid, and precise method for screening amplified short tandem repeats and human identification screening.

  3. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

    PubMed Central

    Ghuman, Alyssa P.; Collins, Stephanie B.; Handa, Hitesh

    2016-01-01

    Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug. PMID:27313895

  4. Laser micromilling of convex microfluidic channels onto glassy carbon for glass molding dies

    NASA Astrophysics Data System (ADS)

    Tseng, Shih-Feng; Chen, Ming-Fei; Hsiao, Wen-Tse; Huang, Chien-Yao; Yang, Chung-Heng; Chen, Yu-Sheng

    2014-06-01

    This study reports the fabrication of convex microfluidic channels on glassy carbon using an ultraviolet laser processing system to produce glass molding dies. The laser processing parameters, including various laser fluences and scanning speeds of galvanometers, were adjusted to mill a convex microchannel on a glassy carbon substrate to identify the effects of material removal. The machined glassy carbon substrate was then applied as a glass molding die to fabricate a glass-based microfluidic biochip. The surface morphology, milled width and depth, and surface roughness of the microchannel die after laser micromilling were examined using a three-dimensional confocal laser scanning microscope. This study also investigates the transcription rate of microchannels after the glass molding process. To produce a 180 μm high microchannel on the GC substrate, the optimal number of milled cycles, laser fluence, and scanning speed were 25, 4.9 J/cm2, and 200 mm/s, respectively. The width, height, and surface roughness of milled convex microchannels were 119.6±0.217 μm, 180.26±0.01 μm, and 0.672±0.08 μm, respectively. These measured values were close to the predicted values and suitable for a glass molding die. After the glass molding process, a typical glass-based microchannel chip was formed at a molding temperature of 660 °C and the molding force of 0.45 kN. The transcription rates of the microchannel width and depth were 100% and 99.6%, respectively. Thus, the proposed approach is suitable for performing in chemical, biochemical, or medical reactions.

  5. Design of a sedimentation hole in a microfluidic channel to remove blood cells from diluted whole blood

    NASA Astrophysics Data System (ADS)

    Kuroda, Chiaki; Ohki, Yoshimichi; Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Makishima, Makoto

    2017-03-01

    With the aim of developing a sensor for rapidly detecting viruses in a drop of blood, in this study, we analyze the shape of a hole in a microfluidic channel in relation to the efficiency of sedimentation of blood cells. The efficiency of sedimentation is examined on the basis of our calculation and experimental results for two types of sedimentation hole, cylindrical and truncated conical holes, focusing on the Boycott effect, which can promote the sedimentation of blood cells from a downward-facing wall. As a result, we demonstrated that blood cells can be eliminated with an efficiency of 99% or higher by retaining a diluted blood sample of about 30 µL in the conical hole for only 2 min. Moreover, we succeeded in detecting the anti-hepatitis B surface antigen antibody in blood using a waveguide-mode sensor equipped with a microfluidic channel having the conical sedimentation hole.

  6. 3D Anastomosed Microvascular Network Model with Living Capillary Networks and Endothelial Cell-Lined Microfluidic Channels.

    PubMed

    Wang, Xiaolin; Phan, Duc T T; George, Steven C; Hughes, Christopher C W; Lee, Abraham P

    2017-01-01

    This protocol describes detailed practical procedures for generating 3D intact and perfusable microvascular network that connects to microfluidic channels without appreciable leakage. This advanced 3D microvascular network model incorporates different stages of vascular development including vasculogenesis, endothelial cell (EC) lining, sprouting angiogenesis, and anastomosis in sequential order. The capillary network is first induced via vasculogenesis in a middle tissue chamber and then EC linings along the microfluidic channel on either side serve as artery and vein. The anastomosis is then induced by sprouting angiogenesis to facilitate tight interconnection between the artery/vein and the capillary network. This versatile device design and its robust construction methodology establish a physiological microcirculation transport model of interconnected perfused vessels from artery to vascularized tissue to vein.

  7. A wide range and high sensitivity four-channel compact electrochemical biosensor for neurotransmitter detection on a microfluidic platform.

    PubMed

    Ghodsevali, Elnaz; Landari, Hamza; Boukadoum, Mounir; Gosselin, Benoit; Miled, Amine

    2016-08-01

    We present a four-channel, high-sensitivity and linearity electrochemical biosensor for neurotransmitter (NT) detection and measurement. Using a multi-channel microfluidic platform makes this biosensor capable of detecting NT-related currents going from nanoamperes to milliamperes, with a sensitivity of the order of picoamperes. Moreover, by using a fully differential potentiostat architecture, the biosensor offers a high common-mode rejection ratio (90 dB), making it appropriate for low-noise and high-sensitive applications. The system was implemented on a 15 mm × 15 mm PCB with direct interface to the microfluidic chambers. It was calibrated with a 5 mM ferrocyanide solution and successfully tested with dopamine at three concentrations. The system shows a minimum sensistivity of 100 pA and consumes 60 mW.

  8. Single cell rheometry with a microfluidic constriction: Quantitative control of friction and fluid leaks between cell and channel walls

    PubMed Central

    Preira, Pascal; Valignat, Marie-Pierre; Bico, José; Théodoly, Olivier

    2013-01-01

    We report how cell rheology measurements can be performed by monitoring the deformation of a cell in a microfluidic constriction, provided that friction and fluid leaks effects between the cell and the walls of the microchannels are correctly taken into account. Indeed, the mismatch between the rounded shapes of cells and the angular cross-section of standard microfluidic channels hampers efficient obstruction of the channel by an incoming cell. Moreover, friction forces between a cell and channels walls have never been characterized. Both effects impede a quantitative determination of forces experienced by cells in a constriction. Our study is based on a new microfluidic device composed of two successive constrictions, combined with optical interference microscopy measurements to characterize the contact zone between the cell and the walls of the channel. A cell squeezed in a first constriction obstructs most of the channel cross-section, which strongly limits leaks around cells. The rheological properties of the cell are subsequently probed during its entry in a second narrower constriction. The pressure force is determined from the pressure drop across the device, the cell velocity, and the width of the gutters formed between the cell and the corners of the channel. The additional friction force, which has never been analyzed for moving and constrained cells before, is found to involve both hydrodynamic lubrication and surface forces. This friction results in the existence of a threshold for moving the cells and leads to a non-linear behavior at low velocity. The friction force can nevertheless be assessed in the linear regime. Finally, an apparent viscosity of single cells can be estimated from a numerical prediction of the viscous dissipation induced by a small step in the channel. A preliminary application of our method yields an apparent loss modulus on the order of 100 Pa s for leukocytes THP-1 cells, in agreement with the literature data. PMID:24404016

  9. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

    PubMed Central

    Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2015-01-01

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer. PMID:26373820

  10. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-Tae; Iqbal, Samir M.

    2015-09-01

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

  11. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels.

    PubMed

    Islam, Muhymin; Bellah, Mohammad Motasim; Sajid, Adeel; Hasan, Mohammad Raziul; Kim, Young-tae; Iqbal, Samir M

    2015-09-16

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

  12. Toward Reservoir-on-a-Chip: Fabricating Reservoir Micromodels by in Situ Growing Calcium Carbonate Nanocrystals in Microfluidic Channels.

    PubMed

    Wang, Wei; Chang, Sehoon; Gizzatov, Ayrat

    2017-08-30

    We introduce a novel and simple method to fabricate calcium carbonate (CaCO3) micromodels by in situ growing a thin layer of CaCO3 nanocrystals with a thickness of 1-2 μm in microfluidic channels. This approach enables us to fabricate synthetic CaCO3 reservoir micromodels having surfaces fully covered with calcite, while the dimensions and geometries of the micromodels are controllable on the basis of the original microfluidic channels. We have tuned the wettability of the CaCO3-coated microchannels at simulated oil reservoir conditions without introducing any chemical additives to the system; thus the resulting oil-wet surface makes the micromodel more faithfully resemble a natural carbonate reservoir rock. With the advantage of its excellent optical transparency, the micromodel allows us to directly visualize the complex multiphase flows and geochemical fluid-calcite interactions by spectroscopic and microscopic imaging techniques. The CaCO3-coated microfluidic channels provide new capabilities as a micromodel system to mimic real carbonate reservoir properties, which would allow us to perform a water-oil displacement experiment in small-volume samples for the rapid screening of candidate fluids for enhanced oil recovery (EOR). The immiscible fluid displacement process within carbonate micromodels has been demonstrated showing the water-oil-carbonate interactions at pore-scale in real time by fluorescence microscopic imaging.

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

  14. Microfluidic electrochemical reactors

    SciTech Connect

    Nuzzo, Ralph G; Mitrovski, Svetlana M

    2011-03-22

    A microfluidic electrochemical reactor includes an electrode and one or more microfluidic channels on the electrode, where the microfluidic channels are covered with a membrane containing a gas permeable polymer. The distance between the electrode and the membrane is less than 500 micrometers. The microfluidic electrochemical reactor can provide for increased reaction rates in electrochemical reactions using a gaseous reactant, as compared to conventional electrochemical cells. Microfluidic electrochemical reactors can be incorporated into devices for applications such as fuel cells, electrochemical analysis, microfluidic actuation, pH gradient formation.

  15. High-throughput and sensitive particle counting by a novel microfluidic differential resistive pulse sensor with multidetecting channels and a common reference channel.

    PubMed

    Song, Yongxin; Yang, Jiandong; Pan, Xinxiang; Li, Dongqing

    2015-02-01

    High-throughput particle counting by a differential resistive pulse sensing method in a microfluidic chip is presented in this paper. A sensitive differential microfluidic sensor with multiple detecting channels and one common reference channel was devised. To test the particle counting performance of this chip, an experimental system which consists of the microfluidic chip, electric resistors, an amplification circuit, a LabView based data acquisition device was developed. The influence of the common reference channel on the S/N of particle detection was investigated. The relationship between the hydraulic pressure drop applied across the detecting channel and the counting throughput was experimentally obtained. The experimental results show that the reference channel designed in this work can improve the S/N by ten times, thus enabling sensitive high-throughput particle counting. Because of the greatly improved S/N, the sensing gate with a size of 25 × 50 × 10 μm (W × L × H) in our chips can detect and count particles larger than 1.5 μm in diameter. The counting throughput increases with the increase in the flowing velocity of the sample solution. An average throughput of 7140/min under a flow rate of 10 μL/min was achieved. Comparing with other methods, the structure of the chip and particle detecting mechanism reported in this paper is simple and sensitive, and does not have the crosstalking problem. Counting throughput can be adjusted simply by changing the number of the detecting channels. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Channel surface patterning of alternating biomimetic protein combinations for enhanced microfluidic tumor cell isolation.

    PubMed

    Launiere, Cari; Gaskill, Marissa; Czaplewski, Gregory; Myung, Ja Hye; Hong, Seungpyo; Eddington, David T

    2012-05-01

    Here, we report a new method for multicomponent protein patterning in a microchannel and also a technique for improving immunoaffinity-based circulating tumor cell (CTC) capture by patterning regions of alternating adhesive proteins using the new method. The first of two proteins, antiepithelial cell adhesion molecule (anti-EpCAM), provides the specificity for CTC capture. The second, E-selectin, increases CTC capture under shear. Patterning regions with and without E-selectin allows captured leukocytes, which also bind E-selectin and are unwanted impurities in CTC isolation, to roll a short distance and detach from the capture surface. This reduces leukocyte capture by up to 82%. The patterning is combined with a leukocyte elution step in which a calcium chelating buffer effectively deactivates E-selectin so that leukocytes may be rinsed away 60% more efficiently than with a buffer containing calcium. The alternating patterning of this biomimetic protein combination, used in conjunction with the elution step, reduces capture of leukocytes while maintaining a high tumor cell capture efficiency that is up to 1.9 times higher than the tumor cell capture efficiency of a surface with only anti-EpCAM. The new patterning technique described here does not require mask alignment and can be used to spatially control the immobilization of any two proteins or protein mixtures inside a sealed microfluidic channel.

  17. Ion-size dependent electroosmosis of viscoelastic fluids in microfluidic channels with interfacial slip

    NASA Astrophysics Data System (ADS)

    Mukherjee, Siddhartha; Goswami, Prakash; Dhar, Jayabrata; Dasgupta, Sunando; Chakraborty, Suman

    2017-07-01

    We report a study on the ion-size dependent electroosmosis of viscoelastic fluids in microfluidic channels with interfacial slip. Here, we derive an analytical solution for the potential distribution in a parallel plate microchannel, where the effects of finite sized ionic species are taken into account by invoking the free energy formalism. Following this, a purely electroosmotic flow of a simplified Phan-Thien-Tanner (sPTT) fluid is considered. For the sPTT model, linear, quadratic, and exponential kernels are chosen for the stress coefficient function describing its viscoelastic nature across various ranges of Deborah number. The theoretical framework presented in our analysis has been successfully compared with experimental results available in the literature. We believe that the implications of the considered effects on the net volumetric throughput will not only provide a deeper theoretical insight to interpret the electrokinetic data in the presence of ionic species but also serve as a fundamental design tool for novel electrokinetically driven lab-on-a-chip biofluidic devices.

  18. Behavior of Caulobacter Crescentus Diagnosed Using a 3-Channel Microfluidic Device

    NASA Astrophysics Data System (ADS)

    Tang, Jay; Morse, Michael; Colin, Remy; Wilson, Laurence

    2015-03-01

    Many motile microorganisms are able to detect chemical gradients in their surroundings in order to bias their motion towards more favorable conditions. We study the biased motility of Caulobacter crescentus, a singly flagellated bacteria, which alternate between forward and backward swimming, driven by its flagella motor, which switches in rotation direction. We observe the swimming patterns of C. crescents in an oxygen gradient, which is established by flowing atmospheric air and pure nitrogen through a 3 parallel channel microfluidic device. In this setup, oxygen diffuses through the PDMS device and the bacterial medium, creating a linear gradient. Using low magnification, dark field microscopy, individual cells are tracked over a large field of view, with particular interest in the cells' motion relative to the oxygen gradient. Utilizing observable differences between backward and forward swimming motion, motor switching events can be identified. By analyzing these run time intervals between motor switches as a function of a cell's local oxygen level, we demonstrate that C. crescentus displays aerotacitc behavior by extending forward swimming run times while moving up an oxygen gradient, resulting in directed motility towards oxygen sources. Additionally, motor switching response is sensitive to both the steepness of the gradient experienced and background oxygen levels with cells exhibiting a logarithmic response to oxygen levels. Work funded by the United States National Science Foundation and by the Rowland Institute at Harvard University.

  19. Coupled lattice-Boltzmann and finite-difference simulation of electroosmosis in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Hlushkou, Dzmitry; Kandhai, Drona; Tallarek, Ulrich

    2004-10-01

    In this article we are concerned with an extension of the lattice-Boltzmann method for the numerical simulation of three-dimensional electroosmotic flow problems in porous media. Our description is evaluated using simple geometries as those encountered in open-channel microfluidic devices. In particular, we consider electroosmosis in straight cylindrical capillaries with a (non)uniform zeta-potential distribution for ratios of the capillary inner radius to the thickness of the electrical double layer from 10 to 100. The general case of heterogeneous zeta-potential distributions at the surface of a capillary requires solution of the following coupled equations in three dimensions: Navier-Stokes equation for liquid flow, Poisson equation for electrical potential distribution, and the Nernst-Planck equation for distribution of ionic species. The hydrodynamic problem has been treated with high efficiency by code parallelization through the lattice-Boltzmann method. For validation velocity fields were simulated in several microcapillary systems and good agreement with results predicted either theoretically or obtained by alternative numerical methods could be established. Results are also discussed with respect to the use of a slip boundary condition for the velocity field at the surface.

  20. Mode competition and destabilization of microfluidic channel flows by the Coriolis force

    NASA Astrophysics Data System (ADS)

    Sengupta, Saunak; Saha, Sandeep; Chakraborty, Suman

    2016-11-01

    Understanding flow stability in inertial microfluidics is very important due to its increased application in medical and chemical engineering. On a steady rotating platform centrifugal actuation drives fluid flow but Coriolis force can destabilize the flow and enhance mixing in a short span. We investigate the role of Coriolis force in micro-mixing and the structure of the roll-cells formed in rotating channel flow using linear stability theory. We conduct a parametric study at different rotation numbers, Reynolds number, axial and spanwise wavenumbers. Our results reveal existence of multiple competing unstable modes (Types I to IV) due to Coriolis force: Types I and II have been reported in literature and are responsible for the formation of evenly-spaced roll-cells. We find new instabilities (Types III and IV) which contribute to the formation of twisted roll cells. The existence of the instabilities is clearly demarcated on a regime map to assist future experiments to identify them. The kinetic energy budget has been analyzed to gain insight into the mechanism of energy transfer by Coriolis force from the mean flow to the perturbations. We make a qualitative comparison of roll-cells predicted by linear stability with previously reported experiments.

  1. Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel

    NASA Astrophysics Data System (ADS)

    Sung, Yongjin; Lue, Niyom; Hamza, Bashar; Martel, Joseph; Irimia, Daniel; Dasari, Ramachandra R.; Choi, Wonshik; Yaqoob, Zahid; So, Peter

    2014-02-01

    The refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. In addition, the refractive index contains rich information related to the metabolism of cells at the cellular and subcellular levels. Here, we report a no-moving-parts approach that provides three-dimensional refractive-index maps of biological samples continuously flowing in a microfluidic channel. Specifically, we use line illumination and off-axis digital holography to record the angular spectra of light scattered from flowing samples at high speed. Applying the scalar diffraction theory, we obtain accurate refractive-index maps of the samples from the measured spectra. Using this method, we demonstrate label-free three-dimensional imaging of live RKO human colon cancer cells and RPMI8226 multiple myeloma cells, and obtain the volume, dry mass, and density of these cells from the measured three-dimensional refractive-index maps. Our results show that the reported method, alone or in combination with the existing flow cytometry techniques, shows promise as a quantitative tool for stain-free characterization of a large number of cells.

  2. Charge injection through nanocomposite electrode in microfluidic channel for electrical lysis of biological cells

    NASA Astrophysics Data System (ADS)

    Mishra, Madhusmita; Krishna, Anil; Chandra, Aman; Shenoy, B. M.; Hegde, G. M.; Mahapatra, D. Roy

    2013-03-01

    Several concepts have been developed in the recent years for nanomaterial based integrated MEMS platform in order to accelerate the process of biological sample preparation followed by selective screening and identification of target molecules. In this context, there exist several challenges which need to be addressed in the process of electrical lysis of biological cells. These are due to (i) low resource settings while achieving maximal lysis (ii) high throughput of target molecules to be detected (iii) automated extraction and purification of relevant molecules such as DNA and protein from extremely small volume of sample (iv) requirement of fast, accurate and yet scalable methods (v) multifunctionality toward process monitoring and (vi) downward compatibility with already existing diagnostic protocols. This paper reports on the optimization of electrical lysis process based on various different nanocomposite coated electrodes placed in a microfluidic channel. The nanocomposites are synthesized using different nanomaterials like Zinc nanorod dispersion in polymer. The efficiency of electrical lysis with various different electrode coatings has been experimentally verified in terms of DNA concentration, amplification and protein yield. The influence of the coating thickness on the injection current densities has been analyzed. We further correlate experimentally the current density vs. voltage relationship with the extent of bacterial cell lysis. A coupled multiphysics based simulation model is used to predict the cell trajectories and lysis efficiencies under various electrode boundary conditions as estimated from experimental results. Detailed in-situ fluorescence imaging and spectroscopy studies are performed to validate various hypotheses.

  3. Passage times of confined cancer cells and deformable particles flowing through a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Khan, Zeina; Kamyabi, Nabiollah; Hussain, Fazle; Vanapalli, Siva

    Circulating tumor cells, the primary cause of cancer metastasis, have to navigate through tight extracellular matrix and capillaries. Unfortunately, understanding of the hydrodynamic interactions between cells and narrow vessel walls is lacking. Using a microfluidic channel of rectangular cross-section, we investigate cell hydrodynamic behavior by measuring cell confinement, passage time through the microchannel, and excess pressure drop. Testing with highly and lowly aggressive cancer cells shows that passage time may not always be indicative of cancer cell aggressiveness as the relationship among passage time, friction and rheology is complex. Transport of deformable particles including droplets of varying viscosity and interfacial tension, as well as elastic particles of different elastic moduli, reveals that passage times depend on particle size and, contrary to prior claims, on viscosity but not on elastic modulus. We also find that particle viscosity and not modulus controls the friction force and lubrication film thickness, suggesting that cancer cell viscosity rather than elasticity controls cell transport on short time-scales.

  4. Enhanced detection of quantum dots labeled protein by simultaneous bismuth electrodeposition into microfluidic channel.

    PubMed

    Medina-Sánchez, Mariana; Miserere, Sandrine; Cadevall, Miquell; Merkoçi, Arben

    2016-02-01

    In this study, we propose an electrochemical immunoassay into a disposable microfluidic platform, using quantum dots (QDs) as labels and their enhanced detection using bismuth as an alternative to mercury electrodes. CdSe@ZnS QDs were used to tag human IgG as a model protein and detected through highly sensitive stripping voltammetry of the dissolved metallic component (cadmium in our case). The modification of the screen printed carbon electrodes (SPCEs) was done by a simple electrodeposition of bismuth that was previously mixed with the sample containing QDs. A magneto-immunosandwich assay was performed using a micromixer. A magnet placed at its outlet in order to capture the magnetic beads used as solid support for the immunoassay. SPCEs were integrated at the end of the channel as detector. Different parameters such as bismuth concentration, flow rate, and incubation times, were optimized. The LOD for HIgG in presence of bismuth was 3.5 ng/mL with a RSD of 13.2%. This LOD was about 3.3-fold lower than the one obtained without bismuth. Furthermore, the sensitivity of the system was increased 100-fold respect to experiments carried out with classical screen-printed electrodes, both in presence of bismuth.

  5. Electrocoalescence mechanisms of microdroplets using localized electric fields in microfluidic channels.

    PubMed

    Zagnoni, Michele; Le Lain, Guillaume; Cooper, Jonathan M

    2010-09-21

    Electrocoalescence of water-in-oil microdroplets in microfluidic channels is an active technique that enables droplet-based mixing functionalities to be achieved in lab-on-a-chip applications. In this work, a characterization of the electrocoalescence mechanisms of water microdroplets in oil is presented, using localized electric field systems. We report a theoretical and experimental description of the electrocoalscence behavior of droplet pairs by varying the physical and fluid dynamic conditions of the phases. Our results demonstrate that localized electric field systems can be reliably used to merge droplets in pairs, regardless of the distance between the drops. The coalescence behavior was dependent upon the viscosity of the continuous phase for water droplets that were separated by a thick layer of oil and upon interfacial tension for droplets that were in close proximity. We showed that these systems have the potential to be used for high-throughput applications and that, unlike other examples of active systems in the literature, the need of droplet synchronization and the application of high voltages is considerably reduced.

  6. Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel

    PubMed Central

    Sung, Yongjin; Lue, Niyom; Hamza, Bashar; Martel, Joseph; Irimia, Daniel; Dasari, Ramachandra R.; Choi, Wonshik; Yaqoob, Zahid; So, Peter

    2014-01-01

    Refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. In addition, RI contains rich information related to the metabolism of cells at the cellular and subcellular levels. Here, we report a no-moving parts approach that provides three-dimensional refractive index maps of biological samples continuously flowing in a microfluidic channel. Specifically, we use line illumination and off-axis digital holography to record the angular spectra of light scattered from flowing samples at high speed. Applying the scalar diffraction theory, we obtain accurate RI maps of the samples from the measured spectra. Using this method, we demonstrate label-free 3-D imaging of live RKO human colon cancer cells and RPMI8226 multiple myeloma cells, and obtain the volume, dry mass and density of these cells from the measured 3-D refractive index maps. Our results show that the reported method, alone or in combination with the existing flow cytometry techniques, promises as a quantitative tool for stain-free characterization of large number of cells. PMID:25419536

  7. Stable nonpolar solvent droplet generation using a poly(dimethylsiloxane) microfluidic channel coated with poly-p-xylylene for a nanoparticle growth.

    PubMed

    Lim, Heejin; Moon, SangJun

    2015-08-01

    Applications of microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS) have been limited to water-based analysis rather than nonpolar solvent based chemistry due to a PDMS swelling problem that occurs by the absorption of the solvents. The absorption and swelling causes PDMS channel deformation in shape, and changes the cross sectional area making it difficult to control the flow rate and concentrations of solution in PDMS microfluidic channels. We propose that poly-p-xylylene polymers (parylenes) are chemical vapors deposited on the surfaces of PDMS channels that alleviate the effect of solvents on the absorption and swelling. The parylene coated surface sustains 3 h with a small volumetric change (less than 22 % of PDMS swelling ratio). By generating an air-nonpolar solvent interface based on droplets in PDMS channel, we confirmed poly-p-xylylene coated PDMS microfluidic channels have the potential to be applicable to nanocrystal growth using nonpolar solvents.

  8. Design of microfluidic channels for magnetic separation of malaria-infected red blood cells

    PubMed Central

    Wu, Wei-Tao; Martin, Andrea Blue; Gandini, Alberto; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

    2016-01-01

    This study is motivated by the development of a blood cell filtration device for removal of malaria-infected, parasitized red blood cells (pRBCs). The blood was modeled as a multi-component fluid using the computational fluid dynamics discrete element method (CFD-DEM), wherein plasma was treated as a Newtonian fluid and the red blood cells (RBCs) were modeled as soft-sphere solid particles which move under the influence of drag, collisions with other RBCs, and a magnetic force. The CFD-DEM model was first validated by a comparison with experimental data from Han et al. 2006 (Han and Frazier 2006) involving a microfluidic magnetophoretic separator for paramagnetic deoxygenated blood cells. The computational model was then applied to a parametric study of a parallel-plate separator having hematocrit of 40% with a 10% of the RBCs as pRBCs. Specifically, we investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest. Simulations compared the efficacy of various geometries upon the stratification efficiency of the pRBCs. For a channel with nominal height of 100 µm, the addition of an upstream constriction of 80% improved the proportion of pRBCs retained adjacent to the magnetic wall (separation efficiency) by almost 2 fold, from 26% to 49%. Further addition of a downstream diffuser reduced remixing, hence improved separation efficiency to 72%. The constriction introduced a greater pressure drop (from 17 to 495 Pa), which should be considered when scaling-up this design for a clinical-sized system. Overall, the advantages of this design include its ability to accommodate physiological hematocrit and high throughput – which is critical for clinical implementation as a blood-filtration system. PMID:27761107

  9. Design of microfluidic channels for magnetic separation of malaria-infected red blood cells.

    PubMed

    Wu, Wei-Tao; Martin, Andrea Blue; Gandini, Alberto; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F

    2016-01-01

    This study is motivated by the development of a blood cell filtration device for removal of malaria-infected, parasitized red blood cells (pRBCs). The blood was modeled as a multi-component fluid using the computational fluid dynamics discrete element method (CFD-DEM), wherein plasma was treated as a Newtonian fluid and the red blood cells (RBCs) were modeled as soft-sphere solid particles which move under the influence of drag, collisions with other RBCs, and a magnetic force. The CFD-DEM model was first validated by a comparison with experimental data from Han et al. 2006 (Han and Frazier 2006) involving a microfluidic magnetophoretic separator for paramagnetic deoxygenated blood cells. The computational model was then applied to a parametric study of a parallel-plate separator having hematocrit of 40% with a 10% of the RBCs as pRBCs. Specifically, we investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest. Simulations compared the efficacy of various geometries upon the stratification efficiency of the pRBCs. For a channel with nominal height of 100 µm, the addition of an upstream constriction of 80% improved the proportion of pRBCs retained adjacent to the magnetic wall (separation efficiency) by almost 2 fold, from 26% to 49%. Further addition of a downstream diffuser reduced remixing, hence improved separation efficiency to 72%. The constriction introduced a greater pressure drop (from 17 to 495 Pa), which should be considered when scaling-up this design for a clinical-sized system. Overall, the advantages of this design include its ability to accommodate physiological hematocrit and high throughput - which is critical for clinical implementation as a blood-filtration system.

  10. Fabrication of Concentrated Fish Oil Emulsions Using Dual-Channel Microfluidization: Impact of Droplet Concentration on Physical Properties and Lipid Oxidation.

    PubMed

    Liu, Fuguo; Zhu, Zhenbao; Ma, Cuicui; Luo, Xiang; Bai, Long; Decker, Eric Andrew; Gao, Yanxiang; McClements, David Julian

    2016-12-21

    Chemically unstable lipophilic bioactives, such as polyunsaturated lipids, often have to be encapsulated in emulsion-based delivery systems before they can be incorporated into foods, supplements, and pharmaceuticals. The objective of this study was to develop highly concentrated emulsion-based fish oil delivery systems using natural emulsifiers. Fish oil-in-water emulsions were fabricated using a highly efficient dual-channel high-pressure microfluidizer. The impact of oil concentration on the formation, physical properties, and oxidative stability of fish oil emulsions prepared using two natural emulsifiers (quillaja saponins and rhamnolipids) and one synthetic emulsifier (Tween-80) was examined. The mean droplet size, polydispersity, and apparent viscosity of the fish oil emulsions increased with increasing oil content. However, physically stable emulsions with high fish oil levels (30 or 40 wt %) could be produced using all three emulsifiers, with rhamnolipids giving the smallest droplet size (d < 160 nm). The stability of the emulsions to lipid oxidation increased as the oil content increased. The oxidative stability of the emulsions also depended on the nature of the emulsifier coating the lipid droplets, with the oxidative stability decreasing in the following order: rhamnolipids > saponins ≈ Tween-80. These results suggest that rhamnolipids may be particularly effective at producing emulsions containing high concentrations of ω-3 polyunsaturated fatty acids-rich fish oil.

  11. Custom 3D printer and resin for 18 μm × 20 μm microfluidic flow channels.

    PubMed

    Gong, Hua; Bickham, Bryce P; Woolley, Adam T; Nordin, Gregory P

    2017-08-22

    While there is great interest in 3D printing for microfluidic device fabrication, to-date the achieved feature sizes have not been in the truly microfluidic regime (<100 μm). In this paper we demonstrate that a custom digital light processor stereolithographic (DLP-SLA) 3D printer and a specifically-designed, low cost, custom resin can readily achieve flow channel cross sections as small as 18 μm × 20 μm. Our 3D printer has a projected image plane resolution of 7.6 μm and uses a 385 nm LED, which dramatically increases the available selection of UV absorbers for resin formulation compared to 3D printers with 405 nm LEDs. Beginning with 20 candidate absorbers, we demonstrate the evaluation criteria and process flow required to develop a high-resolution resin. In doing so, we introduce a new mathematical model for characterizing the resin optical penetration depth based only on measurement of the absorber's molar absorptivity. Our final resin formulation uses 2-nitrophenyl phenyl sulfide (NPS) as the UV absorber. We also develop a novel channel narrowing technique that, together with the new resin and 3D printer resolution, enables small flow channel fabrication. We demonstrate the efficacy of our approach by fabricating 3D serpentine flow channels 41 mm long in a volume of only 0.12 mm(3), and by printing high aspect ratio flow channels <25 μm wide and 3 mm tall. These results indicate that 3D printing is finally positioned to challenge the pre-eminence of methods such as soft lithography for microfluidic device prototyping and fabrication.

  12. Numerical study of the effect of the channel and electrode geometry on the performance of microfluidic fuel cells

    NASA Astrophysics Data System (ADS)

    Ebrahimi Khabbazi, A.; Richards, A. J.; Hoorfar, M.

    Using COMSOL Multiphysics 3.5, 3D numerical models of different microfluidic fuel cells have been developed in this paper to determine the effect of different modifications which have been implemented in the microfluidic fuel cell since its advent. These modifications include the channel geometry aspect ratio and electrode configuration, the third flow between the anolyte and catholyte in the channel (i.e., multi-stream laminar flow), and multiple periodically placed inlets. To be consistent with the convention, the output power of the device is normalized by the electrode surface area; however, the power density calculations are also performed through normalization by the device volume. It is shown that the latter method is more realistic and providing more information from the design point of view since the ultimate goal in designing the microfluidic fuel cell is to fabricate a compact, yet powerful device. Finally, a novel design of the microfluidic fuel cell with a tapered channel is suggested and compared to the non-tapered geometry through the polarization curves. The steps which have been taken in COMSOL to obtain these polarization curves are clearly and thoroughly explained. The Butler-Volmer equation was implemented to incorporate for the electrochemical reactions at the electrodes. The "Conductive Media DC" module, in COMSOL, is used to model the electric fields within the fuel cell. The concentration distributions of the reactant species are obtained using the "Incompressible Navier-Stokes" and "Convection and Diffusion" modules. Solving these equations together predicts the current density for given cell voltage values. The results demonstrate the cell voltage losses due to activation, ohmic and concentration overpotentials. It is shown that for a fixed value of the cell voltage (say 0.45 V), the fuel cell with multiple periodically placed inlets has the highest fuel utilization (i.e., 62.3%); while the "Simple square" geometry depicts 13.8% fuel

  13. Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel.

