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.

Control of the ZnO nanowires nucleation site using microfluidic channels.

PubMed

Lee, Sang Hyun; Lee, Hyun Jung; Oh, Dongcheol; Lee, Seog Woo; Goto, Hiroki; Buckmaster, Ryan; Yasukawa, Tomoyuki; Matsue, Tomokazu; Hong, Soon-Ku; Ko, HyunChul; Cho, Meoung-Whan; Yao, Takafumi

2006-03-09

We report on the growth of uniquely shaped ZnO nanowires with high surface area and patterned over large areas by using a poly(dimethylsiloxane) (PDMS) microfluidic channel technique. The synthesis uses first a patterned seed template fabricated by zinc acetate solution flowing though a microfluidic channel and then growth of ZnO nanowire at the seed using thermal chemical vapor deposition on a silicon substrate. Variations the ZnO nanowire by seed pattern formed within the microfluidic channel were also observed for different substrates and concentrations of the zinc acetate solution. The photocurrent properties of the patterned ZnO nanowires with high surface area, due to their unique shape, were also investigated. These specialized shapes and patterning technique increase the possibility of realizing one-dimensional nanostructure devices such as sensors and optoelectric devices.

Electric field-decoupled electroosmotic pump for microfluidic devices.

PubMed

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

2003-09-26

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

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.

Characterization of printable cellular micro-fluidic channels for tissue engineering.

PubMed

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

2013-06-01

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

Characterization of Printable Cellular Micro-fluidic Channels for Tissue Engineering

PubMed Central

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

2014-01-01

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

Monolithic integration of microfluidic channels and semiconductor lasers.

PubMed

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

2006-08-21

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

Monolithic integration of microfluidic channels and semiconductor lasers

NASA Astrophysics Data System (ADS)

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

2006-08-01

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

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

PubMed

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

2017-01-15

We report a method to suppress streaming potential using an Ag-coated microfluidic channel on a p-type silicon nanowire (SiNW) array measured by a multiplexed electrical readout. The metal layer sets a constant electrical potential along the microfluidic channel for a given reference electrode voltage regardless of the flow velocity. Without the Ag layer, the magnitude and sign of the surface potential change on the SiNW depends on the flow velocity, width of the microfluidic channel and the device's location inside the microfluidic channel with respect to the reference electrode. Noise analysis of the SiNW array with and without the Ag coating in the fluidic channel shows that noise frequency peaks, resulting from the operation of a piezoelectric micropump, are eliminated using the Ag layer with two reference electrodes located at inlet and outlet. This strategy presents a simple platform to eliminate the streaming potential and can become a powerful tool for nanoscale potentiometric biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-03-07

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

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.

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

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

PubMed

Kim, Suntae; Oh, Jonghyun; Cha, Chaenyung

2016-11-01

Microfluidic flow-focusing devices (FFD) are widely used to generate monodisperse droplets and microgels with controllable size, shape and composition for various biomedical applications. However, highly inconsistent and often low viability of cells encapsulated within the microgels prepared via microfluidic FFD has been a major concern, and yet this aspect has not been systematically explored. In this study, we demonstrate that the biocompatibility of microfluidic FFD to fabricate cell-laden microgels can be significantly enhanced by controlling the channel geometry. When a single emulsion ("single") microfluidic FFD is used to fabricate cell-laden microgels, there is a significant decrease and batch-to-batch variability in the cell viability, regardless of their size and composition. It is determined that during droplet generation, some of the cells are exposed to the oil phase which is shown to have a cytotoxic effect. Therefore, a microfluidic device with a sequential ('double') flow-focusing channels is employed instead, in which a secondary aqueous phase containing cells enters the primary aqueous phase, so the cells' exposure to the oil phase is minimized by directing them to the center of droplets. This microfluidic channel geometry significantly enhances the biocompatibility of cell-laden microgels, while maintaining the benefits of a typical microfluidic process. This study therefore provides a simple and yet highly effective strategy to improve the biocompatibility of microfluidic fabrication of cell-laden microgels. Copyright © 2016 Elsevier B.V. All rights reserved.

Microfluidics platform for single-shot dose-response analysis of chloride channel-modulating compounds.

PubMed

Jin, Byung-Ju; Ko, Eun-A; Namkung, Wan; Verkman, A S

2013-10-07

We previously developed cell-based kinetics assays of chloride channel modulators utilizing genetically encoded yellow fluorescent proteins. Fluorescence platereader-based high-throughput screens yielded small-molecule activators and inhibitors of the cAMP-activated chloride channel CFTR and calcium-activated chloride channels, including TMEM16A. Here, we report a microfluidics platform for single-shot determination of concentration-activity relations in which a 1.5 × 1.5 mm square area of adherent cultured cells is exposed for 5-10 min to a pseudo-logarithmic gradient of test compound generated by iterative, two-component channel mixing. Cell fluorescence is imaged following perfusion with an iodide-containing solution to give iodide influx rate at each location in the image field, thus quantifying modulator effects over a wide range of concentrations in a single measurement. IC50 determined for CFTR and TMEM16A activators and inhibitors by single-shot microfluidics were in agreement with conventional plate reader measurements. The microfluidics approach developed here may accelerate the discovery and characterization of chloride channel-targeted drugs.

Protein patterning in polycarbonate microfluidic channels

NASA Astrophysics Data System (ADS)

Thomson, David A.; Hayes, Jason P.; Thissen, Helmut

2004-03-01

In this work protein patterning has been achieved within a polycarbonate microfluidic device. Channel structures were first coated with plasma polymerized allylamine (ALAPP) followed by the "cloud point" deposition of polyethylene oxide (PEO), a protein repellent molecule. Excimer laser micromachining was used to pattern the PEO to control protein localization. Subsequent removal of a sacrificial layer of polycarbonate resulted in the patterned polymer coating only in the channels of a simple fluidic device. Following a final diffusion bonding fabrication step the devices were filled with a buffer containing Streptavidin conjugated with fluorescein, and visualized under a confocal fluorescent microscope. This confirmed that protein adhesion occurred only in laser patterned areas. The ability to control protein adhesion in microfludic channels leads to the possibility of generating arrays of proteins or cells within polymer microfludics for cheap automated biosensors and synthesis systems.

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

PubMed

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

2014-08-01

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

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

PubMed

Doonan, Steven R; Bailey, Ryan C

2017-04-04

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

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

Reconfigurable virtual electrowetting channels.

PubMed

Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

2012-02-21

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

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

2015-12-07

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

Packings of monodisperse emulsions in flat microfluidic channels

NASA Astrophysics Data System (ADS)

Claussen, Ohle; Herminghaus, Stephan; Brinkmann, Martin

2012-06-01

In the lateral confinement of a flat microfluidic channel, monodisperse emulsion droplets spontaneously self-organize in a variety of topologically different packings. The explicit construction of mechanically equilibrated arrangements of effectively two-dimensional congruent droplet shapes reveals the existence of multiple mechanical equilibria depending on channel width W, droplet area Ad, and volume fraction φ of the dispersed phase. The corresponding boundaries of local or global stability are summarized in a packing diagram for congruent droplet shapes in terms of the dimensionless channel width w=W/Ad and φ. In agreement with experimental results, an increasingly strong hysteresis of the transition between single-row and two-row packings is observed during changes of w above a threshold volume fraction of φ*≃0.813.

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

NASA Astrophysics Data System (ADS)

Songok, Joel; Toivakka, Martti

2017-06-01

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

Microfluidic electrochemical reactors

DOEpatents

Nuzzo, Ralph G [Champaign, IL; Mitrovski, Svetlana M [Urbana, IL

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.

Three-dimensional investigations of the threading regime in a microfluidic flow-focusing channel

NASA Astrophysics Data System (ADS)

Gowda, Krishne; Brouzet, Christophe; Lefranc, Thibault; Soderberg, L. Daniel; Lundell, Fredrik

2017-11-01

We study the flow dynamics of the threading regime in a microfluidic flow-focusing channel through 3D numerical simulations and experiments. Making strong filaments from cellulose nano-fibrils (CNF) could potentially steer to new high-performance bio-based composites competing with conventional glass fibre composites. CNF filaments can be obtained through hydrodynamic alignment of dispersed CNF by using the concept of flow-focusing. The aligned structure is locked by diffusion of ions resulting in a dispersion-gel transition. Flow-focusing typically refers to a microfluidic channel system where the core fluid is focused by the two sheath fluids, thereby creating an extensional flow at the intersection. In this study, threading regime corresponds to an extensional flow field generated by the water sheath fluid stretching the dispersed CNF core fluid and leading to formation of long threads. The experimental measurements are performed using optical coherence tomography (OCT) and 3D numerical simulations with OpenFOAM. The prime focus is laid on the 3D characteristics of thread formation such as wetting length of core fluid, shape, aspect ratio of the thread and velocity flow-field in the microfluidic channel.

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

PubMed

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

2015-12-16

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

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

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

Computerized microfluidic cell culture using elastomeric channels and Braille displays.

PubMed

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

2004-11-09

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

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

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.

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.

A cell sorting and trapping microfluidic device with an interdigital channel

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

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.

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

PubMed

Didar, Tohid Fatanat; Tabrizian, Maryam

2012-11-07

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

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.

Fabrication of monolithic microfluidic channels in diamond with ion beam lithography

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

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.

Dynamics of tandem bubble interaction in a microfluidic channel

PubMed Central

Yuan, Fang; Sankin, Georgy; Zhong, Pei

2011-01-01

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

Dynamics of tandem bubble interaction in a microfluidic channel.

PubMed

Yuan, Fang; Sankin, Georgy; Zhong, Pei

2011-11-01

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

Continuously tunable microdroplet-laser in a microfluidic channel.

PubMed

Tang, Sindy K Y; Derda, Ratmir; Quan, Qimin; Lončar, Marko; Whitesides, George M

2011-01-31

This paper describes the generation and optical characterization of a series of dye-doped droplet-based optical microcavities with continuously decreasing radius in a microfluidic channel. A flow-focusing nozzle generated the droplets (~21 μm in radius) using benzyl alcohol as the disperse phase and water as the continuous phase. As these drops moved down the channel, they dissolved, and their size decreased. The emission characteristics from the drops could be matched to the whispering gallery modes from spherical micro-cavities. The wavelength of emission from the drops changed from 700 to 620 nm as the radius of the drops decreased from 21 μm to 7 μm. This range of tunability in wavelengths was larger than that reported in previous work on droplet-based cavities.

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.

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

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

PubMed

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

2014-11-01

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

A cell-laden microfluidic hydrogel.

PubMed

Ling, Yibo; Rubin, Jamie; Deng, Yuting; Huang, Catherine; Demirci, Utkan; Karp, Jeffrey M; Khademhosseini, Ali

2007-06-01

The encapsulation of mammalian cells within the bulk material of microfluidic channels may be beneficial for applications ranging from tissue engineering to cell-based diagnostic assays. In this work, we present a technique for fabricating microfluidic channels from cell-laden agarose hydrogels. Using standard soft lithographic techniques, molten agarose was molded against a SU-8 patterned silicon wafer. To generate sealed and water-tight microfluidic channels, the surface of the molded agarose was heated at 71 degrees C for 3 s and sealed to another surface-heated slab of agarose. Channels of different dimensions were generated and it was shown that agarose, though highly porous, is a suitable material for performing microfluidics. Cells embedded within the microfluidic molds were well distributed and media pumped through the channels allowed the exchange of nutrients and waste products. While most cells were found to be viable upon initial device fabrication, only those cells near the microfluidic channels remained viable after 3 days, demonstrating the importance of a perfused network of microchannels for delivering nutrients and oxygen to maintain cell viability in large hydrogels. Further development of this technique may lead to the generation of biomimetic synthetic vasculature for tissue engineering, diagnostics, and drug screening applications.

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. © 2011 American Chemical Society

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.

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.

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.

Microfluidic sieve valves

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

Stochastic Model of Clogging in a Microfluidic Cell Sorter

NASA Astrophysics Data System (ADS)

Fai, Thomas; Rycroft, Chris

2016-11-01

Microfluidic devices for sorting cells by deformability show promise for various medical purposes, e.g. detecting sickle cell anemia and circulating tumor cells. One class of such devices consists of a two-dimensional array of narrow channels, each column containing several identical channels in parallel. Cells are driven through the device by an applied pressure or flow rate. Such devices allows for many cells to be sorted simultaneously, but cells eventually clog individual channels and change the device properties in an unpredictable manner. In this talk, we propose a stochastic model for the failure of such microfluidic devices by clogging and present preliminary theoretical and computational results. The model can be recast as an ODE that exhibits finite time blow-up under certain conditions. The failure time distribution is investigated analytically in certain limiting cases, and more realistic versions of the model are solved by computer simulation.

Dissolution without disappearing: multicomponent gas exchange for CO2 bubbles in a microfluidic channel.

PubMed

Shim, Suin; Wan, Jiandi; Hilgenfeldt, Sascha; Panchal, Prathamesh D; Stone, Howard A

2014-07-21

We studied the dissolution dynamics of CO2 gas bubbles in a microfluidic channel, both experimentally and theoretically. In the experiments, spherical CO2 bubbles in a flow of a solution of sodium dodecyl sulfate (SDS) first shrink rapidly before attaining an equilibrium size. In the rapid dissolution regime, the time to obtain a new equilibrium is 30 ms regardless of SDS concentration, and the equilibrium radius achieved varies with the SDS concentration. To explain the lack of complete dissolution, we interpret the results by considering the effects of other gases (O2, N2) that are already dissolved in the aqueous phase, and we develop a multicomponent dissolution model that includes the effect of surface tension and the liquid pressure drop along the channel. Solutions of the model for a stationary gas bubble show good agreement with the experimental results, which lead to our conclusion that the equilibrium regime is obtained by gas exchange between the bubbles and liquid phase. Also, our observations from experiments and model calculations suggest that SDS molecules on the gas-liquid interface form a diffusion barrier, which controls the dissolution behaviour and the eventual equilibrium radius of the bubble.

Torque-actuated valves for microfluidics.

PubMed

Weibel, Douglas B; Kruithof, Maarten; Potenta, Scott; Sia, Samuel K; Lee, Andrew; Whitesides, George M

2005-08-01

This paper describes torque-actuated valves for controlling the flow of fluids in microfluidic channels. The valves consist of small machine screws (> or =500 microm) embedded in a layer of polyurethane cast above microfluidic channels fabricated in poly(dimethylsiloxane) (PDMS). The polyurethane is cured photochemically with the screws in place; on curing, it bonds to the surrounding layer of PDMS and forms a stiff layer that retains an impression of the threads of the screws. The valves were separated from the ceiling of microfluidic channels by a layer of PDMS and were integrated into channels using a simple procedure compatible with soft lithography and rapid prototyping. Turning the screws actuated the valves by collapsing the PDMS layer between the valve and channel, controlling the flow of fluids in the underlying channels. These valves have the useful characteristic that they do not require power to retain their setting (on/off). They also allow settings between "on" and "off" and can be integrated into portable, disposable microfluidic devices for carrying out sandwich immunoassays.

Whole-Teflon microfluidic chips

PubMed Central

Ren, Kangning; Dai, Wen; Zhou, Jianhua; Su, Jing; Wu, Hongkai

2011-01-01

Although microfluidics has shown exciting potential, its broad applications are significantly limited by drawbacks of the materials used to make them. In this work, we present a convenient strategy for fabricating whole-Teflon microfluidic chips with integrated valves that show outstanding inertness to various chemicals and extreme resistance against all solvents. Compared with other microfluidic materials [e.g., poly(dimethylsiloxane) (PDMS)] the whole-Teflon chip has a few more advantages, such as no absorption of small molecules, little adsorption of biomolecules onto channel walls, and no leaching of residue molecules from the material bulk into the solution in the channel. Various biological cells have been cultured in the whole-Teflon channel. Adherent cells can attach to the channel bottom, spread, and proliferate well in the channels (with similar proliferation rate to the cells in PDMS channels with the same dimensions). The moderately good gas permeability of the Teflon materials makes it suitable to culture cells inside the microchannels for a long time. PMID:21536918

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

Manipulation of cells' position across a microfluidic channel using a series of continuously varying herringbone structures

NASA Astrophysics Data System (ADS)

Jung, Yugyung; Hyun, Ji-chul; Choi, Jongchan; Atajanov, Arslan; Yang, Sung

2017-12-01

Controlling cells' movement is an important technique in biological analysis that is performed within a microfluidic system. Many external forces are utilized for manipulation of cells, including their position in the channel. These forces can effectively control cells in a desired manner. Most of techniques used to manipulate cells require sophisticated set-ups and equipment to generate desired effect. The exception to this is the use of hydrodynamic force. In this study, a series of continuously varying herringbone structures is proposed for positioning cells in a microfluidic channel using hydrodynamic force. This structure was experimentally developed by changing parameters, such as the length of the herringbone's apex, the length of the herringbone's base and the ratio of the height of the flat channel to the height of the herringbone structure. Results of this study, have demonstrated that the length of the herringbone's apex and the ratio of the heights of the flat channel and the herringbone structure were crucial parameters influencing positioning of cells at 100 μl/h flow rate. The final design was fixed at 170 and 80 μm for the length of herringbone's apex and the length of herringbone's base, respectively. The average position of cells in this device was 34 μm away from the side wall in a 200 μm wide channel. Finally, to substantiate a practical application of the herringbone structure for positioning, cells were randomly introduced into a microfluidic device, containing an array of trapping structures together with a series of herringbone structures along the channel. The cells were moved toward the trapping structure by the herringbone structure and the trapping efficiency was increased. Therefore, it is anticipated that this device will be utilized to continuously control cells' position without application of external forces.

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

PubMed

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

2009-08-12

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

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.

Burst pressure of phaseguide structures of different heights in all-polymer microfluidic channels

NASA Astrophysics Data System (ADS)

Garbarino, Francesca; Kistrup, Kasper; Rizzi, Giovanni; Fougt Hansen, Mikkel

2017-12-01

We present an experimental investigation of the burst/overflow pressure of water and a representative surfactant-containing buffer in microfluidic channels with phaseguide structures oriented at an angle of 90° to the channel length as a function of their height, h . The all-polymer chips were fabricated by injection moulding and sealed by ultrasonic welding. Channels with a height of 200 μ m and widths of 1 mm or 3 mm were investigated for five values of h between 8 μ m and 82 μ m. Phaseguide structures without branches and with branches at angles α   =  45°, 60° and 75° were studied. All phaseguide structures were found able to pin both liquids and the burst pressure was found to increase approximately linearly with the height of the phaseguide from about 100-350 Pa for water and from about 25-200 Pa for the buffer. The burst pressure was found not to depend on the channel width and it was only weakly influenced by the presence of a branch on the phaseguide. For phaseguides with a branch, the liquid was always found to burst at the branch location. The measured burst pressures were compared to those estimated using a simple theory. The knowledge obtained in this study enables simple tuning of liquid spreading and overflow in microfluidic channels by use of phaseguide structures with different heights and it also provides a set of systematic experimental data to be compared with simulations/theory.

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.

Comparison of separation performance of laser-ablated and wet-etched microfluidic devices

PubMed Central

Baker, Christopher A.; Bulloch, Rayford; Roper, Michael G.

2010-01-01

Laser ablation of glass allows for production of microfluidic devices without the need of hydrofluoric acid and photolithography. The goal of this study was to compare the separation performance of microfluidic devices produced using a low-cost laser ablation system and conventional wet etching. During laser ablation, cracking of the glass substrate was prevented by heating the glass to 300°C. A range of laser energy densities was found to produce channel depths ranging from 4 – 35 μm and channel widths from 118 – 162 μm. The electroosmotic flow velocity was lower in laser-ablated devices, 0.110 ± 0.005 cm s−1, as compared to wet-etched microfluidic chips, 0.126 ± 0.003 cm s−1. Separations of both small and large molecules performed on both wet- and laser-ablated devices were compared by examining limits of detection, theoretical plate count, and peak asymmetry. Laser-induced fluorescence detection limits were 10 pM fluorescein for both types of devices. Laser-ablated and wet-etched microfluidic chips had reproducible migration times with ≤ 2.8% RSD and peak asymmetries ranging from 1.0 – 1.8. Numbers of theoretical plates were between 2.8- and 6.2-fold higher on the wet-etched devices compared to laser-ablated devices. Nevertheless, resolution between small and large analytes was accomplished, which indicates that laser ablation may find an application in pedagogical studies of electrophoresis or microfluidic devices, or in settings where hydrofluoric acid cannot be used. PMID:20827468

Reactions in Droplets in Microfluidic Channels

PubMed Central

Song, Helen; Chen, Delai L.; Ismagilov, Rustem F.

2006-01-01

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights. PMID:17086584

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

PubMed

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

2005-08-12

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

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Inherently aligned microfluidic electrodes composed of liquid metal.

PubMed

So, Ju-Hee; Dickey, Michael D

2011-03-07

This paper describes the fabrication and characterization of microelectrodes that are inherently aligned with microfluidic channels and in direct contact with the fluid in the channels. Injecting low melting point alloys, such as eutectic gallium indium (EGaIn), into microchannels at room temperature (or just above room temperature) offers a simple way to fabricate microelectrodes. The channels that define the shape and position of the microelectrodes are fabricated simultaneously with other microfluidic channels (i.e., those used to manipulate fluids) in a single step; consequently, all of the components are inherently aligned. In contrast, conventional techniques require multiple fabrication steps and registration (i.e., alignment of the electrodes with the microfluidic channels), which are technically challenging. The distinguishing characteristic of this work is that the electrodes are in direct contact with the fluid in the microfluidic channel, which is useful for a number of applications such as electrophoresis. Periodic posts between the microelectrodes and the microfluidic channel prevent the liquid metal from entering the microfluidic channel during injection. A thin oxide skin that forms rapidly and spontaneously on the surface of the metal stabilizes mechanically the otherwise low viscosity, high surface tension fluid within the channel. Moreover, the injected electrodes vertically span the sidewalls of the channel, which allows for the application of uniform electric field lines throughout the height of the channel and perpendicular to the direction of flow. The electrodes are mechanically stable over operating conditions commonly used in microfluidic applications; the mechanical stability depends on the magnitude of the applied bias, the nature of the bias (DC vs. AC), and the conductivity of the solutions in the microfluidic channel. Electrodes formed using alloys with melting points above room temperature ensure mechanical stability over all of the

Particle-Based Microfluidic Device for Providing High Magnetic Field Gradients

NASA Technical Reports Server (NTRS)

Wong, Tak S. (Inventor); Lin, Adam Y. (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.

Collapse of triangular channels in a soft elastomer

NASA Astrophysics Data System (ADS)

Tepáyotl-Ramírez, Daniel; Lu, Tong; Park, Yong-Lae; Majidi, Carmel

2013-01-01

We extend classical solutions in contact mechanics to examine the collapse of channels in a soft elastomer. These channels have triangular cross-section and collapse when pressure is applied to the surrounding elastomer. Treating the walls of the channel as indenters that penetrate the channel base, we derive an algebraic mapping between pressure and cross-sectional area. These theoretical predictions are in strong agreement with results that we obtain through finite element analysis and experimental measurements. This is accomplished without data fitting and suggests that the theoretical approach may be generalized to a broad range of cross-sectional geometries in soft microfluidics.

Microfluidic process monitor for industrial solvent extraction system

DOEpatents

Gelis, Artem; Pereira, Candido; Nichols, Kevin Paul Flood

2016-01-12

The present invention provides a system for solvent extraction utilizing a first electrode with a raised area formed on its surface, which defines a portion of a microfluidic channel; a second electrode with a flat surface, defining another portion of the microfluidic channel that opposes the raised area of the first electrode; a reversibly deformable substrate disposed between the first electrode and second electrode, adapted to accommodate the raised area of the first electrode and having a portion that extends beyond the raised area of the first electrode, that portion defining the remaining portions of the microfluidic channel; and an electrolyte of at least two immiscible liquids that flows through the microfluidic channel. Also provided is a system for performing multiple solvent extractions utilizing several microfluidic chips or unit operations connected in series.

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

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

PubMed

Ge, Zhengwei; Wang, Wei; Yang, Chun

2015-02-09

This paper reports rapid microfluidic electrokinetic concentration of deoxyribonucleic acid (DNA) with the Joule heating induced temperature gradient focusing (TGF) by using our proposed combined AC and DC electric field technique. A peak of 480-fold concentration enhancement of DNA sample is achieved within 40s in a simple poly-dimethylsiloxane (PDMS) microfluidic channel of a sudden expansion in cross-section. Compared to a sole DC field, the introduction of an AC field can reduce DC field induced back-pressure and produce sufficient Joule heating effects, resulting in higher concentration enhancement. Within such microfluidic channel structure, negative charged DNA analytes can be concentrated at a location where the DNA electrophoretic motion is balanced with the bulk flow driven by DC electroosmosis under an appropriate temperature gradient field. A numerical model accounting for a combined AC and DC field and back-pressure driven flow effects is developed to describe the complex Joule heating induced TGF processes. The experimental observation of DNA concentration phenomena can be explained by the numerical model. Copyright © 2014 Elsevier B.V. All rights reserved.

Relaxation of microparticles exposed to hydrodynamic forces in microfluidic conduits.

PubMed

Janča, Josef; Halabalová, Věra; Polášek, Vladimír; Vašina, Martin; Menshikova, Anastasia Yu

2011-02-01

The behavior of microparticles exposed to gravitational and lift forces and to the velocity gradient in flow velocity profile formed in microfluidic conduits is studied from the viewpoint of the transient period (the relaxation) between the moment at which a particle starts to be transported by the hydrodynamic flow and the time at which it reaches an equilibrium position, characterized by a balance of all active forces. The theoretical model allowing the calculation of the relaxation time is proposed. The numerical calculus based on the proposed model is compared with the experimental data obtained under different experimental conditions, namely, for different lengths of microfluidic channels, different average linear velocities of the carrier liquid, and different sizes and densities of the particles used in the study. The results are important for the optimization of microfluidic separation units such as microthermal field-flow fractionation channels in which the separation or manipulation of the microparticles of various origin, synthetic, natural, biological, etc., is performed under similar experimental conditions but by applying an additional thermodynamic force.

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

PubMed

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

2017-08-22

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

Toward a solid-phase nucleic acid hybridization assay within microfluidic channels using immobilized quantum dots as donors in fluorescence resonance energy transfer.

PubMed

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

2011-01-01

The optical properties and surface area of quantum dots (QDs) have made them an attractive platform for the development of nucleic acid biosensors based on fluorescence resonance energy transfer (FRET). Solid-phase assays based on FRET using mixtures of immobilized QD-oligonucleotide conjugates (QD biosensors) have been developed. The typical challenges associated with solid-phase detection strategies include non-specific adsorption, slow kinetics of hybridization, and sample manipulation. The new work herein has considered the immobilization of QD biosensors onto the surfaces of microfluidic channels in order to address these challenges. Microfluidic flow can be used to dynamically control stringency by adjustment of the potential in an electrokinetic-based microfluidics environment. The shearing force, Joule heating, and the competition between electroosmotic and electrophoretic mobilities allow the optimization of hybridization conditions, convective delivery of target to the channel surface to speed hybridization, amelioration of adsorption, and regeneration of the sensing surface. Microfluidic flow can also be used to deliver (for immobilization) and remove QD biosensors. QDs that were conjugated with two different oligonucleotide sequences were used to demonstrate feasibility. One oligonucleotide sequence on the QD was available as a linker for immobilization via hybridization with complementary oligonucleotides located on a glass surface within a microfluidic channel. A second oligonucleotide sequence on the QD served as a probe to transduce hybridization with target nucleic acid in a sample solution. A Cy3 label on the target was excited by FRET using green-emitting CdSe/ZnS QD donors and provided an analytical signal to explore this detection strategy. The immobilized QDs could be removed under denaturing conditions by disrupting the duplex that was used as the surface linker and thus allowed a new layer of QD biosensors to be re-coated within the channel

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

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.

Flow rate-pressure drop relation for deformable shallow microfluidic channels

NASA Astrophysics Data System (ADS)

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

2018-04-01

Laminar flow in devices fabricated from soft materials causes deformation of the passage geometry, which affects the flow rate--pressure drop relation. For a given pressure drop, in channels with narrow rectangular cross-section, the flow rate varies as the cube of the channel height, so deformation can produce significant quantitative effects, including nonlinear dependence on the pressure drop [{Gervais, T., El-Ali, J., G\\"unther, A. \\& Jensen, K.\\ F.}\\ 2006 Flow-induced deformation of shallow microfluidic channels.\\ \\textit{Lab Chip} \\textbf{6}, 500--507]. Gervais et. al. proposed a successful model of the deformation-induced change in the flow rate by heuristically coupling a Hookean elastic response with the lubrication approximation for Stokes flow. However, their model contains a fitting parameter that must be found for each channel shape by performing an experiment. We present a perturbation approach for the flow rate--pressure drop relation in a shallow deformable microchannel using the theory of isotropic quasi-static plate bending and the Stokes equations under a lubrication approximation (specifically, the ratio of the channel's height to its width and of the channel's height to its length are both assumed small). Our result contains no free parameters and confirms Gervais et. al.'s observation that the flow rate is a quartic polynomial of the pressure drop. The derived flow rate--pressure drop relation compares favorably with experimental measurements.

