Towards high concentration enhancement of microfluidic temperature gradient focusing of sample solutes using combined AC and DC field induced Joule heating.

PubMed

Ge, Zhengwei; Wang, Wei; Yang, Chun

2011-04-07

It is challenging to continuously concentrate sample solutes in microfluidic channels. We present an improved electrokinetic technique for enhancing microfluidic temperature gradient focusing (TGF) of sample solutes using combined AC and DC field induced Joule heating effects. The introduction of an AC electric field component services dual functions: one is to produce Joule heat for generating temperature gradient; the other is to suppress electroosmotic flow. Consequently the required DC voltages for achieving sample concentration by Joule heating induced TGF are reduced, thereby leading to smaller electroosmotic flow (EOF) and thus backpressure effects. As a demonstration, the proposed technique can lead to concentration enhancement of sample solutes of more than 2500-fold, which is much higher than the existing literature reported microfluidic concentration enhancement by utilizing the Joule heating induced TGF technique.

Transient deformation of a droplet near a microfluidic constriction: A quantitative analysis

NASA Astrophysics Data System (ADS)

Trégouët, Corentin; Salez, Thomas; Monteux, Cécile; Reyssat, Mathilde

2018-05-01

We report on experiments that consist of deforming a collection of monodisperse droplets produced by a microfluidic chip through a flow-focusing device. We show that a proper numerical modeling of the flow is necessary to access the stress applied by the latter on the droplet along its trajectory through the chip. This crucial step enables the full integration of the differential equation governing the dynamical deformation, and consequently the robust measurement of the interfacial tension by fitting the experiments with the calculated deformation. Our study thus demonstrates the feasibility of quantitative in situ rheology in microfluidic flows involving, e.g., droplets, capsules, or cells.

Microfluidic flows of wormlike micellar solutions.

PubMed

Zhao, Ya; Cheung, Perry; Shen, Amy Q

2014-09-01

The widespread use of wormlike micellar solutions is commonly found in household items such as cosmetic products, industrial fluids used in enhanced oil recovery and as drag reducing agents, and in biological applications such as drug delivery and biosensors. Despite their extensive use, there are still many details about the microscopic micellar structure and the mechanisms by which wormlike micelles form under flow that are not clearly understood. Microfluidic devices provide a versatile platform to study wormlike micellar solutions under various flow conditions and confined geometries. A review of recent investigations using microfluidics to study the flow of wormlike micelles is presented here with an emphasis on three different flow types: shear, elongation, and complex flow fields. In particular, we focus on the use of shear flows to study shear banding, elastic instabilities of wormlike micellar solutions in extensional flow (including stagnation and contraction flow field), and the use of contraction geometries to measure the elongational viscosity of wormlike micellar solutions. Finally, we showcase the use of complex flow fields in microfluidics to generate a stable and nanoporous flow-induced structured phase (FISP) from wormlike micellar solutions. This review shows that the influence of spatial confinement and moderate hydrodynamic forces present in the microfluidic device can give rise to a host of possibilities of microstructural rearrangements and interesting flow phenomena. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

Tunable Liquid Gradient Refractive Index (L-GRIN) lens with two degrees of freedom.

PubMed

Mao, Xiaole; Lin, Sz-Chin Steven; Lapsley, Michael Ian; Shi, Jinjie; Juluri, Bala Krishna; Huang, Tony Jun

2009-07-21

We report a tunable optofluidic microlens configuration named the Liquid Gradient Refractive Index (L-GRIN) lens for focusing light within a microfluidic device. The focusing of light was achieved through the gradient refractive index (GRIN) within the liquid medium, rather than via curved refractive lens surfaces. The diffusion of solute (CaCl(2)) between side-by-side co-injected microfluidic laminar flows was utilized to establish a hyperbolic secant (HS) refractive index profile to focus light. Tailoring the refractive index profile by adjusting the flow conditions enables not only tuning of the focal distance (translation mode), but also shifting of the output light direction (swing mode), a second degree of freedom that to our knowledge has yet to be accomplished for in-plane tunable microlenses. Advantages of the L-GRIN lens also include a low fluid consumption rate, competitive focusing performance, and high compatibility with existing microfluidic devices. This work provides a new strategy for developing integrative tunable microlenses for a variety of lab-on-a-chip applications.

Recent Advancements towards Full-System Microfluidics

PubMed Central

Miled, Amine

2017-01-01

Microfluidics is quickly becoming a key technology in an expanding range of fields, such as medical sciences, biosensing, bioactuation, chemical synthesis, and more. This is helping its transformation from a promising R&D tool to commercially viable technology. Fuelling this expansion is the intensified focus on automation and enhanced functionality through integration of complex electrical control, mechanical properties, in situ sensing and flow control. Here we highlight recent contributions to the Sensors Special Issue series called “Microfluidics-Based Microsystem Integration Research” under the following categories: (i) Device fabrication to support complex functionality; (ii) New methods for flow control and mixing; (iii) Towards routine analysis and point of care applications; (iv) In situ characterization; and (v) Plug and play microfluidics. PMID:28757587

Experimental and Computational Investigation of Microbubble Production in Microfluidic Flow-Focusing Devices

NASA Astrophysics Data System (ADS)

Weber, Michael; Shandas, Robin

2005-11-01

Micron-sized bubbles have been effectively used as contrast agents in ultrasound imaging systems and have the potential for many other applications including targeted drug delivery and tumor destruction. The further development of these applications is dependent on precise control of bubble size. Recently, microfluidic flow-focusing systems have emerged as a viable means of producing microbubbles with monodisperse size distributions. These systems focus co-flowing liquid streams surrounding a gas stream through a narrow orifice, producing bubbles in very reproducible manner. In this work, a photopolymerization technique has been used to produce microfludicic flow-focusing devices which were successfully used to produce micron-sized bubbles. The flow dynamics involved in these devices has also been simulated using a volume-of-fluid approach to simultaneously solve the equations of motion for both the gas and liquid phases. Simulations were run with several variations of the flow-focuser geometry (gas inlet width, orifice length, gas-liquid approach angle, etc.) in an effort to produce smaller bubbles and increase the working range of liquid and gas flow rates. These findings are being incorporated into the production of actual devices in an effort to improve the overall effectiveness of the bubble production process.

Smart monolithic integration of inkjet printed thermal flow sensors with fast prototyping polymer microfluidics

NASA Astrophysics Data System (ADS)

Etxebarria, Ikerne; Elizalde, Jorge; Pacios, Roberto

2016-08-01

There is an increasing demand for built-in flow sensors in order to effectively control microfluidic processes due to the high number of available microfluidic applications. The possible solutions should be inexpensive and easy to connect to both, the microscale features and the macro setup. In this paper, we present a novel approach to integrate a printed thermal flow sensor with polymeric microfluidic channels. This approach is focused on merging two high throughput production processes, namely inkjet printing and fast prototyping technologies, in order to produce trustworthy and low cost devices. These two technologies are brought together to obtain a sensor located outside the microfluidic device. This avoids the critical contact between the sensor material and the fluids through the microchannels that can seriously damage the conducting paths under continuous working regimes. In this way, we ensure reliable and stable operation modes. For this application, a silver nanoparticle based ink and cyclic olefin polymer were used. This flow sensor operates linearly in the range of 0-10 μl min-1 for water and 0-20 μl min-1 for ethanol in calorimetric mode. Switching to anemometric mode, the range can be expanded up to 40 μl min-1.

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

Coaxial microreactor for particle synthesis

DOEpatents

Bartsch, Michael; Kanouff, Michael P; Ferko, Scott M; Crocker, Robert W; Wally, Karl

2013-10-22

A coaxial fluid flow microreactor system disposed on a microfluidic chip utilizing laminar flow for synthesizing particles from solution. Flow geometries produced by the mixing system make use of hydrodynamic focusing to confine a core flow to a small axially-symmetric, centrally positioned and spatially well-defined portion of a flow channel cross-section to provide highly uniform diffusional mixing between a reactant core and sheath flow streams. The microreactor is fabricated in such a way that a substantially planar two-dimensional arrangement of microfluidic channels will produce a three-dimensional core/sheath flow geometry. The microreactor system can comprise one or more coaxial mixing stages that can be arranged singly, in series, in parallel or nested concentrically in parallel.

Hydrodynamic lift for single cell manipulation in a femtosecond laser fabricated optofluidic chip

NASA Astrophysics Data System (ADS)

Bragheri, Francesca; Osellame, Roberto

2017-08-01

Single cell sorting based either on fluorescence or on mechanical properties has been exploited in the last years in microfluidic devices. Hydrodynamic focusing allows increasing the efficiency of theses devices by improving the matching between the region of optical analysis and that of cell flow. Here we present a very simple solution fabricated by femtosecond laser micromachining that exploits flow laminarity in microfluidic channels to easily lift the sample flowing position to the channel portion illuminated by the optical waveguides used for single cell trapping and analysis.

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 completely non-contact temperature control platform is developed in Chapter 5 for forensic human identification reactions, based on interferometric temperature sensing and infrared-mediated heating, which simplifies the microfluidic device and its operation. Finally, possible future directions are outlined in Chapter 6 including further simplification of microfluidic instrumentation.

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

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.

3D flow focusing for microfluidic flow cytometry with ultrasonics

NASA Astrophysics Data System (ADS)

Gnyawali, Vaskar; Strohm, Eric M.; Daghighi, Yasaman; van de Vondervoort, Mia; Kolios, Michael C.; Tsai, Scott S. H.

2015-11-01

We are developing a flow cytometer that detects unique acoustic signature waves generated from single cells due to interactions between the cells and ultrasound waves. The generated acoustic waves depend on the size and biomechanical properties of the cells and are sufficient for identifying cells in the medium. A microfluidic system capable of focusing cells through a 10 x 10 μm ultrasound beam cross section was developed to facilitate acoustic measurements of single cells. The cells are streamlined in a hydro-dynamically 3D focused flow in a 300 x 300 μm channel made using PDMS. 3D focusing is realized by lateral sheath flows and an inlet needle (inner diameter 100 μm). The accuracy of the 3D flow focusing is measured using a dye and detecting its localization using confocal microscopy. Each flowing cell would be probed by an ultrasound pulse, which has a center frequency of 375 MHz and bandwidth of 250 MHz. The same probe would also be used for recording the scattered waves from the cells, which would be processed to distinguish the physical and biomechanical characteristics of the cells, eventually identifying them. This technique has potential applications in detecting circulating tumor cells, blood cells and blood-related diseases.

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.

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

A novel microfluidic system for the mass production of Inertial Fusion Energy shells

NASA Astrophysics Data System (ADS)

Inoue, N. T.

2016-04-01

A system which can mass produce millimetre sized spherical polymer shells economically and with high precision will be a great step towards the Inertial Fusion Energy goal. Microfluidics has shown itself to be a disruptive technology, where a rapid and continuous production of compound emulsions can be processed into such shells. Planar emulsion generators co-flow-focus in one step (COFON) and cascaded co-flow- focus (COFUS) enable millimetre compound emulsions to be produced using a one or two step formation process respectively. The co-flow-focus geometry uses symmetric and curved carrier fluid entrance walls to create a focusing orifice-minima and a carrier flow which aids movement and shaping of the dispersed fluid(s) towards the outlet, whilst maintaining operation in the dripping regime. Precision concentric alignment of these compound emulsions remains one of the greatest challenges. However steps to solve this passively using curved channel modulation to perturbate the emulsion have shown that rapid alignment can be achieved. Issues with satellite droplet formation, repeatability of the emulsion generation and cost are also addressed.

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.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

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.

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

PubMed Central

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

2015-01-01

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

Simultaneous ultrasound and photoacoustics based flow cytometry

NASA Astrophysics Data System (ADS)

Gnyawali, Vaskar; Strohm, Eric M.; Tsai, Scott S. H.; Kolios, Michael C.

2018-04-01

We have developed a flow cytometer based on simultaneous detection of ultrasound and photoacoustic waves from individual particles/cells flowing in a microfluidic channel. Our polydimethylsiloxane (PDMS) based hydrodynamic 3-dimensional (3D) flow-focusing microfluidic device contains a cross-junction channel, a micro-needle (ID 100 μm and OD 200 μm) insert, and a 3D printed frame to hold and align a high frequency (center frequency 375 MHz) ultrasound transducer. The focused flow passes through a narrow focal zone with lateral and axial focal lengths of 6-8 μm and 15-20 μm, respectively. Both the lateral and axial alignments are achieved by screwing the transducer to the frame onto the PDMS device. Individual particles pass through an interrogation zone in the microfluidic channel with a collinearly aligned ultrasound transducer and a focused 532 nm wavelength laser beam. The particles are simultaneously insonified by high-frequency ultrasound and irradiated by a laser beam. The ultrasound backscatter and laser generated photoacoustic waves are detected for each passing particle. The backscattered ultrasound and photoacoustic signal are strongly dependent on the size, morphology, mechanical properties, and material properties of the flowing particles; these parameters can be extracted by analyzing unique features in the power spectrum of the signals. Frequencies less than 100 MHz do not have these unique spectral signatures. We show that we can reliably distinguish between different particles in a sample using the acoustic-based flow cytometer. This technique, when extended to biomedical applications, allows us to rapidly analyze the spectral signatures from individual single cells of a large cell population, with applications towards label-free detection and characterization of healthy and diseased cells.

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.

Inertial focusing of spherical particles in rectangular microchannels over a wide range of Reynolds numbers.

PubMed

Liu, Chao; Hu, Guoqing; Jiang, Xingyu; Sun, Jiashu

2015-02-21

Inertial microfluidics has emerged as an important tool for manipulating particles and cells. For a better design of inertial microfluidic devices, we conduct 3D direct numerical simulations (DNS) and experiments to determine the complicated dependence of focusing behaviour on the particle size, channel aspect ratio, and channel Reynolds number. We find that the well-known focusing of the particles at the two centers of the long channel walls occurs at a relatively low Reynolds number, whereas additional stable equilibrium positions emerge close to the short walls with increasing Reynolds number. Based on the numerically calculated trajectories of particles, we propose a two-stage particle migration which is consistent with experimental observations. We further present a general criterion to secure good focusing of particles for high flow rates. This work thus provides physical insight into the multiplex focusing of particles in rectangular microchannels with different geometries and Reynolds numbers, and paves the way for efficiently designing inertial microfluidic devices.

Controlled droplet microfluidic systems for multistep chemical and biological assays.