    PubMed

    Pallaoro, Alessia; Hoonejani, Mehran R; Braun, Gary B; Meinhart, Carl D; Moskovits, Martin

    2015-01-01

    Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file. The spectrally rich SBTs are based on a silver nanoparticle dimer core labeled with a Raman-active small reporter molecule paired with an affinity biomolecule, providing a unique barcode whose presence in a composite SERS spectrum can be deconvoluted. Individual cancer cells passing through the focused laser beam were correctly identified among a proportionally larger number of other cells by their Raman signatures. We examine two deconvolution strategies: principal component analysis and classical least-squares. The deconvolution strategies are used to unmix the overall spectrum to determine the relative contributions between two SBT barcodes, where one SBT barcode indicates neuropilin-1 overexpression, while a second SBT barcode is more universal and indicates unspecific binding to a cell's membrane. Highly reliable results were obtained for all of the cell mixture ratios tested, the lowest being 1 in 100 cells.

  14. Rapid concentration of deoxyribonucleic acid via Joule heating induced temperature gradient focusing in poly-dimethylsiloxane microfluidic channel.

    PubMed

    Ge, Zhengwei; Wang, Wei; Yang, Chun

    2015-02-09

    This paper reports rapid microfluidic electrokinetic concentration of deoxyribonucleic acid (DNA) with the Joule heating induced temperature gradient focusing (TGF) by using our proposed combined AC and DC electric field technique. A peak of 480-fold concentration enhancement of DNA sample is achieved within 40s in a simple poly-dimethylsiloxane (PDMS) microfluidic channel of a sudden expansion in cross-section. Compared to a sole DC field, the introduction of an AC field can reduce DC field induced back-pressure and produce sufficient Joule heating effects, resulting in higher concentration enhancement. Within such microfluidic channel structure, negative charged DNA analytes can be concentrated at a location where the DNA electrophoretic motion is balanced with the bulk flow driven by DC electroosmosis under an appropriate temperature gradient field. A numerical model accounting for a combined AC and DC field and back-pressure driven flow effects is developed to describe the complex Joule heating induced TGF processes. The experimental observation of DNA concentration phenomena can be explained by the numerical model.

  15. Assessment of Joule heating and its effects on electroosmotic flow and electrophoretic transport of solutes in microfluidic channels.

    PubMed

    Tang, Gongyue; Yan, Deguang; Yang, Chun; Gong, Haiqing; Chai, John Chee; Lam, Yee Cheong

    2006-02-01

    Joule heating is inevitable when an electric field is applied across a conducting medium. It would impose limitations on the performance of electrokinetic microfluidic devices. This article presents a 3-D mathematical model for Joule heating and its effects on the EOF and electrophoretic transport of solutes in microfluidic channels. The governing equations were numerically solved using the finite-volume method. Experiments were carried out to investigate the Joule heating associated phenomena and to verify the numerical models. A rhodamine B-based thermometry technique was employed to measure the solution temperature distributions in microfluidic channels. The microparticle image velocimetry technique was used to measure the velocity profiles of EOF under the influence of Joule heating. The numerical solutions were compared with experimental results, and reasonable agreement was found. It is found that with the presence of Joule heating, the EOF velocity deviates from its normal "plug-like" profile. The numerical simulations show that Joule heating not only accelerates the sample transport but also distorts the shape of the sample band.

  16. Controlled delivery of bioactive molecules into live cells using the bacterial mechanosensitive channel MscL

    PubMed Central

    Doerner, Julia F.; Febvay, Sebastien; Clapham, David E.

    2013-01-01

    Bacterial mechanosensitive channels are some of the largest pores in nature. In particular, MscL, with a pore diameter > 25 Å, allows passage of large organic ions and small proteins. Functional MscL reconstitution into lipids has been proposed for applications in vesicular-based drug release. Here we show that these channels can be functionally expressed in mammalian cells to afford rapid controlled uptake of membrane impermeable molecules. We first demonstrate that MscL gating in response to increased membrane tension is preserved in mammalian cell membranes. Molecular delivery is controlled by adopting an established method of MscL charge-induced activation. We then determine pore size limitations using fluorescently labeled model cargoes. Finally, we activate MscL to introduce the cell-impermeable bi-cyclic peptide phalloidin, a specific marker for actin filaments, into cells. We propose that MscL will be a useful tool for gated and controlled delivery of bioactive molecules into cells. PMID:22871809

  17. Spatiotemporal periodicity of dislocation dynamics in a two-dimensional microfluidic crystal flowing in a tapered channel

    NASA Astrophysics Data System (ADS)

    Gai, Ya; Leong, Chia Min; Cai, Wei; Tang, Sindy K. Y.

    2016-10-01

    When a many-body system is driven away from equilibrium, order can spontaneously emerge in places where disorder might be expected. Here we report an unexpected order in the flow of a concentrated emulsion in a tapered microfluidic channel. The velocity profiles of individual drops in the emulsion show periodic patterns in both space and time. Such periodic patterns appear surprising from both a fluid and a solid mechanics point of view. In particular, when the emulsion is considered as a soft crystal under extrusion, a disordered scenario might be expected based on the stochastic nature of dislocation dynamics in microscopic crystals. However, an orchestrated sequence of dislocation nucleation and migration is observed to give rise to a highly ordered deformation mode. This discovery suggests that nanocrystals can be made to deform more controllably than previously thought. It can also lead to novel flow control and mixing strategies in droplet microfluidics.

  18. Joule heating monitoring in a microfluidic channel by observing the Brownian motion of an optically trapped microsphere.

    PubMed

    Brans, Toon; Strubbe, Filip; Schreuer, Caspar; Vandewiele, Stijn; Neyts, Kristiaan; Beunis, Filip

    2015-09-01

    Electric fields offer a variety of functionalities to Lab-on-a-Chip devices. The use of these fields often results in significant Joule heating, affecting the overall performance of the system. Precise knowledge of the temperature profile inside a microfluidic device is necessary to evaluate the implications of heat dissipation. This article demonstrates how an optically trapped microsphere can be used as a temperature probe to monitor Joule heating in these devices. The Brownian motion of the bead at room temperature is compared with the motion when power is dissipated in the system. This gives an estimate of the temperature increase at a specific location in a microfluidic channel. We demonstrate this method with solutions of different ionic strengths, and establish a precision of 0.9 K and an accuracy of 15%. Furthermore, it is demonstrated that transient heating processes can be monitored with this technique, albeit with a limited time resolution.

  19. A process for co-molding a visible-wavelength photonic crystal and microfluidic channel for biosensing applications

    NASA Astrophysics Data System (ADS)

    Srungarapu, Maurya; Snyder, Chloe E.; Kadiyala, Anand; Hamza, Bashar; Liu, Yuxin; Dawson, Jeremy M.

    2013-05-01

    Rapid DNA analysis systems show promise for reduced DNA analysis times and can be used by untrained operators in point-of-use applications. Throughput improvements can be gained by reducing the polymerase chain reaction (PCR) cycle count, which is used in conventional DNA processing to amplify the DNA to an easily measurable amount. A Photonic Crystal (PhC) can be integrated within a microfluidic channel to enhance fluorescence emission, enabling a reduction in PCR cycling. Most PhCs are fabricated using serial top-down fabrication techniques, resulting in a structure that is challenging to integrate with microfluidic system components. Here, we present a co-integration process for fabricating a Silicon master mold consisting of a visible range PhC lattice and a microfluidic channel. This process can be used to co-fabricate microscale channel and nanoscale lattice structures in polymer or thermoplastic materials. Two dimensional visible range PhCs are fabricated by patterning electron beam resist via E-Beam Lithography (EBL). The patterned features (100-300nm features with 200-450nm pitch) are cured to a glass-like material that is used as a direct etch mask for Reactive Ion Etching. A 200μm wide and 25μm high ridge "strip" is fabricated around the PhC region using Photolithography and Deep RIE etching to form the completed channel and lattice mold. Results indicating the quality of nanoscale features resulting from the molding process in Polydimethylsiloxane (PDMS) will be discussed.

  20. Using Three-Phase Flow of Immiscible Liquids to Prevent Coalescence of Droplets in Microfluidic Channels: Criteria to Identify theThird Liquid and Validation with Protein Crystallizations

    SciTech Connect

    Chen, D.; Li, L; Reyes, S; Adamson, D; Ismagilov, R

    2007-01-01

    This manuscript describes the effect of interfacial tensions on three-phase liquid-liquid-liquid flow in microfluidic channels and the use of this flow to prevent microfluidic plugs from coalescing. One problem in using microfluidic plugs as microreactors is the coalescence of adjacent plugs caused by the relative motion of plugs during flow. Here, coalescence of reagent plugs was eliminated by using plugs of a third immiscible liquid as spacers to separate adjacent reagent plugs. This work tested the requirements of interfacial tensions for plugs of a third liquid to be effective spacers. Two candidates satisfying the requirements were identified, and one of these liquids was used in the crystallization of protein human Tdp1 to demonstrate its compatibility with protein crystallization in plugs. This method for identifying immiscible liquids for use as a spacer will also be useful for applications involving manipulation of large arrays of droplets in microfluidic channels.

  1. Effect of nanostructures orientation on electroosmotic flow in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Eng Lim, An; Lim, Chun Yee; Cheong Lam, Yee; Taboryski, Rafael; Rui Wang, Shu

    2017-06-01

    Electroosmotic flow (EOF) is an electric-field-induced fluid flow that has numerous micro-/nanofluidic applications, ranging from pumping to chemical and biomedical analyses. Nanoscale networks/structures are often integrated in microchannels for a broad range of applications, such as electrophoretic separation of biomolecules, high reaction efficiency catalytic microreactors, and enhancement of heat transfer and sensing. Their introduction has been known to reduce EOF. Hitherto, a proper study on the effect of nanostructures orientation on EOF in a microfluidic channel is yet to be carried out. In this investigation, we present a novel fabrication method for nanostructure designs that possess maximum orientation difference, i.e. parallel versus perpendicular indented nanolines, to examine the effect of nanostructures orientation on EOF. It consists of four phases: fabrication of silicon master, creation of mold insert via electroplating, injection molding with cyclic olefin copolymer, and thermal bonding and integration of practical inlet/outlet ports. The effect of nanostructures orientation on EOF was studied experimentally by current monitoring method. The experimental results show that nanolines which are perpendicular to the microchannel reduce the EOF velocity significantly (approximately 20%). This flow velocity reduction is due to the distortion of local electric field by the perpendicular nanolines at the nanostructured surface as demonstrated by finite element simulation. In contrast, nanolines which are parallel to the microchannel have no effect on EOF, as it can be deduced that the parallel nanolines do not distort the local electric field. The outcomes of this investigation contribute to the precise control of EOF in lab-on-chip devices, and fundamental understanding of EOF in devices which utilize nanostructured surfaces for chemical and biological analyses.

  2. Microfluidic sieve valves

    DOEpatents

    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.

  3. Evanescent field-based optical fiber sensing device for measuring the refractive index of liquids in microfluidic channels.

    PubMed

    Polynkin, PaveL; Polynkin, Alexander; Peyghambarian, N; Mansuripur, Masud

    2005-06-01

    We report a simple optical sensing device capable of measuring the refractive index of liquids propagating in microfluidic channels. The sensor is based on a single-mode optical fiber that is tapered to submicrometer dimensions and immersed in a transparent curable soft polymer. A channel for liquid analyte is created in the immediate vicinity of the taper waist. Light propagating through the tapered section of the fiber extends into the channel, making the optical loss in the system sensitive to the refractive-index difference between the polymer and the liquid. The fabrication process and testing of the prototype sensing devices are described. The sensor can operate both as a highly responsive on-off device and in the continuous measurement mode, with an estimated accuracy of refractive-index measurement of approximately 5 x 10(-4).

  4. Between giant oscillations and uniform distribution of droplets: The role of varying lumen of channels in microfluidic networks

    NASA Astrophysics Data System (ADS)

    Cybulski, Olgierd; Jakiela, Slawomir; Garstecki, Piotr

    2015-12-01

    The simplest microfluidic network (a loop) comprises two parallel channels with a common inlet and a common outlet. Recent studies that assumed a constant cross section of the channels along their length have shown that the sequence of droplets entering the left (L) or right (R) arm of the loop can present either a uniform distribution of choices (e.g., RLRLRL⋯) or long sequences of repeated choices (RRR⋯LLL), with all the intermediate permutations being dynamically equivalent and virtually equally probable to be observed. We use experiments and computer simulations to show that even small variation of the cross section along channels completely shifts the dynamics either into the strong preference for highly grouped patterns (RRR⋯LLL) that generate system-size oscillations in flow or just the opposite—to patterns that distribute the droplets homogeneously between the arms of the loop. We also show the importance of noise in the process of self-organization of the spatiotemporal patterns of droplets. Our results provide guidelines for rational design of systems that reproducibly produce either grouped or homogeneous sequences of droplets flowing in microfluidic networks.

  5. Between giant oscillations and uniform distribution of droplets: The role of varying lumen of channels in microfluidic networks.

    PubMed

    Cybulski, Olgierd; Jakiela, Slawomir; Garstecki, Piotr

    2015-12-01

    The simplest microfluidic network (a loop) comprises two parallel channels with a common inlet and a common outlet. Recent studies that assumed a constant cross section of the channels along their length have shown that the sequence of droplets entering the left (L) or right (R) arm of the loop can present either a uniform distribution of choices (e.g., RLRLRL...) or long sequences of repeated choices (RRR...LLL), with all the intermediate permutations being dynamically equivalent and virtually equally probable to be observed. We use experiments and computer simulations to show that even small variation of the cross section along channels completely shifts the dynamics either into the strong preference for highly grouped patterns (RRR...LLL) that generate system-size oscillations in flow or just the opposite-to patterns that distribute the droplets homogeneously between the arms of the loop. We also show the importance of noise in the process of self-organization of the spatiotemporal patterns of droplets. Our results provide guidelines for rational design of systems that reproducibly produce either grouped or homogeneous sequences of droplets flowing in microfluidic networks.

  6. Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications.

    PubMed

    Attalla, R; Ling, C; Selvaganapathy, P

    2016-02-01

    The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print-head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 μm - 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 μm - 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi-layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0-40 m/min) and corresponding flow rates (1-30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

  7. Ultrasonic alignment of bio-functionalized magnetic beads and live cells in PDMS micro-fluidic channel.

    PubMed

    Islam, Afroja T; Siddique, Ariful H; Ramulu, T S; Reddy, Venu; Eu, Young-Jae; Cho, Seung Hyun; Kim, CheolGi

    2012-12-01

    In this work, we demonstrated the alignment of polystyrene latex microspheres (diameter of 1 ~45 μm), bio-functionalized superparamagnetic beads (diameter 2.8 μm), and live cells (average diameter 1 ~2 μm) using an ultrasonic standing wave (USW) in a PDMS microfluidic channel (330 μm width) attached on a Si substrate for bio-medical applications. To generate a standing wave inside the channel, ultrasound of 2.25 MHz resonance frequency (for the channel width) was applied by two ultrasound transducers installed at both sides of the channel which caused the radiation force to concentrate the micro-particles at the single pressure nodal plane of USW. By increasing the frequency to the next resonance condition of the channel, the particles were concentrated in dual nodal planes. Migration time of the micro-particles towards the single nodal plane was recorded as 108 s, 17 s, and 115 s for polystyrene particles of 2 μm diameter, bio-functionalized magnetic beads, and live cells, respectively. These successful alignments of the bio-functionalized magnetic beads along the desired part of the channel can enhance the performance of a sensor which is applicable for the bio-hybrid system and the alignment of live cells without any damage can be used for sample pre-treatment for the application of lab-on-a-chip type bioassays.

  8. Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel

    PubMed Central

    Jun Kang, Yang; Lee, Sang-Joon

    2013-01-01

    Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (μBlood/μPBS) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (QPBSSS/QBloodL). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formula (ABlood (t) = Aα + Aβ exp [−(t − t0)/λBlood]) is selected based on the pressure difference (ΔP = PA − PB) at each junction (A, B) of both side channels. The characteristic time of blood (λBlood) is measured by analyzing the area (ABlood) filled with blood in the bridge channel by selecting an appropriate detection window in the

  9. Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel.

    PubMed

    Jun Kang, Yang; Lee, Sang-Joon

    2013-01-01

    Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (μBlood /μPBS ) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (QPBS (SS) /QBlood (L) ). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formula (ABlood (t) = A α  + A β exp [-(t - t 0 )/λBlood ]) is selected based on the pressure difference (ΔP = PA  - PB ) at each junction (A, B) of both side channels. The characteristic time of blood (λBlood ) is measured by analyzing the area (ABlood ) filled with blood in the bridge channel by selecting an appropriate detection window in

  10. Quantification of the Mass Transfer at Fluid Interfaces in Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Wismeth, Carina; Manhart, Michael; Niessner, Reinhard; Baumann, Thomas

    2017-04-01

    Mass transfer rates at interfaces in a complex porous media are relevant in many environmental applications and control the functions of natural filter systems in subsurface environments. The mass transfer at fluid interfaces is associated with interface convection caused by local inhomogeneities in interface tension and hydrodynamic instabilities at the interface. If there is a surface tension gradient along the surface a shear stress jump is generated that results in fluid motion along the surface that is called Marangoni effect. These spontaneous convection currents can lead to an increased mass transfer of the transition component at the phase boundary and to an increased mixing of the phases. Therefore compensatory currents at the interface can have a significant influence on the subsurface transport of contaminants in the groundwater area, especially in the vadose zone. Using microfluidic channels and advanced experimental techniques it is possible to measure the fluid flow and mass transfer rates directly and to quantify the effect of the Marangoni convection on the mass transfer at interfaces between a non-aqueous liquid and water with high temporal and spatial resolution. The use of fluorescent particles as well as the recording and analysis of their trajectories is intended to visualize interfacial processes and to quantify the mass transfer at fluid phase boundaries. Concentration gradients at the interface are analysed by spectroscopic methods and allow an assessment of the enrichment and depletion at the phase boundaries. Extensive test series provide the experimental basis for quantifying and analysing the impact of the Marangoni effect on the mass transfer rates at interfaces in porous media in subsurface aquatic environments. Within this research project we concentrate on the effect of Marangoni convection on the mass transfer near an 1-octanol-water interface, which serves as a well defined proxy for non-aqueous phase liquids in porous media

  11. A microfluidic platform to study the mechano sensational properties of ion channels

    NASA Astrophysics Data System (ADS)

    Baratchi, Sara; Tovar-Lopez, Francisco J.; Khoshmanesh, Khashayar; Grace, Megan; Darby, William; McIntyre, Peter; Mitchell, Arnan

    2013-12-01

    Microfluidic platforms have been widely considered as an enabling technology for studying the ion transport phenomena of cells under precisely controlled shear stresses. Here, we report the application of a unique microfluidic platform to analyze the response of transgenic TRPV4-HEK293 cells in response to different shear stresses and in one field of view. Applying this system, we show the kinetics of calcium signalling at different shear stresses in TRPV4 positive cells and elucidate the threshold of their response. We show that there is direct correlation between the magnitude of shear stress and percentage of cells that are able to sense that level of shear. Further, we show that shear stress-induced elevation in intracellular calcium levels ([Ca2+]i) is through calcium influx from extracellular sources. The results demonstrate that the microfluidic system has unique capabilities for analysis of shear stress on adhesive cells and that it should be amenable to moderate throughput applications.

  12. Application of a multi-channel microfluidic chip on the simultaneous detection of DNAs by using microbead-quantum dots.

    PubMed

    Le, Ngoc Tam; Kim, Jong Sung

    2014-12-01

    Several researches have shown that cancer is caused by genetic mutations especially in genes involved in cell growth and regulation. Ras family members are frequently found in their mutated, oncogenic forms in human tumors. Mutant RAS proteins are constitutively active, owing to reduce intrinsic GTPase activity and insensitivity to GTPase-activating protein (GAPs). In total, activating mutations in the RAS genes occur in approximately 20% of all human cancers, mainly in codon 12, 13 or 61. Activating mutations in the NRAS gene not only result in the reduction of intrinsic GTPase activity but also in the induction of resistance against molecules inducing such activity. In this paper, we reported a rapid, simple and portable method for detecting the mutant types of NRAS genes codon 12 and 61 simultaneously by using bead-quantum dots (QDs) based multi-channel microfluidic chip. Probe DNAs are conjugated to bead-QDs and packed in the pillars of channels in the microfluidic chip. After injection of target DNAs and intercalating dyes, the fluorescence quenching of QDs by intercalating dye was observed due to FRET phenomena. The platform can be effortlessly applied in other biological and clinical areas.

  13. Hybrid microfluidics: a digital-to-channel interface for in-line sample processing and chemical separations.

    PubMed

    Abdelgawad, Mohamed; Watson, Michael W L; Wheeler, Aaron R

    2009-04-21

    Microchannels can separate analytes faster with higher resolution, higher efficiency and with lower reagent consumption than typical column techniques. Unfortunately, an impediment in the path toward fully integrated microchannel-based labs-on-a-chip is the integration of pre-separation sample processing. Although possible in microchannels, such steps are challenging because of the difficulty in maintaining spatial control over many reagents simultaneously. In contrast, the alternative format of digital microfluidics (DMF), in which discrete droplets are manipulated on an array of electrodes, is well-suited for carrying out sequential chemical reactions. Here, we report the development of the first digital-channel hybrid microfluidic device for integrated pre-processing reactions and chemical separations. The device was demonstrated to be useful for on-chip labeling of amino acids and primary amines in cell lysate, as well as enzymatic digestion of peptide standards, followed by separation in microchannels. Given the myriad applications requiring pre-processing and chemical separations, the hybrid digital-channel format has the potential to become a powerful new tool for micro total analysis systems.

  14. Three-dimensional microfluidic channel with arbitrary length and configuration fabricated inside glass by femtosecond laser direct writing.

    PubMed

    Liao, Yang; Ju, Yongfeng; Zhang, Long; He, Fei; Zhang, Qiang; Shen, Yinglong; Chen, Danping; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

    2010-10-01

    We demonstrate, for the first time to the best of our knowledge, fabrication of three-dimensional microfluidic channels with arbitrary lengths and configurations inside glass by femtosecond laser direct writing. The main fabrication process includes two steps: (1) direct formation of hollow microchannels in a porous glass substrate immersed in water by femtosecond laser ablation and (2) postannealing of the glass substrate at ∼1150°C by which the porous glass can be consolidated. We show that a square-wavelike channel with a total length of ∼1.4 cm and a diameter of ∼64 μm can be easily produced ∼250 μm beneath the glass surface.

  15. A simple PDMS-based microfluidic channel design that removes bubbles for long-term on-chip culture of mammalian cells.

    PubMed

    Zheng, Wenfu; Wang, Zhuo; Zhang, Wei; Jiang, Xingyu

    2010-11-07

    This report shows methods to fabricate polydimethylsiloxane (PDMS) microfluidic systems for long-term (up to 10 day) cell culture. Undesired bubble accumulation in microfluidic channels abruptly changes the microenvironment of adherent cells and leads to the damage and death of cells. Existing bubble trapping approaches have drawbacks such as the need to pause fluid flow, requirement for external vacuum or pressure source, and possible cytotoxicity. This study reports two kinds of integrated bubble trap (IBT) which have excellent properties, including simplicity in structure, ease in fabrication, no interference with the flow, and long-term stability. IBT-A provides the simplest solution to prevent bubbles from entering microfluidic channels. In situ time-lapse imaging experiments indicate that IBT-B is an excellent device both for bubble trapping and debubbling in cell-loaded microfluidics. MC 3T3 E1 cells, cultured in a long and curved microfluidic channel equipped with IBT-B, showed high viability and active proliferation after 10 days of continuous fluid flow. The comprehensive measures taken in our experiments have led to successful long-term, bubble-free, on-chip culture of cells.

  16. Endothelial cell behaviour within a microfluidic mimic of the flow channels of a modular tissue engineered construct

    PubMed Central

    Khan, Omar F.

    2011-01-01

    To study the effect of disturbed flow patterns on endothelial cells, the channels found within a modular tissue engineering construct were reproduced in a microfluidic chip and lined with endothelial cells whose resulting phenotype under flow was assessed using confocal microscopy. Modular tissue engineered constructs formed by the random packing of sub-millimetre, cylindrically shaped, endothelial cell-covered modules into a larger container creates interconnected channels that permit the flow of fluids such as blood. Due to the random packing, the flow path is tortuous and has the potential to create disturbed flow, resulting in an activated endothelium. At an average shear stress of 2.8 dyn cm−2, endothelial cells within channels of varying geometries showed higher amounts of activation, as evidenced by an increase in ICAM-1 and VCAM-1 levels with respect to static controls. VE-cadherin expression also increased, however, it appeared discontinuous around the perimeter of the cells. An increase in flow (15.6 dyn cm−2) was sufficient to reduce ICAM-1 and VCAM-1 expression to a level below that of static controls for many disturbed flow-prone channels that contained branches, curves, expansions and contractions. VE-cadherin expression was also reduced and became discontinuous in all channels, possibly due to paracrine signaling. Other than showing a mild correlation to VE-cadherin, which may be linked through a cAMP-initiated pathway, KLF2 was found to be largely independent of shear stress for this system. To gauge the adhesiveness of the endothelium to leukocytes, THP-1 cells were introduced into flow-conditioned channels and their attachment measured. Relative to static controls, THP-1 adhesion was reduced in straight and bifurcating channels. However, even in the presence of flow, areas where multiple channels converged were found to be the most prone to THP-1 attachment. The microfluidic system enabled a full analysis of the effect of the tortuous flow

  17. Highly stable liquid metal-based pressure sensor integrated with a microfluidic channel.

    PubMed

    Jung, Taekeon; Yang, Sung

    2015-05-21

    Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30-1000 s(-1). The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability.

  18. Highly Stable Liquid Metal-Based Pressure Sensor Integrated with a Microfluidic Channel

    PubMed Central

    Jung, Taekeon; Yang, Sung

    2015-01-01

    Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30–1000 s−1. The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability. PMID:26007732

  19. Dynamic high pressure microfluidization-assisted extraction and bioactivities of Cyperus esculentus (C. esculentus L.) leaves flavonoids.

    PubMed

    Jing, Siqun; Wang, Saisai; Li, Qian; Zheng, Lian; Yue, Li; Fan, Shaoli; Tao, Guanjun

    2016-02-01

    The aim of this work was to study the effect of dynamic high pressure microfluidization (DHPM) on extracting total flavonoids from Cyperus esculentus L. (C. esculentus L.) leaves and to evaluate the antioxidant activity and antibacterial property of these flavonoids. In all the assays, pretreatment with DHPM was found to not only efficiently improve the yield of total flavonoids but also strengthen the antioxidant activity of the total flavonoids. C. esculentus L. leaves flavonoids had pronounced antioxidant activity in vivo that could significantly elevate the content of superoxide dismutase (SOD) without increasing the malondialdehyde (MDA) levels, and could also improve total antioxidant capacity in mice with a dose-dependent fashion. C. esculentus L. leaves flavonoids inhibited the growth of both Gram positive and Gram negative bacteria while no obvious inhibitory effect on Penicillium and Aspergillus could be observed. Our studies indicate that flavonoids from C. esculentus L. leaves can be taken as a natural antioxidant and bacteriostatic substance in food and pharmaceutical industry.

  20. Continuous focusing of microparticles using inertial lift force and vorticity via multi-orifice microfluidic channels.

    PubMed

    Park, Jae-Sung; Song, Suk-Heung; Jung, Hyo-Il

    2009-04-07

    We developed a new microfluidic method for focusing microparticles through the combined use of inertial lift forces and turbulent secondary flows generated in a topographically patterned microchannel. The mechanism of particle focusing is based on the hydrodynamic inertial forces exerted on particles migrating along a non-circular microchannel, i.e.tubular pinch effect and wall effect, which induce particle movement away from walls and along a specific lateral position in the microchannel. With the extraordinary geometry of multi-orifice microchannel, an ordered and focused particle distribution was achieved at central or side regions according to a particle Reynolds number (Re(p)) range. The focusing of particles was controlled by the particle Reynolds number, microchannel length, and volume fraction of particles in suspension. This method will be beneficial in particle focusing processes in a microfluidic device since it offers continuous, high-throughput performance and simple operation.

  1. Multi-Channel Microfluidic Biosensor Platform Applied for Online Monitoring and Screening of Biofilm Formation and Activity

    PubMed Central

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

    2015-01-01

    Bacterial colonization of surfaces and interfaces has a major impact on various areas including biotechnology, medicine, food industries, and water technologies. In most of these areas biofilm development has a strong impact on hygiene situations, product quality, and process efficacies. In consequence, biofilm manipulation and prevention is a fundamental issue to avoid adverse impacts. For such scenario online, non-destructive biofilm monitoring systems become important in many technical and industrial applications. This study reports such a system in form of a microfluidic sensor platform based on the combination of electrical impedance spectroscopy and amperometric current measurement, which allows sensitive online measurement of biofilm formation and activity. A total number of 12 parallel fluidic channels enable real-time online screening of various biofilms formed by different Pseudomonas aeruginosa and Stenotrophomonas maltophilia strains and complex mixed population biofilms. Experiments using disinfectant and antibiofilm reagents demonstrate that the biofilm sensor is able to discriminate between inactivation/killing of bacteria and destabilization of biofilm structures. The impedance and amperometric sensor data demonstrated the high dynamics of biofilms as a consequence of distinct responses to chemical treatment strategies. Gene expression of flagellar and fimbrial genes of biofilms grown inside the microfluidic system supported the detected biofilm growth kinetics. Thus, the presented biosensor platform is a qualified tool for assessing biofilm formation in specific environments and for evaluating the effectiveness of antibiofilm treatment strategies. PMID:25706987

  2. Multi-channel microfluidic biosensor platform applied for online monitoring and screening of biofilm formation and activity.

    PubMed

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

    2015-01-01

    Bacterial colonization of surfaces and interfaces has a major impact on various areas including biotechnology, medicine, food industries, and water technologies. In most of these areas biofilm development has a strong impact on hygiene situations, product quality, and process efficacies. In consequence, biofilm manipulation and prevention is a fundamental issue to avoid adverse impacts. For such scenario online, non-destructive biofilm monitoring systems become important in many technical and industrial applications. This study reports such a system in form of a microfluidic sensor platform based on the combination of electrical impedance spectroscopy and amperometric current measurement, which allows sensitive online measurement of biofilm formation and activity. A total number of 12 parallel fluidic channels enable real-time online screening of various biofilms formed by different Pseudomonas aeruginosa and Stenotrophomonas maltophilia strains and complex mixed population biofilms. Experiments using disinfectant and antibiofilm reagents demonstrate that the biofilm sensor is able to discriminate between inactivation/killing of bacteria and destabilization of biofilm structures. The impedance and amperometric sensor data demonstrated the high dynamics of biofilms as a consequence of distinct responses to chemical treatment strategies. Gene expression of flagellar and fimbrial genes of biofilms grown inside the microfluidic system supported the detected biofilm growth kinetics. Thus, the presented biosensor platform is a qualified tool for assessing biofilm formation in specific environments and for evaluating the effectiveness of antibiofilm treatment strategies.

  3. Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels.

    PubMed

    Haque, Amranul; Gheibi, Pantea; Gao, Yandong; Foster, Elena; Son, Kyung Jin; You, Jungmok; Stybayeva, Gulnaz; Patel, Dipali; Revzin, Alexander

    2016-09-29

    The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-β1. Hepatocytes are not generally thought of as significant producers of GFs-this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function.

  4. Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels

    PubMed Central

    Haque, Amranul; Gheibi, Pantea; Gao, Yandong; Foster, Elena; Son, Kyung Jin; You, Jungmok; Stybayeva, Gulnaz; Patel, Dipali; Revzin, Alexander

    2016-01-01

    The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-β1. Hepatocytes are not generally thought of as significant producers of GFs–this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function. PMID:27681582

  5. Dynamic micro-Hall detection of superparamagnetic beads in a microfluidic channel.

    PubMed

    Aledealat, K; Mihajlović, G; Chen, K; Field, M; Sullivan, G J; Xiong, P; Chase, P B; von Molnár, S

    2010-12-01

    We report integration of an InAs quantum well micro-Hall magnetic sensor with microfluidics and real-time detection of moving superparamagnetic beads. Beads moving within and around the Hall cross area result in positive and negative Hall voltage signals respectively. Relative magnitudes and polarities of the signals measured for a random distribution of immobilized beads over the sensor are in good agreement with calculated values and explain consistently the shape of the dynamic signal.

  6. Long-term improvements to photoluminescence and dispersion stability by flowing SDS-SWNT suspensions through microfluidic channels.

    PubMed

    Silvera-Batista, Carlos A; Weinberg, Philip; Butler, Jason E; Ziegler, Kirk J

    2009-09-09

    Shearing single-walled carbon nanotubes (SWNTs) coated with sodium dodecyl sulfate in microfluidic channels significantly increases the photoluminescence (PL) intensity and dispersion stability of SWNTs. The PL quantum yield (QY) of SWNTs improves by a factor of 3 for initially bright suspensions; on the other hand, SWNT QYs in a "poor" suspension improve by 2 orders of magnitude. In both cases, the QYs of the sheared suspensions are approximately 1%. The increases in PL intensity persist for months and are most prominent in larger diameter SWNTs. These improvements are attributed to surfactant reorganization rather than disaggregation of SWNTs bundles or shear-induced alignment. The results also highlight potential opportunities to eliminate discrepancies in the PL intensity of different suspensions and further improve the PL of SWNTs by tailoring the surfactant structure around SWNTs.