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.

Analysis of Poiseuille Flow Property in Two-Dimensional Mi-cro Channels of Microfluidic Pneumatic Micro-Valve

NASA Astrophysics Data System (ADS)

Yang, Shaohua; Long, Wei; Chen, Yajun

2018-03-01

In this paper, the control mechanism and mathematical description of the microfluidic flow in the microfluidic process of the PDMS membrane type pneumatic micro-valve were studied. The velocity and pressure variation law of the velocity field inside micro valve was analyzed by numerical simulation method. The influence of the two kinds of inlet drive modes on the working effect and the pressure flow characteristics of the pneumatic micro-valve was studied. The structure of the elastic solid valve diaphragm under the dual action of the airway and the liquid channel was analyzed. Deformation and stress distribution. The results show that the gas flow in the gas flow channel under the diaphragm by the vacuum part of the role of the formation of a suction gas vortex, pressure-driven mode was easier under the diaphragm to produce a strong gas vortex, resulting in internal and external pressure to promote diaphragm cut-off liquid channel; In the pressure pneumatic mode, the stress at both ends of the diaphragm was smaller, the membrane was not easy to tear failure.

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.

In-plane cost-effective magnetically actuated valve for microfluidic applications

NASA Astrophysics Data System (ADS)

Pugliese, Marco; Ferrara, Francesco; Bramanti, Alessandro Paolo; Gigli, Giuseppe; Maiorano, Vincenzo

2017-04-01

We present a new in-plane magnetically actuated microfluidic valve. Its simple design includes a circular area joining two channels lying on the same plane. The area is parted by a septum lying on and adhering to a magneto-active polymeric ‘floor’ membrane, keeping the channels normally separated (valve closed). Under the action of a magnetic field, the membrane collapses, letting the liquid flow below the septum (valve open). The valve was extensively characterized experimentally, and modeled and optimized theoretically. The growing interest in lab on chips, especially for diagnostics and precision medicine, is driving researchers towards smart, efficient and low cost solutions to the management of biological samples. In this context, the valve developed in this work represents a useful building-block for microfluidic applications requiring precise flow control, its main features being easy and rapid manufacturing, biocompatibility and low cost.

Optofluidic droplet coalescence on a microfluidic chip

NASA Astrophysics Data System (ADS)

Jung, Jin Ho; Lee, Kyung Heon; Lee, Kang Soo; Cho, Hyunjun; Ha, Byung Hang; Destgeer, Ghulam; Sung, Hyung Jin

2013-11-01

Coalescence is the procedure that two or more droplets fuse during contact to form a larger droplet. Optofluidic droplet coalescence on a microfluidic chip was demonstrated with theoretical and experimental approaches. Droplets were produced in a T-junction geometry and their velocities and sizes were adjusted by flow rate. In order to bring them in a direct contact of coalescence, optical gradient force was used to trap the droplets. A theoretical modeling of the coalescence was derived by combining the optical force and drag force on the droplet. The analytical expression of the optical force on a sphere droplet was employed to estimate the trapping efficiency in the ray optics regime. The drag force acting on the droplet was calculated in terms of the fluid velocity, viscosity and the geometrical parameters of a microfluidic channel. The droplet coalescence was conducted in a microfluidic setup equipped with a 1064 CW laser, focusing optics, a syringe pump, a custom-made stage and a sCMOS camera. The droplets were successfully coalesced using the optical gradient force. The experimental data of coalescence were in good agreement with the prediction. This work was supported by the Creative Research Initiatives program (No.2013-003364) of the National Research Foundation of Korea (MSIP).

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.

Highly transparent and flexible circuits through patterning silver nanowires into microfluidic channels.

PubMed

Sun, Jing; Zhou, Wenhui; Yang, Haibo; Zhen, Xue; Ma, Longfei; Williams, Dirk; Sun, Xudong; Lang, Ming-Fei

2018-05-10

The development of flexible and transparent devices requires completely transparent and flexible circuits (TFCs). To overcome the disadvantages of the previously reported TFCs that are partially transparent, lacking pattern control, or labor consuming, we achieve true TFCs via a facile process with precise pattern control, exhibiting concurrent high transparency, conductivity, flexibility, stretchability, and robustness. A highly transparent and flexible conductive film is first made through spin coating silver nanowires (AgNWs) onto polydimethylsiloxane (PDMS), and demonstrates simultaneous high transparency (90.86%) and low sheet resistance (3.22 Ω sq-1). Taking advantage of microfluidic technology, circuits with ultraprecise and complex patterns from the microscale to milliscale are obtained through spin coating of AgNWs into microfluidic channels on PDMS. Without elaborate processing, this method may be suitable for mass production, which would contribute enormously to potential applications in wearable medical equipment and transparent electronic devices.

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

Expanding imaging capabilities for microfluidics: applicability of darkfield internal reflection illumination (DIRI) to observations in microfluidics.

PubMed

Kawano, Yoshihiro; Otsuka, Chino; Sanzo, James; Higgins, Christopher; Nirei, Tatsuo; Schilling, Tobias; Ishikawa, Takuji

2015-01-01

Microfluidics is used increasingly for engineering and biomedical applications due to recent advances in microfabrication technologies. Visualization of bubbles, tracer particles, and cells in a microfluidic device is important for designing a device and analyzing results. However, with conventional methods, it is difficult to observe the channel geometry and such particles simultaneously. To overcome this limitation, we developed a Darkfield Internal Reflection Illumination (DIRI) system that improved the drawbacks of a conventional darkfield illuminator. This study was performed to investigate its utility in the field of microfluidics. The results showed that the developed system could clearly visualize both microbubbles and the channel wall by utilizing brightfield and DIRI illumination simultaneously. The methodology is useful not only for static phenomena, such as clogging, but also for dynamic phenomena, such as the detection of bubbles flowing in a channel. The system was also applied to simultaneous fluorescence and DIRI imaging. Fluorescent tracer beads and channel walls were observed clearly, which may be an advantage for future microparticle image velocimetry (μPIV) analysis, especially near a wall. Two types of cell stained with different colors, and the channel wall, can be recognized using the combined confocal and DIRI system. Whole-slide imaging was also conducted successfully using this system. The tiling function significantly expands the observing area of microfluidics. The developed system will be useful for a wide variety of engineering and biomedical applications for the growing field of microfluidics.

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

PubMed

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

2013-03-15

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

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.

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.

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

Microfluidics-Based PCR for Fusion Transcript Detection.

PubMed

Chen, Hui

2016-01-01

The microfluidic technology allows the production of network of submillimeter-size fluidic channels and reservoirs in a variety of material systems. The microfluidic-based polymerase chain reaction (PCR) allows automated multiplexing of multiple samples and multiple assays simultaneously within a network of microfluidic channels and chambers that are co-ordinated in controlled fashion by the valves. The individual PCR reaction is performed in nanoliter volume, which allows testing on samples with limited DNA and RNA. The microfluidics devices are used in various types of PCR such as digital PCR and single molecular emulsion PCR for genotyping, gene expression, and miRNA expression. In this chapter, the use of a microfluidics-based PCR for simultaneous screening of 14 known fusion transcripts in patients with leukemia is described.

Motion of an elastic capsule in a square microfluidic channel.

PubMed

Kuriakose, S; Dimitrakopoulos, P

2011-07-01

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

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

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

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.

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

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

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

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.

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.

On-chip micropatterning of plastic (cylic olefin copolymer, COC) microfluidic channels for the fabrication of biomolecule microarrays using photografting methods.

PubMed

Pu, Qiaosheng; Oyesanya, Olufemi; Thompson, Bowlin; Liu, Shantang; Alvarez, Julio C

2007-01-30

This paper reports on the surface modification of plastic microfluidic channels to prepare different biomolecule micropatterns using ultraviolet (UV) photografting methods. The linkage chemistry is based upon UV photopolymerization of acryl monomers to generate thin films (0.01-6 microm) chemically linked to the organic backbone of the plastic surface. The commodity thermoplastic, cyclic olefin copolymer (COC) was selected to build microfluidic chips because of its significant UV transparency and easiness for microfabrication by molding techniques. Once the polyacrylic films were grafted on the COC surface using photomasks, micropatterns of proteins, DNA, and biotinlated conjugates were readily obtained by surface chemical reactions in one or two subsequent steps. The thickness of the photografted films can be tuned from several nanometers up to several micrometers, depending on the reaction conditions. The micropatterned films can be prepared inside the microfluidic channel (on-chip) or on open COC surfaces (off-chip) with densities of functional groups about 10(-7) mol/cm2. Characterization of these films was performed by attenuated-total-reflectance IR spectroscopy, fluorescence microscopy, profilometry, atomic force microscopy, and electrokinetic methods.

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

NASA Astrophysics Data System (ADS)

Caballero-Robledo, Gabriel; Guevara-Pantoja, Pablo

2014-11-01

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

Principles of transverse flow fractionation of microparticles in superhydrophobic channels.

PubMed

Asmolov, Evgeny S; Dubov, Alexander L; Nizkaya, Tatiana V; Kuehne, Alexander J C; Vinogradova, Olga I

2015-07-07

We propose a concept of fractionation of micron-sized particles in a microfluidic device with a bottom wall decorated by superhydrophobic stripes. The stripes are oriented at an angle α to the direction of a driving force, G, which generally includes an applied pressure gradient and gravity. Separation relies on the initial sedimentation of particles under gravity in the main forward flow, and their subsequent lateral deflection near a superhydrophobic wall due to generation of a secondary flow transverse to G. We provide some theoretical arguments allowing us to quantify the transverse displacement of particles in the microfluidic channel, and confirm the validity of theoretical predictions in test experiments with monodisperse fractions of microparticles. Our results can guide the design of superhydrophobic microfluidic devices for efficient sorting of microparticles with a relatively small difference in size and density.

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

NASA Astrophysics Data System (ADS)

Jindal, Rohit

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

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

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

Rapid mask prototyping for microfluidics.

PubMed

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

2016-03-01

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

Rapid mask prototyping for microfluidics

PubMed Central

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

2016-01-01

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks. PMID:27014396

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.

Inertial microfluidic physics.

PubMed

Amini, Hamed; Lee, Wonhee; Di Carlo, Dino

2014-08-07

Microfluidics has experienced massive growth in the past two decades, and especially with advances in rapid prototyping researchers have explored a multitude of channel structures, fluid and particle mixtures, and integration with electrical and optical systems towards solving problems in healthcare, biological and chemical analysis, materials synthesis, and other emerging areas that can benefit from the scale, automation, or the unique physics of these systems. Inertial microfluidics, which relies on the unconventional use of fluid inertia in microfluidic platforms, is one of the emerging fields that make use of unique physical phenomena that are accessible in microscale patterned channels. Channel shapes that focus, concentrate, order, separate, transfer, and mix particles and fluids have been demonstrated, however physical underpinnings guiding these channel designs have been limited and much of the development has been based on experimentally-derived intuition. Here we aim to provide a deeper understanding of mechanisms and underlying physics in these systems which can lead to more effective and reliable designs with less iteration. To place the inertial effects into context we also discuss related fluid-induced forces present in particulate flows including forces due to non-Newtonian fluids, particle asymmetry, and particle deformability. We then highlight the inverse situation and describe the effect of the suspended particles acting on the fluid in a channel flow. Finally, we discuss the importance of structured channels, i.e. channels with boundary conditions that vary in the streamwise direction, and their potential as a means to achieve unprecedented three-dimensional control over fluid and particles in microchannels. Ultimately, we hope that an improved fundamental and quantitative understanding of inertial fluid dynamic effects can lead to unprecedented capabilities to program fluid and particle flow towards automation of biomedicine, materials

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

PubMed

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

2016-09-01

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

Engineering and analysis of surface interactions in a microfluidic herringbone micromixer.

PubMed

Forbes, Thomas P; Kralj, Jason G

2012-08-07

We developed a computational model and theoretical framework to investigate the geometrical optimization of particle-surface interactions in a herringbone micromixer. The enhancement of biomolecule- and particle-surface interactions in microfluidic devices through mixing and streamline disruption holds promise for a variety of applications. This analysis provides guidelines for optimizing the frequency and specific location of surface interactions based on the flow pattern and relative hydraulic resistance between a groove and the effective channel. The channel bottom, i.e., channel surface between grooves, was identified as the dominant location for surface contact. In addition, geometries that decrease the groove-to-channel hydraulic resistance improve contact with the channel top. Thus, herringbone mixers appear useful for a variety of surface-interaction applications, yet they have largely not been employed in an optimized fashion.

Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

PubMed

Salari, A; Gnyawali, V; Griffiths, I M; Karshafian, R; Kolios, M C; Tsai, S S H

2017-11-29

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 μm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 μm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 μm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

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

2013-08-07

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

A picoliter-volume mixer for microfluidic analytical systems.

PubMed

He, B; Burke, B J; Zhang, X; Zhang, R; Regnier, F E

2001-05-01

Mixing confluent liquid streams is an important, but difficult operation in microfluidic systems. This paper reports the construction and characterization of a 100-pL mixer for liquids transported by electroosmotic flow. Mixing was achieved in a microfabricated device with multiple intersecting channels of varying lengths and a bimodal width distribution. All channels running parallel to the direction of flow were 5 microm in width whereas larger 27-microm-width channels ran back and forth through the parallel channel network at a 45 degrees angle. The channel network composing the mixer was approximately 10 microm deep. It was observed that little mixing of the confluent solvent streams occurred in the 100-microm-wide, 300-microm-long mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, after passage through the channel network in the approximately 200-microm-length static mixer bed, mixing was complete as determined by confocal microscopy and CCD detection. Theoretical simulations were also performed in an attempt to describe the extent of mixing in microfabricated systems.

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

NASA Astrophysics Data System (ADS)

Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

2016-11-01

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

A multi-functional bubble-based microfluidic system

PubMed Central

Khoshmanesh, Khashayar; Almansouri, Abdullah; Albloushi, Hamad; Yi, Pyshar; Soffe, Rebecca; Kalantar-zadeh, Kourosh

2015-01-01

Recently, the bubble-based systems have offered a new paradigm in microfluidics. Gas bubbles are highly flexible, controllable and barely mix with liquids, and thus can be used for the creation of reconfigurable microfluidic systems. In this work, a hydrodynamically actuated bubble-based microfluidic system is introduced. This system enables the precise movement of air bubbles via axillary feeder channels to alter the geometry of the main channel and consequently the flow characteristics of the system. Mixing of neighbouring streams is demonstrated by oscillating the bubble at desired displacements and frequencies. Flow control is achieved by pushing the bubble to partially or fully close the main channel. Patterning of suspended particles is also demonstrated by creating a large bubble along the sidewalls. Rigorous analytical and numerical calculations are presented to describe the operation of the system. The examples presented in this paper highlight the versatility of the developed bubble-based actuator for a variety of applications; thus providing a vision that can be expanded for future highly reconfigurable microfluidics. PMID:25906043

Site-specific protein immobilization in a microfluidic chip channel via an IEF-gelation process.

PubMed

Shi, Mianhong; Peng, Youyuan; Yu, Shaoning; Liu, Baohong; Kong, Jilie

2007-05-01

A novel strategy for site-specific protein immobilization via combining chip IEF with low-temperature sol-gel technology, called IEF-GEL here, in the channel of a modified poly(methyl methacrylate) (PMMA) microfluidic chip is proposed in this work. The IEF-GEL process involves firstly IEF for homogeneously dissolved protein in PBS containing alumina sol and carrier ampholyte with prearranged pH gradient, and then gelation locally for protein encapsulation. The process and feasibility of proposed IEF-GEL were investigated by EOF measurements, fluorescence microscopic photography, Raman spectrum and further demonstrated by glucose oxidase (GOx) reactors integrated with end-column electrochemical detection. Site-controllable immobilization of protein was realized in a 30 mm long microfluidic chip channel by the strategy to create a approximately 1.7 mm concentrated FITC-BSA band, which leads to great improvement of the elute peak shape, accomplished with remarkably increased sensitivity, approximately 20 times higher than that without IEF-GEL treatment to GOx reactors. The kinetic response of GOx after IEF-GEL treatment was also investigated. The proposed system holds the advantages of IEF and low-temperature sol-gel technologies, i.e. concentrating the protein to be focused and retaining the biological activity for the gel-embedded protein, thus realizes site-specific immobilization of low-concentration protein at nL volume level.

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

PubMed

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

2015-11-01

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

Pulsed laser triggered high speed microfluidic switch

NASA Astrophysics Data System (ADS)

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

2008-10-01

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

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).

Micro-fluidic channels on nanopatterned substrates: Monitoring protein binding to lipid bilayers with surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

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

2010-04-01

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 micro-fluidic 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.

Microfluidic channel flow cell for simultaneous cryoelectrochemical electron spin resonance.

PubMed

Wain, Andrew J; Compton, Richard G; Le Roux, Rudolph; Matthews, Sinead; Fisher, Adrian C

2007-03-01

A novel microfluidic electrochemical channel flow cell has been constructed for in situ operation in a cylindrical TE011 resonant ESR cavity under variable temperature conditions. The cell has a U-tube configuration, consisting of an inlet and outlet channel which run parallel and contain evaporated gold film working, pseudo-reference, and counter electrodes. This geometry was employed to permit use in conjunction with variable temperature apparatus which does not allow a flow-through approach. The cell is characterized qualitatively and quantitatively using the one-electron reduction of p-bromonitrobenzene in acetonitrile at room temperature as a model system, and the ESR signal-flow rate response is validated by use of three-dimensional digital simulation of the concentration profile for a stable electrogenerated radical species under hydrodynamic conditions. The cell is then used to obtain ESR spectra for a number of radical species in acetonitrile at 233 K, including the radical anions of m- and p-iodonitrobenzene, o-bromonitrobenzene, and m-nitrobenzyl chloride, the latter three being unstable at room temperature. Spectra are also presented for the radical anion of 2-chloranthraquinone and the crystal violet radical, which display improved resolution at low temperatures.

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

PubMed

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

2009-05-07

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

Polymer-based platform for microfluidic systems

DOEpatents

Benett, William [Livermore, CA; Krulevitch, Peter [Pleasanton, CA; Maghribi, Mariam [Livermore, CA; Hamilton, Julie [Tracy, CA; Rose, Klint [Boston, MA; Wang, Amy W [Oakland, CA

2009-10-13

A method of forming a polymer-based microfluidic system platform using network building blocks selected from a set of interconnectable network building blocks, such as wire, pins, blocks, and interconnects. The selected building blocks are interconnectably assembled and fixedly positioned in precise positions in a mold cavity of a mold frame to construct a three-dimensional model construction of a microfluidic flow path network preferably having meso-scale dimensions. A hardenable liquid, such as poly (dimethylsiloxane) is then introduced into the mold cavity and hardened to form a platform structure as well as to mold the microfluidic flow path network having channels, reservoirs and ports. Pre-fabricated elbows, T's and other joints are used to interconnect various building block elements together. After hardening the liquid the building blocks are removed from the platform structure to make available the channels, cavities and ports within the platform structure. Microdevices may be embedded within the cast polymer-based platform, or bonded to the platform structure subsequent to molding, to create an integrated microfluidic system. In this manner, the new microfluidic platform is versatile and capable of quickly generating prototype systems, and could easily be adapted to a manufacturing setting.

Microfluidic quadrupole and floating concentration gradient.

PubMed

Qasaimeh, Mohammad A; Gervais, Thomas; Juncker, David

2011-09-06

The concept of fluidic multipoles, in analogy to electrostatics, has long been known as a particular class of solutions of the Navier-Stokes equation in potential flows; however, experimental observations of fluidic multipoles and of their characteristics have not been reported yet. Here we present a two-dimensional microfluidic quadrupole and a theoretical analysis consistent with the experimental observations. The microfluidic quadrupole was formed by simultaneously injecting and aspirating fluids from two pairs of opposing apertures in a narrow gap formed between a microfluidic probe and a substrate. A stagnation point was formed at the centre of the microfluidic quadrupole, and its position could be rapidly adjusted hydrodynamically. Following the injection of a solute through one of the poles, a stationary, tunable, and movable-that is, 'floating'-concentration gradient was formed at the stagnation point. Our results lay the foundation for future combined experimental and theoretical exploration of microfluidic planar multipoles including convective-diffusive phenomena.

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.

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

PubMed Central

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

2014-01-01

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

Applications of Microfluidics in Quantitative Biology.

PubMed

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

2018-05-01

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

Design of a rapid magnetic microfluidic mixer

NASA Astrophysics Data System (ADS)

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

2015-11-01

Using three-dimensional simulations and experiments, we demonstrate rapid mixing of fluid streams in a microchannel using orbiting magnetic microbeads. We use a lattice Boltzmann model coupled to a Brownian dynamics model to perform numerical simulations that study in depth the effect of system parameters such as channel configuration and fluid and bead velocities. We use our findings to aid the design of an experimental micromixer. Using this experimental device, we demonstrate rapid microfluidic mixing over a compact channel length, and validate our numerical simulation results. Finally, we use numerical simulations to study the physical mechanisms leading to microfluidic mixing in our system. Our findings demonstrate a promising method of rapid microfluidic mixing over a short distance, with applications in lab-on-a-chip sample testing.

Shear-driven motion of supported lipid bilayers in microfluidic channels.

PubMed

Jönsson, Peter; Beech, Jason P; Tegenfeldt, Jonas O; Höök, Fredrik

2009-04-15

In this work, we demonstrate how a lateral motion of a supported lipid bilayer (SLB) and its constituents can be created without relying on self-spreading forces. The force driving the SLB is instead a viscous shear force arising from a pressure-driven bulk flow acting on the SLB that is formed on a glass wall inside a microfluidic channel. In contrast to self-spreading bilayers, this method allows for accurate control of the bilayer motion by altering the bulk flow in the channel. Experiments showed that an egg yolk phosphatidylcholine SLB formed on a glass support moved in a rolling motion under these shear forces, with the lipids in the upper leaflet of the bilayer moving at twice the velocity of the bilayer front. The drift velocity of different lipid probes in the SLB was observed to be sensitive to the interactions between the lipid probe and the surrounding molecules, resulting in drift velocities that varied by up to 1 order of magnitude for the different lipid probes in our experiments. Since the method provides a so far unattainable control of the motion of all molecules in an SLB, we foresee great potential for this technique, alone or in combination with other methods, for studies of lipid bilayers and different membrane-associated molecules.

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.

Reconfigurable microfluidic device with discretized sidewall

PubMed Central

Oono, Masahiro; Yamaguchi, Keisuke; Rasyid, Amirul; Takano, Atsushi; Tanaka, Masato

2017-01-01

Various microfluidic features, such as traps, have been used to manipulate flows, cells, and other particles within microfluidic systems. However, these features often become undesirable in subsequent steps requiring different fluidic configurations. To meet the changing needs of various microfluidic configurations, we developed a reconfigurable microfluidic channel with movable sidewalls using mechanically discretized sidewalls of laterally aligned rectangular pins. The user can deform the channel sidewall at any time after fabrication by sliding the pins. We confirmed that the flow resistance of the straight microchannel could be reversibly adjusted in the range of 101–105 Pa s/μl by manually displacing one of the pins comprising the microchannel sidewall. The reconfigurable microchannel also made it possible to manipulate flows and cells by creating a segmented patterned culture of COS-7 cells and a coculture of human umbilical vein endothelial cells (HUVECs) and human lung fibroblasts (hLFs) inside the microchannel. The reconfigurable microfluidic device successfully maintained a culture of COS-7 cells in a log phase throughout the entire period of 216 h. Furthermore, we performed a migration assay of cocultured HUVEC and hLF spheroids within one microchannel and observed their migration toward each other. PMID:28503247

Droplet motion in microfluidic networks: Hydrodynamic interactions and pressure-drop measurements

NASA Astrophysics Data System (ADS)

Sessoms, D. A.; Belloul, M.; Engl, W.; Roche, M.; Courbin, L.; Panizza, P.

2009-07-01

We present experimental, numerical, and theoretical studies of droplet flows in hydrodynamic networks. Using both millifluidic and microfluidic devices, we study the partitioning of monodisperse droplets in an asymmetric loop. In both cases, we show that droplet traffic results from the hydrodynamic feedback due to the presence of droplets in the outlet channels. We develop a recently-introduced phenomenological model [W. Engl , Phys. Rev. Lett. 95, 208304 (2005)] and successfully confront its predictions to our experimental results. This approach offers a simple way to measure the excess hydrodynamic resistance of a channel filled with droplets. We discuss the traffic behavior and the variations in the corresponding hydrodynamic resistance length Ld and of the droplet mobility β , as a function of droplet interdistance and confinement for channels having circular or rectangular cross sections.

Mechanically activated artificial cell by using microfluidics

NASA Astrophysics Data System (ADS)

Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

2016-09-01

All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology.

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

A compact model for electroosmotic flows in microfluidic devices

NASA Astrophysics Data System (ADS)

Qiao, R.; Aluru, N. R.

2002-09-01

A compact model to compute flow rate and pressure in microfluidic devices is presented. The microfluidic flow can be driven by either an applied electric field or a combined electric field and pressure gradient. A step change in the ζ-potential on a channel wall is treated by a pressure source in the compact model. The pressure source is obtained from the pressure Poisson equation and conservation of mass principle. In the proposed compact model, the complex fluidic network is simplified by an electrical circuit. The compact model can predict the flow rate, pressure distribution and other basic characteristics in microfluidic channels quickly with good accuracy when compared to detailed numerical simulation. Using the compact model, fluidic mixing and dispersion control are studied in a complex microfluidic network.

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

Lab-on-CMOS integration of microfluidics and electrochemical sensors.

PubMed

Huang, Yue; Mason, Andrew J

2013-10-07

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.

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

PubMed

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

2013-09-07

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

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

PubMed

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

2010-10-01

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

Complementary Split-Ring Resonator-Loaded Microfluidic Ethanol Chemical Sensor.

PubMed

Salim, Ahmed; Lim, Sungjoon

2016-10-28

In this paper, a complementary split-ring resonator (CSRR)-loaded patch is proposed as a microfluidic ethanol chemical sensor. The primary objective of this chemical sensor is to detect ethanol's concentration. First, two tightly coupled concentric CSRRs loaded on a patch are realized on a Rogers RT/Duroid 5870 substrate, and then a microfluidic channel engraved on polydimethylsiloxane (PDMS) is integrated for ethanol chemical sensor applications. The resonant frequency of the structure before loading the microfluidic channel is 4.72 GHz. After loading the microfluidic channel, the 550 MHz shift in the resonant frequency is ascribed to the dielectric perturbation phenomenon when the ethanol concentration is varied from 0% to 100%. In order to assess the sensitivity range of our proposed sensor, various concentrations of ethanol are tested and analyzed. Our proposed sensor exhibits repeatability and successfully detects 10% ethanol as verified by the measurement set-up. It has created headway to a miniaturized, non-contact, low-cost, reliable, reusable, and easily fabricated design using extremely small liquid volumes.

Complementary Split-Ring Resonator-Loaded Microfluidic Ethanol Chemical Sensor

PubMed Central

Salim, Ahmed; Lim, Sungjoon

2016-01-01

In this paper, a complementary split-ring resonator (CSRR)-loaded patch is proposed as a microfluidic ethanol chemical sensor. The primary objective of this chemical sensor is to detect ethanol’s concentration. First, two tightly coupled concentric CSRRs loaded on a patch are realized on a Rogers RT/Duroid 5870 substrate, and then a microfluidic channel engraved on polydimethylsiloxane (PDMS) is integrated for ethanol chemical sensor applications. The resonant frequency of the structure before loading the microfluidic channel is 4.72 GHz. After loading the microfluidic channel, the 550 MHz shift in the resonant frequency is ascribed to the dielectric perturbation phenomenon when the ethanol concentration is varied from 0% to 100%. In order to assess the sensitivity range of our proposed sensor, various concentrations of ethanol are tested and analyzed. Our proposed sensor exhibits repeatability and successfully detects 10% ethanol as verified by the measurement set-up. It has created headway to a miniaturized, non-contact, low-cost, reliable, reusable, and easily fabricated design using extremely small liquid volumes. PMID:27801842

Microfluidic Pneumatic Logic Circuits and Digital Pneumatic Microprocessors for Integrated Microfluidic Systems

PubMed Central

Rhee, Minsoung

2010-01-01

We have developed pneumatic logic circuits and microprocessors built with microfluidic channels and valves in polydimethylsiloxane (PDMS). The pneumatic logic circuits perform various combinational and sequential logic calculations with binary pneumatic signals (atmosphere and vacuum), producing cascadable outputs based on Boolean operations. A complex microprocessor is constructed from combinations of various logic circuits and receives pneumatically encoded serial commands at a single input line. The device then decodes the temporal command sequence by spatial parallelization, computes necessary logic calculations between parallelized command bits, stores command information for signal transportation and maintenance, and finally executes the command for the target devices. Thus, such pneumatic microprocessors will function as a universal on-chip control platform to perform complex parallel operations for large-scale integrated microfluidic devices. To demonstrate the working principles, we have built 2-bit, 3-bit, 4-bit, and 8-bit microprecessors to control various target devices for applications such as four color dye mixing, and multiplexed channel fluidic control. By significantly reducing the need for external controllers, the digital pneumatic microprocessor can be used as a universal on-chip platform to autonomously manipulate microfluids in a high throughput manner. PMID:19823730

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

PubMed

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

2005-06-01

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

Simulation of magnetic particles in microfluidic channels

NASA Astrophysics Data System (ADS)

Gusenbauer, Markus; Schrefl, Thomas

2018-01-01

In the field of biomedicine the applications of magnetic beads have increased immensely in the last decade. Drug delivery, magnetic resonance imaging, bioseparation or hyperthermia are only a small excerpt of their usage. Starting from microscaled particles the research is focusing more and more on nanoscaled particles. We are investigating and validating a method for simulating magnetic beads in a microfluidic flow which will help to manipulate beads in a controlled and reproducible manner. We are using the soft-matter simulation package ESPResSo to simulate magnetic particle dynamics in a lattice Boltzmann flow and applied external magnetic fields. Laminar as well as turbulent flow conditions in microfluidic systems can be analyzed while particles tend to agglomerate due to magnetic interactions. The proposed simulation methods are validated with experiments from literature.