PubMed

Kaminski, T S; Garstecki, P

2017-10-16

Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

Microfabrication and Test of a Three-Dimensional Polymer Hydro-focusing Unit for Flow Cytometry Applications

NASA Technical Reports Server (NTRS)

Yang, Ren; Feeback, Daniel L.; Wang, Wanjun

2004-01-01

This paper details a novel three-dimensional (3D) hydro-focusing micro cell sorter for micro flow cytometry applications. The unit was microfabricated by means of SU-8 3D lithography. The 3D microstructure for coaxial sheathing was designed, microfabricated, and tested. Three-dimensional hydro-focusing capability was demonstrated with an experiment to sort labeled tanned sheep erythrocytes (red blood cells). This polymer hydro-focusing microstructure is easily microfabricated and integrated with other polymer microfluidic structures.

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

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

Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach

PubMed Central

Zizzari, Alessandra; Bianco, Monica; Perrone, Elisabetta; Amato, Francesco; Maruccio, Giuseppe; Rendina, Filippo; Arima, Valentina

2017-01-01

Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs). Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow. PMID:29232873

Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-focusing Device for Controlled Drug Delivery

PubMed Central

Xu, Qiaobing; Hashimoto, Michinao; Dang, Tram T.; Hoare, Todd; Kohane, Daniel S.; Whitesides, George M.; Langer, Robert; Anderson, Daniel G.

2009-01-01

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several FDA-approved therapies. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug delivery properties of those particles. Particles were engineered with defined sizes, ranging from 10 μm to 50 μm. These particles were nearly monodisperse (polydispersity index = 3.9 %). We incorporated a model amphiphilic drug (bupivacaine) within the biodegradable matrix of the particles. Kinetic analysis showed that the release of drug from these monodisperse particles was slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibited a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release was attributed to the uniform distribution of drug inside the particles generated using the microfluidic methods. These results demonstrated the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs. PMID:19296563

Morphological tuning of polymeric nanoparticles via microfluidic platform for fuel cell applications.

PubMed

Hasani-Sadrabadi, Mohammad Mahdi; Majedi, Fatemeh Sadat; VanDersarl, Jules John; Dashtimoghadam, Erfan; Ghaffarian, S Reza; Bertsch, Arnaud; Moaddel, Homayoun; Renaud, Philippe

2012-11-21

At nanoscale length scales, the properties of particles change rapidly with the slightest change in dimension. The use of a microfluidic platform enables precise control of sub-100 nm organic nanoparticles (NPs) based on polybenzimidazole. Using hydrodynamic flow focusing, we can control the size and shape of the NPs, which in turn controls a number of particle material properties. The anhydrous proton-conducting nature of the prepared NPs allowed us to make a high-performance ion exchange membrane for fuel cell applications, and microfluidic tuning of the NPs allowed us subsequently to tune the fuel cell performance.

Microfluidic production of polymeric functional microparticles

NASA Astrophysics Data System (ADS)

Jiang, Kunqiang

This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye-bearing beads can function as non-invasive and real-time oxygen micro-sensors. Finally, we report a co-flow microfluidic method to prepare uniform polymer microparticles with macroporous texture, and investigate their application as discrete immunological biosensors for the detection of biological species. The matrix of such microparticles is based on macroporous polymethacrylate polymers configured with tailored pores ranging from hundreds of nanometers to a few microns. Subsequently, we immobilize bioactive antibodies on the particle surface, and demonstrate the immunological performance of these functionalized porous microbeads over a range of antigen concentrations.

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.

Sheathless Size-Based Acoustic Particle Separation

PubMed Central

Guldiken, Rasim; Jo, Myeong Chan; Gallant, Nathan D.; Demirci, Utkan; Zhe, Jiang

2012-01-01

Particle separation is of great interest in many biological and biomedical applications. Flow-based methods have been used to sort particles and cells. However, the main challenge with flow based particle separation systems is the need for a sheath flow for successful operation. Existence of the sheath liquid dilutes the analyte, necessitates precise flow control between sample and sheath flow, requires a complicated design to create sheath flow and separation efficiency depends on the sheath liquid composition. In this paper, we present a microfluidic platform for sheathless particle separation using standing surface acoustic waves. In this platform, particles are first lined up at the center of the channel without introducing any external sheath flow. The particles are then entered into the second stage where particles are driven towards the off-center pressure nodes for size based separation. The larger particles are exposed to more lateral displacement in the channel due to the acoustic force differences. Consequently, different-size particles are separated into multiple collection outlets. The prominent feature of the present microfluidic platform is that the device does not require the use of the sheath flow for positioning and aligning of particles. Instead, the sheathless flow focusing and separation are integrated within a single microfluidic device and accomplished simultaneously. In this paper, we demonstrated two different particle size-resolution separations; (1) 3 μm and 10 μm and (2) 3 μm and 5 μm. Also, the effects of the input power, the flow rate, and particle concentration on the separation efficiency were investigated. These technologies have potential to impact broadly various areas including the essential microfluidic components for lab-on-a-chip system and integrated biological and biomedical applications. PMID:22368502

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

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Microfabrication and Test of a Three-Dimensional Polymer Hydro-Focusing Unit for Flow Cytometry Applications

NASA Technical Reports Server (NTRS)

Yang, Ren; Feedback, Daniel L.; Wang, Wanjun

2004-01-01

This paper details a novel three-dimensional (3D) hydro-focusing micro cell sorter for micro flow cytometry applications. The unit was micro-fabricated by means of SU-8 3D lithography. The 3D microstructure for coaxial sheathing was designed, micro-fabricated, and tested. Three-dimensional hydrofocusing capability was demonstrated with an experiment to sort labeled tanned sheep erythrocytes (red blood cells). This polymer hydro-focusing microstructure is easily micro-fabricated and integrated with other polymer microfluidic structures.

Microfluidic generation of aqueous two-phase system (ATPS) droplets by controlled pulsating inlet pressures.

PubMed

Moon, Byeong-Ui; Jones, Steven G; Hwang, Dae Kun; Tsai, Scott S H

2015-06-07

We present a technique that generates droplets using ultralow interfacial tension aqueous two-phase systems (ATPS). Our method combines a classical microfluidic flow focusing geometry with precisely controlled pulsating inlet pressure, to form monodisperse ATPS droplets. The dextran (DEX) disperse phase enters through the central inlet with variable on-off pressure cycles controlled by a pneumatic solenoid valve. The continuous phase polyethylene glycol (PEG) solution enters the flow focusing junction through the cross channels at a fixed flow rate. The on-off cycles of the applied pressure, combined with the fixed flow rate cross flow, make it possible for the ATPS jet to break up into droplets. We observe different droplet formation regimes with changes in the applied pressure magnitude and timing, and the continuous phase flow rate. We also develop a scaling model to predict the size of the generated droplets, and the experimental results show a good quantitative agreement with our scaling model. Additionally, we demonstrate the potential for scaling-up of the droplet production rate, with a simultaneous two-droplet generating geometry. We anticipate that this simple and precise approach to making ATPS droplets will find utility in biological applications where the all-biocompatibility of ATPS is desirable.

Droplet Breakup in Expansion-contraction Microchannels

PubMed Central

Zhu, Pingan; Kong, Tiantian; Lei, Leyan; Tian, Xiaowei; Kang, Zhanxiao; Wang, Liqiu

2016-01-01

We investigate the influences of expansion-contraction microchannels on droplet breakup in capillary microfluidic devices. With variations in channel dimension, local shear stresses at the injection nozzle and focusing orifice vary, significantly impacting flow behavior including droplet breakup locations and breakup modes. We observe transition of droplet breakup location from focusing orifice to injection nozzle, and three distinct types of recently-reported tip-multi-breaking modes. By balancing local shear stresses and interfacial tension effects, we determine the critical condition for breakup location transition, and characterize the tip-multi-breaking mode quantitatively. In addition, we identify the mechanism responsible for the periodic oscillation of inner fluid tip in tip-multi-breaking mode. Our results offer fundamental understanding of two-phase flow behaviors in expansion-contraction microstructures, and would benefit droplet generation, manipulation and design of microfluidic devices. PMID:26899018

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.

Producing colloids with microfluidics

NASA Astrophysics Data System (ADS)

Pannacci, Nicolas; Willaime, Herve; Tabeling, Patrick

2008-11-01

Submicronic emulsions are commonly used in pharmaceutical, food, cosmetic and material industries. Standard microfluidic tool is particularly convenient to produce in a very controlled way either droplets of typical diameter ranging from 10 to 300 microns with a perfect monodispersity (<3%), or double emulsions as well as double droplets (janus). We report the use of microfluidic devices to produce submicronic objects. We use a hydrodynamic flow-focusing that has the advantage to generate nanodrops in a way that is slightly dependent on the fluids used. The control on such a flow authorizes the adjustment of the diameter of the colloids formed. We will show brownian particles from 860 nm to 1.3 μm in diameter obtained in such way and their clustering into crystals thanks to their high monodispersity. These first experimental results are very promising and make evident the great potential of micro and nano-fluidics to produce nano-emulsions or colloids with very controlled size that metamaterials can require.

Microfluidic generation of particle-stabilized water-in-water emulsions

NASA Astrophysics Data System (ADS)

Abbasi, Niki; Navi, Maryam; Tsai, Scott

2017-11-01

We present a microfluidic platform that generates particle-stabilized water-in-water emulsions, using an aqueous two-phase system (ATPS) of polyethylene glycol (PEG) and Dextran (DEX). DEX droplets are generated passively at a flow focusing junction, in a continuous phase of PEG and carboxylated particles, using weak hydrostatic pressure to drive the flow. As DEX droplets travel inside the microfluidic device, carboxylated particles partition to the interface of the droplets. The number of particles partitioning to the interface of droplets increases as the droplets migrate downstream in the microchannel. As a result, the DEX droplets become stabilized against coalescence. We study the coverage and stability of the DEX droplets further downstream inside a reservoir, by changing the carboxylated particle concentration and the particle size. We anticipate that particle-stabilized water-in-water emulsions may have important biotechnological applications, due to their intrinsic biocompatibility compared to traditional particle-stabilized water-in-oil emulsions, for example for cell encapsulation.

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

PubMed

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

2012-02-07

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

Secondary electroosmotic flow in microchannels with nonuniform and asymmetric Zeta potential

NASA Astrophysics Data System (ADS)

Zhang, Jinbai; He, Guowei; Liu, Feng

2004-11-01

Microfluidics has a broad range of applications in biotechnology, such as sample injection, drug delivering, solution mixing, and separations. All of these techniques require handling fluids in the low Reynolds number (Re) regime. Electroosmotic flow (EOF) or electroosmocitcs is the bulk movement of liquid relative to a stationary surface due to an externally applied electronic field. It is an alternative to pressure-driven flows with convenient implementation The driving force for EOF is dependent on the zeta potential. Previous reseraches focus on the nonuniform Zeta potential. In the present work, we consider nonuniform and asymmetric Zeta potential. The effects of asymmetric Zeta potential on the EOF are investigated analytically and simulated numerically. It is demonstrated that the nonuniform and asymmetric Zeta potential can generate more flow patterns for microfluidic control compared to symmetric Zeta potential.

Predicting Droplet Formation on Centrifugal Microfluidic Platforms

NASA Astrophysics Data System (ADS)

Moebius, Jacob Alfred

Centrifugal microfluidics is a widely known research tool for biological sample and water quality analysis. Currently, the standard equipment used for such diagnostic applications include slow, bulky machines controlled by multiple operators. These machines can be condensed into a smaller, faster benchtop sample-to-answer system. Sample processing is an important step taken to extract, isolate, and convert biological factors, such as nucleic acids or proteins, from a raw sample to an analyzable solution. Volume definition is one such step. The focus of this thesis is the development of a model predicting monodispersed droplet formation and the application of droplets as a technique for volume definition. First, a background of droplet microfluidic platforms is presented, along with current biological analysis technologies and the advantages of integrating such technologies onto microfluidic platforms. Second, background and theories of centrifugal microfluidics is given, followed by theories relevant to droplet emulsions. Third, fabrication techniques for centrifugal microfluidic designs are discussed. Finally, the development of a model for predicting droplet formation on the centrifugal microfluidic platform are presented for the rest of the thesis. Predicting droplet formation analytically based on the volumetric flow rates of the continuous and dispersed phases, the ratios of these two flow rates, and the interfacial tension between the continuous and dispersed phases presented many challenges, which will be discussed in this work. Experimental validation was completed using continuous phase solutions of different interfacial tensions. To conclude, prospective applications are discussed with expected challenges.

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

NASA Astrophysics Data System (ADS)

Amoyav, Benzion; Benny, Ofra

2018-04-01

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

Continuous cell introduction and rapid dynamic lysis for high-throughput single-cell analysis on microfludic chips with hydrodynamic focusing.

PubMed

Xu, Chun-Xiu; Yin, Xue-Feng

2011-02-04

A chip-based microfluidic system for high-throughput single-cell analysis is described. The system was integrated with continuous introduction of individual cells, rapid dynamic lysis, capillary electrophoretic (CE) separation and laser induced fluorescence (LIF) detection. A cross microfluidic chip with one sheath-flow channel located on each side of the sampling channel was designed. The labeled cells were hydrodynamically focused by sheath-flow streams and sequentially introduced into the cross section of the microchip under hydrostatic pressure generated by adjusting liquid levels in the reservoirs. Combined with the electric field applied on the separation channel, the aligned cells were driven into the separation channel and rapidly lysed within 33ms at the entry of the separation channel by Triton X-100 added in the sheath-flow solution. The maximum rate for introducing individual cells into the separation channel was about 150cells/min. The introduction of sheath-flow streams also significantly reduced the concentration of phosphate-buffered saline (PBS) injected into the separation channel along with single cells, thus reducing Joule heating during electrophoretic separation. The performance of this microfluidic system was evaluated by analysis of reduced glutathione (GSH) and reactive oxygen species (ROS) in single erythrocytes. A throughput of 38cells/min was obtained. The proposed method is simple and robust for high-throughput single-cell analysis, allowing for analysis of cell population with considerable size to generate results with statistical significance. Copyright © 2010 Elsevier B.V. All rights reserved.

Liter-scale production of uniform gas bubbles via parallelization of flow-focusing generators.

PubMed

Jeong, Heon-Ho; Yadavali, Sagar; Issadore, David; Lee, Daeyeon

2017-07-25

Microscale gas bubbles have demonstrated enormous utility as versatile templates for the synthesis of functional materials in medicine, ultra-lightweight materials and acoustic metamaterials. In many of these applications, high uniformity of the size of the gas bubbles is critical to achieve the desired properties and functionality. While microfluidics have been used with success to create gas bubbles that have a uniformity not achievable using conventional methods, the inherently low volumetric flow rate of microfluidics has limited its use in most applications. Parallelization of liquid droplet generators, in which many droplet generators are incorporated onto a single chip, has shown great promise for the large scale production of monodisperse liquid emulsion droplets. However, the scale-up of monodisperse gas bubbles using such an approach has remained a challenge because of possible coupling between parallel bubbles generators and feedback effects from the downstream channels. In this report, we systematically investigate the effect of factors such as viscosity of the continuous phase, capillary number, and gas pressure as well as the channel uniformity on the size distribution of gas bubbles in a parallelized microfluidic device. We show that, by optimizing the flow conditions, a device with 400 parallel flow focusing generators on a footprint of 5 × 5 cm 2 can be used to generate gas bubbles with a coefficient of variation of less than 5% at a production rate of approximately 1 L h -1 . Our results suggest that the optimization of flow conditions using a device with a small number (e.g., 8) of parallel FFGs can facilitate large-scale bubble production.