  7. Microfluidic waves

    PubMed Central

    Utz, Marcel; Begley, Matthew R.; Haj-Hariri, Hossein

    2012-01-01

    The propagation of pressure waves in fluidic channels with elastic covers is discussed in view of applications to flow control in microfluidic devices. A theory is presented which describes pressure waves in the fluid that are coupled to bending waves in the elastic cover. At low frequencies, the lateral bending of the cover dominates over longitudinal bending, leading to propagating, non-dispersive longitudinal pressure waves in the channel. The theory addresses effects due to both the finite viscosity and compressibility of the fluid. The coupled waves propagate without dispersion, as long as the wave length is larger than the channel width. It is shown that in channels of typical microfluidic dimensions, wave velocities in the range of a few 10 m s−1 result if the channels are covered by films of a compliant material such as PDMS. The application of this principle to design microfluidic band pass filters based on standing waves is discussed. Characteristic frequencies in the range of a few kHz are readily achieved with quality factors above 30. PMID:21966667

  8. Formation of droplets of alternating composition in microfluidic channels and applications to indexing of concentrations in droplet-based assays.

    PubMed

    Zheng, Bo; Tice, Joshua D; Ismagilov, Rustem F

    2004-09-01

    For screening the conditions for a reaction by using droplets (or plugs) as microreactors, the composition of the droplets must be indexed. Indexing here refers to measuring the concentration of a solute by addition of a marker, either internal or external. Indexing may be performed by forming droplet pairs, where in each pair the first droplet is used to conduct the reaction, and the second droplet is used to index the composition of the first droplet. This paper characterizes a method for creating droplet pairs by generating alternating droplets, of two sets of aqueous solutions in a flow of immiscible carrier fluid within PDMS and glass microfluidic channels. The paper also demonstrates that the technique can be used to index the composition of the droplets, and this application is illustrated by screening conditions of protein crystallization. The fluid properties required to form the steady flow of the alternating droplets in a microchannel were characterized as a function of the capillary number Ca and water fraction. Four regimes were observed. At the lowest values of Ca, the droplets of the two streams coalesced; at intermediate values of Ca the alternating droplets formed reliably. At even higher values of Ca, shear forces dominated and caused formation of droplets that were smaller than the cross-sectional dimension of the channel; at the highest values of Ca, coflowing laminar streams of the two immiscible fluids formed. In addition to screening of protein crystallization conditions, understanding of the fluid flow in this system may extend this indexing approach to other chemical and biological assays performed on a microfluidic chip.

  9. In situ and online monitoring of hydrodynamic flow profiles in microfluidic channels based upon microelectrochemistry: concept, theory, and validation.

    PubMed

    Amatore, Christian; Oleinick, Alexander; Klymenko, Oleksiy V; Svir, Irina

    2005-08-12

    Herein, we propose a method for reconstructing any plausible macroscopic hydrodynamic flow profile occurring locally within a rectangular microfluidic channel. The method is based on experimental currents measured at single or double microband electrodes embedded in one channel wall. A perfectly adequate quasiconformal mapping of spatial coordinates introduced in our previous work [Electrochem. Commun. 2004, 6, 1123] and an exponentially expanding time grid, initially proposed [J. Electroanal. Chem. 2003, 557, 75] in conjunction with the solution of the corresponding variational problem approached by the Ritz method are used for the numerical reconstruction of flow profiles. Herein, the concept of the method is presented and developed theoretically and its validity is tested on the basis of the use of pseudoexperimental currents emulated by simulation of the diffusion-convection problem in a channel flow cell, to which a random Gaussian current noise is added. The flow profiles reconstructed by our method compare successfully with those introduced a priori into the simulations, even when these include significant distortions compared with either classical Poiseuille or electro-osmotic flows.

  10. Janus droplet parallel arrangements using a simple Y-channel flow-focusing microfluidic device

    NASA Astrophysics Data System (ADS)

    Cheng, Long; Cai, Bo; Zuo, Yunfeng; Xiao, Liang; Rao, Lang; He, Zhaobo; Yang, Yi; Liu, Wei; Guo, Shishang; Zhao, Xing-Zhong

    2017-04-01

    Due to its unique advantages such as monodispersity and high throughput, droplet microfluidics has been widely used to generate diverse droplets/particles that have specific structures. Herein, we implemented Janus droplet parallel arrangements in a flow-focusing microchip through regulating corresponding fluid flow rates. Initially, fluorescence dye and PBS buffer solution kept laminar flow before the flow-focusing orifice and then was sheared into Janus droplets. Droplet diameter and corresponding generation frequency could be effectively manipulated. Subsequently, the generation of different Janus droplet parallel arrangements (e.g. monolayer, double-layer or three-layer arrangement) could be achieved by fluid regulation.

  11. In-situ photopolymerization of monodisperse and discoid oxidized methacrylated alginate microgels in a microfluidic channel

    DOE PAGES

    Wang, Shuo; Jeon, Oju; Shankles, Peter G.; ...

    2016-02-03

    Here, we present a simple microfluidic technique to in-situ photopolymerize (by 365 nm ultraviolet) monodisperse oxidized methacrylated alginate (OMA) microgels using a photoinitiator (VA-086). By this technique, we generated monodisperse spherical OMA beads and discoid non-spherical beads with better shape consistency than ionic crosslinking methods do. We found that a high monomer concentration (8 w/v %), a high photoinitiator concentration (1.5 w/v %) and absence of oxygen are critical factors to cure OMA microgels. This photopolymerizing method is an alternative to current methods to form alginate microgels and is a simpler approach to generate non-spherical alginate microgels.

  12. Low-dispersion electrokinetic flows for expanded separation channels in microfluidic systems: multiple faceted interfaces.

    PubMed

    Fiechtner, Gregory J; Cummings, Eric B

    2004-02-20

    A novel methodology to design on-chip conduction channels is presented for expansion of low-dispersion separation channels. Designs are examined using two-dimensional numerical solutions of the Laplace equation with a Monte Carlo technique to model diffusion. The design technique relies on trigonometric relations that apply for ideal electrokinetic flows. Flows are rotated and stretched along the abrupt interface between adjacent regions having differing specific permeability. Multiple interfaces can be placed in series along a channel. The resulting channels can be expanded to extreme widths while minimizing dispersion of injected analyte bands. These channels can provide a long path length for line-of-sight optical absorption measurements. Expanded sections can be reduced to enable point detection at the exit section of the channel. Designed to be shallow, these channels have extreme aspect ratios in the wide section, greatly increasing the surface-to-volume ratio to increase heat removal and decrease unwanted pressure-driven flow. The use of multiple interfaces is demonstrated by considering several three-interface designs. Faceted flow splitters can be constructed to divide channels into any number of exit channels while minimizing dispersion. The resulting manifolds can be used to construct medians for structural support in wide, shallow channels.

  13. On controlling the flow behavior driven by induction electrohydrodynamics in microfluidic channels.

    PubMed

    Li, Yanbo; Ren, Yukun; Liu, Weiyu; Chen, Xiaoming; Tao, Ye; Jiang, Hongyuan

    2017-04-01

    In this study, we develop a nondimensional physical model to demonstrate fluid flow at the micrometer dimension driven by traveling-wave induction electrohydrodynamics (EHD) through direct numerical simulation. In order to realize an enhancement in the pump flow rate as well as a flexible adjustment of anisotropy of flow behavior generated by induction EHD in microchannels, while not adding the risk of causing dielectric breakdown of working solution and material for insulation, a pair of synchronized traveling-wave voltage signals are imposed on double-sided electrode arrays that are mounted on the top and bottom insulating substrate, respectively. Accordingly, we present a model evidence, that not only the pump performance is improved evidently, but a variety of flow profiles, including the symmetrical and parabolic curve, plug-like shape and even biased flow behavior of quite high anisotropy are produced by the device design of "mix-type", "superimposition-type" and "adjustable-type" proposed herein as well, with the resulting controllable fluid motion being able to greatly facilitate an on-demand transportation mode of on-chip bio-microfluidic samples. Besides, automatic conversion in the direction of pump flow is achievable by switching on and off a second voltage wave. Our results provide utilitarian guidelines for constructing flexible electrokinetic framework useful in controllable transportation of particle and fluid samples in modern microfluidic systems. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Elastic effects of dilute polymer solution on bubble generation in a microfluidic flow-focusing channel

    NASA Astrophysics Data System (ADS)

    Kim, Dong Young; Shim, Tae Soup; Kim, Ju Min

    2017-05-01

    Recently, two-phase flow in microfluidics has attracted much attention because of its importance in generating droplets or bubbles that can be used as building blocks for material synthesis and biological applications. However, there are many unresolved issues in understanding droplet and bubble generation processes, especially when complex fluids are involved. In this study, we investigated elastic effects on bubble generation processes in a flow-focusing geometry and the shapes of the produced bubbles flowing through a microchannel. We used dilute polymer solutions with nearly constant shear viscosities so that the shear-thinning effects on bubble generation could be precluded. We observed that a very small amount of polymer (poly(ethylene oxide) at O(10) ppm) significantly affects bubble generation. When the polymer was added to a Newtonian fluid, the fluctuation in bubble size increased notably, which was attributed to the chaotic flow dynamics in the flow-focusing region. In addition, it was demonstrated that the bubbles were thinner along the minor axis in the viscoelastic fluid than they were in the Newtonian fluid. We expect that the current results will contribute to understanding the dynamics of two-phase flow in microchannels and the design and operation of the microfluidic devices to generate microbubbles.

  15. PDMS bonding to a bio-friendly photoresist via self-polymerized poly(dopamine) adhesive for complex protein micropatterning inside microfluidic channels.

    PubMed

    Kim, Miju; Song, Kwang Hoon; Doh, Junsang

    2013-12-01

    Protein micropatterned surfaces integrated with microfluidics are useful in numerous bioanalytical and biological applications. In this study, we demonstrated the fabrication of complex protein micropatterned surfaces within poly(dimethylsiloxane) (PDMS) microfluidic channels by attaching the PDMS channels to bio-friendly photoresist films and subsequently performing microscope projection photolithography (MPP). A muscle-inspired poly(dopamine) (PDA) coating was employed to mediate the bonding between the PDMS and the bio-friendly photoresist poly(2,2-dimethoxy nitrobenzyl methacrylate-r-methyl methacrylate-r-poly(ethylene glycol) methacrylate) (PDMP). By adjusting the dip-coating time for the PDA coating, we could successfully introduce sufficient amounts of functional groups on the PDMP surfaces to mediate strong bonding between the PDMS channels and the PDA-coated PDMP thin films with minimal alteration of the surface properties of the PDMP thin films that are critical for protein micropatterning. Using this novel bonding strategy, we successfully fabricated multiple protein micropatterns and gradient micropatterns of proteins within microfluidic channels. The technique developed in this study will be useful for the fabrication of complex biochips for multiplex bioassays and fundamental cell biological studies.

  16. Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

    PubMed Central

    Merlo, Adlan; Duru, Paul; Risso, Frédéric; Lorthois, Sylvie

    2016-01-01

    Despite the development of microfluidics, experimental challenges are considerable for achieving a quantitative study of phase separation, i.e., the non-proportional distribution of Red Blood Cells (RBCs) and suspending fluid, in microfluidic bifurcations with channels smaller than 20 μm. Yet, a basic understanding of phase separation in such small vessels is needed for understanding the coupling between microvascular network architecture and dynamics at larger scale. Here, we present the experimental methodologies and measurement techniques developed for that purpose for RBC concentrations (tube hematocrits) ranging between 2% and 20%. The maximal RBC velocity profile is directly measured by a temporal cross-correlation technique which enables to capture the RBC slip velocity at walls with high resolution, highlighting two different regimes (flat and more blunted ones) as a function of RBC confinement. The tube hematocrit is independently measured by a photometric technique. The RBC and suspending fluid flow rates are then deduced assuming the velocity profile of a Newtonian fluid with no slip at walls for the latter. The accuracy of this combination of techniques is demonstrated by comparison with reference measurements and verification of RBC and suspending fluid mass conservation at individual bifurcations. The present methodologies are much more accurate, with less than 15% relative errors, than the ones used in previous in vivo experiments. Their potential for studying steady state phase separation is demonstrated, highlighting an unexpected decrease of phase separation with increasing hematocrit in symmetrical, but not asymmetrical, bifurcations and providing new reference data in regimes where in vitro results were previously lacking. PMID:27190568

  17. High-throughput miniaturized microfluidic microscopy with radially parallelized channel geometry.

    PubMed

    Jagannadh, Veerendra Kalyan; Bhat, Bindu Prabhath; Nirupa Julius, Lourdes Albina; Gorthi, Sai Siva

    2016-03-01

    In this article, we present a novel approach to throughput enhancement in miniaturized microfluidic microscopy systems. Using the presented approach, we demonstrate an inexpensive yet high-throughput analytical instrument. Using the high-throughput analytical instrument, we have been able to achieve about 125,880 cells per minute (more than one hundred and twenty five thousand cells per minute), even while employing cost-effective low frame rate cameras (120 fps). The throughput achieved here is a notable progression in the field of diagnostics as it enables rapid quantitative testing and analysis. We demonstrate the applicability of the instrument to point-of-care diagnostics, by performing blood cell counting. We report a comparative analysis between the counts (in cells per μl) obtained from our instrument, with that of a commercially available hematology analyzer.

  18. Engineering optical properties of a graphene oxide metamaterial assembled in microfluidic channels.

    PubMed

    Kravets, V G; Marshall, O P; Nair, R R; Thackray, B; Zhukov, A; Leng, J; Grigorenko, A N

    2015-01-26

    The dense packing of two dimensional flakes by van der Waals forces has enabled the creation of new metamaterials with desirable optical properties. Here we assemble graphene oxide sheets into a three dimensional metamaterial using a microfluidic technique and confirm their ordering via measurements of ellipsometric parameters, polarized optical microscopy, polarized transmission spectroscopy, infrared spectroscopy and scanning electron microscopy. We show that the produced metamaterials demonstrate strong in-plane optical anisotropy (Δn≈0.3 at n≈1.5-1.8) combined with low absorption (k<0.1) and compare them with as-synthesized samples of graphene oxide paper. Our results pave the way for engineered birefringent metamaterials on the basis of two dimensional atomic crystals including graphene and its derivatives.

  19. Mild and Selective C–H Activation of COC Microfluidic Channels Allowing Covalent Multifunctional Coatings

    PubMed Central

    2017-01-01

    Plastics, such as cyclic olefin copolymer (COC), are becoming an increasingly popular material for microfluidics. COC is used, in part, because of its (bio)-chemical resistance. However, its inertness and hydrophobicity can be a major downside for many bioapplications. In this paper, we show the first example of a surface-bound selective C–H activation of COC into alcohol C–OH moieties under mild aqueous conditions at room temperature. The nucleophilic COC–OH surface allows for subsequent covalent attachments, such as of a H-terminated silane. The resulting hybrid material (COC–Si-H) was then modified via a photolithographic hydrosilylation in the presence of ω-functionalized 1-alkenes to form a new highly stable, solvent-resistant hybrid surface. PMID:28481097

  20. Acoustic streaming in a microfluidic channel with a reflector: Case of a standing wave generated by two counterpropagating leaky surface waves

    NASA Astrophysics Data System (ADS)

    Doinikov, Alexander A.; Thibault, Pierre; Marmottant, Philippe

    2017-07-01

    A theory is developed for the modeling of acoustic streaming in a microfluidic channel confined between an elastic solid wall and a rigid reflector. A situation is studied where the acoustic streaming is produced by two leaky surface waves that propagate towards each other in the solid wall and thus form a combined standing wave in the fluid. Full analytical solutions are found for both the linear acoustic field and the field of the acoustic streaming. A dispersion equation is derived that allows one to calculate the wave speed in the system under study. The obtained solutions are used to consider particular numerical examples and to reveal the structure of the acoustic streaming. It is shown that two systems of vortices are established along the boundaries of the microfluidic channel.

  1. Hierarchical supramolecular spinning of nanofibers in a microfluidic channel: tuning nanostructures at a dynamic interface.

    PubMed

    Numata, Munenori; Takigami, Yusuke; Takayama, Momoko; Kozawa, Tomohiro; Hirose, Naoya

    2012-10-08

    One of the fundamental problems in supramolecular chemistry, as well as in material sciences, is how to control the self-assembly of polymers on the nanometer scale and how to spontaneously organize them towards the macroscopic scale. To overcome this problem, inspired by the self-assembly systems in nature, which feature the dynamically controlled self-assembly of biopolymers, we have previously proposed a self-assembly system that uses a dynamic liquid/liquid interface with dimensions in the micrometer regime, thereby allowing polymers to self-assemble under precisely controlled nonequilibrium conditions. Herein, we further extend this system to the creation of hierarchical self-assembled architectures of polysaccharides. A natural polysaccharide, β-1,3-glucan (SPG), and water were injected into opposite "legs" of microfluidic devices that had a Y-shape junction, so that two solvents would gradually mix in the down stem, thereby causing SPG to spontaneously self-assemble along the flow in a head-to-tail fashion, mainly through hydrophobic interactions. In the initial stage, several SPG nanofibers would self-assemble at the Y-junction owing to the shearing force, thereby creating oligomers with a three-way junction point. This unique structure, which could not be created through conventional mixing procedures, has a divergent self-assembly capability. The dynamic flow allows the oligomers to interact continuously with SPG nanofibers that are fed into the Y-junction, thus amplifying the nanostructure along the flow to form SPG networks. Consequently, we were able to create stable, centimeter-length macroscopic polysaccharide strands under the selected flow conditions, which implies that SPG nanofibers were assembled hierarchically in a supramolecular fashion in the dynamic flow. Microscopic observations, including SEM and AFM analysis, revealed the existence of clear hierarchical structures inside the obtained strand. The network structures self-assembled to form

  2. Monolithic cell counter based on 3D hydrodynamic focusing in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Paiè, Petra; Bragheri, Francesca; Osellame, Roberto

    2014-03-01

    Hydrodynamic focusing is a powerful technique frequently used in microfluidics that presents a wide range of applications since it allows focusing the sample flowing in the device to a narrow region in the center of the microchannel. In fact thanks to the laminarity of the fluxes in microchannels it is possible to confine the sample solution with a low flow rate by using a sheath flow with a higher flow rate. This in turn allows the flowing of one sample element at a time in the detection region, thus enabling analysis on single particles. Femtosecond laser micromachining is ideally suited to fabricate device integrating full hydrodynamic focusing functionalities thanks to the intrinsic 3D nature of this technique, especially if compared to expensive and complicated lithographic multi-step fabrication processes. Furthermore, because of the possibility to fabricate optical waveguides with the same technology, it is possible to obtain compact optofluidic devices to perform optical analysis of the sample even at the single cell level, as is the case for optical cell stretchers and sorters. In this work we show the fabrication and the fluidic characterization of extremely compact devices having only two inlets for 2D (both in vertical and horizontal planes) as well as full 3D symmetric hydrodynamic focusing. In addition we prove one of the possible application of the hydrodynamic focusing module, by fabricating and validating (both with polystyrene beads and erythrocytes) a monolithic cell counter obtained by integrating optical waveguides in the 3D hydrodynamic focusing device.

  3. Precise spatial and temporal control of oxygen within in vitro brain slices via microfluidic gas channels.

    PubMed

    Mauleon, Gerardo; Fall, Christopher P; Eddington, David T

    2012-01-01

    The acute brain slice preparation is an excellent model for studying the details of how neurons and neuronal tissue respond to a variety of different physiological conditions. But open slice chambers ideal for electrophysiological and imaging access have not allowed the precise spatiotemporal control of oxygen in a way that might realistically model stroke conditions. To address this problem, we have developed a microfluidic add-on to a commercially available perfusion chamber that diffuses oxygen throughout a thin membrane and directly to the brain slice. A microchannel enables rapid and efficient control of oxygen and can be modified to allow different regions of the slice to experience different oxygen conditions. Using this novel device, we show that we can obtain a stable and homogeneous oxygen environment throughout the brain slice and rapidly alter the oxygen tension in a hippocampal slice. We also show that we can impose different oxygen tensions on different regions of the slice preparation and measure two independent responses, which is not easily obtainable with current techniques.

  4. Characterizing relationship between optical microangiography signals and capillary flow using microfluidic channels

    PubMed Central

    Choi, Woo June; Qin, Wan; Chen, Chieh-Li; Wang, Jingang; Zhang, Qinqin; Yang, Xiaoqi; Gao, Bruce Z.; Wang, Ruikang K.

    2016-01-01

    Optical microangiography (OMAG) is a powerful optical angio-graphic tool to visualize micro-vascular flow in vivo. Despite numerous demonstrations for the past several years of the qualitative relationship between OMAG and flow, no convincing quantitative relationship has been proven. In this paper, we attempt to quantitatively correlate the OMAG signal with flow. Specifically, we develop a simplified analytical model of the complex OMAG, suggesting that the OMAG signal is a product of the number of particles in an imaging voxel and the decorrelation of OCT (optical coherence tomography) signal, determined by flow velocity, inter-frame time interval, and wavelength of the light source. Numerical simulation with the proposed model reveals that if the OCT amplitudes are correlated, the OMAG signal is related to a total number of particles across the imaging voxel cross-section per unit time (flux); otherwise it would be saturated but its strength is proportional to the number of particles in the imaging voxel (concentration). The relationship is validated using microfluidic flow phantoms with various preset flow metrics. This work suggests OMAG is a promising quantitative tool for the assessment of vascular flow. PMID:27446700

  5. Straightforward 3D hydrodynamic focusing in femtosecond laser fabricated microfluidic channels.

    PubMed

    Paiè, Petra; Bragheri, Francesca; Vazquez, Rebeca Martinez; Osellame, Roberto

    2014-06-07

    We report on the use of femtosecond laser irradiation followed by chemical etching as a microfabrication tool for innovative microfluidic networks that implement hydrodynamic focusing. The capability of our microfabrication technology to interconnect microchannels in three dimensions was exploited to demonstrate 2D hydrodynamic focusing, either in the horizontal or in the vertical plane, and full 3D hydrodynamic focusing. In all cases only two inlets were required, one for the sample and one for the sheath flows. Fluidic characterization of all devices was provided. In addition, taking advantage of the possibility to write optical waveguides using the same technology, a monolithic cell counter based on 3D hydrodynamic focusing and integrated optical detection was validated. Counting rates up to 5000 cells s(-1) were achieved in this very compact device, where focusing and counting operations were implemented in less than 1 mm(3). Integration of this hydrodynamic focusing module into several devices fabricated by the same technology as optical cell stretchers and cell sorters is envisaged.

  6. Thermocouples fabricated on trench sidewall in microfluidic channel bonded with film cover

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Takahiro; Shibata, Masahiro; Kumagai, Shinya; Sasaki, Minoru

    2015-03-01

    Thermocouples on a trench sidewall fronting a flow are fabricated by three-dimensional (3D) photolithography. The conventional thermocouples on the wafer top surface are also fabricated. The performances of these devices are compared. Without the flow inside the microchannel, the thermocouple on the trench sidewall shows the same output voltage as that on the wafer top surface positioned 40 µm from the channel. As a static response, when the microchannel is heated and room-temperature air flows inside the channel, the thermocouple on the sidewall shows a lower voltage. As a dynamic response, when hot air flows inside the channel and replaces the room-temperature air, the thermocouple on the sidewall shows a faster response, increasing its output voltage, and the local temperature of the flow can be measured more precisely.

  7. A parallel microfluidic channel fixture fabricated using laser ablated plastic laminates for electrochemical and chemiluminescent biodetection of DNA

    PubMed Central

    Edwards, Thayne L.; Harper, Jason C.; Polsky, Ronen; Lopez, DeAnna M.; Wheeler, David R.; Allen, Amy C.; Brozik, Susan M.

    2011-01-01

    Herein is described the fabrication and use of a plastic multilayer 3-channel microfluidic fixture. Multilayer devices were produced by laser machining of plastic polymethylmethacrylate and polyethyleneterapthalate laminates by ablation. The fixture consisted of an array of nine individually addressable gold or gold/ITO working electrodes, and a resistive platinum heating element. Laser machining of both the fluidic pathways in the plastic laminates, and the stencil masks used for thermal evaporation to form electrode regions on the plastic laminates, enabled rapid and inexpensive implementation of design changes. Electrochemiluminescence reactions in the fixture were achieved and monitored through ITO electrodes. Electroaddressable aryl diazonium chemistry was employed to selectively pattern gold electrodes for electrochemical multianalyte DNA detection from double stranded DNA (dsDNA) samples. Electrochemical detection of dsDNA was achieved by melting of dsDNA molecules in solution with the integrated heater, allowing detection of DNA sequences specific to breast and colorectal cancers with a non-specific binding control. Following detection, the array surface could be renewed via high temperature (95 °C) stripping using the integrated heating element. This versatile and simple method for prototyping devices shows potential for further development of highly integrated, multi-functional bioanalytical devices. PMID:22276087

  8. Three-dimensional continuous particle focusing in a microfluidic channel via standing surface acoustic waves (SSAW)†

    PubMed Central

    Shi, Jinjie; Yazdi, Shahrzad; Lin, Sz-Chin Steven; Ding, Xiaoyun; Chiang, I-Kao; Sharp, Kendra; Huang, Tony Jun

    2014-01-01

    Three-dimensional (3D) continuous microparticle focusing has been achieved in a single-layer polydimethylsiloxane (PDMS) microfluidic channel using a standing surface acoustic wave (SSAW). The SSAW was generated by the interference of two identical surface acoustic waves (SAWs) created by two parallel interdigital transducers (IDTs) on a piezoelectric substrate with a microchannel precisely bonded between them. To understand the working principle of the SSAW-based 3D focusing and investigate the position of the focal point, we computed longitudinal waves, generated by the SAWs and radiated into the fluid media from opposite sides of the microchannel, and the resultant pressure and velocity fields due to the interference and reflection of the longitudinal waves. Simulation results predict the existence of a focusing point which is in good agreement with our experimental observations. Compared with other 3D focusing techniques, this method is non-invasive, robust, energy-efficient, easy to implement, and applicable to nearly all types of microparticles. PMID:21709881

  9. Controlled release of doxorubicin loaded within magnetic thermo-responsive nanocarriers under magnetic and thermal actuation in a microfluidic channel.

    PubMed

    Pernia Leal, Manuel; Torti, Andrea; Riedinger, Andreas; La Fleur, Rocco; Petti, Daniela; Cingolani, Roberto; Bertacco, Riccardo; Pellegrino, Teresa

    2012-12-21

    We report a procedure to grow thermo-responsive polymer shells at the surface of magnetic nanocarriers made of multiple iron oxide superparamagnetic nanoparticles embedded in poly(maleic anhydride-alt-1-ocatadecene) polymer nanobeads. Depending on the comonomers and on their relative composition, tunable phase transition temperatures in the range between 26 and 47 °C under physiological conditions could be achieved. Using a suitable microfluidic platform combining magnetic nanostructures and channels mimicking capillaries of the circulatory system, we demonstrate that thermo-responsive nanobeads are suitable for localized drug delivery with combined thermal and magnetic activation. Below the critical temperature nanobeads are stable in suspension, retain their cargo, and cannot be easily trapped by magnetic fields. Increasing the temperature above the critical temperature causes the aggregation of nanobeads, forming clusters with a magnetic moment high enough to permit their capture by suitable magnetic gradients in close proximity to the targeted zone. At the same time the polymer swelling activates drug release, with characteristic times on the order of one hour for flow rates of the same order as those of blood in capillaries.

  10. Flow rate-pressure drop relation for deformable shallow microfluidic channels

    NASA Astrophysics Data System (ADS)

    Christov, Ivan C.; Cognet, Vincent; Stone, Howard A.

    2013-11-01

    Laminar flow in devices fabricated from PDMS causes deformation of the passage geometry, which affects the flow rate-pressure drop relation. Having an accurate flow rate-pressure drop relation for deformable microchannels is of importance given that the flow rate for a given pressure drop can be as much as 500% of the flow rate predicted by Poiseuille's law for a rigid channel. proposed a successful model of the latter phenomenon by heuristically coupling linear elasticity with the lubrication approximation for Stokes flow. However, their model contains a fitting parameter that must be found for each channel shape by performing an experiment. We present a perturbative derivation of the flow rate-pressure drop relation in a shallow deformable microchannel using Kirchoff-Love theory of isotropic quasi-static plate bending and Stokes' equations under a ``double lubrication'' approximation (i.e., the ratio of the channel's height to its width and of the channel's width to its length are both assumed small). Our result contains no free parameters and confirms Gervais et al.'s observation that the flow rate is a quartic polynomial of the pressure drop. ICC was supported by NSF Grant DMS-1104047 and the U.S. DOE through the LANL/LDRD Program; HAS was supported by NSF Grant CBET-1132835.

  11. Microfluidic device, and related methods

    NASA Technical Reports Server (NTRS)

    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.

  12. A simple method to determine the surface charge in microfluidic channels.

    PubMed

    Mampallil, Dileep; van den Ende, Dirk; Mugele, Frieder

    2010-01-01

    We study EOF through microchannels, made of glass or glass-PDMS, by displacing an electrolyte solution at given concentration with the same electrolyte at a different concentration via an external electric field. When a constant voltage is applied over the channel, the electric current through the channel varies during the displacement process. We propose a simple analytical model that describes the time dependence of the current regardless of the concentration ratio chosen. With this model, which is applicable beyond the Debye-Hückel limit, we are able to quantify the EOF velocity and to determine the surface charge on the microchannel walls from the measured current behavior, as well as the zeta potential at given local electrolyte concentration.

  13. Dielectrophoretic manipulation of a biological and non-biological analytes in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Bennett, Dawn J.

    Micro-total-analytical systems (muTASs) for analyzing chemical/biological substances are now used across a wide variety of applications ranging from biological warfare agent detection to the healthcare industry. The first step in the operation of a muTAS consists of concentrating and separating the analytes of interest from the background matrix and positioning them into selected locations for subsequent analysis. The use of ac electric fields was demonstrated to have promising potential for a muTAS because the application of an ac field suppresses undesirable electrolytic effects in the liquid. The main purpose of this work is to study micro-scale phenomena in a flowing suspension subject to shear and high-gradient strong ac electric field. A microfluidic device equipped with dielectrophoretic gates arranged perpendicular to the flow was designed and fabricated at Sandia National Laboratories. Experiments were conducted on flowing suspensions over a broad range of flow and electric field parameters to investigate how these characteristics affect the concentration and separation of particles. It was found that dipolar interactions between suspended particles subject to a high-gradient ac field and shear lead to a new many-body phenomenon of dielectrophoresis accompanied by the field-induced phase separation in a flowing suspension. As a result, shear and electric stresses strongly compress a layer enriched with particles. The predictions of the proposed electro-hydrodynamic model for the coupled shear, dielectrophoresis, and phase separation in a flowing suspension are shown to be consistent with experimental data even though the model contains no fitting parameters. Both the model and the experiments showed that the concentration volume could be increased up to about 50%. It was demonstrated that the field-induced dielectrophoresis accompanied by the phase separation provides a new method for concentrating particles in focused regions and for separating biological

  14. Label-free study of the function of ion channel protein on a microfluidic optical sensor integrated with artificial cell membrane.

    PubMed

    Li, Zhen; Tang, Yanyan; Zhang, Ling; Wu, Jianmin

    2014-01-21

    A label-free optical sensor was constructed by integrating pH sensing material and supported phospholipid bilayers (SPBs) in a microfluidic chip. The pH sensing material was composed of a double layer structure consisting of chitosan hydrogel and electrochemically etched porous silicon. The pH change in the microchip could induce a reversible swelling of the chitosan hydrogel layer and consequently caused a shift in effective optical thickness (EOT) of the double layer, which could be observed by Fourier transformed reflectometric interference spectroscopy (FT-RIS). After phospholipid bilayers (PLBs) were self-assembled on the sensing layer, the EOT almost remained constant during the cycling of pH from 7.4 to 6.2, indicating the blockage of H(+) translocation by the PLBs. For studying the behavior of ion channel protein, gramicidin A, a typical ion channel protein, was inserted in the SPBs for mimicking the ion transportation function of cell membrane. Due to the H(+) transportation capability of gramicidin A, the optical response to pH change could partially recover. In the presence of Ca(2+), the pore of the ion channel protein was blocked, causing a significant decrease in the EOT response upon pH change. The bio-functionalized microfluidic sensor fabricated in this work will provide a reliable platform for studying the function of ion channel protein, which is an important class of drug targets.