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

PubMed

Le, Ngoc Tam; Kim, Jong Sung

2014-12-01

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

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

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.

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.

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

DOE PAGES

Gai, Ya; Min Leong, Chia; Cai, Wei; ...

2016-10-10

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

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.

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

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

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

PubMed

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

2012-12-01

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

Development of a Pressure Switched Microfluidic Cell Sorter

NASA Astrophysics Data System (ADS)

Ozbay, Baris; Jones, Alex; Gibson, Emily

2009-10-01

Lab on a chip technology allows for the replacement of traditional cell sorters with microfluidic devices which can be produced less expensively and are more compact. Additionally, the compact nature of microfluidic cell sorters may lead to the realization of their application in point-of-care medical devices. Though techniques have been demonstrated previously for sorting in microfluidic devices with optical or electro-osmotic switching, both of these techniques are expensive and more difficult to implement than pressure switching. This microfluidic cell sorter design also allows for easy integration with optical spectroscopy for identification of cell type. Our current microfluidic device was fabricated with polydimethylsiloxane (PDMS), a polymer that houses the channels, which is then chemically bonded to a glass slide. The flow of fluid through the device is controlled by pressure controllers, and the switching of the cells is accomplished with the use of a high performance pressure controller interfaced with a computer. The cells are fed through the channels with the use of hydrodynamic focusing techniques. Once the experimental setup is fully functional the objective will be to determine switching rates, explore techniques to optimize these rates, and experiment with sorting of other biomolecules including DNA.

Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping

PubMed Central

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

2015-01-01

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

Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices.

PubMed

Hulme, S Elizabeth; Shevkoplyas, Sergey S; Whitesides, George M

2009-01-07

This paper describes a method for prefabricating screw, pneumatic, and solenoid valves and embedding them in microfluidic devices. This method of prefabrication and embedding is simple, requires no advanced fabrication, and is compatible with soft lithography. Because prefabrication allows many identical valves to be made at one time, the performance across different valves made in the same manner is reproducible. In addition, the performance of a single valve is reproducible over many cycles of opening and closing: an embedded solenoid valve opened and closed a microfluidic channel more than 100,000 times with no apparent deterioration in its function. It was possible to combine all three types of prefabricated valves in a single microfluidic device to control chemical gradients in a microfluidic channel temporally and spatially.

Calibration of optical coherence tomography angiography with a microfluidic chip

NASA Astrophysics Data System (ADS)

Su, Johnny P.; Chandwani, Rahul; Gao, Simon S.; Pechauer, Alex D.; Zhang, Miao; Wang, Jie; Jia, Yali; Huang, David; Liu, Gangjun

2016-08-01

A microfluidic chip with microchannels ranging from 8 to 96 μm was used to mimic blood vessels down to the capillary level. Blood flow within the microfluidic channels was analyzed with split-spectrum amplitude-decorrelation angiography (SSADA)-based optical coherence tomography (OCT) angiography. It was found that the SSADA decorrelation value was related to both blood flow speed and channel width. SSADA could differentiate nonflowing blood inside the microfluidic channels from static paper. The SSADA decorrelation value was approximately linear with blood flow velocity up to a threshold Vsat of 5.83±1.33 mm/s (mean±standard deviation over the range of channel widths). Beyond this threshold, it approached a saturation value Dsat. Dsat was higher for wider channels, and approached a maximum value Dsm as the channel width became much larger than the beam focal spot diameter. These results indicate that decorrelation values (flow signal) in capillary networks would be proportional to both flow velocity and vessel caliber but would be capped at a saturation value in larger blood vessels. These findings are useful for interpretation and quantification of clinical OCT angiography results.

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

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

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…

Open-source, community-driven microfluidics with Metafluidics.

PubMed

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

2017-06-07

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

Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices

PubMed Central

Hulme, S. Elizabeth; Shevkoplyas, Sergey S.

2011-01-01

This paper describes a method for prefabricating screw, pneumatic, and solenoid valves and embedding them in microfluidic devices. This method of prefabrication and embedding is simple, requires no advanced fabrication, and is compatible with soft lithography. Because prefabrication allows many identical valves to be made at one time, the performance across different valves made in the same manner is reproducible. In addition, the performance of a single valve is reproducible over many cycles of opening and closing: an embedded solenoid valve opened and closed a microfluidic channel more than 100,000 times with no apparent deterioration in its function. It was possible to combine all three types of prefabricated valves in a single microfluidic device to control chemical gradients in a microfluidic channel temporally and spatially. PMID:19209338

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

PubMed

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

2015-09-01

Electric fields offer a variety of functionalities to Lab-on-a-Chip devices. The use of these fields often results in significant Joule heating, affecting the overall performance of the system. Precise knowledge of the temperature profile inside a microfluidic device is necessary to evaluate the implications of heat dissipation. This article demonstrates how an optically trapped microsphere can be used as a temperature probe to monitor Joule heating in these devices. The Brownian motion of the bead at room temperature is compared with the motion when power is dissipated in the system. This gives an estimate of the temperature increase at a specific location in a microfluidic channel. We demonstrate this method with solutions of different ionic strengths, and establish a precision of 0.9 K and an accuracy of 15%. Furthermore, it is demonstrated that transient heating processes can be monitored with this technique, albeit with a limited time resolution. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preliminary assessment for DNA extraction on microfluidic channel

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

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

PubMed Central

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.

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.

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

NASA Astrophysics Data System (ADS)

Chung, Daehan; Gray, Bonnie L.

2017-11-01

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

Electrokinetic focusing injection methods on microfluidic devices.

PubMed

Fu, Lung-Ming; Yang, Ruey-Jen; Lee, Gwo-Bin

2003-04-15

This paper presents an experimental and numerical investigation into electrokinetic focusing injection on microfluidic chips. The valving characteristics on microfluidic devices are controlled through appropriate manipulations of the electric potential strengths during the sample loading and dispensing steps. The present study also addresses the design and testing of various injection systems used to deliver a sample plug. A novel double-cross injection microfluidic chip is fabricated, which employs electrokinetic focusing to deliver sample plugs of variable volume. The proposed design combines several functions of traditional sample plug injection systems on a single microfluidic chip. The injection technique uses an unique sequence of loading steps with different electric potential distributions and magnitudes within the various channels to effectuate a virtual valve.

3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations—a Mini Review

PubMed Central

Chen, Chengpeng; Mehl, Benjamin T.; Munshi, Akash S.; Townsend, Alexandra D.; Spence, Dana M.; Martin, R. Scott

2016-01-01

A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field. PMID:27617038

3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations-a Mini Review.

PubMed

Chen, Chengpeng; Mehl, Benjamin T; Munshi, Akash S; Townsend, Alexandra D; Spence, Dana M; Martin, R Scott

2016-08-21

A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field.

Detection of Micrococcus luteus biofilm formation in microfluidic environments by pH measurement using an ion-sensitive field-effect transistor.

PubMed

Matsuura, Koji; Asano, Yuka; Yamada, Akira; Naruse, Keiji

2013-02-18

Biofilm formation in microfluidic channels is difficult to detect because sampling volumes are too small for conventional turbidity measurements. To detect biofilm formation, we used an ion-sensitive field-effect transistor (ISFET) measurement system to measure pH changes in small volumes of bacterial suspension. Cells of Micrococcus luteus (M. luteus) were cultured in polystyrene (PS) microtubes and polymethylmethacrylate (PMMA)-based microfluidic channels laminated with polyvinylidene chloride. In microtubes, concentrations of bacteria and pH in the suspension were analyzed by measuring turbidity and using an ISFET sensor, respectively. In microfluidic channels containing 20 μL of bacterial suspension, we measured pH changes using the ISFET sensor and monitored biofilm formation using a microscope. We detected acidification and alkalinization phases of M. luteus from the ISFET sensor signals in both microtubes and microfluidic channels. In the alkalinization phase, after 2 day culture, dense biofilm formation was observed at the bottom of the microfluidic channels. In this study, we used an ISFET sensor to detect biofilm formation in clinical and industrial microfluidic environments by detecting alkalinization of the culture medium. 

Identification of viscous droplets' physical properties that determine droplet behaviors in inertial microfluidics

NASA Astrophysics Data System (ADS)

Hur, Soojung Claire

2013-11-01

Inertial effects in microfluidic systems have recently recognized as a robust and passive way of focusing and ordering microscale particles and cells continuously. Moreover, theoretical analysis has shown that there exists a force away from channel walls in Poiseuille flow that locates deformable particles closer to the channel center than rigid counterparts. Then, the particle deformability can be extrapolated from the positions of particles with known sizes in the channel. Here, behaviors of various viscous droplets in inertial flow were investigated to identify critical properties determining their dynamic lateral position. Fluorinated oil solutions (μ = 1.7 mPas and 5 mPas) containing droplets (1mPas< μ<1.3Pas) were injected into a microfluidic channel with a syringe pump (8 < Rc < 50). Interfacial tension between aqueous and oil phases were varied by adding controlled amount of a surfactant. The diameter, a, deformability, Def, and dynamic lateral position, Xeq, were determined using high-speed microscopy. Xeq, was found to correlate with the particle Capillary Number, CaP, regardless of droplet viscosities when CaP <0.02 or CaP >0.2, suggesting that the viscous drag from the continuous phase and the interfacial tension were competing factors determining Xeq. Experimental results suggested that (i) interplay among droplet's viscosity, interfacial tension and inertia of carrier fluid determines dynamic lateral position of droplets and (ii) the dominant property varies at a different regime.

Flow distribution in parallel microfluidic networks and its effect on concentration gradient

PubMed Central

Guermonprez, Cyprien; Michelin, Sébastien; Baroud, Charles N.

2015-01-01

The architecture of microfluidic networks can significantly impact the flow distribution within its different branches and thereby influence tracer transport within the network. In this paper, we study the flow rate distribution within a network of parallel microfluidic channels with a single input and single output, using a combination of theoretical modeling and microfluidic experiments. Within the ladder network, the flow rate distribution follows a U-shaped profile, with the highest flow rate occurring in the initial and final branches. The contrast with the central branches is controlled by a single dimensionless parameter, namely, the ratio of hydrodynamic resistance between the distribution channel and the side branches. This contrast in flow rates decreases when the resistance of the side branches increases relative to the resistance of the distribution channel. When the inlet flow is composed of two parallel streams, one of which transporting a diffusing species, a concentration variation is produced within the side branches of the network. The shape of this concentration gradient is fully determined by two dimensionless parameters: the ratio of resistances, which determines the flow rate distribution, and the Péclet number, which characterizes the relative speed of diffusion and advection. Depending on the values of these two control parameters, different distribution profiles can be obtained ranging from a flat profile to a step distribution of solute, with well-distributed gradients between these two limits. Our experimental results are in agreement with our numerical model predictions, based on a simplified 2D advection-diffusion problem. Finally, two possible applications of this work are presented: the first one combines the present design with self-digitization principle to encapsulate the controlled concentration in nanoliter chambers, while the second one extends the present design to create a continuous concentration gradient within an open flow

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.

Paper-based microfluidic devices by asymmetric calendaring

PubMed Central

Oyola-Reynoso, S.; Frankiewicz, C.; Chang, B.; Chen, J.; Bloch, J.-F.

2017-01-01

We report a simple, efficient, one-step, affordable method to produce open-channel paper-based microfluidic channels. One surface of a sheet of paper is selectively calendared, with concomitant hydrophobization, to create the microfluidic channel. Our method involves asymmetric mechanical modification of a paper surface using a rolling ball (ball-point pen) under a controlled amount of applied stress (σz) to ascertain that only one side is modified. A lubricating solvent (hexane) aids in the selective deformation. The lubricant also serves as a carrier for a perfluoroalkyl trichlorosilane allowing the channel to be made hydrophobic as it is formed. For brevity and clarity, we abbreviated this method as TACH (Targeted Asymmetric Calendaring and Hydrophobization). We demonstrate that TACH can be used to reliably produce channels of variable widths (size of the ball) and depths (number of passes), without affecting the nonworking surface of the paper. Using tomography, we demonstrate that these channels can vary from 10s to 100s of microns in diameter. The created hydrophobic barrier extends around the channel through wicking to ensure no leakages. We demonstrate, through modeling and fabrication, that flow properties of the resulting channels are analogous to conventional devices and are tunable based on associated dimensionless numbers. PMID:28798839

Amorphous silicon balanced photodiode for microfluidic applications

NASA Astrophysics Data System (ADS)

Caputo, Domenico; de Cesare, Giampiero; Nascetti, Augusto; Scipinotti, Riccardo

2013-05-01

In this paper, we present the first integration of an amorphous silicon balanced photosensor with a microfluidic network to perform on-chip detection for biomedical applications, where rejection of large background light intensity is needed. This solution allows to achieve high resolution readout without the need of high dynamic range electronics. The balanced photodiode is constituted by two series-connected a-Si:H/a-SiC:H n-i-p stacked junctions, deposited on a glass substrate. The structure is a three terminal device where two electrodes bias the two diodes in reverse conditions while the third electrode (i.e. the connection point of the two diodes) provides the output signal given by the differential current. The microfluidic network is composed of two channels made in PolyDimetilSiloxane (PDMS) positioned over the glass substrate on the photodiode-side aligning each channel with a diode. This configuration guarantees an optimal optical coupling between luminescence events occurring in the channels and the photosensors. The experiments have been carried out measuring the differential current in identical and different conditions for the two channels. We have found that: the measurement dynamic range can be increased by at least an order of magnitude with respect to conventional photodiodes; the balanced photodiode is able to detect the presence or absence of water in the channel; the presence of fluorescent molecules in the channel can be successful detected by our device without any need of optical filter for the excitation light. These preliminary results demonstrate the successful integration of a microfluidic network with a-Si:H photosensor for on-chip detection in biomedical applications.

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.

Simple, low-cost fabrication of semi-circular channel using the surface tension of solder paste and its application to microfluidic valves.

PubMed

Yan, Sheng; Li, Yuxing; Zhu, Yuanqing; Liu, Minsu; Zhao, Qianbin; Yuan, Dan; Yun, Guolin; Zhang, Shiwu; Wen, Weijia; Tang, Shi-Yang; Li, Weihua

2018-06-01

This work presents a simple, low-cost method to fabricate semi-circular channels using solder paste, which can amalgamate the cooper surface to form a half-cylinder mold using the surface tension of Sn-Pd alloy (the main component in solder paste). This technique enables semi-circular channels to be manufactured with different dimensions. These semi-circular channels will then be integrated with a polymethylmethacrylate frame and machine screws to create miniaturized, portable microfluidic valves for sequential liquid delivery and particle synthesis. This approach avoids complicated fabrication processes and expensive facilities and thus has the potential to be a useful tool for lab-on-a-chip applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A microfluidic approach for hemoglobin detection in whole blood

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Acoustic streaming induced by two orthogonal ultrasound standing waves in a microfluidic channel.

PubMed

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

2018-07-01

A mathematical model is derived for acoustic streaming in a microfluidic channel confined between a solid wall and a rigid reflector. Acoustic streaming is produced by two orthogonal ultrasound standing waves of the same frequency that are created by two pairs of counter-propagating leaky surface waves induced in the solid wall. The magnitudes and phases of the standing waves are assumed to be different. Full analytical solutions are found for the equations of acoustic streaming. The obtained solutions are used in numerical simulations to reveal the structure of the acoustic streaming. It is shown that the interaction of two standing waves leads to the appearance of a cross term in the equations of acoustic streaming. If the phase lag between the standing waves is nonzero, the cross term brings about circular vortices with rotation axes perpendicular to the solid wall of the channel. The vortices make fluid particles rotate and move alternately up and down between the solid wall and the reflector. The obtained results are of immediate interest for acoustomicrofluidic applications such as the ultrasonic micromixing of fluids and the manipulation of microparticles. Copyright © 2018 Elsevier B.V. All rights reserved.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Microfluidic droplet sorting using integrated bilayer micro-valves

NASA Astrophysics Data System (ADS)

Chen, Yuncong; Tian, Yang; Xu, Zhen; Wang, Xinran; Yu, Sicong; Dong, Liang

2016-10-01

This paper reports on a microfluidic device capable of sorting microfluidic droplets utilizing conventional bilayer pneumatic micro-valves as sorting controllers. The device consists of two micro-valves placed symmetrically on two sides of a sorting area, each on top of a branching channel at an inclined angle with respect to the main channel. Changes in transmitted light intensity, induced by varying light absorbance by each droplet, are used to divert the droplet from the sorting area into one of the three outlet channels. When no valve is activated, the droplet flows into the outlet channel in the direction of the main channel. When one of the valves is triggered, the flexible membrane of valve will first be deflected. Once the droplet leaves the detection point, the deflected membrane will immediately return to its default flattened position, thereby exerting a drawing pressure on the droplet and deviating it from its original streamline to the outlet on the same side as the valve. This sorting method will be particularly suitable for numerous large-scale integrated microfluidic systems, where pneumatic micro-valves are already used. Only few structural modifications are needed to achieve droplet sorting capabilities in these systems. Due to the mechanical nature of diverting energy applied to droplets, the proposed sorting method may induce only minimal interference to biological species or microorganisms encapsulated inside the droplets that may accompany electrical, optical and magnetic-based techniques.

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.

An oxidized liquid metal-based microfluidic platform for tunable electronic device applications.

PubMed

Li, Guangyong; Parmar, Mitesh; Lee, Dong-Weon

2015-02-07

Easy movement of oxidized Galinstan in microfluidic channels is a promising way for the wide application of the non-toxic liquid metal. In this paper, two different surface modification techniques (physical and chemical) are reported, which dramatically improve the non-wetting characteristics of oxidized Galinstan in the microfluidic channel. In the physical technique, normal paper textures are transferred to the inner wall of polydimethylsiloxane (PDMS) channels and four types of nanoparticles are then coated on the surface of the wall for further improvement of the non-wetting characteristics. Highest advancing angle of 167° and receding angle of 151° are achieved on the paper-textured PDMS with titanium oxide (TiO2) nanoparticles. In the chemical technique, three types of inorganic acids are employed to generate dual-scale structures on the PDMS surface. The inner wall surface treated with sulfuric acid (H2SO4) shows the highest contact angle of 167° and a low hysteresis of ~14° in the dynamic measurement. Creating, transporting, separating and merging of oxidized Galinstan droplets are successfully demonstrated in the fabricated PDMS microfluidic channels. After optimization of these modification techniques, the potential application of tunable capacitors and electronic filters is realized by using liquid metal-based microfluidic devices.

Microfluidic preparation of polymer nanospheres

NASA Astrophysics Data System (ADS)

Kucuk, Israfil; Edirisinghe, Mohan

2014-12-01

In this work, solid polymer nanospheres with their surface tailored for drug adhesion were prepared using a V-shaped microfluidic junction. The biocompatible polymer solutions were infused using two channels of the microfluidic junction which was also simultaneously fed with a volatile liquid, perfluorohexane using the other channel. The mechanism by which the nanospheres are generated is explained using high speed camera imaging. The polymer concentration (5-50 wt%) and flow rates of the feeds (50-300 µl min-1) were important parameters in controlling the nanosphere diameter. The diameter of the polymer nanospheres was found to be in the range of 80-920 nm with a polydispersity index of 11-19 %. The interior structure and surfaces of the nanospheres prepared were studied using advanced microscopy and showed the presence of fine pores and cracks on surface which can be used as drug entrapment locations.

Droplet based microfluidics.

PubMed

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

2012-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

2016-02-07

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.

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

Optical calorimetry in microfluidic droplets.

PubMed

Chamoun, Jacob; Pattekar, Ashish; Afshinmanesh, Farzaneh; Martini, Joerg; Recht, Michael I

2018-05-29

A novel microfluidic calorimeter that measures the enthalpy change of reactions occurring in 100 μm diameter aqueous droplets in fluoropolymer oil has been developed. The aqueous reactants flow into a microfluidic droplet generation chip in separate fluidic channels, limiting contact between the streams until immediately before they form the droplet. The diffusion-driven mixing of reactants is predominantly restricted to within the droplet. The temperature change in droplets due to the heat of reaction is measured optically by recording the reflectance spectra of encapsulated thermochromic liquid crystals (TLC) that are added to one of the reactant streams. As the droplets travel through the channel, the spectral characteristics of the TLC represent the internal temperature, allowing optical measurement with a precision of ≈6 mK. The microfluidic chip and all fluids are temperature controlled, and the reaction heat within droplets raises their temperature until thermal diffusion dissipates the heat into the surrounding oil and chip walls. Position resolved optical temperature measurement of the droplets allows calculation of the heat of reaction by analyzing the droplet temperature profile over time. Channel dimensions, droplet generation rate, droplet size, reactant stream flows and oil flow rate are carefully balanced to provide rapid diffusional mixing of reactants compared to thermal diffusion, while avoiding thermal "quenching" due to contact between the droplets and the chip walls. Compared to conventional microcalorimetry, which has been used in this work to provide reference measurements, this new continuous flow droplet calorimeter has the potential to perform titrations ≈1000-fold faster while using ≈400-fold less reactants per titration.

Materials for Microfluidic Immunoassays: A Review.

PubMed

Mou, Lei; Jiang, Xingyu

2017-08-01

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

Appendix C: Automated Vitrification of Mammalian Embryos on a Digital Microfluidic Device.

PubMed

Liu, Jun; Pyne, Derek G; Abdelgawad, Mohamed; Sun, Yu

2017-01-01

This chapter introduces a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual microdroplets manipulated on the microfluidic device were used as microvessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

Centrifugal sedimentation for selectively packing channels with silica microbeads in three-dimensional micro/nanofluidic devices.

PubMed

Gong, Maojun; Bohn, Paul W; Sweedler, Jonathan V

2009-03-01

Incorporation of nanofluidic elements into microfluidic channels is one approach for adding filtration and partition functionality to planar microfluidic devices, as well as providing enhanced biomolecular separations. Here we introduce a strategy to pack microfluidic channels with silica nanoparticles and microbeads, thereby indirectly producing functional nanostructures; the method allows selected channels to be packed, here demonstrated so that a separation channel is packed while keeping an injection channel unpacked. A nanocapillary array membrane is integrated between two patterned microfluidic channels that cross each other in vertically separated layers. The membrane serves both as a frit for bead packing and as a fluid communication conduit between microfluidic channels. Centrifugal force-assisted sedimentation is then used to selectively pack the microfluidic channels using an aqueous silica bead suspension loaded into the appropriate inlet reservoirs. This packing approach may be used to simultaneously pack multiple channels with silica microbeads having different sizes and surface properties. The chip design and packing method introduced here are suitable for packing silica particles in sizes ranging from nanometers to micrometers and allow rapid (approximately 10 min) packing with high quality. The liquid/analyte transport characteristics of these packed micro/nanofluidic devices have potential utility in a wide range of applications, including electroosmotic pumping, liquid chromatographic separations, and electrochromatography.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Efficient gas-liquid contact using microfluidic membrane devices with staggered herringbone mixers.

PubMed

Femmer, Tim; Eggersdorfer, Max L; Kuehne, Alexander J C; Wessling, Matthias

2015-08-07

We describe a novel membrane based gas-liquid-contacting device with increased mass transport and reduced pressure loss by combining a membrane with a staggered herringbone static mixer. Herringbone structures are imposed on the microfluidic channel geometry via soft lithography, acting as mixers which introduce secondary flows at the membrane interface. Such flows include Dean vortices and Taylor flows generating effective mixing while improving mass transport and preventing concentration polarization in microfluidic channels. Furthermore, our static herringbone mixer membranes effectively reduce pressure losses leading to devices with enhanced transfer properties for microfluidic gas-liquid contact. We investigate the red blood cell distribution to tailor our devices towards miniaturised extracorporeal membrane oxygenation and improved comfort of patients with lung insufficiencies.

Comparison of Cell Expression Formats for the Characterization of GABAA Channels Using a Microfluidic Patch Clamp System

PubMed Central

Chen, Qin; Yim, Peter D.; Yuan, Nina; Johnson, Juliette; Cook, James M.; Smith, Steve; Ionescu-Zanetti, Cristian; Wang, Zhi-Jian; Arnold, Leggy A.

2012-01-01

Abstract Ensemble recording and microfluidic perfusion are recently introduced techniques aimed at removing the laborious nature and low recording success rates of manual patch clamp. Here, we present assay characteristics for these features integrated into one automated electrophysiology platform as applied to the study of GABAA channels. A variety of cell types and methods of GABAA channel expression were successfully studied (defined as IGABA>500 pA), including stably transfected human embryonic kidney (HEK) cells expressing α1β3γ2 GABAA channels, frozen ready-to-assay (RTA) HEK cells expressing α1β3γ2 or α3β3γ2 GABAA channels, transiently transfected HEK293T cells expressing α1β3γ2 GABAA channels, and immortalized cultures of human airway smooth muscle cells endogenously expressing GABAA channels. Current measurements were successfully studied in multiple cell types with multiple modes of channel expression in response to several classic GABAA channel agonists, antagonists, and allosteric modulators. We obtained success rates above 95% for transiently or stably transfected HEK cells and frozen RTA HEK cells expressing GABAA channels. Tissue-derived immortalized cultures of airway smooth muscle cells exhibited a slightly lower recording success rate of 75% using automated patch, which was much higher than the 5% success rate using manual patch clamp technique by the same research group. Responses to agonists, antagonists, and allosteric modulators compared well to previously reported manual patch results. The data demonstrate that both the biophysics and pharmacologic characterization of GABAA channels in a wide variety of cell formats can be performed using this automated patch clamp system. PMID:22574655

Microfluidic proportional flow controller

PubMed Central

Prentice-Mott, Harrison; Toner, Mehmet; Irimia, Daniel

2011-01-01

Precise flow control in microfluidic chips is important for many biochemical assays and experiments at microscale. While several technologies for controlling fluid flow have been implemented either on- or off-chip, these can provide either high-speed or high-precision control, but seldom could accomplish both at the same time. Here we describe a new on-chip, pneumatically activated flow controller that allows for fast and precise control of the flow rate through a microfluidic channel. Experimental results show that the new proportional flow controllers exhibited a response time of approximately 250 ms, while our numerical simulations suggest that faster actuation down to approximately 50 ms could be achieved with alternative actuation schemes. PMID:21874096

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

Design and characterization of hydrogel-based microfluidic devices with biomimetic solute transport networks

PubMed Central

Koo, Hyung-Jun

2017-01-01

Hydrogel could serve as a matrix material of new classes of solar cells and photoreactors with embedded microfluidic networks. These devices mimic the structure and function of plant leaves, which are a natural soft matter based microfluidic system. These unusual microfluidic-hydrogel devices with fluid-penetrable medium operate on the basis of convective-diffusive mechanism, where the liquid is transported between the non-connected channels via molecular permeation through the hydrogel. We define three key designs of such hydrogel devices, having linear, T-shaped, and branched channels and report results of numerical simulation of the process of their infusion with solute carried by the incoming fluid. The computational procedure takes into account both pressure-driven convection and concentration gradient-driven diffusion in the permeable gel matrix. We define the criteria for evaluation of the fluid infusion rate, uniformity, solute loss by outflow and overall performance. The T-shaped channel network was identified as the most efficient one and was improved further by investigating the effect of the channel-end secondary branches. Our parallel experimental data on the pattern of solute infusions are in excellent agreement with the simulation. These network designs can be applied to a broad range of novel microfluidic materials and soft matter devices with distributed microchannel networks. PMID:28396708

Desktop aligner for fabrication of multilayer microfluidic devices.

PubMed

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

2015-07-01

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

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

A truly Lego®-like modular microfluidics platform

NASA Astrophysics Data System (ADS)

Vittayarukskul, Kevin; Lee, Abraham Phillip

2017-03-01

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

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. © 2015 American Academy of Forensic Sciences.