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

PubMed

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

2013-11-01

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

Bubble production using a Non-Newtonian fluid in microfluidic flow focusing device

NASA Astrophysics Data System (ADS)

Wang, Yi-Lin; Ward, Thomas; Grant, Christine

2012-02-01

We experimentally study the production of micrometer-sized bubbles using microfluidic technology and a flow-focusing geometry. Bubbles are produced by using a mixture containing aqueous polyacrylamide of concentrations ranging from 0.01-0.10% by weight and several solution also containing a sodium-lauryl-sulfate (SLS) surfactant at concentrations ranging 0.01-0.1% by weight. The fluids are driven by controlling the static pressure above a hydrostatic head of the liquid while the disperse phase fluid static pressure is held constant (air). In the absence of surfactant the bubble production is discontinuous. The addition of surfactant stabilizes the bubble production. In each type of experiment, the bubble length l, velocity U and production frequency φ are measured and compared as a function of the inlet pressure ratio. The bubbles exhibit a contraction in their downstream length as a function of the polymer concentration which is investigated.

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.

SAXS on a chip: from dynamics of phase transitions to alignment phenomena at interfaces studied with microfluidic devices.

PubMed

Silva, Bruno F B

2017-09-13

The field of microfluidics offers attractive possibilities to perform novel experiments that are difficult (or even impossible) to perform using conventional bulk and surface-based methods. Such attractiveness comes from several important aspects inherent to these miniaturized devices. First, the flow of fluids under submillimeter confinement typically leads to a drop of inertial forces, meaning that turbulence is practically suppressed. This leads to predictable and controllable flow profiles, along with well-defined chemical gradients and stress fields that can be used for controlled mixing and actuation on the micro and nanoscale. Secondly, intricate microfluidic device designs can be fabricated using cleanroom standard procedures. Such intricate geometries can take diverse forms, designed by researchers to perform complex tasks, that require exquisite control of flow of several components and gradients, or to mimic real world examples, facilitating the establishment of more realistic models. Thirdly, microfluidic devices are usually compatible with in situ or integrated characterization methods that allow constant real-time monitoring of the processes occurring inside the microchannels. This is very different from typical bulk-based methods, where usually one can only observe the final result, or otherwise, take quick snapshots of the evolving process or take aliquots to be analyzed separately. Altogether, these characteristics inherent to microfluidic devices provide researchers with a set of tools that allow not only exquisite control and manipulation of materials at the micro and nanoscale, but also observation of these effects. In this review, we will focus on the use and prospects of combining microfluidic devices with in situ small-angle X-ray scattering (and related techniques such as small-angle neutron scattering and X-ray photon correlation spectroscopy), and their enormous potential for physical-chemical research, mainly in self-assembly and phase-transitions, and surface characterization.

Fundamentals of microfluidics for high school students with no prior knowledge of fluid mechanics.

PubMed

Tandon, Vishal; Peck, Walter

2013-01-01

Three microfluidics-based laboratory exercises were developed and implemented in a high school science classroom setting. The first exercise demonstrated ways in which flows are characterized, including viscosity, turbulence, shear stress, reversibility, compressibility, and hydrodynamic resistance. Students characterized flows in poly(dimethylsiloxane) microfluidic devices in the other two exercises, where they observed the mixing characteristics of laminar flows, and conservation of volumetric flow rate for incompressible flows. In surveys, the students self-reported increased knowledge of microfluidics, and an improved attitude toward science and nanotechnology.

EDITORIAL: Focus on Micro- and Nanofluidics FOCUS ON MICRO- AND NANOFLUIDICS

NASA Astrophysics Data System (ADS)

Ajdari, Armand; Stone, Howard A.

2009-07-01

This focus issue of New Journal of Physics concentrates on recent developments in microfluidics, and related small-scale flow themes. This subject touches on many areas with the common element that they are engaged with understanding, measuring or manipulating flows at the scale of a few hundred microns or smaller. Microfluidics is of interest to many scientists and engineers from many disciplines because it is a toolbox from which they can investigate basic questions in their respective fields. In particular, the field has led to new studies of small-scale fluid flows, especially those dominated by surface effects, which is crucial for understanding electrokinetics, chemical reactions and phase changes, and multiphase systems, including those involving dispersed liquid and gas phases, suspended particles, cells, vesicles, capsules, etc. The lower length scale of these kinds of flows concerns nanoscale manipulation of objects such as DNA or nanoparticles, nanofabrication of surfaces, studies of the flow within nanometers of substrates, etc. Microfluidics has also given rise to technologies because it enables design and implementation of new devices for sensing, detection, measurement, materials characterization, combinatorial discovery, cellular-scale manipulation, miniaturization of reactors, etc. The fact that these systems are small, cheap, physically flexible, portable, multifunctional, and, when they are working, produce measurements quickly, offers many new avenues for innovation. In this issue we highlight contributions from around the world that explore research directions inspired by the manifold possibilities of microfluidics. In particular, the papers include reports of single-phase flows that are driven by electrical fields, so-called electrokinetics. Although the field has its origins in the 19th century, if not even earlier, new theoretical ideas are required to understand dynamics close to charged surfaces, and new applications of the basic ideas are being introduced for driving flows and manipulating suspended particles (e.g. DNA). In addition, the subject of mixing and the study of transport processes coupling diffusion and convection is a necessary component of many studies aimed at lab-on-a-chip environments. At the other extreme from mixing there is interest in the precise placement of particles in microfluidic flows. Although the majority of microfluidic studies focus on the consequences of low Reynolds number motions, the flows can frequently have large enough particle-scale Reynolds numbers that inertial effects can appear. Also, chemical gradients, via osmotic effects, can be significant, and, where surface effects are significant, particle deposition can occur. Multiphase flows constitute another major area of microfluidic research. For example, there has been great interest in using drops as individual containers since both the chemical composition inside and outside the drop can be controlled. Also, the interface between the two phases provides both a natural chemical barrier (surfactants are generally added to reduce the probability of coalescence between drops) as well as potentially being the site for reactions or localized organization of particles suspended in solution. Thus, there is interest in both the controlled breakup of liquid threads, the dynamics of such a thread, which can fold or buckle, and application of these processes to fabricating new materials. Not surprisingly the themes mentioned in this short summary are just a small window into the myriad of ideas being investigated in the research world of small-scale flows that is the playground of micro- and nanofluidics. We are grateful to all of the contributors for their efforts and to the referees, whose feedback has added value to every contribution. We hope you, as readers, will find benefit in the many ideas discussed in this Focus on Micro- and Nanofluidics, which represents a sampling of current activity, including experiment, simulation and theory, in this rapidly developing field. Focus on Micro- and Nanofluidics Contents The anti-lotus leaf effect in nanohydrodynamic bump arrays Keith Morton, Ophelia K C Tsui, Chih-Kuan Tung, James C Sturm, Stephen Y Chou and Robert Austin Transport in nanofluidic systems: a review of theory and applications W Sparreboom, A van den Berg and J C T Eijkel The effects of polymer molecular weight on filament thinning and drop breakup in microchannels P E Arratia, L-A Cramer, J P Gollub and D J Durian Mass transfer and interfacial properties in two-phase microchannel flows Jeffrey D Martin and Steven D Hudson Temporal response of an initially deflected PDMS channel Priyadarshi Panda, Kai P Yuet, Dhananjay Dendukuri, T Alan Hatton and Patrick S Doyle Gas-liquid two-phase flow patterns in rectangular polymeric microchannels: effect of surface wetting properties D Huh, C-H Kuo, J B Grotberg and S Takayama Mixing via thermocapillary generation of flow patterns inside a microfluidic drop María Luisa Cordero, Hans Olav Rolfsnes, Daniel R Burnham, Paul A Campbell, David McGloin and Charles N Baroud Pressure-driven DNA transport across an artificial nanotopography J T Del Bonis-O'Donnell, W Reisner and D Stein Eulerian indicators for predicting and optimizing mixing quality Rob Sturman and Stephen Wiggins Asymmetric flows over symmetric surfaces: capacitive coupling in induced-charge electro-osmosis T S Mansuripur, A J Pascall and T M Squires High-viscosity fluid threads in weakly diffusive microfluidic systems T Cubaud and T G Mason Interfacial mass transport in steady three-dimensional flows in microchannels Joseph D Kirtland, Corey R Siegel and Abraham D Stroock Active connectors for microfluidic drops on demand Jean-Christophe Galas, Denis Bartolo and Vincent Studer Electrokinetic control of sample splitting at a channel bifurcation using isotachophoresis Alexandre Persat and Juan G Santiago Differential inertial focusing of particles in curved low-aspect-ratio microchannels Aman Russom, Amit K Gupta, Sunitha Nagrath, Dino Di Carlo, Jon F Edd and Mehmet Toner Capillary instability on a hydrophilic stripe Raymond L Speth and Eric Lauga Universal nanocolloid deposition patterns: can you see the harmonics of a Taylor cone? Xinguang Cheng and Hsueh-Chia Chang Osmotic manipulation of particles for microfluidic applications B Abécassis, C Cottin-Bizonne, C Ybert, A Ajdari and L Bocquet Scaling the drop size in coflow experiments E Castro-Hernández, V Gundabala, A Fernández-Nieves and J M Gordillo Pattern formation during the evaporation of a colloidal nanoliter drop: a numerical and experimental study Rajneesh Bhardwaj, Xiaohua Fang and Daniel Attinger Topology and shape optimization of induced-charge electro-osmotic micropumps M M Gregersen, F Okkels, M Z Bazant and H Bruus Fabrication of multiphasic and regio-specifically functionalized PRINT® particles of controlled size and shape H Zhang, J K Nunes, S E A Gratton, K P Herlihy, P D Pohlhaus and J M DeSimone Using TIRF microscopy to quantify and confirm efficient mass transfer at the substrate surface of the chemistrode Delai Chen, Wenbin Du and Rustem F Ismagilov Nonlinear electrokinetics at large voltages Martin Z Bazant, Mustafa Sabri Kilic, Brian D Storey and Armand Ajdari Interdiffusion of liquids of different viscosities in a microchannel J Dambrine, B Géraud and J-B Salmon Microfluidic fabrication of microparticles with structural complexity using photocurable emulsion droplets Shin-Hyun Kim, Jae Won Shim, Jong-Min Lim, Su Yeon Lee and Seung-Man Yang

Parallel generation of uniform fine droplets at hundreds of kilohertz in a flow-focusing module.

PubMed

Bardin, David; Kendall, Michael R; Dayton, Paul A; Lee, Abraham P

2013-01-01

Droplet-based microfluidic systems enable a variety of biomedical applications from point-of-care diagnostics with third world implications, to targeted therapeutics alongside medical ultrasound, to molecular screening and genetic testing. Though these systems maintain the key advantage of precise control of the size and composition of the droplet as compared to conventional methods of production, the low rates at which droplets are produced limits translation beyond the laboratory setting. As well, previous attempts to scale up shear-based microfluidic systems focused on increasing the volumetric throughput and formed large droplets, negating many practical applications of emulsions such as site-specific therapeutics. We present the operation of a parallel module with eight flow-focusing orifices in the dripping regime of droplet formation for the generation of uniform fine droplets at rates in the hundreds of kilohertz. Elevating the capillary number to access dripping, generation of monodisperse droplets of liquid perfluoropentane in the parallel module exceeded 3.69 × 10(5) droplets per second, or 1.33 × 10(9) droplets per hour, at a mean diameter of 9.8 μm. Our microfluidic method offers a novel means to amass uniform fine droplets in practical amounts, for instance, to satisfy clinical needs, with the potential for modification to form massive amounts of more complex droplets.

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 may take in its development. PMID:22662067

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

NASA Astrophysics Data System (ADS)

Mbanjwa, Mesuli B.; Chen, Hao; Fourie, Louis; Ngwenya, Sibusiso; Land, Kevin

2014-06-01

Multiplexed or parallelised droplet microfluidic systems allow for increased throughput in the production of emulsions and microparticles, while maintaining a small footprint and utilising minimal ancillary equipment. The current paper demonstrates the design and fabrication of a multiplexed microfluidic system for producing biocatalytic microspheres. The microfluidic system consists of an array of 10 parallel microfluidic circuits, for simultaneous operation to demonstrate increased production throughput. The flow distribution was achieved using a principle of reservoirs supplying individual microfluidic circuits. The microfluidic devices were fabricated in poly (dimethylsiloxane) (PDMS) using soft lithography techniques. The consistency of the flow distribution was determined by measuring the size variations of the microspheres produced. The coefficient of variation of the particles was determined to be 9%, an indication of consistent particle formation and good flow distribution between the 10 microfluidic circuits.

Screening applications in drug discovery based on microfluidic technology

PubMed Central

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

2016-01-01

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

Screening applications in drug discovery based on microfluidic technology.

PubMed

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

2016-01-01

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

Simple and inexpensive micromachined aluminum microfluidic devices for acoustic focusing of particles and cells.

PubMed

Gautam, Gayatri P; Burger, Tobias; Wilcox, Andrew; Cumbo, Michael J; Graves, Steven W; Piyasena, Menake E

2018-05-01

We introduce a new method to construct microfluidic devices especially useful for bulk acoustic wave (BAW)-based manipulation of cells and microparticles. To obtain efficient acoustic focusing, BAW devices require materials that have high acoustic impedance mismatch relative to the medium in which the cells/microparticles are suspended and materials with a high-quality factor. To date, silicon and glass have been the materials of choice for BAW-based acoustofluidic channel fabrication. Silicon- and glass-based fabrication is typically performed in clean room facilities, generates hazardous waste, and can take several hours to complete the microfabrication. To address some of the drawbacks in fabricating conventional BAW devices, we explored a new approach by micromachining microfluidic channels in aluminum substrates. Additionally, we demonstrate plasma bonding of poly(dimethylsiloxane) (PDMS) onto micromachined aluminum substrates. Our goal was to achieve an approach that is both low cost and effective in BAW applications. To this end, we micromachined aluminum 6061 plates and enclosed the systems with a thin PDMS cover layer. These aluminum/PDMS hybrid microfluidic devices use inexpensive materials and are simply constructed outside a clean room environment. Moreover, these devices demonstrate effectiveness in BAW applications as demonstrated by efficient acoustic focusing of polystyrene microspheres, bovine red blood cells, and Jurkat cells and the generation of multiple focused streams in flow-through systems. Graphical abstract The aluminum acoustofluidic device and the generation of multinode focusing of particles.