  15. Selective filling for patterning in microfluidic channels and integration of chromatography in "lab-on-a-chip" devices using sol-gel technology

    NASA Astrophysics Data System (ADS)

    Jindal, Rohit

    The last decade has seen tremendous advancement in the development of miniaturized chemical analysis system also known as "lab-on-a-chip". It is believed that the true potential of these devices will be achieved by integrating various functions such as separation, reaction, sensing, mixing, pumping, injection and detection onto a single chip. The ability to pattern different functionalities is indispensable for the development of highly integrated devices. In this work, a simple method based on the concept of selective filling is described for patterning in the microfluidic channels. It is based on the difference in the free energy of filling between an open and a covered part of the channel. This method was used for the integration of chromatography in the microfluidic devices. A chromatographic column was realized by utilizing sol-gel as an immobilization matrix for entrapping reversed phase chromatographic particles. Localization of the stationary phase was achieved using the selective filling technique. Channels were fabricated in quartz using photolithography and wet etching. Electroosmotic flow was used for manipulating fluid movement in the channels. Cross channel design was used for making a pulse injection of the solutes in the separation channel. An optical fiber setup was developed for carrying out on-chip UV absorbance detection. Stationary phase was created under different sol-gel synthesis conditions. It was established that the sol-gel synthesis carried out under acidic conditions provides the optimum synthesis conditions for creating separation column. Chromatographic performance of the stationary phase material was demonstrated by separating peptides present in a mixture. The sol-gel immobilization method was extended for the integration of micropump in the chip. The micropump enables pumping of the fluid in field free channels. Preliminary results, demonstrating the potential of carbon nanotubes as a support material in the microfluidic channels

  16. Microfluidic pumping through miniaturized channels driven by ultra-high frequency surface acoustic waves

    SciTech Connect

    Shilton, Richie J.; Travagliati, Marco; Beltram, Fabio; Cecchini, Marco

    2014-08-18

    Surface acoustic waves (SAWs) are an effective means to pump fluids through microchannel arrays within fully portable systems. The SAW-driven acoustic counterflow pumping process relies on a cascade phenomenon consisting of SAW transmission through the microchannel, SAW-driven fluid atomization, and subsequent coalescence. Here, we investigate miniaturization of device design, and study both SAW transmission through microchannels and the onset of SAW-driven atomization up to the ultra-high-frequency regime. Within the frequency range from 47.8 MHz to 754 MHz, we show that the acoustic power required to initiate SAW atomization remains constant, while transmission through microchannels is most effective when the channel widths w ≳ 10 λ, where λ is the SAW wavelength. By exploiting the enhanced SAW transmission through narrower channels at ultra-high frequencies, we discuss the relevant frequency-dependent length scales and demonstrate the scaling down of internal flow patterns and discuss their impact on device miniaturization strategies.

  17. Electrochemical impedance measurement of prostate cancer cells using carbon nanotube array electrodes in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Heung Yun, Yeo; Dong, Zhongyun; Shanov, Vesselin N.; Schulz, Mark J.

    2007-11-01

    Highly aligned multi-wall carbon nanotubes were synthesized in the shape of towers and embedded into fluidic channels as electrodes for impedance measurement of LNCaP human prostate cancer cells. Tower electrodes up to 8 mm high were grown and easily peeled off a silicon substrate. The nanotube electrodes were then successfully soldered onto patterned printed circuit boards and cast into epoxy under pressure. After polishing the top of the tower electrodes, RF plasma was used to enhance the electrocatalytic effect by removing excess epoxy and activating the open end of the nanotubes. Electrodeposition of Au particles on the plasma-treated tower electrodes was done at a controlled density. Finally, the nanotube electrodes were embedded into a polydimethylsiloxane (PDMS) channel and electrochemical impedance spectroscopy was carried out with different conditions. Preliminary electrochemical impedance spectroscopy results using deionized water, buffer solution, and LNCaP prostate cancer cells showed that nanotube electrodes can distinguish the different solutions and could be used in future cell-based biosensor development.

  18. Transport coefficients for electrolytes in arbitrarily shaped nano- and microfluidic channels

    NASA Astrophysics Data System (ADS)

    Mortensen, N. A.; Olesen, L. H.; Bruus, H.

    2006-03-01

    We consider laminar flow of incompressible electrolytes in long, straight channels driven by pressure and electro-osmosis. We use a Hilbert space eigenfunction expansion to address the general problem of an arbitrary cross-section and obtain general results in linear-response theory for the hydraulic and electrical transport coefficients which satisfy Onsager relations. In the limit of non-overlapping Debye layers, the transport coefficients are simply expressed in terms of parameters of the electrolyte as well as the geometrical correction factor for the Hagen Poiseuille part of the problem. In particular, we consider the limits of thin non-overlapping as well as strongly overlapping Debye layers, respectively, and calculate the corrections to the hydraulic resistance due to electro-hydrodynamic interactions.

  19. Acoustic streaming produced by a cylindrical bubble undergoing volume and translational oscillations in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Doinikov, Alexander A.; Combriat, Thomas; Thibault, Pierre; Marmottant, Philippe

    2016-09-01

    A theoretical model is developed for acoustic streaming generated by a cylindrical bubble confined in a fluid channel between two planar elastic walls. The bubble is assumed to undergo volume and translational oscillations. The volume oscillation is caused by an imposed acoustic pressure field and generates the bulk scattered wave in the fluid gap and Lamb-type surface waves propagating along the fluid-wall interfaces. The translational oscillation is induced by the velocity field of an external sound source such as another bubble or an oscillatory fluid flow. The acoustic streaming is assumed to result from the interaction of the volume and the translational modes of the bubble oscillations. The general solutions for the linear equations of fluid motion and the equations of acoustic streaming are calculated with no restrictions on the ratio between the viscous penetration depth and the bubble size. Approximate solutions for the limit of low viscosity are provided as well. Simulations of streamline patterns show that the geometry of the streaming resembles flows generated by a source dipole, while the vortex orientation is governed by the driving frequency, bubble size, and the distance of the bubble from the source of translational excitation. Experimental verification of the developed theory is performed using data for streaming generated by bubble pairs.

  20. Acoustic streaming produced by a cylindrical bubble undergoing volume and translational oscillations in a microfluidic channel.

    PubMed

    Doinikov, Alexander A; Combriat, Thomas; Thibault, Pierre; Marmottant, Philippe

    2016-09-01

    A theoretical model is developed for acoustic streaming generated by a cylindrical bubble confined in a fluid channel between two planar elastic walls. The bubble is assumed to undergo volume and translational oscillations. The volume oscillation is caused by an imposed acoustic pressure field and generates the bulk scattered wave in the fluid gap and Lamb-type surface waves propagating along the fluid-wall interfaces. The translational oscillation is induced by the velocity field of an external sound source such as another bubble or an oscillatory fluid flow. The acoustic streaming is assumed to result from the interaction of the volume and the translational modes of the bubble oscillations. The general solutions for the linear equations of fluid motion and the equations of acoustic streaming are calculated with no restrictions on the ratio between the viscous penetration depth and the bubble size. Approximate solutions for the limit of low viscosity are provided as well. Simulations of streamline patterns show that the geometry of the streaming resembles flows generated by a source dipole, while the vortex orientation is governed by the driving frequency, bubble size, and the distance of the bubble from the source of translational excitation. Experimental verification of the developed theory is performed using data for streaming generated by bubble pairs.

  1. A microfluidic pipette array for mechanophenotyping of cancer cells and mechanical gating of mechanosensitive channels

    PubMed Central

    Lee, Lap Man; Liu, Allen P.

    2014-01-01

    Micropipette aspiration measures the mechanical properties of single cells. A traditional micropipette aspiration system requires a bulky infrastructure, and has a low throughput and limited potential for automation. We have developed a simple micro fluidic device, which is able to trap and apply pressure to single cells in designated aspiration arrays. By changing the volume flow rate using a syringe pump, we can accurately exert pressure difference across the trapped cells for pipette aspiration. By examining cell deformation and protrusion length into the pipette under an optical microscope, several important cell mechanical properties such as the cortical tension and the Young’s modulus, can be measured quantitatively using automated image analysis. Using the micro fluidic pipette array, the stiffness of breast cancer cells and healthy breast epithelial cells were measured and compared. Finally, we applied our device to examine the gating threshold of the mechanosensitive channel MscL expressed in mammalian cells. Together, the development of a micro fluidic pipette array could enable rapid mechanophenotyping of individual cells and for mechanotransduction studies. PMID:25361042

  2. Macro-to-micro interfacing to microfluidic channels using 3D-printed templates: application to time-resolved secretion sampling of endocrine tissue.

    PubMed

    Brooks, Jessica C; Ford, Katarena I; Holder, Dylan H; Holtan, Mark D; Easley, Christopher J

    2016-10-21

    Employing 3D-printed templates for macro-to-micro interfacing, a passively operated polydimethysiloxane (PDMS) microfluidic device was designed for time-resolved secretion sampling from primary murine islets and epidiymal white adipose tissue explants. Interfacing in similar devices is typically accomplished through manually punched or drilled fluidic reservoirs. We previously introduced the concept of using hand fabricated polymer inserts to template cell culture and sampling reservoirs into PDMS devices, allowing rapid stimulation and sampling of endocrine tissue. However, fabrication of the fluidic reservoirs was time consuming, tedious, and was prone to errors during device curing. Here, we have implemented computer-aided design and 3D printing to circumvent these fabrication obstacles. In addition to rapid prototyping and design iteration advantages, the ability to match these 3D-printed interface templates with channel patterns is highly beneficial. By digitizing the template fabrication process, more robust components can be produced with reduced fabrication variability. Herein, 3D-printed templates were used for sculpting millimetre-scale reservoirs into the above-channel, bulk PDMS in passively-operated, eight-channel devices designed for time-resolved secretion sampling of murine tissue. Devices were proven functional by temporally assaying glucose-stimulated insulin secretion from <10 pancreatic islets and glycerol secretion from 2 mm adipose tissue explants, suggesting that 3D-printed interface templates could be applicable to a variety of cells and tissue types. More generally, this work validates desktop 3D printers as versatile interfacing tools in microfluidic laboratories.

  3. Controllable liquid colour-changing lenses with microfluidic channels for vision protection, camouflage and optical filtering based on soft lithography fabrication.

    PubMed

    Zhang, Min; Li, Songjing

    2016-01-01

    In this work, liquid colour-changing lenses for vision protection, camouflage and optical filtering are developed by circulating colour liquids through microfluidic channels on the lenses manually. Soft lithography technology is applied to fabricate the silicone liquid colour-changing layers with microfluidic channels on the lenses instead of mechanical machining. To increase the hardness and abrasion resistance of the silicone colour-changing layers on the lenses, proper fabrication parameters such as 6:1 (mass ration) mixing proportion and 100 °C curing temperature for 2 h are approved for better soft lithography process of the lenses. Meanwhile, a new surface treatment for the irreversible bonding of silicone colour-changing layer with optical resin (CR39) substrate lens by using 5 % (volume ratio) 3-Aminopropyltriethoxysilane solution is proposed. Vision protection, camouflage and optical filtering functions of the lenses are investigated with different designs of the channels and multi-layer structures. Each application can not only well achieve their functional demands, but also shows the advantages of functional flexibility, rapid prototyping and good controllability compared with traditional ways. Besides optometry, some other designs and applications of the lenses are proposed for potential utility in the future.

  4. On-line carbon nanotube-based biosensors in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Yun, YeoHeung; Dong, Zhongyun; Shanov, Vesselin N.; Bange, Adam; Heineman, William R.; Halsall, H. Brian; Conforti, Laura; Bhattacharya, Amit; Schulz, Mark J.

    2007-04-01

    Highly aligned double wall carbon nanotubes (DWCNT) and multi-wall carbon nanotubes (MWCNT) were synthesized in the shape of towers and embedded into microchannels for use as a biosensor. The towers were fabricated on a substrate patterned in 1mm x 1mm blocks with 1 mm spacing between the blocks. Chemical vapor deposition was used for the nanotube synthesis process. Patterned towers up to 8 mm high were grown and easily peeled off the silicon substrate. A nanotube electrode was then soldered on printed circuit boards and epoxy was cast into the tower under pressure. After curing, the top of the tower was polished. RF-plasma at 13.56 MHz was used to enhance the electrocatalytic effect of the nanotube electrode by removing excess epoxy and exposing the ends of the nanotubes. Au particles were electrodeposited on the plasma treated tower electrode. Cyclic voltammetry (CV) for the reduction of 6 mM K 3Fe(CN)6 (in a 1.0 M KNO3 supporting electrolyte) was performed to examine the redox behavior of the nanotube tower electrode. Next, a master mold for polydimethylsiloxane (PDMS) was patterned using SU-8 and then a Pt disk electrode was embedded into the PDMS. The final fluidic channel between the epoxy-nanotube electrode and PDMS was sealed using a UV-curing adhesive. Impedance between the Pt and nanotube electrodes was monitored while flowing different solutions and LNCaP prostate cells. The impedance changed in proportion to the concentration of cells in the solution. A needle-type composite microelectrode was then fabricated by injecting a carbon nanotube-epoxy solution into a pulled-glass tube. CV and differential pulse voltammetry (DPV) to detect dopamine were showed a highly linear response with a sensitivity 100 nA/mM. Based on the impedance results using the flowing cells and the CV and DPV results, carbon nanotube microelectrodes are a promising candidate for cancer cell detection and neurotransmitter detection.

  5. Applying microfluidics to electrophysiology.

    PubMed

    Eddington, David T

    2007-01-01

    Microfluidics can be integrated with standard electrophysiology techniques to allow new experimental modalities. Specifically, the motivation for the microfluidic brain slice device is discussed including how the device docks to standard perfusion chambers and the technique of passive pumping which is used to deliver boluses of neuromodulators to the brain slice. By simplifying the device design, we are able to achieve a practical solution to the current unmet electrophysiology need of applying multiple neuromodulators across multiple regions of the brain slice. This is achieved by substituting the standard coverglass substrate of the perfusion chamber with a thin microfluidic device bonded to the coverglass substrate. This was then attached to the perfusion chamber and small holes connect the open-well of the perfusion chamber to the microfluidic channels buried within the microfluidic substrate. These microfluidic channels are interfaced with ports drilled into the edge of the perfusion chamber to access and deliver stimulants. This project represents how the field of microfluidics is transitioning away from proof-of concept device demonstrations and into practical solutions for unmet experimental and clinical needs.

  6. Applying Microfluidics to Electrophysiology

    PubMed Central

    Eddington, David T.

    2007-01-01

    Microfluidics can be integrated with standard electrophysiology techniques to allow new experimental modalities. Specifically, the motivation for the microfluidic brain slice device is discussed including how the device docks to standard perfusion chambers and the technique of passive pumping which is used to deliver boluses of neuromodulators to the brain slice. By simplifying the device design, we are able to achieve a practical solution to the current unmet electrophysiology need of applying multiple neuromodulators across multiple regions of the brain slice. This is achieved by substituting the standard coverglass substrate of the perfusion chamber with a thin microfluidic device bonded to the coverglass substrate. This was then attached to the perfusion chamber and small holes connect the open-well of the perfusion chamber to the microfluidic channels buried within the microfluidic substrate. These microfluidic channels are interfaced with ports drilled into the edge of the perfusion chamber to access and deliver stimulants. This project represents how the field of microfluidics is transitioning away from proof-of concept device demonstrations and into practical solutions for unmet experimental and clinical needs. PMID:18989410

  7. Control of initiation, rate, and routing of spontaneous capillary-driven flow of liquid droplets through microfluidic channels on SlipChip.

    PubMed

    Pompano, Rebecca R; Platt, Carol E; Karymov, Mikhail A; Ismagilov, Rustem F

    2012-01-24

    This Article describes the use of capillary pressure to initiate and control the rate of spontaneous liquid-liquid flow through microfluidic channels. In contrast to flow driven by external pressure, flow driven by capillary pressure is dominated by interfacial phenomena and is exquisitely sensitive to the chemical composition and geometry of the fluids and channels. A stepwise change in capillary force was initiated on a hydrophobic SlipChip by slipping a shallow channel containing an aqueous droplet into contact with a slightly deeper channel filled with immiscible oil. This action induced spontaneous flow of the droplet into the deeper channel. A model predicting the rate of spontaneous flow was developed on the basis of the balance of net capillary force with viscous flow resistance, using as inputs the liquid-liquid surface tension, the advancing and receding contact angles at the three-phase aqueous-oil-surface contact line, and the geometry of the devices. The impact of contact angle hysteresis, the presence or absence of a lubricating oil layer, and adsorption of surface-active compounds at liquid-liquid or liquid-solid interfaces were quantified. Two regimes of flow spanning a 10(4)-fold range of flow rates were obtained and modeled quantitatively, with faster (mm/s) flow obtained when oil could escape through connected channels as it was displaced by flowing aqueous solution, and slower (micrometer/s) flow obtained when oil escape was mostly restricted to a micrometer-scale gap between the plates of the SlipChip ("dead-end flow"). Rupture of the lubricating oil layer (reminiscent of a Cassie-Wenzel transition) was proposed as a cause of discrepancy between the model and the experiment. Both dilute salt solutions and complex biological solutions such as human blood plasma could be flowed using this approach. We anticipate that flow driven by capillary pressure will be useful for the design and operation of flow in microfluidic applications that do not

  8. Control of initiation, rate, and routing of spontaneous capillary-driven flow of liquid droplets through microfluidic channels on SlipChip

    PubMed Central

    Pompano, Rebecca R.; Platt, Carol E.; Karymov, Mikhail A.

    2012-01-01

    This paper describes the use of capillary pressure to initiate and control the rate of spontaneous liquid-liquid flow through microfluidic channels. In contrast to flow driven by external pressure, flow driven by capillary pressure is dominated by interfacial phenomena and is exquisitely sensitive to the chemical composition and geometry of the fluids and channels. A step-wise change in capillary force was initiated on a hydrophobic SlipChip by slipping a shallow channel containing an aqueous droplet into contact with a slightly deeper channel filled with immiscible oil. This action induced spontaneous flow of the droplet into the deeper channel. A model predicting the rate of spontaneous flow was developed based on the balance of net capillary force with viscous flow resistance, using as inputs the liquid-liquid surface tension, the advancing and receding contact angles at the three-phase aqueous-oil-surface contact line, and the geometry of the devices. The impact of contact angle hysteresis, the presence or absence of a lubricating oil layer, and adsorption of surface-active compounds at liquid-liquid or liquid-solid interfaces were quantified. Two regimes of flow spanning a 104-fold range of flow rates were obtained and modeled quantitatively, with faster (mm/s) flow obtained when oil could escape through connected channels as it was displaced by flowing aqueous solution, and slower (micrometer/s) flow obtained when oil escape was mostly restricted to a μm-scale gap between the plates of the SlipChip (“dead-end flow”). Rupture of the lubricating oil layer (reminiscent of a Cassie-Wenzel transition) was proposed as a cause of discrepancy between the model and the experiment. Both dilute salt solutions and complex biological solutions such as human blood plasma could be flowed using this approach. We anticipate that flow driven by capillary pressure will be useful for design and operation of flow in microfluidic applications that do not require external

  9. Thermoosmotic microfluidics.

    PubMed

    Yang, Mingcheng; Ripoll, Marisol

    2016-10-19

    Microchannels with asymmetrically ratcheted walls are here shown to behave as effective and versatile microfluidic pumps if locally heated. When the boundary walls have different temperatures, the confined liquid experiences a temperature gradient along the sawtooth edges, which can induce a thermoosmotic flow. A mesoscale molecular simulation approach is here employed to investigate the flows which are contrasted using an analytical approach. Microchannels can be composed by one or two ratcheted walls which can be straight or cylindrical. Varying the channel geometry can not only change the overall fluid flux, but also vary the flow patters from shear to capillary type, or even to extensional type flows. This scheme does not require multiphase fluids or any movable channel parts, although they are possible to be implemented. The proposed principle is then very versatile to locally manipulate complex fluids, and a promising tool to recover waste heat, to facilitate cooling of microchips, and to manufacture portable lab-on-a-chip devices.

  10. Towards printable open air microfluidics.

    SciTech Connect

    Collord, Andrew; Cook, Adam W.; Clem, Paul Gilbert; Fenton, Kyle Ross; Apblett, Christopher Alan; Branson, Eric D.

    2010-04-01

    We have demonstrated a novel microfluidic technique for aqueous media, which uses super-hydrophobic materials to create microfluidic channels that are open to the atmosphere. We have demonstrated the ability to perform traditional electrokinetic operations such as ionic separations and electrophoresis using these devices. The rate of evaporation was studied and found to increase with decreasing channel size, which places a limitation on the minimum size of channel that could be used for such a device.

  11. Integration of dialysis membranes into a poly(dimethylsiloxane) microfluidic chip for isoelectric focusing of proteins using whole-channel imaging detection.

    PubMed

    Ou, Junjie; Glawdel, Tomasz; Samy, Razim; Wang, Shuwen; Liu, Zhen; Ren, Carolyn L; Pawliszyn, Janusz

    2008-10-01

    A poly(dimethylsiloxane) microfluidic chip-based cartridge is developed and reported here for protein analysis using isoelectic focusing (IEF)-whole-channel imaging detection (WCID) technology. In this design, commercial dialysis membranes are integrated to separate electrolytes and samples and to reduce undesired pressure-driven flow. Fused-silica capillaries are also incorporated in this design for sample injection and channel surface preconditioning. This structure is equivalent to that of a commercial fused-silica capillary-based cartridge for adapting to an IEF analyzer (iCE280 analyzer) to perform IEF-WCID. The successful integration of dialysis membranes into a microfluidic chip significantly improves IEF repeatability by eliminating undesired pressure-driven hydrodynamics and also makes sample injection much easier than that using the first-generation chip as reported recently. In this study, two microfluidic chips with a 100-microm-high, 100-microm-wide and a 200-microm-high, 50-microm-wide microchannel, respectively, were applied for qualitative and quantitative analysis of proteins. The mixture containing six pI markers with a pH range of 3-10 was successfully separated using IEF-WCID. The pH gradient exhibited a good linearity by plotting the pI value versus peak position, and the correlation coefficient reached 0.9994 and 0.9995 separately for the two chips. The separation of more complicated human hemoglobin control sample containing HbA, HbF, HbS, and HbC was also achieved. Additionally, for the quantitative analysis, a good linearity of IEF peak value versus myoglobin concentration in the range of 20-100 microg/mL was obtained.

  12. Microfluidic devices with thick-film electrochemical detection

    DOEpatents

    Wang, Joseph; Tian, Baomin; Sahlin, Eskil

    2005-04-12

    An apparatus for conducting a microfluidic process and analysis, including at least one elongated microfluidic channel, fluidic transport means for transport of fluids through the microfluidic channel, and at least one thick-film electrode in fluidic connection with the outlet end of the microfluidic channel. The present invention includes an integrated on-chip combination reaction, separation and thick-film electrochemical detection microsystem, for use in detection of a wide range of analytes, and methods for the use thereof.

  13. Deformability measurement of red blood cells using a microfluidic channel array and an air cavity in a driving syringe with high throughput and precise detection of subpopulations.

    PubMed

    Kang, Yang Jun; Ha, Young-Ran; Lee, Sang-Joon

    2016-01-07

    Red blood cell (RBC) deformability has been considered a potential biomarker for monitoring pathological disorders. High throughput and detection of subpopulations in RBCs are essential in the measurement of RBC deformability. In this paper, we propose a new method to measure RBC deformability by evaluating temporal variations in the average velocity of blood flow and image intensity of successively clogged RBCs in the microfluidic channel array for specific time durations. In addition, to effectively detect differences in subpopulations of RBCs, an air compliance effect is employed by adding an air cavity into a disposable syringe. The syringe was equally filled with a blood sample (V(blood) = 0.3 mL, hematocrit = 50%) and air (V(air) = 0.3 mL). Owing to the air compliance effect, blood flow in the microfluidic device behaved transiently depending on the fluidic resistance in the microfluidic device. Based on the transient behaviors of blood flows, the deformability of RBCs is quantified by evaluating three representative parameters, namely, minimum value of the average velocity of blood flow, clogging index, and delivered blood volume. The proposed method was applied to measure the deformability of blood samples consisting of homogeneous RBCs fixed with four different concentrations of glutaraldehyde solution (0%-0.23%). The proposed method was also employed to evaluate the deformability of blood samples partially mixed with normal RBCs and hardened RBCs. Thereafter, the deformability of RBCs infected by human malaria parasite Plasmodium falciparum was measured. As a result, the three parameters significantly varied, depending on the degree of deformability. In addition, the deformability measurement of blood samples was successfully completed in a short time (∼10 min). Therefore, the proposed method has significant potential in deformability measurement of blood samples containing hematological diseases with high throughput and precise detection of

  14. Towards a laser-integrated module for marker-free sorting of micrometer-sized particles in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Schwarz, Wolfgang; Bergmann, Anna; Márquez del Pino, Antonio Jorge; Wahl, Dietmar; Rimpf, Dieter; Mappes, Timo; Michalzik, Rainer

    2012-06-01

    In recent years, microfluidic devices have become important tools for cell analysis in biology and medicine. They enable fast and inexpensive analysis with reduced consumption of analytes. However, for optical detection involving FACS (fluorescence-activated cell sorting), sample preparation by attaching an antibody-labeled fluorochrome to the cell is required. Cell tagging by fluorochromes is a mature technology but might affect cell viability and function. In this paper we present a novel concept for marker-free detection and first realization steps. We show the integration of a microfluidic chip and an electrically pumped GaAs-based oxide-confined VECSEL (vertical-extended- cavity surface-emitting laser). Particles in the microchannel flow through the laser resonator and induce a change of the cavity resonance, thus allowing sensitive detection to trigger a subsequent sorting process.

  15. The feasibility of liquid sample microanalysis using polydimethylsiloxane microfluidic chips with in-channel and in-port laser-induced breakdown spectroscopy detection

    NASA Astrophysics Data System (ADS)

    Metzinger, Anikó; Nagy, Andrea; Gáspár, Attila; Márton, Zsuzsanna; Kovács-Széles, Éva; Galbács, Gábor

    2016-12-01

    This study describes the direct interfacing of polydimethylsiloxane (PDMS) microfluidic chips with laser-induced breakdown spectroscopy (LIBS) detection. The changes induced in the PDMS material by nanosecond laser ablation are briefly documented by using optical microscopy and scanning profilometry. The main part of the study focuses on the solution of technical and analytical problems of coupling single-pulse LIBS detection with PDMS microfluidic chips in order to assess the feasibility and performance of the concept of creating a lab-on-a-chip device with LIBS detection (LOC-LIBS). Multiple optical and sample presentation schemes including in-channel and in-port detection were tested, but it was found that LOC-LIBS is only viable and practical with in-port detection outside the chip. It was shown that LOC-LIBS in this configuration is capable of the trace speciation analysis of chromium using as little as 0.5 μL solution volume. The achieved absolute limit of detection was 2 ng.

  16. An evaluation of synthetic and natural supravital stains for the cytological examination of dissociated cells in a microfluidic channel.

    PubMed

    Mojica, W D; Bassey, R

    2015-06-01

    Advances in biotechnology will result in paradigm shifts in both oncology and diagnostics. In pathology, methods such as microfluidics are being explored as delivery tools so that processed cells can serve dual purposes: conventional cytology-based diagnostics and recovery of the same cells for molecular assays. This wet mount-based approach to diagnosis will require staining of these cells by supravital dyes. This study was undertaken to determine the optimal supravital stain for the examination of cells in the wet mount preparations present in microfluidic platforms. Cells were dissociated from portions of tissue similar in size to a traditional core biopsy. These tissue-free cells were separately examined with two synthetic dyes and two natural dyes at varying dilutions. Different dilutions of the synthetic dyes toluidine blue and methylene blue resulted in varying degrees of staining, whereas different dilutions of the natural dyes resulted in fairly constant intensities of colour. These characteristics affected the visualization of cells in wet mount preparations: optimally titered synthetic dyes gave better nuclear detail and cytoplasmic contrast. All four dyes stained the test cells, but to different degrees and intensities. In our assessment, optimally titered synthetic dyes were better suited to the wet mount approach of microfluidics when compared with natural dyes. © 2014 John Wiley & Sons Ltd.

  17. Thin-finger growth and droplet pinch-off in miscible and immiscible displacements in a periodic network of microfluidic channels

    NASA Astrophysics Data System (ADS)

    Budek, Agnieszka; Garstecki, Piotr; Samborski, Adam; Szymczak, Piotr

    2015-11-01

    We report the results of experimental and numerical studies of two-phase flow in a periodic, rectangular network of microfluidic channels. This geometry promotes the formation of anisotropic, dendrite-like structures during viscous fingering experiments. The dendrites then compete with each other for the available flow, which leads to the appearance of hierarchical growth pattern. Combining experiments and numerical simulations, we analyze different growth regimes in such a system, depending on the network geometry and fluid properties. For immiscible fluids, a high degree of screening is present which results in a power-law distribution of finger lengths. Contrastingly, for miscible fluids, strong lateral currents of displaced fluid lead to the detachment of the heads of the longest fingers from their roots, thus preventing their further growth.

  18. Continuously phase-modulated standing surface acoustic waves for separation of particles and cells in microfluidic channels containing multiple pressure nodes

    NASA Astrophysics Data System (ADS)

    Lee, Junseok; Rhyou, Chanryeol; Kang, Byungjun; Lee, Hyungsuk

    2017-04-01

    This paper describes continuously phase-modulated standing surface acoustic waves (CPM-SSAW) and its application for particle separation in multiple pressure nodes. A linear change of phase in CPM-SSAW applies a force to particles whose magnitude depends on their size and contrast factors. During continuous phase modulation, we demonstrate that particles with a target dimension are translated in the direction of moving pressure nodes, whereas smaller particles show oscillatory movements. The rate of phase modulation is optimized for separation of target particles from the relationship between mean particle velocity and period of oscillation. The developed technique is applied to separate particles of a target dimension from the particle mixture. Furthermore, we also demonstrate human keratinocyte cells can be separated in the cell and bead mixture. The separation technique is incorporated with a microfluidic channel spanning multiple pressure nodes, which is advantageous over separation in a single pressure node in terms of throughput.

  19. Microchip CE analysis of amino acids on a titanium dioxide nanoparticles-coated PDMS microfluidic device with in-channel indirect amperometric detection.

    PubMed

    Qiu, Jian-Ding; Wang, Li; Liang, Ru-Ping; Wang, Jing-Wu

    2009-10-01

    In this paper, titanium dioxide nanoparticles (TiO(2) NPs) were employed to construct a functional film on PDMS microfluidic channel surface, which was formed by sequentially immobilizing poly(diallyldimethylammonium chloride) and TiO(2) NPs on PDMS surface by layer-by-layer assembly technique. The modified PDMS microchip exhibited a decreased and stable EOF, which was favorable for the separation of biomolecules with similar migration times. Arginine, phenylalanine, serine and threonine were used as model analytes to evaluate the performance of the modified microchip. The four amino acids were efficiently separated within 100 s in a 3.7 cm long separation channel and successfully detected on the carbon fiber electrode in conjunction with in-channel indirect amperometry. Resolutions and theoretical plate numbers of the analytes were considerably enhanced in the presence of TiO(2) NPs. The modified microchip demonstrated excellent stability and reproducibility with improved RSDs of migration times and peak currents for run-to-run, day-to-day and chip-to-chip analyses, respectively. Variables influencing the separation efficiency and amperometric response, including injection and separation voltage, the working electrode position and buffer concentration, were optimized in detail.

  20. Impact of cross-sectional geometry on mixing performance of spiral microfluidic channels characterized by swirling strength of Dean-vortices

    NASA Astrophysics Data System (ADS)

    Balasubramaniam, Lakshmi; Arayanarakool, Rerngchai; Marshall, Samuel David; Li, Bing; Lee, Poh Seng; Chen, Peter C. Y.

    2017-09-01

    Mixing in a microfluidic system is challenging due to dominant diffusion effects at a microscale (low Reynolds number). In this work, we report the improvement of mixing performance in spiral microchannels of varying cross-sectional geometry and hydraulic diameter. The formation of secondary flow interactions in spiral channels, known as Dean vortices, aid the primary diffusion process. The evolution of these Dean vortices was experimentally visualized along the length of the microchannel by confocal microscopy, and then compared to numerical studies. The cross-sectional geometries of the spiral channels, especially in the case of irregular shapes such as the semi-circular and trapezoidal profiles, were found to be an important factor in tuning the strength of Dean vortices, which in turn dictate the mixing performance, as opposed to diffusion which is more prominent at lower Re. This experiment-based finding has been validated via the evaluation of swirling strength of the working fluid, obtained using a numerical study. The results thus obtained show a mixing performance greater than 90% above a Reynolds number of 20 for most spiral channel designs, making this system suitable for high throughput operation with reduced pressure drop. This work is the first to experimentally and numerically demonstrate, within this operating range (20  <  Re  <  277), the impact on mixing performance in curved microchannels of varying cross-sectional geometries of constant cross-sectional area, and of varying hydraulic diameters for square shaped channels. The capability of these channels to operate at a moderately high Re with enhanced mixing performance and reduced pressure drop would be of great use in large-scale industrial operations, such as complex integrated micro-reactors wherein pressure drop plays a key role.

  1. Comment on ``Taylor dispersion of a solute in a microfluidic channel'' [J. Appl. Phys. 89, 4667 (2001)

    NASA Astrophysics Data System (ADS)

    Dorfman, Kevin D.; Brenner, Howard

    2001-12-01

    In a recent article [J. Appl. Phys. 89, 4667 (2001)], Beard applies Taylor dispersion theory for two-dimensional Poiseuille flow between flat plates to analyze mixing processes occurring at the entrance of a microfluidic T sensor. The classical value of the coefficient of the Taylor dispersivity, 1/210, differs from Beard's result, and this Comment points out elements of Beard's derivation which lead to his erroneous value of 33/560. Moreover, the lateral boundedness of the actual device and the long-time asymptotic nature of Taylor dispersion theory call into question the use of the latter model in the context of the T sensor described in Beard's analysis.

  2. In-situ photopolymerization of monodisperse and discoid oxidized methacrylated alginate microgels in a microfluidic channel

    SciTech Connect

    Wang, Shuo; Jeon, Oju; Shankles, Peter G.; Liu, Yuan; Alsberg, Eben; Retterer, Scott T.; Lee, Bruce P.; Choi, Chang Kyoung

    2016-02-03

    Here, we present a simple microfluidic technique to in-situ photopolymerize (by 365 nm ultraviolet) monodisperse oxidized methacrylated alginate (OMA) microgels using a photoinitiator (VA-086). By this technique, we generated monodisperse spherical OMA beads and discoid non-spherical beads with better shape consistency than ionic crosslinking methods do. We found that a high monomer concentration (8 w/v %), a high photoinitiator concentration (1.5 w/v %) and absence of oxygen are critical factors to cure OMA microgels. This photopolymerizing method is an alternative to current methods to form alginate microgels and is a simpler approach to generate non-spherical alginate microgels.

