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Sample records for bioactivated microfluidic channels

  1. Electrical detection of protein biomarkers using bioactivated microfluidic channels

    PubMed Central

    Javanmard, Mehdi; Talasaz, Amirali H.; Nemat-Gorgani, Mohsen; Pease, Fabian; Ronaghi, Mostafa; Davis, Ronald W.

    2009-01-01

    Current methods used for analyzing biomarkers involve expensive and time consuming techniques like the Sandwich ELISA which require lengthy incubation times, high reagent costs, and bulky optical equipment. We have developed a technique involving the use of a micro-channel with integrated electrodes, functionalized with receptors specific to target biomarkers. We have applied our biochip to the rapid electrical detection and quantification of target protein biomarkers using protein functionalized micro-channels. We successfully demonstrate detection of anti-hCG antibody, at a concentration of 1 ng ml−1 and a dynamic range of three orders of magnitude, in less than one hour. We envision the use of this technique in a handheld device for multiplex high throughput analysis using an array of micro-channels for probing various protein biomarkers in clinically relevant samples such as human serum for cancer detection. PMID:19417910

  2. Electrical detection of protein biomarkers using bioactivated microfluidic channels.

    PubMed

    Javanmard, Mehdi; Talasaz, Amirali H; Nemat-Gorgani, Mohsen; Pease, Fabian; Ronaghi, Mostafa; Davis, Ronald W

    2009-05-21

    Current methods used for analyzing biomarkers involve expensive and time consuming techniques like the Sandwich ELISA which require lengthy incubation times, high reagent costs, and bulky optical equipment. We have developed a technique involving the use of a micro-channel with integrated electrodes, functionalized with receptors specific to target biomarkers. We have applied our biochip to the rapid electrical detection and quantification of target protein biomarkers using protein functionalized micro-channels. We successfully demonstrate detection of anti-hCG antibody, at a concentration of 1 ng ml(-1) and a dynamic range of three orders of magnitude, in less than one hour. We envision the use of this technique in a handheld device for multiplex high throughput analysis using an array of micro-channels for probing various protein biomarkers in clinically relevant samples such as human serum for cancer detection. PMID:19417910

  3. 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.

  4. 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.

  5. 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…

  6. Evaporative cooling in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Maltezos, George; Rajagopal, Aditya; Scherer, Axel

    2006-08-01

    Evaporative cooling is an effective and energy efficient way to rapidly remove heat from a system. Specifically, evaporative cooling in microfluidic channels can provide a cost-effective solution for the cooling of electronic devices and chemical reactors. Here we present microfluidic devices fabricated by using soft-lithography techniques to form simple fluidic junctions between channels carrying refrigerant and channels carrying N2 gas. The effects of channel geometry and delivery pressure on the performance of refrigeration through vaporization of acetone, isopropyl alcohol, and ethyl ether were characterized. By varying gas inlet pressures, refrigerants, and angles of the microfluidic junctions, optimal cooling conditions were found. Refrigeration rates in excess of 40°C/s were measured, and long lasting subzero cooling in the junction could be observed.

  7. 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

  8. 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.

  9. 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

  10. 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. PMID:27021807

  11. Sealing SU-8 microfluidic channels using PDMS

    PubMed Central

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

    2011-01-01

    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 N2 plasma treatment, then allowing the amino groups to react with the residual epoxy groups on SU-8 surface at an elevated temperature. The N2 plasma treatment of PDMS can be conducted using an ordinary plasma chamber and high purity N2, 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. PMID:22662066

  12. Connecting and disconnecting nematic disclination lines in microfluidic channels.

    PubMed

    Agha, Hakam; Bahr, Christian

    2016-05-14

    Disclination lines in nematic liquid crystals can be used as "soft rails" for the transport of colloids or droplets through microfluidic channels [A. Sengupta, C. Bahr and S. Herminghaus, Soft Matter, 2013, 9, 7251]. In the present study we report on a method to connect and disconnect disclination lines in microfluidic channels using the interplay between anchoring, flow, and electric field. We show that the application of an electric field establishes a continuous disclination that spans across a channel region in which a disclination usually would not exist (because of different anchoring conditions), demonstrating an interruptible and reconnectable soft rail for colloidal transport. PMID:27079151

  13. 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.

  14. 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

  15. 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.

  16. Controlled Fabrication of Bioactive Microfibers for Creating Tissue Constructs Using Microfluidic Techniques.

    PubMed

    Cheng, Yao; Yu, Yunru; Fu, Fanfan; Wang, Jie; Shang, Luoran; Gu, Zhongze; Zhao, Yuanjin

    2016-01-20

    The fabrication of heterogeneous microstructures, which exert precise control over the distribution of different cell types within biocompatible constructs, is important for many tissue engineering applications. Here, bioactive microfibers with tunable morphologies, structures, and components are generated and employed for creating different tissue constructs. Multibarrel capillary microfluidics with multiple laminar flows are used for continuously spinning these microfibers. With an immediate gelation reaction of the cell dispersed alginate solutions, the cell-laden alginate microfibers with the tunable morphologies and structures as the designed multiple laminar flows can be generated. The performances of the microfibers in cell culture are improved by incorporating bioactive polymers, such as extracellular matrix (ECM) or methacrylated gelatin (GelMA), into the alginate. It is demonstrated that a series of complex three-dimensional (3D) architectural cellular buildings, including biomimic vessels and scaffolds, can be created using these bioactive microfibers. PMID:26741731

  17. 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.

  18. 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

  19. Retinal synaptic regeneration via microfluidic guiding channels.

    PubMed

    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

  20. Separating Magnetically Labeled and Unlabeled Biological Cells within Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Byvank, Tom; Vieira, Greg; Miller, Brandon; Yu, Bo; Chalmers, Jeffrey; Lee, L. James; Sooryakumar, R.

    2011-03-01

    The transport of microscopic objects that rely on magnetic forces have numerous advantages including flexibility of controlling many design parameters and the long range magnetic interactions generally do not adversely affect biological or chemical interactions. We present results on the use of magnetic micro-arrays imprinted within polydimethylsiloxane (PDMS) microfluidic channels that benefit from these features and the ability to rapidly reprogram the magnetic energy landscape for cell manipulation and sorting applications. A central enabling feature is the very large, tunable, magnetic field gradients (> 10 4) that can be designed within the microfluidic architecture. Through use of antibody-conjugated magnetic microspheres to label biological cells, results on the transport and sorting of heterogeneous cell populations are presented. The effects of micro-array and fluid channel design parameters, competition between magnetic forces and hydrodynamic drag forces, and cell-labeling efficiency on cell separation are discussed.

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

    DOEpatents

    Ledbetter, Micah P.; Savukov, Igor M.; Budker, Dmitry; Shah, Vishal K.; Knappe, Svenja; Kitching, John; Michalak, David J.; Xu, Shoujun; Pines, Alexander

    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.

  2. 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)

  3. 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.

  4. 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

  5. Particle trajectory entanglement in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Marin, Alvaro; Rossi, Massimiliano; Kähler, Christian

    2015-11-01

    Suspensions in motion can show very complex and counterintuitive behavior, particularly at high concentrations. In this talk we show an overlooked phenomenon occurring when a dilute particle solution is forced to travel in a narrow channel (only a few times the particle size). At critical interparticle distances, particles tend to interlace their trajectories forming a sort of hydroclusters only bonded by hydrodynamic interactions. While classical studies on non-Brownian self-diffusivity report average particle displacements of fractions of the particle diameter, the trajectories observed in our system show displacements of several particle diameters. Indeed, such a behavior resemble the deterministic trajectories found by Uspal et al. (Nat. Comm. 4, 2013) with engineered particle doublets. Trajectory statistics are obtained for different shear rates and particle sizes. The results are compared with particle dynamics simulations and analyzed under the light of recent studies on the irreversibility of non-Brownian suspensions (Metzger et al., Phys. Rev. E, 2013) to elucidate the nature of the hydrodynamic interactions entering into play. The reported phenomenon could be applied to promote advective mixing in micro-channels or particle/droplet self-assembly.

  6. Cross-stream migration of compliant particles in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Kilimnik, Alex; Nur, Soojung Claire; di Carlo, Dino; Alexeev, Alexander

    2010-11-01

    Using a 3D hybrid lattice Boltzmann and lattice spring computational method, the motion of rigid and soft particles in a pressure-driven microfluidic flow was examined. The particles were modeled as neutrally buoyant fluid-filled elastic shells. The equilibrium positions of these particles were obtained in a low-Reynolds-number flow while accounting for non-linear inertial effects. Microchannels of different width were examined and it was found that the equilibrium position of the rigid particles moves away from the channel walls as the ratio between particle diameter and channel width increases. Furthermore, it was found that capsule deformability enhances the particle migration toward the channel centerline. The simulation results were compared with experimental data obtained with varying size and viscosity oil droplets suspended in water indicating favorable agreement. These findings could aid in the design of devices to sort particles based on their mechanical stiffness.

  7. 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.

  8. Bisecting Microfluidic Channels with Metallic Nanowires Fabricated by Nanoskiving.

    PubMed

    Kalkman, Gerard A; Zhang, Yanxi; Monachino, Enrico; Mathwig, Klaus; Kamminga, Machteld E; Pourhossein, Parisa; Oomen, Pieter E; Stratmann, Sarah A; Zhao, Zhiyuan; van Oijen, Antoine M; Verpoorte, Elisabeth; Chiechi, Ryan C

    2016-02-23

    This paper describes the fabrication of millimeter-long gold nanowires that bisect the center of microfluidic channels. We fabricated the nanowires by nanoskiving and then suspended them over a trench in a glass structure. The channel was sealed by bonding it to a complementary poly(dimethylsiloxane) structure. The resulting structures place the nanowires in the region of highest flow, as opposed to the walls, where it approaches zero, and expose their entire surface area to fluid. We demonstrate active functionality, by constructing a hot-wire anemometer to measure flow through determining the change in resistance of the nanowire as a function of heat dissipation at low voltage (<5 V). Further, passive functionality is demonstrated by visualizing individual, fluorescently labeled DNA molecules attached to the wires. We measure rates of flow and show that, compared to surface-bound DNA strands, elongation saturates at lower rates of flow and background fluorescence from nonspecific binding is reduced. PMID:26836373

  9. Surface-directed boundary flow in microfluidic channels.

    PubMed

    Huang, Tom T; Taylor, David G; Lim, Kwan Seop; Sedlak, Miroslav; Bashir, Rashid; Mosier, Nathan S; Ladisch, Michael R

    2006-07-01

    Channel geometry combined with surface chemistry enables a stable liquid boundary flow to be attained along the surfaces of a 12 microm diameter hydrophilic glass fiber in a closed semi-elliptical channel. Surface free energies and triangular corners formed by PDMS/glass fiber or OTS/glass fiber surfaces are shown to be responsible for the experimentally observed wetting phenomena and formation of liquid boundary layers that are 20-50 microm wide and 12 microm high. Viewing this stream through a 20 microm slit results in a virtual optical window with a 5 pL liquid volume suitable for cell counting and pathogen detection. The geometry that leads to the boundary layer is a closed channel that forms triangular corners where glass fiber and the OTS coated glass slide or PDMS touch. The contact angles and surfaces direct positioning of the fluid next to the fiber. Preferential wetting of corner regions initiates the boundary flow, while the elliptical cross-section of the channel stabilizes the microfluidic flow. The Young-Laplace equation, solved using fluid dynamic simulation software, shows contact angles that exceed 105 degrees will direct the aqueous fluid to a boundary layer next to a hydrophilic fiber with a contact angle of 5 degrees. We believe this is the first time that an explanation has been offered for the case of a boundary layer formation in a closed channel directed by a triangular geometry with two hydrophobic wetting edges adjacent to a hydrophilic surface. PMID:16800710

  10. 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.

  11. 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

  12. 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. PMID:27472142

  13. 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.

  14. 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.

  15. 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.

  16. 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. PMID:22418188

  17. An Anti-Adhesion Technique in Microfluidic Channel Using Dielectrophoresis for Particle Processing Microfluidic Chip Applications.

    PubMed

    Kang, Dong-Hyun; Kim, Min-Gu; Seo, Hye-Kyoung; Kim, Yong-Jun

    2015-09-01

    Particle adhesion to the walls of microfluidic channels is a prominent cause of deteriorating performance and reliability in miniaturized analytical devices; it can also cause unexpected changes in their structures and operating conditions. Therefore, the demand of anti-adhesion for wall loss reduction on particle processing chips is high. This paper demonstrates an anti-adhesion technique using dielectrophoresis. The proposed technique is applied to a distribution microchannel for a feasibility test and is then applied to a blood plasma filter, which is a human blood cell and plasma separation device. In the distribution microchannel, the application of electric potentials of 0-20 V(pp) at 3 MHz caused the wall loss of polystyrene latex (PSL) particles to decrease with decreasing particle diameter. When an electric potential of 20 V(pp) was applied in a distribution microchannel experiment using PSL particles, the wall loss decreased by 52.7 ± 3% for 10-μm-diameter particles. On the other hand, when a 20 V(pp) electric potential was applied in a distribution microchannel experiment using human blood cells, the wall loss decreased by 66.4 ± 6%. In the blood plasma filter, the wall loss decreased by 54.89 ± 5% at 20 V(pp) and 1 MHz. The purity efficiency of the blood plasma filter was 69.56% without the wall loss reduction technique and 95.14% when the applied electric potential was 20 V(pp). PMID:26485924

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

    PubMed

    Roh, Changhyun; Lee, Jaewoong; Kang, Chankyu

    2016-01-01

    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. PMID:27322239

  20. Fluidic communication between multiple vertically segregated microfluidic channels connected by nanocapillary array membranes.

    PubMed

    Gong, Maojun; Flachsbart, Bruce R; Shannon, Mark A; Bohn, Paul W; Sweedler, Jonathan V

    2008-03-01

    Hybrid microfluidic/nanofluidic devices offer unique capabilities for manipulating and analyzing minute volumes of expensive or hard-to-obtain samples. Here, multilayer poly-(methyl methacrylate) microchips, with multiple spatially isolated microfluidic channels interconnected by nanocapillary array membranes (NCAMs), are fabricated using an adhesive contact printing process. The NCAMs, positioned between the microfluidic channel layers, add functionality to the inter-microchannel fluid transfer unit operation. They do so because the transport of specific analytes through the NCAM can be controlled by adjusting the ionic strength, the polarity of the applied bias, the surface charge density, and the pore size. A simplified, floating injection technique for NCAM-coupled nanofluidic devices is described and compared with conventional biased injection. In the floating injection approach, a voltage is applied across the injection channel and the slight electric field extension at the cross-section is used to transfer analytes through the nanopores to the separation channel. Floating injection excels in plug reproducibility, separation resolution, and operation simplicity, although it decreases assay throughput relative to biased injection. Floating injection can avoid the uneven distribution of analytes in the microfluidic channel that sometimes results from biased injection because of the volume mismatch between NCAM nanopore transport capacity and the supply of fluid. Moreover, the pressure-driven flow caused by the mismatch of the EOFs in the microfluidic channels connected by an NCAM must be considered when using NCAMs with pore diameters below 50 nm. PMID:18288777

  1. 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

  2. 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

  3. 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.

  4. Integrating nanopore sensors within microfluidic channel arrays using controlled breakdown.

    PubMed

    Tahvildari, Radin; Beamish, Eric; Tabard-Cossa, Vincent; Godin, Michel

    2015-03-21

    Nanopore arrays are fabricated by controlled dielectric breakdown (CBD) in solid-state membranes integrated within polydimethylsiloxane (PDMS) microfluidic devices. This technique enables the scalable production of independently addressable nanopores. By confining the electric field within the microfluidic architecture, nanopore fabrication is precisely localized and electrical noise is significantly reduced. Both DNA and protein molecules are detected to validate the performance of this sensing platform. PMID:25631885

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

    PubMed

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

    2015-12-01

    This article describes the development of porous two-ply channels for paper-based microfluidic devices that wick fluids significantly faster than conventional, porous, single-ply channels. The two-ply channels were made by stacking two single-ply channels on top of each other and were fabricated entirely out of paper, wax and toner using two commercially available printers, a convection oven and a thermal laminator. The wicking in paper-based channels was studied and modeled using a modified Lucas-Washburn equation to account for the effect of evaporation, and a paper-based titration device incorporating two-ply channels was demonstrated. PMID:26477676

  6. Soft lithographic patterning of supported lipid bilayers onto a surface and inside microfluidic channels.

    PubMed

    Kim, Pilnam; Lee, Sang Eun; Jung, Ho Sup; Lee, Hea Yeon; Kawai, Tomoji; Suh, Kahp Y

    2006-01-01

    We present simple soft lithographic methods for patterning supported lipid bilayer (SLB) membranes onto a surface and inside microfluidic channels. Micropatterns of polyethylene glycol (PEG)-based polymers were fabricated on glass substrates by microcontact printing or capillary moulding. The patterned PEG surfaces have shown 97 +/- 0.5% reduction in lipid adsorption onto two dimensional surfaces and 95 +/- 1.2% reduction inside microfluidic channels in comparison to glass control. Atomic force microscopy measurements indicated that the deposition of lipid vesicles led to the formation of SLB membranes by vesicle fusion due to hydrophilic interactions with the exposed substrate. Furthermore, the functionality of the patterned SLBs was tested by measuring the binding interactions between biotin (ligand)-labeled lipid bilayer and streptavidin (receptor). SLB arrays were fabricated with spatial resolution down to approximately 500 nm on flat substrate and approximately 1 microm inside microfluidic channels, respectively. PMID:16372069

  7. Characterization of a single cell of Chlorella in a microfluidic channel using amperometric electrode arrays.

    PubMed

    Song, Young Seok; Bai, Seoung Jai

    2014-11-01

    Electrochemical characteristics of O2 and/or mediators secreted by a single cell of Chlorella fusea were analyzed by using amperometric measurements on microelectrodes embedded in a microfluidic device. A single cell was trapped in a microfluidic channel, which simplifies the mass transfer phenomenon, i.e., one-dimensional distribution of solutes in the channel. Such amperometric measurements allowed us to obtain more refined data in a localized space and to understand photosynthetic behavior of algae at the single cell level. In addition, the concentration of a photosynthetic mediator, p-benzoquinone, was numerically calculated by using the finite element method. PMID:24966046

  8. Fabrication of a microfluidic channel with differently modified surfaces with a two component approach

    NASA Astrophysics Data System (ADS)

    Bogunovic, L.; Vosskötter, C.; Anselmetti, D.

    2014-07-01

    We report on a two-component fabrication technique for microfluidic channels, allowing for different chemical or physical surface modifications of channel walls within one single channel. The two components are made of polydimethylsiloxane and prepared via soft lithography independently. After appropriate pre-treatment with the desired functions, the two parts are bonded together using oxygen plasma and a Fineplacer® lambda system. As a proof of concept, we present the combination of electroosmosis and opposing hydrodynamic flow in a microfluidic channel leading to different velocity presigns of the resulting flow on opposite channel walls, due to different surface modifications. These results indicate an intact Pluronic® F108 surface coating after assembly.

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

    PubMed

    Land, Kevin J; Mbanjwa, Mesuli; Korvink, Jan G

    2014-09-01

    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

  10. 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

  11. Carbon nanotube sensors integrated inside a microfluidic channel for water quality monitoring

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Li, Xinghui; Dokmeci, Mehmet R.; Wang, Ming L.

    2011-04-01

    Single-walled carbon nanotubes (SWNTs) with their unique electrical properties and large surface area are remarkable materials for detecting low concentration of toxic and hazardous chemicals (both from the gaseous and liquid phases). Ionic adsorbates in water will attach on to SWNTs and drastically alter their electrical properties. Several SWNTs based pH and chemical sensors have been demonstrated. However, most of them require external components to test and analyze the response of SWNTs to ions inside the liquid samples. Here, we report a water quality monitoring sensor composed of SWNTs integrated inside microfluidic channels and on-chip testing components with a wireless transmission board. To detect multiple analytes in water requires the functionalization of SWNTs with different chemistries. In addition, microfluidic channels are used to guide liquid samples to individual nanotube sensors in an efficient manner. Furthermore, the microfluidic system enables sample mixing and separation before testing. To realize the nanosensors, first microelectrodes were fabricated on an oxidized silicon substrate. Next, PDMS micro channels were fabricated and bonded on the substrate. These channels can be incorporated with a microfluidic system which can be designed to manipulate different analytes for specific molecule detection. Low temperature, solution based Dielectrophoretic (DEP) assembly was conducted inside this microfluidic system which successfully bridged SWNTs between the microelectrodes. The SWNTs sensors were next characterized with different pH buffer solutions. The resistance of SWNTs had a linearly increase as the pH values ranged from 5 to 8. The nanosensor incorporated within the microfluidic system is a versatile platform and can be utilized to detect numerous water pollutants, including toxic organics and microorganisms down to low concentrations. On-chip processing and wireless transmission enables the realization of a full autonomous system for real

  12. 3-dimensional electrode patterning within a microfluidic channel using metal ion implantation.

    PubMed

    Choi, Jae-Woo; Rosset, Samuel; Niklaus, Muhamed; Adleman, James R; Shea, Herbert; Psaltis, Demetri

    2010-03-21

    The application of electrical fields within a microfluidic channel enables many forms of manipulation necessary for lab-on-a-chip devices. Patterning electrodes inside the microfluidic channel generally requires multi-step optical lithography. Here, we utilize an ion-implantation process to pattern 3D electrodes within a fluidic channel made of polydimethylsiloxane (PDMS). Electrode structuring within the channel is achieved by ion implantation at a 40 degrees angle with a metal shadow mask. The advantages of three-dimensional structuring of electrodes within a fluidic channel over traditional planar electrode designs are discussed. Two possible applications are presented: asymmetric particles can be aligned in any of the three axial dimensions with electro-orientation; colloidal focusing and concentration within a fluidic channel can be achieved through dielectrophoresis. Demonstrations are shown with E. coli, a rod shaped bacteria, and indicate the potential that ion-implanted microfluidic channels have for manipulations in the context of lab-on-a-chip devices. PMID:20221568

  13. 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

  14. 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

    2016-01-01

    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

  15. 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.

  16. 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

  17. 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. PMID:27478523

  18. 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

    2016-03-01

    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). PMID:26830018

  19. Two-Dimensional Microfluidics: hydrodynamics of drops and interfaces in flowing smectic liquid crystal channels

    NASA Astrophysics Data System (ADS)

    Qi, Zhiyuan; Nguyen, Zoom; Park, Cheol; Maclennan, Joe; Maclennan, Matt; Clark, Noel

    2012-02-01

    The quantization of film thickness in freely suspended fluid smectic liquid crystal film enables the study of the hydrodynamics of drops and interfaces in 2D. We report microfluidic experiments, in which we observe the hydrodynamics of 2D drops flowing in channels. Using high-speed video microscopy, we track the shape of 2D drops and interfaces, visualizing the deterministic lateral displacement-based separation and pinched flow separation phenomena previously observed only in 3D. Finally, we demonstrate techniques for 2D drop generation and sorting, which will be used for 2D microfluidic applications.

  20. 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

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

    PubMed

    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

  2. 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

  3. 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.

  4. 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.

  5. Easy fabrication of high quality nickel mold for deep polymer microfluidic channels

    NASA Astrophysics Data System (ADS)

    Wong, Ten It; Limantoro, Julian; Phang Fong, Kin; Tan, Christina Yuan Ling; Quan, Chenggen; Sun, Ling Ling; Zhou, Xiaodong

    2016-06-01

    Mass fabrication of disposable microfluidic chips with hot embossing is a key technology for microfluidic chip based biosensors. In this work, we develop a new method of fabricating high quality and highly durable nickel molds for hot embossing polymer chips. The process involves the addition of a thick, patterned layer of negative photoresist AZ-125nxT to a 4″ silicon wafer, followed by nickel electroplating and delamination of the nickel mold. Our investigations found that compared to a pillar mask, a hole mask can minimize the diffraction effect in photolithography of a thick photoresist, reduce the adhesion of the AZ-125nxT to the photomask in photolithography, and facilitate clean development of the photoresist patterns. By optimizing the hot embossing and chip bonding parameters, microfluidic chips with deep channels are achieved.

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

    PubMed

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

    2016-07-01

    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. PMID:27300118

  7. 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.

  8. Study of Spatio-Temporal Immunofluorescence on Bead Patterns in a Microfluidic Channel

    NASA Astrophysics Data System (ADS)

    Sivagnanam, Venkataragavalu; Yang, Hui; Gijs, Martin A. M.

    2010-12-01

    We performed a direct immunoassay inside a microfluidic channel on patterned streptavidin-coated beads, which captured fluorescently-labeled biotin target molecules from a continuous flow. We arranged the beads in a dot array at the bottom of the channel and demonstrated their position- and flow rate-dependent fluorescence. As the target analyte gets gradually depleted from the flow when passing downstream the channel, the highest fluorescence intensity was observed on the most upstream positioned dot patterns. We propose a simple analytical convection model to explain this spatio-temporal fluorescence.

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    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.

  10. 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

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

    PubMed

    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

  12. Examination of laser microbeam cell lysis in a PDMS microfluidic channel using time-resolved imaging.

    PubMed

    Quinto-Su, Pedro A; Lai, Hsuan-Hong; Yoon, Helen H; Sims, Christopher E; Allbritton, Nancy L; Venugopalan, Vasan

    2008-03-01

    We use time-resolved imaging to examine the lysis dynamics of non-adherent BAF-3 cells within a microfluidic channel produced by the delivery of single highly-focused 540 ps duration laser pulses at lambda = 532 nm. Time-resolved bright-field images reveal that the delivery of the pulsed laser microbeam results in the formation of a laser-induced plasma followed by shock wave emission and cavitation bubble formation. The confinement offered by the microfluidic channel constrains substantially the cavitation bubble expansion and results in significant deformation of the PDMS channel walls. To examine the cell lysis and dispersal of the cellular contents, we acquire time-resolved fluorescence images of the process in which the cells were loaded with a fluorescent dye. These fluorescence images reveal cell lysis to occur on the nanosecond to microsecond time scale by the plasma formation and cavitation bubble dynamics. Moreover, the time-resolved fluorescence images show that while the cellular contents are dispersed by the expansion of the laser-induced cavitation bubble, the flow associated with the bubble collapse subsequently re-localizes the cellular contents to a small region. This capacity of pulsed laser microbeam irradiation to achieve rapid cell lysis in microfluidic channels with minimal dilution of the cellular contents has important implications for their use in lab-on-a-chip applications. PMID:18305858

  13. Examination of laser microbeam cell lysis in a PDMS microfluidic channel using time-resolved imaging

    PubMed Central

    Quinto-Su, Pedro A.; Lai, Hsuan-Hong; Yoon, Helen H.; Sims, Christopher E.; Allbritton, Nancy L.; Venugopalan, Vasan

    2008-01-01

    We use time-resolved imaging to examine the lysis dynamics of non-adherent BAF-3 cells within a microfluidic channel produced by the delivery of single highly-focused 540 ps duration laser pulses at λ = 532 nm. Time-resolved bright-field images reveal that the delivery of the pulsed laser microbeam results in the formation of a laser-induced plasma followed by shock wave emission and cavitation bubble formation. The confinement offered by the microfluidic channel constrains substantially the cavitation bubble expansion and results in significant deformation of the PDMS channel walls. To examine the cell lysis and dispersal of the cellular contents, we acquire time-resolved fluorescence images of the process in which the cells were loaded with a fluorescent dye. These fluorescence images reveal cell lysis to occur on the nanosecond to microsecond time scale by the plasma formation and cavitation bubble dynamics. Moreover, the time-resolved fluorescence images show that while the cellular contents are dispersed by the expansion of the laser-induced cavitation bubble, the flow associated with the bubble collapse subsequently re-localizes the cellular contents to a small region. This capacity of pulsed laser microbeam irradiation to achieve rapid cell lysis in microfluidic channels with minimal dilution of the cellular contents has important implications for their use in lab-on-a-chip applications. PMID:18305858

  14. 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.

  15. Lateral transport of solutes in microfluidic channels using electrochemically generated gradients in redox-active surfactants.

    PubMed

    Liu, Xiaoyang; Abbott, Nicholas L

    2011-04-15

    We report principles for a continuous flow process that can separate solutes based on a driving force for selective transport that is generated by a lateral concentration gradient of a redox-active surfactant across a microfluidic channel. Microfluidic channels fabricated with gold electrodes lining each vertical wall were used to electrochemically generate concentration gradients of the redox-active surfactant 11-ferrocenylundecyl-trimethylammonium bromide (FTMA) in a direction perpendicular to the flow. The interactions of three solutes (a hydrophobic dye, 1-phenylazo-2-naphthylamine (yellow AB), an amphiphilic molecule, 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (BODIPY C(5)-HPC), and an organic salt, 1-methylpyridinium-3-sulfonate (MPS)) with the lateral gradients in surfactant/micelle concentration were shown to drive the formation of solute-specific concentration gradients. Two distinct physical mechanisms were identified to lead to the solute concentration gradients: solubilization of solutes by micelles and differential adsorption of the solutes onto the walls of the microchannels in the presence of the surfactant concentration gradient. These two mechanisms were used to demonstrate delipidation of a mixture of BODIPY C(5)-HPC (lipid) and MPS and purification of BODIPY C(5)-HPC from a mixture of BODIPY C(5)-HPC and yellow AB. Overall, the results of this study demonstrate that lateral concentration gradients of redox-active surfactants formed within microfluidic channels can be used to transport solutes across the microfluidic channels in a solute-dependent manner. The approach employs electrical potentials (<1 V) that are sufficiently small to avoid electrolysis of water, can be performed in solutions having high ionic strength (>0.1M), and offers the basis of continuous processes for the purification or separation of solutes in microscale systems. PMID:21446653

  16. 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

  17. Modeling the role of nuclear mechanics in determining cell shape and motility through microfluidic channels

    NASA Astrophysics Data System (ADS)

    Shechter, Jake; Maki, Kara; Das, Moumita

    2014-03-01

    Cell mechanics and migration through tight spaces are critical to life processes such as immune response and fertilization, in several diseases, and in diagnostics and drug delivery. For example, breast cancer cells have been shown to deform more easily and transit more rapidly through microfluidic channels than healthy breast cells. In this computational biophysics project, we simulate a cell moving through a microfluidic channel. We calculate the deformation energy of a model cell, which includes contributions from the cell cytoskeleton and the cell nucleus. We study how the model cell deforms in response to external forces, focusing on the deformability of the cell as it squeezes into and through a microfluidic channel and how the nucleus plays a part in this. Recent experiments suggest that the nucleus can be up to an order of magnitude stiffer than the rest of the cell and our results may provide insights into how the nucleus influences cell mechanics and migration. This work was supported by a FEAD grant from the College of Science at Rochester Institute of Technology.

  18. 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. PMID:26616908

  19. Influence of channel position on sample confinement in two-dimensional planar microfluidic devices.

    PubMed

    Lerch, Margaret A; Hoffman, Michelle D; Jacobson, Stephen C

    2008-02-01

    We report enhanced sample confinement on microfluidic devices using a combination of electrokinetic flow from adjacent control channels and electric field shaping with an array of channels perpendicular to the sample stream. The basic device design consisted of a single first dimension (1D) channel, intersecting an array of 32 or 96 parallel second dimension (2D) channels. To minimize sample dispersion and leakage into the parallel channels as the sample traversed the sample transfer region, control channels were placed to the left and right of the 1D and waste channels. The electrokinetic flow from the control channels confined the sample stream and acted as a buffer between the sample stream and the 2D channels. To further enhance sample confinement, the electric field was shaped parallel to the sample stream by placing the channel array in close proximity to the sample transfer region. Using COMSOL Multiphysics, initial work focused on simulating the electric fields and fluid flows in various device geometries, and the results guided device design. Following the design phase, we fabricated devices with 40, 80, and 120 microm wide control channels and evaluated the sample stream width as a function of the electric field strength ratio in the control and 1D channels (E(C)/E(1D)). For the 32 channel design, the 40 and 80 microm wide control channels produced the most effective sample confinement with stream widths as narrow as 75 microm, and for the 96 channel design, all three control channel widths generated comparable sample stream widths. Comparison of the 32 and 96 channel designs showed sample confinement scaled easily with the length of the sample transfer region. PMID:18231672

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Separation of two phenotypically similar cell types via a single common marker in microfluidic channels.

    PubMed

    Vickers, Dwayne A L; Chory, Emma J; Murthy, Shashi K

    2012-09-21

    To isolate clinically and biologically relevant cell types from a heterogeneous population, fluorescent or magnetic tagging together with knowledge of surface biomarker profiles represents the state of the art. To date, it remains exceedingly difficult to separate phenotypically and physically similar cell types from a mixed population. We report a microfluidic platform engineered to separate two highly similar cell types using a single antibody by taking advantage of subtle variations in surface receptor density and cell size. This platform utilizes antibody-conjugated surfaces in microfluidic channels together with precise modulation of fluid shear stresses to accomplish selective fractionation in a continuous flow process. Antibody conjugation density variation on the adhesive surfaces is achieved by covalently immobilizing an antibody in the presence of poly(ethylene glycol). This platform is used to demonstrate separation of two CD31 positive cell types, human umbilical vein endothelial cells and human micro vascular endothelial cells. PMID:22782544

  5. 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.

  6. 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

  7. 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.

  8. Two-terminal longitudinal hotwire sensor for monitoring the position and speed of advancing liquid fronts in microfluidic channels

    SciTech Connect

    Ryu, Kee Suk; Shaikh, Kashan; Goluch, Edgar; Liu Chang

    2006-03-06

    We report a simple and practical sensor for monitoring both the absolute position and advancing speed of liquid front in a microfluidic channel. The sensor consists of a longitudinal hot wire element - a two-terminal electrical device, with its length spanning the entire channel. The design, materials, fabrication method, and use of this sensor are extremely simple. Characterization results are presented.

  9. 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. PMID:22574656

  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. 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. PMID:23367363

  12. 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

  13. Facile microfluidic channels for acoustophoresis on a budget.

    PubMed

    Samarasekera, Champika; Yeow, John T W

    2015-10-01

    Acoustophoresis is a powerful yet gentle technique for manipulating cells and particles that has quickly earned a place in the lab-on-a-chip toolkit. However, traditional construction techniques for acoustophoretic resonators have typically required prohibitively expensive and laborious processing methods. Here, we propose a highly cost-effective and cleanroom-free construction technique for transversal acoustophoretic resonators. Channels with two different widths of 750 and 300 μm were constructed using a simple glass and polyimide sandwiching technique. Half and full wavelength resonators were then established using 1 and 5 MHz ultrasound respectively and polystyrene beads were successfully manipulated in both types of resonators. This construction technique was then utilized to demonstrate a bifurcation and trifurcation microchannel with 600 μm widths and 2.5 MHz ultrasound. Our approach addresses some of the key drawbacks of acoustophoretic devices by drastically simplifying the fabrication and prototyping of transversal resonators and will assist in expanding this technology from laboratory benches and into the broader market. PMID:26354878

  14. 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

  15. 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.

  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. 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. PMID:24120039

  18. Experimental investigation of magnetically actuated separation using tangential microfluidic channels and magnetic nanoparticles.

    PubMed

    Munir, Ahsan; Zhu, Zanzan; Wang, Jianlong; Zhou, Hong Susan

    2014-06-01

    A novel continuous switching/separation scheme of magnetic nanoparticles (MNPs) in a sub-microlitre fluid volume surrounded by neodymium permanent magnet is studied in this work using tangential microfluidic channels. Polydimethylsiloxane tangential microchannels are fabricated using a novel micromoulding technique that can be done without a clean room and at much lower cost and time. Negligible switching of MNPs is seen in the absence of magnetic field, whereas 90% of switching is observed in the presence of magnetic field. The flow rate of MNPs solution had dramatic impact on separation performance. An optimum value of the flow rate is found that resulted in providing effective MNP separation at much faster rate. Separation performance is also investigated for a mixture containing non-magnetic polystyrene particles and MNPs. It is found that MNPs preferentially moved from lower microchannel to upper microchannel resulting in efficient separation. The proof-of-concept experiments performed in this work demonstrates that microfluidic bioseparation can be efficiently achieved using functionalised MNPs, together with tangential microchannels, appropriate magnetic field strength and optimum flow rates. This work verifies that a simple low-cost magnetic switching scheme can be potentially of great utility for the separation and detection of biomolecules in microfluidic lab-on-a-chip systems. PMID:25014081

  19. 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.

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

    PubMed

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

    2014-09-01

    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 [Formula: see text] and droplet-to-medium viscosity ratio [Formula: see text]. 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 [Formula: see text] with the droplet size [Formula: see text] and viscosity [Formula: see text]. A simple theoretical model is developed to obtain closed form expressions for droplet mobility [Formula: see text] and [Formula: see text]. The predictions of the theoretical model successfully confront the experimental results in terms of the droplet mobility [Formula: see text] and induced hydrodynamic resistance [Formula: see text]. Numerical simulations are carried out using volume-of-fluid model to predict droplet generation and deformation of droplets of different size ratio [Formula: see text] and viscosity ratio [Formula: see text], which compare well with that obtained from the experiments. In a novel effort, we performed experiments to measure the bulk induced hydrodynamic resistance [Formula: see text] of different biological cells (yeast, L6, and HEK 293). The results reveal that the bulk induced hydrodynamic resistance [Formula: see text] is related to the cell concentration and apparent viscosity of the cells. PMID:25538806

  1. Focusing dynamics of finite-sized particles in confined microfluidic channels

    NASA Astrophysics Data System (ADS)

    Xiang, Nan; Huang, Di; Cheng, Jie; Chen, Ke; Zhang, Xinjie; Tang, Wenlai; Ni, Zhonghua

    2016-02-01

    We investigated the focusing dynamics of finite-sized particles in spiral microfluidic channels. The experimental results demonstrated that, unlike for the dynamics of point-sized particles, the Dean flow contributes little to the lateral migration of finite-sized particles. With interests in applying inertial focusing to biomedical applications, the dynamics of finite-sized tumor cells with an added deformability feature were explored and compared with the dynamics of rigid particles. It was found that the deformation of the cells would slow down the inward shifting of the focused cell array. This improved understanding may serve as an important supplement to the knowledge of existing inertial focusing mechanisms.