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…

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.

Enhanced Microfluidic Electromagnetic Measurements

NASA Technical Reports Server (NTRS)

Ricco, Antonio J. (Inventor); Kovacs, Gregory (Inventor); Giovangrandi, Laurent (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.

Single- and two-phase flow in microfluidic porous media analogs based on Voronoi tessellation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Mengjie; Xiao, Feng; Johnson-Paben, Rebecca

2012-01-01

The objective of this study was to create a microfluidic model of complex porous media for studying single and multiphase flows. Most experimental porous media models consist of periodic geometries that lend themselves to comparison with well-developed theoretical predictions. However, most real porous media such as geological formations and biological tissues contain a degree of randomness and complexity that is not adequately represented in periodic geometries. To design an experimental tool to study these complex geometries, we created microfluidic models of random homogeneous and heterogeneous networks based on Voronoi tessellations. These networks consisted of approximately 600 grains separated by amore » highly connected network of channels with an overall porosity of 0.11 0.20. We found that introducing heterogeneities in the form of large cavities within the network changed the permeability in a way that cannot be predicted by the classical porosity-permeability relationship known as the Kozeny equation. The values of permeability found in experiments were in excellent agreement with those calculated from three-dimensional lattice Boltzmann simulations. In two-phase flow experiments of oil displacement with water we found that the surface energy of channel walls determined the pattern of water invasion, while the network topology determined the residual oil saturation. These results suggest that complex network topologies lead to fluid flow behavior that is difficult to predict based solely on porosity. The microfluidic models developed in this study using a novel geometry generation algorithm based on Voronoi tessellation are a new experimental tool for studying fluid and solute transport problems within complex porous media.« less

Three-dimensional fit-to-flow microfluidic assembly.

PubMed

Chen, Arnold; Pan, Tingrui

2011-12-01

Three-dimensional microfluidics holds great promise for large-scale integration of versatile, digitalized, and multitasking fluidic manipulations for biological and clinical applications. Successful translation of microfluidic toolsets to these purposes faces persistent technical challenges, such as reliable system-level packaging, device assembly and alignment, and world-to-chip interface. In this paper, we extended our previously established fit-to-flow (F2F) world-to-chip interconnection scheme to a complete system-level assembly strategy that addresses the three-dimensional microfluidic integration on demand. The modular F2F assembly consists of an interfacial chip, pluggable alignment modules, and multiple monolithic layers of microfluidic channels, through which convoluted three-dimensional microfluidic networks can be easily assembled and readily sealed with the capability of reconfigurable fluid flow. The monolithic laser-micromachining process simplifies and standardizes the fabrication of single-layer pluggable polymeric modules, which can be mass-produced as the renowned Lego(®) building blocks. In addition, interlocking features are implemented between the plug-and-play microfluidic chips and the complementary alignment modules through the F2F assembly, resulting in facile and secure alignment with average misalignment of 45 μm. Importantly, the 3D multilayer microfluidic assembly has a comparable sealing performance as the conventional single-layer devices, providing an average leakage pressure of 38.47 kPa. The modular reconfigurability of the system-level reversible packaging concept has been demonstrated by re-routing microfluidic flows through interchangeable modular microchannel layers.

Cell Blebbing in Confined Microfluidic Environments

PubMed Central

Ibo, Markela; Srivastava, Vasudha; Robinson, Douglas N.; Gagnon, Zachary R.

2016-01-01

Migrating cells can extend their leading edge by forming myosin-driven blebs and F-actin-driven pseudopods. When coerced to migrate in resistive environments, Dictyostelium cells switch from using predominately pseudopods to blebs. Bleb formation has been shown to be chemotactic and can be influenced by the direction of the chemotactic gradient. In this study, we determine the blebbing responses of developed cells of Dictyostelium discoideum to cAMP gradients of varying steepness produced in microfluidic channels with different confining heights, ranging between 1.7 μm and 3.8 μm. We show that microfluidic confinement height, gradient steepness, buffer osmolarity and Myosin II activity are important factors in determining whether cells migrate with blebs or with pseudopods. Dictyostelium cells were observed migrating within the confines of microfluidic gradient channels. When the cAMP gradient steepness is increased from 0.7 nM/μm to 20 nM/μm, cells switch from moving with a mixture of blebs and pseudopods to moving only using blebs when chemotaxing in channels with confinement heights less than 2.4 μm. Furthermore, the size of the blebs increases with gradient steepness and correlates with increases in myosin-II localization at the cell cortex. Reduction of intracellular pressure by high osmolarity buffer or inhibition of myosin-II by blebbistatin leads to a decrease in bleb formation and bleb size. Together, our data reveal that the protrusion type formed by migrating cells can be influenced by the channel height and the steepness of the cAMP gradient, and suggests that a combination of confinement-induced myosin-II localization and cAMP-regulated cortical contraction leads to increased intracellular fluid pressure and bleb formation. PMID:27706201

Rapid antibiotic susceptibility testing in a microfluidic pH sensor.

PubMed

Tang, Yanyan; Zhen, Li; Liu, Jingqing; Wu, Jianmin

2013-03-05

For appropriate selection of antibiotics in the treatment of pathogen infection, rapid antibiotic susceptibility testing (AST) is urgently needed in clinical practice. This study reports the utilization of a microfluidic pH sensor for monitoring bacterial growth rate in culture media spiked with different kinds of antibiotics. The microfluidic pH sensor was fabricated by integration of pH-sensitive chitosan hydrogel with poly(dimethylsiloxane) (PDMS) microfluidic channels. For facilitating the reflectometric interference spectroscopic measurements, the chitosan hydrogel was coated on an electrochemically etched porous silicon chip, which was used as the substrate of the microfluidic channel. Real-time observation of the pH change in the microchannel can be realized by Fourier transform reflectometric interference spectroscopy (FT-RIFS), in which the effective optical thickness (EOT) was selected as the optical signal for indicating the reversible swelling process of chitosan hydrogel stimulated by pH change. With this microfluidic pH sensor, we demonstrate that confinement of bacterial cells in a nanoliter size channel allows rapid accumulation of metabolic products and eliminates the need for long-time preincubation, thus reducing the whole detection time. On the basis of this technology, the whole bacterial growth curve can be obtained in less than 2 h, and consequently rapid AST can be realized. Compared with conventional methods, the AST data acquired from the bacterial growth curve can provide more detailed information for studying the antimicrobial behavior of antibiotics during different stages. Furthermore, the new technology also provides a convenient method for rapid minimal inhibition concentration (MIC) determination of individual antibiotics or the combinations of antibiotics against human pathogens that will find application in clinical and point-of-care medicine.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

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

PubMed

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

2018-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reece, Amy E.; Oakey, John, E-mail: joakey@uwyo.edu

2016-04-15

The controlled and directed focusing of particles within flowing fluids is a problem of fundamental and technological significance. Microfluidic inertial focusing provides passive and precise lateral and longitudinal alignment of small particles without the need for external actuation or sheath fluid. The benefits of inertial focusing have quickly enabled the development of miniaturized flow cytometers, size-selective sorting devices, and other high-throughput particle screening tools. Straight channel inertial focusing device design requires knowledge of fluid properties and particle-channel size ratio. Equilibrium behavior of inertially focused particles has been extensively characterized and the constitutive phenomena described by scaling relationships for straight channelsmore » 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

Microfluidic Serial Dilution Circuit

PubMed Central

Paegel, Brian M.; Grover, William H.; Skelley, Alison M.; Mathies, Richard A.; Joyce, Gerald F.

2008-01-01

In vitro evolution of RNA molecules requires a method for executing many consecutive serial dilutions. To solve this problem, a microfluidic circuit has been fabricated in a three-layer glass-PDMS-glass device. The 400-nL serial dilution circuit contains five integrated membrane valves: three two-way valves arranged in a loop to drive cyclic mixing of the diluent and carryover, and two bus valves to control fluidic access to the circuit through input and output channels. By varying the valve placement in the circuit, carryover fractions from 0.04 to 0.2 were obtained. Each dilution process, which is comprised of a diluent flush cycle followed by a mixing cycle, is carried out with no pipeting, and a sample volume of 400 nL is sufficient for conducting an arbitrary number of serial dilutions. Mixing is precisely controlled by changing the cyclic pumping rate, with a minimum mixing time of 22 s. This microfluidic circuit is generally applicable for integrating automated serial dilution and sample preparation in almost any microfluidic architecture. PMID:17073422

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

A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods

PubMed Central

Chung, Bong Geun; Park, Jeong Won; Hu, Jia Sheng; Huang, Carlos; Monuki, Edwin S; Jeon, Noo Li

2007-01-01

Background Microfluidics is an enabling technology with a number of advantages over traditional tissue culture methods when precise control of cellular microenvironment is required. However, there are a number of practical and technical limitations that impede wider implementation in routine biomedical research. Specialized equipment and protocols required for fabrication and setting up microfluidic experiments present hurdles for routine use by most biology laboratories. Results We have developed and validated a novel microfluidic device that can directly interface with conventional tissue culture methods to generate and maintain controlled soluble environments in a Petri dish. It incorporates separate sets of fluidic channels and vacuum networks on a single device that allows reversible application of microfluidic gradients onto wet cell culture surfaces. Stable, precise concentration gradients of soluble factors were generated using simple microfluidic channels that were attached to a perfusion system. We successfully demonstrated real-time optical live/dead cell imaging of neural stem cells exposed to a hydrogen peroxide gradient and chemotaxis of metastatic breast cancer cells in a growth factor gradient. Conclusion This paper describes the design and application of a versatile microfluidic device that can directly interface with conventional cell culture methods. This platform provides a simple yet versatile tool for incorporating the advantages of a microfluidic approach to biological assays without changing established tissue culture protocols. PMID:17883868

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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.

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

Electrokinetic injection techniques in microfluidic chips.

PubMed

Fu, L M; Yang, R J; Lee, G B; Liu, H H

2002-10-01

The separation efficiency of a microfluidic chip is influenced to a significant degree by the flow field conditions within the injection microchannel. Therefore, an understanding of the physics of the flow within this channel is beneficial in the design and operation of such a system. The configuration of an injection system is determined by the volume of the sample plug that is to be delivered to the separation process. Accordingly, this paper addresses the design and testing of injection systems with a variety of configurations, including a simple cross, a double-T, and a triple-T configuration. This paper also presents the design of a unique multi-T injection configuration. Each injection system cycles through a predetermined series of steps, in which the electric field magnitude and distribution within the various channels is strictly manipulated, to effectuate a virtual valve. The uniquemulti-T configuration injection system presented within this paper has the ability to simulate the functions of the cross, double-T, and triple-T systems through appropriate manipulations of the electric field within its various channels. In other words, the proposed design successfully combines several conventional injection systems within a single microfluidic chip.

Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing.

PubMed

Flachsbart, Bruce R; Wong, Kachuen; Iannacone, Jamie M; Abante, Edward N; Vlach, Robert L; Rauchfuss, Peter A; Bohn, Paul W; Sweedler, Jonathan V; Shannon, Mark A

2006-05-01

The design and fabrication of a multilayered polymer micro-nanofluidic chip is described that consists of poly(methylmethacrylate) (PMMA) layers that contain microfluidic channels separated in the vertical direction by polycarbonate (PC) membranes that incorporate an array of nanometre diameter cylindrical pores. The materials are optically transparent to allow inspection of the fluids within the channels in the near UV and visible spectrum. The design architecture enables nanofluidic interconnections to be placed in the vertical direction between microfluidic channels. Such an architecture allows microchannel separations within the chip, as well as allowing unique operations that utilize nanocapillary interconnects: the separation of analytes based on molecular size, channel isolation, enhanced mixing, and sample concentration. Device fabrication is made possible by a transfer process of labile membranes and the development of a contact printing method for a thermally curable epoxy based adhesive. This adhesive is shown to have bond strengths that prevent leakage and delamination and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels 100 microm in width and 20 microm in depth are contact printed without the adhesive entering the microchannel. The chip is characterized in terms of resistivity measurements along the microfluidic channels, electroosmotic flow (EOF) measurements at different pH values and laser-induced-fluorescence (LIF) detection of green-fluorescent protein (GFP) plugs injected across the nanocapillary membrane and into a microfluidic channel. The results indicate that the mixed polymer micro-nanofluidic multilayer chip has electrical characteristics needed for use in microanalytical systems.

Visual Estimation of Bacterial Growth Level in Microfluidic Culture Systems.

PubMed

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

2018-02-03

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

Controlled microfluidic interfaces for microsensors

NASA Astrophysics Data System (ADS)

Jiang, H.

2009-02-01

Lab on a chip has found many applications in biological and chemical analysis, including pathogen detections. Because these labs on chips involve handling of fluids at the microscale, surface tension profoundly affects the behavior and performance of these systems. Through careful engineering, controlled liquid-liquid or liquid-gas interfaces at the microscale can be formed and used in many interesting applications. In this talk, I will present our work on applying such interfaces to microsensing. These interfaces are created at hydrophobic-hydrophilic boundaries formed within microfluidic channels and pinned by surface tension. We have designed and fabricated a few microsensing techniques including chemical and biological sensing using dissolvable micromembranes in microchannels, chemical and biological sensing at liquid crystals interfacing either air or aqueous solutions, and collection of gaseous samples and aerosols through air-liquid microfludic interfaces. I will next introduce on-chip microlenses and microlens arrays for optical detection, including smart and adaptive liquid microlenses actuated by stimuli-responsive hydrogels, and liquid microlenses in situ formed within microfluidic channels via pneumatic control of droplets.

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

PubMed

Jung, Taekeon; Yang, Sung

2015-05-21

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

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

Microfluidic free-flow zone electrophoresis and isotachophoresis using carbon black nano-composite PDMS sidewall membranes.

PubMed

Fu, Xiaotong; Mavrogiannis, Nicholas; Ibo, Markela; Crivellari, Francesca; Gagnon, Zachary R

2017-01-01

We present a new type of free-flow electrophoresis (FFE) device for performing on-chip microfluidic isotachophoresis and zone electrophoresis. FFE is performed using metal gallium electrodes, which are isolated from a main microfluidic flow channel using thin micron-scale polydimethylsiloxane/carbon black (PDMS/CB) composite membranes integrated directly into the sidewalls of the microfluidic channel. The thin membrane allows for field penetration and effective electrophoresis, but serves to prevent bubble generation at the electrodes from electrolysis. We experimentally demonstrate the ability to use this platform to perform on-chip free-flow electrophoretic separation and isotachophoretic concentration. Due to the small size and simple fabrication procedure, this PDMS/CB platform could be used as a part of an on-chip upstream sample preparation toolkit for portable microfluidic diagnostic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfluidic Devices in Advanced Caenorhabditis elegans Research.

PubMed

Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

2016-08-02

The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

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

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

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Hashim, U.

2017-03-01

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

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

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

PubMed

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

2018-04-15

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Review of Recent Metamaterial Microfluidic Sensors.

PubMed

Salim, Ahmed; Lim, Sungjoon

2018-01-15

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

High-pressure microfluidic control in lab-on-a-chip devices using mobile polymer monoliths.

PubMed

Hasselbrink, Ernest F; Shepodd, Timothy J; Rehm, Jason E

2002-10-01

We have developed a nonstick polymer formulation for creating moving parts inside of microfluidic channels and have applied the technique to create piston-based devices that overcome several microfluidic flow control challenges. The parts were created bycompletely filling the channels of a glass microfluidic chip with the monomer/ solvent/initiator components of a nonstick photopolymer and then selectively exposing the chip to UV light in order to define mobile pistons (or other quasi-two-dimensional shapes) inside the channels. Stops defined in the substrate prevent the part from flushing out of the device but also provide sealing surfaces so that valves and other flow control devices are possible. Sealing against pressures greater than 30 MPa (4,500 psi) and actuation times less than 33 ms are observed. An on-chip check valve, a diverter valve, and a 10-nL pipet are demonstrated. This valving technology, coupled with high-pressure electrokinetic pumps, should make it possible to create a completely integrated HPLC system on a chip.

Microfluidic diffusion diluter: bulging of PDMS microchannels under pressure-driven flow

NASA Astrophysics Data System (ADS)

Holden, Matthew A.; Kumar, Saurabh; Beskok, Ali; Cremer, Paul S.

2003-05-01

The bulging of microfluidic systems during pressure-driven flow is potentially a major consideration for polydimethylsiloxane (PDMS)-based devices. Microchannel cross-sectional areas can change drastically as a function of flow rate and downstream microchannel position. Such geometrical flexibility leads to difficulties in predicting convective/diffusive transport for these systems. We have previously introduced a non-dimensional parameter, kappa, for characterizing convection and diffusion behavior for pressure-driven flow in rigid all-glass systems. This paper describes a modification of that concept for application to non-rigid systems, which is accomplished by incorporating an experimental step to account for the bulging in PDMS/glass microsystems. Specifically, an experimental measurement of channel height by fluorescence microscopy is combined with the aforementioned theory to characterize convective/diffusive behavior at a single location in the device. This allowed the parameter kappa to be determined at that point and applied to predict fluid flow in the subsequent portion of the PDMS microsystem. This procedure was applied to a PDMS/glass microfluidic diffusion dilution (muDD) device designed for generating concentration gradients. Theoretically predicted and experimentally measured distributions of concentrations within the microsystem matched well.

An integrated microfluidic cell for detection, manipulation, and sorting of single micron-sized magnetic beads

NASA Astrophysics Data System (ADS)

Jiang, Z.; Llandro, J.; Mitrelias, T.; Bland, J. A. C.

2006-04-01

A lab-on-a-chip integrated microfluidic cell has been developed for magnetic biosensing, which is comprised of anisotropic magnetoresistance (AMR) sensors optimized for the detection of single magnetic beads and electrodes to manipulate and sort the beads, integrated into a microfluidic channel. The device is designed to read out the real-time signal from 9 μm diameter magnetic beads moving over AMR sensors patterned into 18×4.5 μm rectangles and 10 μm diameter rings and arranged in Wheatstone bridges. The beads are moved over the sensors along a 75×75 μm wide channel patterned in SU8. Beads of different magnetic moments can be sorted through a magnetostatic sorting gate into different branches of the microfluidic channel using a magnetic field gradient applied by lithographically defined 120 nm thick Cu striplines carrying 0.2 A current.

Soft tubular microfluidics for 2D and 3D applications

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Soft tubular microfluidics for 2D and 3D applications

PubMed Central

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

2017-01-01

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs. PMID:28923968

Flow control using audio tones in resonant microfluidic networks: towards cell-phone controlled lab-on-a-chip devices.

PubMed

Phillips, Reid H; Jain, Rahil; Browning, Yoni; Shah, Rachana; Kauffman, Peter; Dinh, Doan; Lutz, Barry R

2016-08-16

Fluid control remains a challenge in development of portable lab-on-a-chip devices. Here, we show that microfluidic networks driven by single-frequency audio tones create resonant oscillating flow that is predicted by equivalent electrical circuit models. We fabricated microfluidic devices with fluidic resistors (R), inductors (L), and capacitors (C) to create RLC networks with band-pass resonance in the audible frequency range available on portable audio devices. Microfluidic devices were fabricated from laser-cut adhesive plastic, and a "buzzer" was glued to a diaphragm (capacitor) to integrate the actuator on the device. The AC flowrate magnitude was measured by imaging oscillation of bead tracers to allow direct comparison to the RLC circuit model across the frequency range. We present a systematic build-up from single-channel systems to multi-channel (3-channel) networks, and show that RLC circuit models predict complex frequency-dependent interactions within multi-channel networks. Finally, we show that adding flow rectifying valves to the network creates pumps that can be driven by amplified and non-amplified audio tones from common audio devices (iPod and iPhone). This work shows that RLC circuit models predict resonant flow responses in multi-channel fluidic networks as a step towards microfluidic devices controlled by audio tones.

3D nanofabrication inside rapid prototyped microfluidic channels showcased by wet-spinning of single micrometre fibres.

PubMed

Lölsberg, Jonas; Linkhorst, John; Cinar, Arne; Jans, Alexander; Kuehne, Alexander J C; Wessling, Matthias

2018-05-01

Microfluidics is an established multidisciplinary research domain with widespread applications in the fields of medicine, biotechnology and engineering. Conventional production methods of microfluidic chips have been limited to planar structures, preventing the exploitation of truly three-dimensional architectures for applications such as multi-phase droplet preparation or wet-phase fibre spinning. Here the challenge of nanofabrication inside a microfluidic chip is tackled for the showcase of a spider-inspired spinneret. Multiphoton lithography, an additive manufacturing method, was used to produce free-form microfluidic masters, subsequently replicated by soft lithography. Into the resulting microfluidic device, a three-dimensional spider-inspired spinneret was directly fabricated in-chip via multiphoton lithography. Applying this unprecedented fabrication strategy, the to date smallest printed spinneret nozzle is produced. This spinneret resides tightly sealed, connecting it to the macroscopic world. Its functionality is demonstrated by wet-spinning of single-digit micron fibres through a polyacrylonitrile coagulation process induced by a water sheath layer. The methodology developed here demonstrates fabrication strategies to interface complex architectures into classical microfluidic platforms. Using multiphoton lithography for in-chip fabrication adopts a high spatial resolution technology for improving geometry and thus flow control inside microfluidic chips. The showcased fabrication methodology is generic and will be applicable to multiple challenges in fluid control and beyond.

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

Microfluidic platform for detection and quantification of magnetic markers

NASA Astrophysics Data System (ADS)

Kokkinis, Georgios; Cardoso, Susana; Giouroudi, Ioanna

2017-05-01

This paper reports on a microfluidic platform with an integrated spin valve giant magneto-resistance (GMR) sensor used for the detection and quantification of single magnetic micromarkers. A microfluidic channel containing the magnetic fluid, microconductors (MCs) for collection of the magnetic markers and a spin valve GMR sensor for detecting the presence of their magnetic stray field were integrated on a single chip. The results show that the sensor is capable of detecting a single magnetic marker with 2.8 μm diameter.

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

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

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.

Integrated single-walled carbon nanotube/microfluidic devices for the study of the sensing mechanism of nanotube sensors.

PubMed

Fu, Qiang; Liu, Jie

2005-07-21

A method to fabricate integrated single-walled carbon nanotube/microfluidic devices was developed. This simple process could be used to directly prepare nanotube thin film transistors within the microfluidic channel and to register SWNT devices with the microfludic channel without the need of an additional alignment step. The microfluidic device was designed to have several inlets that deliver multiple liquid flows to a single main channel. The location and width of each flow in the main channel could be controlled by the relative flow rates. This capability enabled us to study the effect of the location and the coverage area of the liquid flow that contained charged molecules on the conduction of the nanotube devices, providing important information on the sensing mechanism of carbon nanotube sensors. The results showed that in a sensor based on a nanotube thin film field effect transistor, the sensing signal came from target molecules absorbed on or around the nanotubes. The effect from adsorption on metal electrodes was weak.

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

PubMed

Shamloo, Amir; Boodaghi, Miad

2018-03-01

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

Design, fabrication and characterization of an arrayable all-polymer microfluidic valve employing highly magnetic rare-earth composite polymer

NASA Astrophysics Data System (ADS)

Rahbar, Mona; Shannon, Lesley; Gray, Bonnie L.

2016-05-01

We present a new magnetically actuated microfluidic valve that employs a highly magnetic composite polymer (M-CP) containing rare-earth hard-magnetic powder for its actuating element and for its valve seat. The M-CP offers much higher magnetization compared to the soft-magnetic, ferrite-based composite polymers typically used in microfluidic applications. Each valve consists of a permanently magnetized M-CP flap and valve seat mounted on a microfluidic channel system fabricated in poly(dimethylsiloxane) (PDMS). Each valve is actuated under a relatively small external magnetic field of 80 mT provided by a small permanent magnet mounted on a miniature linear actuator. The performance of the valve with different flap thicknesses is characterized. In addition, the effect of the magnetic valve seat on the valve’s performance is also characterized. It is experimentally shown that a valve with a 2.3 mm flap thickness, actuated under an 80 mT magnetic field, is capable of completely blocking liquid flow at a flow rate of 1 ml min-1 for pressures up to 9.65 kPa in microfluidic channels 200 μm wide and 200 μm deep. The valve can also be fabricated into an array for flow switching between multiple microfluidic channels under continuous flow conditions. The performance of arrays of valves for flow routing is demonstrated for flow rates up to 5 ml min-1 with larger microfluidic channels of up to 1 mm wide and 500 μm deep. The design of the valves is compatible with other commonly used polymeric microfluidic components, as well as other components that use the same novel permanently magnetic composite polymer, such as our previously reported cilia-based mixing devices.

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.

A polymeric master replication technology for mass fabrication of poly(dimethylsiloxane) microfluidic devices.

PubMed

Li, Hai-Fang; Lin, Jin-Ming; Su, Rong-Guo; Cai, Zong Wei; Uchiyama, Katsumi

2005-05-01

A protocol of producing multiple polymeric masters from an original glass master mold has been developed, which enables the production of multiple poly(dimethylsiloxane) (PDMS)-based microfluidic devices in a low-cost and efficient manner. Standard wet-etching techniques were used to fabricate an original glass master with negative features, from which more than 50 polymethylmethacrylate (PMMA) positive replica masters were rapidly created using the thermal printing technique. The time to replicate each PMMA master was as short as 20 min. The PMMA replica masters have excellent structural features and could be used to cast PDMS devices for many times. An integration geometry designed for laser-induced fluorescence (LIF) detection, which contains normal deep microfluidic channels and a much deeper optical fiber channel, was successfully transferred into PDMS devices. The positive relief on seven PMMA replica masters is replicated with regard to the negative original glass master, with a depth average variation of 0.89% for 26-microm deep microfluidic channels and 1.16% for the 90 mum deep fiber channel. The imprinted positive relief in PMMA from master-to-master is reproducible with relative standard deviations (RSDs) of 1.06% for the maximum width and 0.46% for depth in terms of the separation channel. The PDMS devices fabricated from the PMMA replica masters were characterized and applied to the separation of a fluorescein isothiocyanate (FITC)-labeled epinephrine sample.

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies

PubMed Central

Fraser, Graham M.; Goldman, Daniel; Ellis, Christopher G.

2016-01-01

Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices. PMID:27829071

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies.

PubMed

Sové, Richard J; Fraser, Graham M; Goldman, Daniel; Ellis, Christopher G

2016-01-01

Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices.

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

PubMed

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

2007-02-09

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

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.

A microfluidic sub-critical water extraction instrument

NASA Astrophysics Data System (ADS)

Sherrit, Stewart; Noell, Aaron C.; Fisher, Anita; Lee, Mike C.; Takano, Nobuyuki; Bao, Xiaoqi; Kutzer, Thomas C.; Grunthaner, Frank

2017-11-01

This article discusses a microfluidic subcritical water extraction (SCWE) chip for autonomous extraction of amino acids from astrobiologically interesting samples. The microfluidic instrument is composed of three major components. These include a mixing chamber where the soil sample is mixed and agitated with the solvent (water), a subcritical water extraction chamber where the sample is sealed with a freeze valve at the chip inlet after a vapor bubble is injected into the inlet channels to ensure the pressure in the chip is in equilibrium with the vapor pressure and the slurry is then heated to ≤200 °C in the SCWE chamber, and a filter or settling chamber where the slurry is pumped to after extraction. The extraction yield of the microfluidic SCWE chip process ranged from 50% compared to acid hydrolysis and 80%-100% compared to a benchtop microwave SCWE for low biomass samples.

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

DOEpatents

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

2008-09-09

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

Fast and sensitive trace analysis of malachite green using a surface-enhanced Raman microfluidic sensor.

PubMed

Lee, Sangyeop; Choi, Junghyun; Chen, Lingxin; Park, Byungchoon; Kyong, Jin Burm; Seong, Gi Hun; Choo, Jaebum; Lee, Yeonjung; Shin, Kyung-Hoon; Lee, Eun Kyu; Joo, Sang-Woo; Lee, Kyeong-Hee

2007-05-08

A rapid and highly sensitive trace analysis technique for determining malachite green (MG) in a polydimethylsiloxane (PDMS) microfluidic sensor was investigated using surface-enhanced Raman spectroscopy (SERS). A zigzag-shaped PDMS microfluidic channel was fabricated for efficient mixing between MG analytes and aggregated silver colloids. Under the optimal condition of flow velocity, MG molecules were effectively adsorbed onto silver nanoparticles while flowing along the upper and lower zigzag-shaped PDMS channel. A quantitative analysis of MG was performed based on the measured peak height at 1615 cm(-1) in its SERS spectrum. The limit of detection, using the SERS microfluidic sensor, was found to be below the 1-2 ppb level and this low detection limit is comparable to the result of the LC-Mass detection method. In the present study, we introduce a new conceptual detection technology, using a SERS microfluidic sensor, for the highly sensitive trace analysis of MG in water.