  3. Suspended microfluidics.

    PubMed

    Casavant, Benjamin P; Berthier, Erwin; Theberge, Ashleigh B; Berthier, Jean; Montanez-Sauri, Sara I; Bischel, Lauren L; Brakke, Kenneth; Hedman, Curtis J; Bushman, Wade; Keller, Nancy P; Beebe, David J

    2013-06-18

    Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics.

  4. Suspended microfluidics

    PubMed Central

    Casavant, Benjamin P.; Berthier, Erwin; Theberge, Ashleigh B.; Berthier, Jean; Montanez-Sauri, Sara I.; Bischel, Lauren L.; Brakke, Kenneth; Hedman, Curtis J.; Bushman, Wade; Keller, Nancy P.; Beebe, David J.

    2013-01-01

    Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics. PMID:23729815

  5. Rapid screening of bioactive compounds from natural products by integrating 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays.

    PubMed

    Zhang, Yufeng; Xiao, Shun; Sun, Lijuan; Ge, Zhiwei; Fang, Fengkai; Zhang, Wen; Wang, Yi; Cheng, Yiyu

    2013-05-13

    A high throughput method was developed for rapid screening and identification of bioactive compounds from traditional Chinese medicine, marine products and other natural products. The system, integrated with five-channel chromatographic separation and dual UV-MS detection, is compatible with in vitro 96-well microplate based bioassays. The stability and applicability of the proposed method was validated by testing radical scavenging capability of a mixture of seven known compounds (rutin, dihydroquercetin, salvianolic acid A, salvianolic acid B, glycyrrhizic acid, rubescensin A and tangeretin). Moreover, the proposed method was successfully applied to the crude extracts of traditional Chinese medicine and a marine sponge from which 12 bioactive compounds were screened and characterized based on their anti-oxidative or anti-tumor activities. In particular, two diterpenoid derivatives, agelasine B and (-)-agelasine D, were identified for the first time as anti-tumor compounds from the sponge Agelas mauritiana, showing a considerable activity toward MCF-7 cells (IC50 values of 7.84±0.65 and 10.48±0.84 μM, respectively). Our findings suggested that the integrated system of 5-channel parallel chromatography coupled with on-line mass spectrometry and microplate based assays can be a versatile and high efficient approach for the discovery of active compounds from natural products. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Applications of microfluidics in quantitative biology.

    PubMed

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

    2017-10-04

    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, we 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. This article is protected by copyright. All rights reserved.

  7. Microfluidic electronics.

    PubMed

    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.

  8. Spatiotemporal periodicity of dislocation dynamics in a two-dimensional microfluidic crystal flowing in a tapered channel

    DOE PAGES

    Gai, Ya; Leong, Chia Min; Cai, Wei; ...

    2016-10-10

    Collective interactions in many-body systems can give rise to unexpected order. Such interactions underlie a wide range of complex phenomena such as swarming in animals and traffic patterns. This work reports an unexpected order in the flow of highly confined and highly concentrated water-in-oil drops, which can be explained and modeled as a soft crystal being extruded in the nanoscale. The findings are important to the understanding of out-of-equilibrium many-body systems, and the flow control of these drops used as microreactors in droplet microfluidics. Furthermore, contrary to the unpredictable microscale crystal deformation process, the discoveries here indicate that nanoscale crystalmore » deformation can be highly ordered and predictable, and imply that the manufacturing of nanocrystalline materials may be easier than perceived.« less

  9. Electric field effects on current–voltage relationships in microfluidic channels presenting multiple working electrodes in the weak-coupling limit

    DOE PAGES

    Contento, Nicholas M.; Bohn, Paul W.

    2014-05-23

    While electrochemical methods are well suited for lab-on-a-chip applications, reliably coupling multiple, electrode-controlled processes in a single microfluidic channel remains a considerable challenge, because the electric fields driving electrokinetic flow make it difficult to establish a precisely known potential at the working electrode(s). The challenge of coupling electrochemical detection with microchip electrophoresis is well known; however, the problem is general, arising in other multielectrode arrangements with applications in enhanced detection and chemical processing. Here, we study the effects of induced electric fields on voltammetric behavior in a microchannel containing multiple in-channel electrodes, using a Fe(CN)6 3/4- model system. When anmore » electric field is induced by applying a cathodic potential at one inchannel electrode, the half-wave potential (E1/2) for the oxidation of ferrocyanide at an adjacent electrode shifts to more negative potentials. The E1/2 value depends linearly on the electric field current at a separate in-channel electrode. The observed shift in E1/2 is quantitatively described by a model, which accounts for the change in solution potential caused by the iR drop along the length of the microchannel. The model, which reliably captures changes in electrode location and solution conductivity, apportions the electric field potential between iR drop and electrochemical potential components, enabling the study of microchannel electric field magnitudes at low applied potentials. In the system studied, the iR component of the electric field potential increases exponentially with applied current before reaching an asymptotic value near 80 % of the total applied potential. The methods described will aid in the development and interpretation of future microchip electrochemistry methods, particularly those that benefit from the coupling of electrokinetic and electrochemical phenomena at low voltages.« less

  10. Electric field effects on current–voltage relationships in microfluidic channels presenting multiple working electrodes in the weak-coupling limit

    SciTech Connect

    Contento, Nicholas M.; Bohn, Paul W.

    2014-05-23

    While electrochemical methods are well suited for lab-on-a-chip applications, reliably coupling multiple, electrode-controlled processes in a single microfluidic channel remains a considerable challenge, because the electric fields driving electrokinetic flow make it difficult to establish a precisely known potential at the working electrode(s). The challenge of coupling electrochemical detection with microchip electrophoresis is well known; however, the problem is general, arising in other multielectrode arrangements with applications in enhanced detection and chemical processing. Here, we study the effects of induced electric fields on voltammetric behavior in a microchannel containing multiple in-channel electrodes, using a Fe(CN)6 3/4- model system. When an electric field is induced by applying a cathodic potential at one inchannel electrode, the half-wave potential (E1/2) for the oxidation of ferrocyanide at an adjacent electrode shifts to more negative potentials. The E1/2 value depends linearly on the electric field current at a separate in-channel electrode. The observed shift in E1/2 is quantitatively described by a model, which accounts for the change in solution potential caused by the iR drop along the length of the microchannel. The model, which reliably captures changes in electrode location and solution conductivity, apportions the electric field potential between iR drop and electrochemical potential components, enabling the study of microchannel electric field magnitudes at low applied potentials. In the system studied, the iR component of the electric field potential increases exponentially with applied current before reaching an asymptotic value near 80 % of the total applied potential. The methods described will aid in the development and interpretation of future microchip electrochemistry methods, particularly those that benefit from the coupling of electrokinetic and electrochemical

  11. Rapid mask prototyping for microfluidics.

    PubMed

    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.

  12. Forensic drug analysis and microfluidics.

    PubMed

    Al-Hetlani, Entesar

    2013-05-01

    The analysis of drugs of abuse in microfluidic devices has the potential to provide solutions to today's on-site analysis challenges. The use of such devices has not been limited to miniaturising conventional analytical methods used routinely in forensic laboratories; new and interesting approaches have been implemented in microfluidics and benefit from the ability to control minute amounts of liquids in the small channels. The microfluidic platforms developed so far have been used successfully to carry out single or multiple analytical processes and offer a great opportunity for new technologies for on-site drug testing. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Ice matrix in reconfigurable microfluidic systems

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  14. Advanced combinational microfluidic multiplexer for fuel cell reactors

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    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.

  15. Double-helix micro-channels on microfluidic chips for enhanced continuous on-chip derivatization followed by electrophoretic separation.

    PubMed

    Peng, Xianglu; Zhao, Lei; Guo, Jinxiu; Yang, Shenghong; Ding, Hui; Wang, Xiayan; Pu, Qiaosheng

    2015-10-15

    Micro-channels that contain a special inner structure are critical for efficient mixing and chemical reactions. In this paper, we described the facile fabrication of an integrated microchip with double-helix type micro-channels to improve mixing efficiency and to facilitate multi-step derivatization reactions prior to electrophoretic separation. With a prepared microchip, reagents, samples and reaction products could be driven through micro-channels by siphon, and no other pumping device was necessary. To test its performance, reductive amination of aldehydes with 8-aminonaphthalene-1,3,6-trisulfonate acid disodium (ANTS) was attempted via microchip electrophoresis with laser induced fluorescence (LIF). The effect of the geometry of the reaction micro-channel on the reaction's efficiency was evaluated. Under the selected conditions, successful derivatization of five aldehydes was realized for highly reproducible analysis. The relative standard deviations of the peak areas for 30 consecutive injections were in the range of 0.28-1.61%. The method was applied for the determination of aldehydes in real samples with standard addition recoveries of 87.8-102.8%. Good tolerance of organic solvents was achieved, and the proposed method can potentially be employed for rapid screening of excessively added aldehyde food flavoring. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Inertial microfluidic physics.

    PubMed

    Amini, Hamed; Lee, Wonhee; Di Carlo, Dino

    2014-08-07

    Microfluidics has experienced massive growth in the past two decades, and especially with advances in rapid prototyping researchers have explored a multitude of channel structures, fluid and particle mixtures, and integration with electrical and optical systems towards solving problems in healthcare, biological and chemical analysis, materials synthesis, and other emerging areas that can benefit from the scale, automation, or the unique physics of these systems. Inertial microfluidics, which relies on the unconventional use of fluid inertia in microfluidic platforms, is one of the emerging fields that make use of unique physical phenomena that are accessible in microscale patterned channels. Channel shapes that focus, concentrate, order, separate, transfer, and mix particles and fluids have been demonstrated, however physical underpinnings guiding these channel designs have been limited and much of the development has been based on experimentally-derived intuition. Here we aim to provide a deeper understanding of mechanisms and underlying physics in these systems which can lead to more effective and reliable designs with less iteration. To place the inertial effects into context we also discuss related fluid-induced forces present in particulate flows including forces due to non-Newtonian fluids, particle asymmetry, and particle deformability. We then highlight the inverse situation and describe the effect of the suspended particles acting on the fluid in a channel flow. Finally, we discuss the importance of structured channels, i.e. channels with boundary conditions that vary in the streamwise direction, and their potential as a means to achieve unprecedented three-dimensional control over fluid and particles in microchannels. Ultimately, we hope that an improved fundamental and quantitative understanding of inertial fluid dynamic effects can lead to unprecedented capabilities to program fluid and particle flow towards automation of biomedicine, materials

  17. Integration of biological ion channels onto optically addressable micro-fluidic electrode arrays for single molecule characterization.

    SciTech Connect

    Brozik, Susan Marie; Frink, Laura J. Douglas; Bachand, George David; Keller, David J.; Patrick, Elizabeth L.; Marshall, Jason A.; Ortiz, Theodore P.; Meyer, Lauren A.; Davis, Ryan W.; Brozik, James A.; Flemming, Jeb Hunter

    2004-12-01

    The challenge of modeling the organization and function of biological membranes on a solid support has received considerable attention in recent years, primarily driven by potential applications in biosensor design. Affinity-based biosensors show great promise for extremely sensitive detection of BW agents and toxins. Receptor molecules have been successfully incorporated into phospholipid bilayers supported on sensing platforms. However, a collective body of data detailing a mechanistic understanding of membrane processes involved in receptor-substrate interactions and the competition between localized perturbations and delocalized responses resulting in reorganization of transmembrane protein structure, has yet to be produced. This report describes a systematic procedure to develop detailed correlation between (recognition-induced) protein restructuring and function of a ligand gated ion channel by combining single molecule fluorescence spectroscopy and single channel current recordings. This document is divided into three sections: (1) reported are the thermodynamics and diffusion properties of gramicidin using single molecule fluorescence imaging and (2) preliminary work on the 5HT{sub 3} serotonin receptor. Thirdly, we describe the design and fabrication of a miniaturized platform using the concepts of these two technologies (spectroscopic and single channel electrochemical techniques) for single molecule analysis, with a longer term goal of using the physical and electronic changes caused by a specific molecular recognition event as a transduction pathway in affinity based biosensors for biotoxin detection.

  18. Enhanced Microfluidic Electromagnetic Measurements

    NASA Technical Reports Server (NTRS)

    Giovangrandi, Laurent (Inventor); Ricco, Antonio J. (Inventor); Kovacs, Gregory (Inventor)

    2015-01-01

    Techniques for enhanced microfluidic impedance spectroscopy include causing a core fluid to flow into a channel between two sheath flows of one or more sheath fluids different from the core fluid. Flow in the channel is laminar. A dielectric constant of a fluid constituting either sheath flow is much less than a dielectric constant of the core fluid. Electrical impedance is measured in the channel between at least a first pair of electrodes. In some embodiments, enhanced optical measurements include causing a core fluid to flow into a channel between two sheath flows of one or more sheath fluids different from the core fluid. An optical index of refraction of a fluid constituting either sheath flow is much less than an optical index of refraction of the core fluid. An optical property is measured in the channel.

  19. Oxygen control with microfluidics.

    PubMed

    Brennan, Martin D; Rexius-Hall, Megan L; Elgass, Laura Jane; Eddington, David T

    2014-11-21

    Cellular function and behavior are affected by the partial pressure of O2, or oxygen tension, in the microenvironment. The level of oxygenation is important, as it is a balance of oxygen availability and oxygen consumption that is necessary to maintain normoxia. Changes in oxygen tension, from above physiological oxygen tension (hyperoxia) to below physiological levels (hypoxia) or even complete absence of oxygen (anoxia), trigger potent biological responses. For instance, hypoxia has been shown to support the maintenance and promote proliferation of regenerative stem and progenitor cells. Paradoxically, hypoxia also contributes to the development of pathological conditions including systemic inflammatory response, tumorigenesis, and cardiovascular disease, such as ischemic heart disease and pulmonary hypertension. Current methods to study cellular behavior in low levels of oxygen tension include hypoxia workstations and hypoxia chambers. These culture systems do not provide oxygen gradients that are found in vivo or precise control at the microscale. Microfluidic platforms have been developed to overcome the inherent limits of these current methods, including lack of spatial control, slow equilibration, and unachievable or difficult coupling to live-cell microscopy. The various applications made possible by microfluidic systems are the topic of this review. In order to understand how the microscale can be leveraged for oxygen control of cells and tissues within microfluidic systems, some background understanding of diffusion, solubility, and transport at the microscale will be presented in addition to a discussion on the methods for measuring the oxygen tension in microfluidic channels. Finally the various methods for oxygen control within microfluidic platforms will be discussed including devices that rely on diffusion from liquid or gas, utilizing on-or-off-chip mixers, leveraging cellular oxygen uptake to deplete the oxygen, relying on chemical reactions in

  20. Direct observation of λ-DNA molecule reversal movement within microfluidic channels under electric field with single molecule imaging technique

    NASA Astrophysics Data System (ADS)

    Fengyun, Yang; Kaige, Wang; Dan, Sun; Wei, Zhao; Hai-qing, Wang; Xin, He; Gui-ren, Wang; Jin-tao, Bai

    2016-07-01

    The electrodynamic characteristics of single DNA molecules moving within micro-/nano-fluidic channels are important in the design of biomedical chips and bimolecular sensors. In this study, the dynamic properties of λ-DNA molecules transferring along the microchannels driven by the external electrickinetic force were systemically investigated with the single molecule fluorescence imaging technique. The experimental results indicated that the velocity of DNA molecules was strictly dependent on the value of the applied electric field and the diameter of the channel. The larger the external electric field, the larger the velocity, and the more significant deformation of DNA molecules. More meaningfully, it was found that the moving directions of DNA molecules had two completely different directions: (i) along the direction of the external electric field, when the electric field intensity was smaller than a certain threshold value; (ii) opposite to the direction of the external electric field, when the electric field intensity was greater than the threshold electric field intensity. The reversal movement of DNA molecules was mainly determined by the competition between the electrophoresis force and the influence of electro-osmosis flow. These new findings will theoretically guide the practical application of fluidic channel sensors and lab-on-chips for precisely manipulating single DNA molecules. Project supported by the National Natural Science Foundation of China (Grant No. 61378083), the International Cooperation Foundation of the National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant No. 2011DFA12220), the Major Research Plan of National Natural Science Foundation of China (Grant No. 91123030), and the Natural Science Foundation of Shaanxi Province of China (Grant Nos. 2010JS110 and 2013SZS03-Z01).

  1. Continuous separation of microparticles in a microfluidic channel via the elasto-inertial effect of non-Newtonian fluid.

    PubMed

    Nam, Jeonghun; Lim, Hyunjung; Kim, Dookon; Jung, Hyunwook; Shin, Sehyun

    2012-04-07

    Pure separation and sorting of microparticles from complex fluids are essential for biochemical analyses and clinical diagnostics. However, conventional techniques require highly complex and expensive labeling processes for high purity separation. In this study, we present a simple and label-free method for separating microparticles with high purity using the elasto-inertial characteristic of a non-Newtonian fluid in microchannel flow. At the inlet, particle-containing sample flow was pushed toward the side walls by introducing sheath fluid from the center inlet. Particles of 1 μm and 5 μm in diameter, which were suspended in viscoelastic fluid, were successfully separated in the outlet channels: larger particles were notably focused on the centerline of the channel at the outlet, while smaller particles continued flowing along the side walls with minimal lateral migration towards the centerline. The same technique was further applied to separate platelets from diluted whole blood. Through cytometric analysis, we obtained a purity of collected platelets of close to 99.9%. Conclusively, our microparticle separation technique using elasto-inertial forces in non-Newtonian fluid is an effective method for separating and collecting microparticles on the basis of size differences with high purity. This journal is © The Royal Society of Chemistry 2012

  2. Microfluidic Biochip Design

    NASA Technical Reports Server (NTRS)

    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

  3. Active, Universal Particle Micromanipulators: CPUs for Microfluidics

    NASA Astrophysics Data System (ADS)

    Mezic, Igor; Bottausci, Frederic

    2007-11-01

    Current designs for Lab-on-a-Chip applications consist of a variety of separate microfluidic chambers and channels for functions such as concentration, separation, reaction and mixing of bioparticles in liquids. Here we advance an alternative concept, named μfCPU, the Microfluidic Central Processing Unit, where the key microfluidic operations are performed within a single enclosure, using software-based inputs rather than physical hardware changes, thus emulating the role of the Central Processing Unit in computers and cells in living organisms. We present an experimental embodiment of such a device and describe a variety of microfluidic manipulation tasks achieved in it by the use of a suite of electromotive and fluidic forces in a time-dependent way to produce on-demand functionality. We also discuss a new microfluidic devices architecture that utilizes μfCPU as the basic processing unit and uses centralized pumping instead of integrated microfluidic pumps.

  4. Production of highly concentrated oil-in-water emulsions using dual-channel microfluidization: Use of individual and mixed natural emulsifiers (saponin and lecithin).

    PubMed

    Luo, Xiang; Zhou, Yanyan; Bai, Long; Liu, Fuguo; Zhang, Ruojie; Zhang, Zipei; Zheng, Bingjing; Deng, Yihui; McClements, David Julian

    2017-06-01

    The fabrication of concentrated oil-in-water emulsions is useful for reducing storage and transportation costs, as well as for providing desirable textural, optical, stability, and release characteristics in commercial products. In this study, 50wt% oil-in-water emulsions were produced from natural emulsifiers using high-pressure dual-channel microfluidization (89.6MPa, 1 pass). The particle size and charge characteristics of emulsions stabilized using a hydrophilic biosurfactant (quillaja saponin) or mixtures of hydrophilic and hydrophobic biosurfactants (quillaja saponin+soy lecithin) were measured. The physical stability of the emulsions was determined during storage under quiescent conditions (pH7, 25°C). The mean droplet diameter and polydispersity decreased with increasing hydrophilic and hydrophobic biosurfactant concentration. Surface potential measurements indicated that interfacial composition depended on the amount of hydrophilic and hydrophobic biosurfactant present. The inclusion of hydrophobic emulsifier in the oil phase and hydrophilic emulsifier in the aqueous phase prior to homogenization, led to the formation of smaller oil droplets than using the hydrophilic emulsifier alone. The relatively small size and polydispersity of the droplets in the mixed-emulsifier systems led to a higher emulsion viscosity and a better aggregation stability, i.e., there was a smaller change in particle size during storage. However, some creaming was still observed in the emulsions due to the presence of a fraction of relatively large droplets. In summary, concentrated emulsions stabilized by mixed biosurfactants may be advantageous for commercial application in certain food, beverage, and pharmaceutical products. Copyright © 2017. Published by Elsevier Ltd.

  5. A tapered channel microfluidic device for comprehensive cell adhesion analysis, using measurements of detachment kinetics and shear stress-dependent motion.

    PubMed

    Rupprecht, Peter; Golé, Laurent; Rieu, Jean-Paul; Vézy, Cyrille; Ferrigno, Rosaria; Mertani, Hichem C; Rivière, Charlotte

    2012-03-01

    We have developed a method for studying cellular adhesion by using a custom-designed microfluidic device with parallel non-connected tapered channels. The design enables investigation of cellular responses to a large range of shear stress (ratio of 25) with a single input flow-rate. For each shear stress, a large number of cells are analyzed (500-1500 cells), providing statistically relevant data within a single experiment. Besides adhesion strength measurements, the microsystem presented in this paper enables in-depth analysis of cell detachment kinetics by real-time videomicroscopy. It offers the possibility to analyze adhesion-associated processes, such as migration or cell shape change, within the same experiment. To show the versatility of our device, we examined quantitatively cell adhesion by analyzing kinetics, adhesive strength and migration behaviour or cell shape modifications of the unicellular model cell organism Dictyostelium discoideum at 21 °C and of the human breast cancer cell line MDA-MB-231 at 37 °C. For both cell types, we found that the threshold stresses, which are necessary to detach the cells, follow lognormal distributions, and that the detachment process follows first order kinetics. In addition, for particular conditions' cells are found to exhibit similar adhesion threshold stresses, but very different detachment kinetics, revealing the importance of dynamics analysis to fully describe cell adhesion. With its rapid implementation and potential for parallel sample processing, such microsystem offers a highly controllable platform for exploring cell adhesion characteristics in a large set of environmental conditions and cell types, and could have wide applications across cell biology, tissue engineering, and cell screening.

  6. Dissolved oxygen sensing using organometallic dyes deposited within a microfluidic environment

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  7. Microfluidic binary phase flow

    NASA Astrophysics Data System (ADS)

    Angelescu, Dan; Menetrier, Laure; Wong, Joyce; Tabeling, Patrick; Salamitou, Philippe

    2004-03-01

    We present a novel binary phase flow regime where the two phases differ substantially in both their wetting and viscous properties. Optical tracking particles are used in order to investigate the details of such multiphase flow inside capillary channels. We also describe microfluidic filters we have developed, capable of separating the two phases based on capillary pressure. The performance of the filters in separating oil-water emulsions is discussed. Binary phase flow has been previously used in microchannels in applications such as emulsion generation, enhancement of mixing and assembly of custom colloidal paticles. Such microfluidic systems are increasingly used in a number of applications spanning a diverse range of industries, such as biotech, pharmaceuticals and more recently the oil industry.

  8. Microfluidic bubble logic.

    PubMed

    Prakash, Manu; Gershenfeld, Neil

    2007-02-09

    We demonstrate universal computation in an all-fluidic two-phase microfluidic system. Nonlinearity is introduced into an otherwise linear, reversible, low-Reynolds number flow via bubble-to-bubble hydrodynamic interactions. A bubble traveling in a channel represents a bit, providing us with the capability to simultaneously transport materials and perform logical control operations. We demonstrate bubble logic AND/OR/NOT gates, a toggle flip-flop, a ripple counter, timing restoration, a ring oscillator, and an electro-bubble modulator. These show the nonlinearity, gain, bistability, synchronization, cascadability, feedback, and programmability required for scalable universal computation. With increasing complexity in large-scale microfluidic processors, bubble logic provides an on-chip process control mechanism integrating chemistry and computation.

  9. Pulsed laser triggered high speed microfluidic switch

    NASA Astrophysics Data System (ADS)

    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.

  10. Microfluidic sieve using intertwined, free-standing carbon nanotube mesh as active medium

    DOEpatents

    Bakajin, Olgica; Noy, Aleksandr

    2007-11-06

    A microfluidic sieve having a substrate with a microfluidic channel, and a carbon nanotube mesh. The carbon nanotube mesh is formed from a plurality of intertwined free-standing carbon nanotubes which are fixedly attached within the channel for separating, concentrating, and/or filtering molecules flowed through the channel. In one embodiment, the microfluidic sieve is fabricated by providing a substrate having a microfluidic channel, and growing the intertwined free-standing carbon nanotubes from within the channel to produce the carbon nanotube mesh attached within the channel.

  11. Optical microfluidics

    SciTech Connect

    Kotz, K.T.; Noble, K.A.; Faris, G.W.

    2004-09-27

    We present a method for the control of small droplets based on the thermal Marangoni effect using laser heating. With this approach, droplets covering five orders of magnitude in volume ({approx}1.7 {mu}L to 14 pL), immersed in decanol, were moved on an unmodified polystyrene surface, with speeds of up to 3 mm/s. When two droplets were brought into contact, they spontaneously fused and rapidly mixed in less than 33 ms. This optically addressed microfluidic approach has many advantages for microfluidic transport, including exceptional reconfigurability, low intersample contamination, large volume range, extremely simple substrates, no electrical connections, and ready scaling to large arrays.

  12. Incorporation of bioactive materials into integrated systems

    NASA Astrophysics Data System (ADS)

    Bunker, Bruce C.; Huber, Dale L.; Manginell, Ronald P.; Kim, Byung-Il; Boal, Andrew K.; Bachand, George D.; Rivera, Susan B.; Bauer, Joseph M.; Matzke, Carolyn M.

    2003-10-01

    Sandia is exploring two classes of integrated systems involving bioactive materials: 1) microfluidic systems that can be used to manipulate biomolecules for applications ranging from counter-terrorism to drug delivery systems, and 2) fluidic systems in which active biomolecules such as motor proteins provide specific functions such as active transport. An example of the first class involves the development of a reversible protein trap based on the integration of the thermally-switchable polymer poly(N-isopropylacrylamide)(PNIPAM) into a micro-hotplate device. To exemplify the second class, we describe the technical challenges associated with integrating microtubules and motor proteins into microfluidic systems for: 1) the active transport of nanoparticle cargo, or 2) templated growth of high-aspect ratio nanowires. These examples illustrate the functions of bioactive materials, synthesis and fabrication issues, mechanisms for switching surface chemistry and active transport, and new techniques such as the interfacial force microscope (IFM) that can be used to characterize bioactive surfaces.

  13. Whole-Teflon microfluidic chips

    PubMed Central

    Ren, Kangning; Dai, Wen; Zhou, Jianhua; Su, Jing; Wu, Hongkai

    2011-01-01

    Although microfluidics has shown exciting potential, its broad applications are significantly limited by drawbacks of the materials used to make them. In this work, we present a convenient strategy for fabricating whole-Teflon microfluidic chips with integrated valves that show outstanding inertness to various chemicals and extreme resistance against all solvents. Compared with other microfluidic materials [e.g., poly(dimethylsiloxane) (PDMS)] the whole-Teflon chip has a few more advantages, such as no absorption of small molecules, little adsorption of biomolecules onto channel walls, and no leaching of residue molecules from the material bulk into the solution in the channel. Various biological cells have been cultured in the whole-Teflon channel. Adherent cells can attach to the channel bottom, spread, and proliferate well in the channels (with similar proliferation rate to the cells in PDMS channels with the same dimensions). The moderately good gas permeability of the Teflon materials makes it suitable to culture cells inside the microchannels for a long time. PMID:21536918

  14. Whole-Teflon microfluidic chips.

    PubMed

    Ren, Kangning; Dai, Wen; Zhou, Jianhua; Su, Jing; Wu, Hongkai

    2011-05-17

    Although microfluidics has shown exciting potential, its broad applications are significantly limited by drawbacks of the materials used to make them. In this work, we present a convenient strategy for fabricating whole-Teflon microfluidic chips with integrated valves that show outstanding inertness to various chemicals and extreme resistance against all solvents. Compared with other microfluidic materials [e.g., poly(dimethylsiloxane) (PDMS)] the whole-Teflon chip has a few more advantages, such as no absorption of small molecules, little adsorption of biomolecules onto channel walls, and no leaching of residue molecules from the material bulk into the solution in the channel. Various biological cells have been cultured in the whole-Teflon channel. Adherent cells can attach to the channel bottom, spread, and proliferate well in the channels (with similar proliferation rate to the cells in PDMS channels with the same dimensions). The moderately good gas permeability of the Teflon materials makes it suitable to culture cells inside the microchannels for a long time.

  15. Channels

    NASA Image and Video Library

    2014-04-29

    Two channels are visible in this image from NASA 2001 Mars Odyssey spacecraft . The smaller one near the bottom did not carve as deeply as the larger channel at the top. The channel near the top of the image is near the origin of Mamers Valles.

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

    NASA Technical Reports Server (NTRS)

    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.

  17. Microfluidic serial dilution circuit.

    PubMed

    Paegel, Brian M; Grover, William H; Skelley, Alison M; Mathies, Richard A; Joyce, Gerald F

    2006-11-01

    In vitro evolution of RNA molecules requires a method for executing many consecutive serial dilutions. To solve this problem, a microfluidic circuit has been fabricated in a three-layer glass-PDMS-glass device. The 400-nL serial dilution circuit contains five integrated membrane valves: three two-way valves arranged in a loop to drive cyclic mixing of the diluent and carryover, and two bus valves to control fluidic access to the circuit through input and output channels. By varying the valve placement in the circuit, carryover fractions from 0.04 to 0.2 were obtained. Each dilution process, which is composed of a diluent flush cycle followed by a mixing cycle, is carried out with no pipeting, and a sample volume of 400 nL is sufficient for conducting an arbitrary number of serial dilutions. Mixing is precisely controlled by changing the cyclic pumping rate, with a minimum mixing time of 22 s. This microfluidic circuit is generally applicable for integrating automated serial dilution and sample preparation in almost any microfluidic architecture.

  18. Droplet based microfluidics.

    PubMed

    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.

  19. Fabrication of plastic microfluidic components

    NASA Astrophysics Data System (ADS)

    Martin, Peter M.; Matson, Dean W.; Bennett, Wendy D.; Hammerstrom, D. J.

    1998-09-01

    Plastic components have many advantages, including ease of fabrication, low cost, chemical inertness, lightweight, and disposability. We report on the fabrication of three plastics-based microfluidic components: a motherboard, a dialysis unit, and a metal sensor. Microchannels, headers, and interconnects were produced in thin sheets (>=50 microns) of polyimide, PMMA, polyethylene, and polycarbonate using a direct-write excimer laser micromachining system. Machined sheets were laminated by thermal and adhesive bonding to form leak-tight microfluidic components. The microfluidic motherboard borrowed the `functionality on a chip' concept from the electronics industry and was the heart of a complex microfluidic analytical device. The motherboard platform was designed to be tightly integrated and self-contained (i.e., liquid flows are all confined within machined microchannels), reducing the need for tubing with fluid distribution and connectivity. This concept greatly facilitated system integration and miniaturization. As fabricated, the motherboard consisted of three fluid reservoirs connected to micropumps by microchannels. The fluids could either be pumped independently or mixed in microchannels prior to being directed to exterior analytical components via outlet ports. The microdialysis device was intended to separate electrolytic solutes from low volume samples prior to mass spectrometric analysis. The device consisted of a dialysis membrane laminated between opposed serpentine microchannels containing the sample fluid and a buffer solution. The laminated metal sensor consisted of fluid reservoirs, micro-flow channels, micropumps, mixing channels, reaction channels, and detector circuitry.

  20. Augmentation of 3-methylcholanthrene-induced bioactivation in the human hepatoma cell line HepG2 by the calcium channel blocker nicardipine.

    PubMed

    Hosaka, Takuomi; Sekimoto, Masashi; Nemoto, Kiyomitsu; Degawa, Masakuni

    2010-03-01

    The abilities of the dihydropyridine calcium channel blocker nicardipine (Nic) to induce cytochrome P450 1 family enzymes (CYP1s) and to enhance the 3-methylcholanthrene (MC)-mediated induction of CYP1s and formation of MC-DNA adduct were examined in the human hepatoma cell line HepG2. The results from real time RT-PCR analysis demonstrated that Nic could induce CYP1 mRNAs and enhance the MC-mediated induction of the CYP1 mRNAs. The luciferase-reporter gene assay using the HepG2-A10 cell line, which has been previously established for the screening of aryl hydrocarbon receptor (AhR) activators, also indicated the augmentation of MC-mediated activation of AhR (induction of luciferase) by Nic, although Nic showed limited capacity for the activation of AhR. Furthermore, the results from the Western blot analysis of CYP1s, the enzyme activity assay, and the assay for MC-DNA adduct formation indicated that Nic could enhance the MC-mediated induction of CYP1s, especially CYP1A1. Furthermore, the intracellular accumulation level of [(3)H]MC after treatment of HepG2 cells with [(3)H]MC significantly increased in the presence of Nic. The present findings demonstrate that Nic can enhance the MC-mediated induction of CYP1s, especially CYP1A1, and the formation of MC-DNA adduct in HepG2 cells. Furthermore, the augmentation of the MC-mediated bioactivation by Nic is demonstrated to occur mainly through an increase in intracellular accumulation of MC.