  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. Screening Reactive Metabolites Bioactivated by Multiple Enzyme Pathways Using a Multiplexed Microfluidic System

    PubMed Central

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

    2012-01-01

    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 measuring 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 damage 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 TD50. Results illustrate the broad utility of the reactive metabolite screening device. PMID:23095952

  4. Use of directly molded poly(methyl methacrylate) channels for microfluidic applications.

    PubMed

    Lee, Sung Hoon; Kang, Do Hyun; Kim, Hong Nam; Suh, Kahp Y

    2010-12-01

    A direct molding method for creating a homogeneous, polymer microfluidic channel is presented. By utilizing capillary rise and subsequent absorption of poly(methyl methacrylate) (PMMA) solution into a solvent-permeable poly(dimethyl siloxane) (PDMS) mold, various circular or elliptic polymer microchannels were fabricated without channel bonding and additional surface modification processes. In addition, the channel diameter was tunable from several micrometres to several hundreds of micrometres by controlling concentration and initial amount of polymer solution for a given PDMS mold geometry. The molded PMMA channels were used for two applications: blocking absorption of Rhodamine B dye and constructing artificial endothelial cell-cultured capillaries. It was observed that the molded PMMA channels effectively prevented absorption and diffusion of Rhodamine molecules over 5 h time span, demonstrating approximately 40 times higher blocking efficiency as compared to porous PDMS channels. Also, calf pulmonary artery endothelial cells (CPAEs) adhered, spread, and proliferated uniformly within the molded microchannels to form near confluency within 3 days and remained viable at day 6 without notable cell death, suggesting high biocompatibility and possibility for emulating in vivo-like three-dimensional architecture of blood vessels. PMID:20938498

  5. 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

  6. 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

  7. Designing self-propelling micro-swimmer that navigates in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Bingham, Ben; Masoud, Hassan; Alexeev, Alexander

    2011-03-01

    Using a fully-coupled computational approach that integrates the lattice Boltzmann model for the hydrodynamics and the lattice spring model for the micromechanics of deformable solids, we design a synthetic micro-swimmer that not only self-propels but also successfully navigates in a low Reynolds number environment of a microfluidic channel. The swimmer body consists of a responsive polymer gel that undergoes periodical swelling and shrinking. Two thin elastic flappers are attached to the opposite sides of the swimmer body. The flappers wiggle driven by swimmer body oscillations and, in this fashion, propel the micro-swimmer through its highly viscous fluid environment. Third, light sensitive flapper is attached in the front of the swimmer and serves to steer its trajectory in microchannel. When exposed to light, the steering flap bends towards the light source. We show that this swimmer can either move straight or turn in the required direction following light signals. Thus, guided by light, the micro-swimmer can successfully navigate towards the target in a microfluidic channel.

  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. PMID:26452845

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

    PubMed Central

    Matsumoto, Yoshimi; Grushnikov, Andrey; Kikuchi, Kazuma; Noji, Hiroyuki; Yamaguchi, Akihito; Yagi, Yasushi

    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. PMID:26872134

  10. 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. PMID:26872134

  11. 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.

  12. Rare cell chemiluminescence detection based on aptamer-specific capture in microfluidic channels.

    PubMed

    Liu, Wu; Wei, Huibin; Lin, Zhen; Mao, Sifeng; Lin, Jin-Ming

    2011-10-15

    An aptamer-based "sandwich" approach combined with the chemiluminescence (CL) analysis was developed for the capture and detection of rare cells on a microfluidic chip. Aptamers were immobilized on microfluidic channels to achieve capture and isolation of the specific cells from a cell mixture. The capture efficiency for target cells was more than 70% with the purity greater than 97%, when the content of the target cells was between 0.5% and 10% in the initial cell mixture. Gold nanoparticles (Au NPs) modified with aptamers were then added in to bind on the cells and trigger a CL reaction. A satisfactory linearity of the log/log calibration curve between the CL intensity and the number of target cells was observed with a low detection limit of 30 target cells in a 3 μL cell mixture. Spiked whole blood samples were also used to verify the practicality of the present method. This work demonstrated the potential application of the cheap and rapid CL detection into the early diagnosis of cancers. PMID:21856143

  13. Poly(dimethylsiloxane) microlens array integrated with microfluidic channel for fluorescence spectroscopy detection

    NASA Astrophysics Data System (ADS)

    Rujihan, Suparat; Damrongsak, Badin; Kittidachachan, Pattareeya

    2013-06-01

    Fluorescence spectroscopy detection has been commonly used in chemical and biochemical applications as it provides a good reliability and high sensitivity. Commercially available fluorescence spectroscopy system is typically bulky and expensive, hence making it inconvenience for on-site measurement which requires portable systems. However, the drawback of small devices is that it has a low detection volume, resulting in low fluorescence signal. In this paper, we report a microfluidic channel implemented with a microlens array for enhancing the performance of fluorescence spectroscopy detection. The microlens array was used to focus an excitation light onto the microchannel, thus expecting the increase in fluorescence detection signal. Both microchannels and microlens arrays were individually fabricated from poly-dimethylsiloxane (PDMS) using low-cost printed-circuit-board master molds. The fabrication and characterization of PDMS-based microlens arrays are discussed. In short, the microlens in plano-convex shape was designed with diameters of 700, 800 and 900 microns. The fabricated microlens arrays were characterized for radius of curvatures, SAGs and focal lengths. The plano-convex microlens array was then integrated into a microfluidic system in order to investigate the overall performance of fluorescence spectroscopy detection. Experiments were conducted with two fluorescence dyes, i.e. Rhodamine 6G and Coumarin 153. The preliminary results revealed that the PDMS microlens array implemented on the designed system shows potential for improving excitation and emission light intensity and, as a consequence, signal to background ratio of the fluorescence spectroscopy detection.

  14. 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).

  15. 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

  16. 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

  17. 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

  18. Refractive Index Sensor Based on a 1D Photonic Crystal in a Microfluidic Channel

    PubMed Central

    Nunes, Pedro S.; Mortensen, Niels Asger; Kutter, Jörg P.; Mogensen, Klaus B.

    2010-01-01

    A refractive index sensor has been fabricated in silicon oxynitride by standard UV lithography and dry etching processes. The refractive index sensor consists of a 1D photonic crystal (PhC) embedded in a microfluidic channel addressed by fiber-terminated planar waveguides. Experimental demonstrations performed with several ethanol solutions ranging from a purity of 96.00% (n = 1.36356) to 95.04% (n = 1.36377) yielded a sensitivity (Δλ/Δn) of 836 nm/RIU and a limit of detection (LOD) of 6 × 10−5 RIU, which is, however, still one order of magnitude higher than the theoretical lower limit of the limit of detection 1.3 × 10−6 RIU. PMID:22294930

  19. 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.

  20. Adhesion assays of endothelial cells on nanopatterned surfaces within a microfluidic channel.

    PubMed

    Hwang, Se Yon; Kwon, Keon Woo; Jang, Kyung-Jin; Park, Min Cheol; Lee, Jeong Sang; Suh, Kahp Y

    2010-04-01

    We present a simple analytical method to measure adhesion of human umbilical vein endothelial cells (HUVECs) and calf pulmonary artery endothelial cells (CPAEs) using nanopatterned, biodegradable poly(lactic-co-glycolic acid) (PLGA) surfaces for potential applications to artificial tissue-engineered blood vessel. Various nanostructured PLGA surfaces (350 nm wide ridges/350 nm grooves, 350 nm ridges/700 nm grooves, 350 nm ridges/1750 nm grooves, 700 nm ridges/350 nm grooves, 1050 nm ridges/350 nm grooves, 1750 nm ridges/350 nm grooves) and flat (unpatterned) surfaces were fabricated on the bottom of polydimethylsiloxane (PDMS) microfluidic channel of 2 mm width and 60 microm height by using thermal imprinting and irreversible channel bonding. To measure adhesion strength of HUVECs and CPAEs, the cells were exposed to a range of shear stress (12, 40, and 80 dyn/cm(2)) within the channels for 20 min after a preculture for 3 days and the remaining cells were counted under each condition. The highest adhesion strength was found on the surface of 700 nm wide ridges, 350 nm wide grooves for both cell types. The enhanced adhesion on nanopatterned surfaces can be attributed to two aspects: (i) contact guidance along the line direction and (ii) clustered focal adhesions. In particular, the contact guidance induced cell alignment along the line directions, which in turn lowers wall shear stress applied to the cell surface, as supported by a simple hydrodynamic model based on cell morphology. PMID:20218573

  1. Surface modification of polymer microfluidic devices using in-channel atom transfer radical polymerization.

    PubMed

    Sun, Xuefei; Liu, Jikun; Lee, Milton L

    2008-07-01

    In-channel atom transfer radical polymerization (ATRP) was used to graft a PEG layer on the surface of microchannels formed in poly(glycidyl methacrylate)-co-(methyl methacrylate) (PGMAMMA) microfluidic devices. The patterned and cover plates were first anchored with ATRP initiator and then thermally bonded together, followed by pumping a solution containing monomer, catalyst, and ligand into the channel to perform ATRP. A PEG-functionalized layer was grafted on the microchannel wall, which resists protein adsorption. X-ray photoelectron spectroscopy (XPS) was used to investigate the initiator-bound surface, and EOF was measured to evaluate the PEG-grafted PGMAMMA microchannel. Fast, efficient, and reproducible separations of amino acids, peptides, and proteins were obtained using the resultant microdevices. Separation efficiencies were higher than 1.0x10(4) plates for a 3.5 cm separation microchannel. Compared with microdevices modified using a previously reported ATRP technique, these in-channel modified microdevices demonstrated better long-term stability. PMID:18615784

  2. Analytical investigations on the effects of substrate kinetics on macromolecular transport and hybridization through microfluidic channels.

    PubMed

    Das, Siddhartha; Subramanian, Kapil; Chakraborty, Suman

    2007-08-01

    In this paper, a generalized surface-kinetics based model is developed to analytically investigate the influences of the substrate types and the buffer compositions on the macromolecular transport and hybridization in microfluidic channels, under electrokinetic influences. For specific illustration, three typical microchannel substrates, namely silanized glass, polycarbonate and PDMS, are considered, in order to obtain analytical expressions for their zeta potentials as a function of the buffer pH and the substrate compositions. The expressions for the zeta potential are subsequently employed to derive the respective velocity distributions, under the application of electric fields of identical strengths in all cases. It is also taken into consideration that the charged macromolecules introduced into these channels are subjected to electrophoretic influences on account of the applied electric fields. Closed form expressions are derived to predict the transport behaviour of the macromolecules and their subsequent hybridization characteristics. From the analysis presented, it is shown that the modification of the channel surface with silane-treatment becomes useful for enhancing the macromolecular transport and surface hybridization, only if the buffer pH permits a large surface charge density. The analytical solutions are also compared with full-scale numerical solutions of the coupled problem of fluid dynamic and macromolecular transport in presence of the pertinent surface reactions, in order to justify the effectiveness of closed-form expressions derived in this study. PMID:17481862

  3. 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. PMID:27463794

  4. 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.

  5. Centimeter-long microfluidic channel with an aspect ratio above 1,000 directly fabricated in fused silica by femtosecond laser micromachining

    NASA Astrophysics Data System (ADS)

    He, Fei; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

    2010-02-01

    Femtosecond laser micromachining has emerged as a promising technique for creating three dimensional (3D) microstructures. As an essential building block for microfluidics, homogeneous microfluidic channel with high aspectratio is indispensable for lab-on-a-chip (LOC) applications. Fused silica is considered to be an excellent substrate material for LOC applications due to its low thermal expansion coefficient, low autofluorescence, and exceptional transmittance over a wide spectral range. Microfluidic channels can be directly fabricated inside fused silica by femtosecond laser direct writing followed by a subsequent wet chemical etching. However, the fabricated channels usually display a tapered feature and highly elliptical cross-section with limited length (usually <5 mm) and poor inner surface smoothness, which would hamper their applications. Herein, we demonstrate direct fabrication of homogeneous microfluidic channels embedded in fused silica by femtosecond laser direct writing, followed by wet chemical etching and glass drawing. With these procedures, the homogeneity of the fabricated channels has become excellent. Namely, the taper of the microchannels is greatly reduced while their cross-sectional shape becomes circular after the drawing. In addition, an inner surface smoothness of ~0.2 nm can be realized by this method. Finally, the glass drawing method can lead to centimeters long microfluidic channels with an aspect ratio as high as ~1,000. We expect that these microfluidic channels will have important applications in optofluidics in the future.

  6. Light-Directed Self-Assembly of Robust Alginate Gels at Precise Locations in Microfluidic Channels.

    PubMed

    Oh, Hyuntaek; Lu, Annie Xi; Javvaji, Vishal; DeVoe, Don L; Raghavan, Srinivasa R

    2016-07-13

    Recently there has been much interest in using light to activate self-assembly of molecules in a fluid, leading to gelation. The advantage of light over other stimuli lies in its spatial selectivity, i.e., its ability to be directed at a precise location, which could be particularly useful in microfluidic applications. However, existing light-responsive fluids are not suitable for these purposes since they do not convert into sufficiently strong gels that can withstand shear. Here, we address this deficiency by developing a new light-responsive system based on the well-known polysaccharide, alginate. The fluid is composed entirely of commercially available components: alginate, a photoacid generator (PAG), and a chelated complex of divalent strontium (Sr(2+)) cations. Upon exposure to ultraviolet (UV) light, the PAG dissociates to release H(+) ions, which in turn induce the release of free Sr(2+) from the chelate. The Sr(2+) ions self-assemble with the alginate chains to give a stiff gel with an elastic modulus ∼2000 Pa and a yield stress ∼400 Pa (this gel is strong enough to be picked up and held by one's fingers). The above fluid is sent through a network of microchannels and a short segment of a specific channel is exposed to UV light. At that point, the fluid is locally transformed into a strong gel in a few minutes, and the resulting gel blocks the flow through that channel while other channels remain open. When the UV light is removed, the gel is gradually diluted by the flow and the channel reopens. We have thus demonstrated a remote-controlled fluidic valve that can be closed by shining light and reopened when the light is removed. In addition, we also show that light-induced gelation of our alginate fluid can be used to deposit biocompatible payloads at specific addresses within a microchannel. PMID:27347595

  7. 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

  8. 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

  9. Microfluidic HPLC-Chip devices with integral channels containing methylstyrenic-based monolithic media.

    PubMed

    Robotti, Karla M; Yin, Hongfeng; Brennen, Reid; Trojer, Lukas; Killeen, Kevin

    2009-10-01

    Polyimide HPLC-Chip devices containing poly(methylstyrene-bis-p-vinylphenyl)ethane (MS/BVPE) stationary phase within the device channels and with wall attachment were prepared by thermally initiated free radical polymerization. The microfluidic devices were coupled to both UV and MS detectors. The potential of the MS/BVPE monolith as an alternative separation media within chip devices was investigated by side-by-side comparisons to particulate media within commercial devices. The chromatographic behavior of this stationary phase was comparable to particulate media for separations of proteins as the average peak width at half-height was equal (6.2 s) for a separation within 8 min under gradient elution conditions. The ability to control the porosity characteristics of the MS/BVPE monolith with changes in polymerization time also extended its utility into small analyte (< 500 Da) applications, although more optimization is needed to match conventional RP media for these applications. The good mechanical stability of the MS/BVPE monolith within the microdevices enabled excellent run-to-run repeatability (%RSD retention time (< or = 0.16) and chip-to-chip reproducibility (%RSD retention time (1.4). The use of this material within enrichment channels also shows its potential value in more complex work flows. PMID:19777457

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

    PubMed

    Goudie, Marcus J; Ghuman, Alyssa P; Collins, Stephanie B; Pidaparti, Ramana M; 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

  11. 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. PMID:26280913

  12. 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.

  13. 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

  14. Microfluidic electrochemical reactors

    DOEpatents

    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. 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

  16. 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.

  17. Microfluidic Channels on Nanopatterned Substrates: Monitoring Protein Binding to Lipid Bilayers with Surface-Enhanced Raman Spectroscopy

    PubMed Central

    Banerjee, Amrita; Perez-Castillejos, R.; Hahn, D.; Smirnov, Alex I.; Grebel, H.

    2013-01-01

    We used Surface Enhanced Raman Spectroscopy (SERS) to detect binding events between streptavidin and biotinylated lipid bilayers. The binding events took place at the surface between microfluidic channels and anodized aluminum oxide (AAO) with the latter serving as substrates. The bilayers were incorporated in the substrate pores. It was revealed that non-bound molecules were easily washed away and that large suspended cells (Salmonella enterica) are less likely to interfere with the monitoring process: when focusing to the lower surface of the channel, one may resolve mostly the bound molecules. PMID:24932024

  18. Various shapes of silicon freestanding microfluidic channels and microstructures in one-step lithography

    NASA Astrophysics Data System (ADS)

    Pal, Prem; Sato, Kazuo

    2009-05-01

    In this research, we have developed and demonstrated a fabrication method for the formation of various shapes of silicon freestanding microfluidic channels and microstructures in one-step photolithography. The fabrication process utilizes the silicon direct wafer bonding with silicon nitride as an intermediate layer, local oxidation of the silicon (LOCOS) process and wet anisotropic etching. Two different types of etchants (non-ionic surfactant (Triton-X-100) added and pure 25 wt% TMAH solutions) are used in series to perform silicon anisotropic etching. Surfactant-added tetramethyl ammonium hydroxide (TMAH) is employed to define the shapes of the structures, while pure TMAH is used to get high undercutting for their fast releasing. The non-ionic surfactant is preferred considering the complementary metal-oxide semiconductor (CMOS) post process issue of wet anisotropic etching. The undercutting at sharp and rounded concave corners, edges aligned along lang1 0 0rang directions, is measured and analyzed in both pure and surfactant-added TMAH solutions. Mask design issues that must be taken into consideration for the fabrication of desired shape and size structures are also presented.

  19. 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.

  20. Cell death along single microfluidic channel after freeze-thaw treatments.

    PubMed

    Li, Yuhui; Wang, Fen; Wang, Hao

    2010-01-01

    Cryotherapy is a prospective green method for malignant tumor treatment. At low temperature, the cell viability relates with the cooling rate, temperature threshold, freezing interface, as well as ice formation. In clinical applications, the growth of ice ball must reach a suitable size as cells could not be all killed at the ice periphery. The cell death ratio at the ice periphery is important for the control of the freezing destruction. The mechanisms of cryoinjury around the ice periphery need thorough understanding. In this paper, a primary freeze-thaw control was carried out in a cell culture microchip. A series of directional freezing processes and cell responses was tested and discussed. The temperature in the microchip was manipulated by a thermoelectric cooler. The necrotic and apoptotic cells under different cryotreatment (duration of the freezing process, freeze-thaw cycle, postculture, etc.) were stained and distinguished by propidium iodide and fluorescein isothiocyanate (FITC)-Annexin V. The location of the ice front was recorded and a cell death boundary which was different from the ice front was observed. By controlling the cooling process in a microfluidic channel, it is possible to recreate a sketch of biological effect during the process of simulated cryosurgery. PMID:20644680

  1. 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

  2. Quantum dot FRET-based probes in thin films grown in microfluidic channels.

    PubMed

    Crivat, Georgeta; Da Silva, Sandra Maria; Reyes, Darwin R; Locascio, Laurie E; Gaitan, Michael; Rosenzweig, Nitsa; Rosenzweig, Zeev

    2010-02-10

    This paper describes the development of new fluorescence resonance energy transfer (FRET)-based quantum dot probes for proteolytic activity. The CdSe/ZnS quantum dots are incorporated into a thin polymeric film, which is prepared by layer-by-layer deposition of alternately charged polyelectrolytes. The quantum dots, which serve as fluorescent donors, are separated from rhodamine acceptor molecules, which are covalently attached to the film surface by a varying number of polyelectrolyte layers. When excited with visible light, the emission color of the polyelectrolyte multilayer film appears orange due to FRET between the quantum dots and molecular acceptors. The emission color changes to green when the rhodamine molecules are removed from the surface by enzymatic cleavage. The new probe design enables the use of quantum dots in bioassays, in this study for real-time monitoring of trypsin activity, while alleviating concerns about their potential toxicity. Application of these quantum dot FRET-based probes in microfluidic channels enables bioanalysis of volume-limited samples and single-cell studies in an in vivo-like environment. PMID:20073459

  3. A simple separation method with a microfluidic channel based on alternating current potential modulation.

    PubMed

    Noh, Hui-Bog; Chandra, Pranjal; Kim, You-Jeong; Shim, Yoon-Bo

    2012-11-20

    A simple separation and detection system based on an electrochemical potential modulated microchannel (EPMM) device was developed for the first time. The application of alternating current (AC) potential to the microfluidic separation channel walls, which were composed of screen printed carbon electrodes, resulted in the oscillation and fluctuation of analytes and in the formation of a perfect flat flow front. These events resulted in an increase in the effective concentration and in the fine separation of samples. The performance of the EPMM device was examined through the analysis of endocrine disruptors (EDs) and heavy metal ions (HMIs) as model compounds. The analytical parameters that affected the separation and detection of EDs and HMIs were studied in terms of AC amplitude, AC frequency, flow rate, buffer concentration, pH, detection potential, and temperature. The separation efficiency was evaluated through measurements of the theoretical plate number (N), the retention time, and the half-peak width. Linear calibration plots for the detection of EDs and HMIs were obtained between 0.15 and 250.0 nM (detection limit 86.4 ± 2.9 pM) and between 0.01 and 10.0 nM (detection limit 9.5 ± 0.3 pM), respectively. The new device was successfully demonstrated with authentic and real samples. PMID:23075295

  4. 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.

  5. 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.

  6. 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

  7. Separating Beads and Cells in Multi-channel Microfluidic Devices Using Dielectrophoresis and Laminar Flow

    PubMed Central

    Millet, Larry J.; Park, Kidong; Watkins, Nicholas N.; Hsia, K. Jimmy; Bashir, Rashid

    2011-01-01

    Microfluidic devices have advanced cell studies by providing a dynamic fluidic environment on the scale of the cell for studying, manipulating, sorting and counting cells. However, manipulating the cell within the fluidic domain remains a challenge and requires complicated fabrication protocols for forming valves and electrodes, or demands specialty equipment like optical tweezers. Here, we demonstrate that conventional printed circuit boards (PCB) can be used for the non-contact manipulation of cells by employing dielectrophoresis (DEP) for bead and cell manipulation in laminar flow fields for bioactuation, and for cell and bead separation in multichannel microfluidic devices. First, we present the protocol for assembling the DEP electrodes and microfluidic devices, and preparing the cells for DEP. Then, we characterize the DEP operation with polystyrene beads. Lastly, we show representative results of bead and cell separation in a multichannel microfluidic device. In summary, DEP is an effective method for manipulating particles (beads or cells) within microfluidic devices. PMID:21339720

  8. 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

  9. Computational study of velocity profile obtained in microfluidic channel bearing a fluidic transistor: toward highly resolved electrophoretic separation.

    PubMed

    Charhrouchni, Issam; Pallandre, Antoine; Le Potier, Isabelle; Deslouis, Claude; Haghiri-Gosnet, Anne-Marie

    2013-03-01

    The present work is a computational study of velocity profiles in microfluidic channels bearing field flow effect transistors (FFET). In particular, this work investigates perturbations and distortions of the sample band during electrophoretic transport in a rectangular separation channel. The EOF heterogeneity and its induced pressure render the predictions of the analytical performances rather complex. In this context, we propose a systematic numerical inquiry that focuses on the distribution of the velocities for several geometries and EOF modulations. We compare the calculated parabolic velocity profiles to the bare glass microchips. Here, the reported parabolic velocity profiles are coherent with recent experimental results that have been published elsewhere. From the presented equations, in such active hybrid microfluidic chip that integrates a FFET gate layer, separation can be optimized by playing on the gate coverage ratio. The flow fields obtained from analytical models allow further investigations about the efficiency and resolution during electrophoresis. The resulting induced pressure gradient and the associated band broadening underline the need to optimize the resolution in the detriment of the efficiency in such active microfluidic chips. PMID:23254905

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

    PubMed

    Ge, Zhengwei; Wang, Wei; Yang, Chun

    2015-02-01

    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. PMID:25597807

  11. Online multi-channel microfluidic chip-mass spectrometry and its application for quantifying noncovalent protein-protein interactions.

    PubMed

    Liu, Wu; Chen, Qiushui; Lin, Xuexia; Lin, Jin-Ming

    2015-03-01

    To establish an automatic and online microfluidic chip-mass spectrometry (chip-MS) system, a device was designed and fabricated for microsampling by a hybrid capillary. The movement of the capillary was programmed by a computer to aspirate samples from different microfluidic channels in the form of microdroplets (typically tens of nanoliters in volume), which were separated by air plugs. The droplets were then directly analyzed by MS via paper spray ionization without any pretreatment. The feasibility and performance were demonstrated by a concentration gradient experiment. Furthermore, after eliminating the effect of nonuniform response factors by an internal standard method, determination of the association constant within a noncovalent protein-protein complex was successfully accomplished with the MS-based titration indicating the versatility and the potential of this novel platform for widespread applications. PMID:25597452

  12. 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.

  13. Microfluidic sieve valves

    SciTech Connect

    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.

  14. Traumatic Burst Fracture with Spinal Channel Involvement Augmentation with Bioactive Strontium-Hydroxyapatite Cement

    PubMed Central

    Masala, S.; Calabria, E.; Nano, G.; Iundusi, R.; Greco, L.; Di Trapano, R.; Tarantino, U.; Simonetti, G.

    2013-01-01

    In November 2011 a 75-year-old man was admitted to our emergency department with a low back pain caused by a traumatic L1 vertebral collapse with backward projection of posterior wall superior third. The indication for neurosurgical instrumentation was placed, although he refused the treatment. Hence he was treated conservatively without a significant improvement up to January 2012 when, still refusing surgery, he accepted to undergo percutaneous vertebroplasty with a novel bioactive injectable strontium-hydroxyapatite cement. Vertebroplasty was performed without complications. A CT scan, performed the day after the procedure, ruled out extravertebral cement leakage. Pain improvement was significant (preprocedure VAS 10, one-week VAS 4) with a gradual decrease up to three months when it stabilized at 2. CT examination after 1 year showed a good cement osseointegration with osteophytic spurs bridging the superior endplate of the level involved to the inferior one of the level above. The new bone ingrowing property of the strontium-hydroxyapatite containing cement permits to extend the treatment indication also to unstable collapses in which the risk of pseudoarthrosis is very high. In this reported case we evaluated the potential role of percutaneous vertebroplasty in traumatic burst fracture with spinal channel involvement. PMID:23984142

  15. Traumatic burst fracture with spinal channel involvement augmentation with bioactive strontium-hydroxyapatite cement.

    PubMed

    Masala, S; Calabria, E; Nano, G; Iundusi, R; Greco, L; Di Trapano, R; Tarantino, U; Simonetti, G

    2013-01-01

    In November 2011 a 75-year-old man was admitted to our emergency department with a low back pain caused by a traumatic L1 vertebral collapse with backward projection of posterior wall superior third. The indication for neurosurgical instrumentation was placed, although he refused the treatment. Hence he was treated conservatively without a significant improvement up to January 2012 when, still refusing surgery, he accepted to undergo percutaneous vertebroplasty with a novel bioactive injectable strontium-hydroxyapatite cement. Vertebroplasty was performed without complications. A CT scan, performed the day after the procedure, ruled out extravertebral cement leakage. Pain improvement was significant (preprocedure VAS 10, one-week VAS 4) with a gradual decrease up to three months when it stabilized at 2. CT examination after 1 year showed a good cement osseointegration with osteophytic spurs bridging the superior endplate of the level involved to the inferior one of the level above. The new bone ingrowing property of the strontium-hydroxyapatite containing cement permits to extend the treatment indication also to unstable collapses in which the risk of pseudoarthrosis is very high. In this reported case we evaluated the potential role of percutaneous vertebroplasty in traumatic burst fracture with spinal channel involvement. PMID:23984142

  16. A touch-and-go lipid wrapping technique in microfluidic channels for rapid fabrication of multifunctional envelope-type gene delivery nanodevices.

    PubMed

    Kitazoe, Katsuma; Wang, Jun; Kaji, Noritada; Okamoto, Yukihiro; Tokeshi, Manabu; Kogure, Kentaro; Harashima, Hideyoshi; Baba, Yoshinobu

    2011-10-01

    Multifunctional envelope-type gene delivery nanodevices (MENDs) are promising non-viral vectors for gene therapy. Though MENDs remain strong in prolonged exposure to blood circulation, have low immunogenic response, and are suitable for gene targeting, their fabrication requires labor-intensive processes. In this work, a novel approach has been developed for rapid fabrication of MENDs by a touch-and-go lipid wrapping technique in a polydimethylsiloxane (PDMS)/glass microfluidic device. The MEND was fabricated on a glass substrate by introduction of a condensed plasmid DNA core into microfluidic channels that have multiple lipid bilayer films. The principle of the MEND fabrication in the microfluidic channels is based on electrostatic interaction between the condensed plasmid DNA cores and the coated lipid bilayer films. The constructed MEND was collected off-chip and characterized by dynamic light scattering. The MEND was constructed within 5 min with a narrow size distribution centered around 200 nm diameter particles. The size of the MEND showed strong dependence on flow velocity of the condensed plasmid DNA core in the microfluidic channels, and thus, could be controlled to provide the optimal size for medical applications. This approach was also proved possible for fabrication of a MEND in multiple channels at the same time. This on-chip fabrication of the MEND was very simple, rapid, convenient, and cost-effective compared with conventional methods. Our results strongly indicated that MENDs fabricated with our microfluidic device have a good potential for medical use. Moreover, MENDs fabricated by this microfluidic device have a great potential for clinical use because the devices are autoclavable and all the fabrication steps can be completed inside closed microfluidic channels without any external contamination. PMID:21829858

  17. Surface modification of microfluidic channels by UV-mediated graft polymerization of non-fouling and ‘smart’ polymers

    NASA Astrophysics Data System (ADS)

    Ebara, Mitsuhiro; Hoffman, John M.; Stayton, Patrick S.; Hoffman, Allan S.

    2007-08-01

    Microfluidic channels prepared from polydimethylsiloxane (PDMS) have been modified by UV-mediated graft polymerization of temperature-responsive polymers (poly[ N-isopropyl acrylamide] or pNIPAAm), temperature- and pH-responsive copolymers (P[NIPAAm-co-acrylic acid (AAc)]), and a non-fouling hydrogel (polyethyleneglycol diacrylate, or PEGDA). This was done by presorbing a photosensitizer (PS) within the PDMS channel surface regions, contacting the different monomer solutions with the PS-containing surface under nitrogen, and irradiating with UV. The pNIPAAm-grafted surface was hydrophilic below its lower critical solution temperature (LCST), resisting non-specific adsorption, while it was hydrophobic above its LCST, now binding pNIPAAm-coated nanoparticles. Combined temperature- and pH-responsive surfaces were also prepared by UV radiation grafting a monomer mixture of pNIPAAm with AAc. The surfaces have been characterized by advancing water contact angle measurements. These smart microfluidic channels should be useful for many applications such as affinity separations and diagnostic assays.

  18. 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. PMID:26764805

  19. 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.

  20. 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. PMID:26842949

  1. 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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    PubMed

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

    2013-08-01

    This paper describes the fabrication of pressure-driven, open-channel microfluidic systems with lateral dimensions of 45-300 microns carved in omniphobic paper using a craft-cutting tool. Vapor phase silanization with a fluorinated alkyltrichlorosilane renders paper omniphobic, but preserves its high gas permeability and mechanical properties. When sealed with tape, the carved channels form conduits capable of guiding liquid transport in the low-Reynolds number regime (i.e. laminar flow). These devices are compatible with complex fluids such as droplets of water in oil. The combination of omniphobic paper and a craft cutter enables the development of new types of valves and switches, such as "fold valves" and "porous switches," which provide new methods to control fluid flow. PMID:23719764

  5. 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

    2010-11-01

    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. PMID:20844778

  6. Fabrication of 3-Dimensional Structure of Metal Oxide Semiconductor Field Effect Transistor Embodied in the Convex Corner of the Silicon Micro-Fluidic Channel

    NASA Astrophysics Data System (ADS)

    Lim, Geunbae; Park, Chin-Sung; Lyu, Hong-Kun; Kim, Dong-Sun; Jeong, Yong-Taek; Park, Hey-Jung; Kim, Hyoung Sik; Shin, Jang-Kyoo; Choi, Pyung; Lee, Jong-Hyun

    2003-06-01

    As micro-fluidic systems and biochemical detection systems are scaled to smaller dimensions, the realization of small and portable biochemical detection systems has become increasingly important. In this paper, we propose a 3-dimensional structure of a metal oxide semiconductor field-effect transistor(3-D MOSFET) using tetramethyl ammonium hydroxide (TMAH) anisotropic etching, which is a suitable device for combining with a micro-fluidic system. After fabricating a trapezoidal micro-fluidic channel, the 3-D MOSFET embodied in the convex corner of the micro-fluidic channel was fabricated. The length of the gate is about 20 μm and the width is about 9 μm. The depth and top width of the trapezoidal micro-fluidic channel are about 8 μm and 60 μm, respectively. The measured drain saturation current of the 3-D MOSFET was about -22 μA at VGS=-5 V and VDS=-5 V, and the device characteristics exhibit a typical MOSFET behavior. Moreover, a gold layer was used for the MOSFET’s gate metal to detect charged biochemical samples using the affinity between gold and thiol.

  7. 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

  8. 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

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

    PubMed

    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

  10. 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. PMID:26304354

  11. Effects of shear on P-selectin deposition in microfluidic channels.

    PubMed

    Shimp, Eddie A; Alsmadi, Nesreen Z; Cheng, Tiffany; Lam, Kevin H; Lewis, Christopher S; Schmidtke, David W

    2016-03-01

    Traditional leukocyte adhesion assays have provided significant insight into the mechanisms of leukocyte rolling in part through the use of homogeneously coated surfaces. These assays typically involve protein coating of glass coverslips or plastic petri dishes applied via a static drop of protein solution. With this approach, it is difficult to spatially control the location of proteins to fabricate surface-bound protein gradients that mimic in vivo situations. Microfluidic patterning of proteins with microfluidic devices has become a popular technique due to the ability to spatially pattern proteins on a cellular scale. Despite the advantages of microfluidic patterning, few studies have systematically investigated the effects of perfusion time, protein concentration, and perfusion shear stress on protein deposition. Herein, we demonstrated the fabrication of both line and step gradients of P-selectin on glass substrates that support cell rolling and adhesion assays. Investigation of the flow conditions during the microfluidic patterning led to several significant findings. We observed that the protein deposition time of 5 min was sufficient to deposit adequate P-selectin to support neutrophil rolling. We demonstrated that the amount of membrane P-selectin (mP-selectin) or recombinant P-selectin (rP-selectin) deposited showed a dependence on the perfusion shear stress between 4.0 and 32.0 dyn/cm(2), while similar studies with fibronectin or fibrinogen showed no shear stress dependence. Finally, we also created step changes in surface adherent protein concentration of P-selectin to characterize leukocyte-rolling behavior in response to sudden changes in ligand density. PMID:27190563

  12. Separation of chiral objects by shear flow in microfluidic channels - Experiment

    NASA Astrophysics Data System (ADS)

    Marcos; Fu, Henry; Powers, Thomas; Stocker, Roman

    2009-03-01

    We use microfluidics to test the prediction that a helix in shear flow drifts across streamlines. We use the non-motile, helical-shaped bacterium Leptospira biflexa as our model chiral object. As the shear in the top and bottom halves of the microchannel has opposite sign, we predict and observe the bacteria in these two regions to drift in opposite directions. The magnitude of the separation is in good agreement with theory.

  13. Tacky cyclic olefin copolymer: a biocompatible bonding technique for the fabrication of microfluidic channels in COC.