Separation of platelets from whole blood using standing surface acoustic waves in a microchannel.

PubMed

Nam, Jeonghun; Lim, Hyunjung; Kim, Dookon; Shin, Sehyun

2011-10-07

Platelet separation from blood is essential for biochemical analyses and clinical diagnosis. In this article, we propose a method to separate platelets from undiluted whole blood using standing surface acoustic waves (SSAWs) in a microfluidic device. A polydimethylsiloxane (PDMS) microfluidic channel was fabricated and integrated with interdigitated transducer (IDT) electrodes patterned on a piezoelectric substrate. To avoid shear-induced activation of platelets, the blood sample flow was hydrodynamically focused by introducing sheath flow from two side-inlets and pressure nodes were designed to locate at side walls. By means of flow cytometric analysis, the RBC clearance ratio from whole blood was found to be over 99% and the purity of platelets was close to 98%. Conclusively, the present technique using SSAWs can directly separate platelets from undiluted whole blood with higher purity than other methods.

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

PubMed

Roh, Changhyun; Lee, Jaewoong; Kang, Chankyu

2016-06-18

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

Continuous form-dependent focusing of non-spherical microparticles in a highly diluted suspension with the help of microfluidic spirals

NASA Astrophysics Data System (ADS)

Roth, Tanja; Sprenger, Lisa; Odenbach, Stefan; Häfeli, Urs O.

2018-04-01

Microfluidic spirals are able to focus non-spherical microparticles in diluted suspension due to the Dean effect. A secondary flow establishes in a curved channel, consisting of two counter-rotating vortices, which transport particles to an equilibrium position near the inner wall of the channel. The relevant size parameter, which is responsible for successful focusing, is the ratio between the particle diameter of a sphere and the hydraulic diameter, which is a characteristic of the microfluidic spiral. A non-spherical particle has not one but several different size parameters. This study investigated the minor and major axes, the equivalent spherical diameter, and the maximal rotational diameter as an equivalent to the spherical diameter. Using a polydimethylsiloxane (PDMS)-based microfluidic device with spirals, experiments were conducted with artificial peanut-shaped and ellipsoidal particles sized between 3 and 9 μm as well as with the bacteria Bacillus subtilis. Our investigations show that the equivalent spherical diameter, the major axis, and the maximal rotational diameter of a non-spherical particle can predict successful focusing. The minor axis is not suitable for this purpose. Non-spherical particles focused when the ratio of their equivalent spherical diameter to the hydraulic diameter of the channel was larger than 0.07. The particles also focused when the ratio between the maximal rotational diameter or the major axis and the hydraulic diameter was larger than 0.01. These results may help us to separate non-spherical biological particles, such as circulating tumor cells or pathogenic bacteria, from blood in future experimental studies.

Fluidic optics

NASA Astrophysics Data System (ADS)

Whitesides, George M.; Tang, Sindy K. Y.

2006-09-01

Fluidic optics is a new class of optical system with real-time tunability and reconfigurability enabled by the introduction of fluidic components into the optical path. We describe the design, fabrication, operation of a number of fluidic optical systems, and focus on three devices, liquid-core/liquid-cladding (L2) waveguides, microfluidic dye lasers, and diffraction gratings based on flowing, crystalline lattices of bubbles, to demonstrate the integration of microfluidics and optics. We fabricate these devices in poly(dimethylsiloxane) (PDMS) with soft-lithographic techniques. They are simple to construct, and readily integrable with microanalytical or lab-on-a-chip systems.

Numerical and experimental evaluation of microfluidic sorting devices.

PubMed

Taylor, Jay K; Ren, Carolyn L; Stubley, G D

2008-01-01

The development of lab-on-a-chip devices calls for the isolation or separation of specific bioparticles or cells. The design of a miniaturized cell-sorting device for handheld operation must follow the strict parameters associated with lab-on-a-chip technology. The limitations include applied voltage, high efficiency of cell-separation, reliability, size, flow control, and cost, among others. Currently used designs have achieved successful levels of cell isolation; however, further improvements in the microfluidic chip design are important to incorporate into larger systems. This study evaluates specific design modifications that contribute to the reduction of required applied potential aiming for developing portable devices, improved operation reliability by minimizing induced pressure disturbance when electrokinetic pumping is employed, and improved flow control by incorporating directing streams achieving dynamic sorting and counting. The chip designs fabricated in glass and polymeric materials include asymmetric channel widths for sample focusing, nonuniform channel depth for minimizing induced pressure disturbance, directing streams to assist particle flow control, and online filters for reducing channel blockage. Fluorescence-based visualization experimental results of electrokinetic focusing, flow field phenomena, and dynamic sorting demonstrate the advantages of the chip design. Numerical simulations in COMSOL are validated by the experimental data and used to investigate the effects of channel geometry and fluid properties on the flow field.

Study on Manipulations of Fluids in Micro-scale and Their Applications in Physical, Bio/chemistry

NASA Astrophysics Data System (ADS)

Zhou, Bingpu

Microfluidics is a highly interdisciplinary research field which manipulates, controls and analyzes fluids in micro-scale for physical and bio/chemical applications. In this thesis, several aspects of fluid manipulations in micro-scale were studied, discussed and employed for demonstrations of practical utilizations. To begin with, mixing in continuous flow microfluidic was raised and investigated. A simple method for mixing actuation based on magnetism was proposed and realized via integration of magnetically functionalized micropillar arrays inside the microfluidic channel.With such technique, microfluidic mixing could be swiftly switched on and off via simple application or retraction of the magnetic field. Thereafter, in Chapter 3 we mainly focused on how to establish stable while tunable concentration gradients inside microfluidic network using a simple design. The proposed scheme could also be modified with on-chip pneumatic actuated valve to realize pulsatile/temporal concentration gradients simultaneously in ten microfluidic branches. We further applied such methodology to obtain roughness gradients onPolydimethylsiloxane (PDMS) surface via combinations of the microfluidic network andphoto-polymerizations. The obtained materials were utilized in parallel cell culture to figure out the relationship between substrate morphologies and the cell behaviors. In the second part of this work, we emphasized on manipulations on microdroplets insidethe microfluidic channel and explored related applications in bio/chemical aspects. Firstly, microdroplet-based microfluidic universal logic gates were successfully demonstrated vialiquid-electronic hybrid divider. For application based on such novel scheme of control lable droplet generation, on-demand chemical reaction within paired microdroplets was presented using IF logic gate. Followed by this, another important operation of microdroplet - splitting -was investigated. Addition lateral continuous flow was applied at the bifurcation as a mediumto controllably divide microdroplets with highly tunable splitting ratios. Related physical mechanism was proposed and such approach was adopted further for rapid synthesis of multi-scale microspheres.

Ultrahigh throughput microfluidic platform for in-air production of microscale droplets

NASA Astrophysics Data System (ADS)

Tirandazi, Pooyan; Healy, John; Hidrovo, Carlos H.

2017-11-01

In-air droplet formation inside microfluidic networks is an alternative technique to the conventional in-liquid systems for creating uniform, microscale droplets. Recent works have highlighted and quantified the use of a gaseous continuous phase for controlled generation of droplets in the Dripping regime in planar structures. Here we demonstrate a new class of non-planar droplet-based systems which rely on controlled breakup of a liquid microjet within a high speed flow of air inside a confined microfluidic flow-focusing PDMS channel. We investigate the physics of confined gas-liquid flows and the effect of geometry on the behavior of a liquid water jet in a gaseous flow. Droplet breakup in the Jetting regime is studied both numerically and experimentally and the results are compared. We show droplet production capability at rates higher than 100 KHz with droplets ranging from 15-30 μm in diameter and a polydispersity index of less than 15%. This work represents an important investigation into the Jetting regime in confined microchannels. The ability to control jet behavior, generation rate, and droplet size in gas-liquid microflows will further expand the potential applications of this system for high throughput operations in material synthesis and biochemical analysis. We acknowledge funding support from NSF CAREER Award Grant CBET-1522841.

Microfluidic oscillators with widely tunable periods

PubMed Central

Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

2013-01-01

We present experiments and theory of a constant flow-driven microfluidic oscillator with widely tunable oscillation periods. This oscillator converts two constant input-flows from a syringe pump into an alternating, periodic output-flow with oscillation periods that can be adjusted to between 0.3 s to 4.1 h by tuning an external membrane capacitor. This capacitor allows multiple adjustable periods at a given input flow-rate, thus providing great flexibility in device operation. Also, we show that a sufficiently large external capacitance, relative to the internal capacitance of the microfluidic valve itself, is a critical requirement for oscillation. These widely tunable microfluidic oscillators are envisioned to be broadly useful for the study of biological rhythms, as on-chip timing sources for microfluidic logic circuits, and other applications that require variation in timed flow switching. PMID:23429765

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.

Microfluidics—from fundamental research to industrial applications

NASA Astrophysics Data System (ADS)

Köster, Sarah

2013-03-01

The advance of microfluidics started in the early 1980s. At the time, researchers realized that many processes and reactions in chemistry and biology, which typically take place on small length scales, can be defined, controlled and understood much better when using tools on equally small length scales. Reactions and reaction kinetics rely on (gradual) concentration differences and microfluidics provides the unique possibility to establish exactly such gradients of solutes, ion concentrations, pH value and so on. Nowadays the variety of specific microfluidic methods is large. In principle, they can be divided into two groups: (i) monophase flow, where miscible (e.g. aqueous) fluids are mixed, mostly by diffusion owing to the laminar flow on small length scales and (ii) multiphase flow, the most prominent example of which is probably droplet microfluidics, where water-in-oil or oil-in-water emulsions are used to encapsulate chemical or biological systems and separate them from each other, much like in 'micron-scale test tubes'. Now, 30 years later, microfluidic techniques are seriously considered for industrial applications, although some important steps in the upscaling process are still missing. The purpose of this special issue is to shed light on the different aspects in microfluidics research starting from fundamental research reaching all the way to industrial applications. The study by Toma and co-workers takes advantage of the controlled diffusive mixing when co-flowing aqueous, miscible solutions. They combine microfluidics with optical, spectroscopic and scattering techniques to study DNA packing. Nunes et al review the different regimes when replacing one of the fluids by an oil phase and varying flow rates and device geometries with a particular emphasis on using multiphase microfluidics for synthesis of particles or fibres. Going into the third dimension by fabricating microfluidic devices with several layers, producing emulsions can also be achieved by so-called 'step emulsification', the physical mechanisms behind which are described by Dangla et al. Tran and co-workers move a considerable step towards applicability of water-in-oil emulsions for biological research and review ultrahigh-throughput methods used for bio-assays. The article by Lagus et al focuses this topic specifically on single-cell experiments. Whereas it is very popular to use emulsions with drop sizes of a few tens of micrometers as 'tiny test tubes' they may also serve as templates for materials fabrication. Gundabala and co-workers combine both aspects by producing so-called 'celloidosomes', which consist of liquid drops decorated with yeast cells at the outer interface. Wang et al fabricate microcrawlers that can be thermally set in motion. Finally, Holtze gives a perspective on the possibility to upscale and apply such methods in industry. The choice of papers shows the wide and diverse applicability of microfluidics in various fields of research. While microfluidics started out as a 'niche' technique for very specific applications and as a tool in fundamental soft and biological matter research, the advancements made during recent years promise further progress in the chemical industry, biomedicine and pharmacology. Advantages such as low sample consumption, single cell accessibility and controlled experimental parameters in general may in the future be exploited for real industrial sized applications. In Journal of Physics D: Applied Physics we find a journal that is ideally positioned to give applied microfluidics research a wide readership across many disciplines. In the publication of this special issue we hope to inspire and encourage microfluidics researchers, and to promote interdisciplinary collaborations. We would like to thank all of the authors for their excellent contributions to this special issue.

Vacuum-assisted cell loading enables shear-free mammalian microfluidic culture

PubMed Central

Kolnik, Martin; Tsimring, Lev S; Hasty, Je

2012-01-01

Microfluidic perfusion cultures for mammalian cells provide a novel means for probing single-cell behavior but require the management of culture parameters such as flow-induced shear stress. Methods to eliminate shear stress generally focus on capturing cells in regions with high resistance to fluid flow. Here, we present a novel trapping design to easily and reliably load a high density of cells into culture chambers that are extremely isolated from potentially damaging flow effects. We utilize a transient on-chip vacuum to remove air from the culture chambers and rapidly replace the volume with a liquid cell suspension. We demonstrate the ability of this simple and robust method to load and culture three commonly used cell lines. We show how the incorporation of an on-chip function generator can be used for dynamic stimulation of cells during long-term continuous perfusion culture. PMID:22961584

A novel microfluidic mixer based on dual-hydrodynamic focusing for interrogating the kinetics of DNA-protein interaction.

PubMed

Li, Ying; Xu, Fei; Liu, Chao; Xu, Youzhi; Feng, Xiaojun; Liu, Bi-Feng

2013-08-21

Kinetic measurement of biomacromolecular interaction plays a significant role in revealing the underlying mechanisms of cellular activities. Due to the small diffusion coefficient of biomacromolecules, it is difficult to resolve the rapid kinetic process with traditional analytical methods such as stopped-flow or laminar mixers. Here, we demonstrated a unique continuous-flow laminar mixer based on microfluidic dual-hydrodynamic focusing to characterize the kinetics of DNA-protein interactions. The time window of this mixer for kinetics observation could cover from sub-milliseconds to seconds, which made it possible to capture the folding process with a wide dynamic range. Moreover, the sample consumption was remarkably reduced to <0.55 μL min⁻¹, over 1000-fold saving in comparison to those reported previously. We further interrogated the interaction kinetics of G-quadruplex and the single-stranded DNA binding protein, indicating that this novel micromixer would be a useful approach for analyzing the interaction kinetics of biomacromolecules.

Dean Flow Dynamics in Low-Aspect Ratio Spiral Microchannels

PubMed Central

Nivedita, Nivedita; Ligrani, Phillip; Papautsky, Ian

2017-01-01

A wide range of microfluidic cell-sorting devices has emerged in recent years, based on both passive and active methods of separation. Curvilinear channel geometries are often used in these systems due to presence of secondary flows, which can provide high throughput and sorting efficiency. Most of these devices are designed on the assumption of two counter rotating Dean vortices present in the curved rectangular channels and existing in the state of steady rotation and amplitude. In this work, we investigate these secondary flows in low aspect ratio spiral rectangular microchannels and define their development with respect to the channel aspect ratio and Dean number. This work is the first to experimentally and numerically investigate Dean flows in microchannels for Re > 100, and show presence of secondary Dean vortices beyond a critical Dean number. We further demonstrate the impact of these multiple vortices on particle and cell focusing. Ultimately, this work offers new insights into secondary flow instabilities for low-aspect ratio, spiral microchannels, with improved flow models for design of more precise and efficient microfluidic devices for applications such as cell sorting and micromixing. PMID:28281579

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.