  1. Flexible packaging and integration of CMOS IC with elastomeric microfluidics

    NASA Astrophysics Data System (ADS)

    Zhang, Bowei; Dong, Quan; Korman, Can E.; Li, Zhenyu; Zaghloul, Mona E.

    2013-05-01

    We have demonstrated flexible packaging and integration of CMOS IC chips with PDMS microfluidics. Microfluidic channels are used to deliver both liquid samples and liquid metals to the CMOS die. The liquid metals are used to realize electrical interconnects to the CMOS chip. As a demonstration we integrated a CMOS magnetic sensor die and matched PDMS microfluidic channels in a flexible package. The packaged system is fully functional under 3cm bending radius. The flexible integration of CMOS ICs with microfluidics enables previously unavailable flexible CMOS electronic systems with fluidic manipulation capabilities, which hold great potential for wearable health monitoring, point-of-care diagnostics and environmental sensing.

  2. Designing Colloidal Molecules with Microfluidics

    PubMed Central

    Shen, Bingqing; Ricouvier, Joshua; Malloggi, Florent

    2016-01-01

    The creation of new colloidal materials involves the design of functional building blocks. Here, a microfluidic method for designing building blocks one by one, at high throughput, with a broad range of shapes is introduced. The method exploits a coupling between hydrodynamic interactions and depletion forces that controls the configurational dynamics of droplet clusters traveling in microfluidic channels. Droplet clusters can be solidified in situ with UV. By varying the flow parameters, clusters are prescribed a given size, geometry, chemical and/or magnetic heterogeneities enabling local bonding. Compact structures (chains, triangles, diamonds, tetrahedrons,...) and noncompact structures, such as crosses and T, difficult to obtain with current techniques are produced. Size dispersions are small (2%) and throughputs are high (30 000 h−1). The work opens a new pathway, based on microfluidics, for designing colloidal building blocks with a potential to enable the creation of new materials. PMID:27840804

  3. Microfluidic process monitor for industrial solvent extraction system

    SciTech Connect

    Gelis, Artem; Pereira, Candido; Nichols, Kevin Paul Flood

    2016-01-12

    The present invention provides a system for solvent extraction utilizing a first electrode with a raised area formed on its surface, which defines a portion of a microfluidic channel; a second electrode with a flat surface, defining another portion of the microfluidic channel that opposes the raised area of the first electrode; a reversibly deformable substrate disposed between the first electrode and second electrode, adapted to accommodate the raised area of the first electrode and having a portion that extends beyond the raised area of the first electrode, that portion defining the remaining portions of the microfluidic channel; and an electrolyte of at least two immiscible liquids that flows through the microfluidic channel. Also provided is a system for performing multiple solvent extractions utilizing several microfluidic chips or unit operations connected in series.

  4. Detection of enzyme inhibitors in crude natural extracts using droplet-based microfluidics coupled to HPLC.

    PubMed

    Ochoa, Abraham; Álvarez-Bohórquez, Enrique; Castillero, Eduardo; Olguin, Luis F

    2017-04-04

    Natural product screening for new bioactive compounds can greatly benefit from low reagents consumption and high throughput capacity of droplet-based microfluidic systems. However, the creation of large droplet libraries in which each droplet carries a different compound is a challenging task. A possible solution is to use an HPLC coupled to a droplet generating microfluidic device to sequentially encapsulate the eluting compounds. In this work we demonstrate the feasibility of carrying out enzyme inhibiting assays inside nano-liter droplets with the different components of a natural crude extract after being separated by a coupled HPLC column. In the droplet formation zone, the eluted components are mixed with an enzyme and a fluorogenic substrate that permits to follow the enzymatic reaction in the presence of each chromatographic peak and identify those inhibiting the enzyme activity. Using a fractal shape channel design and automated image analysis we were able to identify inhibitors of Clostridium perfringens neuraminidase present in a root extract of the Pelargonium sidoides plant. This work demonstrates the feasibility of bioprofiling a natural crude extract after being separated in HPLC using microfluidic droplets on-line and represents an advance in the miniaturization of natural products screening.

  5. Bioactive Peptides

    PubMed Central

    Daliri, Eric Banan-Mwine; Oh, Deog H.; Lee, Byong H.

    2017-01-01

    The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development. PMID:28445415

  6. Bioactive Peptides.

    PubMed

    Daliri, Eric Banan-Mwine; Oh, Deog H; Lee, Byong H

    2017-04-26

    The increased consumer awareness of the health promoting effects of functional foods and nutraceuticals is the driving force of the functional food and nutraceutical market. Bioactive peptides are known for their high tissue affinity, specificity and efficiency in promoting health. For this reason, the search for food-derived bioactive peptides has increased exponentially. Over the years, many potential bioactive peptides from food have been documented; yet, obstacles such as the need to establish optimal conditions for industrial scale production and the absence of well-designed clinical trials to provide robust evidence for proving health claims continue to exist. Other important factors such as the possibility of allergenicity, cytotoxicity and the stability of the peptides during gastrointestinal digestion would need to be addressed. This review discusses our current knowledge on the health effects of food-derived bioactive peptides, their processing methods and challenges in their development.

  7. Laser Ablation of Polymer Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Killeen, Kevin

    2004-03-01

    Microfluidic technology is ideal for processing precious samples of limited volumes. Some of the most important classes of biological samples are both high in sample complexity and low in concentration. Combining the elements of sample pre-concentration, chemical separation and high sensitivity detection with chemical identification is essential for realizing a functional microfluidic based analysis system. Direct write UV laser ablation has been used to rapidly fabricate microfluidic devices capable of high performance liquid chromatography (HPLC)-MS. These chip-LC/MS devices use bio-compatible, solvent resistant and flexible polymer materials such as polyimide. A novel microfluidic to rotary valve interface enables, leak free, high pressure fluid switching between multiple ports of the microfluidic chip-LC/MS device. Electrospray tips with outer dimension of 50 um and inner of 15 um are formed by ablating the polymer material concentrically around a multilayer laminated channel structure. Biological samples of digested proteins were used to evaluate the performance of these microfluidic devices. Liquid chromatography separation and similar sample pretreatments have been performed using polymeric microfluidic devices with on-chip separation channels. Mass spectrometry was performed using an Agilent Technologies 1100 series ion trap mass spectrometer. Low fmol amounts of protein samples were positively and routinely identified by searching the MS/MS spectral data against protein databases. The sensitivity and separation performance of the chip-LC devices has been found to be comparable to state of the art nano-electrospray systems.

  8. Smartphone quantifies Salmonella from paper microfluidics.

    PubMed

    Park, Tu San; Li, Wenyue; McCracken, Katherine E; Yoon, Jeong-Yeol

    2013-12-21

    Smartphone-based optical detection is a potentially easy-to-use, handheld, true point-of-care diagnostic tool for the early and rapid detection of pathogens. Paper microfluidics is a low-cost, field-deployable, and easy-to-use alternative to conventional microfluidic devices. Most paper-based microfluidic assays typically utilize dyes or enzyme-substrate binding, while bacterial detection on paper microfluidics is rare. We demonstrate a novel application of smartphone-based detection of Salmonella on paper microfluidics. Each paper microfluidic channel was pre-loaded with anti-Salmonella Typhimurium and anti-Escherichia coli conjugated submicroparticles. Dipping the paper microfluidic device into the Salmonella solutions led to the antibody-conjugated particles that were still confined within the paper fibers to immunoagglutinate. The extent of immunoagglutination was quantified by evaluating Mie scattering from the digital images taken at an optimized angle and distance with a smartphone. A smartphone application was designed and programmed to allow the user to position the smartphone at an optimized angle and distance from the paper microfluidic device, and a simple image processing algorithm was implemented to calculate and display the bacterial concentration on the smartphone. The detection limit was single-cell-level and the total assay time was less than one minute.

  9. Microfluidic Device

    NASA Technical Reports Server (NTRS)

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

    2017-01-01

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

  10. Microfluidic Device

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

  11. Microfluidic Device

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

  12. Microfluidic Device

    NASA Technical Reports Server (NTRS)

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

    2017-01-01

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

  13. High-Voltage CMOS Controller for Microfluidics.

    PubMed

    Khorasani, M; Behnam, M; van den Berg, L; Backhouse, C J; Elliott, D G

    2009-04-01

    A high-voltage microfluidic controller designed using DALSA semiconductor's 0.8-mum low-voltage/high-voltage complementary metal-oxide semiconductor/double diffused metal-oxide semiconductor process is presented. The chip's four high-voltage output drivers can switch 300 V, and the dc-dc boost converter can generate up to 68 V using external passive components. This integrated circuit represents an advancement in microfluidic technology when used in conjunction with a charge coupling device (CCD)-based optical system and a glass microfluidic channel, enabling a portable and cost-efficient platform for genetic analysis.

  14. Nanoembossing of thermoplastic polymers for microfluidic applications

    NASA Astrophysics Data System (ADS)

    Studer, V.; Pépin, A.; Chen, Y.

    2002-05-01

    We present a method for the fabrication of plastic microfluidic devices based on nanoembossing and thermal bonding. By nanoembossing of thermoplastic polymer pellets, both microfluidic deep channels and high resolution features can be formed using a silicon mold fabricated by electron beam lithography and reactive ion etching. By thermal bonding with another plastic sheet, the fabricated microfluidic devices can be sealed without clogging. Observation of pressure driven and electrokinetic flows through high density pillar arrays indicates the feasibility of nanofluidic analysis using plastic devices.

  15. Analogy among microfluidics, micromechanics, and microelectronics.

    PubMed

    Li, Sheng-Shian; Cheng, Chao-Min

    2013-10-07

    We wish to illuminate the analogous link between microfluidic-based devices, and the already established pairing of micromechanics and microelectronics to create a triangular/three-way scientific relationship as a means of interlinking familial disciplines and accomplishing two primary goals: (1) to facilitate the modeling of multidisciplinary domains; and, (2) to enable us to co-simulate the entire system within a compact circuit simulator (e.g., Cadence or SPICE). A microfluidic channel-like structure embedded in a micro-electro-mechanical resonator via our proposed CMOS-MEMS technology is used to illustrate the connections among microfluidics, micromechanics, and microelectronics.

  16. Microfluidic dielectrophoretic sorter using gel vertical electrodes

    PubMed Central

    Luo, Jason; Nelson, Edward L.; Li, G. P.; Bachman, Mark

    2014-01-01

    We report the development and results of a two-step method for sorting cells and small particles in a microfluidic device. This approach uses a single microfluidic channel that has (1) a microfabricated sieve which efficiently focuses particles into a thin stream, followed by (2) a dielectrophoresis (DEP) section consisting of electrodes along the channel walls for efficient continuous sorting based on dielectric properties of the particles. For our demonstration, the device was constructed of polydimethylsiloxane, bonded to a glass surface, and conductive agarose gel electrodes. Gold traces were used to make electrical connections to the conductive gel. The device had several novel features that aided performance of the sorting. These included a sieving structure that performed continuous displacement of particles into a single stream within the microfluidic channel (improving the performance of downstream DEP, and avoiding the need for additional focusing flow inlets), and DEP electrodes that were the full height of the microfluidic walls (“vertical electrodes”), allowing for improved formation and control of electric field gradients in the microfluidic device. The device was used to sort polymer particles and HeLa cells, demonstrating that this unique combination provides improved capability for continuous DEP sorting of particles in a microfluidic device. PMID:24926390

  17. Digital microfluidic processing of mammalian embryos for vitrification.

    PubMed

    Pyne, Derek G; Liu, Jun; Abdelgawad, Mohamed; Sun, Yu

    2014-01-01

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

  18. Develpment of a Microfluidic Device for the Study of Breast Cancer Cell Migration

    DTIC Science & Technology

    2005-09-01

    Corporation, Ossining, NY), forming a covalent bond and completing the microfluidic network. All channels were made of PDMS with glass bottoms... Microfluidics Prior to the cell migration experiment, the 400-[tm wide migration channel was coated with 2 ýtg/ml collagen type IV at room temperature for 30...r 0 200 400 0 200 400 600 800 0 200 400 600 800 Distance Across Channel (4rm) Fig. 1 Schematic diagrams of the microfluidic chemotaxis chambers. (a) A

  19. Microfluidic preparation of polymer nanospheres

    NASA Astrophysics Data System (ADS)

    Kucuk, Israfil; Edirisinghe, Mohan

    2014-12-01

    In this work, solid polymer nanospheres with their surface tailored for drug adhesion were prepared using a V-shaped microfluidic junction. The biocompatible polymer solutions were infused using two channels of the microfluidic junction which was also simultaneously fed with a volatile liquid, perfluorohexane using the other channel. The mechanism by which the nanospheres are generated is explained using high speed camera imaging. The polymer concentration (5-50 wt%) and flow rates of the feeds (50-300 µl min-1) were important parameters in controlling the nanosphere diameter. The diameter of the polymer nanospheres was found to be in the range of 80-920 nm with a polydispersity index of 11-19 %. The interior structure and surfaces of the nanospheres prepared were studied using advanced microscopy and showed the presence of fine pores and cracks on surface which can be used as drug entrapment locations.

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

    PubMed

    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.

  1. Microfluidic parallel circuit for measurement of hydraulic resistance.

    PubMed

    Choi, Sungyoung; Lee, Myung Gwon; Park, Je-Kyun

    2010-08-31

    We present a microfluidic parallel circuit that directly compares the test channel of an unknown hydraulic resistance with the reference channel with a known resistance, thereby measuring the unknown resistance without any measurement setup, such as standard pressure gauges. Many of microfluidic applications require the precise transport of fluid along a channel network with complex patterns. Therefore, it is important to accurately characterize and measure the hydraulic resistance of each channel segment, and determines whether the device principle works well. However, there is no fluidic device that includes features, such as the ability to diagnose microfluidic problems by measuring the hydraulic resistance of a microfluidic component in microscales. To address the above need, we demonstrate a simple strategy to measure an unknown hydraulic resistance, by characterizing the hydraulic resistance of microchannels with different widths and defining an equivalent linear channel of a microchannel with repeated patterns of a sudden contraction and expansion.

  2. Surface Micromachine Microfluidics: Design, Fabrication, Packaging, and Characterization

    SciTech Connect

    Galambos, Paul; Eaton, William P.; Shul, Randy; Willison, Christi Gober; Sniegowski, Jeffrey J.; Miller, Samuel L.; Guttierez, Daniel

    1999-06-30

    The field of microfluidics is undergoing rapid growth in terms of new device and system development. Among the many methods of fabricating microfluidic devices and systems, surface micromachining is relatively underrepresented due to difficulties in the introduction of fluids into the very small channels produced, packaging problems, and difficulties in device and system characterization. The potential advantages of using surface micromachining including compatibility with the existing integrated circuit tool set, integration of electronic sensing and actuation with microfluidics, and fluid volume minimization. In order to explore these potential advantages we have developed first generation surface micromachined microfluidic devices (channels) using an adapted pressure sensor fabrication process to produce silicon nitride channels, and the SUMMiT process to produce polysilicon channels. The channels were characterized by leak testing and flow rate vs. pressure measurements. The fabrication processes used and results of these tests are reported in this paper.

  3. Microfluidic interconnects

    DOEpatents

    Benett, William J.; Krulevitch, Peter A.

    2001-01-01

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

  4. Packaging of electro-microfluidic devices

    DOEpatents

    Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Watson, Robert D.

    2002-01-01

    A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

  5. Packaging of electro-microfluidic devices

    DOEpatents

    Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Zamora, David Lee; Watson, Robert D.

    2003-04-15

    A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

  6. Microfluidics and Microfabrication in a Chemical Engineering Lab

    ERIC Educational Resources Information Center

    Archer, Shivaun D.

    2011-01-01

    Microfluidics, the manipulation of fluids in channels with micron dimensions, has emerged as an exciting new field that impacts the broad area of nano/microtechnology. This is an important area to train the next generation of chemical engineers. This paper describes an experiment where students are given a problem to design a microfluidic mixer…

  7. Microfluidics and Microfabrication in a Chemical Engineering Lab

    ERIC Educational Resources Information Center

    Archer, Shivaun D.

    2011-01-01

    Microfluidics, the manipulation of fluids in channels with micron dimensions, has emerged as an exciting new field that impacts the broad area of nano/microtechnology. This is an important area to train the next generation of chemical engineers. This paper describes an experiment where students are given a problem to design a microfluidic mixer…

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

    PubMed Central

    Otvos, Reka A.; Krishnamoorthy Iyer, Janaki; van Elk, René; Ulens, Chris; Niessen, Wilfried M. A.; Somsen, Govert W.; Kini, R. Manjunatha; Smit, August B.; Kool, Jeroen

    2015-01-01

    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. PMID:26114334

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

    PubMed

    Otvos, Reka A; Iyer, Janaki Krishnamoorthy; van Elk, René; Ulens, Chris; Niessen, Wilfried M A; Somsen, Govert W; Kini, R Manjunatha; Smit, August B; Kool, Jeroen

    2015-06-24

    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.

  10. Channels

    NASA Image and Video Library

    2015-11-20

    Today's VIS image shows a number of unnamed channels located on the northeastern margin of Terra Sabaea. Orbit Number: 61049 Latitude: 33.5036 Longitude: 58.6967 Instrument: VIS Captured: 2015-09-18 12:54 http://photojournal.jpl.nasa.gov/catalog/PIA20097

  11. PREFACE: Nano- and microfluidics Nano- and microfluidics

    NASA Astrophysics Data System (ADS)

    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

  12. Rapid Protein Separations in Microfluidic Devices

    NASA Technical Reports Server (NTRS)

    Fan, Z. H.; Das, Champak; Xia, Zheng; Stoyanov, Alexander V.; Fredrickson, Carl K.

    2004-01-01

    This paper describes fabrication of glass and plastic microfluidic devices for protein separations. Although the long-term goal is to develop a microfluidic device for two-dimensional gel electrophoresis, this paper focuses on the first dimension-isoelectric focusing (IEF). A laser-induced fluorescence (LIF) imaging system has been built for imaging an entire channel in an IEF device. The whole-channel imaging eliminates the need to migrate focused protein bands, which is required if a single-point detector is used. Using the devices and the imaging system, we are able to perform IEF separations of proteins within minutes rather than hours in traditional bench-top instruments.

  13. Rapid Protein Separations in Microfluidic Devices

    NASA Technical Reports Server (NTRS)

    Fan, Z. H.; Das, Champak; Xia, Zheng; Stoyanov, Alexander V.; Fredrickson, Carl K.

    2004-01-01

    This paper describes fabrication of glass and plastic microfluidic devices for protein separations. Although the long-term goal is to develop a microfluidic device for two-dimensional gel electrophoresis, this paper focuses on the first dimension-isoelectric focusing (IEF). A laser-induced fluorescence (LIF) imaging system has been built for imaging an entire channel in an IEF device. The whole-channel imaging eliminates the need to migrate focused protein bands, which is required if a single-point detector is used. Using the devices and the imaging system, we are able to perform IEF separations of proteins within minutes rather than hours in traditional bench-top instruments.

  14. Self-propelled autonomous nanomotors meet microfluidics.

    PubMed

    Kherzi, Bahareh; Pumera, Martin

    2016-10-14

    Self-propelled autonomous nano/micromotors are in the forefront of current materials science and technology research. These small machines convert chemical energy from the environment into propulsion, and they can move autonomously in the environment and are capable of chemotaxis or magnetotaxis. They can be used for drug delivery, microsurgeries or environmental remediation. It is of immense interest from a future biomedical application point of view to understand the motion of the nano/micromotors in microfluidic channels. In this minireview, we review the progress on the use of nano/micromotors in microfluidic channels and lab-on-chip devices.

  15. Microfluidic Biochip Design

    NASA Technical Reports Server (NTRS)

    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.

  16. Integration of an optical CMOS sensor with a microfluidic channel allows a sensitive readout for biological assays in point-of-care tests.

    PubMed

    Van Dorst, Bieke; Brivio, Monica; Van Der Sar, Elfried; Blom, Marko; Reuvekamp, Simon; Tanzi, Simone; Groenhuis, Roelf; Adojutelegan, Adewole; Lous, Erik-Jan; Frederix, Filip; Stuyver, Lieven J

    2016-04-15

    In this manuscript, a microfluidic detection module, which allows a sensitive readout of biological assays in point-of-care (POC) tests, is presented. The proposed detection module consists of a microfluidic flow cell with an integrated Complementary Metal-Oxide-Semiconductor (CMOS)-based single photon counting optical sensor. Due to the integrated sensor-based readout, the detection module could be implemented as the core technology in stand-alone POC tests, for use in mobile or rural settings. The performance of the detection module was demonstrated in three assays: a peptide, a protein and an antibody detection assay. The antibody detection assay with readout in the detection module proved to be 7-fold more sensitive that the traditional colorimetric plate-based ELISA. The protein and peptide assay showed a lower limit of detection (LLOD) of 200 fM and 460 fM respectively. Results demonstrate that the sensitivity of the immunoassays is comparable with lab-based immunoassays and at least equal or better than current mainstream POC devices. This sensitive readout holds the potential to develop POC tests, which are able to detect low concentrations of biomarkers. This will broaden the diagnostic capabilities at the clinician's office and at patient's home, where currently only the less sensitive lateral flow and dipstick POC tests are implemented.

  17. Universally applicable three-dimensional hydrodynamic microfluidic flow focusing.

    PubMed

    Chiu, Yu-Jui; Cho, Sung Hwan; Mei, Zhe; Lien, Victor; Wu, Tsung-Feng; Lo, Yu-Hwa

    2013-05-07

    We have demonstrated a microfluidic device that can not only achieve three-dimensional flow focusing but also confine particles to the center stream along the channel. The device has a sample channel of smaller height and two sheath flow channels of greater height, merged into the downstream main channel where 3D focusing effects occur. We have demonstrated that both beads and cells in our device display significantly lower CVs in velocity and position distributions as well as reduced probability of coincidental events than they do in conventional 2D-confined microfluidic channels. The improved particle confinement in the microfluidic channel is highly desirable for microfluidic flow cytometers and in fluorescence-activated cell sorting (FACS). We have also reported a novel method to measure the velocity of each individual particle in the microfluidic channel. The method is compatible with the flow cytometer setup and requires no sophisticated visualization equipment. The principles and methods of device design and characterization can be applicable to many types of microfluidic systems.

  18. Expanding imaging capabilities for microfluidics: applicability of darkfield internal reflection illumination (DIRI) to observations in microfluidics.

    PubMed

    Kawano, Yoshihiro; Otsuka, Chino; Sanzo, James; Higgins, Christopher; Nirei, Tatsuo; Schilling, Tobias; Ishikawa, Takuji

    2015-01-01

    Microfluidics is used increasingly for engineering and biomedical applications due to recent advances in microfabrication technologies. Visualization of bubbles, tracer particles, and cells in a microfluidic device is important for designing a device and analyzing results. However, with conventional methods, it is difficult to observe the channel geometry and such particles simultaneously. To overcome this limitation, we developed a Darkfield Internal Reflection Illumination (DIRI) system that improved the drawbacks of a conventional darkfield illuminator. This study was performed to investigate its utility in the field of microfluidics. The results showed that the developed system could clearly visualize both microbubbles and the channel wall by utilizing brightfield and DIRI illumination simultaneously. The methodology is useful not only for static phenomena, such as clogging, but also for dynamic phenomena, such as the detection of bubbles flowing in a channel. The system was also applied to simultaneous fluorescence and DIRI imaging. Fluorescent tracer beads and channel walls were observed clearly, which may be an advantage for future microparticle image velocimetry (μPIV) analysis, especially near a wall. Two types of cell stained with different colors, and the channel wall, can be recognized using the combined confocal and DIRI system. Whole-slide imaging was also conducted successfully using this system. The tiling function significantly expands the observing area of microfluidics. The developed system will be useful for a wide variety of engineering and biomedical applications for the growing field of microfluidics.

  19. Expanding Imaging Capabilities for Microfluidics: Applicability of Darkfield Internal Reflection Illumination (DIRI) to Observations in Microfluidics

    PubMed Central

    Kawano, Yoshihiro; Otsuka, Chino; Sanzo, James; Higgins, Christopher; Nirei, Tatsuo; Schilling, Tobias; Ishikawa, Takuji

    2015-01-01

    Microfluidics is used increasingly for engineering and biomedical applications due to recent advances in microfabrication technologies. Visualization of bubbles, tracer particles, and cells in a microfluidic device is important for designing a device and analyzing results. However, with conventional methods, it is difficult to observe the channel geometry and such particles simultaneously. To overcome this limitation, we developed a Darkfield Internal Reflection Illumination (DIRI) system that improved the drawbacks of a conventional darkfield illuminator. This study was performed to investigate its utility in the field of microfluidics. The results showed that the developed system could clearly visualize both microbubbles and the channel wall by utilizing brightfield and DIRI illumination simultaneously. The methodology is useful not only for static phenomena, such as clogging, but also for dynamic phenomena, such as the detection of bubbles flowing in a channel. The system was also applied to simultaneous fluorescence and DIRI imaging. Fluorescent tracer beads and channel walls were observed clearly, which may be an advantage for future microparticle image velocimetry (μPIV) analysis, especially near a wall. Two types of cell stained with different colors, and the channel wall, can be recognized using the combined confocal and DIRI system. Whole-slide imaging was also conducted successfully using this system. The tiling function significantly expands the observing area of microfluidics. The developed system will be useful for a wide variety of engineering and biomedical applications for the growing field of microfluidics. PMID:25748425

  20. Living anionic polymerization using a microfluidic reactor

    SciTech Connect

    Iida, Kazunori; Chastek, Thomas Q.; Beers, Kathryn L.; Cavicchi, Kevin A.; Chun, Jaehun; Fasolka, Michael J.

    2009-02-01

    Living anionic polymerizations were conducted within aluminum-polyimide microfluidic devices. Polymerizations of styrene in cyclohexane were carried out at various conditions, including elevated temperature (60 °C) and high monomer concentration (42%, by volume). The reactions were safely maintained at a controlled temperature at all points in the reactor. Conducting these reactions in a batch reactor results in uncontrolled heat generation with potentially dangerous rises in pressure. Moreover, the microfluidic nature of these devices allows for flexible 2D designing of the flow channel. Four flow designs were examined (straight, periodically pinched, obtuse zigzag, and acute zigzag channels). The ability to use the channel pattern to increase the level of mixing throughout the reactor was evaluated. When moderately high molecular mass polymers with increased viscosity were made, the patterned channels produced polymers with narrower PDI, indicating that passive mixing arising from the channel design is improving the reaction conditions.

  1. Living anionic polymerization using a microfluidic reactor.

    PubMed

    Iida, Kazunori; Chastek, Thomas Q; Beers, Kathryn L; Cavicchi, Kevin A; Chun, Jaehun; Fasolka, Michael J

    2009-01-21

    Living anionic polymerizations were conducted within aluminum-polyimide microfluidic devices. Polymerizations of styrene in cyclohexane were carried out at various conditions, including elevated temperature (60 degrees C) and high monomer concentration (42%, by volume). The reactions were safely maintained at a controlled temperature at all points in the reactor. Conducting these reactions in a batch reactor results in uncontrolled heat generation with potentially dangerous rises in pressure. Moreover, the microfluidic nature of these devices allows for flexible 2D designing of the flow channel. Four flow designs were examined (straight, periodically pinched, obtuse zigzag, and acute zigzag channels). The ability to use the channel pattern to increase the level of mixing throughout the reactor was evaluated. When moderately high molecular mass polymers with increased viscosity were made, the patterned channels produced polymers with narrower PDI, indicating that passive mixing arising from the channel design is improving the reaction conditions.

  2. Microfluidic interconnects

    DOEpatents

    Benett, William J.; Krulevitch, Peter A.

    2001-01-01

    A miniature connector for introducing microliter quantities of solutions into microfabricated fluidic devices, and which incorporates a molded ring or seal set into a ferrule cartridge, with or without a compression screw. The fluidic connector, for example, joins standard high pressure liquid chromatography (HPLC) tubing to 1 mm diameter holes in silicon or glass, enabling ml-sized volumes of sample solutions to be merged with .mu.l-sized devices. The connector has many features, including ease of connect and disconnect; a small footprint which enables numerous connectors to be located in a small area; low dead volume; helium leak-tight; and tubing does not twist during connection. Thus the connector enables easy and effective change of microfluidic devices and introduction of different solutions in the devices.

  3. Nanostructured microfluidic digestion system for rapid high-performance proteolysis.

    PubMed

    Cheng, Gong; Hao, Si-Jie; Yu, Xu; Zheng, Si-Yang

    2015-02-07

    A novel microfluidic protein digestion system with a nanostructured and bioactive inner surface was constructed by an easy biomimetic self-assembly strategy for rapid and effective proteolysis in 2 minutes, which is faster than the conventional overnight digestion methods. It is expected that this work would contribute to rapid online digestion in future high-throughput proteomics.

  4. Microfluidics-Based PCR for Fusion Transcript Detection.

    PubMed

    Chen, Hui

    2016-01-01

    The microfluidic technology allows the production of network of submillimeter-size fluidic channels and reservoirs in a variety of material systems. The microfluidic-based polymerase chain reaction (PCR) allows automated multiplexing of multiple samples and multiple assays simultaneously within a network of microfluidic channels and chambers that are co-ordinated in controlled fashion by the valves. The individual PCR reaction is performed in nanoliter volume, which allows testing on samples with limited DNA and RNA. The microfluidics devices are used in various types of PCR such as digital PCR and single molecular emulsion PCR for genotyping, gene expression, and miRNA expression. In this chapter, the use of a microfluidics-based PCR for simultaneous screening of 14 known fusion transcripts in patients with leukemia is described.

  5. Nanofluidic interfaces in microfluidic networks

    SciTech Connect

    Millet, Larry J.; Doktycz, Mitchel John; Retterer, Scott T.

    2015-09-24

    The integration of nano- and microfluidic technologies enables the construction of tunable interfaces to physical and biological systems across relevant length scales. The ability to perform chemical manipulations of miniscule sample volumes is greatly enhanced through these technologies and extends the ability to manipulate and sample the local fluidic environments at subcellular, cellular and community or tissue scales. Here we describe the development of a flexible surface micromachining process for the creation of nanofluidic channel arrays integrated within SU-8 microfluidic networks. The use of a semi-porous, silicon rich, silicon nitride structural layer allows rapid release of the sacrificial silicon dioxide during the nanochannel fabrication. Nanochannel openings that form the interface to biological samples are customized using focused ion beam milling. The compatibility of these interfaces with on-chip microbial culture is demonstrated.

  6. Nanofluidic interfaces in microfluidic networks

    DOE PAGES

    Millet, Larry J.; Doktycz, Mitchel John; Retterer, Scott T.

    2015-09-24

    The integration of nano- and microfluidic technologies enables the construction of tunable interfaces to physical and biological systems across relevant length scales. The ability to perform chemical manipulations of miniscule sample volumes is greatly enhanced through these technologies and extends the ability to manipulate and sample the local fluidic environments at subcellular, cellular and community or tissue scales. Here we describe the development of a flexible surface micromachining process for the creation of nanofluidic channel arrays integrated within SU-8 microfluidic networks. The use of a semi-porous, silicon rich, silicon nitride structural layer allows rapid release of the sacrificial silicon dioxidemore » during the nanochannel fabrication. Nanochannel openings that form the interface to biological samples are customized using focused ion beam milling. The compatibility of these interfaces with on-chip microbial culture is demonstrated.« less

  7. Tunable Microfluidic Microlasers

    DTIC Science & Technology

    2011-09-01

    particularly convenient material for microfluidic experiments with LC. Figure 7: A droplet of E7 nematic liquid crystal on a PDMS...AFRL-AFOSR-UK-TR-2011-0039 TUNABLE MICROFLUIDIC MICROLASERS Francesco Simoni Universita Politecnica delle Marche...DATES COVERED (From – To) 15 June 2010 – 15 June 2011 4. TITLE AND SUBTITLE TUNABLE MICROFLUIDIC MICROLASERS 5a. CONTRACT NUMBER FA8655

  8. Development & Characterization of Multifunctional Microfluidic Materials

    NASA Astrophysics Data System (ADS)

    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

  9. Microfluidic Devices in Advanced Caenorhabditis elegans Research.

    PubMed

    Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

    2016-08-02

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Polymer-based platform for microfluidic systems

    DOEpatents

    Benett, William [Livermore, CA; Krulevitch, Peter [Pleasanton, CA; Maghribi, Mariam [Livermore, CA; Hamilton, Julie [Tracy, CA; Rose, Klint [Boston, MA; Wang, Amy W [Oakland, CA

    2009-10-13

    A method of forming a polymer-based microfluidic system platform using network building blocks selected from a set of interconnectable network building blocks, such as wire, pins, blocks, and interconnects. The selected building blocks are interconnectably assembled and fixedly positioned in precise positions in a mold cavity of a mold frame to construct a three-dimensional model construction of a microfluidic flow path network preferably having meso-scale dimensions. A hardenable liquid, such as poly (dimethylsiloxane) is then introduced into the mold cavity and hardened to form a platform structure as well as to mold the microfluidic flow path network having channels, reservoirs and ports. Pre-fabricated elbows, T's and other joints are used to interconnect various building block elements together. After hardening the liquid the building blocks are removed from the platform structure to make available the channels, cavities and ports within the platform structure. Microdevices may be embedded within the cast polymer-based platform, or bonded to the platform structure subsequent to molding, to create an integrated microfluidic system. In this manner, the new microfluidic platform is versatile and capable of quickly generating prototype systems, and could easily be adapted to a manufacturing setting.