    PubMed

    Keller, Nico; Nargang, Tobias M; Runck, Matthias; Kotz, Frederik; Striegel, Andreas; Sachsenheimer, Kai; Klemm, Denis; Länge, Kerstin; Worgull, Matthias; Richter, Christiane; Helmer, Dorothea; Rapp, Bastian E

    2016-04-26

    Cyclic olefin copolymer (COC) is widely used in microfluidics due to its UV-transparency, its biocompatibility and high chemical resistance. Here we present a fast and cost-effective solvent bonding technique, which allows for the efficient bonding of protein-patterned COC structures. The bonding process is carried out at room temperature and takes less than three minutes. Enzyme activity is retained upon bonding and microstructure deformation does not occur. PMID:27040493

  14. 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

  15. 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. PMID:25706987

  16. Flow-through functionalized PDMS microfluidic channels with dextran derivative for ELISAs.

    PubMed

    Yu, Ling; Li, Chang Ming; Liu, Yingshuai; Gao, Jie; Wang, Wei; Gan, Ye

    2009-05-01

    In this work, a dextran modified PDMS microfluidic ELISA device was fabricated. The dextran functionalization was conducted with a simple, economic and fast flow-through process in a fabricated PDMS microfluidic device, and demonstrated significant enhancement of hydrophilicity and efficient covalent immobilization of proteins on the PDMS microchannel surface. The device was used to simultaneously detect multiple important biomarker IL-5, HBsAg, and IgG, showing a limit of detection of 100 pg mL(-1) and a dynamic range of 5 orders of magnitude, which significantly improved the performance of the reported hydrophobic and plasma-treated hydrophilic PDMS flow-through immunoassay devices. The fabricated PDMS device demonstrated its capability for colorimetric detection of proteins through direct observation by human eyes. Thus, this work not only demonstrates great potential to fabricate an economical and sensitive lab-on-chip system for high throughput screening of various infectious diseases, but also provides an opportunity to develop a portable microfluidic ELISA device via human eye examination for heath point-of-care services. PMID:19370243

  17. Microfluidic waves.

    PubMed

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

    2011-11-21

    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

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

    PubMed

    Wang, Shuo; Jeon, Oju; Shankles, Peter G; Liu, Yuan; Alsberg, Eben; Retterer, Scott T; Lee, Bruce P; Choi, Chang Kyoung

    2016-01-01

    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. PMID:26865901

  19. Fast acoustic tweezers for the two-dimensional manipulation of individual particles in microfluidic channels

    NASA Astrophysics Data System (ADS)

    Tran, S. B. Q.; Marmottant, P.; Thibault, P.

    2012-09-01

    This paper presents a microfluidic device that implements standing surface acoustic waves in order to handle single cells, droplets, and generally particles. The particles are moved in a very controlled manner by the two-dimensional drifting of a standing wave array, using a slight frequency modulation of two ultrasound emitters around their resonance. These acoustic tweezers allow any type of motion at velocities up to few ×10 mm/s, while the device transparency is adapted for optical studies. The possibility of automation provides a critical step in the development of lab-on-a-chip cell sorters and it should find applications in biology, chemistry, and engineering domains.

  20. Chemical vapor deposition of aminopropyl silanes in microfluidic channels for highly efficient microchip capillary electrophoresis-electrospray ionization-mass spectrometry.

    PubMed

    Batz, Nicholas G; Mellors, J Scott; Alarie, Jean Pierre; Ramsey, J Michael

    2014-04-01

    We describe a chemical vapor deposition (CVD) method for the surface modification of glass microfluidic devices designed to perform electrophoretic separations of cationic species. The microfluidic channel surfaces were modified using aminopropyl silane reagents. Coating homogeneity was inferred by precise measurement of the separation efficiency and electroosmotic mobility for multiple microfluidic devices. Devices coated with (3-aminopropyl)di-isopropylethoxysilane (APDIPES) yielded near diffusion-limited separations and exhibited little change in electroosmotic mobility between pH 2.8 and pH 7.5. We further evaluated the temporal stability of both APDIPES and (3-aminopropyl)triethoxysilane (APTES) coatings when stored for a total of 1 week under vacuum at 4 °C or filled with pH 2.8 background electrolyte at room temperature. Measurements of electroosmotic flow (EOF) and separation efficiency during this time confirmed that both coatings were stable under both conditions. Microfluidic devices with a 23 cm long, serpentine electrophoretic separation channel and integrated nanoelectrospray ionization emitter were CVD coated with APDIPES and used for capillary electrophoresis (CE)-electrospray ionization (ESI)-mass spectrometry (MS) of peptides and proteins. Peptide separations were fast and highly efficient, yielding theoretical plate counts over 600,000 and a peak capacity of 64 in less than 90 s. Intact protein separations using these devices yielded Gaussian peak profiles with separation efficiencies between 100,000 and 400,000 theoretical plates. PMID:24655020

  1. Detection of Streptavidin-Biotin Protein Complexes Using Three-Dimensional MOSFET in the Si Micro-Fluidic Channel

    NASA Astrophysics Data System (ADS)

    Han, Dae-Il; Kim, Dong-Sun; Park, Jee-Eun; Shin, Jang-Kyoo; Kong, Seong-Ho; Choi, Pyung; Lee, Jong-Hyun; Lim, Geunbae

    2005-07-01

    To detect the electrical reaction characteristics of streptavidin-biotin protein complexes, a three-dimensional (3-D) p-channel metal oxide semiconductor field effect transistor (PMOSFET)-type biosensor was fabricated in the convex corner of a micro-fluidic channel by tetramethyl ammonium hydroxide (TMAH) anisotropic etching. Au, which has a chemical affinity with thiol, was used as the gate metal for immobilizing a self-assembled monolayer (SAM). The SAM was used to immobilize streptavidin. The hydroxyl group of SAM was bound with the amine group of streptavidin. After that, streptavidin and biotin were bound by their high affinity (Ka˜ 1015 Mol-1). The measurements were performed in phosphate-buffered saline (PBS; pH 6.4, 20 mM) solution. Ag/AgCl was used as the reference electrode. The bindings of SAM, streptavidin and biotin caused a variation in the drain current of the 3-D MOSFET. To verify the interaction among the SAM, streptavidin and biotin, surface plasmon resonance (SPR) measurement was performed.

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

    PubMed

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

    2016-05-01

    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

  3. High throughput assay of diffusion through Cx43 gap junction channels with a microfluidic chip.

    PubMed

    Bathany, Cédric; Beahm, Derek; Felske, James D; Sachs, Frederick; Hua, Susan Z

    2011-02-01

    This paper describes a microfluidic-based assay capable of measuring gap-junction mediated dye diffusion in cultured cells. The technique exploits multistream laminar flow to selectively expose cells to different environments, enabling continuous loading of cells in one compartment while monitoring, in real time, dye diffusion into cells of a neighboring compartment. A simple one-dimensional diffusion model fit to the data extracted the diffusion coefficient of four different dyes, 5-(6)-carboxyfluorescein, 5-chloromethylfluorescein, Oregon green 488 carboxylic acid, and calcein. Different inhibitors were assayed for their ability to reduce dye coupling. The chip can screen multiple inhibitors in parallel in the same cell preparation, demonstrating its potential for high throughput. The technique provides a convenient method to measure gap junction mediated diffusion and a screen for drugs that affect gap junction communication. PMID:21182279

  4. 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. PMID:26781098

  5. Characteristics and Modeling of a Nonplanar Nonrectangular Metal Oxide Semiconductor Field Effect Transistor for Charge Sensing in the Si Micro-Fluidic Channel

    NASA Astrophysics Data System (ADS)

    Lim, Geunbae; Kim, Dong-Sun; Lyu, Hong-Kun; Park, Hey-Jung; Shin, Jang-Kyoo; Choi, Pyung; Lee, Jong-Hyun; Lee, Minho

    2004-06-01

    In this work, a nonplanar, nonrectangular metal-oxide-semiconductor field effect transistor (MOSFET) with an asymmetrical channel structure for sensing charge in the Si micro-fluidic channel was fabricated, and the electrical characteristics of the fabricated three-dimensional (3-D) MOSFET were measured. The device was formed in the convex corner of a Si micro-fluidic channel using tetramethyl ammonium hydroxide (TMAH) anistropic etching solution, so that it would be suitable for combination with a micro-fluidic system. We approximated the nonplanar, nonrectangular 3-D MOSFET to a two-dimensional rectangular structure using the Schwartz-Christoffel transformation. The LEVEL1 device parameters of the 3-D MOSFET were extracted from the measured electrical device characteristics and were used in a simulation program with integrated circuit emphasis (SPICE) simulation. The measured and simulated results for the 3-D MOSFET were compared and found to show good agreement. We also investigated the feasibility of the proposed 3-D MOSFET as a charge sensor for detecting charged biomolecules.

  6. 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.

  7. Stable and Simple Immobilization of Proteinase K Inside Glass Tubes and Microfluidic Channels.

    PubMed

    Küchler, Andreas; Bleich, Julian N; Sebastian, Bernhard; Dittrich, Petra S; Walde, Peter

    2015-11-25

    Engyodontium album proteinase K (proK) is widely used for degrading proteinaceous impurities during the isolation of nucleic acids from biological samples, or in proteomics and prion research. Toward applications of proK in flow reactors, a simple method for the stable immobilization of proK inside glass micropipette tubes was developed. The immobilization of the enzyme was achieved by adsorption of a dendronized polymer-enzyme conjugate from aqueous solution. This conjugate was first synthesized from a polycationic dendronized polymer (denpol) and proK and consisted, on average, of 2000 denpol repeating units and 140 proK molecules, which were attached along the denpol chain via stable bis-aryl hydrazone bonds. Although the immobilization of proK inside the tube was based on nonspecific, noncovalent interactions only, the immobilized proK did not leak from the tube and remained active during prolonged storage at 4 °C and during continuous operation at 25 °C and pH = 7.0. The procedure developed was successfully applied for the immobilization of proK on a glass/PDMS (polydimethylsiloxane) microchip, which is a requirement for applications in the field of proK-based protein analysis with such type of microfluidic devices. PMID:26536248

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

    PubMed

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

    2016-07-01

    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

  9. Influences of Adhesion Variability on the "Living" Dynamics of Filamentous Bacteria in Microfluidic Channels.

    PubMed

    Jahnke, Justin P; Terrell, Jessica L; Smith, Austin M; Cheng, Xuanhong; Stratis-Cullum, Dimitra N

    2016-01-01

    Microfabricated devices have increasingly incorporated bacterial cells for microscale studies and exploiting cell-based functions in situ. However, the role of surface interactions in controlling the bacterial cell behavior is not well understood. In this study, microfluidic substrates of varied bacterial-binding affinity were used to probe the interaction-driven behavior of filamentous Escherichia coli. In particular, cell alignment under controlled shear flow as well as subsequent orientation and filamentation were compared between cells presenting distinct outer membrane phenotypes. We demonstrated that filaments retained position under flow, which allowed for dynamic single-cell monitoring with in situ elongation of over 100 μm for adherent cells. This maximum was not reached by planktonic cells and was, therefore, adhesion-dependent. The bound filaments initially aligned with flow under a range of flow rates and their continual elongation was traced in terms of length and growth path; analysis demonstrated that fimbriae-mediated adhesion increased growth rate, increased terminal length, as well as dramatically changed the adherent geometry, particularly buckling behavior. The effects to filament length and buckling were further exaggerated by the strongest, specificity-driven adhesion tested. Such surface-guided control of the elongation process may be valuable to yield interesting "living" filamentous structures in microdevices. In addition, this work may offer a biomedically relevant platform for further elucidation of filamentation as an immune-resistant morphology. Overall, this work should inspire broader exploration of microfabricated devices for the study and application of single bacterial cells. PMID:27483214

  10. 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

  11. 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.

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

    PubMed

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

    2011-12-01

    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

  13. 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

  14. 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.

  15. Thin-Film Drainage and Droplet Adhesion in a Microfluidic Channel

    NASA Astrophysics Data System (ADS)

    Hui, Jonathan; Wang, Wei; Huang, Peter

    2013-11-01

    In many multiphase fluid processes, such as in petroleum extraction and biochemical analysis, one often sees the lodging of immiscible droplets that block flow in a conduit. The absence of a thin-film lubrication layer surrounding adhered droplets significantly increases the threshold pressure gradient required to induce bulk flows. In this work, we investigate the thin-film drainage process that leads to droplet adhesion and study how coating droplets with charged surfactants or solid particles can prevent direct contact between the droplets and channel wall. We report on our current computational and experimental results of an oversized gas droplet in a water-filled flow channel under the influence of surface tension and interfacial electrostatic repulsion.

  16. Multi-Parameter Cell Affinity Chromatography: Separation and Analysis in a Single Microfluidic Channel

    PubMed Central

    Li, Peng; Gao, Yan; Pappas, Dimitri

    2012-01-01

    The ability to sort and capture more than one cell type from a complex sample will enable a wide variety of studies of cell proliferation, death, and the analysis of disease states. In this work, we integrated a pneumatic actuated control layer to an affinity separation layer to create different antibody coating regions on the same fluidic channel. The comparison of different antibody capture capabilities to the same cell line was demonstrated by flowing Ramos cells through anti-CD19 and anti-CD71 coated regions in the same channel, respectively. It was determined that cell capture density on anti-CD19 region was 2.44±0.13 times higher than on anti-CD71 coated region. This approach can be used to test different affinity molecules for selectivity and capture efficiency using a single cell line in one separation. Selective capture of Ramos and HuT 78 cells from a mixture was also demonstrated using two antibody regions in the same channel. Greater than 90% purity was obtained on both capture areas in both continuous flow and stop flow separation modes. A four-region antibody coated device was then fabricated to study the simultaneous, serial capture of three different cell lines. In this case the device showed effective capture of cells in a single separation channel, opening up the possibility of multiple cell sorting. Multi-parameter sequential blood sample analysis was also demonstrated with high capture specificity (>97% for both CD19+ and CD4+ leukocytes). The chip can also be used to selectively treat cells after affinity separation. PMID:22958145

  17. 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.

  18. In-Channel Atom-Transfer Radical Polymerization of Thermoset Polyester Microfluidic Devices for Bioanalytical Applications

    PubMed Central

    Pan, Tao; Fiorini, Gina S.; Chiu, Daniel T.; Woolley, Adam T.

    2012-01-01

    A new technique for polymer microchannel surface modification, called in-channel atom-transfer radical polymerization, has been developed and applied in the surface derivatization of thermoset polyester (TPE) microdevices with poly(ethylene glycol) (PEG). X-ray photoelectron spectroscopy, electroosmotic flow (EOF), and contact angle measurements indicate that PEG has been grafted on the TPE surface. Moreover, PEG-modified microchannels have much lower and more pH-stable EOF, more hydrophilic surfaces and reduced nonspecific protein adsorption. Capillary electrophoresis separation of amino acid and peptide mixtures in these PEG-modified TPE microchips had good reproducibility. Phosducin-like protein and phosphorylated phosducin-like protein were also separated to measure the phosphorylation efficiency. Our results indicate that PEG-grafted TPE microchips have broad potential application in biomolecular analysis. PMID:17640094

  19. 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

  20. 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. PMID:27247877

  1. Redox-Magnetohydrodynamic Microfluidics Without Channels and Compatible with Electrochemical Detection Under Immunoassay Conditions

    PubMed Central

    Weston, Melissa C.; Nash, Christena K.; Fritsch, Ingrid

    2010-01-01

    A unique capability of redox-magnetohydrodynamics (redox-MHD) for handling liquids on a small scale was demonstrated. A 1.2-μL solution plug was pumped from an injection site to a detector without the need for a channel to direct the flow. The redox pumping species did not interfere with enzymatic activity in a solution compatible with enzyme-linked immunoassays. Alkaline phosphatase (AP), a common enzyme label, converted p-aminophenyl phosphate (PAPP) to p-aminophenol (PAPR) in the presence of 2.5 mM Ru(NH3)6Cl2 and 2.5 mM Ru(NH3)6 Cl3, in 0.1 M Tris buffer (pH=9). A solution plug containing PAPP (no AP) was pumped through the surrounding solution containing AP (no PAPP), and the enzymatically-generated PAPR was easily detected and distinguishable electrochemically from the pumping species with square wave voltammetry down to 0.1 mM concentrations. The test device consisted of a silicon chip containing individually-addressable microband electrodes, placed on a 0.5-T NdFeB permanent magnet with the field oriented perpendicular to the chip. A 8.0-mm wide × 15.5-mm long × 1.5-mm high volume of solution was contained by a poly(dimethylsiloxane) gasket and capped with a glass slide. A steady-state fluid velocity of ~30 μm/s was generated in a reinforcing flow configuration between oppositely polarized sets of pumping electrodes with ~2.1 μA. PMID:20681513

  2. Redox-magnetohydrodynamic microfluidics without channels and compatible with electrochemical detection under immunoassay conditions.

    PubMed

    Weston, Melissa C; Nash, Christena K; Fritsch, Ingrid

    2010-09-01

    A unique capability of redox-magnetohydrodynamics (redox-MHD) for handling liquids on a small scale was demonstrated. A 1.2 muL solution plug was pumped from an injection site to a detector without the need for a channel to direct the flow. The redox pumping species did not interfere with enzymatic activity in a solution compatible with enzyme-linked immunoassays. Alkaline phosphatase (AP), a common enzyme label, converted p-aminophenyl phosphate (PAPP) to p-aminophenol (PAP(R)) in the presence of 2.5 mM Ru(NH(3))(6)Cl(2) and 2.5 mM Ru(NH(3))(6) Cl(3), in 0.1 M Tris buffer (pH = 9). A solution plug containing PAPP (no AP) was pumped through the surrounding solution containing AP (no PAPP), and the enzymatically generated PAP(R) was easily detected and distinguishable electrochemically from the pumping species with square wave voltammetry down to 0.1 mM concentrations. The test device consisted of a silicon chip containing individually addressable microband electrodes, placed on a 0.5 T NdFeB permanent magnet with the field oriented perpendicular to the chip. A 8.0 mm wide x 15.5 mm long x 1.5 mm high volume of solution was contained by a poly(dimethylsiloxane) gasket and capped with a glass slide. A steady-state fluid velocity of approximately 30 mum/s was generated in a reinforcing flow configuration between oppositely polarized sets of pumping electrodes with approximately 2.1 muA. PMID:20681513

  3. 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.

  4. 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.

  5. 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.

  6. One-step in-mould modification of PDMS surfaces and its application in the fabrication of self-driven microfluidic channels.

    PubMed

    Fatona, Ayodele; Chen, Yang; Reid, Michael; Brook, Michael A; Moran-Mirabal, Jose M

    2015-11-21

    Poly(dimethylsiloxane) (PDMS) has become the material of choice for fabricating microfluidic channels for lab-on-a-chip applications. Key challenges that limit the use of PDMS in microfluidic applications are its hydrophobic nature, and the difficulty in obtaining stable surface modifications. Although a number of approaches exist to render PDMS hydrophilic, they suffer from reversion to hydrophobicity and, frequently, surface cracking or roughening. In this study, we describe a one-step in-mould method for the chemical modification of PDMS surfaces, and its use to assess the ability of different surfactants to render PDMS surfaces hydrophilic. Thin films of ionic and non-ionic surfactants were patterned into an array format, transferred onto silicone pre-polymer, and subsequently immobilized onto the PDMS surface during vulcanization. The hydrophilicity of the resulting surfaces was assessed by contact angle measurements. The wettability was observed to be dependent on the chemical structure of the surfactants, their concentration and interactions with PDMS. The morphology of modified PDMS surfaces and their change after wetting and drying cycles were visualized using atomic force microscopy. Our results show that while all surfactants tested can render PDMS surfaces hydrophilic through the in-mould modification, only those modified with PEG-PDMS-PEG copolymer surfactants were stable over wetting/dying cycles and heat treatments. Finally, the in-mould functionalization approach was used to fabricate self-driven microfluidic devices that exhibited steady flow rates, which could be tuned by the device geometry. It is anticipated that the in-mould method can be applied to a range of surface modifications for applications in analytical separations, biosensing, cell isolation and small molecule discovery. PMID:26400365

  7. 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

    2016-01-01

    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

  8. Microfluidic fuel cells

    NASA Astrophysics Data System (ADS)

    Kjeang, Erik

    Microfluidic fuel cell architectures are presented in this thesis. This work represents the mechanical and microfluidic portion of a microfluidic biofuel cell project. While the microfluidic fuel cells developed here are targeted to eventual integration with biocatalysts, the contributions of this thesis have more general applicability. The cell architectures are developed and evaluated based on conventional non-biological electrocatalysts. The fuel cells employ co-laminar flow of fuel and oxidant streams that do not require a membrane for physical separation, and comprise carbon or gold electrodes compatible with most enzyme immobilization schemes developed to date. The demonstrated microfluidic fuel cell architectures include the following: a single cell with planar gold electrodes and a grooved channel architecture that accommodates gaseous product evolution while preventing crossover effects; a single cell with planar carbon electrodes based on graphite rods; a three-dimensional hexagonal array cell based on multiple graphite rod electrodes with unique scale-up opportunities; a single cell with porous carbon electrodes that provides enhanced power output mainly attributed to the increased active area; a single cell with flow-through porous carbon electrodes that provides improved performance and overall energy conversion efficiency; and a single cell with flow-through porous gold electrodes with similar capabilities and reduced ohmic resistance. As compared to previous results, the microfluidic fuel cells developed in this work show improved fuel cell performance (both in terms of power density and efficiency). In addition, this dissertation includes the development of an integrated electrochemical velocimetry approach for microfluidic devices, and a computational modeling study of strategic enzyme patterning for microfluidic biofuel cells with consecutive reactions.

  9. 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

  10. Effects of fluid medium flow and spatial temperature variation on acoustophoretic motion of microparticles in microfluidic channels.

    PubMed

    Liu, Zhongzheng; Kim, Yong-Joe; Wang, Han; Han, Arum

    2016-01-01

    A numerical modeling method for accurately predicting the acoustophoretic motion of compressible microparticles in microfluidic devices is presented to consider the effects of fluid medium flow and spatial temperature variation that can significantly influence the acoustophoretic motion. In the proposed method, zeroth-order fluid medium flow and temperature, and first- and second-order acoustic fields in the microfluidic devices are first calculated by applying quadratic mapping functions and a second-order finite difference method (FDM) to perturbed mass, momentum, and energy conservation equations and state equation. Then, the acoustic radiation force is obtained based on the Gorkov's acoustic radiation force equation and applied to the Newton's Equation of Motion to calculate the microparticle motion. The proposed method was validated by comparing its results to a commercial software package, COMSOL Multiphysics results, one-dimensional, analytical modeling results, and experimental results. It is shown that the fluid medium flow affects the acoustic radiation force and streaming significantly, resulting in the acoustic radiation force and streaming prediction errors of 10.9% and 67.4%, respectively, when the fluid medium flow speed is increased from 0 to 1 m/s. A local temperature elevation from 20 °C to 22 °C also results in the prediction errors of 88.4% and 73.4%. PMID:26827029

  11. 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. PMID:22711057

  12. Capture and separation of biomolecules using magnetic beads in a simple microfluidic channel without an external flow device.

    PubMed

    Wang, Jingjing; Morabito, Kenneth; Erkers, Tom; Tripathi, Anubhav

    2013-11-01

    The use of microfluidic devices and magnetic beads for applications in biotechnology has been extensively explored over the past decade. Many elaborate microfluidic chips have been used in efficient systems for biological assays. However most fail to achieve the ideal point of care (POC) status, as they require larger conventional external devices in conjunction with the microchip. This paper presents a simple technique to capture and separate biomolecules using magnetic bead movement on a microchip without the use of an external flow device. This microchip consisted of two well reservoirs (W1 and W2) connected via a tapered microchannel. Beads were dragged through the microchannel between the two wells at an equivalent speed to a permanent magnet that moved alongside the microchip. More than 95% of beads were transferred from W1 to W2 within 2 min at an average velocity of 0.7 mm s(-1). Enzymatic reactions were employed to test our microchip. Specifically, three assays were performed using the streptavidin coated magnetic beads as a solid support to capture and transfer biomolecules: (1) non-specific adsorption of the substrate, 6-8-difluoro-4-methylumbelliferyl phosphate (DiFMUP), (2) capture of the enzyme, biotinylated alkaline phosphatase (AP), and (3) separation of AP from DiFMUP. Our non-specific adsorption assay indicated that the microchip was capable of transferring the beads with less than 0.002% carryover of DiFMUP. Our capture assay indicated efficient capture and transfer of AP with beads to W2 containing DiFMUP, where the transferred AP converted 100% of DiFMUP to DiFMU within 15 minutes. Our separation assay showed effective separation of AP from DiFMUP and elucidated the binding capacity of the beads for AP. The leftover unbound AP in W1 converted 100% of DiFMUP within 10 minutes and samples with less than the full bead capacity of AP (i.e. all AP was transferred) did not convert any of the DiFMUP. The immobilization of AP on the bead surface

  13. Simultaneous determination of various bioactive redox components in Shuang-Huang-Lian preparations using a novel three-channel isocratic elution liquid chromatography with electrochemical detection system.

    PubMed

    Chen, Liangmian; Hakamata, Hideki; Kusu, Fumiyo; Wang, Zhimin; Gao, Huimin; Kotani, Akira

    2014-07-01

    A novel three-channel isocratic elution high performance liquid chromatography with electrochemical detection (3LC-ECD) system was developed for the simultaneous determination of various bioactive redox components in Shuang-Huang-Lian (SHL) preparations. This 3LC-ECD system consists of three isocratic elution flow ways, two switching valves, four columns, and three electrochemical detectors. Through alternately rotating switching valves to change the elution flow way, six caffeoylquinic acids, four flavonoids, and one phenylethanoid glycoside compound were simultaneously determined within 70 min by the present 3LC-ECD method, in which three compounds of protocatechuic aldehyde, propyl gallate, and kaempferol were used as internal standards. The results demonstrated that the present 3LC-ECD method has achieved desired linearity (r>0.999), precision (relative standard deviation <2.5%), accuracy (recovery, 95.6-103.6%), and high sensitivity (limit of detection, 0.11-0.90 ng/mL). In addition, we successfully determined the contents of these 11 bioactive redox components in 14 batches of SHL oral liquid and 12 batches of SHL lyophilized powder for injection produced by different manufacturers in China. PMID:24657677

  14. 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.

  15. Microfluidic Generation of Haptotactic Gradients through 3D Collagen Gels for Enhanced Neurite Growth

    PubMed Central

    Sundararaghavan, Harini G.; Masand, Shirley N.

    2011-01-01

    Abstract We adapted a microfluidic system used previously to generate durotactic gradients of stiffness in a 3D collagen gel, to produce haptotactic gradients of adhesive ligands through the collagen gel. Oligopeptide sequences that included bioactive peptide sequences from laminin, YIGSR, or IKVAV, were grafted separately onto type I collagen using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Solutions of peptide-grafted collagen and untreated collagen were then used as source and sink input solutions, respectively, in an H-shaped microfluidic network fabricated using traditional soft lithography. One-dimensional gradients of the peptide-grafted collagen solution were generated in the channel that connected the source and sink channels, and these gradients became immobilized upon self-assembly of the collagen into a 3D fibrillar gel. The slope and average concentration of the gradients were adjusted by changing the concentration of the source solutions and by changing the length of the cross-channel. A separate, underlying channel in the microfluidic construct allowed the introduction of a chick embryo dorsal root ganglion into the network. Neurites from these explants grew significantly longer up steep gradients of YIGSR, but shallow gradients of IKVAV in comparison to untreated collagen controls. When these two gradients were presented in combination, the bias in growth acceleration was the largest and most consistent. No differences were observed in the number of neurites choosing to grow up or down the gradients in any condition. These results suggest that the incorporation of distinct gradients of multiple bioactive ligands can improve directional acceleration of regenerating axons. PMID:21473683

  16. 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. PMID:26022783

  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. 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).

  20. 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

  1. Osteocyte culture in microfluidic devices.

    PubMed

    Wei, Chao; Fan, Beiyuan; Chen, Deyong; Liu, Chao; Wei, Yuanchen; Huo, Bo; You, Lidan; Wang, Junbo; Chen, Jian

    2015-01-01

    This paper presents a microfluidic device (poly-dimethylsiloxane micro channels bonded with glass slides) enabling culture of MLO-Y4 osteocyte like cells. In this study, on-chip collagen coating, cell seeding and culture, as well as staining were demonstrated in a tubing-free manner where gravity was used as the driving force for liquid transportation. MLO-Y4 cells were cultured in microfluidic channels with and without collagen coating where cellular images in a time sequence were taken and analyzed, confirming the positive effect of collagen coating on phenotype maintaining of MLO-Y4 cells. The proliferating cell nuclear antigen based proliferation assay was used to study cellular proliferation, revealing a higher proliferation rate of MLO-Y4 cells seeded in microfluidic channels without collagen coating compared to the substrates coated with collagen. Furthermore, the effects of channel dimensions (variations in width and height) on the viability of MLO-Y4 cells were explored based on the Calcein-AM and propidium iodide based live/dead assay and the Hoechst 33258 based apoptosis assay, locating the correlation between the decrease in channel width or height and the decrease in cell viability. As a platform technology, this microfluidic device may function as a new cell culture model enabling studies of osteocytes. PMID:25713691

  2. Osteocyte culture in microfluidic devices

    PubMed Central

    Wei, Chao; Fan, Beiyuan; Chen, Deyong; Wei, Yuanchen; Huo, Bo; You, Lidan; Wang, Junbo; Chen, Jian

    2015-01-01

    This paper presents a microfluidic device (poly-dimethylsiloxane micro channels bonded with glass slides) enabling culture of MLO-Y4 osteocyte like cells. In this study, on-chip collagen coating, cell seeding and culture, as well as staining were demonstrated in a tubing-free manner where gravity was used as the driving force for liquid transportation. MLO-Y4 cells were cultured in microfluidic channels with and without collagen coating where cellular images in a time sequence were taken and analyzed, confirming the positive effect of collagen coating on phenotype maintaining of MLO-Y4 cells. The proliferating cell nuclear antigen based proliferation assay was used to study cellular proliferation, revealing a higher proliferation rate of MLO-Y4 cells seeded in microfluidic channels without collagen coating compared to the substrates coated with collagen. Furthermore, the effects of channel dimensions (variations in width and height) on the viability of MLO-Y4 cells were explored based on the Calcein-AM and propidium iodide based live/dead assay and the Hoechst 33258 based apoptosis assay, locating the correlation between the decrease in channel width or height and the decrease in cell viability. As a platform technology, this microfluidic device may function as a new cell culture model enabling studies of osteocytes. PMID:25713691

  3. Design and fabrication of a microfluidic circuitboard

    NASA Astrophysics Data System (ADS)

    Schabmueller, C. G. J.; Koch, M.; Evans, A. G. R.; Brunnschweiler, A.

    1999-06-01

    This paper reports the design and fabrication of a micromachined microfluidic circuitboard. The circuitboard consists of a Pyrex wafer in which trenches and connection holes are etched. Channels are then formed by anodically bonding a silicon wafer to the Pyrex wafer. On top of this, various microfluidic devices can be mounted via the anodic bonding technique. This allows a simple way of mass production of different microfluidic systems. To realize other microfluidic systems only the mask layout for creating the channels in the Pyrex wafer has to be changed. The microfluidic circuitboard has been successfully fabricated and single devices have been surface mounted. A whole system has been tested and it proved to be functional and without any leakage.

  4. Use of a porous membrane for gas bubble removal in microfluidic channels: physical mechanisms and design criteria

    NASA Astrophysics Data System (ADS)

    Xu, Jie; Vaillant, Regis; Attinger, Daniel

    2010-11-01

    We demonstrate and explain a simple and efficient way to remove gas bubbles from microchannels, by integrating a hydrophobic porous membrane on top of the microchannel. A prototype chip is made in PMMA with the ability to completely filter gas plugs out of a segmented flow at rates up to 7.4 μL/s/mm^2. In our device, gas plugs in a water stream are generated continuously from a T-junction and are then transported towards the gas removal section, where they slide along and vent through a hydrophobic membrane. To achieve complete gas removal without membrane leakage, our analysis shows that four necessary operating criteria are needed. These criteria are verified by experimental results. The first criterion is that the bubble length needs to be larger than the channel diameter. The second criterion is that the bubble should stay on the membrane for a time sufficient to transport all the gas through the membrane. The third criterion is that the bubble travel speed should be lower than a critical value: otherwise a stable liquid film between the bubble and the membrane prevents mass transfer. The fourth criterion is that the pressure difference across the membrane should not be larger than the Laplace pressure to prevent water from leaking through the membrane. Experiments on our device show a good agreement with these criteria.

  5. 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.

  6. Microfluidics with Gel Emulsions

    NASA Astrophysics Data System (ADS)

    Priest, Craig; Surenjav, Enkhtuul; Herminghaus, Stephan; Seemann, Ralf

    2006-03-01

    Microfluidic processing is usually achieved using single phase liquids. Instead, we use monodisperse emulsions to compartment liquids within microchannel geometries. At low continuous phase volume fractions, droplets self-organize to form well-defined arrangements, analogous to foam. While it is well-known that confined geometries can induce rearrangement of foam compartments at the millimeter-scale, similar dynamics are also expected for gel emulsions. We have studied online generation, organization and manipulation of gel emulsions using a variety of microchannel geometries. ``Passive'' reorganization, based on fixed channel geometries, can be supplemented by ``active'' manipulation by incorporating a ferrofluid phase. A ferromagnetic phase facilitates reorganization of liquid compartments on demand using an electromagnetic trigger. Moreover, coalescence between adjacent compartments within a gel emulsion can be induced using electrical potential. Microfluidics using gel emulsions will be well-suited for combinatorial chemistry, DNA sequencing, drug screening and protein crystallizations.

  7. Sol-gel modified poly(dimethylsiloxane) microfluidic devices with high electroosmotic mobilities and hydrophilic channel wall characteristics.

    PubMed

    Roman, Gregory T; Hlaus, Tyler; Bass, Kevin J; Seelhammer, Todd G; Culbertson, Christopher T

    2005-03-01

    Using a sol-gel method, we have fabricated poly(dimethylsiloxane) (PDMS) microchips with SiO2 particles homogeneously distributed within the PDMS polymer matrix. These particles are approximately 10 nm in diameter. To fabricate such devices, PDMS (Sylgard 184) was cast against SU-8 molds. After curing, the chips were carefully removed from the mold and sealed against flat, cured pieces of PDMS to form enclosed channel manifolds. These chips were then solvated in tetraethyl orthosilicate (TEOS), causing them to expand. Subsequently, the chips were placed in an aqueous solution containing 2.8% ethylamine and heated to form nanometer-sized SiO2 particles within the cross-linked PDMS polymer. The water contact angle for the PDMS-SiO2 chips was approximately 90.2 degrees compared to a water contact angle for Sylgard 184 of approximately 108.5 degrees . More importantly, the SiO2 modified PDMS chips showed no rhodamine B absorption after 4 h, indicating a substantially more hydrophilic and nonabsorptive surface than native PDMS. Initial electroosmotic mobilities (EOM) of (8.3+/-0.2)x10(-4) cm2/(V.s) (RSD=2.6% (RSD is relative standard deviation); n=10) were measured. This value was approximately twice that of native Sylgard 184 PDMS chips (4.21+/-0.09)x10(-4) cm2/(V.s) (RSD=2.2%; n=10) and 55% greater than glass chips (5.3+/-0.4)x10(-4) cm2/(V.s) (RSD=7.7%; n=5). After 60 days of dry storage, the EOM was (7.6+/-0.3)x10(-4) cm2/(V.s) (RSD=3.9%; n=3), a decrease of only 8% below that of the initially measured value. Separations performed on these devices generated 80,000-100,000 theoretical plates in 6-14 s for both tetramethylrhodamine succidimidyl ester and fluorescein-5-isothiocyanate derivatized amino acids. The separation distance was 3.5 cm. Plots of peak variance vs analyte migration times gave diffusion coefficients which indicate that the separation efficiencies are within 15% of the diffusion limit. PMID:15732926

  8. 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.

  9. Microfluidic conductimetric bioreactor.

    PubMed

    Limbut, Warakorn; Loyprasert, Suchera; Thammakhet, Chongdee; Thavarungkul, Panote; Tuantranont, Adisorn; Asawatreratanakul, Punnee; Limsakul, Chusak; Wongkittisuksa, Booncharoen; Kanatharana, Proespichaya

    2007-06-15

    A microfluidic conductimetric bioreactor has been developed. Enzyme was immobilized in the microfluidic channel on poly-dimethylsiloxane (PDMS) surface via covalent binding method. The detection unit consisted of two gold electrodes and a laboratory-built conductimetric transducer to monitor the increase in the conductivity of the solution due to the change of the charges generated by the enzyme-substrate catalytic reaction. Urea-urease was used as a representative analyte-enzyme system. Under optimum conditions urea could be determined with a detection limit of 0.09 mM and linearity in the range of 0.1-10 mM (r=0.9944). The immobilized urease on the microchannel chip provided good stability (>30 days of operation time) and good repeatability with an R.S.D. lower than 2.3%. Good agreement was obtained when urea concentrations of human serum samples determined by the microfluidic flow injection conductimetric bioreactor system were compared to those obtained using the Berthelot reaction (P<0.05). After prolong use the immobilized enzyme could be removed from the PDMS microchannel chip enabling new active enzyme to be immobilized and the chip to be reused. PMID:17289366

  10. 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.