Laser ablated micropillar energy directors for ultrasonic welding of microfluidic systems

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

Flow control for a paper-based microfluidic device by adjusting permeability of paper

NASA Astrophysics Data System (ADS)

Jang, Ilhoon; Kim, Gangjune; Song, Simon

2014-11-01

The paper-based microfluidics has attracted intensive attention as a prospective substitute for conventional microfluidic substrates used for a point-of-care diagnostics due to its superior advantages such as the cost effectiveness and production simplicity. Generally, a paper-based microfluidic device utilizes capillary force to drive a flow. Recent studies on flow control in such a device aimed at obtaining accurate and quantitative results by varying a channel geometry like width and length. According to the Darcy's law describing a flow in a porous media like paper, a flow rate can be adjusted the permeability of paper. In this study, we investigate a flow control method by adjusting the permeability of paper. We utilize the wax printing for the adjustment and the fabrication of paper channels. A rectangular wax pattern was printed on one inlet channel of a Y-channel geometry. By varying the brightness of the wax pattern, a relationship between the flow rate and permeability changes due to the wax was investigated. As a result, we obtained an effective permeability contour with respect to the wax pattern length and brightness. In addition, we developed a paper-based micromixer of which the mixing ratio was controlled precisely by adjusting the permeability.

Mixing in microfluidic devices and enhancement methods.

PubMed

Ward, Kevin; Fan, Z Hugh

2015-09-01

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.

"Hot-wire" microfluidic flowmeter based on a microfiber coupler.

PubMed

Yan, Shao-Cheng; Liu, Zeng-Yong; Li, Cheng; Ge, Shi-Jun; Xu, Fei; Lu, Yan-Qing

2016-12-15

Using an optical microfiber coupler (MC), we present a microfluidic platform for strong direct or indirect light-liquid interaction by wrapping a MC around a functionalized capillary. The light propagating in the MC and the liquid flowing in the capillary can be combined and divorced smoothly, keeping a long-distance interaction without the conflict of input and output coupling. Using this approach, we experimentally demonstrate a "hot-wire" microfluidic flowmeter based on a gold-integrated helical MC device. The microfluid inside the glass channel takes away the heat, then cools the MC and shifts the resonant wavelength. Due to the long-distance interaction and high temperature sensitivity, the proposed microfluidic flowmeter shows an ultrahigh flow rate sensitivity of 2.183 nm/(μl/s) at a flow rate of 1 μl/s. The minimum detectable change of the flow rate is around 9 nl/s at 1 μl/s.

Compact and controlled microfluidic mixing and biological particle capture

NASA Astrophysics Data System (ADS)

Ballard, Matthew; Owen, Drew; Mills, Zachary Grant; Hesketh, Peter J.; Alexeev, Alexander

2016-11-01

We use three-dimensional simulations and experiments to develop a multifunctional microfluidic device that performs rapid and controllable microfluidic mixing and specific particle capture. Our device uses a compact microfluidic channel decorated with magnetic features. A rotating magnetic field precisely controls individual magnetic microbeads orbiting around the features, enabling effective continuous-flow mixing of fluid streams over a compact mixing region. We use computer simulations to elucidate the underlying physical mechanisms that lead to effective mixing and compare them with experimental mixing results. We study the effect of various system parameters on microfluidic mixing to design an efficient micromixer. We also experimentally and numerically demonstrate that orbiting microbeads can effectively capture particles transported by the fluid, which has major implications in pre-concentration and detection of biological particles including various cells and bacteria, with applications in areas such as point-of-care diagnostics, biohazard detection, and food safety. Support from NSF and USDA is gratefully acknowledged.

Generation of digitized microfluidic filling flow by vent control.

PubMed

Yoon, Junghyo; Lee, Eundoo; Kim, Jaehoon; Han, Sewoon; Chung, Seok

2017-06-15

Quantitative microfluidic point-of-care testing has been translated into clinical applications to support a prompt decision on patient treatment. A nanointerstice-driven filling technique has been developed to realize the fast and robust filling of microfluidic channels with liquid samples, but it has failed to provide a consistent filling time owing to the wide variation in liquid viscosity, resulting in an increase in quantification errors. There is a strong demand for simple and quick flow control to ensure accurate quantification, without a serious increase in system complexity. A new control mechanism employing two-beam refraction and one solenoid valve was developed and found to successfully generate digitized filling flow, completely free from errors due to changes in viscosity. The validity of digitized filling flow was evaluated by the immunoassay, using liquids with a wide range of viscosity. This digitized microfluidic filling flow is a novel approach that could be applied in conventional microfluidic point-of-care testing. Copyright © 2016 Elsevier B.V. All rights reserved.

Review of Recent Metamaterial Microfluidic Sensors

PubMed Central

Salim, Ahmed

2018-01-01

Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require only microliter–nanoliter sample for sensing. Simple design, easy fabrication process, light weight prototype, and instant measurements are advantages as compared to conventional (optical, electrochemical and biological) sensing systems. Inkjet-printed flexible sensors find their utilization in rapidly growing wearable electronics and health-monitoring flexible devices. Adequate sensitivity and repeatability of these low profile microfluidic sensors make them a potential candidate for point-of-care testing which novice patients can use reliably. Aside from degraded sensitivity and lack of selectivity in all practical microwave chemical sensors, they require an instrument, such as vector network analyzer for measurements and not readily available as a self-sustained portable sensor. This review article presents state-of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive devices ranging from gigahertz to terahertz range) with an emphasis on metamaterial sensing circuit and microfluidic detection. We also highlight challenges and strategies to cope these issues which set future directions. PMID:29342953

Entropy-based separation of yeast cells using a microfluidic system of conjoined spheres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Kai-Jian; Qin, S.-J., E-mail: shuijie.qin@gmail.com; Bai, Zhong-Chen

2013-11-21

A physical model is derived to create a biological cell separator that is based on controlling the entropy in a microfluidic system having conjoined spherical structures. A one-dimensional simplified model of this three-dimensional problem in terms of the corresponding effects of entropy on the Brownian motion of particles is presented. This dynamic mechanism is based on the Langevin equation from statistical thermodynamics and takes advantage of the characteristics of the Fokker-Planck equation. This mechanism can be applied to manipulate biological particles inside a microfluidic system with identical, conjoined, spherical compartments. This theoretical analysis is verified by performing a rapid andmore » a simple technique for separating yeast cells in these conjoined, spherical microfluidic structures. The experimental results basically match with our theoretical model and we further analyze the parameters which can be used to control this separation mechanism. Both numerical simulations and experimental results show that the motion of the particles depends on the geometrical boundary conditions of the microfluidic system and the initial concentration of the diffusing material. This theoretical model can be implemented in future biophysics devices for the optimized design of passive cell sorters.« less

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Enhanced performance of microfluidic soft pressure sensors with embedded solid microspheres

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Frequency-Switchable Microfluidic CSRR-Loaded QMSIW Band-Pass Filter Using a Liquid Metal Alloy

PubMed Central

Eom, Seunghyun; Memon, Muhammad Usman; Lim, Sungjoon

2017-01-01

In this paper, we have proposed a frequency-switchable complementary split-ring resonator (CSRR)-loaded quarter-mode substrate-integrated-waveguide (QMSIW) band-pass filter. For frequency switching, a microfluidic channel and liquid metal are used. The liquid metal used is eutectic gallium-indium (EGaIn), consisting of 24.5% indium and 75.5% gallium. The microfluidic channels are built using the elastomer polydimethylsiloxane (PDMS) and three-dimensional-printed microfluidic channel frames. The CSRR-loaded QMSIW band-pass filter is designed to have two states. Before the injection of the liquid metal, the measured center frequency and fractional bandwidths are 2.205 GHz and 6.80%, respectively. After injection, the center frequency shifts from 2.205 GHz to 2.56 GHz. Although the coupling coefficient is practically unchanged, the fractional bandwidth changes from 6.8% to 9.38%, as the CSRR shape changes and the external quality factor decreases. After the removal of the liquid metal, the measured values are similar to the values recorded before the liquid metal was injected. The repeatability of the frequency-switchable mechanism is, therefore, verified. PMID:28350355

Biocompatibility of Tygon® tubing in microfluidic cell culture.

PubMed

Jiang, Xiao; Jeffries, Rex E; Acosta, Miguel A; Tikunov, Andrey P; Macdonald, Jeffrey M; Walker, Glenn M; Gamcsik, Michael P

2015-02-01

Growth of the MDA-MB-231 breast cancer cell line in microfluidic channels was inhibited when culture media was delivered to the channels via microbore Tygon® tubing. Culture media incubated within this tubing also inhibited growth of these cells in conventional 96-well plates. These detrimental effects were not due to depletion of critical nutrients due to adsorption of media components onto the tubing surface. A pH change was also ruled out as a cause. Nuclear magnetic resonance spectroscopy of the cell growth media before and after incubation in the tubing confirmed no detectable loss of media components but did detect the presence of additional unidentified signals in the aliphatic region of the spectrum. These results indicate leaching of a chemical species from microbore Tygon® tubing that can affect cell growth in microfluidic devices.

Microfluidic mixing through oscillatory transverse perturbations

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

DNA Molecules in Microfluidic Oscillatory Flow

PubMed Central

Chen, Y.-L.; Graham, M.D.; de Pablo, J.J.; Jo, K.; Schwartz, D.C.

2008-01-01

The conformation and dynamics of a single DNA molecule undergoing oscillatory pressure-driven flow in microfluidic channels is studied using Brownian dynamics simulations, accounting for hydrodynamic interactions between segments in the bulk and between the chain and the walls. Oscillatory flow provides a scenario under which the polymers may remain in the channel for an indefinite amount of time as they are stretched and migrate away from the channel walls. We show that by controlling the chain length, flow rate and oscillatory flow frequency, we are able to manipulate the chain extension and the chain migration from the channel walls. The chain stretch and the chain depletion layer thickness near the wall are found to increase as the Weissenberg number increases and as the oscillatory frequency decreases. PMID:19057656

High-sensitivity microfluidic calorimeters for biological and chemical applications.

PubMed

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

2009-09-08

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.

Sample flow switching techniques on microfluidic chips.

PubMed

Pan, Yu-Jen; Lin, Jin-Jie; Luo, Win-Jet; Yang, Ruey-Jen

2006-02-15

This paper presents an experimental investigation into electrokinetically focused flow injection for bio-analytical applications. A novel microfluidic device for microfluidic sample handling is presented. The microfluidic chip is fabricated on glass substrates using conventional photolithographic and chemical etching processes and is bonded using a high-temperature fusion method. The proposed valve-less device is capable not only of directing a single sample flow to a specified output port, but also of driving multiple samples to separate outlet channels or even to a single outlet to facilitate sample mixing. The experimental results confirm that the sample flow can be electrokinetically pre-focused into a narrow stream and guided to the desired outlet port by means of a simple control voltage model. The microchip presented within this paper has considerable potential for use in a variety of applications, including high-throughput chemical analysis, cell fusion, fraction collection, sample mixing, and many other applications within the micro-total-analysis systems field.

Dissolved oxygen sensing using organometallic dyes deposited within a microfluidic environment

NASA Astrophysics Data System (ADS)

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

2008-02-01

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

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

DOEpatents

Jacobson, Stephen C.; Ramsey, J. Michael

2004-09-14

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

A hydrophilic polymer based microfluidic system with planar patch clamp electrode array for electrophysiological measurement from cells.

PubMed

Xu, Baojian; Ye, WeiWei; Zhang, Yu; Shi, JingYu; Chan, ChunYu; Yao, XiaoQiang; Yang, Mo

2014-03-15

This paper presents a microfluidic planar patch clamp system based on a hydrophilic polymer poly(ethylene glycol) diacrylate (PEGDA) for whole cell current recording. The whole chip is fabricated by UV-assisted molding method for both microfluidic channel structure and planar electrode partition. This hydrophilic patch clamp chip has demonstrated a relatively high gigaseal success rate of 44% without surface modification compared with PDMS based patch clamp devices. This chip also shows a capability of rapid intracellular and extracellular solution exchange with high stability of gigaseals. The capillary flow kinetic experiments demonstrate that the flow rates of PEGDA microfluidic channels are around two orders of magnitude greater than those for PDMS-glass channels with the same channel dimensions. This hydrophilic polymer based patch clamp chips have significant advantages over current PDMS elastomer based systems such as no need for surface modification, much higher success rate of cell gigaseals and rapid solution exchange with stable cell gigaseals. Our results indicate the potential of these devices to serve as useful tools for pharmaceutical screening and biosensing tasks. © 2013 Elsevier B.V. All rights reserved.

On-chip gradient generation in 256 microfluidic cell cultures: simulation and experimental validation.

PubMed

Somaweera, Himali; Haputhanthri, Shehan O; Ibraguimov, Akif; Pappas, Dimitri

2015-08-07

A microfluidic diffusion diluter was used to create a stable concentration gradient for dose response studies. The microfluidic diffusion diluter used in this study consisted of 128 culture chambers on each side of the main fluidic channel. A calibration method was used to find unknown concentrations with 12% error. Flow rate dependent studies showed that changing the flow rates generated different gradient patterns. Mathematical simulations using COMSOL Multi-physics were performed to validate the experimental data. The experimental data obtained for the flow rate studies agreed with the simulation results. Cells could be loaded into culture chambers using vacuum actuation and cultured for long times under low shear stress. Decreasing the size of the culture chambers resulted in faster gradient formation (20 min). Mass transport into the side channels of the microfluidic diffusion diluter used in this study is an important factor in creating the gradient using diffusional mixing as a function of the distance. To demonstrate the device's utility, an H2O2 gradient was generated while culturing Ramos cells. Cell viability was assayed in the 256 culture chambers, each at a discrete H2O2 concentration. As expected, the cell viability for the high concentration side channels increased (by injecting H2O2) whereas the cell viability in the low concentration side channels decreased along the chip due to diffusional mixing as a function of distance. COMSOL simulations were used to identify the effective concentration of H2O2 for cell viability in each side chamber at 45 min. The gradient effects were confirmed using traditional H2O2 culture experiments. Viability of cells in the microfluidic device under gradient conditions showed a linear relationship with the viability of the traditional culture experiment. Development of the microfluidic device used in this study could be used to study hundreds of concentrations of a compound in a single experiment.

SAW-Based Phononic Crystal Microfluidic Sensor—Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications

PubMed Central

Lucklum, Ralf; Zubtsov, Mikhail; Schmidt, Marc-Peter; Mukhin, Nikolay V.; Hirsch, Soeren

2017-01-01

The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept. PMID:28946609

SAW-Based Phononic Crystal Microfluidic Sensor-Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications.

PubMed

Oseev, Aleksandr; Lucklum, Ralf; Zubtsov, Mikhail; Schmidt, Marc-Peter; Mukhin, Nikolay V; Hirsch, Soeren

2017-09-23

The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept.

Controllable picoliter pipetting using hydrophobic microfluidic valves

NASA Astrophysics Data System (ADS)

Zhang, M.; Huang, J.; Qian, X.; Mi, S.; Wang, X.

2017-06-01

A picoliter pipetting technique using the microfluidic method is presented. Utilizing the hydrophobic self-assembled monolayer films patterned in microchannels as pressure-controlled valves, a small volume of liquid can be separated by a designed channel trap and then ejected from the channel end at a higher pressure. The liquid trap section is composed of a T-shaped channel junction and a hydrophobic patch. The liquid volume can be precisely controlled by varying the distance of the hydrophobic patch from the T-junction. By this means, liquid less than 100 pl can be separated and pipetted. The developed device is potentially useful for sample dispensing in biological, medical, and chemical applications.

Microfluidics enables multiplex evaluation of the same cells for further studies.

PubMed

Mojica, W D; Oh, K W; Lee, H; Furlani, E P; Sykes, D; Sands, A M

2016-08-01

The continuous discovery of biomarkers and their evolving use for the diagnosis and guidance of therapy for patients with cancer has increased awareness of the need to triage biospecimens properly. On occasion, cytology samples are the only type of biospecimen available for analysis. Often, the current approach for these latter specimens is cytopathology-centric, with cells limited to examination by bright field microscopy. When specimens are paucicellular, there is often insufficient material for ancillary testing. Therefore, a need exists to develop an alternative approach that allows for the multiplexed analysis of cells when they are limited in number. In recent previous publications, we demonstrated that clinically derived cells from tissue are suitable for evaluation in a microfluidic device. In our current endeavour, we seek to expand upon those findings and determine if those same cells can be recovered for further analysis. A microfluidic channel was designed, fabricated and tested using cytology specimens generated from tissue specimens. The cytological features of the cells tested were examined prior to entering the channel; they were then compared to similar cells while in the channel, and upon recovery from the channel. Recovery of DNA and proteins were also tested. The morphology of the tested cells was not compromised in either the channel or upon recovery. More importantly, the integrity of the cells remained intact, with the recovery of proteins and high molecular weight DNA possible. We developed and tested an alternative approach to the processing of cytopathology specimens that enables multiplexed evaluation. Using microfluidics, cytological examination of biopecimens can be performed, but in contrast to existing approaches, the same cells examined can be recovered for downstream analysis. © 2015 John Wiley & Sons Ltd.

Systematic characterization of degas-driven flow for poly(dimethylsiloxane) microfluidic devices

DOE PAGES

Liang, David Y.; Tentori, Augusto M.; Dimov, Ivan K.; ...

2011-01-01

Degas-driven flow is a novel phenomenon used to propel fluids in poly(dimethylsiloxane) (PDMS)-based microfluidic devices without requiring any external power. This method takes advantage of the inherently high porosity and air solubility of PDMS by removing air molecules from the bulk PDMS before initiating the flow. The dynamics of degas-driven flow are dependent on the channel and device geometries and are highly sensitive to temporal parameters. These dependencies have not been fully characterized, hindering broad use of degas-driven flow as a microfluidic pumping mechanism. Here, we characterize, for the first time, the effect of various parameters on the dynamics ofmore » degas-driven flow, including channel geometry, PDMS thickness, PDMS exposure area, vacuum degassing time, and idle time at atmospheric pressure before loading. We investigate the effect of these parameters on flow velocity as well as channel fill time for the degas-driven flow process. Using our devices, we achieved reproducible flow with a standard deviation of less than 8% for flow velocity, as well as maximum flow rates of up to 3 nL/s and mean flow rates of approximately 1-1.5 nL/s. Parameters such as channel surface area and PDMS chip exposure area were found to have negligible impact on degas-driven flow dynamics, whereas channel cross-sectional area, degas time, PDMS thickness, and idle time were found to have a larger impact. In addition, we develop a physical model that can predict mean flow velocities within 6% of experimental values and can be used as a tool for future design of PDMS-based microfluidic devices that utilize degas-driven flow.« less

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.

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

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

DOEpatents

Frechet, Jean M. J. [Oakland, CA; Svec, Frantisek [Alameda, CA; Rohr, Thomas [Leiden, NL

2008-10-07

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

Nanofluidic interfaces in microfluidic networks

DOE PAGES

Millet, Larry J.; Doktycz, Mitchel John; Retterer, Scott T.

2015-09-24

The integration of nano- and microfluidic technologies enables the construction of tunable interfaces to physical and biological systems across relevant length scales. The ability to perform chemical manipulations of miniscule sample volumes is greatly enhanced through these technologies and extends the ability to manipulate and sample the local fluidic environments at subcellular, cellular and community or tissue scales. Here we describe the development of a flexible surface micromachining process for the creation of nanofluidic channel arrays integrated within SU-8 microfluidic networks. The use of a semi-porous, silicon rich, silicon nitride structural layer allows rapid release of the sacrificial silicon dioxidemore » during the nanochannel fabrication. Nanochannel openings that form the interface to biological samples are customized using focused ion beam milling. The compatibility of these interfaces with on-chip microbial culture is demonstrated.« less

Microfluidic viscometers for shear rheology of complex fluids and biofluids

PubMed Central

Wang, William S.; Vanapalli, Siva A.

2016-01-01

The rich diversity of man-made complex fluids and naturally occurring biofluids is opening up new opportunities for investigating their flow behavior and characterizing their rheological properties. Steady shear viscosity is undoubtedly the most widely characterized material property of these fluids. Although widely adopted, macroscale rheometers are limited by sample volumes, access to high shear rates, hydrodynamic instabilities, and interfacial artifacts. Currently, microfluidic devices are capable of handling low sample volumes, providing precision control of flow and channel geometry, enabling a high degree of multiplexing and automation, and integrating flow visualization and optical techniques. These intrinsic advantages of microfluidics have made it especially suitable for the steady shear rheology of complex fluids. In this paper, we review the use of microfluidics for conducting shear viscometry of complex fluids and biofluids with a focus on viscosity curves as a function of shear rate. We discuss the physical principles underlying different microfluidic viscometers, their unique features and limits of operation. This compilation of technological options will potentially serve in promoting the benefits of microfluidic viscometry along with evincing further interest and research in this area. We intend that this review will aid researchers handling and studying complex fluids in selecting and adopting microfluidic viscometers based on their needs. We conclude with challenges and future directions in microfluidic rheometry of complex fluids and biofluids. PMID:27478521

Symmetry-breaking bifurcations and enhanced mixing in microfluidic cross-slots

NASA Astrophysics Data System (ADS)

Poole, Rob; Haward, Simon; Oliveira, Paulo; Alves, Manuel

2014-11-01

We investigate, both experimentally and numerically, a new subcritical bifurcation phenomenon for a Newtonian fluid flowing through three-dimensional cross-slot geometries. At low Reynolds numbers the flow remains steady and symmetric. For the case of square inlets and outlets, at a critical Reynolds number of approximately 40 (based on average velocity) a pitchfork bifurcation is observed beyond which the unstable symmetrical solution is replaced by a pair of steady asymmetric solutions. Sensitivity of this critical Reynolds number to the initial conditions of the simulation, resulting in a small degree of hysteresis, suggests a subcritical instability. At higher flowrates the flow becomes unsteady. The effects of channel aspect ratio are investigated on the critical conditions and excellent agreement is found between three-dimensional finite volume simulations and flow visualisation experiments in microfluidic channels. Finally we suggest this new flow bifurcation could be an effective method of enhancing mixing in microfluidic channels as significant increases in mixing quality are observed beyond the bifurcation. This enhancement occurs at flowrates more than a factor of two smaller than those observed in the well-known T-channel micromixer.

Optimization of monolithic columns for microfluidic devices

NASA Astrophysics Data System (ADS)

Pagaduan, Jayson V.; Yang, Weichun; Woolley, Adam T.

2011-06-01

Monolithic columns offer advantages as solid-phase extractors because they offer high surface area that can be tailored to a specific function, fast mass transport, and ease of fabrication. Porous glycidyl methacrylate-ethylene glycol dimethacrylate monoliths were polymerized in-situ in microfluidic devices, without pre-treatment of the poly(methyl methacrylate) channel surface. Cyclohexanol, 1-dodecanol and Tween 20 were used to control the pore size of the monoliths. The epoxy groups on the monolith surface can be utilized to immobilize target-specific probes such as antibodies, aptamers, or DNA for biomarker detection. Microfluidic devices integrated with solid-phase extractors should be useful for point-of-care diagnostics in detecting specific biomarkers from complex biological fluids.

Role of Structural Asymmetry in Controlling Drop Spacing in Microfluidic Ladder Networks

NASA Astrophysics Data System (ADS)

Wang, William; Maddala, Jeevan; Vanapalli, Siva; Rengasamy, Raghunathan

2012-02-01

Manipulation of drop spacing is crucial to many processes in microfluidic devices including drop coalescence, detection and storage. Microfluidic ladder networks ---where two droplet-carrying parallel channels are connected by narrow bypass channels through which the motion of drops is forbidden---have been proposed as a means to control relative separation between pairs of drops. Prior studies in microfluidic ladder networks with vertical bypasses, which possess fore-aft structural symmetry, have revealed that pairs of drops can only undergo reduction in drop spacing at the ladder exit. We investigate the dynamics of drops in microfluidic ladder networks with both vertical and slanted bypasses. Our analytical results indicate that unlike symmetric ladder networks, structural asymmetry introduced by a single slanted bypass can be used to modulate the relative spacing between drops, enabling them to contract, synchronize, expand or even flip at the ladder exit. Our experiments confirm all the behaviors predicted by theory. Numerical analysis further shows that ladders containing several identical bypasses can only linearly transform the input drop spacing. Finally, we find that ladders with specific combinations of vertical and slanted bypasses can generate non-linear transformation of input drop spacing, despite the absence of drop decision-making events at the bypass junctions.

Pen-on-paper strategy for point-of-care testing: Rapid prototyping of fully written microfluidic biosensor.

PubMed

Li, Zedong; Li, Fei; Xing, Yue; Liu, Zhi; You, Minli; Li, Yingchun; Wen, Ting; Qu, Zhiguo; Ling Li, Xiao; Xu, Feng

2017-12-15

Paper-based microfluidic biosensors have recently attracted increasing attentions in point-of-care testing (POCT) territories benefiting from their affordable, accessible and eco-friendly features, where technologies for fabricating such biosensors are preferred to be equipment free, easy-to-operate and capable of rapid prototyping. In this work, we developed a pen-on-paper (PoP) strategy based on two custom-made pens, i.e., a wax pen and a conductive-ink pen, to fully write paper-based microfluidic biosensors through directly writing both microfluidic channels and electrodes. Particularly, the proposed wax pen is competent to realize one-step fabrication of wax channels on paper, as the melted wax penetrates into paper during writing process without any post-treatments. The practical applications of the fabricated paper-based microfluidic biosensors are demonstrated by both colorimetric detection of Salmonella typhimurium DNA with detection limit of 1nM and electrochemical measurement of glucose with detection limit of 1mM. The developed PoP strategy for making microfluidic biosensors on paper characterized by true simplicity, prominent portability and excellent capability for rapid prototyping shows promising prospect in POCT applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-10-21

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

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

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

Equilibrium gas-oil ratio measurements using a microfluidic technique.

PubMed

Fisher, Robert; Shah, Mohammad Khalid; Eskin, Dmitry; Schmidt, Kurt; Singh, Anil; Molla, Shahnawaz; Mostowfi, Farshid

2013-07-07

A method for measuring the equilibrium GOR (gas-oil ratio) of reservoir fluids using microfluidic technology is developed. Live crude oils (crude oil with dissolved gas) are injected into a long serpentine microchannel at reservoir pressure. The fluid forms a segmented flow as it travels through the channel. Gas and liquid phases are produced from the exit port of the channel that is maintained at atmospheric conditions. The process is analogous to the production of crude oil from a formation. By using compositional analysis and thermodynamic principles of hydrocarbon fluids, we show excellent equilibrium between the produced gas and liquid phases is achieved. The GOR of a reservoir fluid is a key parameter in determining the equation of state of a crude oil. Equations of state that are commonly used in petroleum engineering and reservoir simulations describe the phase behaviour of a fluid at equilibrium state. Therefore, to accurately determine the coefficients of an equation of state, the produced gas and liquid phases have to be as close to the thermodynamic equilibrium as possible. In the examples presented here, the GORs measured with the microfluidic technique agreed with GOR values obtained from conventional methods. Furthermore, when compared to conventional methods, the microfluidic technique was simpler to perform, required less equipment, and yielded better repeatability.

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

PubMed

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

2011-07-21

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

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.

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

PubMed

Watanabe, Masashi

2011-04-07

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

Microfluidic flow rate detection based on integrated optical fiber cantilever.

PubMed

Lien, Victor; Vollmer, Frank

2007-10-01

We demonstrate an integrated microfluidic flow sensor with ultra-wide dynamic range, suitable for high throughput applications such as flow cytometry and particle sorting/counting. A fiber-tip cantilever transduces flow rates to optical signal readout, and we demonstrate a dynamic range from 0 to 1500 microL min(-1) for operation in water. Fiber-optic sensor alignment is guided by preformed microfluidic channels, and the dynamic range can be adjusted in a one-step chemical etch. An overall non-linear response is attributed to the far-field angular distribution of single-mode fiber output.

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.

Collapse of Non-Rectangular Channels in a Soft Elastomer

NASA Astrophysics Data System (ADS)

Tepayotl-Ramirez, Daniel; Park, Yong-Lae; Lu, Tong; Majidi, Carmel

2013-03-01

We examine the collapse of microchannels in a soft elastomer by treating the sidewalls as in- denters that penetrate the channel base. This approach leads to a closed-form algebraic mapping between applied pressure and cross-sectional deformation that are in strong agreement with ex- perimental measurements and Finite Element Analysis (FEA) simulation. Applications of this new approach to modeling soft microchannel collapse range from lab-on-a-chip microfluidics for pressure-controlled protein filtration to soft-matter pressures sensing. We demonstrate the latter by comparing theoretical predictions with experimental measurements of the pressure-controlled electrical resistance of liquid-phase Gallium alloy microchannels embedded in a soft silicone elas- tomer.

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.

Low-cost feedback-controlled syringe pressure pumps for microfluidics applications.