  12. Mechanically activated artificial cell by using microfluidics

    NASA Astrophysics Data System (ADS)

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-09-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology.

  13. Mechanically activated artificial cell by using microfluidics

    PubMed Central

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-01-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology. PMID:27610921

  14. Bioactive glasses as accelerators of apatite bioactivity.

    PubMed

    Vallet-Regí, M; Rámila, A; Padilla, S; Muñoz, B

    2003-09-01

    Synthetic carbonatehydroxyapatite is the ceramic closest to the mineral component of human bone and seems, therefore, the optimum material to use in osseous implants. However, in vitro assays performed to determine its bioactivity have shown no positive results after 2 months of assay. With the aim of improving this bioactivity, a new biphasic material was synthesized composed mainly of synthetic carbonatehydroxyapatite and only 5% of a sol-gel bioactive glass. In vitro assays were assessed to determine the bioactive behavior of this new material and revealed that the addition of a minimal amount of bioactive glass is enough to induce bioactivity on synthetic carbonatehydroxyapatites.

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

    ERIC Educational Resources Information Center

    King, Travis L.

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    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…

  17. Reconfigurable virtual electrowetting channels.

    PubMed

    Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

    2012-02-21

    Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

  18. Soft tubular microfluidics for 2D and 3D applications.

    PubMed

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

    2017-09-18

    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.

  19. Fundamentals and applications of inertial microfluidics: a review.

    PubMed

    Zhang, Jun; Yan, Sheng; Yuan, Dan; Alici, Gursel; Nguyen, Nam-Trung; Ebrahimi Warkiani, Majid; Li, Weihua

    2016-01-07

    In the last decade, inertial microfluidics has attracted significant attention and a wide variety of channel designs that focus, concentrate and separate particles and fluids have been demonstrated. In contrast to conventional microfluidic technologies, where fluid inertia is negligible and flow remains almost within the Stokes flow region with very low Reynolds number (Re ≪ 1), inertial microfluidics works in the intermediate Reynolds number range (~1 < Re < ~100) between Stokes and turbulent regimes. In this intermediate range, both inertia and fluid viscosity are finite and bring about several intriguing effects that form the basis of inertial microfluidics including (i) inertial migration and (ii) secondary flow. Due to the superior features of high-throughput, simplicity, precise manipulation and low cost, inertial microfluidics is a very promising candidate for cellular sample processing, especially for samples with low abundant targets. In this review, we first discuss the fundamental kinematics of particles in microchannels to familiarise readers with the mechanisms and underlying physics in inertial microfluidic systems. We then present a comprehensive review of recent developments and key applications of inertial microfluidic systems according to their microchannel structures. Finally, we discuss the perspective of employing fluid inertia in microfluidics for particle manipulation. Due to the superior benefits of inertial microfluidics, this promising technology will still be an attractive topic in the near future, with more novel designs and further applications in biology, medicine and industry on the horizon.

  20. Fundamentals of microfluidic cell culture in controlled microenvironments†

    PubMed Central

    Young, Edmond W. K.; Beebe, David J.

    2010-01-01

    Microfluidics has the potential to revolutionize the way we approach cell biology research. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. One of the key benefits of microfluidics for basic biology is the ability to control parameters of the cell microenvironment at relevant length and time scales. Considerable progress has been made in the design and use of novel microfluidic devices for culturing cells and for subsequent treatment and analysis. With the recent pace of scientific discovery, it is becoming increasingly important to evaluate existing tools and techniques, and to synthesize fundamental concepts that would further improve the efficiency of biological research at the microscale. This tutorial review integrates fundamental principles from cell biology and local microenvironments with cell culture techniques and concepts in microfluidics. Culturing cells in microscale environments requires knowledge of multiple disciplines including physics, biochemistry, and engineering. We discuss basic concepts related to the physical and biochemical microenvironments of the cell, physicochemical properties of that microenvironment, cell culture techniques, and practical knowledge of microfluidic device design and operation. We also discuss the most recent advances in microfluidic cell culture and their implications on the future of the field. The goal is to guide new and interested researchers to the important areas and challenges facing the scientific community as we strive toward full integration of microfluidics with biology. PMID:20179823

  1. Parallel imaging microfluidic cytometer.

    PubMed

    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.

  2. Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing.

    PubMed

    Liao, Yang; Song, Jiangxin; Li, En; Luo, Yong; Shen, Yinglong; Chen, Danping; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

    2012-02-21

    The creation of complex three-dimensional (3D) microfluidic systems has attracted significant attention from both scientific and applied research communities. However, it is still a formidable challenge to build 3D microfluidic structures with arbitrary configurations using conventional planar lithographic fabrication methods. Here, we demonstrate rapid fabrication of high-aspect-ratio microfluidic channels with various 3D configurations in glass substrates by femtosecond laser direct writing. Based on this approach, we demonstrate a 3D passive microfluidic mixer and characterize its functionalities. This technology will enable rapid construction of complex 3D microfluidic devices for a wide array of lab-on-a-chip applications.

  3. Droplet Microfluidic System with On-Demand Trapping and Releasing of Droplet for Drug Screening Applications.

    PubMed

    Courtney, Matthew; Chen, Xiaoming; Chan, Sarah; Mohamed, Tarek; Rao, Praveen P N; Ren, Carolyn L

    2017-01-03

    96-Well plate has been the traditional method used for screening drug compounds libraries for potential bioactivity. Although this method has been proven successful in testing dose-response analysis, the microliter consumption of expensive reagents and hours of reaction and analysis time call for innovative methods for improvements. This work demonstrates a droplet microfluidic platform that has the potential to significantly reduce the reagent consumption and shorten the reaction and analysis time by utilizing nanoliter-sized droplets as a replacement of wells. This platform is evaluated by applying it to screen drug compounds that inhibit the tau-peptide aggregation, a phenomena related to Alzheimer's disease. In this platform, sample reagents are first dispersed into nanolitre-sized droplets by an immiscible carrier oil and then these droplets are trapped on-demand in the downstream of the microfluidic device. The relative decrease in fluorescence through drug inhibition is characterized using an inverted epifluorescence microscope. Finally, the trapped droplets are released on-demand after each test by manipulating the applied pressures to the channel network which allows continuous processing. The testing results agree well with that obtained from 96-well plates with much lower sample consumption (∼200 times lower than 96-well plate) and reduced reaction time due to increased surface volume ratio (2.5 min vs 2 h).

  4. Aptamer entrapment in microfluidic channel using one-step sol-gel process, in view of the integration of a new selective extraction phase for lab-on-a-chip.

    PubMed

    Perréard, Camille; d'Orlyé, Fanny; Griveau, Sophie; Liu, Baohong; Bedioui, Fethi; Varenne, Anne

    2017-10-01

    There is a great demand for integrating sample treatment into μTASs. In this context, we developed a new sol-gel phase for extraction of trace compounds in complex matrices. For this purpose, the incorporation of aptamers in silica-based gel within PDMS/glass microfluidic channels was performed for the first time by a one-step sol-gel process. The effective gel attachment onto microchannel walls and aptamer incorporation in the polymerized gel were evaluated using fluorescence microscopy. A good gel stability and aptamer incorporation inside the microchannel was demonstrated upon rinsing and over storage time. The ability of gel-encapsulated aptamers to interact with its specific target (either sulforhodamine B as model fluorescent target, or diclofenac, a pain killer drug) was assessed too. The binding capacity of entrapped aptamers was quantified (in the micromolar range) and the selectivity of the interaction was evidenced. Preservation of aptamers binding affinity to target molecules was therefore demonstrated. Dissociation constant of the aptamer-target complex and interaction selectivity were evaluated similar to those in bulk solution. This opens the way to new selective on-chip SPE techniques for sample pretreatment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Enzymatic Reactions in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Ristenpart, W. D.; Wan, J.; Stone, H. A.

    2008-11-01

    We establish simple scaling laws for enzymatic reactions in microfluidic devices, and we demonstrate that kinetic parameters obtained conventionally using multiple stop-flow experiments may instead be extracted from a single microfluidic experiment. Introduction of an enzyme and substrate species in different arms of a Y-shaped channel allows the two species to diffuse across the parallel streamlines and to begin reacting. Measurements of the product concentration versus distance down the channel provide information about the kinetics of the reaction. In the limit where the enzyme is much larger (and thus less diffusive) than the substrate, we show that near the entrance the total amount of product (P) formed varies as a power law in the distance x down the channel. For reactions that follow standard Michaelis-Menten kinetics, the power law takes the form P˜(Vmax/Km) x^5/2, where Vmax and Km are the maximum reaction rate and Michaelis constant respectively. If a large excess of substrate is used, then Km is identified by measuring Vmax far downstream where the different species are completely mixed by diffusion. Numerical simulations and experiments using the bioluminescent reaction between luciferase and ATP as a model system are both shown to accord with the model. We discuss the implications for significant savings in the amount of time and enzyme required for determination of kinetic parameters.

  6. Microfluidic reactors for diagnostics applications.

    PubMed

    McCalla, Stephanie E; Tripathi, Anubhav

    2011-08-15

    Diagnostic assays are an important part of health care, both in the clinic and in research laboratories. In addition to improving treatments and clinical outcomes, rapid and reliable diagnostics help track disease epidemiology, curb infectious outbreaks, and further the understanding of chronic illness. Disease markers such as antigens, RNA, and DNA are present at low concentrations in biological samples, such that the majority of diagnostic assays rely on an amplification reaction before detection is possible. Ideally, these amplification reactions would be sensitive, specific, inexpensive, rapid, integrated, and automated. Microfluidic technology currently in development offers many advantages over conventional benchtop reactions that help achieve these goals. The small reaction volumes and energy consumption make reactions cheaper and more efficient in a microfluidic reactor. Additionally, the channel architecture could be designed to perform multiple tests or experimental steps on one integrated, automated platform. This review explores the current research on microfluidic reactors designed to aid diagnostic applications, covering a broad spectrum of amplification techniques and designs.

  7. Surface-micromachined microfluidic devices

    DOEpatents

    Galambos, Paul C.; Okandan, Murat; Montague, Stephen; Smith, James H.; Paul, Phillip H.; Krygowski, Thomas W.; Allen, James J.; Nichols, Christopher A.; Jakubczak, II, Jerome F.

    2003-01-01

    Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators.

  8. Patterning of PMMA microfluidic parts using screen printing process

    NASA Astrophysics Data System (ADS)

    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.

  9. Microfluidic DNA extraction using a patterned aluminum oxide membrane

    NASA Astrophysics Data System (ADS)

    Kim, Jungkyu; Gale, Bruce K.

    2006-01-01

    A DNA extraction system was designed and fabricated using an AOM (aluminum oxide membrane) with 200 nm pores and PDMS microfluidic channels. The membrane was patterned using soft lithography techniques and SU-8 photolithography on the membrane. After making the pattern with SU-8, the AOM was observed using an SEM (scanning electro microscope) to verify the AOM structure was not damaged. From the SEM images, the AOM structure was not different after modification with SU-8. To complete the system, a PDMS mold for the microfluidic channels was made by soft lithography. Using the SU-8 mold, PDMS microchannels were cast using PDMS with a low polymer to curing agent ratio to provide adhesion between the patterned membrane and microfluidic channel. Then, the patterned membrane was sandwiched between PDMS microfluidic channels in a parallel format. The completed system was tested with 10ug of Lambda DNA mixed with the fluorescent dye SYBR Green I. Following DNA extraction, the surface of each well was examined with fluorescence microscopy while embedded in the microfluidic system. Extracted and immobilized DNA on the AOM was observed in almost every separation well. This microsystem, referred to as a membrane-on-a-chip, has potential applications in high-throughput DNA extraction and analysis, with the possibility of being integrated into polymer-based microfluidic systems.

  10. Microfluidic Wheatstone bridge for rapid sample analysis.

    PubMed

    Tanyeri, Melikhan; Ranka, Mikhil; Sittipolkul, Natawan; Schroeder, Charles M

    2011-12-21

    We developed a microfluidic analogue of the classic Wheatstone bridge circuit for automated, real-time sampling of solutions in a flow-through device format. We demonstrate precise control of flow rate and flow direction in the "bridge" microchannel using an on-chip membrane valve, which functions as an integrated "variable resistor". We implement an automated feedback control mechanism in order to dynamically adjust valve opening, thereby manipulating the pressure drop across the bridge and precisely controlling fluid flow in the bridge channel. At a critical valve opening, the flow in the bridge channel can be completely stopped by balancing the flow resistances in the Wheatstone bridge device, which facilitates rapid, on-demand fluid sampling in the bridge channel. In this article, we present the underlying mechanism for device operation and report key design parameters that determine device performance. Overall, the microfluidic Wheatstone bridge represents a new and versatile method for on-chip flow control and sample manipulation.

  11. Integrating plasmonic diagnostics and microfluidics

    PubMed Central

    Niu, Lifang; Zhang, Nan; Liu, Hong; Zhou, Xiaodong; Knoll, Wolfgang

    2015-01-01

    Plasmonics is generally divided into two categories: surface plasmon resonance (SPR) of electromagnetic modes propagating along a (noble) metal/dielectric interface and localized SPRs (LSPRs) on nanoscopic metallic structures (particles, rods, shells, holes, etc.). Both optical transducer concepts can be combined with and integrated in microfluidic devices for biomolecular analyte detections, with the benefits of small foot-print for point-of-care detection, low-cost for one-time disposal, and ease of being integrated into an array format. The key technologies in such integration include the plasmonic chip, microfluidic channel fabrication, surface bio-functionalization, and selection of the detection scheme, which are selected according to the specifics of the targeting analytes. This paper demonstrates a few examples of the many versions of how to combine plasmonics and integrated microfluidics, using different plasmonic generation mechanisms for different analyte detections. One example is a DNA sensor array using a gold film as substrate and surface plasmon fluorescence spectroscopy and microscopy as the transduction method. This is then compared to grating-coupled SPR for poly(ethylene glycol) thiol interaction detected by angle interrogation, gold nanohole based LSPR chip for biotin-strepavidin detection by wavelength shift, and gold nanoholes/nanopillars for the detection of prostate specific antigen by quantum dot labels excited by the LSPR. Our experimental results exemplified that the plasmonic integrated microfluidics is a promising tool for understanding the biomolecular interactions and molecular recognition process as well as biosensing, especially for on-site or point-of-care diagnostics. PMID:26392832

  12. Integrating plasmonic diagnostics and microfluidics.

    PubMed

    Niu, Lifang; Zhang, Nan; Liu, Hong; Zhou, Xiaodong; Knoll, Wolfgang

    2015-09-01

    Plasmonics is generally divided into two categories: surface plasmon resonance (SPR) of electromagnetic modes propagating along a (noble) metal/dielectric interface and localized SPRs (LSPRs) on nanoscopic metallic structures (particles, rods, shells, holes, etc.). Both optical transducer concepts can be combined with and integrated in microfluidic devices for biomolecular analyte detections, with the benefits of small foot-print for point-of-care detection, low-cost for one-time disposal, and ease of being integrated into an array format. The key technologies in such integration include the plasmonic chip, microfluidic channel fabrication, surface bio-functionalization, and selection of the detection scheme, which are selected according to the specifics of the targeting analytes. This paper demonstrates a few examples of the many versions of how to combine plasmonics and integrated microfluidics, using different plasmonic generation mechanisms for different analyte detections. One example is a DNA sensor array using a gold film as substrate and surface plasmon fluorescence spectroscopy and microscopy as the transduction method. This is then compared to grating-coupled SPR for poly(ethylene glycol) thiol interaction detected by angle interrogation, gold nanohole based LSPR chip for biotin-strepavidin detection by wavelength shift, and gold nanoholes/nanopillars for the detection of prostate specific antigen by quantum dot labels excited by the LSPR. Our experimental results exemplified that the plasmonic integrated microfluidics is a promising tool for understanding the biomolecular interactions and molecular recognition process as well as biosensing, especially for on-site or point-of-care diagnostics.

  13. Integrated Microfluidic Reactors.

    PubMed

    Lin, Wei-Yu; Wang, Yanju; Wang, Shutao; Tseng, Hsian-Rong

    2009-12-01

    Microfluidic reactors exhibit intrinsic advantages of reduced chemical consumption, safety, high surface-area-to-volume ratios, and improved control over mass and heat transfer superior to the macroscopic reaction setting. In contract to a continuous-flow microfluidic system composed of only a microchannel network, an integrated microfluidic system represents a scalable integration of a microchannel network with functional microfluidic modules, thus enabling the execution and automation of complicated chemical reactions in a single device. In this review, we summarize recent progresses on the development of integrated microfluidics-based chemical reactors for (i) parallel screening of in situ click chemistry libraries, (ii) multistep synthesis of radiolabeled imaging probes for positron emission tomography (PET), (iii) sequential preparation of individually addressable conducting polymer nanowire (CPNW), and (iv) solid-phase synthesis of DNA oligonucleotides. These proof-of-principle demonstrations validate the feasibility and set a solid foundation for exploring a broad application of the integrated microfluidic system.

  14. Thermophoresis of DNA determined by microfluidic fluorescence.

    PubMed

    Duhr, S; Arduini, S; Braun, D

    2004-11-01

    We describe a microfluidic all-optical technique to measure the thermophoresis of molecules. Within micrometer-thick chambers, we heat aqueous solutions with a micrometer-sized focus of infrared light. The temperature increase of about 1 K is monitored with temperature-sensitive fluorescent dyes. We test the approach in measuring the thermophoresis of DNA. We image the concentration of DNA in a second fluorescence-color channel. DNA is depleted away from the heated spot. The profile of depletion is fitted by the thermophoretic theory to reveal the Soret coefficient. We evaluate the method with numerical 3D calculations of temperature profiles, drift, convection and thermophoretic depletion using finite element methods. The approach opens new ways to monitor thermophoresis at the single molecule level, near boundaries and in complex mixtures. The flexible microfluidic setting is a good step towards microfluidic applications of thermophoresis in biotechnology.

  15. Microfluidic systems for single DNA dynamics

    PubMed Central

    Mai, Danielle J.; Brockman, Christopher

    2012-01-01

    Recent advances in microfluidics have enabled the molecular-level study of polymer dynamics using single DNA chains. Single polymer studies based on fluorescence microscopy allow for the direct observation of non-equilibrium polymer conformations and dynamical phenomena such as diffusion, relaxation, and molecular stretching pathways in flow. Microfluidic devices have enabled the precise control of model flow fields to study the non-equilibrium dynamics of soft materials, with device geometries including curved channels, cross-slots, and microfabricated obstacles and structures. This review explores recent microfluidic systems that have advanced the study of single polymer dynamics, while identifying new directions in the field that will further elucidate the relationship between polymer microstructure and bulk rheological properties. PMID:23139700

  16. Thermophoresis of DNA determined by microfluidic fluorescence

    NASA Astrophysics Data System (ADS)

    Duhr, S.; Arduini, S.; Braun, D.

    2004-11-01

    We describe a microfluidic all-optical technique to measure the thermophoresis of molecules. Within micrometer-thick chambers, we heat aqueous solutions with a micrometer-sized focus of infrared light. The temperature increase of about 1 K is monitored with temperature-sensitive fluorescent dyes. We test the approach in measuring the thermophoresis of DNA. We image the concentration of DNA in a second fluorescence-color channel. DNA is depleted away from the heated spot. The profile of depletion is fitted by the thermophoretic theory to reveal the Soret coefficient. We evaluate the method with numerical 3D calculations of temperature profiles, drift, convection and thermophoretic depletion using finite element methods. The approach opens new ways to monitor thermophoresis at the single molecule level, near boundaries and in complex mixtures. The flexible microfluidic setting is a good step towards microfluidic applications of thermophoresis in biotechnology.

  17. Commercialization of microfluidic devices.

    PubMed

    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.

  18. Microfluidics for manipulating cells.

    PubMed

    Mu, Xuan; Zheng, Wenfu; Sun, Jiashu; Zhang, Wei; Jiang, Xingyu

    2013-01-14

    Microfluidics, a toolbox comprising methods for precise manipulation of fluids at small length scales (micrometers to millimeters), has become useful for manipulating cells. Its uses range from dynamic management of cellular interactions to high-throughput screening of cells, and to precise analysis of chemical contents in single cells. Microfluidics demonstrates a completely new perspective and an excellent practical way to manipulate cells for solving various needs in biology and medicine. This review introduces and comments on recent achievements and challenges of using microfluidics to manipulate and analyze cells. It is believed that microfluidics will assume an even greater role in the mechanistic understanding of cell biology and, eventually, in clinical applications.

  19. Micro-fluidic interconnect

    DOEpatents

    Okandan, Murat; Galambos, Paul C.; Benavides, Gilbert L.; Hetherington, Dale L.

    2006-02-28

    An apparatus for simultaneously aligning and interconnecting microfluidic ports is presented. Such interconnections are required to utilize microfluidic devices fabricated in Micro-Electromechanical-Systems (MEMS) technologies, that have multiple fluidic access ports (e.g. 100 micron diameter) within a small footprint, (e.g. 3 mm.times.6 mm). Fanout of the small ports of a microfluidic device to a larger diameter (e.g. 500 microns) facilitates packaging and interconnection of the microfluidic device to printed wiring boards, electronics packages, fluidic manifolds etc.

  20. [Application of microfluidics in aquatic environmental pollution analysis].

    PubMed

    Wang, Hu; Wei, Jun-Feng; Zheng, Guo-Xia

    2014-04-01

    Recently, a new type of chip technology, microfluidics, has received global attention for its rapid analysis speed, low reagent consumption, small size and simple operation, etc. Based on a micro-channel network and supported by a Micro-Electro-Mechanic System (MEMS), this technology integrates all the functions of a laboratory into one small piece of chip, which is called "lab on the chip". This paper presented a brief introduction about microfluidics and its representative developments. Future prospects in the aspects of instrument miniaturization, system integration, chip materials, and detection techniques, as well as the implementation of microfluidics in aquatic environmental pollutant analysis were thoroughly discussed. Some problems faced now were put forward. With the rapid progress in the microfluidics, a universal low-cost microchip capable of high speed multi-channel detection and integrated with many kinds of detection methods would be the research focus in the future.

  1. Nanoparticle detection by microfluidic resistive pulse sensor with optical evidence

    NASA Astrophysics Data System (ADS)

    Zhang, Hongpeng; Song, Yongxin; Pan, Xinxiang; Sun, Yuqing; Li, Dongqing; Jiang, Jihai

    2010-12-01

    This paper reports a device that performs nanoparticle detection with a microfluidic differential Resistive Pulse Sensor (RPS). By using a single microfluidic channel with two detecting arm channels placed at the two ends of the sensing section, the microfluidic differential RPS can achieve a high sensitivity allowing the detection of nanometer size particles. Two-stage differential amplification is used to further increase the signal-to-noise ratio. This method is able to detect nanoparticles of 490nm on a microfluidic chip. An 8μm gate and a 2.7μm gate detected the 490 nm particle. The electrical signal was with optical evidence. The result showed 2.7μm chip can realize signal to noise ratio higher than 10. The method described in this paper is simple and can be applied to develop a compact device without the need of bulky, sophisticated electronic instruments or complicated nano-fabrication processes.

  2. Bubble-induced damping in displacement-driven microfluidic flows.

    PubMed

    Lee, Jongho; Rahman, Faizur; Laoui, Tahar; Karnik, Rohit

    2012-08-01

    Bubble damping in displacement-driven microfluidic flows was theoretically and experimentally investigated for a Y-channel microfluidic network. The system was found to exhibit linear behavior for typical microfluidic flow conditions. The bubbles induced a low-pass filter behavior with a characteristic cutoff frequency that scaled proportionally with flow rate and inversely with bubble volume and exhibited a minimum with respect to the relative resistances of the connecting channels. A theoretical model based on the electrical circuit analogy was able to predict experimentally observed damping of fluctuations with excellent agreement. Finally, a flowmeter with high resolution (0.01 μL/min) was demonstrated as an application of the bubble-aided stabilization. This study may aid in the design of many other bubble-stabilized microfluidic systems.

  3. Desktop aligner for fabrication of multilayer microfluidic devices

    NASA Astrophysics Data System (ADS)

    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.

  4. Desktop aligner for fabrication of multilayer microfluidic devices.

    PubMed

    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.

  5. Desktop aligner for fabrication of multilayer microfluidic devices

    PubMed Central

    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

    2015-01-01

    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. PMID:26233409

  6. Vascular smooth muscle cell culture in microfluidic devices

    PubMed Central

    Wei, Y. C.; Chen, F.; Zhang, T.; Chen, D. Y.; Jia, X.; Wang, J. B.; Guo, W.; Chen, J.

    2014-01-01

    This paper presents a microfluidic device enabling culture of vascular smooth muscle cells (VSMCs) where extracellular matrix coating, VSMC seeding, culture, and immunostaining are demonstrated in a tubing-free manner. By optimizing droplet volume differences between inlets and outlets of micro channels, VSMCs were evenly seeded into microfluidic devices. Furthermore, the effects of extracellular matrix (e.g., collagen, poly-l-Lysine (PLL), and fibronectin) on VSMC proliferation and phenotype expression were explored. As a platform technology, this microfluidic device may function as a new VSMC culture model enabling VSMC studies. PMID:25379109

  7. Smart Microfluidic Electrochemical DNA Sensors with Signal Processing Circuits

    NASA Astrophysics Data System (ADS)

    Sawada, Kazuaki; Oda, Chigusa; Takao, Hidekuni; Ishida, Makoto

    2007-05-01

    A smart microfluidic DNA sensor with an integrated signal-processing circuit for electrochemical analysis has been successfully fabricated. The sensor comprises an integrated electrochemical sensing electrode, a microfluidic channel-type reactor, and operational amplifiers for electrochemical measurement. The microfluidic reactor employs a laminar flow principle. Generally, a relatively large and expensive system is necessary for electrochemical measurement. In the fabricated smart chip, signal-processing circuits for measuring cyclic-voltammogram characteristics are integrated, permitting cyclic-voltammograms to be successively measured, using only two simple sources of electrical power.

  8. The processing technology of PMMA micro-fluidic chip

    NASA Astrophysics Data System (ADS)

    Mu, Lili; Rong, Li; Guo, Shuheng; Liu, Qiong

    2016-01-01

    In order to enrich the production method of micro-fluidic chip and simplify its processing technology, the paper discussed the double-sided adhesive layer for channel layer, with PMMA (polymethyl methacrylate) for fabrication of microfluidic chip with the cover plate and the bottom plate. Taking 40 mm (long) x 20 mm (wide) x 2.2 mm (thick) liquid drop to separate the microfluidic chip as an example, details the design and machining process of the chip. Experiments show that surface quality is high and processing speed is fast when using this technology to process the chip. Thus, it can realize the mass production of micro fluidic chip.

  9. Surface-Micromachined Microfluidic Devices

    DOEpatents

    Galambos, Paul C.; Okandan, Murat; Montague, Stephen; Smith, James H.; Paul, Phillip H.; Krygowski, Thomas W.; Allen, James J.; Nichols, Christopher A.; Jakubczak, II, Jerome F.

    2004-09-28

    Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators. Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators.

  10. Microfluidic Compartmentalized Directed Evolution

    PubMed Central

    Paegel, Brian M.; Joyce, Gerald F.

    2010-01-01

    Summary Directed evolution studies often make use of water-in-oil compartments, which conventionally are prepared by bulk emulsification, a crude process that generates non-uniform droplets and can damage biochemical reagents. A microfluidic emulsification circuit was devised that generates uniform water-in-oil droplets (21.9 ± 0.8 μm radius) with high throughput (107–108 droplets per hour). The circuit contains a radial array of aqueous flow nozzles that intersect a surrounding oil flow channel. This device was used to evolve RNA enzymes with RNA ligase activity, selecting enzymes that could resist inhibition by neomycin. Each molecule in the population had the opportunity to undergo 108-fold selective amplification within its respective compartment. Then the progeny RNAs were harvested and used to seed new compartments. During five rounds of this procedure, the enzymes acquired mutations that conferred resistance to neomycin and caused some enzymes to become dependent on neomycin for optimal activity. PMID:20659684

  11. Microfluidic reflow pumps.

    PubMed

    Haslam, Bryan; Tsai, Long-Fang; Anderson, Ryan R; Kim, Seunghyun; Hu, Weisheng; Nordin, Gregory P

    2015-07-01

    A new microfluidic pump, termed a reflow pump, is designed to operate with a sub-μl sample volume and transport it back and forth between two pneumatically actuated reservoirs through a flow channel typically containing one or more sensor surfaces. The ultimate motivation is to efficiently use the small sample volume in conjunction with convection to maximize analyte flux to the sensor surface(s) in order to minimize sensor response time. In this paper, we focus on the operational properties of the pumps themselves (rather than the sensor surfaces), and demonstrate both two-layer and three-layer polydimethylsiloxane reflow pumps. For the three-layer pump, we examine the effects of reservoir actuation pressure and actuation period, and demonstrate average volumetric flow rates as high as 500 μl/min. We also show that the two-layer design can pump up to 93% of the sample volume during each half period and demonstrate integration of a reflow pump with a single-chip microcantilever array to measure maximum flow rate.

  12. Materials for microfluidic chip fabrication.

    PubMed

    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

  13. Microfluidic distillation chip for methanol concentration detection.

    PubMed

    Wang, Yao-Nan; Liu, Chan-Chiung; Yang, Ruey-Jen; Ju, Wei-Jhong; Fu, Lung-Ming

    2016-03-17

    An integrated microfluidic distillation system is proposed for separating a mixed ethanol-methanol-water solution into its constituent components. The microfluidic chip is fabricated using a CO2 laser system and comprises a serpentine channel, a boiling zone, a heating zone, and a cooled collection chamber filled with de-ionized (DI) water. In the proposed device, the ethanol-methanol-water solution is injected into the microfluidic chip and driven through the serpentine channel and into the collection chamber by means of a nitrogen carrier gas. Following the distillation process, the ethanol-methanol vapor flows into the collection chamber and condenses into the DI water. The resulting solution is removed from the collection tank and reacted with a mixed indicator. Finally, the methanol concentration is inversely derived from the absorbance measurements obtained using a spectrophotometer. The experimental results show the proposed microfluidic system achieves an average methanol distillation efficiency of 97%. The practicality of the proposed device is demonstrated by detecting the methanol concentrations of two commercial fruit wines. It is shown that the measured concentration values deviate by no more than 3% from those obtained using a conventional bench top system.

  14. Logic control of microfluidics with smart colloid.

    PubMed

    Wang, Limu; Zhang, Mengying; Li, Jiaxing; Gong, Xiuqing; Wen, Weijia

    2010-11-07

    We report the successful realization of a microfluidic chip with switching and corresponding inverting functionalities. The chips are identical logic control components incorporating a type of smart colloid, giant electrorheological fluid (GERF), which possesses reversible characteristics via a liquid-solid phase transition under external electric field. Two pairs of electrodes embedded on the sides of two microfluidic channels serve as signal input and output, respectively. One, located in the GERF micro-channel is used to control the flow status of GERF, while another one in the ither micro-fluidic channel is used to detect the signal generated with a passing-by droplet (defined as a signal droplet). Switching of the GERF from the suspended state (off-state) to the flowing state (on-state) or vice versa in the micro-channel is controlled by the appearance of signal droplets whenever they pass through the detection electrode. The output on-off signals can be easily demonstrated, clearly matching with GERF flow status. Our results show that such a logic switch is also a logic IF gate, while its inverter functions as a NOT gate.

  15. Orientation-Based Control of Microfluidics

    PubMed Central

    Norouzi, Nazila; Bhakta, Heran C.; Grover, William H.

    2016-01-01

    Most microfluidic chips utilize off-chip hardware (syringe pumps, computer-controlled solenoid valves, pressure regulators, etc.) to control fluid flow on-chip. This expensive, bulky, and power-consuming hardware severely limits the utility of microfluidic instruments in resource-limited or point-of-care contexts, where the cost, size, and power consumption of the instrument must be limited. In this work, we present a technique for on-chip fluid control that requires no off-chip hardware. We accomplish this by using inert compounds to change the density of one fluid in the chip. If one fluid is made 2% more dense than a second fluid, when the fluids flow together under laminar flow the interface between the fluids quickly reorients to be orthogonal to Earth’s gravitational force. If the channel containing the fluids then splits into two channels, the amount of each fluid flowing into each channel is precisely determined by the angle of the channels relative to gravity. Thus, any fluid can be routed in any direction and mixed in any desired ratio on-chip simply by holding the chip at a certain angle. This approach allows for sophisticated control of on-chip fluids with no off-chip control hardware, significantly reducing the cost of microfluidic instruments in point-of-care or resource-limited settings. PMID:26950700

  16. A Microfluidic Platform for Interfacial Electrophoretic Deposition

    NASA Astrophysics Data System (ADS)

    Joung, Young Soo; Moran, Jeffrey; Jones, Andrew; Bailey, Eric; Buie, Cullen

    2014-11-01

    Composite membranes of hydrogel and carbon nanotubes (CNTs) are fabricated using electrophoretic deposition (EPD) at the interface of two immiscible liquids in microfluidic channels. Microfluidic channels, which have two parallel electrodes at the walls, are used to create electric fields across the interface of oil and water continuously supplied into the channels. Depending on the Reynolds (Re) and Weber (We) numbers of oil and water, we observe different formations of the interface. Once we find the optimal Re and We to create a planar interface in the channel, we apply an electric field across the interface for EPD of CNTs and/or silver (Ag) nanorods dispersed in water. During EPD, particles migrate to the oil/water interface, where cross-linking of polymers is induced to form composite hydrogel membranes. Properties of the composite hydrogel films are controlled by electric fields, CNT concentrations, and both Re and We numbers, allowing for continuous production. This fabrication method is effective to create composite polymer membranes placed in microfluidic devices with tunable electrical, mechanical, and biological properties. Potential applications include fabrication of doped hydrogels for drug delivery, conductive hydrogels for biological sensing, and electron permeable membranes for water splitting and osmotic power generation.