  11. Size-based microfluidic multimodal microparticle sorter.

    PubMed

    Wang, Xiao; Papautsky, Ian

    2015-03-01

    Microfluidic sorting of synthetic and biological microparticles has attracted much interest in recent years. Inertial microfluidics uses hydrodynamic forces to manipulate migration of such microparticles in microfluidic channels to achieve passive sorting based on size with high throughput. However, most inertial microfluidic devices are only capable of bimodal separation with a single cutoff diameter and a well-defined size difference. These limitations inhibit efficient separation of real-world samples that often include heterogeneous mixtures of multiple microparticle components. Our design overcomes these challenges to achieve continuous multimodal sorting of microparticles with high resolution and high tunability of separation cutoff diameters. We demonstrate separations with flexible modulation of the separation bandwidth and the passband location. Our approach offers a number of benefits, including straightforward system design, easily and precisely tuned cutoff diameters, high separation resolution, and high throughput. Ultimately, the unique multimodal separation functionality significantly broadens applications of inertial microfluidics in sorting of complex microparticle samples. PMID:25590954

  12. 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.

  13. Digital Microfluidic Logic Gates

    NASA Astrophysics Data System (ADS)

    Zhao, Yang; Xu, Tao; Chakrabarty, Krishnendu

    Microfluidic computing is an emerging application for microfluidics technology. We propose microfluidic logic gates based on digital microfluidics. Using the principle of electrowetting-on-dielectric, AND, OR, NOT and XOR gates are implemented through basic droplet-handling operations such as transporting, merging and splitting. The same input-output interpretation enables the cascading of gates to create nontrivial computing systems. We present a potential application for microfluidic logic gates by implementing microfluidic logic operations for on-chip HIV test.

  14. 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.

  15. 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.

  16. 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. PMID:24162816

  17. 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.

  18. 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.

  19. Analogy among microfluidics, micromechanics, and microelectronics.

    PubMed

    Li, Sheng-Shian; Cheng, Chao-Min

    2013-10-01

    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. PMID:23963526

  20. 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

  1. Digital Microfluidic Processing of Mammalian Embryos for Vitrification

    PubMed Central

    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. PMID:25250666

  2. 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

    2015-07-01

    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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. Nanostructured microfluidic digestion system for rapid high-performance proteolysis

    PubMed Central

    Cheng, Gong; Hao, Si-Jie; Yu, Xu

    2014-01-01

    A novel microfluidic protein digestion system with 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. PMID:25511010

  10. 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

  11. 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.

  12. 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.

  13. Electrochemical velocimetry on centrifugal microfluidic platforms.

    PubMed

    Abi-Samra, Kameel; Kim, Tae-Hyeong; Park, Dong-Kyu; Kim, Nahui; Kim, Jintae; Kim, Hanshin; Cho, Yoon-Kyoung; Madou, Marc

    2013-08-21

    Expanding upon recent applications of interfacing electricity with centrifugal microfluidic platforms, we introduce electrochemical velocimetry to monitor flow in real-time on rotating fluidic devices. Monitoring flow by electrochemical techniques requires a simple, compact setup of miniaturized electrodes that are embedded within a microfluidic channel and are connected to a peripherally-located potentiostat. On-disc flow rates, determined by electrochemical velocimetry, agreed well with theoretically expected values and with optical measurements. As an application of the presented techniques, the dynamic process of droplet formation and release was recorded, yielding critical information about droplet frequency and volume. Overall, the techniques presented in this work advance the field of centrifugal microfluidics by offering a powerful tool, previously unavailable, to monitor flow in real-time on rotating microfluidic systems. PMID:23787459

  14. 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. PMID:26599482

  15. 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.

  16. 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

  17. 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.

  18. Experimental and numerical studies on standing surface acoustic wave microfluidics.

    PubMed

    Mao, Zhangming; Xie, Yuliang; Guo, Feng; Ren, Liqiang; Huang, Po-Hsun; Chen, Yuchao; Rufo, Joseph; Costanzo, Francesco; Huang, Tony Jun

    2016-02-01

    Standing surface acoustic waves (SSAW) are commonly used in microfluidics to manipulate cells and other micro/nano particles. However, except for a simple one-dimensional (1D) harmonic standing waves (HSW) model, a practical model that can predict particle behaviour in SSAW microfluidics is still lacking. Herein, we established a two-dimensional (2D) SSAW microfluidic model based on the basic theory in acoustophoresis and our previous modelling strategy to predict the acoustophoresis of microparticles in SSAW microfluidics. This 2D SSAW microfluidic model considers the effects of boundary vibrations, channel materials, and channel dimensions on the acoustic propagation; as an experimental validation, the acoustophoresis of microparticles under continuous flow through narrow channels made of PDMS and silicon was studied. The experimentally observed motion of the microparticles matched well with the numerical predictions, while the 1D HSW model failed to predict many of the experimental observations. Particularly, the 1D HSW model cannot account for particle aggregation on the sidewall in PDMS channels, which is well explained by our 2D SSAW microfluidic model. Our model can be used for device design and optimization in SSAW microfluidics. PMID:26698361

  19. Microfluidics in amino acid analysis.

    PubMed

    Pumera, Martin

    2007-07-01

    Microfluidic devices have been widely used to derivatize, separate, and detect amino acids employing many different strategies. Virtually zero-dead volume interconnections and fast mass transfer in small volume microchannels enable dramatic increases in on-chip derivatization reaction speed, while only minute amounts of sample and reagent are needed. Due to short channel path, fast subsecond separations can be carried out. With sophisticated miniaturized detectors, the whole analytical process can be integrated on one platform. This article reviews developments of lab-on-chip technology in amino acid analysis, it shows important design features such as sample preconcentration, precolumn and postcolumn amino acid derivatization, and unlabeled and labeled amino acid detection with focus on advanced designs. The review also describes important biomedical and space exploration applications of amino acid analysis on microfluidic devices. PMID:17542043

  20. Nanofluidic interfaces in microfluidic networks

    DOE PAGESBeta

    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

  1. 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.

  2. Channel

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA03693 Channel

    This channel is located south of Iani Chaos.

    Image information: VIS instrument. Latitude -10.9N, Longitude 345.5E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  3. 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

  4. 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

  5. Microfluidic Devices in Advanced Caenorhabditis elegans Research.

    PubMed

    Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

    2016-01-01

    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. PMID:27490525

  6. Nonlinear Dynamics and Control in Microfluidic Networks

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Researchers currently use abundant external devices (e.g., pumps and computers) to achieve precise flow dynamics in microfluidic systems. Here, I show our use of network concepts and computational methods to design microfluidic systems that do not depend on external devices yet still exhibit a diverse range of flow dynamics. I present an example of a microfluidic channel described by a nonlinear pressure-flow relation and show that complex flow behavior can emerge in systems designed around this channel. By controlling the pressure at only a single terminal in such a system, I demonstrate the ability to switch the direction of fluid flow through intermediate channels not directly connected to the controlled terminal. I also show that adding (or removing) flow channels to a system can result in unexpected changes in the total mass flow rate, depending on the network structure of the system. We expect this work to both expand the applicability of microfluidics and promote scaling up of current experiments. This research was funded by the National Science Foundation.

  7. Polymer-based platform for microfluidic systems

    DOEpatents

    Benett, William; Krulevitch, Peter; Maghribi, Mariam; Hamilton, Julie; Rose, Klint; Wang, Amy W.

    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.

  8. Mechanically activated artificial cell by using microfluidics.

    PubMed

    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

  9. 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

  10. 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…

  11. 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

    2016-01-01

    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. PMID:26584257

  12. 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

  13. Dielectric elastomer actuators for active microfluidic control

    NASA Astrophysics Data System (ADS)

    McCoul, David; Murray, Coleman; Di Carlo, Dino; Pei, Qibing

    2013-04-01

    Dielectric elastomers with low modulus and large actuation strain have been investigated for applications in which they serve as "active" microfluidic channel walls. Anisotropically prestrained acrylic elastomer membranes are bonded to cover open trenches formed on a silicone elastomer substrate. Actuation of the elastomer membranes increases the cross-sectional area of the resulting channels, in turn controlling hydraulic flow rate and pressure. Bias voltage increases the active area of the membranes, allowing intrachannel pressure to alter channel geometry. The channels have also demonstrated the ability to actively clear a blockage. Applications may include adaptive microfilters, micro-peristaltic pumps, and reduced-complexity lab-on-a-chip devices.

  14. Microfluidic sorting of microtissues.

    PubMed

    Buschke, D G; Resto, P; Schumacher, N; Cox, B; Tallavajhula, A; Vivekanandan, A; Eliceiri, K W; Williams, J C; Ogle, B M

    2012-03-01

    Increasingly, invitro culture of adherent cell types utilizes three-dimensional (3D) scaffolds or aggregate culture strategies to mimic tissue-like, microenvironmental conditions. In parallel, new flow cytometry-based technologies are emerging to accurately analyze the composition and function of these microtissues (i.e., large particles) in a non-invasive and high-throughput way. Lacking, however, is an accessible platform that can be used to effectively sort or purify large particles based on analysis parameters. Here we describe a microfluidic-based, electromechanical approach to sort large particles. Specifically, sheath-less asymmetric curving channels were employed to separate and hydrodynamically focus particles to be analyzed and subsequently sorted. This design was developed and characterized based on wall shear stress, tortuosity of the flow path, vorticity of the fluid in the channel, sorting efficiency and enrichment ratio. The large particle sorting device was capable of purifying fluorescently labelled embryoid bodies (EBs) from unlabelled EBs with an efficiency of 87.3% ± 13.5%, and enrichment ratio of 12.2 ± 8.4 (n = 8), while preserving cell viability, differentiation potential, and long-term function. PMID:22505992

  15. Parallel Imaging Microfluidic Cytometer

    PubMed Central

    Ehrlich, Daniel J.; McKenna, Brian K.; Evans, James G.; Belkina, Anna C.; Denis, Gerald V.; Sherr, David; 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 flow cytometry (FACS) and microscope-based high-content screening (HCS). The PMC (i) lends itself to fast processing of large numbers of samples, (ii) adds a 1-D 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 approximately 6–10 minutes, about 30-times the speed of most current FACS systems. In 1-D intracellular imaging, the PMC can obtain protein localization using HCS marker strategies at many times the sample throughput of 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. PMID:21704835

  16. Forming particle chains in inertial microfluidic devices

    NASA Astrophysics Data System (ADS)

    Hood, Kaitlyn; Liu, Lawrence; Roper, Marcus

    2015-11-01

    Particles in microfluidic devices at finite Reynolds number self-assemble into evenly-spaced chains, which can be exploited in inertial microfluidic devices for flow cytometry, high speed imaging, and entrapment. While the location and number of chains can be manipulated by changing the channel geometry, the particle interactions are not understood well enough to manipulate the spacing between particles. We present a mathematical model of particle interactions and the formation of particle chains. We will address the following questions: Is there a preferred particle spacing? What are the conditions needed for chain formation?

  17. 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.

  18. Real time detection of lysozyme by pulsed streaming potentials using polyclonal antibodies immobilized on a renewable nonfouling surface inside plastic microfluidic channels.

    PubMed

    Luna-Vera, Fernando; Ferguson, Josephus D; Alvarez, Julio C

    2011-03-15

    A composite surface was prepared on cyclic olefin copolymer (COC) microchannels by UV-photografting of polyethylene glycol acrylate (PEGA) and poly(acrylic acid) (PAA) films. A PEGA layer of globular particles with average thickness of 60 nm was formed after 15 min of polymerization. Real time monitoring by pulsed streaming potentials demonstrated the ability of the PEGA layer to inhibit the adhesion of five different nonspecific adsorbing proteins when compared with pristine COC. Roughness determined by atomic force microscopy (AFM) after PAA grafting on COC-PEGA at different UV illumination times suggests that PAA formation is initiated at the free space in between the PEGA particles. Carboxylic groups activated with N-hydroxysuccinimide and N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide were used to bind anti-lysozyme polyclonal antibodies. The composite COC-PEGA-PAA-anti-lysozyme surface demonstrated its ability to detect lysozyme with a dynamic range between 140 and 860 nM. Linearity was maintained even when samples were spiked with 250 nM of cytochrome as interfering species. The equilibrium constant K(eq) for the adsorption of Ly on COC-PEGA-PAA-anti-Ly was estimated to be 2.7 × 10(6) M(-1), and it shows that this kinetic approach of monitoring the surface charge is also useful to estimate affinity interactions for proteins in label free fashion. The regeneration of the surface exhibited an average percentage of recovery of ∼97% for each of six adsorption-regeneration cycles. This feature enables curve calibration on a single microfluidic chip because each point of the curve has a reproducible and renewable surface. PMID:21322582

  19. Single-mode and tunable microfluidic dye lasers

    NASA Astrophysics Data System (ADS)

    Kristensen, A.; Balslev, S.; Gersborg-Hansen, M.; Bilenberg, B.; Rasmussen, T.; Nilsson, D.

    2006-08-01

    We present a technology for miniaturized, chip-based liquid dye lasers, which may be integrated with microfluidic networks and planar waveguides without addition of further process steps. The microfluidic dye lasers consist of a microfluidic channel with an embedded optical resonator. The lasers are operated with Rhodamine 6G laser dye dissolved in a suitable solvent, such as ethanol or ethylene glycol, and optically pumped at 532 nm with a pulsed, frequency doubled Nd:YAG laser. Both vertically and laterally emitting devices are realized. A vertically emitting Fabry-Perot microcavity laser is integrated with a microfluidic mixer, to demonstrate realtime wavelength tunability. Two major challenges of this technology are addressed: lasing threshold and fluidic handling. Low threshold, in-plane emission and integration with polymer waveguides and microfluidic networks is demonstrated with distributed feed-back lasers. The challenge of fluidic handling is addressed by hybridization with mini-dispensers, and by applying capillary filling of the laser devices.

  20. 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. PMID:26392832

  1. 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

  2. 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.

  3. 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

  4. 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.

  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. 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.

  7. 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.

  8. Electrochemical sensing in paper-based microfluidic devices.

    PubMed

    Nie, Zhihong; Nijhuis, Christian A; Gong, Jinlong; Chen, Xin; Kumachev, Alexander; Martinez, Andres W; Narovlyansky, Max; Whitesides, George M

    2010-02-21

    This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, microPEDs). The microPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the microPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world. PMID:20126688

  9. Phaseguides: a paradigm shift in microfluidic priming and emptying.

    PubMed

    Vulto, Paul; Podszun, Susann; Meyer, Philipp; Hermann, Carsten; Manz, Andreas; Urban, Gerald A

    2011-05-01

    Phaseguide technology gives complete control over filling and emptying of any type of microfluidic structures, independent of the chamber and channel geometry. The technique is based on a step-wise advancement of the liquid-air interface using the meniscus pinning effect. In this paper, the main effects and parameters underlying the phaseguiding principle are discussed and a demonstration is given of its potential for dead angle filling, spatially controlled phaseguide overflow and sequential phaseguide overflow, all accumulating in a passive valving approach. Phaseguides represent a new direction in microfluidic design thinking that will prove a leap forward towards more simple, flexible and reliable microfluidic systems. PMID:21394334

  10. 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

  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. PMID:26221199

  12. Microfluidic reflow pumps

    PubMed Central

    Haslam, Bryan; Tsai, Long-Fang; Anderson, Ryan R.; Kim, Seunghyun; Hu, Weisheng; Nordin, Gregory P.

    2015-01-01

    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. PMID:26221199

  13. 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.

  14. 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. PMID:26920777

  15. Orientation-Based Control of Microfluidics.

    PubMed

    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. 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

  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. 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.

  19. A novel microfluidic chip based on fiber sensor

    NASA Astrophysics Data System (ADS)

    Su, Bo; Duan, Guoteng; Han, Xue

    2013-08-01

    We have fabricated a novel microfluidic chip based on fiber sensor with casting PDMS method. The optical fiber is used to transmit excitation light, so the diameter of the excitation beam is decreased to 93μm. In order to improve the coupling efficiency of the excitation light in the fiber, the optical fiber collimation device is used to couple beam. The microfluidic chip consists of multimode optical fiber, PDMS cover slab and PDMS base slab. The mould of cover slab is made through twice exposal, however the base slab is achieved using once exposal only. The depths of microfluidic channel and optical fiber channel in the PDMS cover slab are 50μm and 90μm, respectively, and the optical fiber channel in the PDMS base slab is only 40μm. This design can make the centers of the microfluidic channel and the fiber channel in the same point, so the microfluidic channel and the optical fiber can be aimed at easily. In addition, the size of microfluidic channel depth is near the size of light spot of optical fiber, so the detection sensitivity is improved without using the optical focusing system. The detection system of the microfluidic chip is manufactured and it composed of high voltage modules, darkroom, LED light source, photomultiplier and data acquisition circuit, moreover, the software of the detection system is developed. The high voltage modules with four 2kV are used to control the sample amount in the separation channel, so the sensitivity is improved. The microfluidic chip is placed in the darkroom to avoid the interference of external light. The high brightness blue light emitting diode (LED) is used as excitation light sources for inducing fluorescence detection through coupling the LED light into the optical fiber. The photomultiplier is used to amplify the fluorescence signals and the function of data acquisition circuit is data collection and data processing. Under the control of software, the experiment process can be implemented easily. As an

  20. 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

  1. 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. PMID:23478651

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Microfluidic peroxidase biochip for polyphenol synthesis.

    PubMed

    Srinivasan, Aravind; Wu, Xiaoqiu; Lee, Moo-Yeal; Dordick, Jonathan S

    2003-03-01

    An enzyme-containing microfluidic biochip has been developed for the oxidative polymerization of phenols. The biochip consists of a simple T-junction with two feed reservoirs 20 mm apart and a microreaction channel 30 mm long. The channel is 15 microm deep and 200 microm wide at the center, giving a reaction volume of 90 nL. The biochip was fabricated using conventional photolithographic methods on a glass substrate etched using a HF-based solution. Fluid transport was enabled using electroosmotic flow. Soybean peroxidase was used as the phenol oxidizing catalyst, and in the presence of p-cresol and H(2)O(2), essentially complete conversion of the H(2)O(2) (the limiting substrate) occurred in the microchannel at a flow rate of ca. 290 nL/min. Thus, peroxidase was found to be intrinsically active even upon dramatic scale-down as achieved in microfluidic reactors. These results were extended to a series of phenols, thereby demonstrating that the microfluidic peroxidase reactor may have application in high-throughput screening of phenolic polymerization reactions for use in phenolic resin synthesis. Finally, rapid growth of poly(p-cresol) on the walls of the microreaction channel could be performed in the presence of higher H(2)O(2) concentrations. This finding suggests that solution-phase peroxidase catalysis can be used in the controlled deposition of polymers on the walls of microreactors. PMID:12514805

  7. 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. PMID:27478521

  8. 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. PMID:26131999

  9. A pump-free membrane-controlled perfusion microfluidic platform.

    PubMed

    Goral, Vasiliy N; Tran, Elizabeth; Yuen, Po Ki

    2015-09-01

    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

  10. 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.

  11. 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

  12. Microfluidic production of polymeric functional microparticles

    NASA Astrophysics Data System (ADS)

    Jiang, Kunqiang

    -bearing beads can function as non-invasive and real-time oxygen micro-sensors. Finally, we report a co-flow microfluidic method to prepare uniform polymer microparticles with macroporous texture, and investigate their application as discrete immunological biosensors for the detection of biological species. The matrix of such microparticles is based on macroporous polymethacrylate polymers configured with tailored pores ranging from hundreds of nanometers to a few microns. Subsequently, we immobilize bioactive antibodies on the particle surface, and demonstrate the immunological performance of these functionalized porous microbeads over a range of antigen concentrations.

  13. Biomimetic microfluidic device for in vitro antihypertensive drug evaluation.

    PubMed

    Li, Lei; Lv, Xiaoqing; Ostrovidov, Serge; Shi, Xuetao; Zhang, Ning; Liu, Jing

    2014-07-01

    Microfluidic devices have emerged as revolutionary, novel platforms for in vitro drug evaluation. In this work, we developed a facile method for evaluating antihypertensive drugs using a microfluidic chip. This microfluidic chip was generated using the elastic material poly(dimethylsiloxane) (PDMS) and a microchannel structure that simulated a blood vessel as fabricated on the chip. We then cultured human umbilical vein endothelial cells (HUVECs) inside the channel. Different pressures and shear stresses could be applied on the cells. The generated vessel mimics can be used for evaluating the safety and effects of antihypertensive drugs. Here, we used hydralazine hydrochloride as a model drug. The results indicated that hydralazine hydrochloride effectively decreased the pressure-induced dysfunction of endothelial cells. This work demonstrates that our microfluidic system provides a convenient and cost-effective platform for studying cellular responses to drugs under mechanical pressure. PMID:24673554

  14. Microfluidic chemical reaction circuits

    DOEpatents

    Lee, Chung-cheng; Sui, Guodong; Elizarov, Arkadij; Kolb, Hartmuth C.; Huang, Jiang; Heath, James R.; Phelps, Michael E.; Quake, Stephen R.; Tseng, Hsian-rong; Wyatt, Paul; Daridon, Antoine

    2012-06-26

    New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.

  15. A novel microfluidic flow focusing method

    PubMed Central

    Jiang, Hai; Weng, Xuan; Li, Dongqing

    2014-01-01

    A new microfluidic method that allows hydrodynamic focusing in a microchannel with two sheath flows is demonstrated. The microchannel network consists of a T-shaped main channel and two T-shaped branch channels. The flows of the sample stream and the sheath streams in the microchannel are generated by electroosmotic flow-induced pressure gradients. In comparison with other flow focusing methods, this novel method does not expose the sample to electrical field, and does not need any external pumps, tubing, and valves. PMID:25538810

  16. Electro-Microfluidic Packaging

    SciTech Connect

    BENAVIDES, GILBERT L.; GALAMBOS, PAUL C.

    2002-06-01

    Electro-microfluidics is experiencing explosive growth in new product developments. There are many commercial applications for electro-microfluidic devices such as chemical sensors, biological sensors, and drop ejectors for both printing and chemical analysis. The number of silicon surface micromachined electro-microfluidic products is likely to increase. Manufacturing efficiency and integration of microfluidics with electronics will become important. Surface micromachined microfluidic devices are manufactured with the same tools as IC's (integrated circuits) and their fabrication can be incorporated into the IC fabrication process. In order to realize applications for devices must be developed. An Electro-Microfluidic Dual In-line Package (EMDIP{trademark}) was developed surface micromachined electro-microfluidic devices, a practical method for getting fluid into these to be a standard solution that allows for both the electrical and the fluidic connections needed to operate a great variety of electro-microfluidic devices. The EMDIP{trademark} includes a fan-out manifold that, on one side, mates directly with the 200 micron diameter Bosch etched holes found on the device, and, on the other side, mates to lager 1 mm diameter holes. To minimize cost the EMDIP{trademark} can be injection molded in a great variety of thermoplastics which also serve to optimize fluid compatibility. The EMDIP{trademark} plugs directly into a fluidic printed wiring board using a standard dual in-line package pattern for the electrical connections and having a grid of multiple 1 mm diameter fluidic connections to mate to the underside of the EMDIP{trademark}.

  17. Surface acoustic wave microfluidics

    PubMed Central

    Ding, Xiaoyun; Li, Peng; Lin, Sz-Chin Steven; Stratton, Zackary S.; Nama, Nitesh; Guo, Feng; Slotcavage, Daniel; Mao, Xiaole; Shi, Jinjie; Costanzo, Francesco; Huang, Tony Jun

    2014-01-01

    The recent introduction of surface acoustic wave (SAW) technology onto lab-on-a-chip platforms has opened a new frontier in microfluidics. The advantages provided by such SAW microfluidics are numerous: simple fabrication, high biocompatibility, fast fluid actuation, versatility, compact and inexpensive devices and accessories, contact-free particle manipulation, and compatibility with other microfluidic components. We believe that these advantages enable SAW microfluidics to play a significant role in a variety of applications in biology, chemistry, engineering, and medicine. In this review article, we discuss the theory underpinning SAWs and their interactions with particles and the contacting fluids in which they are suspended. We then review the SAW-enabled microfluidic devices demonstrated to date, starting with devices that accomplish fluid mixing and transport through the use of travelling SAW; we follow that by reviewing the more recent innovations achieved with standing SAW that enable such actions as particle/cell focusing, sorting, and patterning. Finally, we look forward and appraise where the discipline of SAW microfluidics could go next. PMID:23900527

  18. Layer-by-layer Collagen Deposition in Microfluidic Devices for Microtissue Stabilization.

    PubMed

    McCarty, William J; Prodanov, Ljupcho; Bale, Shyam Sundhar; Bhushan, Abhinav; Jindal, Rohit; Yarmush, Martin L; Usta, O Berk

    2015-01-01

    Although microfluidics provides exquisite control of the cellular microenvironment, culturing cells within microfluidic devices can be challenging. 3D culture of cells in collagen type I gels helps to stabilize cell morphology and function, which is necessary for creating microfluidic tissue models in microdevices. Translating traditional 3D culture techniques for tissue culture plates to microfluidic devices is often difficult because of the limited channel dimensions. In this method, we describe a technique for modifying native type I collagen to generate polycationic and polyanionic collagen solutions that can be used with layer-by-layer deposition to create ultrathin collagen assemblies on top of cells cultured in microfluidic devices. These thin collagen layers stabilize cell morphology and function, as shown using primary hepatocytes as an example cell, allowing for the long term culture of microtissues in microfluidic devices. PMID:26485274

  19. Bioactivation of particles

    DOEpatents

    Pinaud, Fabien; King, David; Weiss, Shimon

    2011-08-16

    Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

  20. Flexible packaging of solid-state integrated circuit chips with elastomeric microfluidics

    NASA Astrophysics Data System (ADS)

    Zhang, Bowei; Dong, Quan; Korman, Can E.; Li, Zhenyu; Zaghloul, Mona E.

    2013-01-01

    A flexible technology is proposed to integrate smart electronics and microfluidics all embedded in an elastomer package. The microfluidic channels are used to deliver both liquid samples and liquid metals to the integrated circuits (ICs). The liquid metals are used to realize electrical interconnects to the IC chip. This avoids the traditional IC packaging challenges, such as wire-bonding and flip-chip bonding, which are not compatible with current microfluidic technologies. As a demonstration we integrated a CMOS magnetic sensor chip and associate microfluidic channels on a polydimethylsiloxane (PDMS) substrate that allows precise delivery of small liquid samples to the sensor. Furthermore, the packaged system is fully functional under bending curvature radius of one centimetre and uniaxial strain of 15%. The flexible integration of solid-state ICs with microfluidics enables compact flexible electronic and lab-on-a-chip systems, which hold great potential for wearable health monitoring, point-of-care diagnostics and environmental sensing among many other applications.

  1. A metering rotary nanopump for microfluidic systems.

    PubMed

    Darby, Scott G; Moore, Matthew R; Friedlander, Troy A; Schaffer, David K; Reiserer, Ron S; Wikswo, John P; Seale, Kevin T

    2010-12-01

    We describe the design, fabrication, and testing of a microfabricated metering rotary nanopump for the purpose of driving fluid flow in microfluidic devices. The miniature peristaltic pump is composed of a set of microfluidic channels wrapped in a helix around a central camshaft in which a non-cylindrical cam rotates. The cam compresses the helical channels to induce peristaltic flow as it is rotated. The polydimethylsiloxane (PDMS) nanopump design is able to produce intermittent delivery or removal of several nanolitres of fluid per revolution as well as consistent continuous flow rates ranging from as low as 15 nL min(-1) to above 1.0 µL min(-1). At back pressures encountered in typical microfluidic devices, the pump acts as a high impedance flow source. The durability, biocompatibility, ease of integration with soft-lithographic fabrication, the use of a simple rotary motor instead of multiple synchronized pneumatic or mechanical actuators, and the absence of power consumption or fluidic conductance in the resting state all contribute to a compact pump with a low cost of fabrication and versatile implementation. This suggests that the pump design may be useful for a wide variety of biological experiments and point of care devices. PMID:20959938

  2. A metering rotary nanopump for microfluidic systems

    PubMed Central

    Darby, Scott G.; Moore, Matthew R.; Friedlander, Troy A.; Schaffer, David K.; Reiserer, Ron S.; Wikswo, John P.

    2014-01-01

    We describe the design, fabrication, and testing of a microfabricated metering rotary nanopump for the purpose of driving fluid flow in microfluidic devices. The miniature peristaltic pump is composed of a set of microfluidic channels wrapped in a helix around a central cam shaft in which a non-cylindrical cam rotates. The cam compresses the helical channels to induce peristaltic flow as it is rotated. The polydimethylsiloxane (PDMS) nanopump design is able to produce intermittent delivery or removal of several nanoliters of fluid per revolution as well as consistent continuous flow rates ranging from as low as 15 nL/min to above 1.0 µL/min. At back pressures encountered in typical microfluidic devices, the pump acts as a high impedance flow source. The durability, biocompatibility, ease of integration with soft-lithographic fabrication, the use of a simple rotary motor instead of multiple synchronized pneumatic or mechanical actuators, and the absence of power consumption or fluidic conductance in the resting state all contribute to a compact pump with a low cost of fabrication and versatile implementation. This suggests that the pump design may be useful for a wide variety of biological experiments and point of care devices. PMID:20959938

  3. Punch card programmable microfluidics.

    PubMed

    Korir, George; Prakash, Manu

    2015-01-01

    Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word "PUNCHCARD MICROFLUIDICS" using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world. PMID:25738834

  4. Differentially photo-crosslinked polymers enable self-assembling microfluidics

    PubMed Central

    Jamal, Mustapha; Zarafshar, Aasiyeh M.; Gracias, David H.

    2012-01-01

    An important feature of naturally self-assembled systems such as leaves and tissues is that they are curved and have embedded fluidic channels that enable the transport of nutrients to, or removal of waste from, specific three-dimensional (3D) regions. Here, we report the self-assembly of photopatterned polymers, and consequently microfluidic devices, into curved geometries. We discovered that differentially photo-crosslinked SU-8 films spontaneously and reversibly curved upon film de-solvation and re-solvation. Photolithographic patterning of the SU-8 films enabled the self-assembly of cylinders, cubes, and bidirectionally folded sheets. We integrated polydimethylsiloxane (PDMS) microfluidic channels with these SU-8 films to self-assemble curved microfluidic networks. PMID:22068594

  5. Rapid fabrication of supercapacitor electrodes using bionanoscaffolds in capillary microfluidics

    NASA Astrophysics Data System (ADS)

    Zang, F.; Chu, S.; Gerasopoulos, K.; Culver, J. N.; Ghodssi, R.

    2015-12-01

    This paper reports the utilization of capillary microfluidics to rapidly create nanostructure-patterned electrodes for energy storage applications. Using patterned photoresist as open-channel capillary microfluidics, Tobacco mosaic virus (TMV) bio-nanoscaffolds suspended in solution are autonomously delivered onto planar gold electrodes over a 1 cm2 area. The TMVs assemble on the electrode and form a dense bio-nanoscaffold layer due to enhanced evaporation-assisted assembly in the open-channel capillary microfluidic device within an hour. The TMV structures are coated with Ni/NiO through electroless plating and thermal oxidation to form supercapacitor electrodes. The galvanostatic charge/discharge cycle showed a 3.6-fold increase in areal capacitance for the nanostructured electrode compared to planar structures.

  6. Lensfree sensing on a microfluidic chip using plasmonic nanoapertures

    PubMed Central

    Khademhosseinieh, Bahar; Biener, Gabriel; Sencan, Ikbal; Su, Ting-Wei; Coskun, Ahmet F.; Ozcan, Aydogan

    2010-01-01

    We demonstrate lensfree on-chip sensing within a microfluidic channel using plasmonic nanoapertures that are illuminated by a partially coherent quasimonochromatic source. In this approach, lensfree diffraction patterns of metallic nanoapertures located at the bottom of a microfluidic channel are recorded using an optoelectronic sensor-array. These lensfree diffraction patterns can then be rapidly processed, using phase recovery techniques, to back propagate the optical fields to an arbitrary depth, creating digitally focused complex transmission patterns. Cross correlation of these patterns enables lensfree on-chip sensing of the local refractive index surrounding the near-field of the plasmonic nanoapertures. Based on this principle, we experimentally demonstrate lensfree sensing of refractive index changes as small as ∼2×10−3. This on-chip sensing approach could be quite useful for development of label-free microarray technologies by multiplexing thousands of plasmonic structures on the same microfluidic chip, which can significantly increase the throughput of sensing. PMID:21203381

  7. 3D Printed Multimaterial Microfluidic Valve.

    PubMed

    Keating, Steven J; Gariboldi, Maria Isabella; Patrick, William G; Sharma, Sunanda; Kong, David S; Oxman, Neri

    2016-01-01

    We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics. PMID:27525809

  8. Magnetic Tethering of Microswimmers in Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Chawan, Aschvin; Jana, Saikat; Ghosh, Suvojit; Jung, Sunghwan; Puri, Ishwar

    2013-03-01

    Exercising control over animal locomotion is well known in the macro world. In the micro-scale world, such methods require more sophistication. We magnetize Paramecium multimicronucleatum by internalization of magnetite nanoparticles coated with bovine serum albumin (BSA). This enables control of their motion in a microfluidic device using a magnetic field. Miniature permanent magnets embedded within the device are used to tether the magnetized organisms to specific locations along a micro-channel. Ciliary beatings of the microswimmer generate shear flows nearby. We apply this setup to enhance cross-stream mixing in a microfluidic device by supplementing molecular diffusion. The device is similar to an active micromixer but requires no external power sources or artificial actuators. We optically characterize the effectiveness of the mechanism in a variety of flow situations.

  9. 3D Printed Multimaterial Microfluidic Valve

    PubMed Central

    Patrick, William G.; Sharma, Sunanda; Kong, David S.; Oxman, Neri

    2016-01-01

    We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics. PMID:27525809

  10. Dry-mass sensing for microfluidics

    NASA Astrophysics Data System (ADS)

    Müller, T.; White, D. A.; Knowles, T. P. J.

    2014-11-01

    We present an approach for interfacing an electromechanical sensor with a microfluidic device for the accurate quantification of the dry mass of analytes within microchannels. We show that depositing solutes onto the active surface of a quartz crystal microbalance by means of an on-chip microfluidic spray nozzle and subsequent solvent removal provides the basis for the real-time determination of dry solute mass. Moreover, this detection scheme does not suffer from the decrease in the sensor's quality factor and the viscous drag present if the measurement is performed in a liquid environment, yet allows solutions to be analysed. We demonstrate the sensitivity and reliability of our approach by controlled deposition of nanogram levels of salt and protein from a micrometer-sized channel.

  11. Cell-based bioassays in microfluidic systems

    NASA Astrophysics Data System (ADS)

    Itle, Laura J.; Zguris, Jeanna C.; Pishko, Michael V.

    2004-12-01

    The development of cell-based bioassays for high throughput drug screening or the sensing of biotoxins is contingent on the development of whole cell sensors for specific changes in intracellular conditions and the integration of those systems into sample delivery devices. Here we show the feasibility of using a 5-(and-6)-carboxy SNARF-1, acetoxymethyl ester, acetate, a fluorescent dye capable of responding to changes in intracellular pH, as a detection method for the bacterial endotoxin, lipopolysaccharide. We used photolithography to entrap cells with this dye within poly(ethylene) glyocol diacrylate hydrogels in microfluidic channels. After 18 hours of exposure to lipopolysaccharide, we were able to see visible changes in the fluorescent pattern. This work shows the feasibility of using whole cell based biosensors within microfluidic networks to detect cellular changes in response to exogenous agents.

  12. Dynamical systems techniques for enhancing microfluidic mixing

    NASA Astrophysics Data System (ADS)

    Balasuriya, Sanjeeva

    2015-09-01

    Achieving rapid mixing is often desirable in microfluidic devices, for example in improving reation rates in biotechnological assays. Enhancing mixing within a particular context is often achieved by introducing problem-specific strategies such as grooved or twisted channels, ac electromagnetic fields or oscillatory microsyringe flows. Evaluating the efficiency of these methods is challenging since either experimental fabrication and sensing, or computationally expensive direct numerical simulations with complicated boundary conditions, are required. A review of how mixing can be quantified when velocity fields have been obtained from such situations is presented. A less-known alternative to these methods is offered by dynamical systems, which characterizes the motion of collective fluid parcel trajectories by studying crucial interior flow barriers which move unsteadily, but nevertheless strongly govern mixing possibilities. The methodology behind defining these barriers and quantifying the fluid transport influenced by them is explained. Their application towards several microfluidic situations (e.g. best cross-flow positioning in cross-channel micromixers, usage of channel curvature to enhance mixing within microdroplets traveling in a channel, optimum frequencies of velocity agitations to use) is discussed.