Influence of clay particles on microfluidic-based preparation of hydrogel composite microsphere

NASA Astrophysics Data System (ADS)

Hong, Joung Sook

2016-05-01

For the successful fabrication of a hydrogel composite microsphere, this study aimed to investigate the influence of clay particles on microsphere formation in a microfluidic device which has flow focusing and a 4.5:1 contraction channel. A poly alginic acid solution (2.0 wt.%) with clay particles was used as the dispersed phase to generate drops in an oil medium, which then merged with drops of a CaCl2 solution for gelation. Drop generations were observed with different flow rates and particles types. When the flow rate increased, drop generation was enhanced and drop size decreased by the build-up of more favorable hydrodynamic flow conditions to detach the droplets. The addition of a small amount of particles insignificantly changed the drop generation behavior even though it reduced interfacial tension and increased the viscosity of the solution. Instead, clays particles significantly affected hydro-gelation depending on the hydrophobicity of particles, which produced further heterogeneity in the shape and size of microsphere.

Breast Cancer Tissue Bioreactor for Direct Interrogation and Observation of Response to Antitumor Therapies

DTIC Science & Technology

2012-07-01

regulate microfluidic flow rates within the TTB, including flow channel height variation and incorporation of valves (see Figure 2 and Supplemental...cartridge. As an alternative to individual channel TURN valve -adjusted flow regulators, we investigated use of pre-fabricated microfluidic flow resistance...Small Parts, Inc. and B) Microfluidic manifolds with built-in TURN valves . Supplemental Figure S3. Simplified 2D and 3D diffusional model

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.

Vacuum-driven power-free microfluidics utilizing the gas solubility or permeability of polydimethylsiloxane (PDMS).

PubMed

Xu, Linfeng; Lee, Hun; Jetta, Deekshitha; Oh, Kwang W

2015-10-21

Suitable pumping methods for flow control remain a major technical hurdle in the path of biomedical microfluidic systems for point-of-care (POC) diagnostics. A vacuum-driven power-free micropumping method provides a promising solution to such a challenge. In this review, we focus on vacuum-driven power-free microfluidics based on the gas solubility or permeability of polydimethylsiloxane (PDMS); degassed PDMS can restore air inside itself due to its high gas solubility or gas permeable nature. PDMS allows the transfer of air into a vacuum through it due to its high gas permeability. Therefore, it is possible to store or transfer air into or through the gas soluble or permeable PDMS in order to withdraw liquids into the embedded dead-end microfluidic channels. This article provides a comprehensive look at the physics of the gas solubility and permeability of PDMS, a systematic review of different types of vacuum-driven power-free microfluidics, and guidelines for designing solubility-based or permeability-based PDMS devices, alongside existing applications. Advanced topics and the outlook in using micropumping that utilizes the gas solubility or permeability of PDMS will be also discussed. We strongly recommend that microfluidics and lab-on-chip (LOC) communities harness vacuum energy to develop smart vacuum-driven microfluidic systems.

Development of a Mechatronic Syringe Pump to Control Fluid Flow in a Microfluidic Device Based on Polyimide Film

NASA Astrophysics Data System (ADS)

Sek Tee, Kian; Sharil Saripan, Muhammad; Yap, Hiung Yin; Fhong Soon, Chin

2017-08-01

With the advancement in microfluidic technology, fluid flow control for syringe pump is always essential. In this paper, a mechatronic syringe pump will be developed and customized to control the fluid flow in a poly-dimethylsiloxane (PDMS) microfluidic device based on a polyimide laminating film. The syringe pump is designed to drive fluid with flow rates of 100 and 1000 μl/min which intended to drive continuous fluid in a polyimide based microfluidic device. The electronic system consists of an Arduino microcontroller board and a uni-polar stepper motor. In the system, the uni-polar stepper motor was coupled to a linear slider attached to the plunger of a syringe pump. As the motor rotates, the plunger pumps the liquid out of the syringe. The accuracy of the fluid flow rate was determined by adjusting the number of micro-step/revolution to drive the stepper motor to infuse fluid into the microfluidic device. With the precise control of the electronic system, the syringe pump could accurately inject fluid volume at 100 and 1000 μl/min into a microfluidic device.

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 devices to facilitate a multi-functional lab-on-a-chip for mammalian cell manipulations.

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

PubMed

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

2017-04-15

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

Label-free in-flow detection of single DNA molecules using glass nanopipettes.

PubMed

Gong, Xiuqing; Patil, Amol V; Ivanov, Aleksandar P; Kong, Qingyuan; Gibb, Thomas; Dogan, Fatma; deMello, Andrew J; Edel, Joshua B

2014-01-07

With the view of enhancing the functionality of label-free single molecule nanopore-based detection, we have designed and developed a highly robust, mechanically stable, integrated nanopipette-microfluidic device which combines the recognized advantages of microfluidic systems and the unique properties/advantages of nanopipettes. Unlike more typical planar solid-state nanopores, which have inherent geometrical constraints, nanopipettes can be easily positioned at any point within a microfluidic channel. This is highly advantageous, especially when taking into account fluid flow properties. We show that we are able to detect and discriminate between DNA molecules of varying lengths when motivated through a microfluidic channel, upon the application of appropriate voltage bias across the nanopipette. The effects of applied voltage and volumetric flow rates have been studied to ascertain translocation event frequency and capture rate. Additionally, by exploiting the advantages associated with microfluidic systems (such as flow control and concomitant control over analyte concentration/presence), we show that the technology offers a new opportunity for single molecule detection and recognition in microfluidic devices.

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

PubMed

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

2015-01-07

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

Laser-induced fluorescence detection platform for point-of-care testing

NASA Astrophysics Data System (ADS)

Berner, Marcel; Hilbig, Urs; Schubert, Markus B.; Gauglitz, Günter

2017-08-01

Point-of-care testing (POCT) devices for continuous low-cost monitoring of critical patient parameters require miniaturized and integrated setups for performing quick high-sensitivity analyses, away from central clinical laboratories. This work presents a novel and promising laser-induced fluorescence platform for measurements in direct optical test formats that leads towards such powerful POCT devices based on fluorescence-labeled immunoassays. Ultimate sensitivity of thin film photodetectors, integrated with microfluidics, and a comprehensive optimization of all system components aim at low-level signal detection in the targeted biosensor application. The setup acquires fluorescence signals from the volume of a microfluidic channel. An innovative sandwiching process forms a flow channel in the microfluidic chips by embedding laser-cut double-sided adhesive tapes. The custom fit of amorphous silicon based photodiode arrays to the geometry of the flow channel enables miniaturization, fully adequate for POCT devices. A free-beam laser excitation with line focus provides excellent alignment stability, allows for easy and reliable swapping of the disposable microfluidic chips, and therewith greatly improves the ease of use of the resulting integrated device. As a proof-of-concept of this novel in-volume measurement approach, the limit of detection for the dye DY636-COOH in pure water as a model fluorophore is examined and found to be 26 nmol l-1 .

Morphological comparison of PVA scaffolds obtained by gas foaming and microfluidic foaming techniques.

PubMed

Colosi, Cristina; Costantini, Marco; Barbetta, Andrea; Pecci, Raffaella; Bedini, Rossella; Dentini, Mariella

2013-01-08

In this article, we have exploited a microfluidic foaming technique for the generation of highly monodisperse gas-in-liquid bubbles as a templating system for scaffolds characterized by an ordered and homogeneous porous texture. An aqueous poly(vinyl alcohol) (PVA) solution (containing a surfactant) and a gas (argon) are injected simultaneously at constant flow rates in a flow-focusing device (FFD), in which the gas thread breaks up to form monodisperse bubbles. Immediately after its formation, the foam is collected and frozen in liquid nitrogen, freeze-dried, and cross-linked with glutaraldehyde. In order to highlight the superior morphological quality of the obtained porous material, a comparison between this scaffold and another one, also constituted of PVA but obtained with a traditional gas foaming technique, was carried out. Such a comparison has been conducted by analyzing electron microscopy and X-ray microtomographic images of the two samples. It turned out that the microfluidic produced scaffold was characterized by much more uniform porous texture than the gas-foaming one as witnessed by narrower pore size, interconnection, and wall thickness distributions. On the other side, scarce pore interconnectivity, relatively low pore volume, and limited production rate represent, by now, the principal disadvantages of microfluidic foaming as scaffold fabrication method, emphasizing the kind of improvement that this technique needs to undergo.

Rapid microfluidic thermal cycler for nucleic acid amplification

DOEpatents

Beer, Neil Reginald; Vafai, Kambiz

2015-10-27

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

Acoustic Microfluidics for Bioanalytical Application

NASA Astrophysics Data System (ADS)

Lopez, Gabriel

2013-03-01

This talk will present new methods the use of ultrasonic standing waves in microfluidic systems to manipulate microparticles for the purpose of bioassays and bioseparations. We have recently developed multi-node acoustic focusing flow cells that can position particles into many parallel flow streams and have demonstrated the potential of such flow cells in the development of high throughput, parallel flow cytometers. These experiments show the potential for the creation of high throughput flow cytometers in applications requiring high flow rates and rapid detection of rare cells. This talk will also present the development of elastomeric capture microparticles and their use in acoustophoretic separations. We have developed simple methods to form elastomeric particles that are surface functionalized with biomolecular recognition reagents. These compressible particles exhibit negative acoustic contrast in ultrasound when suspended in aqueous media, blood serum or diluted blood. These particles can be continuously separated from cells by flowing them through a microfluidic device that uses an ultrasonic standing wave to align the blood cells, which exhibit positive acoustic contrast, at a node in the acoustic pressure distribution while aligning the negative acoustic contrast elastomeric particles at the antinodes. Laminar flow of the separated particles to downstream collection ports allows for collection of the separated negative contrast particles and cells. Separated elastomeric particles were analyzed via flow cytometry to demonstrate nanomolar detection for prostate specific antigen in aqueous buffer and picomolar detection for IgG in plasma and diluted blood samples. This approach has potential applications in the development of rapid assays that detect the presence of low concentrations of biomarkers (including biomolecules and cells) in a number of biological sample types. We acknowledge support through the NSF Research Triangle MRSEC.

Papers Based Electrochemical Biosensors: From Test Strips to Paper-Based Microfluidics

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

Liu, Bingwen; Du, Dan; Hua, Xin

2014-05-08

Papers based biosensors such as lateral flow test strips and paper-based microfluidic devices (or paperfluidics) are inexpensive, rapid, flexible, and easy-to-use analytical tools. An apparent trend in their detection is to interpret sensing results from qualitative assessment to quantitative determination. Electrochemical detection plays an important role in quantification. This review focuses on electrochemical (EC) detection enabled biosensors. The first part provides detailed examples in paper test strips. The second part gives an overview of paperfluidics engaging EC detections. The outlook and recommendation of future directions of EC enabled biosensors are discussed in the end.

A simplified sheathless cell separation approach using combined gravitational-sedimentation-based prefocusing and dielectrophoretic separation.

PubMed

Luo, Tao; Fan, Lei; Zeng, Yixiao; Liu, Ya; Chen, Shuxun; Tan, Qiulin; Lam, Raymond H W; Sun, Dong

2018-05-04

Prefocusing of the cell mixture is necessary for achieving a high-efficiency and continuous dielectrophoretic (DEP) cell separation. However, prefocusing through sheath flow requires a complex and tedious peripheral system for multi-channel fluid control, hindering the integration of DEP separation systems with other microfluidic functionalities for comprehensive clinical and biological tasks. This paper presented a simplified sheathless cell separation approach that combines gravitational-sedimentation-based sheathless prefocusing and DEP separation methods. Through gravitational sedimentation in a tubing, which was inserted into the inlet of a microfluidic chip with an adjustable steering angle, the cells were focused into a stream at the upstream region of a microchannel prior to separation. Then, a DEP force was applied at the downstream region of the microchannel for the active separation of the cells. Through this combined strategy, the peripheral system for the sheath flow was no longer required, and thus the integration of cell separation system with additional microfluidic functionalities was facilitated. The proposed sheathless scheme focused the mixture of cells with different sizes and dielectric properties into a stream in a wide range of flow rates without changing the design of the microfluidic chip. The DEP method is a label-free approach that can continuously separate cells on the basis of the sizes or dielectric properties of the cells and thus capable of greatly flexible cell separation. The efficiency of the proposed approach was experimentally assessed according to its performance in the separation of human acute monocytic leukemia THP-1 cells from yeast cells with respect to different sizes and THP-1 cells from human acute myelomonocytic leukemia OCI-AML3 cells with respect to different dielectric properties. The experimental results revealed that the separation efficiency of the method can surpass 90% and thus effective in separating cells on the basis of either size or dielectric property.

Optimized open-flow mixing: insights from microbubble streaming

NASA Astrophysics Data System (ADS)

Rallabandi, Bhargav; Wang, Cheng; Guo, Lin; Hilgenfeldt, Sascha

2015-11-01

Microbubble streaming has been developed into a robust and powerful flow actuation technique in microfluidics. Here, we study it as a paradigmatic system for microfluidic mixing under a continuous throughput of fluid (open-flow mixing), providing a systematic optimization of the device parameters in this practically important situation. Focusing on two-dimensional advective stirring (neglecting diffusion), we show through numerical simulation and analytical theory that mixing in steady streaming vortices becomes ineffective beyond a characteristic time scale, necessitating the introduction of unsteadiness. By duty cycling the streaming, such unsteadiness is introduced in a controlled fashion, leading to exponential refinement of the advection structures. The rate of refinement is then optimized for particular parameters of the time modulation, i.e. a particular combination of times for which the streaming is turned ``on'' and ``off''. The optimized protocol can be understood theoretically using the properties of the streaming vortices and the throughput Poiseuille flow. We can thus infer simple design principles for practical open flow micromixing applications, consistent with experiments. Current Address: Mechanical and Aerospace Engineering, Princeton University.

Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling

NASA Astrophysics Data System (ADS)

Shang, Yuqin; Zeng, Yun; Zeng, Yong

2016-02-01

Protein glycosylation is one of the key processes that play essential roles in biological functions and dysfunctions. However, progress in glycomics has considerably lagged behind genomics and proteomics, due in part to the enormous challenges in analysis of glycans. Here we present a new integrated and automated microfluidic lectin barcode platform to substantially improve the performance of lectin array for focused glycomic profiling. The chip design and flow control were optimized to promote the lectin-glycan binding kinetics and speed of lectin microarray. Moreover, we established an on-chip lectin assay which employs a very simple blocking method to effectively suppress the undesired background due to lectin binding of antibodies. Using this technology, we demonstrated focused differential profiling of tissue-specific glycosylation changes of a biomarker, CA125 protein purified from ovarian cancer cell line and different tissues from ovarian cancer patients in a fast, reproducible, and high-throughput fashion. Highly sensitive CA125 detection was also demonstrated with a detection limit much lower than the clinical cutoff value for cancer diagnosis. This microfluidic platform holds the potential to integrate with sample preparation functions to construct a fully integrated “sample-to-answer” microsystem for focused differential glycomic analysis. Thus, our technology should present a powerful tool in support of rapid advance in glycobiology and glyco-biomarker development.

Integrated Microfluidic Lectin Barcode Platform for High-Performance Focused Glycomic Profiling

PubMed Central

Shang, Yuqin; Zeng, Yun; Zeng, Yong

2016-01-01

Protein glycosylation is one of the key processes that play essential roles in biological functions and dysfunctions. However, progress in glycomics has considerably lagged behind genomics and proteomics, due in part to the enormous challenges in analysis of glycans. Here we present a new integrated and automated microfluidic lectin barcode platform to substantially improve the performance of lectin array for focused glycomic profiling. The chip design and flow control were optimized to promote the lectin-glycan binding kinetics and speed of lectin microarray. Moreover, we established an on-chip lectin assay which employs a very simple blocking method to effectively suppress the undesired background due to lectin binding of antibodies. Using this technology, we demonstrated focused differential profiling of tissue-specific glycosylation changes of a biomarker, CA125 protein purified from ovarian cancer cell line and different tissues from ovarian cancer patients in a fast, reproducible, and high-throughput fashion. Highly sensitive CA125 detection was also demonstrated with a detection limit much lower than the clinical cutoff value for cancer diagnosis. This microfluidic platform holds the potential to integrate with sample preparation functions to construct a fully integrated “sample-to-answer” microsystem for focused differential glycomic analysis. Thus, our technology should present a powerful tool in support of rapid advance in glycobiology and glyco-biomarker development. PMID:26831207

Rapid prototyping polymers for microfluidic devices and high pressure injections.

PubMed

Sollier, Elodie; Murray, Coleman; Maoddi, Pietro; Di Carlo, Dino

2011-11-21

Multiple methods of fabrication exist for microfluidic devices, with different advantages depending on the end goal of industrial mass production or rapid prototyping for the research laboratory. Polydimethylsiloxane (PDMS) has been the mainstay for rapid prototyping in the academic microfluidics community, because of its low cost, robustness and straightforward fabrication, which are particularly advantageous in the exploratory stages of research. However, despite its many advantages and its broad use in academic laboratories, its low elastic modulus becomes a significant issue for high pressure operation as it leads to a large alteration of channel geometry. Among other consequences, such deformation makes it difficult to accurately predict the flow rates in complex microfluidic networks, change flow speed quickly for applications in stop-flow lithography, or to have predictable inertial focusing positions for cytometry applications where an accurate alignment of the optical system is critical. Recently, other polymers have been identified as complementary to PDMS, with similar fabrication procedures being characteristic of rapid prototyping but with higher rigidity and better resistance to solvents; Thermoset Polyester (TPE), Polyurethane Methacrylate (PUMA) and Norland Adhesive 81 (NOA81). In this review, we assess these different polymer alternatives to PDMS for rapid prototyping, especially in view of high pressure injections with the specific example of inertial flow conditions. These materials are compared to PDMS, for which magnitudes of deformation and dynamic characteristics are also characterized. We provide a complete and systematic analysis of these materials with side-by-side experiments conducted in our lab that also evaluate other properties, such as biocompatibility, solvent compatibility, and ease of fabrication. We emphasize that these polymer alternatives, TPE, PUMA and NOA, have some considerable strengths for rapid prototyping when bond strength, predictable operation at high pressure, or transitioning to commercialization are considered important for the application.

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.

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

PubMed Central

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. PMID:24404051

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.

"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.

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.

Microfluidics and Coagulation Biology

PubMed Central

Colace, Thomas V.; Tormoen, Garth W.

2014-01-01

The study of blood ex vivo can occur in closed or open systems, with or without flow. Microfluidic devices facilitate measurements of platelet function, coagulation biology, cellular biorheology, adhesion dynamics, pharmacology, and clinical diagnostics. An experimental session can accommodate 100s to 1000s of unique clotting events. Using microfluidics, thrombotic events can be studied on defined surfaces of biopolymers, matrix proteins, and tissue factor under constant flow rate or constant pressure drop conditions. Distinct shear rates can be created on a device with a single perfusion pump. Microfluidic devices facilitated the determination of intraluminal thrombus permeability and the discovery that platelet contractility can be activated by a sudden decrease in flow. Microfluidics are ideal for multicolor imaging of platelets, fibrin, and phosphatidylserine and provide a human blood analog to the mouse injury models. Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics. PMID:23642241

Computational analysis of integrated biosensing and shear flow in a microfluidic vascular model

NASA Astrophysics Data System (ADS)

Wong, Jeremy F.; Young, Edmond W. K.; Simmons, Craig A.

2017-11-01

Fluid flow and flow-induced shear stress are critical components of the vascular microenvironment commonly studied using microfluidic cell culture models. Microfluidic vascular models mimicking the physiological microenvironment also offer great potential for incorporating on-chip biomolecular detection. In spite of this potential, however, there are few examples of such functionality. Detection of biomolecules released by cells under flow-induced shear stress is a significant challenge due to severe sample dilution caused by the fluid flow used to generate the shear stress, frequently to the extent where the analyte is no longer detectable. In this work, we developed a computational model of a vascular microfluidic cell culture model that integrates physiological shear flow and on-chip monitoring of cell-secreted factors. Applicable to multilayer device configurations, the computational model was applied to a bilayer configuration, which has been used in numerous cell culture applications including vascular models. Guidelines were established that allow cells to be subjected to a wide range of physiological shear stress while ensuring optimal rapid transport of analyte to the biosensor surface and minimized biosensor response times. These guidelines therefore enable the development of microfluidic vascular models that integrate cell-secreted factor detection while addressing flow constraints imposed by physiological shear stress. Ultimately, this work will result in the addition of valuable functionality to microfluidic cell culture models that further fulfill their potential as labs-on-chips.

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.

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.

Optofluidic bioimaging platform for quantitative phase imaging of lab on a chip devices using digital holographic microscopy.

PubMed

Pandiyan, Vimal Prabhu; John, Renu

2016-01-20

We propose a versatile 3D phase-imaging microscope platform for real-time imaging of optomicrofluidic devices based on the principle of digital holographic microscopy (DHM). Lab-on-chip microfluidic devices fabricated on transparent polydimethylsiloxane (PDMS) and glass substrates have attained wide popularity in biological sensing applications. However, monitoring, visualization, and characterization of microfluidic devices, microfluidic flows, and the biochemical kinetics happening in these devices is difficult due to the lack of proper techniques for real-time imaging and analysis. The traditional bright-field microscopic techniques fail in imaging applications, as the microfluidic channels and the fluids carrying biological samples are transparent and not visible in bright light. Phase-based microscopy techniques that can image the phase of the microfluidic channel and changes in refractive indices due to the fluids and biological samples present in the channel are ideal for imaging the fluid flow dynamics in a microfluidic channel at high resolutions. This paper demonstrates three-dimensional imaging of a microfluidic device with nanometric depth precisions and high SNR. We demonstrate imaging of microelectrodes of nanometric thickness patterned on glass substrate and the microfluidic channel. Three-dimensional imaging of a transparent PDMS optomicrofluidic channel, fluid flow, and live yeast cell flow in this channel has been demonstrated using DHM. We also quantify the average velocity of fluid flow through the channel. In comparison to any conventional bright-field microscope, the 3D depth information in the images illustrated in this work carry much information about the biological system under observation. The results demonstrated in this paper prove the high potential of DHM in imaging optofluidic devices; detection of pathogens, cells, and bioanalytes on lab-on-chip devices; and in studying microfluidic dynamics in real time based on phase changes.

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

PubMed

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

2016-11-23

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

Electrokinetic dispersion in microfluidic separation systems

NASA Astrophysics Data System (ADS)

Molho, Joshua Irving

Numerous efforts have focused on engineering miniaturized chemical analysis devices that are faster, more portable and consume smaller volumes of expensive reagents than their macroscale counterparts. Many of these analysis devices employ electrokinetic effects to transport picoliter volumes of liquids and to separate chemical species from an initially mixed sample volume. In these microfluidic separation systems, dispersion must be minimized to obtain the highest resolution separation possible. This work focuses on modeling, simulation and experimental measurement of two electrokinetic dispersion mechanisms that can reduce the effectiveness of microfluidic separation systems: dispersion resulting from non-uniform wall zeta-potential, and dispersion caused by microchannel turns. When the surface of a microchannel has non-uniform zeta-potential (e.g., if the surface charge varies along the length of the microchannel), an applied electric field creates both electroosmotic and pressure-driven flow. A caged-fluorescence imaging technique was used to visualize the dispersion caused by this electrokinetically induced pressure-driven flow. A simple model for a single channel with an axially varying surface charge is presented and compared to experimental measurements. Microchannel turns have been shown to create dispersion of electrokinetically transported analyte bands. Using a method of moments analysis, a model is developed that quantifies this dispersion and identifies the conditions under which turn dispersion limits the resolution of a microfluidic separation system. Measurements using the caged-fluorescence visualization technique were used to verify this model. New turn geometries are presented and were optimized using both a reduced parameter technique as well as a more generalized, numerical shape optimization approach. These improved turn designs were manufactured using two fabrication techniques and then tested experimentally. The turn optimization approaches and resulting turn geometries described here are shown to reduce turn dispersion to less than 1% of the dispersion caused by unoptimized, constant-width turns.

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.

Lagrangian 3D tracking of fluorescent microscopic objects in motion

NASA Astrophysics Data System (ADS)

Darnige, T.; Figueroa-Morales, N.; Bohec, P.; Lindner, A.; Clément, E.

2017-05-01

We describe the development of a tracking device, mounted on an epi-fluorescent inverted microscope, suited to obtain time resolved 3D Lagrangian tracks of fluorescent passive or active micro-objects in microfluidic devices. The system is based on real-time image processing, determining the displacement of a x, y mechanical stage to keep the chosen object at a fixed position in the observation frame. The z displacement is based on the refocusing of the fluorescent object determining the displacement of a piezo mover keeping the moving object in focus. Track coordinates of the object with respect to the microfluidic device as well as images of the object are obtained at a frequency of several tenths of Hertz. This device is particularly well adapted to obtain trajectories of motile micro-organisms in microfluidic devices with or without flow.

Lagrangian 3D tracking of fluorescent microscopic objects in motion.

PubMed

Darnige, T; Figueroa-Morales, N; Bohec, P; Lindner, A; Clément, E

2017-05-01

We describe the development of a tracking device, mounted on an epi-fluorescent inverted microscope, suited to obtain time resolved 3D Lagrangian tracks of fluorescent passive or active micro-objects in microfluidic devices. The system is based on real-time image processing, determining the displacement of a x, y mechanical stage to keep the chosen object at a fixed position in the observation frame. The z displacement is based on the refocusing of the fluorescent object determining the displacement of a piezo mover keeping the moving object in focus. Track coordinates of the object with respect to the microfluidic device as well as images of the object are obtained at a frequency of several tenths of Hertz. This device is particularly well adapted to obtain trajectories of motile micro-organisms in microfluidic devices with or without flow.

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

Thermally induced light-driven microfluidics using a MOEMS-based laser scanner for particle manipulation

NASA Astrophysics Data System (ADS)

Kremer, Matthias P.; Tortschanoff, Andreas

2014-03-01

One key challenge in the field of microfluidics and lab-on-a-chip experiments for biological or chemical applications is the remote manipulation of fluids, droplets and particles. These can be volume elements of reactants, particles coated with markers, cells or many others. Light-driven microfluidics is one way of accomplishing this challenge. In our work, we manipulated micrometre sized polystyrene beads in a microfluidic environment by inducing thermal flows. Therefore, the beads were held statically in an unstructured microfluidic chamber, containing a dyed watery solution. Inside this chamber, the beads were moved along arbitrary trajectories on a micrometre scale. The experiments were performed, using a MOEMS (micro-opto-electro-mechanical-systems)-based laser scanner with a variable focal length. This scanner system is integrated in a compact device, which is flexibly applicable to various microscope setups. The device utilizes a novel approach for varying the focal length, using an electrically tunable lens. A quasi statically driven MOEMS mirror is used for beam steering. The combination of a tunable lens and a dual axis micromirror makes the device very compact and robust and is capable of positioning the laser focus at any arbitrary location within a three dimensional working space. Hence, the developed device constitutes a valuable extension to manually executed microfluidic lab-on-chip experiments.

Integrated microfluidic platforms for investigating neuronal networks

NASA Astrophysics Data System (ADS)

Kim, Hyung Joon

This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA (multielectrode array) or nanowire electrode array to study electrophysiology in neuronal network. Also, "diode-like" microgrooves to control the number of neuronal processes is embedded in this platform. Chapter 6 concludes with a possible future direction of this work. Interfacing micro/nanotechnology with primary neuron culture would open many doors in fundamental neuroscience research and also biomedical innovation.

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.

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

Srivastava, Nimisha; Singh, Anup K

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

Controlling particle trajectories using oscillating microbubbles

NASA Astrophysics Data System (ADS)

Jalikop, Shreyas; Wang, Cheng; Hilgenfeldt, Sascha

2010-11-01

In many applications of microfluidics and biotechnology, such as cytometry and drug delivery, it is vital to manipulate the trajectories of microparticles such as vesicles or cells. On this small scale, inertial or gravitational effects are often too weak to exploit. We propose a mechanism to selectively trap and direct particles based on their size in creeping transport flows (Re1). We employ Rayleigh-Nyborg-Westervelt (RNW) streaming generated by an oscillating microbubble, which in turn generates a streaming flow component around the mobile particles. The result is an attractive interaction that draws the particle closer to the bubble. The impenetrability of the bubble interface destroys time-reversal symmetry and forces the particles onto either narrow trajectory bundles or well-defined closed trajectories, where they are trapped. The effect is dependent on particle size and thus allows for the passive focusing and sorting of selected sizes, on scales much smaller than the geometry of the microfluidic device. The device could eliminate the need for complicated microchannel designs with external magnetic or electric fields in applications such as particle focusing and size-based sorting.

Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

PubMed

Sakai, Yusuke; Hattori, Koji; Yanagawa, Fumiki; Sugiura, Shinji; Kanamori, Toshiyuki; Nakazawa, Kohji

2014-07-01

Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combined surface-enhanced Raman spectroscopy biotags and microfluidic platform for quantitative ratiometric discrimination between noncancerous and cancerous cells in flow

NASA Astrophysics Data System (ADS)

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

2013-01-01

Surface-enhanced Raman spectroscopy (SERS) biotags (SBTs) that carry peptides as cell recognition moieties were made from polymer-encapsulated silver nanoparticle dimers, infused with unique Raman reporter molecules. We previously demonstrated their potential use for identification of malignant cells, a central goal in cancer research, through a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Progress has been made toward the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to evaluate the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension, then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We have found that using SBTs ratiometrically can provide cell identification in flow, insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

Microfluidic Foaming: A Powerful Tool for Tailoring the Morphological and Permeability Properties of Sponge-like Biopolymeric Scaffolds.

PubMed

Costantini, Marco; Colosi, Cristina; Jaroszewicz, Jakub; Tosato, Alessia; Święszkowski, Wojciech; Dentini, Mariella; Garstecki, Piotr; Barbetta, Andrea

2015-10-28

Ordered porous polymeric materials can be engineered to present highly ordered pore arrays and uniform and tunable pore size. These features prompted a number of applications in tissue engineering, generation of meta materials, and separation and purification of biomolecules and cells. Designing new and efficient vistas for the generation of ordered porous materials is an active area of research. Here we investigate the potential of microfluidic foaming within a flow-focusing (FF) geometry in producing 3D regular sponge-like polymeric matrices with tailored morphological and permeability properties. The challenge in using microfluidic systems for the generation of polymeric foams is in the high viscosity of the continuous phase. We demonstrate that as the viscosity of the aqueous solution increases, the accessible range of foam bubble fraction (Φb) and bubble diameter (Db) inside the microfluidic chip tend to narrow progressively. This effect limits the accessible range of geometric properties of the resulting materials. We further show that this problem can be rationally tackled by appropriate choice of the concentration of the polymer. We demonstrate that via such optimization, the microfluidic assisted synthesis of porous materials becomes a facile and versatile tool for generation of porous materials with a wide range of pore size and pore volume. Moreover, we demonstrate that the size of interconnects among pores-for a given value of the gas fraction-can be tailored through the variation of surfactant concentration. This, in turn, affects the permeability of the materials, a factor of key importance in flow-through applications and in tissue engineering.

Design of portable ultraminiature flow cytometers for medical diagnostics

NASA Astrophysics Data System (ADS)

Leary, James F.

2018-02-01

Design of portable microfluidic flow/image cytometry devices for measurements in the field (e.g. initial medical diagnostics) requires careful design in terms of power requirements and weight to allow for realistic portability. True portability with high-throughput microfluidic systems also requires sampling systems without the need for sheath hydrodynamic focusing both to avoid the need for sheath fluid and to enable higher volumes of actual sample, rather than sheath/sample combinations. Weight/power requirements dictate use of super-bright LEDs with top-hat excitation beam architectures and very small silicon photodiodes or nanophotonic sensors that can both be powered by small batteries. Signal-to-noise characteristics can be greatly improved by appropriately pulsing the LED excitation sources and sampling and subtracting noise in between excitation pulses. Microfluidic cytometry also requires judicious use of small sample volumes and appropriate statistical sampling by microfluidic cytometry or imaging for adequate statistical significance to permit real-time (typically in less than 15 minutes) initial medical decisions for patients in the field. This is not something conventional cytometry traditionally worries about, but is very important for development of small, portable microfluidic devices with small-volume throughputs. It also provides a more reasonable alternative to conventional tubes of blood when sampling geriatric and newborn patients for whom a conventional peripheral blood draw can be problematical. Instead one or two drops of blood obtained by pin-prick should be able to provide statistically meaningful results for use in making real-time medical decisions without the need for blood fractionation, which is not realistic in the doctor's office or field.

Regulation of DNA conformations and dynamics in flows with hybrid field microfluidics.

PubMed

Ren, Fangfang; Zu, Yingbo; Kumar Rajagopalan, Kartik; Wang, Shengnian

2012-01-01

Visualizing single DNA dynamics in flow provides a wealth of physical insights in biophysics and complex flow study. However, large signal fluctuations, generated from diversified conformations, deformation history dependent dynamics and flow induced stochastic tumbling, often frustrate its wide adoption in single molecule and polymer flow study. We use a hybrid field microfluidic (HFM) approach, in which an electric field is imposed at desired locations and appropriate moments to balance the flow stress on charged molecules, to effectively regulate the initial conformations and the deformation dynamics of macromolecules in flow. With λ-DNA and a steady laminar shear flow as the model system, we herein studied the performance of HFM on regulating DNA trapping, relaxation, coil-stretch transition, and accumulation. DNA molecules were found to get captured in the focused planes when motions caused by flow, and the electric field were balanced. The trapped macromolecules relaxed in two different routes while eventually became more uniform in size and globule conformations. When removing the electric field, the sudden stretching dynamics of DNA molecules exhibited a more pronounced extension overshoot in their transient response under a true step function of flow stress while similar behaviors to what other pioneering work in steady shear flow. Such regulation strategies could be useful to control the conformations of other important macromolecules (e.g., proteins) and help better reveal their molecular dynamics.

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

PubMed

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

2018-02-20

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

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

PubMed Central

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

2016-01-01

Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications. PMID:27886051

In situ formation of leak-free polyethylene glycol (PEG) membranes in microfluidic fuel cells.

PubMed

Ho, W F; Lim, K M; Yang, K-L

2016-11-29

Membraneless microfluidic fuel cells operated under two co-laminar flows often face serious fuel cross-over problems, especially when flow rates are close to zero. In this study, we show that polyethylene glycol (PEG) monomers can be cross-linked inside microfluidic channels to form leak-free PEG membranes, which prevent mixing of two incompatible electrolyte solutions while allowing diffusion of certain molecules (e.g. glucose) and ions. By using PEG monomers of different molecular weights and cross-linking conditions, we are able to tailor selectivity of the membrane to allow passage of glucose while blocking larger molecules such as trypan blue. As a proof of principle, a microfluidic fuel cell with a PEG membrane and two incompatible electrolytes (acid and base) is demonstrated. Thanks to the leak-free nature of the PEG membrane, these two electrolytes do not mix together even at very slow flow rates. This microfluidic fuel cell is able to generate a voltage up to ∼450 mV from 10 mM of glucose with a flow rate of 20 μL min -1 . This microfluidic fuel cell is potentially useful as a miniature power source for many applications.

Buckling of Dielectric Elastomeric Plates for Electrically Active Microfludic Pumps

NASA Astrophysics Data System (ADS)

Holmes, Douglas; Tavakol, Behrouz; Bozlar, Michael; Froehlicher, Guillaume; Stone, Howard; Aksay, Ilhan

2013-11-01

Fluid flow can be directed and controlled by a variety of mechanisms within industrial and biological environments. Advances in microfluidic technology have required innovative ways to control fluid flow on a small scale, and the ability to actively control fluid flow within microfluidic devices is crucial for advancements in nanofluidics, biomedical fluidic devices, and digital microfluidics. In this work, we present a means for microfluidic control via the electrical actuation of thin, flexible valves within microfluidic channels. These structures consist of a dielectric elastomer confined between two compliant electrodes that can be actively and reversibly buckle out of plane to pump fluids from an applied voltage. The out-of-plane deformation can be quantified using two parameters: net change in surface area and the shape of deformation. Change in surface area depends on the voltage, while the deformation shape, which significantly affects the flow rate, is a function of voltage, and the pressure and volume of the chambers on each side of the thin plate. The use of solid electrodes enables a robust and reversible pumping mechanism that will have will enable advancements in rapid microfluidic diagnostics, adaptive materials, and artificial muscles.

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

PubMed

Josephides, Dimitris N; Sajjadi, Shahriar

2015-01-27

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

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 limits of inertial focusing for technological applications.« less

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.

Electrokinetically driven continuous-flow enrichment of colloidal particles by Joule heating induced temperature gradient focusing in a convergent-divergent microfluidic structure.

PubMed

Zhao, Cunlu; Ge, Zhengwei; Song, Yongxin; Yang, Chun

2017-09-07

Enrichment of colloidal particles in continuous flow has not only numerous applications but also poses a great challenge in controlling physical forces that are required for achieving particle enrichment. Here, we for the first time experimentally demonstrate the electrokinetically-driven continuous-flow enrichment of colloidal particles with Joule heating induced temperature gradient focusing (TGF) in a microfluidic convergent-divergent structure. We consider four mechanisms of particle transport, i.e., advection due to electroosmosis, electrophoresis, dielectrophoresis and, and further clarify their roles in the particle enrichment. It is experimentally determined and numerically verified that the particle thermophoresis plays dominant roles in enrichment of all particle sizes considered in this study and the combined effect of electroosmosis-induced advection and electrophoresis is mainly to transport particles to the zone of enrichment. Specifically, the enrichment of particles is achieved with combined DC and AC voltages rather than a sole DC or AC voltage. A numerical model is formulated with consideration of the abovementioned four mechanisms, and the model can rationalize the experimental observations. Particularly, our analysis of numerical and experimental results indicates that thermophoresis which is usually an overlooked mechanism of material transport is crucial for the successful electrokinetic enrichment of particles with Joule heating induced TGF.

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

PubMed

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

2014-06-05

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

Wettability control on fluid-fluid displacements in patterned microfluidics

NASA Astrophysics Data System (ADS)

Zhao, Benzhong; MacMinn, Christopher; Juanes, Ruben

2015-11-01

Two-phase flow in porous media is important in many natural and industrial processes. While it is well known the wetting properties of porous media can vary drastically depending on the media and the pore fluids, their effect continues to challenge our microscopic and macroscopic descriptions. We conduct experiments via radial displacement of silicone oil by water in microfluidic devices patterned with vertical posts. These devices allow for flow visualization in a complex but well-defined microstructure. Additionally, the surface energy of the devices can be tuned over a wide range of contact angles. We perform injection experiments with highly unfavorable mobility contrast at rates over four orders of magnitude. We focus on three wetting conditions: drainage θ = 120°, weak imbibition θ = 60°, and strong imbibition θ = 7°. In drainage, we see a transition from viscous fingering at high capillary numbers to a morphology that differs from capillary fingering. In weak imbibition, we observe stabilization of flow due to cooperative invasion at the pore scale. In strong imbibition, we find the flow is heavily influenced by a precursor front that emanates from the main imbibition front. Our work shows the important, yet intricate, impact of wettability on immiscible flow in porous media.

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 conventional procedure (45 min) and our microfluidic approach (12 min).

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.

Monodisperse alginate microgel formation in a three-dimensional microfluidic droplet generator.

PubMed

Lian, Meng; Collier, C Patrick; Doktycz, Mitchel J; Retterer, Scott T

2012-01-01

Droplet based microfluidic systems provide an ideal platform for partitioning and manipulating aqueous samples for analysis. Identifying stable operating conditions under which droplets are generated is challenging yet crucial for real-world applications. A novel three-dimensional microfluidic platform that facilitates the consistent generation and gelation of alginate-calcium hydrogel microbeads for microbial encapsulation, over a broad range of input pressures, in the absence of surfactants is described. The unique three-dimensional design of the fluidic network utilizes a height difference at the junction between the aqueous sample injection and organic carrier channels to induce droplet formation via a surface tension enhanced self-shearing mechanism. Combined within a flow-focusing geometry, under constant pressure control, this arrangement facilitates predictable generation of droplets over a much broader range of operating conditions than that of conventional two-dimensional systems. The impact of operating pressures and geometry on droplet gelation, aqueous and organic material flow rates, microbead size, and bead generation frequency are described. The system presented provides a robust platform for encapsulating single microbes in complex mixtures into individual hydrogel beads, and provides the foundation for the development of a complete system for sorting and analyzing microbes at the single cell level.

Monodisperse alginate microgel formation in a three-dimensional microfluidic droplet generator

PubMed Central

Lian, Meng; Collier, C. Patrick; Doktycz, Mitchel J.; Retterer, Scott T.

2012-01-01

Droplet based microfluidic systems provide an ideal platform for partitioning and manipulating aqueous samples for analysis. Identifying stable operating conditions under which droplets are generated is challenging yet crucial for real-world applications. A novel three-dimensional microfluidic platform that facilitates the consistent generation and gelation of alginate-calcium hydrogel microbeads for microbial encapsulation, over a broad range of input pressures, in the absence of surfactants is described. The unique three-dimensional design of the fluidic network utilizes a height difference at the junction between the aqueous sample injection and organic carrier channels to induce droplet formation via a surface tension enhanced self-shearing mechanism. Combined within a flow-focusing geometry, under constant pressure control, this arrangement facilitates predictable generation of droplets over a much broader range of operating conditions than that of conventional two-dimensional systems. The impact of operating pressures and geometry on droplet gelation, aqueous and organic material flow rates, microbead size, and bead generation frequency are described. The system presented provides a robust platform for encapsulating single microbes in complex mixtures into individual hydrogel beads, and provides the foundation for the development of a complete system for sorting and analyzing microbes at the single cell level. PMID:24198865

Behaviour and design considerations for continuous flow closed-open-closed liquid microchannels.

PubMed

Melin, Jessica; van der Wijngaart, Wouter; Stemme, Göran

2005-06-01

This paper introduces a method of combining open and closed microchannels in a single component in a novel way which couples the benefits of both open and closed microfluidic systems and introduces interesting on-chip microfluidic behaviour. Fluid behaviour in such a component, based on continuous pressure driven flow and surface tension, is discussed in terms of cross sectional flow behaviour, robustness, flow-pressure performance, and its application to microfluidic interfacing. The closed-open-closed microchannel possesses the versatility of upstream and downstream closed microfluidics along with open fluidic direct access. The device has the advantage of eliminating gas bubbles present upstream when these enter the open channel section. The unique behaviour of this device opens the door to applications including direct liquid sample interfacing without the need for additional and bulky sample tubing.