  17. Intensely oscillating cavitation bubble in microfluidics

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    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.

  18. Fabrication of a hybrid PDMS/SU-8/quartz microfluidic chip for enhancing UV absorption whole-channel imaging detection sensitivity and application for isoelectric focusing of proteins.

    PubMed

    Ou, Junjie; Glawdel, Tomasz; Ren, Carolyn L; Pawliszyn, Janusz

    2009-07-07

    A poly(dimethylsiloxane)(PDMS)/SU-8/quartz hybrid chip was developed and applied in the isoelectric focusing (IEF) of proteins with ultraviolet (UV) absorbance-based whole-channel imaging detection (UV-WCID). Each hybrid chip was made of three layers: a PDMS flat top substrate, a bottom quartz substrate and a middle layer of SU-8 photoresist. The SU-8 serves two purposes: it contains the microchannel used for IEF separation, and acts as an optical slit that absorbs UV light below 300 nm improving detection sensitivity in WCID. The novel hybrid design demonstrates a two to three times improvement in sensitivity over a comparable PDMS/PDMS design. In addition, the hybrid chip exhibits increased heat dissipation due to the superior thermal conductivity of the bottom quartz substrate allowing for larger electric fields to be used in separations. The hybrid design with IEF-UV-WCID was successful in resolving a complicated sample, hemoglobin control, with high fidelity.

  19. TiO2 patterns with wide photo-induced wettability change by a combination of reactive sputtering process and surface modification in a microfluidic channel

    NASA Astrophysics Data System (ADS)

    Kobayashi, Taizo; Konishi, Satoshi

    2015-11-01

    This paper reports the formation of TiO2 patterns with a wide range of photo-induced wettability switching from high hydrophobic to superhydrophilic states for on-chip liquid manipulation. TiO2 thin films with rough surface morphology were formed by a combination of optimised reactive sputtering and CF4 plasma etching. Octadecylphosphonic acid self-assembled monolayer (ODP-SAM) surface modification was applied to the surface-roughened TiO2 thin films in order to obtain a highly hydrophobic surface initially. Photocatalytic decomposition of ODP-SAM on the surface-roughened TiO2 by ultraviolet (UV) irradiation caused a wetting transition from the Cassie-Baxter state to the Wenzel state. Switching of the flow direction into branch channels was also demonstrated by utilising the photoresponsive wettability of the surface-modified TiO2 patterns on a fluidic chip.

  20. Appendix C: Automated Vitrification of Mammalian Embryos on a Digital Microfluidic Device.

    PubMed

    Liu, Jun; Pyne, Derek G; Abdelgawad, Mohamed; Sun, Yu

    2017-01-01

    This chapter introduces a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual microdroplets manipulated on the microfluidic device were used as microvessels 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.

  1. Microfluidics and Coagulation Biology

    PubMed Central

    Colace, Thomas V.; Tormoen, Garth W.

    2014-01-01

    The study of blood ex vivo can occur in closed or open systems, with or without flow. Microfluidic devices facilitate measurements of platelet function, coagulation biology, cellular biorheology, adhesion dynamics, pharmacology, and clinical diagnostics. An experimental session can accommodate 100s to 1000s of unique clotting events. Using microfluidics, thrombotic events can be studied on defined surfaces of biopolymers, matrix proteins, and tissue factor under constant flow rate or constant pressure drop conditions. Distinct shear rates can be created on a device with a single perfusion pump. Microfluidic devices facilitated the determination of intraluminal thrombus permeability and the discovery that platelet contractility can be activated by a sudden decrease in flow. Microfluidics are ideal for multicolor imaging of platelets, fibrin, and phosphatidylserine and provide a human blood analog to the mouse injury models. Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics. PMID:23642241

  2. Microfluidic probe: a new tool for integrating microfluidic environments and electronic wafer-probing.

    PubMed

    Routenberg, David A; Reed, Mark A

    2010-01-07

    We demonstrate a new tool for integrating microfluidic channels with commonly used electronic probing techniques. The "microfluidic probe" allows rapid and repeatable fluidic and electronic addressing of small die sites on a variety of substrate types without the need for permanent modification or dicing of the device wafers. We also use the probe to demonstrate locally patterned chemical modification of a substrate. The probes are easily fabricated using standard soft-lithography and basic machining making this a widely accessible technique for electronics and fluidics researchers.

  3. Unconventional microfluidics: expanding the discipline.

    PubMed

    Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S; Huang, Tony Jun

    2013-04-21

    Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields-and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such "unconventional" microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline.

  4. Unconventional microfluidics: expanding the discipline

    PubMed Central

    Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S.; Huang, Tony Jun

    2014-01-01

    Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields—and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such “unconventional” microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline. PMID:23478651

  5. Integrated opto-microfluidics platforms in lithium niobate crystals for sensing applications

    NASA Astrophysics Data System (ADS)

    Bettella, G.; Pozza, G.; Zaltron, A.; Ciampolillo, M. V.; Argiolas, N.; Sada, C.; Chauvet, M.; Guichardaz, B.

    2015-02-01

    In micro-analytical chemistry and biology applications, droplet microfluidic technology holds great promise for efficient lab-on-chip systems where higher levels of integration of different stages on the same platform is constantly addressed. The possibility of integration of opto-microfluidic functionalities in lithium niobate (LiNbO3) crystals is presented. Microfluidic channels were directly engraved in a LiNbO3 substrate by precision saw cutting, and illuminated by optical waveguides integrated on the same substrate. The morphological characterization of the microfluidic channel and the optical response of the coupled optical waveguide were tested. In particular, the results indicate that the optical properties of the constituents dispersed in the fluid flowing in the microfluidic channel can be monitored in situ, opening to new compact optical sensor prototypes based on droplets generation and optical analysis of the relative constituents.

  6. Immobilization of trypsin in the layer-by-layer coating of graphene oxide and chitosan on in-channel glass fiber for microfluidic proteolysis.

    PubMed

    Bao, Huimin; Chen, Qiwen; Zhang, Luyan; Chen, Gang

    2011-12-21

    In this report, trypsin was immobilized in the layer-by-layer (LBL) coating of graphene oxide (GO) and chitosan on a piece of glass fiber to fabricate microchip bioreactor for efficient proteolysis. LBL deposition driven by electrostatic forces easily took place on the surface of the glass fiber, providing mild environmental conditions so that the denaturation and autolysis of the immobilized trypsin was minimized. Prior to use, a piece of the prepared trypsin-immobilized glass fiber was inserted into the channel of a microchip to form a core-changeable bioreactor. The novel GO-based bioreactor can be regenerated by changing its fiber core. The feasibility and performance of the unique bioreactor were demonstrated by the tryptic digestion of bovine serum albumin, myoglobin, cytochrome c, and hemoglobin and the digestion time was significantly reduced to less than 10 s. The obtained digests were identified by MALDI-TOF MS. The digestion performance of the core-changeable GO-based microchip bioreactor was comparable to that of 12-h in-solution tryptic digestion. The novel microchip bioreactor is simple and efficient, offering great promise for high-throughput protein identification.

  7. Evaluation of Manufacturing Processes for Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Laura Jáuregui, Ana; Siller, Héctor R.; Rodriguez, Ciro A.; Elías-Zúñiga, Alex

    2009-11-01

    In this paper several micro-mechanical manufacturing technologies were studied in order to characterize their performance for making miniaturized geometries known as micro-channels, which are the main geometric features of micro-fluidic devices. The technologies used were Micro-End Milling, Wire Electro Discharge Machiningesol Sandblasting and Abrasive Water Jet. Their capabilities were compared with Lithography capabilities, which is the conventional process for micro-channel manufacturing. The evaluation consists in a comprehensive study of surface quality and topography, made with the help of advanced contact and non-contact devices over each prototype made by each technology. Also economical considerations have been taken into account in order to choose the most appropriate manufacturing process for the prototyping of micro-fluidic devices. The results show that Micro-End Milling process can compete with Lithography, in terms of achieving acceptable levels of product quality and economics.

  8. Microfluidic systems for electrochemical and biological studies

    SciTech Connect

    Ackler, H., LLNL

    1998-05-01

    Microfluidic devices with microelectrodes have the potential to enable studies of phenomena at size scales where behavior may be dominated by different mechanisms than at macroscales. Through our work developing microfluidic devices for dielectrophoretic separation and sensing of cells and particles, we have fabricated devices from which general or more specialized research devices may be derived. Fluid channels from 80 {micro}m wide X 20 {micro}m deep to 1 mm wide to 200 {micro}m deep have been fabricated in glass, with lithographically patterned electrodes from 10 to 80 {micro}m wide on one or both sides on the channels and over topographies tens of microns in heights. the devices are designed to easily interface to electronic and fluidic interconnect packages that permit reuse of devices, rather than one-time use, crude glue-based methods. Such devices may be useful for many applications of interest to the electrochemical and biological community.

  9. Direct digital manufacturing of autonomous centrifugal microfluidic device

    NASA Astrophysics Data System (ADS)

    Ukita, Yoshiaki; Takamura, Yuzuru; Utsumi, Yuichi

    2016-06-01

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

  10. Effects of BmKNJX11, a bioactive polypeptide purified from Buthus martensi Karsch, on sodium channels in rat dorsal root ganglion neurons.

    PubMed

    Wang, Xi-Jie; An, Shan-Shan; Cheng, Hong; Xu, San-Hua; Cheng, Jie; Lu, Wei; Gao, Rong; Xiao, Hang

    2009-01-01

    A long-chain polypeptide BmKNJX11 was purified from the venom of Asian scorpion Buthus martensi Karsch (BmK) by a combination of gel filtration, ion-exchange chromatography, and reverse-phase high-performance liquid chromatography. The molecular mass was found to be 7036.85 Da by electrospray ionization mass spectrometry. The first 15 N-terminal amino acid sequence of BmKNJX11 was determined to be GRDAY IADSE NCTYT by Edman degradation. With whole cell recording, BmKNJX11 inhibited tetrodotoxin-sensitive voltage-gated sodium channels (TTX-S VGSC) in freshly isolated rat dorsal root ganglion (DRG) neurons in a concentration- and voltage-dependent manner. At a concentration of 40 mug/ml BmKNJX11 lowered the activation threshold and produced negative shifting of TTX-S sodium current (I(Na)) activation curve. In addition, BmKNJX11 induced shifting of the steady-state inactivation curve to the left, delayed the recovery of TTX-S I(Na) from inactivation, and also reduced the fraction of available sodium channels. These results suggested that BmKNJX11 might exert effects on VGSC by binding to a specific site. Considering that TTX-S VGSC expressed in DRG neurons play a critical role in nociceptive transmission, the interaction of BmKNJX11 with TTX-S VGSC might lead to a change in excitability of nociceptive afferent fibers, which may be involved in the observed peripheral pain expression.

  11. Method Of Packaging And Assembling Electro-Microfluidic Devices

    DOEpatents

    Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Zamora, David Lee; Watson, Robert D.

    2004-11-23

    A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

  12. Fluid delivery manifolds and microfluidic systems

    DOEpatents

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

    2017-02-28

    Embodiments of fluid distribution manifolds, cartridges, and microfluidic systems are described herein. Fluid distribution manifolds may include an insert member and a manifold base and may define a substantially closed channel within the manifold when the insert member is press-fit into the base. Cartridges described herein may allow for simultaneous electrical and fluidic interconnection with an electrical multiplex board and may be held in place using magnetic attraction.

  13. Microfluidic particle sorting utilizing inertial lift force.

    PubMed

    Nieuwstadt, Harm A; Seda, Robinson; Li, David S; Fowlkes, J Brian; Bull, Joseph L

    2011-02-01

    A simple passive microfluidic device that continuously separates microparticles is presented. Its development is motivated by the need for specific size micro perfluorocarbon (PFC) droplets to be used for a novel gas embolotherapy method. The device consists of a rectangular channel in which inertial lift forces are utilized to separate particles in lateral distance. At the entrance of the channel, particles are introduced at the center by focusing the flow from a center channel with flow from two side channels. Downstream, large particles will occupy a lateral equilibrium position in shorter axial distance than small particles. At the exit of the channel, flow containing large particles is separated from flow containing small particles. It is shown that 10.2-μm diameter microspheres can be separated from 3.0-μm diameter microspheres with a separation efficiency of 69-78% and a throughput in the order of 2 ·10⁴ particles per minute. Computational Fluid Dynamics (CFD) calculations were done to calculate flow fields and verify theoretical particle trajectories. Theory underlying this research shows that higher separation efficiencies for very specific diameter cut-off are possible. This microfluidic channel design has a simple structure and can operate without external forces which makes it feasible for lab-on-a-chip (LOC) applications.

  14. Microfluidics and microbial engineering.

    PubMed

    Kou, Songzi; Cheng, Danhui; Sun, Fei; Hsing, I-Ming

    2016-02-07

    The combination of microbial engineering and microfluidics is synergistic in nature. For example, microfluidics is benefiting from the outcome of microbial engineering and many reported point-of-care microfluidic devices employ engineered microbes as functional parts for the microsystems. In addition, microbial engineering is facilitated by various microfluidic techniques, due to their inherent strength in high-throughput screening and miniaturization. In this review article, we firstly examine the applications of engineered microbes for toxicity detection, biosensing, and motion generation in microfluidic platforms. Secondly, we look into how microfluidic technologies facilitate the upstream and downstream processes of microbial engineering, including DNA recombination, transformation, target microbe selection, mutant characterization, and microbial function analysis. Thirdly, we highlight an emerging concept in microbial engineering, namely, microbial consortium engineering, where the behavior of a multicultural microbial community rather than that of a single cell/species is delineated. Integrating the disciplines of microfluidics and microbial engineering opens up many new opportunities, for example in diagnostics, engineering of microbial motors, development of portable devices for genetics, high throughput characterization of genetic mutants, isolation and identification of rare/unculturable microbial species, single-cell analysis with high spatio-temporal resolution, and exploration of natural microbial communities.

  15. How boundaries shape chemical delivery in microfluidics

    NASA Astrophysics Data System (ADS)

    Aminian, Manuchehr; Bernardi, Francesca; Camassa, Roberto; Harris, Daniel M.; McLaughlin, Richard M.

    2016-12-01

    Many microfluidic systems—including chemical reaction, sample analysis, separation, chemotaxis, and drug development and injection—require control and precision of solute transport. Although concentration levels are easily specified at injection, pressure-driven transport through channels is known to spread the initial distribution, resulting in reduced concentrations downstream. Here we document an unexpected phenomenon: The channel’s cross-sectional aspect ratio alone can control the shape of the concentration profile along the channel length. Thin channels (aspect ratio << 1) deliver solutes arriving with sharp fronts and tapering tails, whereas thick channels (aspect ratio ~ 1) produce the opposite effect. This occurs for rectangular and elliptical pipes, independent of initial distributions. Thus, it is possible to deliver solute with prescribed distributions, ranging from gradual buildup to sudden delivery, based only on the channel dimensions.

  16. A Continuous-Flow, Microfluidic Fraction Collection Device

    PubMed Central

    Baker, Christopher; Roper, Michael G.

    2010-01-01

    A microfluidic device is presented that performs electrophoretic separation coupled with fraction collection. Effluent from the 3.5 cm separation channel was focused via two sheath flow channels into one of seven collection channels. By holding the collection channels at ground potential and varying the voltage ratio at the two sheath flow channels, the separation effluent was directed to either specific collection channels, or could be swept past all channels in a defined time period. As the sum of the voltages applied to the two sheath flow channels was constant, the electric field remained at 275 V/cm during the separation regardless of the collection channel used. The constant potential in the separation channel allowed uninterrupted separation for late-migrating peaks while early-migrating peaks were being collected. To minimize the potential for carryover between fractions, the device geometry was optimized using a three-level factorial model. The optimum conditions were a 22.5° angle between the sheath flow channels and the separation channel, and a 350 µm length of channel between the separation outlet and the fraction channels. Using these optimized dimensions, the device performance was evaluated by separation and fraction collection of a fluorescently-labeled amino acid mixture. The ability to fraction collect on a microfluidic platform will be especially useful during automated or continuous operation of these devices or to collect precious samples. PMID:20730040

  17. Solidification of a Charged Colloidal Dispersion Investigated Using Microfluidic Pervaporation.

    PubMed

    Ziane, Nadia; Salmon, Jean-Baptiste

    2015-07-28

    We investigate the dynamics of solidification of a charged colloidal dispersion using an original microfluidic technique referred to as micropervaporation. This technique exploits pervaporation within a microfluidic channel to extract the solvent of a dilute colloidal dispersion. Pervaporation concentrates the colloids in a controlled way up to the tip of the channel until a wet solid made of closely packed colloids grows and invades the microfluidic channel. For the charged dispersion under study, we however evidence a liquid to solid transition (LST) preceding the formation of the solid, owing to the presence of long-range electrostatic interactions. This LST is associated with the nucleation and growth of domains confined in the channel. These domains are then compacted anisotropically up to forming a wet solid of closely packed colloids. This solid then invades the whole channel as in directional drying with a growth rate which depends on the microfluidic geometry. In the final steps of the solidification, we observed the occurrence of cracks and shear bands, the delamination of the wet solid from the channel walls, and its invasion by a receding air front. Interestingly, this air front follows specific patterns within the solid which reveal different microscopic colloidal organizations.

  18. Nanomaterials meet microfluidics.

    PubMed

    Pumera, Martin

    2011-05-28

    Nanomaterials and lab-on-a-chip platforms have undergone enormous development during the past decade. Here, we present an overview of how microfluidics benefited from the use of nanomaterials for the enhanced separation and detection of analytes. We also discuss how nanomaterials benefit from microfluidics in terms of synthesis and in terms of the simulation of environments for nanomotors and nanorobots. In our opinion, the "marriage" of nanomaterials and microfluidics is highly beneficial and is expected to solve vital challenges in related fields. © The Royal Society of Chemistry 2011

  19. Microfluidic viscometers for shear rheology of complex fluids and biofluids.

    PubMed

    Gupta, Siddhartha; Wang, William S; Vanapalli, Siva A

    2016-07-01

    The rich diversity of man-made complex fluids and naturally occurring biofluids is opening up new opportunities for investigating their flow behavior and characterizing their rheological properties. Steady shear viscosity is undoubtedly the most widely characterized material property of these fluids. Although widely adopted, macroscale rheometers are limited by sample volumes, access to high shear rates, hydrodynamic instabilities, and interfacial artifacts. Currently, microfluidic devices are capable of handling low sample volumes, providing precision control of flow and channel geometry, enabling a high degree of multiplexing and automation, and integrating flow visualization and optical techniques. These intrinsic advantages of microfluidics have made it especially suitable for the steady shear rheology of complex fluids. In this paper, we review the use of microfluidics for conducting shear viscometry of complex fluids and biofluids with a focus on viscosity curves as a function of shear rate. We discuss the physical principles underlying different microfluidic viscometers, their unique features and limits of operation. This compilation of technological options will potentially serve in promoting the benefits of microfluidic viscometry along with evincing further interest and research in this area. We intend that this review will aid researchers handling and studying complex fluids in selecting and adopting microfluidic viscometers based on their needs. We conclude with challenges and future directions in microfluidic rheometry of complex fluids and biofluids.

  20. Microfluidic viscometers for shear rheology of complex fluids and biofluids

    PubMed Central

    Wang, William S.; Vanapalli, Siva A.

    2016-01-01

    The rich diversity of man-made complex fluids and naturally occurring biofluids is opening up new opportunities for investigating their flow behavior and characterizing their rheological properties. Steady shear viscosity is undoubtedly the most widely characterized material property of these fluids. Although widely adopted, macroscale rheometers are limited by sample volumes, access to high shear rates, hydrodynamic instabilities, and interfacial artifacts. Currently, microfluidic devices are capable of handling low sample volumes, providing precision control of flow and channel geometry, enabling a high degree of multiplexing and automation, and integrating flow visualization and optical techniques. These intrinsic advantages of microfluidics have made it especially suitable for the steady shear rheology of complex fluids. In this paper, we review the use of microfluidics for conducting shear viscometry of complex fluids and biofluids with a focus on viscosity curves as a function of shear rate. We discuss the physical principles underlying different microfluidic viscometers, their unique features and limits of operation. This compilation of technological options will potentially serve in promoting the benefits of microfluidic viscometry along with evincing further interest and research in this area. We intend that this review will aid researchers handling and studying complex fluids in selecting and adopting microfluidic viscometers based on their needs. We conclude with challenges and future directions in microfluidic rheometry of complex fluids and biofluids. PMID:27478521

  1. Application of electron conformational-genetic algorithm approach to 1,4-dihydropyridines as calcium channel antagonists: pharmacophore identification and bioactivity prediction.

    PubMed

    Geçen, Nazmiye; Sarıpınar, Emin; Yanmaz, Ersin; Sahin, Kader

    2012-01-01

    Two different approaches, namely the electron conformational and genetic algorithm methods (EC-GA), were combined to identify a pharmacophore group and to predict the antagonist activity of 1,4-dihydropyridines (known calcium channel antagonists) from molecular structure descriptors. To identify the pharmacophore, electron conformational matrices of congruity (ECMC)-which include atomic charges as diagonal elements and bond orders and interatomic distances as off-diagonal elements-were arranged for all compounds. The ECMC of the compound with the highest activity was chosen as a template and compared with the ECMCs of other compounds within given tolerances to reveal the electron conformational submatrix of activity (ECSA) that refers to the pharmacophore. The genetic algorithm was employed to search for the best subset of parameter combinations that contributes the most to activity. Applying the model with the optimum 10 parameters to training (50 compounds) and test (22 compounds) sets gave satisfactory results (R(2)(training)= 0.848, R(2)(test))= 0.904, with a cross-validated q(2) = 0.780).

  2. Construction of programmable interconnected 3D microfluidic networks

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

    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.

  3. A pump-free membrane-controlled perfusion microfluidic platform

    PubMed Central

    Goral, Vasiliy N.; Tran, Elizabeth; Yuen, Po Ki

    2015-01-01

    In this article, we present a microfluidic platform for passive fluid pumping for pump-free perfusion cell culture, cell-based assay, and chemical applications. By adapting the passive membrane-controlled pumping principle from the previously developed perfusion microplate, which utilizes a combination of hydrostatic pressure generated by different liquid levels in the wells and fluid wicking through narrow strips of a porous membrane connecting the wells to generate fluid flow, a series of pump-free membrane-controlled perfusion microfluidic devices was developed and their use for pump-free perfusion cell culture and cell-based assays was demonstrated. Each pump-free membrane-controlled perfusion microfluidic device comprises at least three basic components: an open well for generating fluid flow, a micron-sized deep chamber/channel for cell culture or for fluid connection, and a wettable porous membrane for controlling the fluid flow. Each component is fluidically connected either by the porous membrane or by the micron-sized deep chamber/channel. By adapting and incorporating the passive membrane-controlled pumping principle into microfluidic devices, all the benefits of microfluidic technologies, such as small sample volumes, fast and efficient fluid exchanges, and fluid properties at the micro-scale, can be fully taken advantage of with this pump-free membrane-controlled perfusion microfluidic platform. PMID:26392835

  4. A microfluidic gas damper for stabilizing gas pressure in portable microfluidic systems.

    PubMed

    Zhang, Xinjie; Zhu, Zhixian; Xiang, Nan; Ni, Zhonghua

    2016-09-01

    Pressure fluctuations, which invariably occur in microfluidic systems, usually result in the unstable fluid delivery in microfluidic channels. In this work, a novel microfluidic gas damper is proposed and applied for providing stable fluid-driving pressures. Then, a pressure-driven flow setup is constructed to investigate the gas damping characteristics of our damper. Since the pressure-driven flow setup functions as a resistor-capacitor low-pass filter, the damper significantly decreases the amplitude of the input pressures via self-regulating its pneumatic resistance. In addition, the gas volume and pressure frequency are found to have direct effects on the pressure fluctuations. The practical application of the gas damper is examined through a portable pressure-driven system, which consists of an air blower, a gas damper, and a centrifuge tube. By periodically pressing the air blower, precise flow rates with low throughput (∼9.64 μl min(-1)) and high throughput (∼1367.15 μl min(-1)) are successfully delivered. Future integration of our microfluidic gas damper with miniaturized pressure generators (e.g., peristaltic or pressure-driven micropumps) can fully exploit the potential of the gas damper for low-cost, portable microfluidics where stable pressures or flow rates are required.

  5. Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian fluids

    PubMed Central

    Kartalov, Emil P.; Walker, Christopher; Taylor, Clive R.; Anderson, W. French; Scherer, Axel

    2006-01-01

    We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complexity of microfluidic architecture. We apply the vias to printing nested bioarrays and building autoregulatory devices. A current source is demonstrated, while a diode and a rectifier are derived; all are building blocks for analog circuitry in Newtonian fluids. We also describe microfluidic septa and their applications. Vias lay the foundation for a new generation of microfluidic devices. PMID:16888040

  6. Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian fluids.

    PubMed

    Kartalov, Emil P; Walker, Christopher; Taylor, Clive R; Anderson, W French; Scherer, Axel

    2006-08-15

    We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complexity of microfluidic architecture. We apply the vias to printing nested bioarrays and building autoregulatory devices. A current source is demonstrated, while a diode and a rectifier are derived; all are building blocks for analog circuitry in Newtonian fluids. We also describe microfluidic septa and their applications. Vias lay the foundation for a new generation of microfluidic devices.

  7. Phonons in active microfluidic crystals

    NASA Astrophysics Data System (ADS)

    Tsang, Alan Cheng Hou; Kanso, Eva

    2016-11-01

    One-dimensional crystals of driven particles confined in quasi two-dimensional microfluidic channels have been shown to exhibit propagating sound waves in the form of 'phonons', including both transverse and longitudinal normal modes. Here, we focus on one-dimensional crystals of motile particles in uniform external flows. We study the propagation of phonons in the context of an idealized model that accounts for hydrodynamic interactions among the motile particles. We obtain a closed-form analytical expression for the dispersion relation of the phonons. In the moving frame of reference of the crystals, the traveling directions of the phonons depend on the intensity of the external flow, and are exactly opposite for the transverse and longitudinal modes. We further investigate the stability of the phonons and show that the longitudinal mode is linearly stable, whereas the transverse mode is subject to an instability arising from the activity and orientation dynamics of the motile particles. These findings are important for understanding the propagation of disturbances and instabilities in confined motile particles, and could generate practical insights into the transport of motile cells in microfluidic devices.

  8. USB-driven microfluidic chips on printed circuit boards.

    PubMed

    Li, Jiang; Wang, Yixuan; Dong, Enkai; Chen, Haosheng

    2014-03-07

    A technology is presented to fabricate a microfluidic chip in which the microchannels and the microelectrodes of sensors are integrated directly into the copper sheet on a printed circuit board. Then, we demonstrate an application of the generation of oil-in-water and water-in-oil emulsion droplets on this microfluidic chip driven by a USB interface, and the droplet size is detected by the microelectrodes on the downstream microchannel. The integration of the microfluidic chip is improved by the direct connection of the channels to the microelectrodes of the driving unit and of the sensors on the same substrate, and it is a promising way to integrate microfluidics into a more complex micro electrical-mechanical system (MEMS).

  9. Compact and controlled microfluidic mixing and biological particle capture

    NASA Astrophysics Data System (ADS)

    Ballard, Matthew; Owen, Drew; Mills, Zachary Grant; Hesketh, Peter J.; Alexeev, Alexander

    2016-11-01

    We use three-dimensional simulations and experiments to develop a multifunctional microfluidic device that performs rapid and controllable microfluidic mixing and specific particle capture. Our device uses a compact microfluidic channel decorated with magnetic features. A rotating magnetic field precisely controls individual magnetic microbeads orbiting around the features, enabling effective continuous-flow mixing of fluid streams over a compact mixing region. We use computer simulations to elucidate the underlying physical mechanisms that lead to effective mixing and compare them with experimental mixing results. We study the effect of various system parameters on microfluidic mixing to design an efficient micromixer. We also experimentally and numerically demonstrate that orbiting microbeads can effectively capture particles transported by the fluid, which has major implications in pre-concentration and detection of biological particles including various cells and bacteria, with applications in areas such as point-of-care diagnostics, biohazard detection, and food safety. Support from NSF and USDA is gratefully acknowledged.

  10. A truly Lego®-like modular microfluidics platform

    NASA Astrophysics Data System (ADS)

    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.

  11. The promise of microfluidic artificial lungs.

    PubMed

    Potkay, Joseph A

    2014-11-07

    Microfluidic or microchannel artificial lungs promise to enable a new class of truly portable, therapeutic artificial lungs through feature sizes and blood channel designs that closely mimic those found in their natural counterpart. These new artificial lungs could potentially: 1) have surface areas and priming volumes that are a fraction of current technologies thereby decreasing device size and reducing the foreign body response; 2) contain blood flow networks in which cells and platelets experience pressures, shear stresses, and branching angles that copy those in the human lung thereby improving biocompatibility; 3) operate efficiently with room air, eliminating the need for gas cylinders and complications associated with hyperoxemia; 4) exhibit biomimetic hydraulic resistances, enabling operation with natural pressures and eliminating the need for blood pumps; and, 5) provide increased gas exchange capacity enabling respiratory support for active patients. This manuscript reviews recent research efforts in microfluidic artificial lungs targeted at achieving the advantages above, investigates the ultimate performance and scaling limits of these devices using a proven mathematical model, and discusses the future challenges that must be overcome in order for microfluidic artificial lungs to be applied in the clinic. If all of these promising advantages are realized and the remaining challenges are met, microfluidic artificial lungs could revolutionize the field of pulmonary rehabilitation.

  12. Recent Advances in Magnetic Microfluidic Biosensors

    PubMed Central

    Giouroudi, Ioanna

    2017-01-01

    The development of portable biosening devices for the detection of biological entities such as biomolecules, pathogens, and cells has become extremely significant over the past years. Scientific research, driven by the promise for miniaturization and integration of complex laboratory equipment on inexpensive, reliable, and accurate devices, has successfully shifted several analytical and diagnostic methods to the submillimeter scale. The miniaturization process was made possible with the birth of microfluidics, a technology that could confine, manipulate, and mix very small volumes of liquids on devices integrated on standard silicon technology chips. Such devices are then directly translating the presence of these entities into an electronic signal that can be read out with a portable instrumentation. For the aforementioned tasks, the use of magnetic markers (magnetic particles—MPs—functionalized with ligands) in combination with the application of magnetic fields is being strongly investigated by research groups worldwide. The greatest merits of using magnetic fields are that they can be applied either externally or from integrated microconductors and they can be well-tuned by adjusting the applied current on the microconductors. Moreover, the magnetic markers can be manipulated inside microfluidic channels by high gradient magnetic fields that can in turn be detected by magnetic sensors. All the above make this technology an ideal candidate for the development of such microfluidic biosensors. In this review, focus is given only to very recent advances in biosensors that use microfluidics in combination with magnetic sensors and magnetic markers/nanoparticles. PMID:28684665

  13. Integrated microfluidic biochips for DNA microarray analysis.

    PubMed

    Liu, Robin Hui; Dill, Kilian; Fuji, H Sho; McShea, Andy

    2006-03-01

    A fully integrated and self-contained microfluidic biochip device has been developed to automate the fluidic handling steps required to perform a gene expression study of the human leukemia cell line (K-562). The device consists of a DNA microarray semiconductor chip with 12,000 features and a microfluidic cartridge that consists of microfluidic pumps, mixers, valves, fluid channels and reagent storage chambers. Microarray hybridization and subsequent fluidic handling and reactions (including a number of washing and labeling steps) were performed in this fully automated and miniature device before fluorescent image scanning of the microarray chip. Electrochemical micropumps were integrated in the cartridge to provide pumping of liquid solutions. A micromixing technique based on gas bubbling generated by electrochemical micropumps was developed. Low-cost check valves were implemented in the cartridge to prevent cross-talk of the stored reagents. A single-color transcriptional analysis of K-562 cells with a series of calibration controls (spiked-in controls) was performed to characterize this new platform with regard to sensitivity, specificity and dynamic range. The device detected sample RNAs with a concentration as low as 0.375 pM. Detection was quantitative over more than 3 orders of magnitude. Experiments also demonstrated that chip-to-chip variability was low, indicating that the integrated microfluidic devices eliminate manual fluidic handling steps that can be a significant source of variability in genomic analysis.

  14. Microfluidic enzymatic biosensing systems: A review.

    PubMed

    Mross, Stefan; Pierrat, Sebastien; Zimmermann, Tom; Kraft, Michael

    2015-08-15

    Microfluidic biosensing systems with enzyme-based detection have been exte