  13. Microfluidic device capable of sensing ultrafast chemiluminescence.

    PubMed

    Kim, Young-Teck; Ko, Seok Oh; Lee, Ji Hoon

    2009-05-15

    Based on the principle of liquid core waveguide, a novel microfluidic device with micro-scale detection window capable of sensing flashlight emitted from rapid 1,1'-oxalyldi-4-methylimidazole (OD4MI) chemiluminescence (CL) reaction was fabricated. Light emitted from OD4MI CL reaction occurring in the micro-dimensional pentagonal detection window (length of each line segment: 900.0 microm, depth: 50.0 microm) of the microfluidic device with two inlets and one outlet was so bright that it was possible to take an image every 1/30 s at the optimal focusing distance (60 cm) using a commercial digital camera. Peaks obtained using a flow injection analysis (FIA) system with the micro-scale detection window and OD4MI CL detection show excellent resolution and reproducibility without any band-broadening observed in analytical devices having additional reaction channel(s) to measure light generated from slow CL reaction. Maximum height (H(max)) and area (A) of peak, reproducibility and sensitivity observed in the FIA system with the microfluidic device and OD4MI CL detection depends on (1) the mole ratio between bis(2,4,6-trichlorophenyl) oxalate and 4-methyl imidazole yielding OD4MI, (2) the flow rate to mix OD4MI, H(2)O(2) and 1-AP in the detection window of the microfluidic device, and (3) H(2)O(2) concentration. We obtained linear calibration curves with wide dynamic ranges using H(max) and A. The detection limit of 1-AP determined with H(max) and A was as low as 0.05 fmole/injection (signal/background=3.0). PMID:19269463

  14. Simple Check Valves for Microfluidic Devices

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  15. Rapid prototyping of multiphase microfluidics with robotic cutters

    NASA Astrophysics Data System (ADS)

    Li, Zidong; Zhao, Zhengtuo; Lo, Joe Fu-jiou

    2014-03-01

    Microfluidic devices offer novel techniques to address biological and biomedical issues. Standard microfluidic fabrication uses photolithography to pattern channels on silicon wafers with high resolution. Even the relatively straightforward SU8 and soft lithography in microfluidics require investing and training in photolithography, which is also time consuming due to complicated thick resist procedures, including sensitive substrate pretreatment, coating, soft bake, expose, post-exposure bake, and developing steps. However, for applications where low resolution (>200 μm) and high turn-around (> 4 designs/day) prototyping are met with little or no lithography infrastructure, robotic cutters [1] offer flexible options for making glass and PDMS microfluidics. We describe the use of robotics cutters for designing microfluidic geometries, and compliment it with safe glass etching, with depths down to 60 μm. Soft lithography patterning of 200 μm thick PDMS membrane was also explored. Without high equipment investment and lengthy student training, both glass and PDMS microfluidics can be achieved in small facilities using this technique.

  16. Antigen-Responsive, Microfluidic Valves for Single Use Diagnostics

    PubMed Central

    Berron, Brad J.; May, Allison M.; Zheng, Zheng; Balasubramaniam, Vivek

    2014-01-01

    The growing need for medical diagnostics in resource limited settings is driving the development of simple, standalone immunoassay devices. A capillary flow device using polymerization based amplification is capable of blocking a microfluidic channel in response to target biomaterials, enabling multiple modes of detection that require little or no supplemental instrumentation. PMID:22218407

  17. Microfluidic platforms for mechanobiology

    PubMed Central

    Polacheck, William J.; Li, Ran; Uzel, Sebastien G. M.

    2013-01-01

    Mechanotransduction has been a topic of considerable interest since early studies demonstrated a link between mechanical force and biological response. Until recently, studies of fundamental phenomena were based either on in vivo experiments with limited control or direct access, or on large-scale in vitro studies lacking many of the potentially important physiological factors. With the advent of microfluidics, many of the previous limitations of in vitro testing were eliminated or reduced through greater control or combined functionalities. At the same time, imaging capabilities were tremendously enhanced. In this review, we discuss how microfluidics has transformed the study of mechanotransduction. This is done in the context of the various cell types that exhibit force-induced responses and the new biological insights that have been elucidated. We also discuss new microfluidic studies that could produce even more realistic models of in vivo conditions by combining multiple stimuli or creating a more realistic microenvironment. PMID:23649165

  18. Microfluidic Mixing: A Review

    PubMed Central

    Lee, Chia-Yen; Chang, Chin-Lung; Wang, Yao-Nan; Fu, Lung-Ming

    2011-01-01

    The aim of microfluidic mixing is to achieve a thorough and rapid mixing of multiple samples in microscale devices. In such devices, sample mixing is essentially achieved by enhancing the diffusion effect between the different species flows. Broadly speaking, microfluidic mixing schemes can be categorized as either “active”, where an external energy force is applied to perturb the sample species, or “passive”, where the contact area and contact time of the species samples are increased through specially-designed microchannel configurations. Many mixers have been proposed to facilitate this task over the past 10 years. Accordingly, this paper commences by providing a high level overview of the field of microfluidic mixing devices before describing some of the more significant proposals for active and passive mixers. PMID:21686184

  19. Real-time detection of neurite outgrowth using microfluidic device

    NASA Astrophysics Data System (ADS)

    Kim, Samhwan; Jang, Jongmoon; Choi, Hongsoo; Moon, Cheil

    2013-05-01

    We developed a simple method for real-time detection of the neurite outgrowth using microfluidic device. Our microfluidic device contains three compartmentalized channels which are for cell seeding, hydrogel and growth factors. Collagen gel is filled in the middle channel and pheochromocytoma (PC12) cells are seeded in the left channel. To induce differentiation of PC12 cells, 50 ng/ml to1000 ng/ml of nerve growth factor (NGF) is introduced into the right channel. After three days of NGF treatment, PC12 cells begin to extend neurites and formed neurite network from sixth day. Quantification of neurite outgrowth is analyzed by measuring the total area of neurites. On sixth day, the area is doubled compared to the area on third day and increases by 20 times on ninth day.

  20. Punch Card Programmable Microfluidics

    PubMed Central

    Korir, George; Prakash, Manu

    2015-01-01

    Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word “PUNCHCARD MICROFLUIDICS” using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world. PMID:25738834

  1. Centrifugal microfluidic platforms: advanced unit operations and applications.

    PubMed

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

    2015-10-01

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

  2. Lab-on-CMOS Integration of Microfluidics and Electrochemical Sensors

    PubMed Central

    Huang, Yue; Mason, Andrew J.

    2013-01-01

    This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms. PMID:23939616

  3. Grafting of antibodies inside integrated microfluidic-microoptic devices by means of automated microcontact printing

    PubMed Central

    Bou Chakra, Elie; Hannes, Benjamin; Vieillard, Julien; Mansfield, Colin D.; Mazurczyk, Radoslav; Bouchard, Aude; Potempa, Jan; Krawczyk, Stanislas; Cabrera, Michel

    2009-01-01

    A novel approach to integrating biochip and microfluidic devices is reported in which microcontact printing is a key fabrication technique. The process is performed using an automated microcontact printer that has been developed as an application-specific tool. As proof-of-concept the instrument is used to consecutively and selectively graft patterns of antibodies at the bottom of a glass channel for use in microfluidic immunoassays. Importantly, feature collapse due to over compression of the PDMS stamp is avoided by fine control of the stamp’s compression during contact. The precise alignment of biomolecules at the intersection of microfluidic channel and integrated optical waveguides has been achieved, with antigen detection performed via fluorescence excitation. Thus, it has been demonstrated that this technology permits sequential microcontact printing of isolated features consisting of functional biomolecules at any position along a microfluidic channel and also that it is possible to precisely align these features with existing components. PMID:20161128

  4. Experimental Microfluidic System

    NASA Technical Reports Server (NTRS)

    Culbertson, Christopher; Gonda, Steve; Ramsey, John Michael

    2005-01-01

    The ultimate goal of this project is to integrate microfluidic devices with NASA's space bioreactor systems. In such a system, the microfluidic device would provide realtime feedback control of the bioreactor by monitoring pH, glucose, and lactate levels in the cell media; and would provide an analytical capability to the bioreactor in exterrestrial environments for monitoring bioengineered cell products and health changes in cells due to environmental stressors. Such integrated systems could be used as biosentinels both in space and on planet surfaces. The objective is to demonstrate the ability of microfabricated devices to repeatedly and reproducibly perform bead cytometry experiments in micro, lunar, martian, and hypergravity (1.8g).

  5. Microfluidic CARS cytometry

    PubMed Central

    Wang, Han-Wei; Bao, Ning; Le, Thuc T.; Lu, Chang; Cheng, Ji-Xin

    2009-01-01

    Coherent anti-stokes Raman scattering (CARS) flow cytometry was demonstrated by combining a laser-scanning CARS microscope with a polydimethylsiloxane (PDMS) based microfluidic device. Line-scanning across the hydrodynamically focused core stream was performed for detection of flowing objects. Parameters were optimized by utilizing polystyrene beads as flowing particles. Population measurements of adipocytes isolated from mouse fat tissues demonstrated the viability of microfluidic CARS cytometry for quantitation of adipocyte size distribution. CARS cytometry could be a new modality for quantitative analysis with vibrational selectivity. PMID:18542688

  6. Microfluidic Flame Barrier

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  7. Active pneumatic control of centrifugal microfluidic flows for lab-on-a-chip applications.

    PubMed

    Clime, Liviu; Brassard, Daniel; Geissler, Matthias; Veres, Teodor

    2015-06-01

    This paper reports a novel method of controlling liquid motion on a centrifugal microfluidic platform based on the integration of a regulated pressure pump and a programmable electromechanical valving system. We demonstrate accurate control over the displacement of liquids within the system by pressurizing simultaneously multiple ports of the microfluidic device while the platform is rotating at high speed. Compared to classical centrifugal microfluidic platforms where liquids are solely driven by centrifugal and capillary forces, the method presented herein adds a new degree of freedom for fluidic manipulation, which represents a paradigm change in centrifugal microfluidics. We first demonstrate how various core microfluidic functions such as valving, switching, and reverse pumping (i.e., against the centrifugal field) can be easily achieved by programming the pressures applied at dedicated access ports of the microfluidic device. We then show, for the first time, that the combination of centrifugal force and active pneumatic pumping offers the possibility of mixing fluids rapidly (~0.1 s) and efficiently based on the creation of air bubbles at the bottom of a microfluidic reservoir. Finally, the suitability of the developed platform for performing complex bioanalytical assays in an automated fashion is demonstrated in a DNA harvesting experiment where recovery rates of about 70% were systematically achieved. The proposed concept offers the interesting prospect to decouple basic microfluidic functions from specific material properties, channel dimensions and fabrication tolerances, surface treatments, or on-chip active components, thus promoting integration of complex assays on simple and low-cost microfluidic cartridges. PMID:25860103

  8. Particle manipulation through polymer solutions in microfluidic processes

    NASA Astrophysics Data System (ADS)

    Del Giudice, F.; D'Avino, G.; Villone, M. M.; Greco, F.; Maffettone, P. L.

    2015-12-01

    Manipulation of particles suspended in fluids flowing in microfluidic channels is required in a variety of biological, diagnostic and therapeutic applications. For instance, alignment of particles into a tight stream is a necessary step prior to counting, detecting, and sorting. Generally, this task is accomplished by using a Newtonian fluid as suspending medium and by properly fabricating a complex device aimed to displace particle trajectories. In the last years, however, the use of polymeric liquids in microfluidic processes has received a growing interest. Indeed, the addition of a small amount of polymer in a Newtonian suspension flowing in a channel promotes "internal" forces that can be exploited to manipulate the trajectories of suspended particles in simple devices. In this work, we show the possibility to align particles in simple square-shaped microfluidic channels by exploiting viscoelastic forces in flowing suspending liquids. Experiments have been performed to investigate the effect of the channel length, flow rate, confinement ratio (i.e., the ratio between the particle and channel size) and fluid rheology on the particle alignment. Finally, we present experimental results where particle alignment induced by fluid viscoelasticity is combined with magnetophoresis to deflect magnetic beads in a H-shaped channel. High-efficiency separation of magnetic and non-magnetic beads is demonstrated.

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

    PubMed

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

    2015-01-01

    We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s-1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library. PMID:25759752

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

    PubMed Central

    Tangen, Uwe; Sharma, Abhishek

    2015-01-01

    We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s–1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library. PMID:25759752

  11. Microfluidic bead suspension hopper.

    PubMed

    Price, Alexander K; MacConnell, Andrew B; Paegel, Brian M

    2014-05-20

    Many high-throughput analytical platforms, from next-generation DNA sequencing to drug discovery, rely on beads as carriers of molecular diversity. Microfluidic systems are ideally suited to handle and analyze such bead libraries with high precision and at minute volume scales; however, the challenge of introducing bead suspensions into devices before they sediment usually confounds microfluidic handling and analysis. We developed a bead suspension hopper that exploits sedimentation to load beads into a microfluidic droplet generator. A suspension hopper continuously delivered synthesis resin beads (17 μm diameter, 112,000 over 2.67 h) functionalized with a photolabile linker and pepstatin A into picoliter-scale droplets of an HIV-1 protease activity assay to model ultraminiaturized compound screening. Likewise, trypsinogen template DNA-coated magnetic beads (2.8 μm diameter, 176,000 over 5.5 h) were loaded into droplets of an in vitro transcription/translation system to model a protein evolution experiment. The suspension hopper should effectively remove any barriers to using suspensions as sample inputs, paving the way for microfluidic automation to replace robotic library distribution. PMID:24761972

  12. Polar stimulation and constrained cell migration in microfluidic channels†

    PubMed Central

    Agrawal, Nitin; Mitchison, Timothy; Toner, Mehmet

    2010-01-01

    Asymmetrical delivery of stimuli to moving cells for perturbing spatially-heterogeneous intracellular signaling is an experimental challenge not adequately met by existing technologies. Here, we report a robust microfluidic platform allowing localized treatment of the front and/or back of moving cells which crawl through narrow channels that they completely occlude. The enabling technical element for this study is a novel design for precise, passive balancing of flow inside the microfluidic device by contacting two fluid streams before splitting them again. The microchannels constrain cell morphology and induce qualitative and quantitative changes in neutrophil chemotaxis that mimic cells crawling through tissues. PMID:18030401

  13. Microfluidic Screening of Electric Fields for Electroporation

    PubMed Central

    Garcia, Paulo A.; Ge, Zhifei; Moran, Jeffrey L.; Buie, Cullen R.

    2016-01-01

    Electroporation is commonly used to deliver molecules such as drugs, proteins, and/or DNA into cells, but the mechanism remains poorly understood. In this work a rapid microfluidic assay was developed to determine the critical electric field threshold required for inducing bacterial electroporation. The microfluidic device was designed to have a bilaterally converging channel to amplify the electric field to magnitudes sufficient to induce electroporation. The bacterial cells are introduced into the channel in the presence of SYTOX®, which fluorescently labels cells with compromised membranes. Upon delivery of an electric pulse, the cells fluoresce due to transmembrane influx of SYTOX® after disruption of the cell membranes. We calculate the critical electric field by capturing the location within the channel of the increase in fluorescence intensity after electroporation. Bacterial strains with industrial and therapeutic relevance such as Escherichia coli BL21 (3.65 ± 0.09 kV/cm), Corynebacterium glutamicum (5.20 ± 0.20 kV/cm), and Mycobacterium smegmatis (5.56 ± 0.08 kV/cm) have been successfully characterized. Determining the critical electric field for electroporation facilitates the development of electroporation protocols that minimize Joule heating and maximize cell viability. This assay will ultimately enable the genetic transformation of bacteria and archaea considered intractable and difficult-to-transfect, while facilitating fundamental genetic studies on numerous diverse microbes. PMID:26893024

  14. Microfluidic Screening of Electric Fields for Electroporation

    NASA Astrophysics Data System (ADS)

    Garcia, Paulo A.; Ge, Zhifei; Moran, Jeffrey L.; Buie, Cullen R.

    2016-02-01

    Electroporation is commonly used to deliver molecules such as drugs, proteins, and/or DNA into cells, but the mechanism remains poorly understood. In this work a rapid microfluidic assay was developed to determine the critical electric field threshold required for inducing bacterial electroporation. The microfluidic device was designed to have a bilaterally converging channel to amplify the electric field to magnitudes sufficient to induce electroporation. The bacterial cells are introduced into the channel in the presence of SYTOX®, which fluorescently labels cells with compromised membranes. Upon delivery of an electric pulse, the cells fluoresce due to transmembrane influx of SYTOX® after disruption of the cell membranes. We calculate the critical electric field by capturing the location within the channel of the increase in fluorescence intensity after electroporation. Bacterial strains with industrial and therapeutic relevance such as Escherichia coli BL21 (3.65 ± 0.09 kV/cm), Corynebacterium glutamicum (5.20 ± 0.20 kV/cm), and Mycobacterium smegmatis (5.56 ± 0.08 kV/cm) have been successfully characterized. Determining the critical electric field for electroporation facilitates the development of electroporation protocols that minimize Joule heating and maximize cell viability. This assay will ultimately enable the genetic transformation of bacteria and archaea considered intractable and difficult-to-transfect, while facilitating fundamental genetic studies on numerous diverse microbes.

  15. Microfluidic Screening of Electric Fields for Electroporation.

    PubMed

    Garcia, Paulo A; Ge, Zhifei; Moran, Jeffrey L; Buie, Cullen R

    2016-01-01

    Electroporation is commonly used to deliver molecules such as drugs, proteins, and/or DNA into cells, but the mechanism remains poorly understood. In this work a rapid microfluidic assay was developed to determine the critical electric field threshold required for inducing bacterial electroporation. The microfluidic device was designed to have a bilaterally converging channel to amplify the electric field to magnitudes sufficient to induce electroporation. The bacterial cells are introduced into the channel in the presence of SYTOX(®), which fluorescently labels cells with compromised membranes. Upon delivery of an electric pulse, the cells fluoresce due to transmembrane influx of SYTOX(®) after disruption of the cell membranes. We calculate the critical electric field by capturing the location within the channel of the increase in fluorescence intensity after electroporation. Bacterial strains with industrial and therapeutic relevance such as Escherichia coli BL21 (3.65 ± 0.09 kV/cm), Corynebacterium glutamicum (5.20 ± 0.20 kV/cm), and Mycobacterium smegmatis (5.56 ± 0.08 kV/cm) have been successfully characterized. Determining the critical electric field for electroporation facilitates the development of electroporation protocols that minimize Joule heating and maximize cell viability. This assay will ultimately enable the genetic transformation of bacteria and archaea considered intractable and difficult-to-transfect, while facilitating fundamental genetic studies on numerous diverse microbes. PMID:26893024

  16. Characterizing Cell Mechanics with AFM and Microfluidics

    NASA Astrophysics Data System (ADS)

    Walter, N.; Micoulet, A.; Suresh, S.; Spatz, J. P.

    2007-03-01

    Cell mechanical properties and functionality are mainly determined by the cytoskeleton, besides the cell membrane, the nucleus and the cytosol, and depend on various parameters e.g. surface chemistry and rigidity, surface area and time available for cell spreading, nutrients and drugs provided in the culture medium. Human epithelial pancreatic and mammary cancer cells and their keratin intermediate filaments are the main focus of our work. We use Atomic Force Microscopy (AFM) to study cells adhering to substrates and Microfluidic Channels to probe cells in suspension, respectively. Local and global properties are extracted by varying AFM probe tip size and the available adhesion area for cells. Depth-sensing, instrumented indentation tests with AFM show a clear difference in contact stiffness for cells that are spread of controlled substrates and those that are loosely attached. Microfluidic Channels are utilized in parallel to evaluate cell deformation and ``flow resistance'', which are dependent on channel cross section, flow rate, cell nucleus size and the mechanical properties of cytoskeleton and membrane. The results from the study are used to provide some broad and quantitative assessments of the connections between cellular/subcellular mechanics and biochemical origins of disease states.

  17. Microfluidic Biosensing Systems Using Magnetic Nanoparticles

    PubMed Central

    Giouroudi, Ioanna; Keplinger, Franz

    2013-01-01

    In recent years, there has been rapidly growing interest in developing hand held, sensitive and cost-effective on-chip biosensing systems that directly translate the presence of certain bioanalytes (e.g., biomolecules, cells and viruses) into an electronic signal. The impressive and rapid progress in micro- and nanotechnology as well as in biotechnology enables the integration of a variety of analytical functions in a single chip. All necessary sample handling and analysis steps are then performed within the chip. Microfluidic systems for biomedical analysis usually consist of a set of units, which guarantees the manipulation, detection and recognition of bioanalytes in a reliable and flexible manner. Additionally, the use of magnetic fields for performing the aforementioned tasks has been steadily gaining interest. This is because magnetic fields can be well tuned and applied either externally or from a directly integrated solution in the biosensing system. In combination with these applied magnetic fields, magnetic nanoparticles are utilized. Some of the merits of magnetic nanoparticles are the possibility of manipulating them inside microfluidic channels by utilizing high gradient magnetic fields, their detection by integrated magnetic microsensors, and their flexibility due to functionalization by means of surface modification and specific binding. Their multi-functionality is what makes them ideal candidates as the active component in miniaturized on-chip biosensing systems. In this review, focus will be given to the type of biosening systems that use microfluidics in combination with magnetoresistive sensors and detect the presence of bioanalyte tagged with magnetic nanoparticles. PMID:24022689

  18. Microfab-less Microfluidic Capillary Electrophoresis Devices

    PubMed Central

    Segato, Thiago P.; Bhakta, Samir A.; Gordon, Matthew; Carrilho, Emanuel; Willis, Peter A.; Jiao, Hong; Garcia, Carlos D.

    2013-01-01

    Compared to conventional bench-top instruments, microfluidic devices possess advantageous characteristics including great portability potential, reduced analysis time (minutes), and relatively inexpensive production, putting them on the forefront of modern analytical chemistry. Fabrication of these devices, however, often involves polymeric materials with less-than-ideal surface properties, specific instrumentation, and cumbersome fabrication procedures. In order to overcome such drawbacks, a new hybrid platform is proposed. The platform is centered on the use of 5 interconnecting microfluidic components that serve as the injector or reservoirs. These plastic units are interconnected using standard capillary tubing, enabling in-channel detection by a wide variety of standard techniques, including capacitively-coupled contactless conductivity detection (C4D). Due to the minimum impact on the separation efficiency, the plastic microfluidic components used for the experiments discussed herein were fabricated using an inexpensive engraving tool and standard Plexiglas. The presented approach (named 52-platform) offers a previously unseen versatility: enabling the assembly of the platform within minutes using capillary tubing that differs in length, diameter, or material. The advantages of the proposed design are demonstrated by performing the analysis of inorganic cations by capillary electrophoresis on soil samples from the Atacama Desert. PMID:23585815

  19. Microfluidic tissue model for live cell screening.

    PubMed

    Lee, Philip J; Gaige, Terry A; Ghorashian, Navid; Hung, Paul J

    2007-01-01

    We have developed a microfluidic platform modeled after the physiologic microcirculation for multiplexed tissue-like culture and high-throughput analysis. Each microfabricated culture unit consisted of three functional components: a 50 microm wide cell culture pocket, an artificial endothelial barrier with 2 microm pores, and a nutrient transport channel. This configuration enabled a high density of cancer cells to be maintained for over 1 week in a solid tumor-like morphology when fed with continuous flow. The microfluidic chip contained 16 parallel units for "flow cell" based experiments where live cells were exposed to a soluble factor and analyzed via fluorescence microscopy or flow-through biochemistry. Each fluidically independent tissue unit contained approximately 500 cells fed with a continuous flow of 10 nL/min. As a demonstration, the toxicity profile of the anti-cancer drug paclitaxel was collected on HeLa cells cultured in the microfluidic format and compared with a 384-well dish for up to 5 days of continuous drug exposure. PMID:17585775

  20. Microfluidic integration for automated targeted proteomic assays.

    PubMed

    Hughes, Alex J; Lin, Robert K C; Peehl, Donna M; Herr, Amy E

    2012-04-17

    A dearth of protein isoform-based clinical diagnostics currently hinders advances in personalized medicine. A well-organized protein biomarker validation process that includes facile measurement of protein isoforms would accelerate development of effective protein-based diagnostics. Toward scalable protein isoform analysis, we introduce a microfluidic "single-channel, multistage" immunoblotting strategy. The multistep assay performs all immunoblotting steps: separation, immobilization of resolved proteins, antibody probing of immobilized proteins, and all interim wash steps. Programmable, low-dispersion electrophoretic transport obviates the need for pumps and valves. A three-dimensional bulk photoreactive hydrogel eliminates manual blotting. In addition to simplified operation and interfacing, directed electrophoretic transport through our 3D nanoporous reactive hydrogel yields superior performance over the state-of-the-art in enhanced capture efficiency (on par with membrane electroblotting) and sparing consumption of reagents (ca. 1 ng antibody), as supported by empirical and by scaling analyses. We apply our fully integrated microfluidic assay to protein measurements of endogenous prostate specific antigen isoforms in (i) minimally processed human prostate cancer cell lysate (1.1 pg limit of detection) and (ii) crude sera from metastatic prostate cancer patients. The single-instrument functionality establishes a scalable microfluidic framework for high-throughput targeted proteomics, as is relevant to personalized medicine through robust protein biomarker verification, systematic characterization of new antibody probes for functional proteomics, and, more broadly, to characterization of human biospecimen repositories. PMID:22474344

  1. Mixing in microfluidic devices and enhancement methods

    PubMed Central

    Ward, Kevin; Fan, Z Hugh

    2015-01-01

    Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel’s hydraulic diameter, flow velocity, and solution’s kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types. PMID:26549938

  2. A Droplet Microfluidic Platform for Automating Genetic Engineering.

    PubMed

    Gach, Philip C; Shih, Steve C C; Sustarich, Jess; Keasling, Jay D; Hillson, Nathan J; Adams, Paul D; Singh, Anup K

    2016-05-20

    We present a water-in-oil droplet microfluidic platform for transformation, culture and expression of recombinant proteins in multiple host organisms including bacteria, yeast and fungi. The platform consists of a hybrid digital microfluidic/channel-based droplet chip with integrated temperature control to allow complete automation and integration of plasmid addition, heat-shock transformation, addition of selection medium, culture, and protein expression. The microfluidic format permitted significant reduction in consumption (100-fold) of expensive reagents such as DNA and enzymes compared to the benchtop method. The chip contains a channel to continuously replenish oil to the culture chamber to provide a fresh supply of oxygen to the cells for long-term (∼5 days) cell culture. The flow channel also replenished oil lost to evaporation and increased the number of droplets that could be processed and cultured. The platform was validated by transforming several plasmids into Escherichia coli including plasmids containing genes for fluorescent proteins GFP, BFP and RFP; plasmids with selectable markers for ampicillin or kanamycin resistance; and a Golden Gate DNA assembly reaction. We also demonstrate the applicability of this platform for transformation in widely used eukaryotic organisms such as Saccharomyces cerevisiae and Aspergillus niger. Duration and temperatures of the microfluidic heat-shock procedures were optimized to yield transformation efficiencies comparable to those obtained by benchtop methods with a throughput up to 6 droplets/min. The proposed platform offers potential for automation of molecular biology experiments significantly reducing cost, time and variability while improving throughput. PMID:26830031

  3. Submillisecond organic synthesis: Outpacing Fries rearrangement through microfluidic rapid mixing.

    PubMed

    Kim, Heejin; Min, Kyoung-Ik; Inoue, Keita; Im, Do Jin; Kim, Dong-Pyo; Yoshida, Jun-ichi

    2016-05-01

    In chemical synthesis, rapid intramolecular rearrangements often foil attempts at site-selective bimolecular functionalization. We developed a microfluidic technique that outpaces the very rapid anionic Fries rearrangement to chemoselectively functionalize iodophenyl carbamates at the ortho position. Central to the technique is a chip microreactor of our design, which can deliver a reaction time in the submillisecond range even at cryogenic temperatures. The microreactor was applied to the synthesis of afesal, a bioactive molecule exhibiting anthelmintic activity, to demonstrate its potential for practical synthesis and production. PMID:27151864

  4. Remotely powered distributed microfluidic pumps and mixers based on miniature diodes.

    PubMed

    Chang, Suk Tai; Beaumont, Erin; Petsev, Dimiter N; Velev, Orlin D

    2008-01-01

    We demonstrate new principles of microfluidic pumping and mixing by electronic components integrated into a microfluidic chip. The miniature diodes embedded into the microchannel walls rectify the voltage induced between their electrodes from an external alternating electric field. The resulting electroosmotic flows, developed in the vicinity of the diode surfaces, were utilized for pumping or mixing of the fluid in the microfluidic channel. The flow velocity of liquid pumped by the diodes facing in the same direction linearly increased with the magnitude of the applied voltage and the pumping direction could be controlled by the pH of the solutions. The transverse flow driven by the localized electroosmotic flux between diodes oriented oppositely on the microchannel was used in microfluidic mixers. The experimental results were interpreted by numerical simulations of the electrohydrodynamic flows. The techniques may be used in novel actively controlled microfluidic-electronic chips. PMID:18094769

  5. SmartBuild-a truly plug-n-play modular microfluidic system.

    PubMed

    Yuen, Po Ki

    2008-08-01

    In this Technical Note, for the first time, a truly "plug-n-play" modular microfluidic system (SmartBuild Plug-n-Play Modular Microfluidic System) is presented for designing and building integrated modular microfluidic systems for biological and chemical applications. The modular microfluidic system can be built by connecting multiple microfluidic components together to form a larger integrated system. The SmartBuild System comprises of a motherboard with interconnect channels/grooves, fitting components, microchannel inserts with different configurations and microchips/modules with different functionalities. Also, heaters, micropumps and valving systems can be designed and used in the system. Examples of an integrated mixing system and reaction systems are presented here to demonstrate the versatility of the SmartBuild System. PMID:18651081

  6. Direct integration of MEMS, dielectric pumping and cell manipulation with reversibly bonded gecko adhesive microfluidics

    NASA Astrophysics Data System (ADS)

    Warnat, S.; King, H.; Wasay, A.; Sameoto, D.; Hubbard, T.

    2016-09-01

    We present an approach to form a microfluidic environment on top of MEMS dies using reversibly bonded microfluidics. The reversible polymeric microfluidics moulds bond to the MEMS die using a gecko-inspired gasket architecture. In this study the formed microchannels are demonstrated in conjunction with a MEMS mechanical single cell testing environment for BioMEMS applications. A reversible microfluidics placement technique with an x-y and rotational accuracy of  ±2 µm and 1° respectively on a MEMS die was developed. No leaks were observed during pneumatic pumping of common cell media (PBS, sorbitol, water, seawater) through the fluidic channels. Thermal chevron actuators were successful operated inside this fluidic environment and a performance deviation of ~15% was measured compared to an open MEMS configuration. Latex micro-spheres were pumped using traveling wave di-electrophoresis and compared to an open (no-microfluidics) configuration with velocities of 24 µm s‑1 and 20 µm s‑1.

  7. Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping.

    PubMed

    Liu, Jixiao; Fu, Hai; Yang, Tianhang; Li, Songjing

    2015-09-01

    To sequentially handle fluids is of great significance in quantitative biology, analytical chemistry, and bioassays. However, the technological options are limited when building such microfluidic sequential processing systems, and one of the encountered challenges is the need for reliable, efficient, and mass-production available microfluidic pumping methods. Herein, we present a bubble-free and pumping-control unified liquid handling method that is compatible with large-scale manufacture, termed multilayer microfluidic sample isolated pumping (mμSIP). The core part of the mμSIP is the selective permeable membrane that isolates the fluidic layer from the pneumatic layer. The air diffusion from the fluidic channel network into the degassing pneumatic channel network leads to fluidic channel pressure variation, which further results in consistent bubble-free liquid pumping into the channels and the dead-end chambers. We characterize the mμSIP by comparing the fluidic actuation processes with different parameters and a flow rate range of 0.013 μl/s to 0.097 μl/s is observed in the experiments. As the proof of concept, we demonstrate an automatic sequential fluid handling system aiming at digital assays and immunoassays, which further proves the unified pumping-control and suggests that the mμSIP is suitable for functional microfluidic assays with minimal operations. We believe that the mμSIP technology and demonstrated automatic sequential fluid handling system would enrich the microfluidic toolbox and benefit further inventions. PMID:26487904

  8. Femtosecond laser-drilled capillary integrated into a microfluidic device

    SciTech Connect

    Kim, Tyson N.; Campbell, Kyle; Groisman, Alex; Kleinfeld, David; Schaffer, Chris B.

    2005-05-16

    Recent growth in microfluidic technology is, to a large extent, driven by soft lithography, a high-throughput fabrication technique where polymer materials, such as poly(dimethyl) siloxane (PDMS), are molded to form microscopic channel networks. Nevertheless, the channel architectures that can be obtained by molding are limited. We address this limitation by using femtosecond laser micromachining to add unmoldable features to the microfluidic devices. We apply laser ablation to drill microcapillaries, with diameters as small as 0.5 {mu}m and aspect ratios as high as 800:1, in the walls of molded PDMS channels. Finally, we use a laser-drilled microcapillary to trap a polystyrene bead by suction and hold it against a shear flow.

  9. Thermally driven microfluidic pumping via reversible shape memory polymers

    NASA Astrophysics Data System (ADS)

    Robertson, J. M.; Rodriguez, R. X.; Holmes, L. R., Jr.; Mather, P. T.; Wetzel, E. D.

    2016-08-01

    The need exists for autonomous microfluidic pumping systems that utilize environmental cues to transport fluid within a network of channels for such purposes as heat distribution, self-healing, or optical reconfiguration. Here, we report on reversible thermally driven microfluidic pumping enabled by two-way shape memory polymers. After developing a suitable shape memory polymer (SMP) through variation in the crosslink density, thin and flexible microfluidic devices were constructed by lamination of plastic films with channels defined by laser-cutting of double-sided adhesive film. SMP blisters integrated into the devices provide thermally driven pumping, while opposing elastic blisters are used to generate backpressure for reversible operation. Thermal cycling of the device was found to drive reversible fluid flow: upon heating to 60 °C, the SMP rapidly contracted to fill the surface channels with a transparent fluid, and upon cooling to 8 °C the flow reversed and the channel re-filled with black ink. Combined with a metallized backing layer, this device results in refection of incident light at high temperatures and absorption of light (at the portions covered with channels) at low temperatures. We discuss power-free, autonomous applications ranging from thermal regulation of structures to thermal indication via color change.

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

    PubMed

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

    2015-04-01

    The nematode worm Caenorhabditis elegans has been employed as a popular model organism in many fields of biological research. In this paper, we present a microfluidic device for facilitating chemical testing using C. elegans. For testing chemicals on chip, the device houses single nematodes in microfluidic chambers and precisely adjusts the chamber's chemical environment during experiments. Eight nematodes can be readily loaded into the chambers through separate loading channels in a quick and gentle manner. In addition, a custom-made software with a graphic user interface is also created for quantitative analysis of locomotion parameters (swimming frequency and bend amplitude) of the nematodes in response to chemical stimuli, thus greatly enhancing the efficiency of data collection. We perform proof-of-concept experiments using two chemicals, zinc ion (Zn(2+)) and glucose, to demonstrate the effectiveness of the microfluidic device. PMID:25744157

  11. On-chip Microfluidic Multimodal Swimmer toward 3D Navigation

    PubMed Central

    Barbot, Antoine; Decanini, Dominique; Hwang, Gilgueng

    2016-01-01

    Mobile microrobots have a promising future in various applications. These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D (Three Dimensional) maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various in-vitro biologic or in-vivo biomedical applications. PMID:26791433

  12. On-chip Microfluidic Multimodal Swimmer toward 3D Navigation.

    PubMed

    Barbot, Antoine; Decanini, Dominique; Hwang, Gilgueng

    2016-01-01

    Mobile microrobots have a promising future in various applications. These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D (Three Dimensional) maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various in-vitro biologic or in-vivo biomedical applications. PMID:26791433

  13. Patterned Plasmonic Nanoparticle Arrays for Microfluidic and Multiplexed Biological Assays.

    PubMed

    He, Jie; Boegli, Michelle; Bruzas, Ian; Lum, William; Sagle, Laura

    2015-11-17

    For applications ranging from medical diagnostics and drug screening to chemical and biological warfare detection, inexpensive, rapid-readout, portable devices are required. Localized surface plasmon resonance (LSPR) technologies show substantial promise toward meeting these goals, but the generation of portable, multiplexed and/or microfluidic devices incorporating sensitive nanoparticle arrays is only in its infancy. Herein, we have combined photolithography with Hole Mask Colloidal lithography to pattern uniform nanoparticle arrays for both microfluidic and multiplexed devices. The first proof-of-concept study is carried out with 5- and 7-channel microfluidic devices to acquire one-shot binding curves and protein binding kinetic data. The second proof-of-concept study involved the fabrication of a 96-spot plate that can be inserted into a standard plate reader for the multiplexed detection of protein binding. This versatile fabrication technique should prove useful in next generation chips for bioassays and genetic screening. PMID:26494412

  14. Silk-microfluidics for advanced biotechnological applications: A progressive review.

    PubMed

    Konwarh, Rocktotpal; Gupta, Prerak; Mandal, Biman B

    2016-01-01

    Silk based biomaterials have not only carved a unique niche in the domain of regenerative medicine but new avenues are also being explored for lab-on-a-chip applications. It is pertinent to note that biospinning of silk represents nature's signature microfluidic-maneuver. Elucidation of non-Newtonian flow of silk in the glands of spiders and silkworms has inspired researchers to fabricate devices for continuous extrusion and concentration of silk. Microfluidic channel networks within porous silk scaffolds ensure optimal nutrient and oxygen supply apart from serving as precursors for vascularization in tissue engineering applications. On the other hand, unique topographical features and surface wettability of natural silk fibers have inspired development of a number of simple and cost-effective devices for applications like blood typing and chemical sensing. This review mirrors the recent progress and challenges in the domain of silk-microfluidics for prospective avant-garde applications in the realm of biotechnology. PMID:27165254

  15. On-chip Microfluidic Multimodal Swimmer toward 3D Navigation

    NASA Astrophysics Data System (ADS)

    Barbot, Antoine; Decanini, Dominique; Hwang, Gilgueng

    2016-01-01

    Mobile microrobots have a promising future in various applications. These include targeted drug delivery, local measurement, biopsy or microassembly. Studying mobile microrobots inside microfluidics is an essential step towards such applications. But in this environment that was not designed for the robot, integration process and propulsion robustness still pose technological challenges. In this paper, we present a helical microrobot with three different motions, designed to achieve these goals. These motions are rolling, spintop motion and swimming. Through these multiple motions, microrobots are able to selectively integrate a chip through a microfluidic channel. This enables them to perform propulsion characterizations, 3D (Three Dimensional) maneuverability, particle cargo transport manipulation and exit from the chip. The microrobot selective integration inside microfluidics could lead to various in-vitro biologic or in-vivo biomedical applications.