PubMed

Lake, John R; Heyde, Keith C; Ruder, Warren C

2017-01-01

Microfluidics are widely used in research ranging from bioengineering and biomedical disciplines to chemistry and nanotechnology. As such, there are a large number of options for the devices used to drive and control flow through microfluidic channels. Commercially available syringe pumps are probably the most commonly used instruments for this purpose, but are relatively high-cost and have inherent limitations due to their flow profiles when they are run open-loop. Here, we present a low-cost ($110) syringe pressure pump that uses feedback control to regulate the pressure into microfluidic chips. Using an open-source microcontroller board (Arduino), we demonstrate an easily operated and programmable syringe pump that can be run using either a PID or bang-bang control method. Through feedback control of the pressure at the inlets of two microfluidic geometries, we have shown stability of our device to within ±1% of the set point using a PID control method and within ±5% of the set point using a bang-bang control method with response times of less than 1 second. This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips.

Low-cost feedback-controlled syringe pressure pumps for microfluidics applications

PubMed Central

Lake, John R.; Heyde, Keith C.

2017-01-01

Microfluidics are widely used in research ranging from bioengineering and biomedical disciplines to chemistry and nanotechnology. As such, there are a large number of options for the devices used to drive and control flow through microfluidic channels. Commercially available syringe pumps are probably the most commonly used instruments for this purpose, but are relatively high-cost and have inherent limitations due to their flow profiles when they are run open-loop. Here, we present a low-cost ($110) syringe pressure pump that uses feedback control to regulate the pressure into microfluidic chips. Using an open-source microcontroller board (Arduino), we demonstrate an easily operated and programmable syringe pump that can be run using either a PID or bang-bang control method. Through feedback control of the pressure at the inlets of two microfluidic geometries, we have shown stability of our device to within ±1% of the set point using a PID control method and within ±5% of the set point using a bang-bang control method with response times of less than 1 second. This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips. PMID:28369134

Suspended microfluidics.

PubMed

Casavant, Benjamin P; Berthier, Erwin; Theberge, Ashleigh B; Berthier, Jean; Montanez-Sauri, Sara I; Bischel, Lauren L; Brakke, Kenneth; Hedman, Curtis J; Bushman, Wade; Keller, Nancy P; Beebe, David J

2013-06-18

Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics.

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

On utilizing alternating current-flow field effect transistor for flexibly manipulating particles in microfluidics and nanofluidics

PubMed Central

Liu, Weiyu; Shao, Jinyou; Ren, Yukun; Liu, Jiangwei; Tao, Ye; Jiang, Hongyuan; Ding, Yucheng

2016-01-01

By imposing a biased gate voltage to a center metal strip, arbitrary symmetry breaking in induced-charge electroosmotic flow occurs on the surface of this planar gate electrode, a phenomenon termed as AC-flow field effect transistor (AC-FFET). In this work, the potential of AC-FFET with a shiftable flow stagnation line to flexibly manipulate micro-nano particle samples in both a static and continuous flow condition is demonstrated via theoretical analysis and experimental validation. The effect of finite Debye length of induced double-layer and applied field frequency on the manipulating flexibility factor for static condition is investigated, which indicates AC-FFET turns out to be more effective for achieving a position-controllable concentrating of target nanoparticle samples in nanofluidics compared to the previous trial in microfluidics. Besides, a continuous microfluidics-based particle concentrator/director is developed to deal with incoming analytes in dynamic condition, which exploits a design of tandem electrode configuration to consecutively flow focus and divert incoming particle samples to a desired downstream branch channel, as prerequisite for a following biochemical analysis. Our physical demonstrations with AC-FFET prove valuable for innovative designs of flexible electrokinetic frameworks, which can be conveniently integrated with other microfluidic or nanofluidic components into a complete lab-on-chip diagnostic platform due to a simple electrode structure. PMID:27190570

On utilizing alternating current-flow field effect transistor for flexibly manipulating particles in microfluidics and nanofluidics.

PubMed

Liu, Weiyu; Shao, Jinyou; Ren, Yukun; Liu, Jiangwei; Tao, Ye; Jiang, Hongyuan; Ding, Yucheng

2016-05-01

By imposing a biased gate voltage to a center metal strip, arbitrary symmetry breaking in induced-charge electroosmotic flow occurs on the surface of this planar gate electrode, a phenomenon termed as AC-flow field effect transistor (AC-FFET). In this work, the potential of AC-FFET with a shiftable flow stagnation line to flexibly manipulate micro-nano particle samples in both a static and continuous flow condition is demonstrated via theoretical analysis and experimental validation. The effect of finite Debye length of induced double-layer and applied field frequency on the manipulating flexibility factor for static condition is investigated, which indicates AC-FFET turns out to be more effective for achieving a position-controllable concentrating of target nanoparticle samples in nanofluidics compared to the previous trial in microfluidics. Besides, a continuous microfluidics-based particle concentrator/director is developed to deal with incoming analytes in dynamic condition, which exploits a design of tandem electrode configuration to consecutively flow focus and divert incoming particle samples to a desired downstream branch channel, as prerequisite for a following biochemical analysis. Our physical demonstrations with AC-FFET prove valuable for innovative designs of flexible electrokinetic frameworks, which can be conveniently integrated with other microfluidic or nanofluidic components into a complete lab-on-chip diagnostic platform due to a simple electrode structure.

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

PubMed

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

2017-11-01

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

From functional structure to packaging: full-printing fabrication of a microfluidic chip.

PubMed

Zheng, Fengyi; Pu, Zhihua; He, Enqi; Huang, Jiasheng; Yu, Bocheng; Li, Dachao; Li, Zhihong

2018-05-24

This paper presents a concept of a full-printing methodology aiming at convenient and fast fabrication of microfluidic devices. For the first time, we achieved a microfluidic biochemical sensor with all functional structures fabricated by inkjet printing, including electrodes, immobilized enzymes, microfluidic components and packaging. With the cost-effective and rapid process, this method provides the possibility of quick model validation of a novel lab-on-chip system. In this study, a three-electrode electrochemical system was integrated successfully with glucose oxidase immobilization gel and sealed in an ice channel, forming a disposable microfluidic sensor for glucose detection. This fully-printed chip was characterized and showed good sensitivity and a linear section at a low-level concentration of glucose (0-10 mM). With the aid of automatic equipment, the fully-printed sensor can be massively produced with low cost.

3D printed Lego®-like modular microfluidic devices based on capillary driving.

PubMed

Nie, Jing; Gao, Qing; Qiu, Jing-Jiang; Sun, Miao; Liu, An; Shao, Lei; Fu, Jian-Zhong; Zhao, Peng; He, Yong

2018-03-12

The field of how to rapidly assemble microfluidics with modular components continuously attracts researchers' attention, however, extra efforts must be devoted to solving the problems of leaking and aligning between individual modules. This paper presents a novel type of modular microfluidic device, driven by capillary force. There is no necessity for a strict seal or special alignment, and its open structures make it easy to integrate various stents and reactants. The key rationale for this method is to print different functional modules with a low-cost three-dimensional (3D) printer, then fill the channels with capillary materials and assemble them with plugs like Lego ® bricks. This rapidly reconstructed modular microfluidic device consists of a variety of common functional modules and other personalized modules, each module having a unified standard interface for easy assembly. As it can be printed by a desktop 3D printer, the manufacturing process is simple and efficient, with controllable regulation of the flow channel scale. Through diverse combinations of different modules, a variety of different functions can be achieved, without duplicating the manufacturing process. A single module can also be taken out for testing and analysis. What's more, combined with basic circuit components, it can serve as a low-cost Lego ® -like modular microfluidic circuits. As a proof of concept, the modular microfluidic device has been successfully demonstrated and used for stent degradation and cell cultures, revealing the potential use of this method in both chemical and biological research.

Physical context for theoretical approaches to sediment transport magnitude-frequency analysis in alluvial channels

NASA Astrophysics Data System (ADS)

Sholtes, Joel; Werbylo, Kevin; Bledsoe, Brian

2014-10-01

Theoretical approaches to magnitude-frequency analysis (MFA) of sediment transport in channels couple continuous flow probability density functions (PDFs) with power law flow-sediment transport relations (rating curves) to produce closed-form equations relating MFA metrics such as the effective discharge, Qeff, and fraction of sediment transported by discharges greater than Qeff, f+, to statistical moments of the flow PDF and rating curve parameters. These approaches have proven useful in understanding the theoretical drivers behind the magnitude and frequency of sediment transport. However, some of their basic assumptions and findings may not apply to natural rivers and streams with more complex flow-sediment transport relationships or management and design scenarios, which have finite time horizons. We use simple numerical experiments to test the validity of theoretical MFA approaches in predicting the magnitude and frequency of sediment transport. Median values of Qeff and f+ generated from repeated, synthetic, finite flow series diverge from those produced with theoretical approaches using the same underlying flow PDF. The closed-form relation for f+ is a monotonically increasing function of flow variance. However, using finite flow series, we find that f+ increases with flow variance to a threshold that increases with flow record length. By introducing a sediment entrainment threshold, we present a physical mechanism for the observed diverging relationship between Qeff and flow variance in fine and coarse-bed channels. Our work shows that through complex and threshold-driven relationships sediment transport mode, channel morphology, flow variance, and flow record length all interact to influence estimates of what flow frequencies are most responsible for transporting sediment in alluvial channels.

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

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

Effects of surface properties on droplet formation inside a microfluidic device

NASA Astrophysics Data System (ADS)

Steinhaus, Ben; Shen, Amy

2004-11-01

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

Microfluidic array platform for simultaneous lipid bilayer membrane formation.

PubMed

Zagnoni, M; Sandison, M E; Morgan, H

2009-01-01

In recent years, protein array technologies have found widespread applications in proteomics. However, new methods for high-throughput analysis of protein-protein and protein-compound interactions are still required. In this paper, an array of lipid bilayer membranes formed within a microfluidic system with integrated electrodes is presented. The system is comprised of three layers that are clamped together, thus rendering the device cleanable and reusable. The device microfluidics enable the simultaneous formation of an array of lipid bilayers using a previously developed air-exposure technique, thereby avoiding the need to manually form individual bilayers. The Ag/AgCl electrodes allow for ion channel measurements, each of the sites being independently addressable. Typically, a 50% yield in simultaneous lipid bilayer formation over 12 sites was obtained and ion channel recordings have been acquired over multiple sites. This system has great potential for the development of an automatable platform of suspended lipid bilayer arrays.

Microfluidic Platform for Analyzing the Thermotaxis of C. elegans in a Linear Temperature Gradient.

PubMed

Yoon, Sunhee; Piao, Hailing; Jeon, Tae-Joon; Kim, Sun Min

2017-01-01

Caenorhabditis elegans (C. elegans), which shares a considerable amount of characteristics with human genes is one of the important model organisms for the study of behavioral responses. Thermotaxis is a representative behavior response of C. elegans; C. elegans stores the cultivation temperature in thermosensory neurons and moves to the cultivation temperature region in a temperature variation. In this study, we developed a microfluidic system for effective thermotaxis analysis of C. elegans. The microfluidic channel was fabricated using polydimethylsiloxane (PDMS) by soft lithography process. The temperature gradient (15 - 20°C) was generated in the microchannel and controlled by Peltier modules attached to the bottom of the channel. The thermotaxis of wild type (N2), tax-4(p678) and ttx-7(nj50) mutants were effectively analyzed using this microfluidic system. We believe that this system can be employed as a basic platform for studying the neural circuit of C. elegans responding to external stimuli.

Chip in a lab: Microfluidics for next generation life science research

PubMed Central

Streets, Aaron M.; Huang, Yanyi

2013-01-01

Microfluidic circuits are characterized by fluidic channels and chambers with a linear dimension on the order of tens to hundreds of micrometers. Components of this size enable lab-on-a-chip technology that has much promise, for example, in the development of point-of-care diagnostics. Micro-scale fluidic circuits also yield practical, physical, and technological advantages for studying biological systems, enhancing the ability of researchers to make more precise quantitative measurements. Microfluidic technology has thus become a powerful tool in the life science research laboratory over the past decade. Here we focus on chip-in-a-lab applications of microfluidics and survey some examples of how small fluidic components have provided researchers with new tools for life science research. PMID:23460772

Embellishment of microfluidic devices via femtosecond laser micronanofabrication for chip functionalization.

PubMed

Wang, Juan; He, Yan; Xia, Hong; Niu, Li-Gang; Zhang, Ran; Chen, Qi-Dai; Zhang, Yong-Lai; Li, Yan-Feng; Zeng, Shao-Jiang; Qin, Jian-Hua; Lin, Bing-Cheng; Sun, Hong-Bo

2010-08-07

This paper demonstrates the embellishment of existing microfluidic devices with integrated three dimensional (3D) micronanostructures via femtosecond laser micronanofabrication, which, for the first time, proves two-photon photopolymerization (TPP) to be a powerful technology for chip functionalization. As representative examples, microsieves with various pore shape and adjustable pore size were successfully fabricated inside a conventional glass-based microfluidic channel prepared by wet etching for microparticle separation. Moreover, a fish scale like microfilter was also fabricated and appointed as a one-way valve, which showed excellent performance as we expected. These results indicate that such embellishment of microfluidic devices is simple, low cost, flexible and easy to access. We believe that, combined with TPP, the application of lab-on-chip devices would be further extended.

Concurrent DNA Preconcentration and Separation in Bipolar Electrode-Based Microfluidic Device

PubMed Central

Song, Hongjun; Wang, Yi; Garson, Charles; Pant, Kapil

2015-01-01

This paper presents a bipolar electrode (BPE) device in a microfluidic dual-channel design for concurrent preconcentration and separation of composite DNA containing samples. The novelty of the present effort relies on the combination of BPE-induced ion concentration polarization (ICP) and end-labeled free-solution electrophoresis (ELFSE). The ion concentration polarization effect arising from the faradaic reaction on the BPE is utilized to exert opposing electrophoretic and electroosmotic forces on the DNA samples. Meanwhile, end-labeled free-solution electrophoresis alters the mass-charge ratio to enable simultaneous DNA separation in free solution. The microfluidic device was fabricated using standard and soft lithography techniques to form gold-on-glass electrode capped with a PDMS microfluidic channel. Experimental testing with various DNA samples was carried out over a range of applied electric field. Concentration ratios up to 285× within 5 minutes for a 102-mer DNA, and concurrent preconcentration and free-solution separation of binary mixture of free and bound 102-mer DNA within 6 minutes was demonstrated. The effect of applied electric field was also interrogated with respect to pertinent performance metrics of preconcentration and separation. PMID:26005497

Computational Analysis of Enhanced Magnetic Bioseparation in Microfluidic Systems with Flow-Invasive Magnetic Elements

PubMed Central

Khashan, S. A.; Alazzam, A.; Furlani, E. P.

2014-01-01

A microfluidic design is proposed for realizing greatly enhanced separation of magnetically-labeled bioparticles using integrated soft-magnetic elements. The elements are fixed and intersect the carrier fluid (flow-invasive) with their length transverse to the flow. They are magnetized using a bias field to produce a particle capture force. Multiple stair-step elements are used to provide efficient capture throughout the entire flow channel. This is in contrast to conventional systems wherein the elements are integrated into the walls of the channel, which restricts efficient capture to limited regions of the channel due to the short range nature of the magnetic force. This severely limits the channel size and hence throughput. Flow-invasive elements overcome this limitation and enable microfluidic bioseparation systems with superior scalability. This enhanced functionality is quantified for the first time using a computational model that accounts for the dominant mechanisms of particle transport including fully-coupled particle-fluid momentum transfer. PMID:24931437

Additive manufacturing of microfluidic glass chips

NASA Astrophysics Data System (ADS)

Kotz, F.; Helmer, D.; Rapp, B. E.

2018-02-01

Additive manufacturing has gained great interest in the microfluidic community due to the numerous channel designs which can be tested in the early phases of a lab-on-a-chip device development. High resolution additive manufacturing like microstereolithography is largely associated with polymers. Polymers are at a disadvantage compared to other materials due to their softness and low chemical resistance. Whenever high chemical and thermal resistance combined with high optical transparency is needed, glasses become the material of choice. However, glasses are difficult to structure at the microscale requiring hazardous chemicals for etching processes. In this work we present additive manufacturing and high resolution patterning of microfluidic chips in transparent fused silica glass using stereolithography and microlithography. We print an amorphous silica nanocomposite at room temperature using benchtop stereolithography printers and a custom built microlithography system based on a digital mirror device. Using microlithography we printed structures with tens of micron resolution. The printed part is then converted to a transparent fused silica glass using thermal debinding and sintering. Printing of a microfluidic chip can be done within 30 minutes. The heat treatment can be done within two days.

Cooperative suction by vertical capillary array pump for controlling flow profiles of microfluidic sensor chips.

PubMed

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

2012-10-18

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.

Single nanopore transport of synthetic and biological polyelectrolytes in three-dimensional hybrid microfluidic/nanofluidic devices

DOE PAGES

King, Travis L.; Gatimu, Enid N.; Bohn, Paul W.

2009-01-02

This paper presents a study of electrokinetic transport in single nanopores integrated into vertically-stacked three-dimensional hybrid microfluidic/nanofluidic structures. In these devices single nanopores, created by focused ion beam (FIB) milling in thin polymer films, provide fluidic connection between two vertically separated, perpendicular microfluidic channels. Experiments address both systems in which the nanoporous membrane is composed of the same (homojunction) or different (heterojunction) polymer as the microfluidic channels. These devices are then used to study the electrokinetic transport properties of synthetic (i.e., polystyrene sulfonate and polyallylamine) and biological (i.e.,DNA) polyelectrolytes across these nanopores. Single nanopore transport of polyelectrolytes across these nanoporesmore » using both electrical current measurements and confocal microscopy. Both optical and electrical measurements indicate that electroosmotic transport is predominant over electrophoresis in single nanopores with d > 180 nm, consistent with results obtained under similar conditions for nanocapillary array membranes.« less

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

Shrink film patterning by craft cutter: complete plastic chips with high resolution/high-aspect ratio channel.

PubMed

Taylor, Douglas; Dyer, David; Lew, Valerie; Khine, Michelle

2010-09-21

This paper presents a rapid, ultra-low-cost approach to fabricate microfluidic devices using a polyolefin shrink film and a digital craft cutter. The shrinking process (with a 95% reduction in area) results in relatively uniform and consistent microfluidic channels with smooth surfaces, vertical sidewalls, and high aspect ratio channels with lateral resolutions well beyond the tool used to cut them. The thermal bonding of the layers results in strongly bonded devices. Complex microfluidic designs are easily designed on the fly and protein assays are also readily integrated into the device. Full device characterization including channel consistency, optical properties, and bonding strength are assessed in this technical note.

Implementation of an optimized microfluidic mixer in alumina employing femtosecond laser ablation

NASA Astrophysics Data System (ADS)

Juodėnas, M.; Tamulevičius, T.; Ulčinas, O.; Tamulevičius, S.

2018-01-01

Manipulation of liquids at the lowest levels of volume and dimension is at the forefront of materials science, chemistry and medicine, offering important time and resource saving applications. However, manipulation by mixing is troublesome at the microliter and lower scales. One approach to overcome this problem is to use passive mixers, which exploit structural obstacles within microfluidic channels or the geometry of channels themselves to enforce and enhance fluid mixing. Some applications require the manipulation and mixing of aggressive substances, which makes conventional microfluidic materials, along with their fabrication methods, inappropriate. In this work, implementation of an optimized full scale three port microfluidic mixer is presented in a slide of a material that is very hard to process but possesses extreme chemical and physical resistance—alumina. The viability of the selected femtosecond laser fabrication method as an alternative to conventional lithography methods, which are unable to process this material, is demonstrated. For the validation and optimization of the microfluidic mixer, a finite element method (FEM) based numerical modeling of the influence of the mixer geometry on its mixing performance is completed. Experimental investigation of the laminar flow geometry demonstrated very good agreement with the numerical simulation results. Such a laser ablation microfabricated passive mixer structure is intended for use in a capillary force assisted nanoparticle assembly setup (CAPA).

Fluid delivery manifolds and microfluidic systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renzi, Ronald F.; Sommer, Gregory J.; Singh, Anup K.

2017-02-28

Embodiments of fluid distribution manifolds, cartridges, and microfluidic systems are described herein. Fluid distribution manifolds may include an insert member and a manifold base and may define a substantially closed channel within the manifold when the insert member is press-fit into the base. Cartridges described herein may allow for simultaneous electrical and fluidic interconnection with an electrical multiplex board and may be held in place using magnetic attraction.

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

PubMed

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

2016-06-20

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

Microfluidic LC Device with Orthogonal Sample Extraction for On-Chip MALDI-MS Detection

PubMed Central

Lazar, Iulia M.; Kabulski, Jarod L.

2013-01-01

A microfluidic device that enables on-chip matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) detection for liquid chromatography (LC) separations is described. The device comprises an array of functional elements to carry out LC separations, integrates a novel microchip-MS interface to facilitate the orthogonal transposition of the microfluidic LC channel into an array of reservoirs, and enables sensitive MALDI-MS detection directly from the chip. Essentially, the device provides a snapshot MALDI-MS map of the content of the separation channel present on the chip. The detection of proteins with biomarker potential from MCF10A breast epithelial cell extracts, and detection limits in the low fmol range, are demonstrated. In addition, the design of the novel LC-MALDI-MS chip entices the promotion of a new concept for performing sample separations within the limited time-frame that accompanies the dead-volume of a separation channel. PMID:23592150

Investigation of the capillary flow through open surface microfluidic structures

NASA Astrophysics Data System (ADS)

Taher, Ahmed; Jones, Benjamin; Fiorini, Paolo; Lagae, Liesbet

2017-02-01

The passive nature of capillary microfluidics for pumping and actuation of fluids is attractive for many applications including point of care medical diagnostics. For such applications, there is often the need to spot dried chemical reagents in the bottom of microfluidic channels after device fabrication; it is often more practical to have open surface devices (i.e., without a cover or lid). However, the dynamics of capillary driven flow in open surface devices have not been well studied for many geometries of interest. In this paper, we investigate capillary flow in an open surface microchannel with a backward facing step. An analytical model is developed to calculate the capillary pressure as the liquid-vapor interface traverses a backward facing step in an open microchannel. The developed model is validated against results from Surface Evolver liquid-vapor surface simulations and ANSYS Fluent two-phase flow simulations using the volume of fluid approach. Three different aspect ratios (inlet channel height by channel width) were studied. The analytical model shows good agreement with the simulation results from both modeling methods for all geometries. The analytical model is used to derive an expression for the critical aspect ratio (the minimum channel aspect ratio for flow to proceed across the backward facing step) as a function of contact angle.

Direct etch method for microfludic channel and nanoheight post-fabrication by picoliter droplets

NASA Astrophysics Data System (ADS)

Demirci, Utkan; Toner, Mehmet

2006-01-01

Photolithography is an expensive and significant step in microfabrication. Approaches that could change lithography would create an impact on semiconductor industry and microelectromechanical systems technologies. We demonstrate a direct etching method by ejecting etchant droplets at desired locations by using microdroplet ejector arrays. This method could be used for easy fabrication of poly(dimethylsiloxane) microfluidic channels and nanometer height postlike structures in microfluidic channels.

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

Microfluidic etching and oxime-based tailoring of biodegradable polyketoesters.

PubMed

Barrett, Devin G; Lamb, Brian M; Yousaf, Muhammad N

2008-09-02

A straightforward, flexible, and inexpensive method to etch biodegradable poly(1,2,6-hexanetriol alpha-ketoglutarate) films is reported. Microfluidic delivery of the etchant, a solution of NaOH, can create micron-scale channels through local hydrolysis of the polyester film. In addition, the presence of a ketone in the repeat unit allows for prior or post chemoselective modifications, enabling the design of functionalized microchannels. Delivery of oxyamine tethered ligands react with ketone groups on the polyketoester to generate covalent oxime linkages. By thermally sealing an etched film to a second flat surface, poly(1,2,6-hexanetriol alpha-ketoglutarate) can be used to create biodegradable microfluidic devices. In order to determine the versatility of the microfluidic etch technique, poly(epsilon-caprolactone) was etched with acetone. This strategy provides a facile method for the direct patterning of biodegradable materials, both through etching and chemoselective ligand immobilization.

Microfluidics-based, time-resolved mechanical phenotyping of cells using high-speed imaging

NASA Astrophysics Data System (ADS)

Belotti, Yuri; Conneely, Michael; Huang, Tianjun; McKenna, Stephen; Nabi, Ghulam; McGloin, David

2017-07-01

We demonstrate a single channel hydrodynamic stretching microfluidic device that relies on high-speed imaging to allow repeated dynamic cell deformation measurements. Experiments on prostate cancer cells suggest richer data than current approaches.

Micro Machining of Injection Mold Inserts for Fluidic Channel of Polymeric Biochips

PubMed Central

Jung, Woo-Chul; Heo, Young-Moo; Yoon, Gil-Sang; Shin, Kwang-Ho; Chang, Sung-Ho; Kim, Gun-Hee; Cho, Myeong-Woo

2007-01-01

Recently, the polymeric micro-fluidic biochip, often called LOC (lab-on-a-chip), has been focused as a cheap, rapid and simplified method to replace the existing biochemical laboratory works. It becomes possible to form miniaturized lab functionalities on a chip with the development of MEMS technologies. The micro-fluidic chips contain many micro-channels for the flow of sample and reagents, mixing, and detection tasks. Typical substrate materials for the chip are glass and polymers. Typical techniques for microfluidic chip fabrication are utilizing various micro pattern forming methods, such as wet-etching, micro-contact printing, and hot-embossing, micro injection molding, LIGA, and micro powder blasting processes, etc. In this study, to establish the basis of the micro pattern fabrication and mass production of polymeric micro-fluidic chips using injection molding process, micro machining method was applied to form micro-channels on the LOC molds. In the research, a series of machining experiments using micro end-mills were performed to determine optimum machining conditions to improve surface roughness and shape accuracy of designed simplified micro-channels. Obtained conditions were used to machine required mold inserts for micro-channels using micro end-mills. Test injection processes using machined molds and COC polymer were performed, and then the results were investigated.

High-volume production of single and compound emulsions in a microfluidic parallelization arrangement coupled with coaxial annular world-to-chip interfaces.

PubMed

Nisisako, Takasi; Ando, Takuya; Hatsuzawa, Takeshi

2012-09-21

This study describes a microfluidic platform with coaxial annular world-to-chip interfaces for high-throughput production of single and compound emulsion droplets, having controlled sizes and internal compositions. The production module consists of two distinct elements: a planar square chip on which many copies of a microfluidic droplet generator (MFDG) are arranged circularly, and a cubic supporting module with coaxial annular channels for supplying fluids evenly to the inlets of the mounted chip, assembled from blocks with cylinders and holes. Three-dimensional flow was simulated to evaluate the distribution of flow velocity in the coaxial multiple annular channels. By coupling a 1.5 cm × 1.5 cm microfluidic chip with parallelized 144 MFDGs and a supporting module with two annular channels, for example, we could produce simple oil-in-water (O/W) emulsion droplets having a mean diameter of 90.7 μm and a coefficient of variation (CV) of 2.2% at a throughput of 180.0 mL h(-1). Furthermore, we successfully demonstrated high-throughput production of Janus droplets, double emulsions and triple emulsions, by coupling 1.5 cm × 1.5 cm - 4.5 cm × 4.5 cm microfluidic chips with parallelized 32-128 MFDGs of various geometries and supporting modules with 3-4 annular channels.

Plasma treatments of wool fiber surface for microfluidic applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeon, So-Hyoun; Hwang, Ki-Hwan; Lee, Jin Su

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 thismore » 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.« less

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

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.

A microfluidics-based technique for automated and rapid labeling of cells for flow cytometry

NASA Astrophysics Data System (ADS)

Patibandla, Phani K.; Estrada, Rosendo; Kannan, Manasaa; Sethu, Palaniappan

2014-03-01

Flow cytometry is a powerful technique capable of simultaneous multi-parametric analysis of heterogeneous cell populations for research and clinical applications. In recent years, the flow cytometer has been miniaturized and made portable for application in clinical- and resource-limited settings. The sample preparation procedure, i.e. labeling of cells with antibodies conjugated to fluorescent labels, is a time consuming (˜45 min) and labor-intensive procedure. Microfluidics provides enabling technologies to accomplish rapid and automated sample preparation. Using an integrated microfluidic device consisting of a labeling and washing module, we demonstrate a new protocol that can eliminate sample handling and accomplish sample and reagent metering, high-efficiency mixing, labeling and washing in rapid automated fashion. The labeling module consists of a long microfluidic channel with an integrated chaotic mixer. Samples and reagents are precisely metered into this device to accomplish rapid and high-efficiency mixing. The mixed sample and reagents are collected in a holding syringe and held for up to 8 min following which the mixture is introduced into an inertial washing module to obtain ‘analysis-ready’ samples. The washing module consists of a high aspect ratio channel capable of focusing cells to equilibrium positions close to the channel walls. By introducing the cells and labeling reagents in a narrow stream at the center of the channel flanked on both sides by a wash buffer, the elution of cells into the wash buffer away from the free unbound antibodies is accomplished. After initial calibration experiments to determine appropriate ‘holding time’ to allow antibody binding, both modules were used in conjunction to label MOLT-3 cells (T lymphoblast cell line) with three different antibodies simultaneously. Results confirm no significant difference in mean fluorescence intensity values for all three antibodies labels (p < 0.01) between the

A microfluidic thermometer: Precise temperature measurements in microliter- and nanoliter-scale volumes

PubMed Central

McKenzie, Brittney A.