  16. "Smart" mobile affinity matrix for microfluidic immunoassays.

    PubMed

    Malmstadt, Noah; Hoffman, Allan S; Stayton, Patrick S

    2004-08-01

    There is a current need for simple methods for immobilizing biomolecules within microfluidic channels. Here, a technique is reported for reversibly immobilizing immunoassay components in a channel zone that can be simply controlled by integrated heating elements. Latex beads were modified with the temperature-responsive polymer poly(N-isopropylacrylamide)(PNIPAAm) and co-modified with biotinylated poly(ethylene glycol)(PEG). PNIPAAm undergoes a hydrophilic-to-hydrophobic transition when the temperature is raised above the lower critical solution temperature (LCST)( approximately 28 degrees C in the solutions used here). This reversible transition drives the aggregation and dis-aggregation of the modified beads in heated zones within poly(ethylene terephthalate)(PET) microchannels. Biotinylated monoclonal antibodies for the drug digoxin were bound via streptavidin to the biotin-PEG-coated beads. These antibody-functionalized beads were then reversibly immobilized by aggregation and hydrophobic adhesion to the surface of PET microfluidic channels in response to a thermal stimulus. The antibodies on the beads immobilized in the channel were shown to bind digoxin and a competitor fluorescent ligand from a flow stream in a quantitative competitive assay format that reported the digoxin concentration. The antibodies could be replenished for each immunoassay trial, using the reversible, temperature-controlled immobilization process. This technique allows reagent immobilization immediately prior to an analytical procedure, following the removal of previously utilized beads, guaranteeing fresh and active immobilized biomolecules. Furthermore, it provides a simple approach to multiplexing through the simultaneous or sequential injection of different antibody-coated bead species, potentially at multiple sites in the integrated device channels. PMID:15269814

  17. Microfluidic large-scale integration.

    PubMed

    Thorsen, Todd; Maerkl, Sebastian J; Quake, Stephen R

    2002-10-18

    We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory. PMID:12351675

  18. A perspective on paper-based microfluidics: Current status and future trends

    PubMed Central

    Li, Xu; Ballerini, David R.; Shen, Wei

    2012-01-01

    “Paper-based microfluidics” or “lab on paper,” as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors’ point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system

  19. Studies on spectroscopy of glycerol in THz range using microfluidic chip-integrated micropump

    NASA Astrophysics Data System (ADS)

    Su, Bo; Han, Xue; Wu, Ying; Zhang, Cunlin

    2014-11-01

    Terahertz time-domain spectroscopy (THz-TDS) is a detection method of biological molecules with label-free, non-ionizing, non-intrusive, no pollution and real-time monitoring. But owing to the strong THz absorption by water, it is mainly used in the solid state detection of biological molecules. In this paper, we present a microfluidic chip technique for detecting biological liquid samples using the transmission type of THz-TDS system. The microfluidic channel of the microfluidic chip is fabricated in the quartz glass using Micro-Electro-Mechanical System (MEMS) technology and sealed with polydimethylsiloxane (PDMS) diaphragm. The length, width and depth of the microfluidic channel are 25mm, 100μm and 50μm, respectively. The diameter of THz detection zone in the microfluidic channel is 4mm. The thicknesses of quartz glass and PDMS diaphragm are 1mm and 250μm, individually. Another one of the same quartz glass is used to bond with the PDMS for the rigidity and air tightness of the microfluidic chip. In order to realize the automation of sampling and improve the control precise of fluid, a micropump, which comprises PDMS diaphragm, pump chamber, diffuser and nozzle and flat vibration motor, is integrated on the microfluidic chip. The diffuser and nozzle are fabricated on both sides of the pump chamber, which is covered with PDMS diaphragm. The flat vibration motor is stuck on the PDMS diaphragm as the actuator. We study the terahertz absorption spectroscopy characteristics of glycerol with the concentration of 98% in the microfluidic chip by the aid of the THz-TDS system, and the feasibility of the microfluidic chip for the detection of liquid samples is proved.

  20. Magnetoactive Sponges for Dynamic Control of Microfluidic Flow Patterns in Microphysiological Systems

    PubMed Central

    Yen, Ringo; Chan, Hon Fai; Leong, Kam W; Truskey, George A; Zhao, Xuanhe

    2014-01-01

    We developed a microfluidic flow-control system capable of dynamically generating various flow patterns on demand. The flow-control system is based on novel magnetoactive sponges embedded in microfluidic flow channels. Applying a non-uniform magnetic field compresses the magnetoactive sponge, significantly reducing porosity and hydraulic conductivity. Tuning the applied magnetic field can dynamically vary the flow rate in the microfluidic channel. Pulsatile and physiological flow patterns with frequency between 1 and 3 Hz, flow rates between 0.5 and 10 μL/min and duration over 3 weeks have been achieved. Smooth muscle cells in engineered blood vessels perfused for 7 days aligned perpendicular to the flow direction under pulsatile but not steady flow, similar to the in vivo orientation. Owing to its various advantages over traditional flow-control methods, the new system potentially has important applications in microfluidic-based microphysiological systems to simulate the physiological nature of blood flow. PMID:24310854

  1. Microfluidic colloid filtration

    PubMed Central

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J. C.; Wessling, Matthias

    2016-01-01

    Filtration of natural and colloidal matter is an essential process in today’s water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a “cake layer” – often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level. PMID:26927706

  2. The Microfluidic Jukebox

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  3. Surface Acoustic Wave Microfluidics

    NASA Astrophysics Data System (ADS)

    Yeo, Leslie Y.; Friend, James R.

    2014-01-01

    Fluid manipulations at the microscale and beyond are powerfully enabled through the use of 10-1,000-MHz acoustic waves. A superior alternative in many cases to other microfluidic actuation techniques, such high-frequency acoustics is almost universally produced by surface acoustic wave devices that employ electromechanical transduction in wafer-scale or thin-film piezoelectric media to generate the kinetic energy needed to transport and manipulate fluids placed in adjacent microfluidic structures. These waves are responsible for a diverse range of complex fluid transport phenomena - from interfacial fluid vibration and drop and confined fluid transport to jetting and atomization - underlying a flourishing research literature spanning fundamental fluid physics to chip-scale engineering applications. We highlight some of this literature to provide the reader with a historical basis, routes for more detailed study, and an impression of the field's future directions.

  4. Microfluidic colloid filtration.

    PubMed

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J C; Wessling, Matthias

    2016-01-01

    Filtration of natural and colloidal matter is an essential process in today's water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a "cake layer" - often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level. PMID:26927706

  5. Microfluidic colloid filtration

    NASA Astrophysics Data System (ADS)

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J. C.; Wessling, Matthias

    2016-03-01

    Filtration of natural and colloidal matter is an essential process in today’s water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a “cake layer” - often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level.

  6. The Microfluidic Jukebox

    PubMed Central

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

    2014-01-01

    Music is a form of art interweaving people of all walks of life. Through subtle changes in frequencies, a succession of musical notes forms a melody which is capable of mesmerizing the minds of people. With the advances in technology, we are now able to generate music electronically without relying solely on physical instruments. Here, we demonstrate a musical interpretation of droplet-based microfluidics as a form of novel electronic musical instruments. Using the interplay of electric field and hydrodynamics in microfluidic devices, well controlled frequency patterns corresponding to musical tracks are generated in real time. This high-speed modulation of droplet frequency (and therefore of droplet sizes) may also provide solutions that reconciles high-throughput droplet production and the control of individual droplet at production which is needed for many biochemical or material synthesis applications. PMID:24781785

  7. Reconfigurable microfluidic dilution for high-throughput quantitative assays.

    PubMed

    Fan, Jinzhen; Li, Baoqing; Xing, Siyuan; Pan, Tingrui

    2015-06-21

    This paper reports a reconfigurable microfluidic dilution device for high-throughput quantitative assays, which can easily produce discrete logarithmic/binary concentration profiles ranging from 1 to 100-fold dilution in parallel from a fixed sample volume (e.g., 10 μL) without any assistance of continuous fluidic pump or robotic automation. The integrated dilution generation chip consists of switchable distribution and collection channels, metering reservoirs, reaction chambers, and pressure-activatable Laplace valves. Following the sequential loading of a sample, a diluent, and a detection reagent into their individual metering chambers, the top microfluidic layer can be reconfigured to collect the metered chemicals into the reaction chambers in parallel, where detection will be conducted. To facilitate mixing and reaction in the microchambers, two acoustic microstreaming actuation mechanisms have been investigated for easy integrability and accessibility. Furthermore, the microfluidic dilution generator has been characterized by both colorimetric and fluorescent means. A further demonstration of the generic usage of the quantitative dilution chip has utilized the commonly available bicinchoninic acid (BCA) assay to analyse the protein concentrations of human tissue extracts. In brief, the microfluidic dilution generator offers a high-throughput high-efficiency quantitative analytical alternative to conventional quantitative assay platforms, by simple manipulation of a minute amount of chemicals in a compact microfluidic device with minimal equipment requirement, which can serve as a facile tool for biochemical and biological analyses in regular laboratories, point-of-care settings and low-resource environments. PMID:25994379

  8. High-sensitivity microfluidic calorimeters for biological and chemical applications

    PubMed Central

    Lee, Wonhee; Fon, Warren; Axelrod, Blake W.; Roukes, Michael L.

    2009-01-01

    High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described. PMID:19706406

  9. Teaching microfluidic diagnostics using Jell-O(®) chips.

    PubMed

    Yang, Cheng Wei T; Lagally, Eric T

    2013-01-01

    Microfluidics has emerged as a versatile technology that has found many applications, including DNA chips, fuel cells, and diagnostics. As the field of microfluidic diagnostics grows, it is important to introduce the principles of this technology to young students and the general public. The objective of this project was to create a simple and effective method that could be used to teach key microfluidics concepts using easily accessible materials. Similar to the poly(dimethylsiloxane) soft lithography technique, a Jell-O(®) "chip" is produced by pouring a mixture of Jell-O(®) and gelatine solution into a mold, which is constructed using foam plate, coffee stirrers, and double-sided tape. The plate is transferred to a 4°C refrigerator for curing, and then the Jell-O(®) chip is peeled off for experimental demonstrations. Three types of chips have been fabricated with different molds: a JELLO mold, a Y-channel mold, and a pH-sensor mold. Using these devices, the basics of microfluidic diagnostics can be demonstrated in one or two class periods. The method described in this chapter provides teachers with a fast and inexpensive way to introduce this technology, and students with a fun and hands-on way to understand the basics of microfluidic diagnostics. PMID:23329433

  10. Pneumatic oscillator circuits for timing and control of integrated microfluidics.

    PubMed

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

    2013-11-01

    Frequency references are fundamental to most digital systems, providing the basis for process synchronization, timing of outputs, and waveform synthesis. Recently, there has been growing interest in digital logic systems that are constructed out of microfluidics rather than electronics, as a possible means toward fully integrated laboratory-on-a-chip systems that do not require any external control apparatus. However, the full realization of this goal has not been possible due to the lack of on-chip frequency references, thus requiring timing signals to be provided from off-chip. Although microfluidic oscillators have been demonstrated, there have been no reported efforts to characterize, model, or optimize timing accuracy, which is the fundamental metric of a clock. Here, we report pneumatic ring oscillator circuits built from microfluidic valves and channels. Further, we present a compressible-flow analysis that differs fundamentally from conventional circuit theory, and we show the utility of this physically based model for the optimization of oscillator stability. Finally, we leverage microfluidic clocks to demonstrate circuits for the generation of phase-shifted waveforms, self-driving peristaltic pumps, and frequency division. Thus, pneumatic oscillators can serve as on-chip frequency references for microfluidic digital logic circuits. On-chip clocks and pumps both constitute critical building blocks on the path toward achieving autonomous laboratory-on-a-chip devices. PMID:24145429

  11. Pneumatic oscillator circuits for timing and control of integrated microfluidics

    PubMed Central

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

    2013-01-01

    Frequency references are fundamental to most digital systems, providing the basis for process synchronization, timing of outputs, and waveform synthesis. Recently, there has been growing interest in digital logic systems that are constructed out of microfluidics rather than electronics, as a possible means toward fully integrated laboratory-on-a-chip systems that do not require any external control apparatus. However, the full realization of this goal has not been possible due to the lack of on-chip frequency references, thus requiring timing signals to be provided from off-chip. Although microfluidic oscillators have been demonstrated, there have been no reported efforts to characterize, model, or optimize timing accuracy, which is the fundamental metric of a clock. Here, we report pneumatic ring oscillator circuits built from microfluidic valves and channels. Further, we present a compressible-flow analysis that differs fundamentally from conventional circuit theory, and we show the utility of this physically based model for the optimization of oscillator stability. Finally, we leverage microfluidic clocks to demonstrate circuits for the generation of phase-shifted waveforms, self-driving peristaltic pumps, and frequency division. Thus, pneumatic oscillators can serve as on-chip frequency references for microfluidic digital logic circuits. On-chip clocks and pumps both constitute critical building blocks on the path toward achieving autonomous laboratory-on-a-chip devices. PMID:24145429

  12. Exploration of microfluidic devices based on multi-filament threads and textiles: A review

    PubMed Central

    Nilghaz, A.; Ballerini, D. R.; Shen, W.

    2013-01-01

    In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future. PMID:24086179

  13. Exploration of microfluidic devices based on multi-filament threads and textiles: A review.

    PubMed

    Nilghaz, A; Ballerini, D R; Shen, W

    2013-01-01

    In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future. PMID:24086179

  14. 96-well format-based microfluidic platform for parallel interconnection of multiple multicellular spheroids.

    PubMed

    Kim, Jin-Young; Fluri, David A; Kelm, Jens M; Hierlemann, Andreas; Frey, Olivier

    2015-06-01

    In this article, we present a microfluidic platform, compatible with conventional 96-well formats, that enables facile and parallelized culturing and testing of spherical microtissues in a standard incubator. The platform can accommodate multiple microtissues (up to 66) of different cell types, formed externally by using the hanging-drop method, and enables microtissue interconnection through microfluidic channels for continuous media perfusion or dosage of substances. The platform contains 11 separate channels, and each channel has six tissue compartments. Primary rat liver tissues were cultured over 8 days, and multiple tumor tissues (HCT116) were exposed to various concentrations of 5-fluorouracil for platform characterization. PMID:25524491

  15. AC magnetohydrodynamic microfluidic switch

    SciTech Connect

    Lemoff, A V; Lee, A P

    2000-03-02

    A microfluidic switch has been demonstrated using an AC Magnetohydrodynamic (MHD) pumping mechanism in which the Lorentz force is used to pump an electrolytic solution. By integrating two AC MHD pumps into different arms of a Y-shaped fluidic circuit, flow can be switched between the two arms. This type of switch can be used to produce complex fluidic routing, which may have multiple applications in {micro}TAS.

  16. Buckling of dielectric elastomeric plates for soft, electrically active microfluidic pumps.

    PubMed

    Tavakol, Behrouz; Bozlar, Michael; Punckt, Christian; Froehlicher, Guillaume; Stone, Howard A; Aksay, Ilhan A; Holmes, Douglas P

    2014-07-21

    Elastic instabilities, when properly implemented within soft, mechanical structures, can generate advanced functionality. In this work, we use the voltage-induced buckling of thin, flexible plates to pump fluids within a microfluidic channel. The soft electrodes that enable electrical actuation are compatible with fluids, and undergo large, reversible deformations. We quantified the onset of voltage-induced buckling, and measured the flow rate within the microchannel. This embeddable, flexible microfluidic pump will aid in the generation of new stand-alone microfluidic devices that require a tunable flow rate. PMID:24905688

  17. High-pressure microfluidics

    NASA Astrophysics Data System (ADS)

    Hjort, K.

    2015-03-01

    When using appropriate materials and microfabrication techniques, with the small dimensions the mechanical stability of microstructured devices allows for processes at high pressures without loss in safety. The largest area of applications has been demonstrated in green chemistry and bioprocesses, where extraction, synthesis and analyses often excel at high densities and high temperatures. This is accessible through high pressures. Capillary chemistry has been used since long but, just like in low-pressure applications, there are several potential advantages in using microfluidic platforms, e.g., planar isothermal set-ups, large local variations in geometries, dense form factors, small dead volumes and precisely positioned microstructures for control of reactions, catalysis, mixing and separation. Other potential applications are in, e.g., microhydraulics, exploration, gas driven vehicles, and high-pressure science. From a review of the state-of-art and frontiers of high pressure microfluidics, the focus will be on different solutions demonstrated for microfluidic handling at high pressures and challenges that remain.

  18. Preparation and validation of low cost microfluidic chips using a shrinking approach.

    PubMed

    Focaroli, S; Mazzitelli, S; Falconi, M; Luca, G; Nastruzzi, C

    2014-10-21

    The present paper describes the production of microfluidic chips using an approach based on shrinkable biocompatible polymers (i.e. agarose) for the production of size controlled microfluidic channels. In addition, all steps of chip production were carried out using an inexpensive approach that uses low cost chemicals and equipment. The produced chips were then validated by producing monodisperse polymeric microparticles for drug delivery and hydrogel microfibers for cell embedding. PMID:25144915

  19. Dynamic cell culture: a microfluidic function generator for live cell microscopy.

    PubMed

    Lee, Philip J; Gaige, Terry A; Hung, Paul J

    2009-01-01

    We present a microfluidic system for time-lapsed, live cell microscopy with the ability to control solution exchange via a dynamic flow controller. The application specific microfluidic plates are designed to maintain adherent and non-adherent cell types for multiple days with continuous medium perfusion. Upstream channels with flow controlled via custom software allow the delivery of unique exposure profiles to the cultured cells, such as square waves, step functions, ramps, etc. PMID:19209350

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

    NASA Astrophysics Data System (ADS)

    Walczak, Rafał; Adamski, Krzysztof

    2015-08-01

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

  1. Laser microfluidics: fluid actuation by light

    NASA Astrophysics Data System (ADS)

    Delville, Jean-Pierre; de Saint Vincent, Matthieu Robert; Schroll, Robert D.; Chraïbi, Hamza; Issenmann, Bruno; Wunenburger, Régis; Lasseux, Didier; Zhang, Wendy W.; Brasselet, Etienne

    2009-03-01

    The development of microfluidic devices is still hindered by the lack of robust fundamental building blocks that constitute any fluidic system. An attractive approach is optical actuation because light field interaction is contactless and dynamically reconfigurable, and solutions have been anticipated through the use of optical forces to manipulate microparticles in flows. Following the concept of an 'optical chip' advanced from the optical actuation of suspensions, we propose in this survey new routes to extend this concept to microfluidic two-phase flows. First, we investigate the destabilization of fluid interfaces by the optical radiation pressure and the formation of liquid jets. We analyze the droplet shedding from the jet tip and the continuous transport in laser-sustained liquid channels. In the second part, we investigate a dissipative light-flow interaction mechanism consisting in heating locally two immiscible fluids to produce thermocapillary stresses along their interface. This opto-capillary coupling is implemented in adequate microchannel geometries to manipulate two-phase flows and propose a contactless optical toolbox including valves, droplet sorters and switches, droplet dividers or droplet mergers. Finally, we discuss radiation pressure and opto-capillary effects in the context of the 'optical chip' where flows, channels and operating functions would all be performed optically on the same device.

  2. Microfluidic Radiometal Labeling Systems for Biomolecules

    SciTech Connect

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

    2011-12-29

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

  3. Particle ordering in inertially focused microfluidic flows

    NASA Astrophysics Data System (ADS)

    Humphry, Katherine; Kulkarni, Pandurang; di Carlo, Dino; Edd, Jon; Toner, Mehmet; Morris, Jeffrey; Weitz, David; Stone, Howard

    2008-11-01

    We study inertially driven focusing of particles [1], which has recently been exploited in a controlled fashion in microfluidic devices [2]. In particular, we characterize the focusing as a function of particle and channel Reynolds number by reporting particle position in directions perpendicular to the flow, and a large distance from the fluid inlet. Focusing of dilute suspensions leads to a linear arrangement of particles whose spacing is primarily a function of concentration and channel aspect ratio. All results are compared with simulations, which provide mechanistic insights into particle behavior.[1] G. Segré and A. Silberberg, Nature 189, 209 (1961). [2] D. Di Carlo, D. Irimia, R. G. Tompkins, and M. Toner, Proc. Nat. Acad. Sci. U.S.A. 104, 18892 (2007).

  4. Gravity-induced swirl of nanoparticles in microfluidics.

    PubMed

    Zhao, Chao; Oztekin, Alparslan; Cheng, Xuanhong

    2013-04-01

    Parallel flows of two fluids in microfluidic devices are used for miniaturized chemistry, physics, biology and bioengineering studies, and the streams are often considered to remain parallel. However, as the two fluids do not always have the same density, interface reorientation induced by density stratification is unavoidable. In this paper, flow characteristics of an aqueous polystyrene nanofluid and a sucrose-densified aqueous solution flowing parallel in microchannels are examined. Nanoparticles 100 nm in diameter are used in the study. The motion of the nanoparticles is simulated using the Lagrangian description and directly observed by a confocal microscope. Matched results are obtained from computational and empirical analysis. Although solution density homogenizes rapidly resulting from a fast diffusion of sucrose in water, the nanofluid is observed to rotate for an extended period. Angular displacement of the nanofluid depends on the ratio of gravitational force to viscous force, Re/Fr (2), where Re is the Reynolds number and Fr is the Froude number. In the developing region at the steady state, the angular displacement is related to y/D h, the ratio between distance from the inlet and the hydraulic diameter of the microfluidic channel. The development of nanofluid flow feature also depends on h/w, the ratio of microfluidic channel's height to width. The quantitative description of the angular displacement of nanofluid will aid rational designs of microfluidic devices utilizing multistream, multiphase flows. PMID:24563612

  5. Development of a microplate reader compatible microfluidic chip for ELISA.

    PubMed

    Hou, Fenghua; Zhang, Qin; Yang, Jianping; Li, Xinchun; Yang, Xiujuan; Wang, Shuping; Cheng, Zhiyi

    2012-08-01

    We report a novel microfluidic device use for sandwich enzyme-linked immunoassay assay (ELISA). The related procedures including the introduction of reagents, dilution and distribution of samples, as well as immobilization of enzyme can be readily carried out on a poly (dimethylsiloxane) (PDMS) chip. Particularly, this microfluidic chip comprising of two distinct parallel units, and has an identical dimension as a conventional microtiter plate, which offers access to the directly quantitative detection by the microplate reader. Gradient-concentration reacting solutions at six different concentrations level generated by the microfluidic channel network are simultaneously transported to 24 reaction chambers to form enzymatic products. Alkaline phosphatase (ALP), 4-methylumbelliferyl phosphate (4-MUP) and KH(2)PO(4) are used as enzyme-substrate-inhibitor model, to demonstrate the utility of the developed microchip-based enzyme inhibitor assay. Various conditions such as the surface treatment of chip channels, fluids velocities, substrate concentration, and buffer pH are investigated. The present microfluidic device for ELISA holds several advantages, for instance frugal usage of samples and reagents, less of operating time, favorably integrated configuration, ease of manipulation, and could be explored to a variety of high throughput drug screening. PMID:22526682

  6. Monolithical integration of polymer-based microfluidic structures on application-specific integrated circuits

    NASA Astrophysics Data System (ADS)

    Chemnitz, Steffen; Schafer, Heiko; Schumacher, Stephanie; Koziy, Volodymyr; Fischer, Alexander; Meixner, Alfred J.; Ehrhardt, Dietmar; Bohm, Markus

    2003-04-01

    In this paper, a concept for a monolithically integrated chemical lab on microchip is presented. It contains an ASIC (Application Specific Integrated Circuit), an interface to the polymer based microfluidic layer and a Pyrex glass cap. The top metal layer of the ASIC is etched off and replaced by a double layer metallization, more suitable to microfluidic and electrophoresis systems. The metallization consists of an approximately 50 nm gold layer and a 10 nm chromium layer, acting as adhesion promoter. A necessary prerequisite is a planarized ASIC topography. SU-8 is used to serve as microfluidic structure because of its excellent aspect ratio. This polymer layer contains reservoirs, channels, mixers and electrokinetic micro pumps. The typical channel cross section is 10μm"10μm. First experimental results on a microfluidic pump, consisting of pairs of interdigitated electrodes on the bottom of the channel and without any moving parts show a flow of up to 50μm per second for low AC-voltages in the range of 5 V for aqueous fluids. The microfluidic system is irreversibly sealed with a 150μm thick Pyrex glass plate bonded to the SU-8-layer, supported by oxygen plasma. Due to capillary forces and surfaces properties of the walls the system is self-priming. The technologies for the fabrication of the microfluidic system and the preparation of the interface between the lab layer and the ASIC are presented.

  7. Negative Enrichment of Target Cells by Microfluidic Affinity Chromatography

    PubMed Central

    Li, Peng; Gao, Yan; Pappas, Dimitri

    2011-01-01

    A three-dimensional microfluidic channel was developed for high purity cell separations. This system featured high capture affinity using multiple vertical inlets to an affinity surface. In cell separations, positive selection (capture of the target cell) is usually employed. Negative enrichment, the capture of non-target cells and elution of target cells, has distinct advantages over positive selection. In negative enrichment, target cells are not labeled, and are not subjected to strenuous elution conditions or dilution. As a result, negative enrichment systems are amenable to multi-step processes in microfluidic systems. In previous work, we reported cell capture enhancement effects at vertical inlets to the affinity surface. In this study, we designed a chip that has multiple vertical and horizontal channels, forming a three-dimensional separation system. Enrichment of target cells showed separation purities of 92-96%, compared with straight-channel systems (77% purity). A parallelized chip was also developed for increased sample throughput. A two-channel showed similar separation purity with twice the sample flow rate. This microfluidic system, featuring high separation purity, ease of fabrication and use, is suitable for cell separations when subsequent analysis of target cells is required. PMID:21939198

  8. Monolithic microfluidic concentrators and mixers

    DOEpatents

    Frechet, Jean M.; Svec, Frantisek; Yu, Cong; Rohr, Thomas

    2005-05-03

    Microfluidic devices comprising porous monolithic polymer for concentration, extraction or mixing of fluids. A method for in situ preparation of monolithic polymers by in situ initiated polymerization of polymer precursors within microchannels of a microfluidic device and their use for solid phase extraction (SPE), preconcentration, concentration and mixing.

  9. Electrostatic Control of Bioactivity

    SciTech Connect

    Goldberger, Joshua E.; Berns, Eric J.; Bitton, Ronit; Newcomb, Christina J.; Stupp, Samuel I.

    2012-03-15

    The power of independence: When exhibited on the surface of self-assembling peptide-amphiphile nanofibers, the hydrophobic laminin-derived IKVAV epitope induced nanofiber bundling through interdigitation with neighboring fibers and thus decreased the bioactivity of the resulting materials. The inclusion of charged amino acids in the peptide amphiphiles disrupted the tendency to bundle and led to significantly enhanced neurite outgrowth.

  10. New bioactive lipids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  11. New bioactive fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  12. New Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...

  13. Bioactivity of degradable polymer sutures coated with bioactive glass.

    PubMed

    Bretcanu, Oana; Verné, Enrica; Borello, Luisa; Boccaccini, Aldo R

    2004-08-01

    Novel bioactive materials have been prepared by coating violet resorbable Vicryl sutures with a bioactive glass powder derived from a co-precipitation method. Two techniques have been chosen for the composite preparation: pressing the sutures in a bed of glass powder and slurry-dipping of sutures in liquid suspensions of bioactive glass powders. The uniformity and thickness of the coatings obtained by the two methods were compared. The bioactivity of the sutures with and without bioactive glass coating was tested by soaking in an inorganic acellular simulated body fluid (SBF). The composite sutures were characterised by XRD, SEM and FTIR analyses before and after soaking in SBF solution to assess the formation of hydroxyapatite on their surfaces, which is a qualitative measure of their bioactivity. The possible use of bioactive sutures to produce tissue engineering scaffolds and as reinforcement of resorbable calcium phosphates is discussed. PMID:15477741

  14. System-level simulation of liquid filling in microfluidic chips.

    PubMed

    Song, Hongjun; Wang, Yi; Pant, Kapil

    2011-06-01

    Liquid filling in microfluidic channels is a complex process that depends on a variety of geometric, operating, and material parameters such as microchannel geometry, flow velocity∕pressure, liquid surface tension, and contact angle of channel surface. Accurate analysis of the filling process can provide key insights into the filling time, air bubble trapping, and dead zone formation, and help evaluate trade-offs among the various design parameters and lead to optimal chip design. However, efficient modeling of liquid filling in complex microfluidic networks continues to be a significant challenge. High-fidelity computational methods, such as the volume of fluid method, are prohibitively expensive from a computational standpoint. Analytical models, on the other hand, are primarily applicable to idealized geometries and, hence, are unable to accurately capture chip level behavior of complex microfluidic systems. This paper presents a parametrized dynamic model for the system-level analysis of liquid filling in three-dimensional (3D) microfluidic networks. In our approach, a complex microfluidic network is deconstructed into a set of commonly used components, such as reservoirs, microchannels, and junctions. The components are then assembled according to their spatial layout and operating rationale to achieve a rapid system-level model. A dynamic model based on the transient momentum equation is developed to track the liquid front in the microchannels. The principle of mass conservation at the junction is used to link the fluidic parameters in the microchannels emanating from the junction. Assembly of these component models yields a set of differential and algebraic equations, which upon integration provides temporal information of the liquid filling process, particularly liquid front propagation (i.e., the arrival time). The models are used to simulate the transient liquid filling process in a variety of microfluidic constructs and in a multiplexer, representing a

  15. Enabling Technologies for Microfluidic Flow Control and Detection

    NASA Astrophysics Data System (ADS)

    Leslie, Daniel Christopher

    Advances in microfluidic technologies have expanded conventional chemical and biological techniques to the point where we can envision rapid, inexpensive and portable analysis. Among the numerous challenges in the development of portable, chip-based technologies are simple flow control and detection strategies, which will be essential to widespread acceptance and implementation at both the point-of-care and in locales with limited facilities/resources. The research presented in this dissertation is focused on the development of precise flow control techniques and new, simplified detection technologies aimed at addressing these challenges. An introduction to the concepts important to microfluidics and a brief history to the field are presented in Chapter 1. Chapter 2 will present the development of a technique for the precise control of small volumes of liquids, where well-studied electrical circuit concepts are employed to create frequency-dependent microfluidic circuits. In this system, elastomeric thin films act as fluidic capacitors and diodes, which, when combined with resistors (channels), make fluidic circuits that are described by analytical models. Metering of two separate chemical inputs with a single oscillatory pneumatic control line is demonstrated by combining simple fluidic circuits (i.e., band-pass filters) to significantly reduce the external hardware required for microfluidic flow control. In order to quantify multiple flow profiles in microfluidic circuits, a novel multiplexed flow measurement method using visible dyes is introduced in Chapter 3 and rapidly determines individual flow in connected channels, post-fabrication device quality and solution viscosity. Another thrust of this dissertation research has been to develop miniaturized bioanalytical systems. Chapter 4 describes the adaption of a nucleic-acid-tagged antibody protein detection reaction to a microfluidic platform for detection of down to 5 E. coli O157:H7 cells. Furthermore, a

  16. Porous bioactive materials

    NASA Astrophysics Data System (ADS)

    Zhang, Kai

    Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size <50 nm) sol-gel BGs in simulated body fluid (SBF). Apatite formation and 3DOM-BG degradation rates increased with the decrease of soaking ratio. Apatite induction time in SBF increased with 3DOM-BG calcination temperature (600--800°C). Apatite formation and 3DOMBG degradation were slightly enhanced for a phosphate containing composition. Large 3DOM-BG particles formed less apatite and degraded less completely as compared with small particles. An increase in macropore size slowed down 3DOM-BG degradation and apatite formation processes. After heating the converted apatite at a temperature higher than 700°C, highly crystalline hydroxyapatite and a minor tri-calcium phosphate phase formed. 3DOM-BGs have potential applications as bone/periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a

  17. Ultralow-loss waveguide crossings for the integration of microfluidics and optical waveguide sensors

    NASA Astrophysics Data System (ADS)

    Wang, Zheng; Yan, Hai; Wang, Zongxing; Zou, Yi; Yang, Chun-Ju; Chakravarty, Swapnajit; Subbaraman, Harish; Tang, Naimei; Xu, Xiaochuan; Fan, D. L.; Wang, Alan X.; Chen, Ray T.

    2015-03-01

    Integrating photonic waveguide sensors with microfluidics is promising in achieving high-sensitivity and cost-effective biological and chemical sensing applications. One challenge in the integration is that an air gap would exist between the microfluidic channel and the photonic waveguide when the micro-channel and the waveguide intersect. The air gap creates a path for the fluid to leak out of the micro-channel. Potential solutions, such as oxide deposition followed by surface planarization, would introduce additional fabrication steps and thus are ineffective in cost. Here we propose a reliable and efficient approach for achieving closed microfluidic channels on a waveguide sensing chip. The core of the employed technique is to add waveguide crossings, i.e., perpendicularly intersecting waveguides, to block the etched trenches and prevent the fluid from leaking through the air gap. The waveguide crossings offer a smooth interface for microfluidic channel bonding while bring negligible additional propagation loss (0.024 dB/crossing based on simulation). They are also efficient in fabrication, which are patterned and fabricated in the same step with waveguides. We experimentally integrated microfluidic channels with photonic crystal (PC) microcavity sensor chips on silicon-on-insulator substrate and demonstrated leak-free sensing measurement with waveguide crossings. The microfluidic channel was made from polydimethylsiloxane (PDMS) and pressure bonded to the silicon chip. The tested flow rates can be varied from 0.2 μL/min to 200 μL/min. Strong resonances from the PC cavity were observed from the transmission spectra. The spectra also show that the waveguide crossings did not induce any significant additional loss or alter the resonances.

  18. Pen microfluidics: rapid desktop manufacturing of sealed thermoplastic microchannels

    PubMed Central

    Rahmanian, Omid

    2013-01-01

    A unique technique for the rapid fabrication of thermoplastic microfluidic chips is described. The method enables the realization of fully-sealed microchannels in around one hour while requiring only minimal infrastructure by taking advantage of a solvent swelling mechanism that allows raised features to be patterned on the surface of homogeneous thermoplastic materials. Patterning is achieved without photolithography by simply drawing the desired microchannel pattern onto the polymer surface using a suitable ink as a masking layer, either manually or under robotic control, followed by timed exposure to solvent vapor to yield a desired depth for the masked channel features. The channels are then permanently sealed through solvent bonding of the microchannel chip to a mating thermoplastic substrate. The process is demonstrated using cyclic olefin copolymer as a thermoplastic material, with fully operational microfluidic devices fabricated following a true desktop manufacturing model suitable for rapid prototyping. PMID:23344819

  19. Geometric effects in microfluidics on heterogeneous cell stress using an Eulerian-Lagrangian approach.

    PubMed

    Warren, K M; Mpagazehe, J N; LeDuc, P R; Higgs, C F

    2016-02-01

    The response of individual cells at the micro-scale in cell mechanics is important in understanding how they are affected by changing environments. To control cell stresses, microfluidics can be implemented since there is tremendous control over the geometry of the devices. Designing microfluidic devices to induce and manipulate stress levels on biological cells can be aided by computational modeling approaches. Such approaches serve as an efficient precursor to fabricating various microfluidic geometries that induce predictable levels of stress on biological cells, based on their mechanical properties. Here, a three-dimensional, multiphase computational fluid dynamics (CFD) modeling approach was implemented for soft biological materials. The computational model incorporates the physics of the particle dynamics, fluid dynamics and solid mechanics, which allows us to study how stresses affect the cells. By using an Eulerian-Lagrangian approach to treat the fluid domain as a continuum in the microfluidics, we are conducting studies of the cells' movement and the stresses applied to the cell. As a result of our studies, we were able to determine that a channel with periodically alternating columns of obstacles was capable of stressing cells at the highest rate, and that microfluidic systems can be engineered to impose heterogenous cell stresses through geometric configuring. We found that when using controlled geometries of the microfluidics channels with staggered obstructions, we could increase the maximum cell stress by nearly 200 times over cells flowing through microfluidic channels with no obstructions. Incorporating computational modeling in the design of microfluidic configurations for controllable cell stressing could help in the design of microfludic devices for stressing cells such as cell homogenizers. PMID:26753780

  20. Microfluidic Cell Culture Device

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  1. Spatial Manipulation with Microfluidics

    PubMed Central

    Lin, Benjamin; Levchenko, Andre

    2015-01-01

    Biochemical gradients convey information through space, time, and concentration, and are ultimately capable of spatially resolving distinct cellular phenotypes, such as differentiation, proliferation, and migration. How these gradients develop, evolve, and function during development, homeostasis, and various disease states is a subject of intense interest across a variety of disciplines. Microfluidic technologies have become essential tools for investigating gradient sensing in vitro due to their ability to precisely manipulate fluids on demand in well-controlled environments at cellular length scales. This review will highlight their utility for studying gradient sensing along with relevant applications to biology. PMID:25905100

  2. Spatial manipulation with microfluidics.

    PubMed

    Lin, Benjamin; Levchenko, Andre

    2015-01-01

    Biochemical gradients convey information through space, time, and concentration, and are ultimately capable of spatially resolving distinct cellular phenotypes, such as differentiation, proliferation, and migration. How these gradients develop, evolve, and function during development, homeostasis, and various disease states is a subject of intense interest across a variety of disciplines. Microfluidic technologies have become essential tools for investigating gradient sensing in vitro due to their ability to precisely manipulate fluids on demand in well-controlled environments at cellular length scales. This review will highlight their utility for studying gradient sensing along with relevant applications to biology. PMID:25905100

  3. Geometric pumping in autophoretic channels.

    PubMed

    Michelin, Sébastien; Montenegro-Johnson, Thomas D; De Canio, Gabriele; Lobato-Dauzier, Nicolas; Lauga, Eric

    2015-08-01

    Many microfluidic devices use macroscopic pressure differentials to overcome viscous friction and generate flows in microchannels. In this work, we investigate how the chemical and geometric properties of the channel walls can drive a net flow by exploiting the autophoretic slip flows induced along active walls by local concentration gradients of a solute species. We show that chemical patterning of the wall is not required to generate and control a net flux within the channel, rather channel geometry alone is sufficient. Using numerical simulations, we determine how geometric characteristics of the wall influence channel flow rate, and confirm our results analytically in the asymptotic limit of lubrication theory. PMID:26000567

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

    PubMed

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

    2014-11-21

    Reliable, autonomous, internally self-powered microfluidic pumps are in critical demand for rapid point-of-care (POC) devices, integrated molecular-diagnostic platforms, and drug delivery systems. Here we report on a Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation (SIMPLE), which is disposable, autonomous, easy to use and fabricate, robust, and cost efficient, as a solution for self-powered microfluidic POC devices. The imbibition pump introduces the working liquid which is sucked into a porous material (paper) upon activation. The suction of the working liquid creates a reduced pressure in the analytical channel and induces the sequential sample flow into the microfluidic circuits. It requires no external power or control and can be simply activated by a fingertip press. The flow rate can be programmed by defining the shape of utilized porous material: by using three different paper shapes with circular section angles 20°, 40° and 60°, three different volume flow rates of 0.07 μL s(-1), 0.12 μL s(-1) and 0.17 μL s(-1) are demonstrated at 200 μm × 600 μm channel cross-section. We established the SIMPLE pumping of 17 μL of sample; however, the sample volume can be increased to several hundreds of μL. To demonstrate the design, fabrication, and characterization of SIMPLE, we used a simple, robust and cheap foil-laminating fabrication technique. The SIMPLE can be integrated into hydrophilic or hydrophobic materials-based microfluidic POC devices. Since it is also applicable to large-scale manufacturing processes, we anticipate that a new chapter of a cost effective, disposable, autonomous POC diagnostic chip is addressed with this technical innovation. PMID:25231831

  5. Microfluidics-Based Laser Guided Cell-Micropatterning System

    PubMed Central

    Erdman, Nick; Schmidt, Lucas; Qin, Wan; Yang, Xiaoqi; Lin, Yongliang; DeSilva, Mauris N; Gao, Bruce Z.

    2014-01-01

    The ability to place individual cells into an engineered microenvironment in a cell-culture model is critical for the study of in vivo-relevant cell-cell and cell-extracellular matrix interactions. Microfluidics provides a high-throughput modality to inject various cell types into a microenvironment. Laser guided systems provide the high spatial and temporal resolution necessary for single-cell micropatterning. Combining these two techniques, the authors designed, constructed, tested, and evaluated 1) a novel removable microfluidics-based cell-delivery biochip and 2) a combined system that uses the novel biochip coupled with a laser guided cell-micropatterning system to place individual cells into both 2D and 3D arrays. Cell-suspensions of chick forebrain neurons and glial cells were loaded into their respective inlet reservoirs and traversed the microfluidic channels until reaching the outlet ports. Individual cells were trapped and guided from the outlet of a microfluidic channel to a target site on the cell-culture substrate. At the target site, 2D and 3D pattern arrays were constructed with micron-level accuracy. Single-cell manipulation was accomplished at a rate of 150 μm/s in the radial plane and 50 μm/s in the axial direction of the laser beam. Results demonstrated that a single-cell can typically be patterned in 20-30 seconds, and that highly accurate and reproducible cellular arrays and systems can be achieved through coupling the microfluidics-based cell-delivery biochip with the laser guided system. PMID:25190714

  6. Microfluidics-based laser cell-micropatterning system.

    PubMed

    Erdman, Nick; Schmidt, Lucas; Qin, Wan; Yang, Xiaoqi; Lin, Yongliang; DeSilva, Mauris N; Gao, Bruce Z

    2014-09-01

    The ability to place individual cells into an engineered microenvironment in a cell-culture model is critical for the study of in vivo relevant cell-cell and cell-extracellular matrix interactions. Microfluidics provides a high-throughput modality to inject various cell types into a microenvironment. Laser guided systems provide the high spatial and temporal resolution necessary for single-cell micropatterning. Combining these two techniques, the authors designed, constructed, tested and evaluated (1) a novel removable microfluidics-based cell-delivery biochip and (2) a combined system that uses the novel biochip coupled with a laser guided cell-micropatterning system to place individual cells into both two-dimensional (2D) and three-dimensional (3D) arrays. Cell-suspensions of chick forebrain neurons and glial cells were loaded into their respective inlet reservoirs and traversed the microfluidic channels until reaching the outlet ports. Individual cells were trapped and guided from the outlet of a microfluidic channel to a target site on the cell-culture substrate. At the target site, 2D and 3D pattern arrays were constructed with micron-level accuracy. Single-cell manipulation was accomplished at a rate of 150 μm s(-1) in the radial plane and 50 μm s(-1) in the axial direction of the laser beam. Results demonstrated that a single-cell can typically be patterned in 20-30 s, and that highly accurate and reproducible cellular arrays and systems can be achieved through coupling the microfluidics-based cell-delivery biochip with the laser guided system. PMID:25190714

  7. Electro-Microfluidic Packaging

    NASA Astrophysics Data System (ADS)

    Benavides, G. L.; Galambos, P. C.

    2002-06-01

    There are many examples of electro-microfluidic products that require cost effective packaging solutions. Industry has responded to a demand for products such as drop ejectors, chemical sensors, and biological sensors. Drop ejectors have consumer applications such as ink jet printing and scientific applications such as patterning self-assembled monolayers or ejecting picoliters of expensive analytes/reagents for chemical analysis. Drop ejectors can be used to perform chemical analysis, combinatorial chemistry, drug manufacture, drug discovery, drug delivery, and DNA sequencing. Chemical and biological micro-sensors can sniff the ambient environment for traces of dangerous materials such as explosives, toxins, or pathogens. Other biological sensors can be used to improve world health by providing timely diagnostics and applying corrective measures to the human body. Electro-microfluidic packaging can easily represent over fifty percent of the product cost and, as with Integrated Circuits (IC), the industry should evolve to standard packaging solutions. Standard packaging schemes will minimize cost and bring products to market sooner.

  8. Mechanisms of Nitrite Bioactivation

    PubMed Central

    Kim-Shapiro, Daniel B.; Gladwin, Mark T.

    2014-01-01

    It is now accepted that the anion nitrite, once considered an inert oxidation product of nitric oxide (NO), contributes to hypoxic vasodilation, physiological blood pressure control, and redox signaling. As such, its application in therapeutics is being actively testing in pre-clinical models and in human phase I–II clinical trials. Major pathways for nitrite bioactivation involve its reduction to NO by members of the hemoglobin or molybdopterin family of proteins, or catalyzed dysproportionation. These conversions occur preferentially under hypoxic and acidic conditions. A number of enzymatic systems reduce nitrite to NO and their activity and importance are defined by oxygen tension, specific organ system and allosteric and redox effectors. In this work, we review different proposed mechanisms of nitrite bioactivation, focusing on analysis of kinetics and experimental evidence for the relevance of each mechanism under different conditions. PMID:24315961

  9. Surface enhanced Raman spectroscopy for microfluidic pillar arrayed separation chips

    SciTech Connect

    Taylor, Lisa; Kirchner, Teresa B; Lavrik, Nickolay V; Sepaniak, Michael

    2012-01-01

    Numerous studies have addressed the challenges of implementing miniaturized microfluidic platforms for chemical and biological separation applications. However, the integration of real time detection schemes capable of providing valuable sample information under continuous, ultra low volume flow regimes has not fully been addressed. In this report we present a chip based chromatography system comprising of a pillar array separation column followed by a reagent channel for passive mixing of a silver colloidal solution into the eluent stream to enable surface enhanced Raman spectroscopy (SERS) detection. Our design is the first integrated chip based microfluidic device to combine pressure driven separation capability with real time SERS detection. With this approach we demonstrate the ability to collect distinctive SERS spectra with or without complete resolution of chromatographic bands. Computational fluidic dynamic (CFD) simulations are used to model the diffusive mixing behavior and velocity profiles of the two confluent streams in the microfluidic channels. We evaluate the SERS spectral band intensity and chromatographic efficiency of model analytes with respect to kinetic factors as well as signal acquisition rates. Additionally, we discuss the use of a pluronic modified silver colloidal solution as a means of eliminating contamination generally caused by nanoparticle adhesion to channel surfaces.

  10. Tunable microfluidic optical devices with an integrated microlens array

    NASA Astrophysics Data System (ADS)

    Hong, Kuang-Sheng; Wang, Jing; Sharonov, Alexey; Chandra, Dinesh; Aizenberg, Joanna; Yang, Shu

    2006-08-01

    Interest in dynamically tuning light has attracted great attention to the fabrication of tunable microlens arrays. Here we discuss the fabrication and characterization of a simple, robust, yet tunable microfluidic optical device with an integrated microlens array. The microfluidic device with a desired channel structure was micromachined on a polycarbonate plate with a resolution of up to 100 µm, followed by thermal bonding two plates above their glass transition temperature. The microlens arrays were replica molded on a glass slide, which was then attached to the polycarbonate plates. By simply actuating the liquids with variable refractive index into the fluidic channel to immerse the lens arrays without moving or deformation of microlenses, a large change of focal length of more than ten times (f = 0.74-8.53) was achieved. When a dye-containing liquid was pumped into the microfluidic channel to cover the lenses, the light transmission through the lenses was reduced from about 95% to 55% when the dye concentration was increased to 10 w/v%. The knowledge we gain from these studies will provide important insights to construct new, adaptive, micro-scale optical devices with multiple functionalities.

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

    DOEpatents

    Frechet, Jean M. J.; Svec, Frantisek; Rohr, Thomas

    2008-10-07

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

  12. A simple and versatile microfluidic cell density gradient generator for quantum dot cytotoxicity assay.

    PubMed

    Wu, Jing; Chen, Qiushui; Liu, Wu; Lin, Jin-Ming

    2013-05-21

    In this work, a simple and versatile microfluidic cell density gradient generator was successfully developed for cytotoxicity of quantum dots (QDs) assay. The microfluidic cell density gradient generator is composed of eight parallel channels which are respectively surrounded by 1-8 microwells with optimized length and width. The cells fall into microwells by gravity and the cell densities are obviously dependent of microwell number. In a case study, HepG2 and MCF-7 cells were successfully utilized for generating cell density gradients on the microfluidic chip. The microfluidic cell density gradient generator was proved to be easily handled, cell-friendly and could be used to conduct the subsequent cell-based assay. As a proof-of-concept, QD cytotoxicity was evaluated and the results exhibited obvious cell density-dependence. For comparison, QD cytotoxicity was also investigated with a series of cell densities infused by pipette tips. Higher reproducibility was observed on the microfluidic cell density gradient generator and cell density was demonstrated to be a vital factor in cytotoxic study. With higher efficiency, controllability and reproducibility, the microfluidic cell density gradient generator could be integrated into microfluidic analysis systems to promote chip-based biological assay. PMID:23538998

  13. Bioactive glass in tissue engineering

    PubMed Central

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  14. Adjustable, rapidly switching microfluidic gradient generation using focused travelling surface acoustic waves

    SciTech Connect

    Destgeer, Ghulam; Im, Sunghyuk; Hang Ha, Byung; Ho Jung, Jin; Ahmad Ansari, Mubashshir; Jin Sung, Hyung

    2014-01-13

    We demonstrate a simple device to generate chemical concentration gradients in a microfluidic channel using focused travelling surface acoustic waves (F-TSAW). A pair of curved interdigitated metal electrodes deposited on the surface of a piezoelectric (LiNbO{sub 3}) substrate disseminate high frequency sound waves when actuated by an alternating current source. The F-TSAW produces chaotic acoustic streaming flow upon its interaction with the fluid inside a microfluidic channel, which mixes confluent streams of chemicals in a controlled fashion for an adjustable and rapidly switching gradient generation.

  15. Active microfluidic mixer chip

    NASA Astrophysics Data System (ADS)

    Niu, Xize; Liu, Liyu; Wen, Weijia; Sheng, Ping

    2006-04-01

    We report the design and fabrication of a chaotic mixer based on the electrorheological (ER) fluid-controlled valves. The flow in the main channel is perturbed by liquid flow in orthogonal side channels, driven by hydrodynamic pulsating pumps. Each pulsating pump consists of a chamber with diaphragm plus two out-of-phase ER valves operating in a push-pull mode. All the valves, pumps, and mixing channels are integrated in one polydimethylsioxane chip. Mixing characteristics in the main channel are controlled by the strength and frequency of external electric fields applied on the ER fluid.

  16. Real-time monitoring system for microfluidics

    NASA Astrophysics Data System (ADS)

    Sapuppo, F.; Cantelli, G.; Fortuna, L.; Arena, P.; Bucolo, M.

    2007-05-01

    A new non-invasive real-time system for the monitoring and control of microfluidodynamic phenomena is proposed. The general purpose design of such system is suitable for in vitro and in vivo experimental setup and therefore for microfluidic application in the biomedical field such as lab-on-chip and for research studies in the field of microcirculation. The system consists of an ad hoc optical setup for image magnification providing images suitable for image acquisition and processing. The optic system was designed and developed using discrete opto-mechanic components mounted on a breadboard in order to provide an optic path accessible at any point where the information needs to be acquired. The optic sensing, acquisition, and processing were performed using an integrated vision system based on the Cellular Nonlinear Networks (CNNs) analogic technology called Focal Plane Processor (FPP, Eye-RIS, Anafocus) and inserted in the optic path. Ad hoc algorithms were implemented for the real-time analysis and extraction of fluido-dynamic parameters in micro-channels. They were tested on images recorded during in vivo microcirculation experiments on hamsters and then they were applied on images optically acquired and processed in real-time during in vitro experiments on a continuous microfluidic device (serpentine mixer, ThinXXS) with a two-phase fluid.

  17. Characterization of microfluidic human epidermal keratinocyte culture

    PubMed Central

    O’Neill, Adrian T.; Monteiro-Riviere, Nancy A.

    2008-01-01

    Human epidermal keratinocytes (HEK) are skin cells of primary importance in maintaining the body’s defensive barrier and are used in vitro to assess the irritation potential and toxicity of chemical compounds. Microfluidic systems hold promise for high throughput irritant and toxicity assays, but HEK growth kinetics have yet to be characterized within microscale culture chambers. This research demonstrates HEK patterning on microscale patches of Type I collagen within microfluidic channels and maintenance of these cells under constant medium perfusion for 72 h. HEK were shown to maintain 93.0%–99.6% viability at 72 h under medium perfusion ranging from 0.025–0.4 μl min−1. HEK maintained this viability while ∼100% confluent—a level not possible in 96 well plates. Microscale HEK cultures offer the ability to precisely examine the morphology, behavior and viability of individual cells which may open the door to new discoveries in toxicological screening methods and wound healing techniques. PMID:19002858

  18. Microfluidics, Chromatography, and Atomic-Force Microscopy

    NASA Technical Reports Server (NTRS)

    Anderson, Mark

    2008-01-01

    A Raman-and-atomic-force microscope (RAFM) has been shown to be capable of performing several liquid-transfer and sensory functions essential for the operation of a microfluidic laboratory on a chip that would be used to perform rapid, sensitive chromatographic and spectro-chemical analyses of unprecedentedly small quantities of liquids. The most novel aspect of this development lies in the exploitation of capillary and shear effects at the atomic-force-microscope (AFM) tip to produce shear-driven flow of liquids along open microchannels of a microfluidic device. The RAFM can also be used to perform such functions as imaging liquids in microchannels; removing liquid samples from channels for very sensitive, tip-localized spectrochemical analyses; measuring a quantity of liquid adhering to the tip; and dip-pen deposition from a chromatographic device. A commercial Raman-spectroscopy system and a commercial AFM were integrated to make the RAFM so as to be able to perform simultaneous topographical AFM imaging and surface-enhanced Raman spectroscopy (SERS) at the AFM tip. The Raman-spectroscopy system includes a Raman microprobe attached to an optical microscope, the translation stage of which is modified to accommodate the AFM head. The Raman laser excitation beam, which is aimed at the AFM tip, has a wavelength of 785 nm and a diameter of about 5 m, and its power is adjustable up to 10 mW. The AFM is coated with gold to enable tip-localized SERS.

  19. 3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate

    PubMed Central

    2015-01-01

    This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime. PMID:26070023

  20. Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications

    PubMed Central

    O'Neill, P. F.; Ben Azouz, A.; Vázquez, M.; Liu, J.; Marczak, S.; Slouka, Z.; Chang, H. C.; Diamond, D.; Brabazon, D.

    2014-01-01

    The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and studies in drug transport and induced-release of adenosine triphosphate from erythrocytes. PMID:25538804

  1. Multiplexed microfluidic blotting of proteins and nucleic acids by parallel, serpentine microchannels.

    PubMed

    He, Sha; Zhang, Yi; Wang, Pei; Xu, Xingzhi; Zhu, Kui; Pan, Wenying; Liu, Wenwen; Cai, Kaiyong; Sun, Jiashu; Zhang, Wei; Jiang, Xingyu

    2015-01-01

    This work develops a high-throughput, high-efficiency and straightforward microfluidic blotting method for analyzing proteins and nucleic acids. Sample solutions containing antibodies (for protein detection) or hybridization probes (for nucleic acid detection) are introduced into the parallel, serpentine microchannels to specifically recognize the immobilized targets on the substrate, achieving the identification of multiple targets in multiple samples simultaneously. The loading control, molecular weight markers, and antigen/antibody titration are designed and integrated into the microfluidic chip, thus allowing for the quantification of proteins and nucleic acids. Importantly, we could easily distinguish the adjacent blotting bands inside parallel microchannels, which may be difficult to achieve in conventional blotting. The small dimensions of microfluidic channels also help to reduce the amount of probing molecules and to accelerate the biochemical reaction. Our microfluidic blotting could bypass the steps of blocking and washing, further reducing the operation time and complexity. PMID:25342223

  2. A microfluidic tubing method and its application for controlled synthesis of polymeric nanoparticles.

    PubMed

    Wang, Jidong; Chen, Wenwen; Sun, Jiashu; Liu, Chao; Yin, Qifang; Zhang, Lu; Xianyu, Yunlei; Shi, Xinghua; Hu, Guoqing; Jiang, Xingyu

    2014-05-21

    This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h(-1), resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications. PMID:24675980

  3. 3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate.

    PubMed

    Gowers, Sally A N; Curto, Vincenzo F; Seneci, Carlo A; Wang, Chu; Anastasova, Salzitsa; Vadgama, Pankaj; Yang, Guang-Zhong; Boutelle, Martyn G

    2015-08-01

    This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime. PMID:26070023

  4. Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications.

    PubMed

    O'Neill, P F; Ben Azouz, A; Vázquez, M; Liu, J; Marczak, S; Slouka, Z; Chang, H C; Diamond, D; Brabazon, D

    2014-09-01

    The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and studies in drug transport and induced-release of adenosine triphosphate from erythrocytes. PMID:25538804

  5. Development of novel microfluidic platforms for neural stem cell research

    NASA Astrophysics Data System (ADS)

    Chung, Bonggeun

    also developed a microfluidic multi-injector (MMI) that can generate temporal and spatial concentration gradients. MMI consists of fluidic channels and control channels with pneumatically actuated on-chip barrier valves. Repetitive actuations of on-chip valves control pulsatile release of solution that establishes microscopic chemical gradients. The development of novel gradient-generating microfluidic platforms will help in advancing our understanding of brain development and provide a versatile tool with basic and applied studies in stem cell biology.

  6. Solvent resistant microfluidic DNA synthesizer.

    PubMed

    Huang, Yanyi; Castrataro, Piero; Lee, Cheng-Chung; Quake, Stephen R

    2007-01-01

    We fabricated a microfluidic DNA synthesizer out of perfluoropolyether (PFPE), an elastomer with excellent chemical compatibility which makes it possible to perform organic chemical reactions, and synthesized 20-mer oligonucleotides on chip. PMID:17180201

  7. Gravity-induced swirl of nanoparticles in microfluidics

    PubMed Central

    Zhao, Chao; Oztekin, Alparslan

    2013-01-01

    Parallel flows of two fluids in microfluidic devices are used for miniaturized chemistry, physics, biology and bioengineering studies, and the streams are often considered to remain parallel. However, as the two fluids do not always have the same density, interface reorientation induced by density stratification is unavoidable. In this paper, flow characteristics of an aqueous polystyrene nanofluid and a sucrose-densified aqueous solution flowing parallel in microchannels are examined. Nanoparticles 100 nm in diameter are used in the study. The motion of the nanoparticles is simulated using the Lagrangian description and directly observed by a confocal microscope. Matched results are obtained from computational and empirical analysis. Although solution density homogenizes rapidly resulting from a fast diffusion of sucrose in water, the nanofluid is observed to rotate for an extended period. Angular displacement of the nanofluid depends on the ratio of gravitational force to viscous force, Re/Fr2, where Re is the Reynolds number and Fr is the Froude number. In the developing region at the steady state, the angular displacement is related to y/Dh, the ratio between distance from the inlet and the hydraulic diameter of the microfluidic channel. The development of nanofluid flow feature also depends on h/w, the ratio of microfluidic channel’s height to width. The quantitative description of the angular displacement of nanofluid will aid rational designs of microfluidic devices utilizing multistream, multiphase flows. PMID:24563612

  8. Microfluidic Mixing Technology for a Universal Health Sensor

    NASA Technical Reports Server (NTRS)

    Chan, Eugene Y.; Bae, Candice

    2009-01-01

    A highly efficient means of microfluidic mixing has been created for use with the rHEALTH sensor an elliptical mixer and passive curvilinear mixing patterns. The rHEALTH sensor provides rapid, handheld, complete blood count, cell differential counts, electrolyte measurements, and other lab tests based on a reusable, flow-based microfluidic platform. These geometries allow for cleaning in a reusable manner, and also allow for complete mixing of fluid streams. The microfluidic mixing is performed by flowing two streams of fluid into an elliptical or curvilinear design that allows the combination of the flows into one channel. The mixing is accomplished by either chaotic advection around micro - fluidic loops. All components of the microfluidic chip are flow-through, meaning that cleaning solution can be introduced into the chip to flush out cells, plasma proteins, and dye. Tests were performed on multiple chip geometries to show that cleaning is efficient in any flowthrough design. The conclusion from these experiments is that the chip can indeed be flushed out with microliter volumes of solution and biological samples are cleaned readily from the chip with minimal effort. The technology can be applied in real-time health monitoring at patient s bedside or in a doctor s office, and real-time clinical intervention in acute situations. It also can be used for daily measurement of hematocrit for patients on anticoagulant drugs, or to detect acute myocardial damage outside a hospital.

  9. A Microfluidic Model of Biomimetically Breathing Pulmonary Acinar Airways.

    PubMed

    Fishler, Rami; Sznitman, Josué

    2016-01-01

    Quantifying respiratory flow characteristics in the pulmonary acinar depths and how they influence inhaled aerosol transport is critical towards optimizing drug inhalation techniques as well as predicting deposition patterns of potentially toxic airborne particles in the pulmonary alveoli. Here, soft-lithography techniques are used to fabricate complex acinar-like airway structures at the truthful anatomical length-scales that reproduce physiological acinar flow phenomena in an optically accessible system. The microfluidic device features 5 generations of bifurcating alveolated ducts with periodically expanding and contracting walls. Wall actuation is achieved by altering the pressure inside water-filled chambers surrounding the thin PDMS acinar channel walls both from the sides and the top of the device. In contrast to common multilayer microfluidic devices, where the stacking of several PDMS molds is required, a simple method is presented to fabricate the top chamber by embedding the barrel section of a syringe into the PDMS mold. This novel microfluidic setup delivers physiological breathing motions which in turn give rise to characteristic acinar air-flows. In the current study, micro particle image velocimetry (µPIV) with liquid suspended particles was used to quantify such air flows based on hydrodynamic similarity matching. The good agreement between µPIV results and expected acinar flow phenomena suggest that the microfluidic platform may serve in the near future as an attractive in vitro tool to investigate directly airborne representative particle transport and deposition in the acinar regions of the lungs. PMID:27214269

  10. A glass microfluidic chip adhesive bonding method at room temperature

    NASA Astrophysics Data System (ADS)

    Pan, Yu-Jen; Yang, Ruey-Jen

    2006-12-01

    This paper presents a novel method using UV epoxy resin for the bonding of glass blanks and patterned plates at room temperature. There is no need to use a high-temperature thermal fusion process and therefore avoid damaging temperature-sensitive metals in a microchip. The proposed technique has the further advantage that the sealed glass blanks and patterned plates can be separated by the application of adequate heat. In this way, the microchip can be opened, the fouling microchannels may be easily cleaned-up and the plates then re-bonded to recycle the microchip. The proposed sealing method is used to bond a microfluidic device, and the bonding strength is then investigated in a series of chemical resistance tests conducted in various chemicals. Leakage of solution was evaluated in a microfluidic chip using pressure testing to 1.792 × 102 kPa (26 psi), and the microchannel had no observable leak. Electrical leakage between channels was tested by comparing the resistances of two bonding methods, and the result shows no significant electrical leakage. The performance of the device obtained from the proposed bonding method is compared with that of the thermal fusion bonding technique for an identical microfluidic device. It is found that identical results are obtained under the same operating conditions. The proposed method provides a simple, quick and inexpensive method for sealing glass microfluidic chips.

  11. Microfluidic ultrasonic particle separators with engineered node locations and geometries

    DOEpatents

    Rose, Klint A; Fisher, Karl A; Wajda, Douglas A; Mariella, Jr., Raymond P; Bailey, Christoppher; Dehlinger, Dietrich; Shusteff, Maxim; Jung, Byoungsok; Ness, Kevin D

    2014-05-20

    An ultrasonic microfluidic system includes a separation channel for conveying a sample fluid containing small particles and large particles, flowing substantially parallel, adjacent to a recovery fluid, with which it is in contact. An acoustic transducer produces an ultrasound standing wave, that generates a pressure field having at least one node of minimum pressure amplitude. An acoustic extension structure is located proximate to said separation channel for positioning said acoustic node off center in said acoustic area and concentrating the large particles in said recovery fluid stream.

  12. Microfluidic ultrasonic particle separators with engineered node locations and geometries

    SciTech Connect

    Rose, Klint A; Fisher, Karl A; Wajda, Douglas A; Mariella, Jr., Raymond P; Bailey, Christopher; Dehlinger, Dietrich; Shusteff, Maxim; Jung, Byoungsok; Ness, Kevin D

    2015-03-31

    An ultrasonic microfluidic system includes a separation channel for conveying a sample fluid containing small particles and large particles, flowing substantially parallel, adjacent to a recovery fluid, with which it is in contact. An acoustic transducer produces an ultrasound standing wave, that generates a pressure field having at least one node of minimum, pressure amplitude. An acoustic extension structure is located proximate to said separation channel for positioning said acoustic node off center in said acoustic area and concentrating the large particles in said recovery fluid stream.

  13. Microfluidic ultrasonic particle separators with engineered node locations and geometries

    DOEpatents

    Rose, Klint A.; Fisher, Karl A.; Wajda, Douglas A.; Mariella, Jr., Raymond P.; Bailey, Christopher; Dehlinger, Dietrich; Shusteff, Maxim; Jung, Byoungsok; Ness, Kevin D.

    2016-04-26

    An ultrasonic microfluidic system includes a separation channel for conveying a sample fluid containing small particles and large particles, flowing substantially parallel, adjacent to a recovery fluid, with which it is in contact. An acoustic transducer produces an ultrasound standing wave, that generates a pressure field having at least one node of minimum pressure amplitude. An acoustic extension structure is located proximate to said separation channel for positioning said acoustic node off center in said acoustic area and concentrating the large particles in said recovery fluid stream.

  14. Passive microfluidic array card and reader

    DOEpatents

    Dugan, Lawrence Christopher; Coleman, Matthew A.

    2011-08-09

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

  15. Fabrication of functional materials in microfluidics

    NASA Astrophysics Data System (ADS)

    Shum, Ho Cheung

    In this thesis, we present a study on how droplets prepared in microfluidics can be used for fabrication of functional materials. We utilize the high degree of fluidic control enabled by miniaturizing the channels to achieve monodisperse single and multiple emulsion with high encapsulation efficiency. By engineering the interfaces of such emulsions and/or applying appropriate reactions, novel functional materials have been fabricated for encapsulation and release applications and for carrying out reactions in confined environments. Glass capillary microfluidics is used in the majority of the thesis. Glass offers excellent solvent resistance to most organic solvents needed for fabricating the desired materials. In Chapter 1, we describe a double-emulsion-templated approach to form polymer vesicles, also known as polymersomes. By dissolving amphiphilic block copolymers in a volatile solvent, which forms the shell layer of double emulsions, polymersomes are formed after evaporation of the volatile solvent. In Chapter 2, we apply the same approach to fabricate phospholipid vesicles. In Chapter 3, we investigate the physics of membrane formation at interfaces laden with amphiphilic diblock copolymers. In Chapter 4, we fabricate polymersomes with multiple compaitalents by using controlled double emulsion drops with multiple inner droplets as templates. In Chapter 5, we describe a non-microfluidic approach for fabricating similar polymersomes with large number of compartments. In Chapter 6, we show that the double-emulsion templated approach for forming polymersomes can be applied to two-dimensional stamped devices, which can be easily scaled up for production of large amount of polymersomes. Apart from polymersomes, controlled emulsions can also be used for generating other functional materials. In Chapter 7, we use double emulsion drops as microreactors for fabricating particles of hydroxyapatite. In Chapter 8, we generate solid capsules by emulsifying a molten phase as

  16. Field-effect flow control in a polydimethylsiloxane-based microfluidic system.

    PubMed

    Buch, J S; Wang, P C; DeVoe, D L; Lee, C S

    2001-10-01

    The application of the field-effect for direct control of electroosmosis in a polydimethylsiloxane (PDMS)-based microfluidic system, constructed on a silicon wafer with a 2.0 microm electrically insulating layer of silicon dioxide, is demonstrated. This microfluidic system consists of a 2.0 cm open microchannel fabricated on a PDMS slab, which can reversibly adhere to the silicon wafer to form a hybrid microfluidic device. Aside from mechanically serving as a robust bottom substrate to seal the channel and support the microfluidic system, the silicon wafer is exploited to achieve field-effect flow control by grounding the semiconductive silicon medium. When an electric field is applied through the channel, a radial electric potential gradient is created across the silicon dioxide layer that allows for direct control of the zeta potential and the resulting electroosmotic flow (EOF). By configuring this microfluidic system with two power supplies at both ends of the microchannel, the applied electric potentials can be varied for manipulating the polarity and the magnitude of the radial electric potential gradient across the silicon dioxide layer. At the same time, the longitudinal potential gradient through the microchannel, which is used to induce EOF, is held constant. The results of EOF control in this hybrid microfluidic system are presented for phosphate buffer at pH 3 and pH 5. It is also demonstrated that EOF control can be performed at higher solution pH of 6 and 7.4 by modifying the silicon wafer surface with cetyltrimethylammonium bromide (CTAB) prior to assembly of the hybrid microfluidic system. Results of EOF control from this study are compared with those reported in the literature involving the use of other microfluidic devices under comparable solution conditions. PMID:11700719

  17. Electrodes for microfluidic applications

    DOEpatents

    Crocker, Robert W.; Harnett, Cindy K.; Rognlien, Judith L.

    2006-08-22

    An electrode device for high pressure applications. These electrodes, designed to withstand pressure of greater than 10,000 psi, are adapted for use in microfluidic devices that employ electrokinetic or electrophoretic flow. The electrode is composed, generally, of an outer electrically insulating tubular body having a porous ceramic frit material disposed in one end of the outer body. The pores of the porous ceramic material are filled with an ion conductive polymer resin. A conductive material situated on the upper surface of the porous ceramic frit material and, thus isolated from direct contact with the electrolyte, forms a gas diffusion electrode. A metal current collector, in contact with the gas diffusion electrode, provides connection to a voltage source.

  18. Microfluidic serial dilution ladder.

    PubMed

    Ahrar, Siavash; Hwang, Michelle; Duncan, Philip N; Hui, Elliot E

    2014-01-01

    Serial dilution is a fundamental procedure that is common to a large number of laboratory protocols. Automation of serial dilution is thus a valuable component for lab-on-a-chip systems. While a handful of different microfluidic strategies for serial dilution have been reported, approaches based on continuous flow mixing inherently consume larger amounts of sample volume and chip real estate. We employ valve-driven circulatory mixing to address these issues and also introduce a novel device structure to store each stage of the dilution process. The dilution strategy is based on sequentially mixing the rungs of a ladder structure. We demonstrate a 7-stage series of 1 : 1 dilutions with R(2) equal to 0.995 in an active device area of 1 cm(2). PMID:24231765

  19. Digital Microfluidic Cell Culture.

    PubMed

    Ng, Alphonsus H C; Li, Bingyu Betty; Chamberlain, M Dean; Wheeler, Aaron R

    2015-01-01

    Digital microfluidics (DMF) is a droplet-based liquid-handling technology that has recently become popular for cell culture and analysis. In DMF, picoliter- to microliter-sized droplets are manipulated on a planar surface using electric fields, thus enabling software-reconfigurable operations on individual droplets, such as move, merge, split, and dispense from reservoirs. Using this technique, multistep cell-based processes can be carried out using simple and compact instrumentation, making DMF an attractive platform for eventual integration into routine biology workflows. In this review, we summarize the state-of-the-art in DMF cell culture, and describe design considerations, types of DMF cell culture, and cell-based applications of DMF. PMID:26643019

  20. Inertial Focusing in Microfluidics

    PubMed Central

    Martel, Joseph M.; Toner, Mehmet

    2015-01-01

    When Segré and Silberberg in 1961 witnessed particles in a laminar pipe flow congregating at an annulus in the pipe, scientists were perplexed and spent decades learning why such behavior occurred, finally understanding that it was caused by previously unknown forces on particles in an inertial flow. The advent of microfluidics opened a new realm of possibilities for inertial focusing in the processing of biological fluids and cellular suspensions and created a field that is now rapidly expanding. Over the past five years, inertial focusing has enabled high-throughput, simple, and precise manipulation of bodily fluids for a myriad of applications in point-of-care and clinical diagnostics. This review describes the theoretical developments that have made the field of inertial focusing what it is today and presents the key applications that will make inertial focusing a mainstream technology in the future. PMID:24905880

  1. A Programmable MicroFluidic Processor: Integrated and Hybrid Solutions

    SciTech Connect

    Rose, K A

    2002-05-10

    The Programmable Fluidic Processor (PFP), a device conceived of by researchers at MD Anderson Cancer Center, is a reconfigurable and programmable bio-chemical analysis system designed for handheld operation in a variety of applications. Unlike most microfluidic systems which utilize channels to control fluids, the PFP device is a droplet-based system. The device is based on dielectrophoresis; a fluid transport phenomenon that utilizes mismatched polarizability between a droplet and its medium to induce droplet mobility. In the device, sample carrying droplets are polarized by an array of electrodes, individually addressable by subsurface microelectronics. My research focused on the development of a polymer-based microfluidic injection system for injecting these droplets onto the electrode array. The first of two device generations fabricated at LLNL was designed using extensive research and modeling performed by MD Anderson and Coventor. Fabricating the first generation required several iterations and design changes in order to generate an acceptable device for testing. Difficulties in planar fabrication of the fluidic system and a narrow channel design necessitated these changes. The second generation device incorporated modifications of the previous generation and improved on deficiencies discovered during experimentation with the initial device. Extensive modeling of the injection channels and fluid storage chamber also aided in redesigning the device's microfluidic system. A micromolding technique with interlocking features enabled precise alignments and dimensional control, critical requirements for device optimization. Fabrication of a final device will be fully integrated with the polymer-based microfluidics bonded directly to the silicon-based microelectronics. The optimized design and process flow developed in the trial generations will readily transfer to this approach.