2017-01-01

Measuring the temperature of a sample is a fundamental need in many biological and chemical processes. When the volume of the sample is on the microliter or nanoliter scale (e.g., cells, microorganisms, precious samples, or samples in microfluidic devices), accurate measurement of the sample temperature becomes challenging. In this work, we demonstrate a technique for accurately determining the temperature of microliter volumes using a simple 3D-printed microfluidic chip. We accomplish this by first filling “microfluidic thermometer” channels on the chip with substances with precisely known freezing/melting points. We then use a thermoelectric cooler to create a stable and linear temperature gradient along these channels within a measurement region on the chip. A custom software tool (available as online Supporting Information) is then used to find the locations of solid-liquid interfaces in the thermometer channels; these locations have known temperatures equal to the freezing/melting points of the substances in the channels. The software then uses the locations of these interfaces to calculate the temperature at any desired point within the measurement region. Using this approach, the temperature of any microliter-scale on-chip sample can be measured with an uncertainty of about a quarter of a degree Celsius. As a proof-of-concept, we use this technique to measure the unknown freezing point of a 50 microliter volume of solution and demonstrate its feasibility on a 400 nanoliter sample. Additionally, this technique can be used to measure the temperature of any on-chip sample, not just near-zero-Celsius freezing points. We demonstrate this by using an oil that solidifies near room temperature (coconut oil) in a microfluidic thermometer to measure on-chip temperatures well above zero Celsius. By providing a low-cost and simple way to accurately measure temperatures in small volumes, this technique should find applications in both research and educational

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

PubMed

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

2008-04-01

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

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

2015-10-07

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

A novel microfluidic valve controlledby induced charge electro-osmotic flow

NASA Astrophysics Data System (ADS)

Wang, Chengfa; Song, Yongxin; Pan, Xinxiang; Li, Dongqing

2016-07-01

In this paper, a novel microfluidic valve by utilizing induced charge electro-osmotic flow (ICEOF) is proposed and analyzed. The key part of the microfluidic valve is a Y-shaped microchannel. A small metal plate is placed at each corner of the junction of the Y-shaped microchannel. When a DC electrical field is applied through the channels, electro-osmotic flows occur in the channels, and two vortices will be formed near each of the metal plates due to the ICEOF. The two vortices behave like virtual ‘blocking columns’ to restrain and direct the flow in the Y-channel. In this paper, effects of the length of the metal plates, the applied voltages, the width of the microchannel, the zeta potential of the non-metal microchannel wall, and the orientation of the branch channels on the flow switching between two outlet channels are numerically investigated. The results show that the flow switching between the two outlet channels can be flexibly achieved by adjusting the applied DC voltages. The critical switching voltage (CSV), under which one outlet channel is closed, decreases with the increase in the metal plate length and the orientation angle of the outlet channels. The CSV, however, increases with the increase in the inlet voltage, the width of the microchannel, and the absolute value of the zeta potential of the non-metal microchannel wall. Compared with other types of micro-valves, the proposed micro-valve is simple in structure without any moving parts. Only a DC power source is needed for its actuation, thus it can operate automatically by controlling the applied voltages.

Quasi-3D Modeling and Efficient Simulation of Laminar Flows in Microfluidic Devices.

PubMed

Islam, Md Zahurul; Tsui, Ying Yin

2016-10-03

A quasi-3D model has been developed to simulate the flow in planar microfluidic systems with low Reynolds numbers. The model was developed by decomposing the flow profile along the height of a microfluidic system into a Fourier series. It was validated against the analytical solution for flow in a straight rectangular channel and the full 3D numerical COMSOL Navier-Stokes solver for flow in a T-channel. Comparable accuracy to the full 3D numerical solution was achieved by using only three Fourier terms with a significant decrease in computation time. The quasi-3D model was used to model flows in a micro-flow cytometer chip on a desktop computer and good agreement between the simulation and the experimental results was found.

Integrated microelectrode array and microfluidics for temperature clamp of sensory neurons in culture.

PubMed

Pearce, Thomas M; Wilson, J Adam; Oakes, S George; Chiu, Shing-Yan; Williams, Justin C

2005-01-01

A device for cell culture is presented that combines MEMS technology and liquid-phase photolithography to create a microfluidic chip that influences and records electrical cellular activity. A photopolymer channel network is formed on top of a multichannel microelectrode array. Preliminary results indicated successful local thermal control within microfluidic channels and control of lamina position over the electrode array. To demonstrate the biological application of such a device, adult dissociated dorsal root ganglion neurons with a subpopulation of thermally-sensitive cells are attached onto the electrode array. Using laminar flow, dynamic control of local temperature of the neural cells was achieved while maintaining a constant chemical culture medium. Recording the expected altered cellular activity confirms the success of the integrated device.

Double emulsions from a capillary array injection microfluidic device.

PubMed

Shang, Luoran; Cheng, Yao; Wang, Jie; Ding, Haibo; Rong, Fei; Zhao, Yuanjin; Gu, Zhongze

2014-09-21

A facile microfluidic device was developed by inserting an annular capillary array into a collection channel for single-step emulsification of double emulsions. By inserting multiple inner-phase solutions into the capillary array, multicomponent double emulsions or microcapsules with inner droplets of different content could also be obtained from the device.

Microfluidic bead-based diodes with targeted circular microchannels for low Reynolds number applications.

PubMed

Sochol, Ryan D; Lu, Albert; Lei, Jonathan; Iwai, Kosuke; Lee, Luke P; Lin, Liwei

2014-05-07

Self-regulating fluidic components are critical to the advancement of microfluidic processors for chemical and biological applications, such as sample preparation on chip, point-of-care molecular diagnostics, and implantable drug delivery devices. Although researchers have developed a wide range of components to enable flow rectification in fluidic systems, engineering microfluidic diodes that function at the low Reynolds number (Re) flows and smaller scales of emerging micro/nanofluidic platforms has remained a considerable challenge. Recently, researchers have demonstrated microfluidic diodes that utilize high numbers of suspended microbeads as dynamic resistive elements; however, using spherical particles to block fluid flow through rectangular microchannels is inherently limited. To overcome this issue, here we present a single-layer microfluidic bead-based diode (18 μm in height) that uses a targeted circular-shaped microchannel for the docking of a single microbead (15 μm in diameter) to rectify fluid flow under low Re conditions. Three-dimensional simulations and experimental results revealed that adjusting the docking channel geometry and size to better match the suspended microbead greatly increased the diodicity (Di) performance. Arraying multiple bead-based diodes in parallel was found to adversely affect system efficacy, while arraying multiple diodes in series was observed to enhance device performance. In particular, systems consisting of four microfluidic bead-based diodes with targeted circular-shaped docking channels in series revealed average Di's ranging from 2.72 ± 0.41 to 10.21 ± 1.53 corresponding to Re varying from 0.1 to 0.6.

Transferring vertically aligned carbon nanotubes onto a polymeric substrate using a hot embossing technique for microfluidic applications.

PubMed

Mathur, A; Roy, S S; McLaughlin, J A

2010-07-06

We explored the hot embossing method for transferring vertically aligned carbon nanotubes (CNTs) into microfluidic channels, fabricated on poly-methyl-methacrylate (PMMA). Patterned and unpatterned CNTs were synthesized by microwave plasma-enhanced chemical vapour deposition on silicon to work as a stamp. For hot embossing, 115 degrees C and 1 kN force for 2 min were found to be the most suitable parameters for the complete transfer of aligned CNTs on the PMMA microchannel. Raman and SEM studies were used to analyse the microstructure of CNTs before and after hot embossing. The PMMA microparticles with dimensions (approx. 10 microm in diameter) similar to red blood cells were successfully filtered using laminar flow through these microfluidic channels. Finally, a microfluidic-based point-of-care device for blood filtration and detection of bio-molecules is drawn schematically.

Transferring vertically aligned carbon nanotubes onto a polymeric substrate using a hot embossing technique for microfluidic applications

PubMed Central

Mathur, A.; Roy, S. S.; McLaughlin, J. A.

2010-01-01

We explored the hot embossing method for transferring vertically aligned carbon nanotubes (CNTs) into microfluidic channels, fabricated on poly-methyl-methacrylate (PMMA). Patterned and unpatterned CNTs were synthesized by microwave plasma-enhanced chemical vapour deposition on silicon to work as a stamp. For hot embossing, 115°C and 1 kN force for 2 min were found to be the most suitable parameters for the complete transfer of aligned CNTs on the PMMA microchannel. Raman and SEM studies were used to analyse the microstructure of CNTs before and after hot embossing. The PMMA microparticles with dimensions (approx. 10 µm in diameter) similar to red blood cells were successfully filtered using laminar flow through these microfluidic channels. Finally, a microfluidic-based point-of-care device for blood filtration and detection of bio-molecules is drawn schematically. PMID:20147316

Rapid fabrication of microfluidic chips based on the simplest LED lithography

NASA Astrophysics Data System (ADS)

Li, Yue; Wu, Ping; Luo, Zhaofeng; Ren, Yuxuan; Liao, Meixiang; Feng, Lili; Li, Yuting; He, Liqun

2015-05-01

Microfluidic chips are generally fabricated by a soft lithography method employing commercial lithography equipment. These heavy machines require a critical room environment and high lamp power, and the cost remains too high for most normal laboratories. Here we present a novel microfluidics fabrication method utilizing a portable ultraviolet (UV) LED as an alternative UV source for photolithography. With this approach, we can repeat several common microchannels as do these conventional commercial exposure machines, and both the verticality of the channel sidewall and lithography resolution are proved to be acceptable. Further microfluidics applications such as mixing, blood typing and microdroplet generation are implemented to validate the practicability of the chips. This simple but innovative method decreases the cost and requirement of chip fabrication dramatically and may be more popular with ordinary laboratories.

Ion channel electrophysiology via integrated planar patch-clamp chip with on-demand drug exchange.

PubMed

Chen, Chang-Yu; Tu, Ting-Yuan; Jong, De-Shien; Wo, Andrew M

2011-06-01

Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays. Copyright © 2011 Wiley Periodicals, Inc.

Digital microfluidics: Droplet based logic gates

NASA Astrophysics Data System (ADS)

Cheow, Lih Feng; Yobas, Levent; Kwong, Dim-Lee

2007-01-01

The authors present microfluidic logic gates based on two-phase flows at low Reynold's number. The presence and the absence of a dispersed phase liquid (slug) in a continuous phase liquid represent 1 and 0, respectively. The working principle of these devices is based on the change in hydrodynamic resistance for a channel containing droplets. Logical operations including AND, OR, and NOT are demonstrated, and may pave the way for microfludic system automation and computation.

Tape underlayment rotary-node (TURN) valves for simple on-chip microfluidic flow control

PubMed Central

Markov, Dmitry A.; Manuel, Steven; Shor, Leslie M.; Opalenik, Susan R.; Wikswo, John P.; Samson, Philip C.

2013-01-01

We describe a simple and reliable fabrication method for producing multiple, manually activated microfluidic control valves in polydimethylsiloxane (PDMS) devices. These screwdriver-actuated valves reside directly on the microfluidic chip and can provide both simple on/off operation as well as graded control of fluid flow. The fabrication procedure can be easily implemented in any soft lithography lab and requires only two specialized tools – a hot-glue gun and a machined brass mold. To facilitate use in multi-valve fluidic systems, the mold is designed to produce a linear tape that contains a series of plastic rotary nodes with small stainless steel machine screws that form individual valves which can be easily separated for applications when only single valves are required. The tape and its valves are placed on the surface of a partially cured thin PDMS microchannel device while the PDMS is still on the soft-lithographic master, with the master providing alignment marks for the tape. The tape is permanently affixed to the microchannel device by pouring an over-layer of PDMS, to form a full-thickness device with the tape as an enclosed underlayment. The advantages of these Tape Underlayment Rotary-Node (TURN) valves include parallel fabrication of multiple valves, low risk of damaging a microfluidic device during valve installation, high torque, elimination of stripped threads, the capabilities of TURN hydraulic actuators, and facile customization of TURN molds. We have utilized these valves to control microfluidic flow, to control the onset of molecular diffusion, and to manipulate channel connectivity. Practical applications of TURN valves include control of loading and chemokine release in chemotaxis assay devices, flow in microfluidic bioreactors, and channel connectivity in microfluidic devices intended to study competition and predator / prey relationships among microbes. PMID:19859812

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

PubMed Central

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

2016-01-01

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

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.

Small volume low mechanical stress cytometry using computer-controlled Braille display microfluidics.

PubMed

Tung, Yi-Chung; Torisawa, Yu-suke; Futai, Nobuyuki; Takayama, Shuichi

2007-11-01

This paper describes a micro flow cytometer system designed for efficient and non-damaging analysis of samples with small numbers of precious cells. The system utilizes actuation of Braille-display pins for micro-scale fluid manipulation and a fluorescence microscope with a CCD camera for optical detection. The microfluidic chip is fully disposable and is composed of a polydimethylsiloxane (PDMS) slab with microchannel features sealed against a thin deformable PDMS membrane. The channels are designed with diffusers to alleviate pulsatile flow behaviors inherent in pin actuator-based peristaltic pumping schemes to maximize hydrodynamic focusing of samples with minimal disturbances in the laminar streams within the channel. A funnel connected to the microfluidic channel is designed for efficient loading of samples with small number of cells and is also positioned on the chip to prevent physical damages of the samples by the squeezing actions of Braille pins during actuation. The sample loading scheme was characterized by both computational fluidic dynamics (CFD) simulation and experimental observation. A fluorescein solution was first used for flow field investigation, followed by use of fluorescence beads with known relative intensities for optical detection performance calibration. Murine myoblast cells (C2C12) were exploited to investigate cell viability for the sample loading scheme of the device. Furthermore, human promyelocytic leukemia (HL60) cells stained by hypotonic DNA staining buffer were also tested in the system for cell cycle analysis. The ability to efficiently analyze cellular samples where the number of cells is small was demonstrated by analyzing cells from a single embryoid body derived from mouse embryonic stem cells. Consequently, the designed microfluidic device reported in this paper is promising for easy-to-use, small sample size flow cytometric analysis, and has potential to be further integrated with other Braille display-based microfluidic

A Magnetic Resonance (MR) Microscopy System using a Microfluidically Cryo-Cooled Planar Coil

PubMed Central

Koo, Chiwan; Godley, Richard F.; Park, Jaewon; McDougall, Mary P.; Wright, Steven M.; Han, Arum

2011-01-01

We present the development of a microfluidically cryo-cooled planar coil for magnetic resonance (MR) microscopy. Cryogenically cooling radiofrequency (RF) coils for magnetic resonance imaging (MRI) can improve the signal to noise ratio (SNR) of the experiment. Conventional cryostats typically use a vacuum gap to keep samples to be imaged, especially biological samples, at or near room temperature during cryo-cooling. This limits how close a cryo-cooled coil can be placed to the sample. At the same time, a small coil-to-sample distance significantly improves the MR imaging capability due to the limited imaging depth of planar MR microcoils. These two conflicting requirements pose challenges to the use of cryo-cooling in MR microcoils. The use of a microfluidic based cryostat for localized cryo-cooling of MR microcoils is a step towards eliminating these constraints. The system presented here consists of planar receive-only coils with integrated cryo-cooling microfluidic channels underneath, and an imaging surface on top of the planar coils separated by a thin nitrogen gas gap. Polymer microfluidic channel structures fabricated through soft lithography processes were used to flow liquid nitrogen under the coils in order to cryo-cool the planar coils to liquid nitrogen temperature (−196°C). Two unique features of the cryo-cooling system minimize the distance between the coil and the sample: 1) The small dimension of the polymer microfluidic channel enables localized cooling of the planar coils, while minimizing thermal effects on the nearby imaging surface. 2) The imaging surface is separated from the cryo-cooled planar coil by a thin gap through which nitrogen gas flows to thermally insulate the imaging surface, keeping it above 0°C and preventing potential damage to biological samples. The localized cooling effect was validated by simulations, bench testing, and MR imaging experiments. Using this cryo-cooled planar coil system inside a 4.7 Tesla MR system

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices.

PubMed

Shiroma, Letícia S; Piazzetta, Maria H O; Duarte-Junior, Gerson F; Coltro, Wendell K T; Carrilho, Emanuel; Gobbi, Angelo L; Lima, Renato S

2016-05-16

This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al.

Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices

PubMed Central

Shiroma, Letícia S.; Piazzetta, Maria H. O.; Duarte-Junior, Gerson F.; Coltro, Wendell K. T.; Carrilho, Emanuel; Gobbi, Angelo L.; Lima, Renato S.

2016-01-01

This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al. PMID:27181918

Geometrical effect characterization of femtosecond-laser manufactured glass microfluidic chips based on optical manipulation of submicroparticles

NASA Astrophysics Data System (ADS)

Kotsifaki, Domna G.; Mackenzie, Mark D.; Polydefki, Georgia; Kar, Ajoy K.; Makropoulou, Mersini; Serafetinides, Alexandros A.

2017-12-01

Microfluidic devices provide a platform with wide ranging applications from environmental monitoring to disease diagnosis. They offer substantive advantages but are often not optimized or designed to be used by nonexpert researchers. Microchannels of a microanalysis platform and their geometrical characterization are of eminent importance when designing such devices. We present a method that is used to optimize each microchannel within a device using high-throughput particle manipulation. For this purpose, glass-based microfluidic devices, with three-dimensional channel networks of several geometrical sizes, were fabricated by employing laser fabrication techniques. The effect of channel geometry was investigated by employing an optical tweezer. The optical trapping force depends on the flow velocity that is associated with the dimensions of the microchannel. We observe a linear dependence of the trapping efficiency and of the fluid flow velocity, with the channel dimensions. We determined that the highest trapping efficiency was achieved for microchannels with aspect ratio equal to one. Numerical simulation validated the impact of the device design dimensions on the trapping efficiency. This investigation indicates that the geometrical characteristics, the flow velocity, and trapping efficiency are crucial and should be considered when fabricating microfluidic devices for cell studies.

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

Electrofluidic Circuit-Based Microfluidic Viscometer for Analysis of Newtonian and Non-Newtonian Liquids under Different Temperatures.

PubMed

Lee, Tse-Ang; Liao, Wei-Hao; Wu, Yi-Fan; Chen, Yeng-Long; Tung, Yi-Chung

2018-02-06

This paper reports a microfluidic viscometer with an integrated pressure sensor based on electrofluidic circuits, which are electrical circuits constructed by ionic liquid-filled microfluidic channels. The electrofluidic circuit provides a pressure-sensing scheme with great long-term and thermal stability. The viscosity of the tested fluidic sample is estimated by its flow resistance, which is a function of pressure drop, flow rate, and the geometry of the microfluidic channel. The viscometer can be exploited to measure viscosity of either Newtonian or non-Newtonian power-law fluid under various shear rates (3-500 1/s) and temperatures (4-70 °C) with small sample volume (less than 400 μL). The developed sensor-integrated microfluidic viscometer is made of poly(dimethylsiloxane) (PDMS) with transparent electrofluidic circuit, which makes it feasible to simultaneously image samples under tests. In addition, the entire device is disposable to prevent cross-contamination between samples, which is desired for various chemical and biomedical applications. In the experiments, viscosities of Newtonian fluids, glycerol water solutions with different concentrations and a mixture of pyrogallol and sodium hydroxide (NaOH), and non-Newtonian fluids, xanthan gum solutions and human blood samples, have been characterized. The results demonstrate that the developed microfluidic viscometer provides a convenient and useful platform for practical viscosity characterization of fluidic samples for a wide variety of applications.

Assembly of multiple cell gradients directed by three-dimensional microfluidic channels.

PubMed

Li, Yiwei; Feng, Xiaojun; Wang, Yachao; Du, Wei; Chen, Peng; Liu, Chao; Liu, Bi-Feng

2015-08-07

Active control over the cell gradient is essential for understanding biological systems and the reconstitution of the functionality of many types of tissues, particularly for organ-on-a-chip. Here, we propose a three-dimensional (3D) microfluidic strategy for generating controllable cell gradients. In this approach, a homogeneous cell suspension is loaded into a 3D stair-shaped PDMS microchannel to generate a cell gradient within 10 min by sedimentation. We demonstrate that cell gradients of various profiles (exponential and piecewise linear) can be achieved by precisely controlling the height of each layer during the fabrication. With sequential seeding, we further demonstrate the generation of two overlapping cell gradients on the same glass substrate with pre-defined designs. The cell gradient-based QD cytotoxicity assay also demonstrated that cell behaviors and resistances were regulated by the changes in cell density. These results reveal that the proposed 3D microfluidic strategy provides a simple and versatile means for establishing controllable gradients in cell density, opening up a new avenue for reconstructing functional tissues.

Microfluidic mixing using orbiting magnetic microbeads

NASA Astrophysics Data System (ADS)

Ballard, Matthew; Owen, Drew; Mao, Wenbin; Hesketh, Peter; Alexeev, Alexander

2013-11-01

Using three-dimensional simulations and experiments, we examine mixing in a microfluidic channel that incorporates a hybrid passive-active micromixer. The passive part of the mixer consists of a series of angled parallel ridges lining the top microchannel wall. The active component of the mixer is made up of microbeads rotating around small pillars on the bottom of the microchannel. In our simulations, we use a binary fluid lattice Boltzmann model to simulate the system and characterize the microfluidic mixing in the system. We consider the passive and active micromixers separately and evaluate their combined effect on the mixing of binary fluids. We compare our simulations with the experimental results obtained in a microchannel with magnetically actuated microbeads. Our findings guide the design of an efficient micromixer to be used in sampling in complex fluids. Financial support from NSF (CBET-1159726) is gratefully acknowledged.

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

PubMed Central

2013-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2009-10-01

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

Microfluidic EBG Sensor Based on Phase-Shift Method Realized Using 3D Printing Technology

PubMed Central

Radonić, Vasa; Birgermajer, Slobodan; Kitić, Goran

2017-01-01

In this article, we propose a novel microfluidic microstrip electromagnetic band gap (EBG) sensor realized using cost-effective 3D printing technology. Microstrip sensor allows monitoring of the fluid properties flowing in the microchannel embedded between the microstrip line and ground plane. The sensor’s operating principle is based on the phase-shift method, which allows the characterization at a single operating frequency of 6 GHz. The defected electromagnetic band gap (EBG) structure is realized as a pattern in the microstrip ground plane to improve sensor sensitivity. The designed microfluidic channel is fabricated using a fused deposition modelling (FDM) 3D printing process without additional supporting layers, while the conductive layers are realized using sticky aluminium tape. The measurement results show that the change of permittivity of the fluid in the microfluidic channel from 1 to 80 results in the phase-shift difference of almost 90°. The potential application is demonstrated through the implementation of a proposed sensor for the detection of toluene concentration in toluene–methanol mixture where various concentrations of toluene were analysed. PMID:28420217

Microfluidic EBG Sensor Based on Phase-Shift Method Realized Using 3D Printing Technology.

PubMed

Radonić, Vasa; Birgermajer, Slobodan; Kitić, Goran

2017-04-18

In this article, we propose a novel microfluidic microstrip electromagnetic band gap (EBG) sensor realized using cost-effective 3D printing technology. Microstrip sensor allows monitoring of the fluid properties flowing in the microchannel embedded between the microstrip line and ground plane. The sensor's operating principle is based on the phase-shift method, which allows the characterization at a single operating frequency of 6 GHz. The defected electromagnetic band gap (EBG) structure is realized as a pattern in the microstrip ground plane to improve sensor sensitivity. The designed microfluidic channel is fabricated using a fused deposition modelling (FDM) 3D printing process without additional supporting layers, while the conductive layers are realized using sticky aluminium tape. The measurement results show that the change of permittivity of the fluid in the microfluidic channel from 1 to 80 results in the phase-shift difference of almost 90°. The potential application is demonstrated through the implementation of a proposed sensor for the detection of toluene concentration in toluene-methanol mixture where various concentrations of toluene were analysed.

Microfluidic devices with permeable polymer barriers for capture and transport of biomolecules and cells.

PubMed

Lee, Ho Suk; Chu, Wai Keung; Zhang, Kun; Huang, Xiaohua

2013-09-07

We report a method for fabricating permeable polymer microstructure barriers in polydimethylsiloxane (PDMS) microfluidic devices and the use of the devices to capture and transport DNA and cells. The polymer microstructure in a desired location in a fluidic channel is formed in situ by the polymerization of acrylamide and polyethylene diacrylate cross-linker (PEG-DA) monomer in a solution which is trapped in the location using a pair of PDMS valves. The porous polymer microstructure provides a mechanical barrier to convective fluid flow in the channel or between two microfluidic chambers while it still conducts ions or small charged species under an electric field, allowing for the rapid capture and transport of biomolecules and cells by electrophoresis. We have demonstrated the application of the devices for the rapid capture and efficient release of bacteriophage λ genomic DNA, solution exchange and for the transport and capture of HeLa cells. Our devices will enable the multi-step processing of biomolecules and cells or individual cells within a single microfluidic chamber.

Quasi-3D Modeling and Efficient Simulation of Laminar Flows in Microfluidic Devices

PubMed Central

Islam, Md. Zahurul; Tsui, Ying Yin

2016-01-01

A quasi-3D model has been developed to simulate the flow in planar microfluidic systems with low Reynolds numbers. The model was developed by decomposing the flow profile along the height of a microfluidic system into a Fourier series. It was validated against the analytical solution for flow in a straight rectangular channel and the full 3D numerical COMSOL Navier-Stokes solver for flow in a T-channel. Comparable accuracy to the full 3D numerical solution was achieved by using only three Fourier terms with a significant decrease in computation time. The quasi-3D model was used to model flows in a micro-flow cytometer chip on a desktop computer and good agreement between the simulation and the experimental results was found. PMID:27706104

In-air microfluidics enables rapid fabrication of emulsions, suspensions, and 3D modular (bio)materials

PubMed Central

Visser, Claas Willem; Kamperman, Tom; Karbaat, Lisanne P.; Lohse, Detlef; Karperien, Marcel

2018-01-01

Microfluidic chips provide unparalleled control over droplets and jets, which have advanced all natural sciences. However, microfluidic applications could be vastly expanded by increasing the per-channel throughput and directly exploiting the output of chips for rapid additive manufacturing. We unlock these features with in-air microfluidics, a new chip-free platform to manipulate microscale liquid streams in the air. By controlling the composition and in-air impact of liquid microjets by surface tension–driven encapsulation, we fabricate monodisperse emulsions, particles, and fibers with diameters of 20 to 300 μm at rates that are 10 to 100 times higher than chip-based droplet microfluidics. Furthermore, in-air microfluidics uniquely enables module-based production of three-dimensional (3D) multiscale (bio)materials in one step because droplets are partially solidified in-flight and can immediately be printed onto a substrate. In-air microfluidics is cytocompatible, as demonstrated by additive manufacturing of 3D modular constructs with tailored microenvironments for multiple cell types. Its in-line control, high throughput and resolution, and cytocompatibility make in-air microfluidics a versatile platform technology for science, industry, and health care. PMID:29399628

Displacement of particles in microfluidics by laser-generated tandem bubbles

NASA Astrophysics Data System (ADS)

Lautz, Jaclyn; Sankin, Georgy; Yuan, Fang; Zhong, Pei

2010-11-01

The dynamic interaction between laser-generated tandem bubble and individual polystyrene particles of 2 and 10 μm in diameter is studied in a microfluidic channel (25 μm height) by high-speed imaging and particle image velocimetry. The asymmetric collapse of the tandem bubble produces a pair of microjets and associated long-lasting vortices that can propel a single particle to a maximum velocity of 1.4 m/s in 30 μs after the bubble collapse with a resultant directional displacement up to 60 μm in 150 μs. This method may be useful for high-throughput cell sorting in microfluidic devices.

High-throughput synchronization of mammalian cell cultures by spiral microfluidics.

PubMed

Lee, Wong Cheng; Bhagat, Ali Asgar S; Lim, Chwee Teck

2014-01-01

The development of mammalian cell cycle synchronization techniques has greatly advanced our understanding of many cellular regulatory events and mechanisms specific to different phases of the cell cycle. In this chapter, we describe a high-throughput microfluidic-based approach for cell cycle synchronization. By exploiting the relationship between cell size and its phase in the cell cycle, large numbers of synchronized cells can be obtained by size fractionation in a spiral microfluidic channel. Protocols for the synchronization of primary cells such as mesenchymal stem cells, and immortal cell lines such as Chinese hamster ovarian cells (CHO-CD36) and HeLa cells are provided as examples.