  2. Mixing in polymeric microfluidic devices.

    SciTech Connect

    Schunk, Peter Randall; Sun, Amy Cha-Tien; Davis, Robert H.; Brotherton, Christopher M. (University of Colorado at Boulder, Boulder, CO)

    2006-04-01

    This SAND report describes progress made during a Sandia National Laboratories sponsored graduate fellowship. The fellowship was funded through an LDRD proposal. The goal of this project is development and characterization of mixing strategies for polymeric microfluidic devices. The mixing strategies under investigation include electroosmotic flow focusing, hydrodynamic focusing, physical constrictions and porous polymer monoliths. For electroosmotic flow focusing, simulations were performed to determine the effect of electroosmotic flow in a microchannel with heterogeneous surface potential. The heterogeneous surface potential caused recirculations to form within the microchannel. These recirculations could then be used to restrict two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the mixing region surface potential to the average channel surface potential was made large in magnitude and negative in sign, and when the ratio of the characteristic convection time to the characteristic diffusion time was minimized. Based on these results, experiments were performed to evaluate the manipulation of surface potential using living-radical photopolymerization. The material chosen to manipulate typically exhibits a negative surface potential. Using living-radical surface grafting, a positive surface potential was produced using 2-(Dimethylamino)ethyl methacrylate and a neutral surface was produced using a poly(ethylene glycol) surface graft. Simulations investigating hydrodynamic focusing were also performed. For this technique, mixing is enhanced by using a tertiary fluid stream to constrict the two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the tertiary flow stream flow-rate to the mixing streams flow-rate was maximized. Also, like the electroosmotic focusing mixer, mixing was also maximized when the ratio of the characteristic convection time to the

  3. Digital Microfluidics Sample Analyzer

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  4. Real-time Functional Analysis of Inertial Microfluidic Devices via Spectral Domain Optical Coherence Tomography.

    PubMed

    Dong, Biqin; Chen, Siyu; Zhou, Fan; Chan, Christina H Y; Yi, Ji; Zhang, Hao F; Sun, Cheng

    2016-01-01

    We report the application of spectral-domain optical coherence tomography (SD-OCT) technology that enables real-time functional analysis of sorting microparticles and cells in an inertial microfluidic device. We demonstrated high-speed, high-resolution acquisition of cross-sectional images at a frame rate of 350 Hz, with a lateral resolution of 3 μm and an axial resolution of 1 μm within the microfluidic channel filled with water. We analyzed the temporal sequence of cross-sectional SD-OCT images to determine the position and diameter of microspheres in a spiral microfluidic channel under various flow rates. We used microspheres with known diameters to validate the sub-micrometer precision of the particle size analysis based on a scattering model of spherical microparticles. An additional investigation of sorting live HT-29 cells in the spiral microfluidic channel indicated that the distribution of cells within in the microchannel has a close correspondence with the cells' size distribution. The label-free real-time imaging and analysis of microscale particles in flow offers robustness for practical applications with live cells and allows us to better understand the mechanisms of particle separations in microfluidic sorting systems. PMID:27619202

  5. A contact line pinning based microfluidic platform for modelling physiological flows.

    PubMed

    Tung, Chih-kuan; Krupa, Oleh; Apaydin, Elif; Liou, Jr-Jiun; Diaz-Santana, Anthony; Kim, Beum Jun; Wu, Mingming

    2013-10-01

    This work introduces a contact line pinning based microfluidic platform for the generation of interstitial and intramural flows within a three dimensional (3D) microenvironment for cellular behaviour studies. A contact line pinning method was used to confine a natively derived biomatrix, collagen, in microfluidic channels without walls. By patterning collagen in designated wall-less channels, we demonstrated and validated the intramural flows through a microfluidic channel bounded by a monolayer of endothelial cells (mimic of a vascular vessel), as well as slow interstitial flows within a cell laden collagen matrix using the same microfluidic platform. The contact line pinning method ensured the generation of an engineered endothelial tube with straight walls, and spatially uniform interstitial fluid flows through the cell embedded 3D collagen matrix. Using this device, we demonstrated that the breast tumour cells' (MDA-MB-231 cell line) morphology and motility were modulated by the interstitial flows, and the motility of a sub-population of the cells was enhanced by the presence of the flow. The presented microfluidic platform provides a basic framework for studies of cellular behaviour including cell transmigration, growth, and adhesion under well controlled interstitial and intramural flows, and within a physiologically realistic 3D co-culture setting. PMID:23917952

  6. Melt Crystallization in Microfluidics for Sample Concentration

    NASA Astrophysics Data System (ADS)

    Sharif-Kashani, Pooria; Pirouz Kavehpour, H.

    2010-11-01

    Melt crystallization in microfluidics is a novel approach to concentrate/purify a diverse range of samples from particles to ions. In this technique, the difference in solubility of solutes in the liquid and solid phase of the solvent drives the transport of the solutes. Consequently, this method has the advantage of being non-invasive and entirely thermally-actuated with no moving parts. A fluid sample is frozen in a microchannel and melting zones are passed repeatedly through the stationary sample to increase the concentration of solute at one end. The device is constructed using a thermoelectric cooler to freeze the sample and thin-film resistive heaters to create melting zones. The heaters are operated independently, allowing them to be switched on or off to create a localized melting zone in the channel. The performance of the system is successfully tested for a variety of samples including aqueous solutions and water containing micro-particles.

  7. Microfluidics with compound ``bubble-drops''

    NASA Astrophysics Data System (ADS)

    Khan, Saif A.; Duraiswamy, Suhanya

    2008-11-01

    ``Bubble-drops'' are compound fluid particles comprising a gas bubble and liquid drop that flow as a single fluid object through another immiscible liquid in a microchannel network. These fluid particles represent discrete multiphase `quanta', and expand the sphere of application of droplet microfluidics to inter-phase phenomena. We present here a simple method to generate monodisperse bubble-drop trains in microfabricated channel networks. The difference in drag force exerted on flowing bubbles and drops by the immiscible carrier liquid implies different translational speeds, thus providing the driving force for bubble-drop formation. We outline the criteria for stable generation and analyze factors influencing bubble-drop dynamics. We will also highlight several applications in chemical and biological synthesis and screening.

  8. Microfluidic adhesion induced by subsurface microstructures.

    PubMed

    Majumder, Abhijit; Ghatak, Animangsu; Sharma, Ashutosh

    2007-10-12

    Natural adhesives in the feet of different arthropods and vertebrates show strong adhesion as well as excellent reusability. Whereas the hierarchical structures on the surface are known to have a substantial effect on adhesion, the role of subsurface structures such as the network of microchannels has not been studied. Inspired by these bioadhesives, we generated elastomeric layers with embedded air- or oil-filled microchannels. These adhesives showed remarkable enhancement of adhesion ( approximately 30 times), which results from the crack-arresting properties of the microchannels, together with the surface stresses caused by the capillary force. The importance of the thickness of the adhesive layer, channel diameter, interchannel spacing, and vertical position within the adhesive has been examined for developing an optimal design of this microfluidic adhesive. PMID:17932295

  9. Broad spectrum bioactive sunscreens.

    PubMed

    Velasco, Maria Valéria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, André Rolim

    2008-11-01

    The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm. PMID:18662760

  10. Demonstration of an integrated electroactive polymer actuator on a microfluidic electrophoresis device.

    PubMed

    Price, Alexander K; Anderson, Kristen M; Culbertson, Christopher T

    2009-07-21

    The construction of microfluidic devices from siloxane-based polymers is widely reported in the current literature. While the use of these materials is primarily due to their rapid and facile fabrication, low cost and robustness, they also have the ability to function as smart materials. This feature, however, has not been commonly exploited in conjunction with their fluid-handling capabilities. Siloxanes are considered smart materials because their shapes can be modified in the presence of an electric field. The energy in the electric field can be transduced into mechanical energy and directly coupled with a microfabricated channel network in order to affect or initiate the movement of fluids. Here, we present a novel microfluidic device into which an electroactive polymer (EAP) actuation unit is integrated. The EAP actuation unit features a microfluidic channel placed above a patterned electrode. The patterned electrode is insulated from the channel by an EAP layer that is composed of PDMS. When a potential is applied across the EAP layer, it changes shape, which also changes the volume of the microfluidic channel above it. With this proof-of-concept device we demonstrated the ability to inject plugs of sample on a standard electrophoresis cross chip solely by changing the magnitude of the electric field between the channel and the electrode. Using an EAP actuation unit, the size of the injection plugs can be varied as a function of the electric field, the active area of the EAP actuation unit and the softness of the EAP. PMID:19568678

  11. Parametric analysis of a novel semi-circular microfluidic CD-ELISA valve

    PubMed Central

    2011-01-01

    CD-ELISA uses the microfluidic ranking method and centrifugal force to control the testing solution as it flows into the reaction region. The most challenging part of CD-ELISA is controlling the flow process for different biological testing solutions, i.e. the controlling sequence for the microfluidic channel valves. The microfluidic channel valve is therefore the most important fluid channel structure for CD-ELISA. In this study, we propose a valve design suitable for a wide range rotational speeds which can be applied for mass production (molding). Together with supporting experiments, simulation based on two-phase flow theory is used in this study, and the feasibility of this novel valve design is confirmed. Influencing design factors for the microfluidic channel valves in CD-ELISA are investigated, including various shapes of the arc, distance d, radius r, the location of the center of the circle, and the contact angle. From both the experimental results and the simulated results, it is evident that the narrowest channel width and the contact angle are the primary factors influencing valve burst frequency. These can be used as the main controlling factors during the design. PMID:22059903

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

    PubMed Central

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

    2014-01-01

    For devices such as bio-/chemical sensors in microfluidic systems, flow fluctuations result in noise in the sensor output. Here, we demonstrate in-line monitoring of flow fluctuations with a cantilever-like sensor integrated in a microfluidic channel. The cantilevers are fabricated in different materials (SU-8 and SiN) and with different thicknesses. The integration of arrays of holes with different hole size and number of holes allows the modification of device sensitivity, theoretical detection limit and measurement range. For an average flow in the microliter range, the cantilever deflection is directly proportional to the flow rate fluctuations in the microfluidic channel. The SiN cantilevers show a detection limit below 1 nL/min and the thinnest SU-8 cantilevers a detection limit below 5 nL/min. Finally, the sensor is applied for in-line monitoring of flow fluctuations generated by external pumps connected to the microfluidic system. PMID:24366179

  13. Microfluidic Pneumatic Cages: A Novel Approach for In-chip Crystal Trapping, Manipulation and Controlled Chemical Treatment.

    PubMed

    Abrishamkar, Afshin; Paradinas, Markos; Bailo, Elena; Rodriguez-Trujillo, Romen; Pfattner, Raphael; Rossi, René M; Ocal, Carmen; deMello, Andrew J; Amabilino, David B; Puigmartí-Luis, Josep

    2016-01-01

    The precise localization and controlled chemical treatment of structures on a surface are significant challenges for common laboratory technologies. Herein, we introduce a microfluidic-based technology, employing a double-layer microfluidic device, which can trap and localize in situ and ex situ synthesized structures on microfluidic channel surfaces. Crucially, we show how such a device can be used to conduct controlled chemical reactions onto on-chip trapped structures and we demonstrate how the synthetic pathway of a crystalline molecular material and its positioning inside a microfluidic channel can be precisely modified with this technology. This approach provides new opportunities for the controlled assembly of structures on surface and for their subsequent treatment. PMID:27500740

  14. A numerical study of droplet trapping in microfluidic devices

    NASA Astrophysics Data System (ADS)

    Nagel, Mathias; Brun, P.-T.; Gallaire, François

    2014-03-01

    Microfluidic channels are powerful means of control of minute volumes such as droplets. These droplets are usually conveyed at will in an externally imposed flow which follows the geometry of the micro-channel. It has recently been pointed out by Dangla et al. ["Trapping microfluidic drops in wells of surface energy," Phys. Rev. Lett. 107(12), 124501 (2011)] that the motion of transported droplets may also be stopped in the flow, when they are anchored to grooves which are etched in the channels top wall. This feature of the channel geometry explores a direction that is usually uniform in microfluidics. Herein, this anchoring effect exploiting the three spatial directions is studied combining a depth averaged fluid description and a geometrical model that accounts for the shape of the droplet in the anchor. First, the presented method is shown to enable the capture and release droplets in numerical simulations. Second, this tool is used in a numerical investigation of the physical mechanisms at play in the capture of the droplet: a localized reduced Laplace pressure jump is found on its interface when the droplet penetrates the groove. This modified boundary condition helps the droplet cope with the linear pressure drop in the surrounding fluid. Held on the anchor the droplet deforms and stretches in the flow. The combination of these ingredients leads to recover the scaling law for the critical capillary number at which the droplets exit the anchors C a^{star} ∝ h2/R2 where h is the channel height and R the droplet undeformed radius.

  15. Electrocoalescence based serial dilution of microfluidic droplets

    PubMed Central

    Bhattacharjee, Biddut; Vanapalli, Siva A.

    2014-01-01

    Dilution of microfluidic droplets where the concentration of a reagent is incrementally varied is a key operation in drop-based biological analysis. Here, we present an electrocoalescence based dilution scheme for droplets based on merging between moving and parked drops. We study the effects of fluidic and electrical parameters on the dilution process. Highly consistent coalescence and fine resolution in dilution factor are achieved with an AC signal as low as 10 V even though the electrodes are separated from the fluidic channel by insulator. We find that the amount of material exchange between the droplets per coalescence event is high for low capillary number. We also observe different types of coalescence depending on the flow and electrical parameters and discuss their influence on the rate of dilution. Overall, we find the key parameter governing the rate of dilution is the duration of coalescence between the moving and parked drop. The proposed design is simple incorporating the channel electrodes in the same layer as that of the fluidic channels. Our approach allows on-demand and controlled dilution of droplets and is simple enough to be useful for assays that require serial dilutions. The approach can also be useful for applications where there is a need to replace or wash fluid from stored drops. PMID:25379096

  16. Fabrication of gravity-driven microfluidic device

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  17. Functional polymer sheet patterning using microfluidics.

    PubMed

    Li, Minggan; Humayun, Mouhita; Kozinski, Janusz A; Hwang, Dae Kun

    2014-07-22

    Poly(dimethylsiloxane) (PDMS)-based microfluidics provide a novel approach to advanced material synthesis. While PDMS has been successfully used in a wide range of industrial applications, due to the weak mechanical property channels generally possess low aspect ratios (AR) and thus produce microparticles with similarly low ARs. By increasing the channel width to nearly 1 cm, AR to 267, and implementing flow lithography, we were able to establish the slit-channel lithography. Not only does this allow us to synthesize sheet materials bearing multiscale features and tunable chemical anisotropy but it also allows us to fabricate functional layered sheet structures in a one-step, high-throughput fashion. We showcased the technique's potential role in various applications, such as the synthesis of planar material with micro- and nanoscale features, surface morphologies, construction of tubular and 3D layered hydrogel tissue scaffolds, and one-step formation of radio frequency identification (RFID) tags. The method introduced offers a novel route to functional sheet material synthesis and sheet system fabrication. PMID:24967616

  18. Microfluidic assembly of multiscale soft materials

    NASA Astrophysics Data System (ADS)

    Leng, Lian; Guenther, Axel

    2010-11-01

    The vast majority of materials found in nature are characterized by length scales that span several orders of magnitude. Material properties such as porosity, permeability and elasticity are therefore locally and directionally tuned to their (biological) function and adapted to local environmental conditions. We use a massively scaled microfluidic approach to synthetically define multiscale complex fluids and soft materials with precisely tunable, non-isentropic bulk properties. Two or more fluids are separately introduced to the device that consists of fifteen vertically bonded and fluidically connected substrate layers, and guided to an exit section that either consists of 23 equidistantly spaced channels or a 23 x 15 channel array. The flow rates through individual channels are computer-controlled. Upon entering a reservoir in a flow-focusing configuration, a spatially organized fluid with characteristic length scales of 250 microns and 10 mm was defined, and retained via a chemical reaction. To illustrate different soft material morphologies in one, two or three directions, we demonstrate the formation of isolated fibers (1D); planar graded and barcoded materials (2D); graded bulk materials and perfusable matrices (3D).

  19. Microfluidics for simultaneous quantification of platelet adhesion and blood viscosity

    PubMed Central

    Yeom, Eunseop; Park, Jun Hong; Kang, Yang Jun; Lee, Sang Joon

    2016-01-01

    Platelet functions, including adhesion, activation, and aggregation have an influence on thrombosis and the progression of atherosclerosis. In the present study, a new microfluidic-based method is proposed to estimate platelet adhesion and blood viscosity simultaneously. Blood sample flows into an H-shaped microfluidic device with a peristaltic pump. Since platelet aggregation may be initiated by the compression of rotors inside the peristaltic pump, platelet aggregates may adhere to the H-shaped channel. Through correlation mapping, which visualizes decorrelation of the streaming blood flow, the area of adhered platelets (APlatelet) can be estimated without labeling platelets. The platelet function is estimated by determining the representative index IA·T based on APlatelet and contact time. Blood viscosity is measured by monitoring the flow conditions in the one side channel of the H-shaped device. Based on the relation between interfacial width (W) and pressure ratio of sample flows to the reference, blood sample viscosity (μ) can be estimated by measuring W. Biophysical parameters (IA·T, μ) are compared for normal and diabetic rats using an ex vivo extracorporeal model. This microfluidic-based method can be used for evaluating variations in the platelet adhesion and blood viscosity of animal models with cardiovascular diseases under ex vivo conditions. PMID:27118101

  20. Mechanically robust microfluidics and bulk wave acoustics to sort microparticles

    NASA Astrophysics Data System (ADS)

    Dauson, Erin R.; Gregory, Kelvin B.; Greve, David W.; Healy, Gregory P.; Oppenheim, Irving J.

    2016-04-01

    Sorting microparticles (or cells, or bacteria) is significant for scientific, medical and industrial purposes. Research groups have used lithium niobate SAW devices to produce standing waves, and then to align microparticles at the node lines in polydimethylsiloxane (PDMS, silicone) microfluidic channels. The "tilted angle" (skewed) configuration is a recent breakthrough producing particle trajectories that cross multiple node lines, making it practical to sort particles. However, lithium niobate wafers and PDMS microfluidic channels are not mechanically robust. We demonstrate "tilted angle" microparticle sorting in novel devices that are robust, rapidly prototyped, and manufacturable. We form our microfluidic system in a rigid polymethyl methacrylate (PMMA, acrylic) prism, sandwiched by lead-zirconium-titanate (PZT) wafers, operating in through-thickness mode with inertial backing, that produce standing bulk waves. The overall configuration is compact and mechanically robust, and actuating PZT wafers in through-thickness mode is highly efficient. Moving to this novel configuration introduced new acoustics questions involving internal reflections, but we show experimental images confirming the intended nodal geometry. Microparticles in "tilted angle" devices display undulating trajectories, where deviation from the straight path increases with particle diameter and with excitation voltage to create the mechanism by which particles are sorted. We show a simplified analytical model by which a "phase space" is constructed to characterize effective particle sorting, and we compare our experimental data to the predictions from that simplified model; precise correlation is not expected and is not observed, but the important physical trends from the model are paralleled in the measured particle trajectories.

  1. Microfluidic pretreatment of bacterial cells for analysis of intracellular contents

    NASA Astrophysics Data System (ADS)

    Wang, Hsiang-Yu; Lu, Chang; Banada, Padmapriya P.; Jagadeesan, Balamurugan; Bhunia, Arun K.

    2005-11-01

    Electrical lysis of biological cells on a microfluidic platform has been raising a lot of interests due to its applications in rapid recovering intracellular contents without introducing lytic agents. In this study, we demonstrated a simple microfluidic device which lysed green fluorescent protein (GFP) expressing E. coli cells under continuous DC voltage while cells flowed through. The cell lysis only happened in a defined section of a microfluidic channel due to the local field amplification by geometric modification. The geometric modification also effectively decreased the required voltage for lysis by several folds. We found that a local field strength of 1500V/cm was required for lysis of nearly 100% of E. coli cells. This lysis field strength was considerably lower than the value reported in the literature, possibly due to the longer duration of the field. The lysis was witnessed by plate count and fluorescence spectroscopy. The devices were fabricated using low-cost soft lithography with channel widths considerably larger than the cell size to avoid clogging and ensure stable performance. Our tool will be ideal for high throughput processing of a large number of cells. Furthermore, the application of continuous DC field makes it straightforward to couple our cell lysis device with on-chip electrophoresis to realize the integration of cell pretreatment and chemical analysis. In principle, the same approach can also be applied for the lysis of mammalian cells and for the electroporation and transfection.

  2. Plasma treatments of wool fiber surface for microfluidic applications

    SciTech Connect

    Jeon, So-Hyoun; Hwang, Ki-Hwan; Lee, Jin Su; Boo, Jin-Hyo; Yun, Sang H.

    2015-09-15

    Highlights: • We used atmospheric plasma for tuning the wettability of wool fibers. • The wicking rates of the wool fibers increased with increasing treatment time. • The increasing of wettability results in removement of fatty acid on the wool surface. - Abstract: Recent progress in health diagnostics has led to the development of simple and inexpensive systems. Thread-based microfluidic devices allow for portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, controlling the flow rate of wool thread, which is a very important part of thread-based microfluidic devices, is quite difficult. For this reason, we focused on thread-based microfluidics in the study. We developed a method of changing the wettability of hydrophobic thread, including wool thread. Thus, using natural wool thread as a channel, we demonstrate herein that the manipulation of the liquid flow, such as micro selecting and micro mixing, can be achieved by applying plasma treatment to wool thread. In addition to enabling the flow control of the treated wool channels consisting of all natural substances, this procedure will also be beneficial for biological sensing devices. We found that wools treated with various gases have different flow rates. We used an atmospheric plasma with O{sub 2}, N{sub 2} and Ar gases.

  3. Magnetophoretic-based microfluidic device for DNA isolation

    PubMed Central

    Hale, C.; Darabi, J.

    2014-01-01

    This paper presents a continuous flow microfluidic device for the separation of DNA from blood using magnetophoresis for biological applications and analysis. This microfluidic bio-separation device has several benefits, including decreased sample handling, smaller sample and reagent volumes, faster isolation time, and decreased cost to perform DNA isolation. One of the key features of this device is the use of short-range magnetic field gradients, generated by a micro-patterned nickel array on the bottom surface of the separation channel. In addition, the device utilizes an array of oppositely oriented, external permanent magnets to produce strong long-range field gradients at the interfaces between magnets, further increasing the effectiveness of the device. A comprehensive simulation is performed using COMSOL Multiphysics to study the effect of various parameters on the magnetic flux within the separation channel. Additionally, a microfluidic device is designed, fabricated, and tested to isolate DNA from blood. The results show that the device has the capability of separating DNA from a blood sample with a purity of 1.8 or higher, a yield of up to 33 μg of polymerase chain reaction ready DNA per milliliter of blood, and a volumetric throughput of up to 50 ml/h. PMID:25379103

  4. Multi-layer microfluidic glass chips for microanalytical applications.

    PubMed

    Daridon, A; Fascio, V; Lichtenberg, J; Wütrich, R; Langen, H; Verpoorte, E; de Rooij, N F

    2001-09-01

    A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed. When the new glass-based device for flow-injection analysis of ammonia was compared with our first-generation chips based on silicon micromachining, concentration sensitivity was higher, because of the longer path-length of the optical cuvette. The dependence of dispersion on velocity profile and on channel cross-sectional geometry is discussed. The rapid implementation of the devices for an organic synthesis reaction, the Wittig reaction, is also briefly described. PMID:11678200

  5. Microfluidic cellular enrichment and separation through differences in viscoelastic deformation.

    PubMed

    Wang, Gonghao; Crawford, Kaci; Turbyfield, Cory; Lam, Wilbur; Alexeev, Alexander; Sulchek, Todd

    2015-01-21

    We report a microfluidic approach to separate and enrich a mixture of two cell types based on differences in cell viscoelastic behavior during repeated compressions and relaxation events. As proof of concept, we demonstrate that variations in viscoelasticity affect the flow trajectory of one type of leukemia cell line (K562) in relation to another leukemia cell line (HL60) as well as healthy leukocytes. These differences in cell trajectory can be utilized to enrich and sort K562 cells from HL60 cells and leukocytes. The microfluidic device utilizes periodic, diagonal ridges to compress and translate the cells laterally perpendicular to channel axis. The ridge spacing is tuned to allow relaxation of the K562 cells but not the HL60 cells or leukocytes. Therefore, the periodic compression laterally translates weakly viscous cells, while highly viscous cells respond to hydrodynamic circulation forces generated by the slanted ridges. As a result, cell sorting has strong dependency on cell viscosity. We use atomic force microscopy and high-speed optical microscopy to measure cell stiffness, cell relaxation rate constant, and cell size for all cell types. With properly designed microfluidic channels, we can optimize the enrichment of K562 cells from HL60 and leukocytes. PMID:25411722

  6. Microfluidics for simultaneous quantification of platelet adhesion and blood viscosity.

    PubMed

    Yeom, Eunseop; Park, Jun Hong; Kang, Yang Jun; Lee, Sang Joon

    2016-01-01

    Platelet functions, including adhesion, activation, and aggregation have an influence on thrombosis and the progression of atherosclerosis. In the present study, a new microfluidic-based method is proposed to estimate platelet adhesion and blood viscosity simultaneously. Blood sample flows into an H-shaped microfluidic device with a peristaltic pump. Since platelet aggregation may be initiated by the compression of rotors inside the peristaltic pump, platelet aggregates may adhere to the H-shaped channel. Through correlation mapping, which visualizes decorrelation of the streaming blood flow, the area of adhered platelets (APlatelet) can be estimated without labeling platelets. The platelet function is estimated by determining the representative index IA·T based on APlatelet and contact time. Blood viscosity is measured by monitoring the flow conditions in the one side channel of the H-shaped device. Based on the relation between interfacial width (W) and pressure ratio of sample flows to the reference, blood sample viscosity (μ) can be estimated by measuring W. Biophysical parameters (IA·T, μ) are compared for normal and diabetic rats using an ex vivo extracorporeal model. This microfluidic-based method can be used for evaluating variations in the platelet adhesion and blood viscosity of animal models with cardiovascular diseases under ex vivo conditions. PMID:27118101

  7. Comparison of Inlet Geometry in Microfluidic Cell Affinity Chromatography

    PubMed Central

    Li, Peng; Tian, Yu; Pappas, Dimitri

    2011-01-01

    Cell separation based on microfluidic affinity chromatography is a widely used methodology in cell analysis research when rapid separations with high purity are needed. Several successful examples have been reported with high separation efficiency and purity; however, cell capture at the inlet area and inlet design has not been extensively described or studied. The most common inlets—used to connect the microfluidic chip to pumps, tubing, etc—are vertical (top-loading) inlets and parallel (in-line) inlets. In this work, we investigated the cell capture behavior near the affinity chip inlet area and compared the different performance of vertical inlet devices and parallel inlet devices. Vertical inlet devices showed significant cell capture capability near the inlet area, which led to the formation of cell blockages as the separation progressed. Cell density near the inlet area was much higher than the remaining channel, while for parallel inlet chips cell density at the inlet area was similar to the rest of the channel. In this paper, we discuss the effects of inlet type on chip fabrication, nonspecific binding, cell capture efficiency, and separation purity. We also discuss the possibility of using vertical inlets in negative selection separations. Our findings show that inlet design is critical and must be considered when fabricating cell affinity microfluidic devices. PMID:21207967

  8. Recent Progress of Microfluidics in Translational Applications

    PubMed Central

    Liu, Zongbin; Han, Xin

    2016-01-01

    Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. PMID:27091777

  9. Recent Progress of Microfluidics in Translational Applications.

    PubMed

    Liu, Zongbin; Han, Xin; Qin, Lidong

    2016-04-01

    Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. PMID:27091777

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

    PubMed

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

    2014-10-01

    We present a simple, rapid, benchtop, Foil Assisted Rapid Molding (FARM) method for the fabrication of microfluidic devices. This novel technique involves the use of aluminium foil, pen and an X-Y plotter to create semi-circular or plano-concave, shallow microchannels. It is an easy do-it-yourself (DIY) technique for creating a microfluidic device in three simple steps: (1) create a channel design using the CAD software, (2) plot the patterns on aluminium foil and (3) use the reverse of the engraved foil as a mold to create microfluidic devices. In this report, we present a detailed study of the proposed method by varying a range of parameters such as foil thickness, tip material, and tip sizes and by investigating their effect on the creation of channels with varying geometry. Furthermore, we demonstrated the cytocompatibility of these devices in vitro. PMID:25102283

  11. Cooperative Suction by Vertical Capillary Array Pump for Controlling Flow Profiles of Microfluidic Sensor Chips

    PubMed Central

    Horiuchi, Tsutomu; Hayashi, Katsuyoshi; Seyama, Michiko; Inoue, Suzuyo; Tamechika, Emi

    2012-01-01

    A passive pump consisting of integrated vertical capillaries has been developed for a microfluidic chip as an useful component with an excellent flow volume and flow rate. A fluidic chip built into a passive pump was used by connecting the bottoms of all the capillaries to a top surface consisting of a thin layer channel in the microfluidic chip where the thin layer channel depth was smaller than the capillary radius. As a result the vertical capillaries drew fluid cooperatively rather than independently, thus exerting the maximum suction efficiency at every instance. This meant that a flow rate was realized that exhibited little variation and without any external power or operation. A microfluidic chip built into this passive pump had the ability to achieve a quasi-steady rather than a rapidly decreasing flow rate, which is a universal flow characteristic in an ordinary capillary. PMID:23202035

  12. An integrated microfluidic chip with 40 MHz lead-free transducer for fluid analysis.

    PubMed

    Lee, S T F; Lam, K H; Lei, L; Zhang, X M; Chan, H L W

    2011-02-01

    The design, fabrication, and evaluation of a high-frequency transducer made from lead-free piezoceramic for the application of microfluidic analysis is described. Barium strontium zirconate titanate [(Ba(0.95)Sr(0.05))(Zr(0.05)Ti(0.95))O(3), abbreviated as BSZT] ceramic has been chosen to be the active element of the transducer. The center frequency and bandwidth of this high-frequency ultrasound transducer have been measured to be 43 MHz and 56.1%, respectively. The transducer was integrated into a microfluidic channel and used to measure the sound velocity and attenuation of the liquid flowing in the channel. Results suggest that lead-free high-frequency transducers could be used for in situ analysis of property of the fluid flowing through the microfluidic system. PMID:21361626

  13. Automated centrifugal-microfluidic platform for DNA purification using laser burst valve and coriolis effect.

    PubMed

    Choi, Min-Seong; Yoo, Jae-Chern

    2015-04-01

    We report a fully automated DNA purification platform with a micropored membrane in the channel utilizing centrifugal microfluidics on a lab-on-a-disc (LOD). The microfluidic flow in the LOD, into which the reagents are injected for DNA purification, is controlled by a single motor and laser burst valve. The sample and reagents pass successively through the micropored membrane in the channel when each laser burst valve is opened. The Coriolis effect is used by rotating the LOD bi-directionally to increase the purity of the DNA, thereby preventing the mixing of the waste and elution solutions. The total process from the lysed sample injection into the LOD to obtaining the purified DNA was finished within 7 min with only one manual step. The experimental result for Salmonella shows that the proposed microfluidic platform is comparable to the existing devices in terms of the purity and yield of DNA. PMID:25737025

  14. Gecko gaskets for self-sealing and high-strength reversible bonding of microfluidics.

    PubMed

    Wasay, A; Sameoto, D

    2015-07-01

    We report in this work a novel reversible bonding technique for elastomeric microfluidic devices by integrating gecko-inspired dry adhesives with microfluidic channels which greatly enhances the bonding strength of reversibly sealed channels. The concept is applicable to nearly any elastomer and can be used to bond against any smooth surface which allows for van der Waals interactions. It does not require any solvents or glues or sources for plasma activation or thermal-compressive loading to aid the bonding process and is achievable at zero extra cost. We also demonstrate a quick fabrication technique involving soft master thermo-compressive molding of these microfluidic devices with thermoplastic elastomers. The resultant devices can be used for both pressure driven and non-pressure driven flows. We report the maximum contained pressure of these devices manufactured from two grades of styrene ethylene butylene styrene (SEBS) by conducting a burst pressure test with various substrates. PMID:26016928

  15. Flow Manipulation in Thread-Based Microfluidics by Tuning the Wettability of Wool.

    PubMed

    Jeon, So-Hyoun; Hwang, Ki-Hwan; Jung, Won Suk; Seo, Hyeon-Jin; Nam, Sung Woo; Boo, Jin-Hyo; Yun, Sang H

    2015-02-01

    Recent progress in thread-based microfluidic devices has provided portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, capillary-driven liquid flow in a single thread, a crucial aspect of thread-based microfluidics, is difficult to control. Among potential materials, hydrophobic wool thread is an appropriate candidate for liquid flow control in thread-based microfluidics because its wettability can be readily tuned by the introduction of a natural color pigment, thereby manipulating flow. Thus, utilizing natural wool thread as a channel, we demonstrate here that liquid flow manipulations, such as microselecting and micromixing, can be achieved by coating the complex Al(III) (Alum) brazilein onto wool thread. In addition to enabling flow control, the coated wool channels consisting entirely of naturally occurring substances will be beneficial for biological sensing devices. PMID:26349307

  16. Bioactivity in Organic Chemistry Courses.

    ERIC Educational Resources Information Center

    Ferguson, Lloyd N.

    1980-01-01

    Presented are three ways in which bioactivity of organic compounds has been introduced in organic chemistry courses. One is to point out a typical bioactivity of a given functional group. A second is to discuss biorganic mechanisms. A third is to draw structure-activity correlations (SAR). (Author/HM)

  17. Miniaturized Bioaffinity Assessment Coupled to Mass Spectrometry for Guided Purification of Bioactives from Toad and Cone Snail

    PubMed Central

    Heus, Ferry; Otvos, Reka A.; Aspers, Ruud L. E. G.; van Elk, Rene; Halff, Jenny I.; Ehlers, Andreas W.; Dutertre, Sébastien; Lewis, Richard J.; Wijmenga, Sybren; Smit, August B.; Niessen, Wilfried M. A.; Kool, Jeroen

    2014-01-01

    A nano-flow high-resolution screening platform, featuring a parallel chip-based microfluidic bioassay and mass spectrometry coupled to nano-liquid chromatography, was applied to screen animal venoms for nicotinic acetylcholine receptor like (nAChR) affinity by using the acetylcholine binding protein, a mimic of the nAChR. The potential of this microfluidic platform is demonstrated by profiling the Conus textile venom proteome, consisting of over 1,000 peptides. Within one analysis (<90 min, 500 ng venom injected), ligands are detected and identified. To show applicability for non-peptides, small molecular ligands such as steroidal ligands were identified in skin secretions from two toad species (Bufo alvarius and Bufo marinus). Bioactives from the toad samples were subsequently isolated by MS-guided fractionation. The fractions analyzed by NMR and a radioligand binding assay with α7-nAChR confirmed the identity and bioactivity of several new ligands. PMID:24833338

  18. Microfluidic 3D cell culture: from tools to tissue models.

    PubMed

    van Duinen, Vincent; Trietsch, Sebastiaan J; Joore, Jos; Vulto, Paul; Hankemeier, Thomas

    2015-12-01

    The transition from 2D to 3D cell culture techniques is an important step in a trend towards better biomimetic tissue models. Microfluidics allows spatial control over fluids in micrometer-sized channels has become a valuable tool to further increase the physiological relevance of 3D cell culture by enabling spatially controlled co-cultures, perfusion flow and spatial control over of signaling gradients. This paper reviews most important developments in microfluidic 3D culture since 2012. Most efforts were exerted in the field of vasculature, both as a tissue on its own and as part of cancer models. We observe that the focus is shifting from tool building to implementation of specific tissue models. The next big challenge for the field is the full validation of these models and subsequently the implementation of these models in drug development pipelines of the pharmaceutical industry and ultimately in personalized medicine applications. PMID:26094109

  19. A valve-less microfluidic peristaltic pumping method

    PubMed Central

    Zhang, Xiannian; Chen, Zitian

    2015-01-01

    We demonstrate a valve-less microfluidic peristaltic pumping method which enables the delivery of continuous nanoliter-scale flow with high precision. The fluid is driven by squeezing the microchannels embedded in a poly(dimethylsiloxane) device with rolling cams or bearings. We achieve continuous and uniform flow with velocity range from 1 to 500 nl/s, with outflow volume error within 3 nl. The devices show enhanced backpressure resistance up to 340 kPa. This method also shows great flexibility. By altering the channels' layout, emulsions and plugs can be generated easily. These low-cost and easy-to-fabricate micro-pumps offer novel approaches for liquid actuation in various microfluidic applications. PMID:25759751

  20. Diffusionless fluid transport and routing using novel microfluidic devices.

    SciTech Connect

    Barrett, Louise Mary; Shediac, Renee; Reichmuth, David S.

    2006-11-01

    Microfluidic devices have been proposed for 'Lab-on-a-Chip' applications for nearly a decade. Despite the unquestionable promise of these devices to allow rapid, sensitive and portable biochemical analysis, few practical devices exist. It is often difficult to adapt current laboratory techniques to the microscale because bench-top methods use discrete liquid volumes, while most current microfluidic devices employ streams of liquid confined in a branching network of micron-scale channels. The goal of this research was to use two phase liquid flows, creating discrete packets of liquid. Once divided into discrete packets, the packets can be moved controllably within the microchannels without loss of material. Each packet is equivalent to a minute test tube, holding a fraction from a separation or an aliquot to be reacted. We report on the fabrication of glass and PDMS (polydimethylsiloxane) devices that create and store packets.