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

In this article, a transparent integrated microfluidic device composed of a 3D-printed thin-layer flow cell (3D-PTLFC) and an S-shaped screen-printed electrode (SPE) has been designed and fabricated for heavy metal ion stripping analysis. A finite element modeling (FEM) simulation is employed to optimize the shape of the electrode, the direction of the inlet pipeline, the thin-layer channel height and the sample flow rate to enhance the electron-enrichment efficiency for stripping analysis. The results demonstrate that the S-shaped SPE configuration matches the channel in 3D-PTLFC perfectly for the anodic stripping behavior of the heavy metal ions. Under optimized conditions, a wide linear range of 1-80 µg l-1 is achieved for Pb2+ detection with a limit of 0.3 µg l-1 for the microfluidic device. Thus, the obtained integrated microfluidic device proves to be a promising approach for heavy metal ions stripping analysis with low cost and high performance.

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

DOEpatents

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

2015-11-17

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

Droplet electric separator microfluidic device for cell sorting

NASA Astrophysics Data System (ADS)

Guo, Feng; Ji, Xing-Hu; Liu, Kan; He, Rong-Xiang; Zhao, Li-Bo; Guo, Zhi-Xiao; Liu, Wei; Guo, Shi-Shang; Zhao, Xing-Zhong

2010-05-01

A simple and effective droplet electric separator microfluidic device was developed for cell sorting. The aqueous droplet without precharging operation was influenced to move a distance in the channel along the electric field direction by applying dc voltage on the electrodes beside the channel, which made the target droplet flowing to the collector. Single droplet can be isolated in a sorting rate of ˜100 Hz with microelectrodes under a required pulse. Single or multiple mammalian cell (HePG2) encapsulated in the surfactant free alginate droplet could be sorted out respectively. This method may be used for single cell operation or analysis.

Hybrid microfluidics combined with active and passive approaches for continuous cell separation.

PubMed

Yan, Sheng; Zhang, Jun; Yuan, Dan; Li, Weihua

2017-01-01

Microfluidics, which is classified as either active or passive, is capable of separating cells of interest from a complex and heterogeneous sample. Active methods utilise external fields such as electric, magnetic, acoustic, and optical to drive cells for separation, while passive methods utilise channel structures, intrinsic hydrodynamic forces, and steric hindrances to manipulate cells. However, when processing complex biological samples such as whole blood with rare cells, separation with a single module microfluidic device is difficult. Hybrid microfluidics is an emerging technique, which utilises active and passive methods whilst fulfilling higher requirements for stable performance, versatility, and convenience, including (i) the ability to process multi-target cells, (ii) enhanced ability for multiplexed separation, (iii) higher sensitivity, and (iv) tunability for a wider operational range. This review introduces the fundamental physics and typical formats for subclasses of hybrid microfluidic devices based on their different physical fields; presents current examples of cell sorting to highlight the advantage and usefulness of hybrid microfluidics on biomedicine, and then discusses the challenges and perspective of future development and the promising direction of research in this field. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2012-11-18

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

Microfluidic separation of magnetic nanoparticles on an ordered array of magnetized micropillars

NASA Astrophysics Data System (ADS)

Orlandi, G.; Kuzhir, P.; Izmaylov, Y.; Alves Marins, J.; Ezzaier, H.; Robert, L.; Doutre, F.; Noblin, X.; Lomenech, C.; Bossis, G.; Meunier, A.; Sandoz, G.; Zubarev, A.

2016-06-01

Microfluidic separation of magnetic particles is based on their capture by magnetized microcollectors while the suspending fluid flows past the microcollectors inside a microchannel. Separation of nanoparticles is often challenging because of strong Brownian motion. Low capture efficiency of nanoparticles limits their applications in bioanalysis. However, at some conditions, magnetic nanoparticles may undergo field-induced aggregation that amplifies the magnetic attractive force proportionally to the aggregate volume and considerably increases nanoparticle capture efficiency. In this paper, we have demonstrated the role of such aggregation on an efficient capture of magnetic nanoparticles (about 80 nm in diameter) in a microfluidic channel equipped with a nickel micropillar array. This array was magnetized by an external uniform magnetic field, of intensity as low as 6-10 kA/m, and experiments were carried out at flow rates ranging between 0.3 and 30 μ L /min . Nanoparticle capture is shown to be mostly governed by the Mason number Ma, while the dipolar coupling parameter α does not exhibit a clear effect in the studied range, 1.4 < α < 4.5. The capture efficiency Λ shows a strongly decreasing Mason number behavior, Λ ∝M a-1.78 within the range 32 ≤ Ma ≤ 3250. We have proposed a simple theoretical model which considers destructible nanoparticle chains and gives the scaling behavior, Λ ∝M a-1.7 , close to the experimental findings.

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.

Development of a microfluidic perfusion 3D cell culture system

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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.

Pneumatic oscillator circuits for timing and control of integrated microfluidics.

PubMed

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

2013-11-05

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

A microfluidic multi-injector for gradient generation.

PubMed

Chung, Bong Geun; Lin, Francis; Jeon, Noo Li

2006-06-01

This paper describes a microfluidic multi-injector (MMI) that can generate temporal and spatial concentration gradients of soluble molecules. Compared to conventional glass micropipette-based methods that generate a single gradient, the MMI exploits microfluidic integration and actuation of multiple pulsatile injectors to generate arbitrary overlapping gradients that have not previously been possible. The MMI device is fabricated in poly(dimethylsiloxane) (PDMS) using multi-layer soft lithography and consists of fluidic channels and control channels with pneumatically actuated on-chip barrier valves. Repetitive actuation of on-chip valves control pulsatile release of solution that establishes microscopic chemical gradients around the orifice. The volume of solution released per actuation cycle ranged from 30 picolitres to several hundred picolitres and increased linearly with the duration of valve opening. The shape of the measured gradient profile agreed closely with the simulated diffusion profile from a point source. Steady state gradient profiles could be attained within 10 minutes, or less with an optimized pulse sequence. Overlapping gradients from 2 injectors were generated and characterized to highlight the advantages of MMI over conventional micropipette assays. The MMI platform should be useful for a wide range of basic and applied studies on chemotaxis and axon guidance.

In Situ Fabrication of 3D Ag@ZnO Nanostructures for Microfluidic Surface-Enhanced Raman Scattering Systems

PubMed Central

2015-01-01

In this work, we develop an in situ method to grow highly controllable, sensitive, three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrates via an optothermal effect within microfluidic devices. Implementing this approach, we fabricate SERS substrates composed of Ag@ZnO structures at prescribed locations inside microfluidic channels, sites within which current fabrication of SERS structures has been arduous. Conveniently, properties of the 3D Ag@ZnO nanostructures such as length, packing density, and coverage can also be adjusted by tuning laser irradiation parameters. After exploring the fabrication of the 3D nanostructures, we demonstrate a SERS enhancement factor of up to ∼2 × 106 and investigate the optical properties of the 3D Ag@ZnO structures through finite-difference time-domain simulations. To illustrate the potential value of our technique, low concentrations of biomolecules in the liquid state are detected. Moreover, an integrated cell-trapping function of the 3D Ag@ZnO structures records the surface chemical fingerprint of a living cell. Overall, our optothermal-effect-based fabrication technique offers an effective combination of microfluidics with SERS, resolving problems associated with the fabrication of SERS substrates in microfluidic channels. With its advantages in functionality, simplicity, and sensitivity, the microfluidic-SERS platform presented should be valuable in many biological, biochemical, and biomedical applications. PMID:25402207

On the theoretical velocity distribution and flow resistance in natural channels

NASA Astrophysics Data System (ADS)

Moramarco, Tommaso; Dingman, S. Lawrence

2017-12-01

The velocity distribution in natural channels is of considerable interest for streamflow measurements to obtain information on discharge and flow resistance. This study focuses on the comparison of theoretical velocity distributions based on 1) entropy theory, and 2) the two-parameter power law. The analysis identifies the correlation between the parameters of the distributions and defines their dependence on the geometric and hydraulic characteristics of the channel. Specifically, we investigate how the parameters are related to the flow resistance in terms of Manning roughness, shear velocity and water surface slope, and several formulae showing their relationships are proposed. Velocity measurements carried out in the past 20 years at Ponte Nuovo gauged section along the Tiber River, central Italy, are the basis for the analysis.

Microfluidic rectifier based on poly(dimethylsiloxane) membrane and its application to a micropump.

PubMed

Wang, Yao-Nan; Tsai, Chien-Hsiung; Fu, Lung-Ming; Lin Liou, Lung-Kai

2013-01-01

A microfluidic rectifier incorporating an obstructed microchannel and a PDMS membrane is proposed. During forward flow, the membrane deflects in the upward direction; thereby allowing the fluid to pass over the obstacle. Conversely, during reverse flow, the membrane seals against the obstacle, thereby closing the channel and preventing flow. It is shown that the proposed device can operate over a wide pressure range by increasing or decreasing the membrane thickness as required. A microfluidic pump is realized by integrating the rectifier with a simple stepper motor mechanism. The experimental results show that the pump can achieve a vertical left height of more than 2 m. Moreover, it is shown that a maximum flow rate of 6.3 ml/min can be obtained given a membrane thickness of 200 μm and a motor velocity of 80 rpm. In other words, the proposed microfluidic rectifier not only provides an effective means of preventing reverse flow but also permits the realization of a highly efficient microfluidic pump.

Fabrication of robust tooling for mass production of polymeric microfluidic devices

NASA Astrophysics Data System (ADS)

Fu, G.; Tor, S. B.; Loh, N. H.; Hardt, D. E.

2010-08-01

Polymer microfluidic devices are gaining popularity for bio-applications. In both commonly used methods for the fabrication of polymer microfluidic devices, i.e. injection molding and hot-embossing, the quality of a mold insert is of high importance. Micro powder injection molding (μPIM) provides a suitable option for metal mold insert fabrication. In this paper, two mold inserts with micro-features of different patterns and sizes were produced using 316L stainless steel powder and an in-house binder system. The mold inserts were successfully used to produce cyclic olefin copolymer (COC, trade name TOPAS) micromixer plates with micro-channels of widths 100 µm and 50 µm. Compared with CNC-machined hot work steel mold inserts, the quality of the micro-channels is better as far as geometrical quality and dimensional tolerance are concerned. However, surface finish and flatness of the μPIM mold inserts are inferior to those of CNC-machined mold inserts.

A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation.

PubMed

Wu, Huei-Wen; Hsiao, Yi-Hsing; Chen, Chih-Chen; Yet, Shaw-Fang; Hsu, Chia-Hsien

2016-07-06

The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

Hyperuniform materials made with microfluidics

NASA Astrophysics Data System (ADS)

Yazhgur, Pavel; Ricouvier, Joshua; Pierrat, Romain; Carminati, RéMi; Tabeling, Patrick

Hyperuniform materials, being disordered systems with suppressed long-scale fluctuations, now attract a significant scientific interest, especially due to their potential applications for disordered photonic materials production. In our project we study a jammed packing of oil droplets in water. The droplets are produced in a PDMS microfluidic chip and directly assembled in a microfluidic channel. By varying the fluid pressures we manage to sharply control the droplet production and thereby govern the structural properties of the obtained material. The pseudo-2D (a monolayer of droplets) and 3D systems are investigated. Our results show that at appropriate experimental conditions droplets self-organize in hyperuniform patterns. Our electromagnetic simulations also show that the obtained material can be transparent while staying optically dense. As far as we know, the proposed material is one of the first examples of experimentally made hyperuniform materials. We hope that our studies will help to establish a new way of disordered photonic materials production. The Microflusa project receives funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 664823.

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.

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

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.

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.

3D pulsed laser-triggered high-speed microfluidic fluorescence-activated cell sorter

PubMed Central

Chen, Yue; Wu, Ting-Hsiang; Kung, Yu-Chun; Teitell, Michael A.; Chiou, Pei-Yu

2014-01-01

We report a 3D microfluidic pulsed laser-triggered fluorescence-activated cell sorter capable of sorting at a throughput of 23,000 cells sec−1 with 90% purity in high-purity mode and at a throughput of 45,000 cells sec−1 with 45% purity in enrichment mode in one stage and in a single channel. This performance is realized by exciting laser-induced cavitation bubbles in a 3D PDMS microfluidic channel to generate high-speed liquid jets that deflect detected fluorescent cells and particles focused by 3D sheath flows. The ultrafast switching mechanism (20 μsec complete on-off cycle), small liquid jet perturbation volume, and three-dimensional sheath flow focusing for accurate timing control of fast (1.5 m sec−1) passing cells and particles are three critical factors enabling high-purity sorting at high-throughput in this sorter. PMID:23844418

Development of a general method for obtaining the geometry of microfluidic networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Razavi, Mohammad Sayed, E-mail: m.sayedrazavi@gmail.com; Salimpour, M. R.; Shirani, Ebrahim

2014-01-15

In the present study, a general method for geometry of fluidic networks is developed with emphasis on pressure-driven flows in the microfluidic applications. The design method is based on general features of network's geometry such as cross-sectional area and length of channels. Also, the method is applicable to various cross-sectional shapes such as circular, rectangular, triangular, and trapezoidal cross sections. Using constructal theory, the flow resistance, energy loss and performance of the network are optimized. Also, by this method, practical design strategies for the fabrication of microfluidic networks can be improved. The design method enables rapid prediction of fluid flowmore » in the complex network of channels and is very useful for improving proper miniaturization and integration of microfluidic networks. Minimization of flow resistance of the network of channels leads to universal constants for consecutive cross-sectional areas and lengths. For a Y-shaped network, the optimal ratios of consecutive cross-section areas (A{sub i+1}/A{sub i}) and lengths (L{sub i+1}/L{sub i}) are obtained as A{sub i+1}/A{sub i} = 2{sup −2/3} and L{sub i+1}/L{sub i} = 2{sup −1/3}, respectively. It is shown that energy loss in the network is proportional to the volume of network. It is also seen when the number of channels is increased both the hydraulic resistance and the volume occupied by the network are increased in a similar manner. Furthermore, the method offers that fabrication of multi-depth and multi-width microchannels should be considered as an integral part of designing procedures. Finally, numerical simulations for the fluid flow in the network have been performed and results show very good agreement with analytic results.« less

Use of Ice-Nucleating Proteins To Improve the Performance of Freeze-Thaw Valves in Microfluidic Devices.

PubMed

Gaiteri, Joseph C; Henley, W Hampton; Siegfried, Nathan A; Linz, Thomas H; Ramsey, J Michael

2017-06-06

Currently, reliable valving on integrated microfluidic devices fabricated from rigid materials is confined to expensive and complex methods. Freeze-thaw valves (FTVs) can provide a low cost, low complexity valving mechanism, but reliable implementation of them has been greatly hindered by the lack of ice nucleation sites within the valve body's small volume. Work to date has required very low temperatures (on the order of -40 °C or colder) to induce freezing without nucleation sites, making FTVs impractical due to instrument engineering challenges. Here, we report the use of ice-nucleating proteins (INPs) to induce ice formation at relatively warm temperatures in microfluidic devices. Microfluidic channels were filled with buffers containing femtomolar INP concentrations from Pseudomonas syringae. The channels were cooled externally with simple, small-footprint Peltier thermoelectric coolers (TECs), and the times required for channel freezing (valve closure) and thawing (valve opening) were measured. Under optimized conditions in plastic chips, INPs made sub-10 s actuations possible at TEC temperatures as warm as -13 °C. Additionally, INPs were found to have no discernible inhibitory effects in model enzyme-linked immunosorbent assays or polymerase chain reactions, indicating their compatibility with microfluidic systems that incorporate these widely used bioassays. FTVs with INPs provide a much needed reliable valving scheme for rigid plastic devices with low complexity, low cost, and no moving parts on the device or instrument. The reduction in freeze time, accessible actuation temperatures, chemical compatibility, and low complexity make the implementation of compact INP-based FTV arrays practical and attractive for the control of integrated biochemical assays.

Micro-Raman Technology to Interrogate Two-Phase Extraction on a Microfluidic Device.

PubMed

Nelson, Gilbert L; Asmussen, Susan E; Lines, Amanda M; Casella, Amanda J; Bottenus, Danny R; Clark, Sue B; Bryan, Samuel A

2018-05-21

Microfluidic devices provide ideal environments to study solvent extraction. When droplets form and generate plug flow down the microfluidic channel, the device acts as a microreactor in which the kinetics of chemical reactions and interfacial transfer can be examined. Here, we present a methodology that combines chemometric analysis with online micro-Raman spectroscopy to monitor biphasic extractions within a microfluidic device. Among the many benefits of microreactors is the ability to maintain small sample volumes, which is especially important when studying solvent extraction in harsh environments, such as in separations related to the nuclear fuel cycle. In solvent extraction, the efficiency of the process depends on complex formation and rates of transfer in biphasic systems. Thus, it is important to understand the kinetic parameters in an extraction system to maintain a high efficiency and effectivity of the process. This monitoring provided concentration measurements in both organic and aqueous plugs as they were pumped through the microfluidic channel. The biphasic system studied was comprised of HNO 3 as the aqueous phase and 30% (v/v) tributyl phosphate in n-dodecane comprised the organic phase, which simulated the plutonium uranium reduction extraction (PUREX) process. Using pre-equilibrated solutions (post extraction), the validity of the technique and methodology is illustrated. Following this validation, solutions that were not equilibrated were examined and the kinetics of interfacial mass transfer within the biphasic system were established. Kinetic results of extraction were compared to kinetics already determined on a macro scale to prove the efficacy of the technique.

Multimodal Microchannel and Nanowell-Based Microfluidic Platforms for Bioimaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Tao; Smallwood, Chuck R.; Zhu, Ying

2017-03-30

Modern live-cell imaging approaches permit real-time visualization of biological processes. However, limitations for unicellular organism trapping, culturing and long-term imaging can preclude complete understanding of how such microorganisms respond to perturbations in their local environment or linking single-cell variability to whole population dynamics. We have developed microfluidic platforms to overcome prior technical bottlenecks to allow both chemostat and compartmentalized cellular growth conditions using the same device. Additionally, a nanowell-based platform enables a high throughput approach to scale up compartmentalized imaging optimized within the microfluidic device. These channel and nanowell platforms are complementary, and both provide fine control over the localmore » environment as well as the ability to add/replace media components at any experimental time point.« less

Adaptation of a Simple Microfluidic Platform for High-Dimensional Quantitative Morphological Analysis of Human Mesenchymal Stromal Cells on Polystyrene-Based Substrates.

PubMed

Lam, Johnny; Marklein, Ross A; Jimenez-Torres, Jose A; Beebe, David J; Bauer, Steven R; Sung, Kyung E

2017-12-01

Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.

Investigation on microfluidic particles manipulation by holographic 3D tracking strategies

NASA Astrophysics Data System (ADS)

Cacace, Teresa; Paturzo, Melania; Memmolo, Pasquale; Vassalli, Massimo; Fraldi, Massimiliano; Mensitieri, Giuseppe; Ferraro, Pietro

2017-06-01

We demonstrate a 3D holographic tracking method to investigate particles motion in a microfluidic channel while unperturbed while inducing their migration through microfluidic manipulation. Digital holography (DH) in microscopy is a full-field, label-free imaging technique able to provide quantitative phase-contrast. The employed 3D tracking method is articulated in steps. First, the displacements along the optical axis are assessed by numerical refocusing criteria. In particular, an automatic refocusing method to recover the particles axial position is implemented employing a contrast-based refocusing criterion. Then, the transverse position of the in-focus object is evaluated through quantitative phase map segmentation methods and centroid-based 2D tracking strategy. The introduction of DH is thus suggested as a powerful approach for control of particles and biological samples manipulation, as well as a possible aid to precise design and implementation of advanced lab-on-chip microfluidic devices.

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

PubMed

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

2016-02-01

In this study, we propose an electrochemical immunoassay into a disposable microfluidic platform, using quantum dots (QDs) as labels and their enhanced detection using bismuth as an alternative to mercury electrodes. CdSe@ZnS QDs were used to tag human IgG as a model protein and detected through highly sensitive stripping voltammetry of the dissolved metallic component (cadmium in our case). The modification of the screen printed carbon electrodes (SPCEs) was done by a simple electrodeposition of bismuth that was previously mixed with the sample containing QDs. A magneto-immunosandwich assay was performed using a micromixer. A magnet placed at its outlet in order to capture the magnetic beads used as solid support for the immunoassay. SPCEs were integrated at the end of the channel as detector. Different parameters such as bismuth concentration, flow rate, and incubation times, were optimized. The LOD for HIgG in presence of bismuth was 3.5 ng/mL with a RSD of 13.2%. This LOD was about 3.3-fold lower than the one obtained without bismuth. Furthermore, the sensitivity of the system was increased 100-fold respect to experiments carried out with classical screen-printed electrodes, both in presence of bismuth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of nanostructures orientation on electroosmotic flow in a microfluidic channel

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

Experimental test of scaling of mixing by chaotic advection in droplets moving through microfluidic channels

PubMed Central

Song, Helen; Bringer, Michelle R.; Tice, Joshua D.; Gerdts, Cory J.; Ismagilov, Rustem F.

2006-01-01

This letter describes an experimental test of a simple argument that predicts the scaling of chaotic mixing in a droplet moving through a winding microfluidic channel. Previously, scaling arguments for chaotic mixing have been described for a flow that reduces striation length by stretching, folding, and reorienting the fluid in a manner similar to that of the baker’s transformation. The experimentally observed flow patterns within droplets (or plugs) resembled the baker’s transformation. Therefore, the ideas described in the literature could be applied to mixing in droplets to obtain the scaling argument for the dependence of the mixing time, t~(aw/U)log(Pe), where w [m] is the cross-sectional dimension of the microchannel, a is the dimensionless length of the plug measured relative to w, U [m s−1] is the flow velocity, Pe is the Péclet number (Pe=wU/D), and D [m2s−1] is the diffusion coefficient of the reagent being mixed. Experiments were performed to confirm the scaling argument by varying the parameters w, U, and D. Under favorable conditions, submillisecond mixing has been demonstrated in this system. PMID:17940580

Rapid and inexpensive fabrication of polymeric microfluidic devices via toner transfer masking

PubMed Central

Easley, Christopher J.; Benninger, Richard K. P.; Shaver, Jesse H.; Head, W. Steven; Piston, David W.

2009-01-01

Summary An alternative fabrication method is presented for production of masters for single- or multilayer polymeric microfluidic devices in a standard laboratory environment, precluding the need for a cleanroom. This toner transfer masking (TTM) method utilizes an office laser printer to generate a toner pattern which is thermally transferred to a metal master to serve as a mask for etching. With master fabrication times as little as one hour (depending on channel depth) using commercially-available equipment and supplies, this approach should make microfluidic technology more widely accessible to the non-expert—even the non-scientist. The cost of fabrication consumables was estimated to be < $1 per master, over an order of magnitude decrease in consumable costs compared to standard photolithography. In addition, the use of chemical etching allows accurate control over the height of raised features (i.e., channel depths), allowing the flexibility to fabricate multiple depths on a single master with little added time. Resultant devices are shown capable of pneumatic valving, three-dimensional channel formation (using layer-connecting vias), droplet fluidics, and cell imaging and staining. The multiple-depth capabilities of the method are proven useful for cellular analysis by fabrication of handheld, disposable devices used for trapping and imaging of live murine pancreatic islets. The precise fluidic control provided by the microfluidic platform allows subsequent fixing and staining of these cells without significant movement, thus spatial correlation of imaging and staining is attainable—even with rare alpha cells that constitute only ∼10% of the islet cells. PMID:19350094

Electrochemical immunoassay on a microfluidic device with sequential injection and flushing functions.

PubMed

Nashida, Norihiro; Satoh, Wataru; Fukuda, Junji; Suzuki, Hiroaki

2007-06-15

An integrated microfluidic device with injecting, flushing, and sensing functions was realized using valves that operate based on direct electrowetting. The device consisted of two substrates: a glass substrate with driving and sensing electrodes and a poly(dimethylsiloxane) (PDMS) substrate. Microfluidic transport was achieved using the spontaneous movement of solutions in hydrophilic flow channels formed with a dry-film photoresist layer. The injection and flushing of solutions were controlled by gold working electrodes, which functioned as valves. The valves were formed either in the channels or in a through-hole in the glass substrate. To demonstrate the system's applicability to an immunoassay, the detection of immobilized antigens was performed as a partial simulation of a sandwich immunoassay. Human alpha-fetoprotein (AFP) or an anti-human AFP antibody was immobilized on a platinum working electrode in the chamber using a plasma-polymerized film (PPF). By applying a potential to the injection valves, necessary solutions were injected one by one through the channels into a reaction chamber at the center of the chip and incubated for reasonable periods of time. The solutions were then flushed through the flushing valve and absorbed in a filter paper placed under the device. After incubation with the corresponding antibodies labeled with glucose oxidase (GOD), electrochemical detection was conducted. In both cases, the obtained current depended on the amount of immobilized antigen. The calibration curves were sigmoidal, and the detection limit was 0.1 ng. The developed microfluidic system could potentially be a fundamental component for a micro immunoassay of the next generation.

A Microfluidic System for the Investigation of Tumor Cell Extravasation.

PubMed

Kühlbach, Claudia; da Luz, Sabrina; Baganz, Frank; Hass, Volker C; Mueller, Margareta M

2018-05-23

Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion of the tumor cells to the endothelium and their transendothelial migration. However, the molecular mechanisms that are underlying this process are still not fully understood. Novel three dimensional (3D) models for research on the metastatic cascade include the use of microfluidic devices. Different from two dimensional (2D) models, these devices take cell⁻cell, structural, and mechanical interactions into account. Here we introduce a new microfluidic device in order to study tumor extravasation. The device consists of three different parts, containing two microfluidic channels and a porous membrane sandwiched in between them. A smaller channel together with the membrane represents the vessel equivalent and is seeded separately with primary endothelial cells (EC) that are isolated from the lung artery. The second channel acts as reservoir to collect the migrated tumor cells. In contrast to many other systems, this device does not need an additional coating to allow EC growth, as the primary EC that is used produces their own basement membrane. VE-Cadherin, an endothelial adherence junction protein, was expressed in regular localization, which indicates a tight barrier function and cell⁻cell connections of the endothelium. The EC in the device showed in vivo-like behavior under flow conditions. The GFP-transfected tumor cells that were introduced were of epithelial or mesenchymal origin and could be observed by live cell imaging, which indicates tightly adherent tumor cells to the endothelial lining under different flow conditions. These results suggest that the new device can be used for research on molecular requirements, conditions, and mechanism of extravasation

Microfluidic perfusion culture.

PubMed

Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

2014-01-01

Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion culture system is convenient technique to carry out the perfusion culture of animal cells in a microfluidic device. Here, we describe a general theory on microfluid network design, microfabrication technique, and experimental technique for pressure-driven perfusion culture in an 8 × 8 microchamber array on a glass slide-sized microchip made out of PDMS.

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

PubMed

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

2016-06-01

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

A magnetic resonance (MR) microscopy system using a microfluidically cryo-cooled planar coil.

PubMed

Koo, Chiwan; Godley, Richard F; Park, Jaewon; McDougall, Mary P; Wright, Steven M; Han, Arum

2011-07-07

We present the development of a microfluidically cryo-cooled planar coil for magnetic resonance (MR) microscopy. Cryogenically cooling radiofrequency (RF) coils for magnetic resonance imaging (MRI) can improve the signal to noise ratio (SNR) of the experiment. Conventional cryostats typically use a vacuum gap to keep samples to be imaged, especially biological samples, at or near room temperature during cryo-cooling. This limits how close a cryo-cooled coil can be placed to the sample. At the same time, a small coil-to-sample distance significantly improves the MR imaging capability due to the limited imaging depth of planar MR microcoils. These two conflicting requirements pose challenges to the use of cryo-cooling in MR microcoils. The use of a microfluidic based cryostat for localized cryo-cooling of MR microcoils is a step towards eliminating these constraints. The system presented here consists of planar receive-only coils with integrated cryo-cooling microfluidic channels underneath, and an imaging surface on top of the planar coils separated by a thin nitrogen gas gap. Polymer microfluidic channel structures fabricated through soft lithography processes were used to flow liquid nitrogen under the coils in order to cryo-cool the planar coils to liquid nitrogen temperature (-196 °C). Two unique features of the cryo-cooling system minimize the distance between the coil and the sample: (1) the small dimension of the polymer microfluidic channel enables localized cooling of the planar coils, while minimizing thermal effects on the nearby imaging surface. (2) The imaging surface is separated from the cryo-cooled planar coil by a thin gap through which nitrogen gas flows to thermally insulate the imaging surface, keeping it above 0 °C and preventing potential damage to biological samples. The localized cooling effect was validated by simulations, bench testing, and MR imaging experiments. Using this cryo-cooled planar coil system inside a 4.7 Tesla MR system

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.

Binary particle separation in droplet microfluidics using acoustophoresis

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Vacuum/compression valving (VCV) using parrafin-wax on a centrifugal microfluidic CD platform.

PubMed

Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Moebius, Jacob; Joseph, Karunan; Arof, Hamzah; Madou, Marc

2013-01-01

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.

Vacuum/Compression Valving (VCV) Using Parrafin-Wax on a Centrifugal Microfluidic CD Platform

PubMed Central

Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Moebius, Jacob; Joseph, Karunan; Arof, Hamzah; Madou, Marc

2013-01-01

This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control. PMID:23505528

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.