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

PubMed

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

2008-10-01

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

Enhancement of microfluidic particle separation using cross-flow filters with hydrodynamic focusing

PubMed Central

Chiu, Yun-Yen; Huang, Chen-Kang

2016-01-01

A microfluidic chip is proposed to separate microparticles using cross-flow filtration enhanced with hydrodynamic focusing. By exploiting a buffer flow from the side, the microparticles in the sample flow are pushed on one side of the microchannels, lining up to pass through the filters. Meanwhile a larger pressure gradient in the filters is obtained to enhance separation efficiency. Compared with the traditional cross-flow filtration, our proposed mechanism has the buffer flow to create a moving virtual boundary for the sample flow to actively push all the particles to reach the filters for separation. It further allows higher flow rates. The device only requires soft lithograph fabrication to create microchannels and a novel pressurized bonding technique to make high-aspect-ratio filtration structures. A mixture of polystyrene microparticles with 2.7 μm and 10.6 μm diameters are successfully separated. 96.2 ± 2.8% of the large particle are recovered with a purity of 97.9 ± 0.5%, while 97.5 ± 0.4% of the small particle are depleted with a purity of 99.2 ± 0.4% at a sample throughput of 10 μl/min. The experiment is also conducted to show the feasibility of this mechanism to separate biological cells with the sample solutions of spiked PC3 cells in whole blood. By virtue of its high separation efficiency, our device offers a label-free separation technique and potential integration with other components, thereby serving as a promising tool for continuous cell filtration and analysis applications. PMID:26858812

Photo-actuation of liquids for light-driven microfluidics: state of the art and perspectives.

PubMed

Baigl, Damien

2012-10-07

Using light to control liquid motion is a new paradigm for the actuation of microfluidic systems. We review here the different principles and strategies to induce or control liquid motion using light, which includes the use of radiation pressure, optical tweezers, light-induced wettability gradients, the thermocapillary effect, photosensitive surfactants, the chromocapillary effect, optoelectrowetting, photocontrolled electroosmotic flows and optical dielectrophoresis. We analyze the performance of these approaches to control using light many kinds of microfluidic operations involving discrete pL- to μL-sized droplets (generation, driving, mixing, reaction, sorting) or fluid flows in microchannels (valve operation, injection, pumping, flow rate control). We show that a complete toolbox is now available to control microfluidic systems by light. We finally discuss the perspectives of digital optofluidics as well as microfluidics based on all optical fluidic chips and optically reconfigurable devices.

Purely-elastic flow instabilities and elastic turbulence in microfluidic cross-slot devices

PubMed Central

Sousa, P. C.; Pinho, F. T.

2018-01-01

We experimentally investigate the dynamics of viscoelastic fluid flows in cross-slot microgeometries under creeping flow conditions. We focus on the unsteady flow regime observed at high Weissenberg numbers (Wi) with the purpose of understanding the underlying flow signature of elastic turbulence. The effects of the device aspect ratio and fluid rheology on the unsteady flow state are investigated. Visualization of the flow patterns and time-resolved micro-particle image velocimetry were carried out to study the fluid flow behavior for a wide range of Weissenberg numbers. A periodic flow behavior is observed at low Weissenberg numbers followed by a more complex dynamics as Wi increases, eventually leading to the onset of elastic turbulence for very high Weissenberg numbers. PMID:29376533

A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

NASA Astrophysics Data System (ADS)

Cook, Andrew; Belsare, Sayali; Giorgio, Todd; Mu, Richard

2014-11-01

Analysis of circulating tumor cells (CTCs) can be critical for studying how tumors grow and metastasize, in addition to personalizing treatment for cancer patients. CTCs are rare events in blood, making it difficult to remove CTCs from the blood stream. Two microfluidic devices have been developed to separate CTCs from blood. The first is a double spiral device that focuses cells into streams, the positions of which are determined by cell diameter. The second device uses ligand-coated magnetic nanoparticles that selectively attach to CTCs. The nanoparticles then pull CTCs out of solution using a magnetic field. These two devices will be combined into a single 2-stage microfluidic device that will capture CTCs more efficiently than either device on its own. The first stage depletes the number of blood cells in the sample by size-based separation. The second stage will magnetically remove CTCs from solution for study and culturing. Thus far, size-based separation has been achieved. Research will also focus on understanding the equations that govern fluid dynamics and magnetic fields in order to determine how the manipulation of microfluidic parameters, such as dimensions and flow rate, will affect integration and optimization of the 2-stage device. NSF-CREST: Center for Physics and Chemistry of Materials. HRD-0420516; Department of Defense, Peer Reviewed Medical Research Program Award W81XWH-13-1-0397.

Single step sequential polydimethylsiloxane wet etching to fabricate a microfluidic channel with various cross-sectional geometries

NASA Astrophysics Data System (ADS)

Wang, C.-K.; Liao, W.-H.; Wu, H.-M.; Lo, Y.-H.; Lin, T.-R.; Tung, Y.-C.

2017-11-01

Polydimethylsiloxane (PDMS) has become a widely used material to construct microfluidic devices for various biomedical and chemical applications due to its desirable material properties and manufacturability. PDMS microfluidic devices are usually fabricated using soft lithography replica molding methods with master molds made of photolithogrpahy patterned photoresist layers on silicon wafers. The fabricated microfluidic channels often have rectangular cross-sectional geometries with single or multiple heights. In this paper, we develop a single step sequential PDMS wet etching process that can be used to fabricate microfluidic channels with various cross-sectional geometries from single-layer PDMS microfluidic channels. The cross-sections of the fabricated channel can be non-rectangular, and varied along the flow direction. Furthermore, the fabricated cross-sectional geometries can be numerically simulated beforehand. In the experiments, we fabricate microfluidic channels with various cross-sectional geometries using the developed technique. In addition, we fabricate a microfluidic mixer with alternative mirrored cross-sectional geometries along the flow direction to demonstrate the practical usage of the developed technique.

Generation of Monodisperse Liquid Droplets in a Microfluidic Chip Using a High-Speed Gaseous Microflow

NASA Astrophysics Data System (ADS)

Tirandazi, Pooyan; Hidrovo, Carlos

2015-11-01

Over the last few years, microfluidic systems known as Lab-on-a-Chip (LOC) and micro total analysis systems (μTAS) have been increasingly developed as essential components for numerous biochemical applications. Droplet microfluidics, however, provides a distinctive attribute for delivering and processing discrete as well as ultrasmall volumes of fluid, which make droplet-based systems more beneficial over their continuous-phase counterparts. Droplet generation in its conventional scheme usually incorporates the injection of a liquid (water) into a continuous immiscible liquid (oil) medium. In this study we demonstrate a novel scheme for controlled generation of monodisperse droplets in confined gas-liquid microflows. We experimentally investigate the manipulation of water droplets in flow-focusing configurations using a high inertial air stream. Different flow regimes are observed by varying the gas and liquid flow rates, among which, the ``dripping regime'' where monodisperse droplets are generated is of great importance. The controlled size and generation rate of droplets in this region provide the capability for precise and contaminant-free delivery of microliter to nanoliter volumes of fluid. Furthermore, the high speed droplets generated in this method represent the basis for a new approach based on droplet pair collisions for fast efficient micromixing which provides a significant development in modern LOC and μTAS devices. This project is currently being supported by an NSF CAREER Award grant CBET-1151091.

Real rock-microfluidic flow cell: A test bed for real-time in situ analysis of flow, transport, and reaction in a subsurface reactive transport environment.

PubMed

Singh, Rajveer; Sivaguru, Mayandi; Fried, Glenn A; Fouke, Bruce W; Sanford, Robert A; Carrera, Martin; Werth, Charles J

2017-09-01

Physical, chemical, and biological interactions between groundwater and sedimentary rock directly control the fundamental subsurface properties such as porosity, permeability, and flow. This is true for a variety of subsurface scenarios, ranging from shallow groundwater aquifers to deeply buried hydrocarbon reservoirs. Microfluidic flow cells are now commonly being used to study these processes at the pore scale in simplified pore structures meant to mimic subsurface reservoirs. However, these micromodels are typically fabricated from glass, silicon, or polydimethylsiloxane (PDMS), and are therefore incapable of replicating the geochemical reactivity and complex three-dimensional pore networks present in subsurface lithologies. To address these limitations, we developed a new microfluidic experimental test bed, herein called the Real Rock-Microfluidic Flow Cell (RR-MFC). A porous 500μm-thick real rock sample of the Clair Group sandstone from a subsurface hydrocarbon reservoir of the North Sea was prepared and mounted inside a PDMS microfluidic channel, creating a dynamic flow-through experimental platform for real-time tracking of subsurface reactive transport. Transmitted and reflected microscopy, cathodoluminescence microscopy, Raman spectroscopy, and confocal laser microscopy techniques were used to (1) determine the mineralogy, geochemistry, and pore networks within the sandstone inserted in the RR-MFC, (2) analyze non-reactive tracer breakthrough in two- and (depth-limited) three-dimensions, and (3) characterize multiphase flow. The RR-MFC is the first microfluidic experimental platform that allows direct visualization of flow and transport in the pore space of a real subsurface reservoir rock sample, and holds potential to advance our understandings of reactive transport and other subsurface processes relevant to pollutant transport and cleanup in groundwater, as well as energy recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

Microwave Dielectric Heating of Drops in Microfluidic Devices†

PubMed Central

Issadore, David; Humphry, Katherine J.; Brown, Keith A.; Sandberg, Lori; Weitz, David; Westervelt, Robert M.

2010-01-01

We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has a large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picoliter drop of water and this enables very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperatures as large as 30°C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature, such as PCR amplification of DNA, and can benefit from this new technique. PMID:19495453

Magnetic water-in-water droplet microfluidics

NASA Astrophysics Data System (ADS)

Navi, Maryam; Abbasi, Niki; Tsai, Scott

2017-11-01

Aqueous two-phase systems (ATPS) have shown to be ideal candidates for replacing the conventional water-oil systems used in droplet microfluidics. We use an ATPS of Polyethylene Glycol (PEG) and Dextran (DEX) for microfluidic generation of magnetic water-in-water droplets. As ferrofluid partitions to DEX phase, there is no significant diffusion of ferrofluid at the interface of the droplets, rendering generation of magnetic DEX droplets in a non-magnetic continuous phase of PEG possible. In this system, both phases are water-based and highly biocompatible. We microfluidically generate magnetic DEX droplets at a flow-focusing junction in a jetting regime. We sort the droplets based on their size by placing a permanent magnet downstream of the droplet generation region, and show that the deflection of droplets is in good agreement with a mathematical model. We also show that the magnetic DEX droplets can be stabilized by lysozyme and be used for separation of single cell containing water-in-water droplets. This system of magnetic water-in-water droplet manipulation may find biomedical applications such as single-cell studies and drug delivery.

Monodisperse Polyethylene Glycol Diacrylate Hydrogel Microsphere Formation by Oxygen-Controlled Photopolymerization in a Microfluidic Device

PubMed Central

Krutkramelis, K.; Xia, B.; Oakey, J.

2016-01-01

PEG-based hydrogels have become widely used as drug delivery and tissue scaffolding materials. Common among PEG hydrogel-forming polymers are photopolymerizable acrylates such as polyethylene glycol diacrylate (PEGDA). Microfluidics and microfabrication technologies have recently enabled the miniaturization of PEGDA structures, thus enabling many possible applications for nano- and micro- structured hydrogels. The presence of oxygen, however, dramatically inhibits the photopolymerization of PEGDA, which in turn frustrates hydrogel formation in environments of persistently high oxygen concentration. Using PEGDA that has been emulsified in fluorocarbon oil via microfluidic flow focusing within polydimethylsiloxane (PDMS) devices, we show that polymerization is completely inhibited below critical droplet diameters. By developing an integrated model incorporating reaction kinetics and oxygen diffusion, we demonstrate that the critical droplet diameter is largely determined by the oxygen transport rate, which is dictated by the oxygen saturation concentration of the continuous oil phase. To overcome this fundamental limitation, we present a nitrogen micro-jacketed microfluidic device to reduce oxygen within the droplet, enabling the continuous on-chip photopolymerization of microscale PEGDA particles. PMID:26987384

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.

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

Simulation of electrokinetic flow in microfluidic channels

NASA Astrophysics Data System (ADS)

Sabur, Romena; Matin, M.

2005-08-01

Electrokinetic phenomena become an increasingly efficient fluid transport mechanism in micro- and nano-fluidic fields. These phenomena have also been applied successfully in microfluidic devices to achieve particle separation, pre-concentration and mixing. Electrokinetic is the flow produced by the action of an electric field on a fluid with a net charge, where the charged ions of fluid are able to drag the whole solution through the channels in the microfluidic device from one analyzing point to the other. We will present the simulation results of electrokinetic transports of fluid in various typical micro-channel geometries such as T-channel, Y-channel, cross channel and straight channel. In practice, high-speed micro-PIV technique is used to measure transient fluidic phenomena in a microfluidic channel. Particle Image Velocimetry (PIV) systems provide two- or three-dimensional velocity maps in flows using whole field techniques based on imaging the light scattered by small particles in the flow illuminated by a laser light sheet. The system generally consists of an epifluorescent microscope, CW laser and a high-speed CMOS of CCD camera. The flow of a liquid, (water for example), containing fluorescent particle is then analyzed in a counter microchannel by the highly accurate PIV method. One can then compare the simulated and experimental microfluidic flow due to electroosmotic effect.

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 synthesis, and chemical process control.

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.

A Microfluidics-based Pulpal Arteriole Blood Flow Phantom for Validation of Doppler Ultrasound Devices in Pulpal Blood Flow Velocity Measurement.

PubMed

Kim, Dohyun; Park, Sung-Ho

2016-11-01

Recently, Doppler ultrasound has been used for the measurement of pulpal blood flow in human teeth. However, the reliability of this method has not been verified. In this study, we developed a model to simulate arteriole blood flow within the dental pulp by using microfluidics. This arteriole simulator, or flow phantom, was used to determine the reliability of measurements obtained by using a Doppler ultrasound device. A microfluidic chip was fabricated by using the soft lithography technique, and blood-mimicking fluid was pumped through the channel by a microfluidic system. A Doppler ultrasound device was used for the measurement of flow velocity. The peak, mean, and minimal flow velocities obtained from the phantom and the Doppler ultrasound device were compared by using linear regression analysis and Pearson correlation coefficient. Bland-Altman analyses were performed to evaluate the velocity differences between the flow generated by the phantom and the flow measurements made with the Doppler ultrasound device. The microfluidic system was able to generate the flow profiles as intended, and the fluid flow could be monitored and controlled by the software program. There were excellent linear correlations between the peak, mean, and minimal flow velocities of the phantom and those of the Doppler ultrasound device (r = 0.94-0.996, P < .001). However, the velocities were overestimated by the Doppler ultrasound device. This phantom provides opportunities for research and education involving the Doppler ultrasound technique in dentistry. Although Doppler ultrasound can be an effective tool for the measurement of pulpal blood flow velocity, it is essential to validate and calibrate the device before clinical use. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Spontaneous oscillations in microfluidic networks

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Microfluidic magnetic switching valves based on aggregates of magnetic nanoparticles: Effects of aggregate length and nanoparticle sizes

NASA Astrophysics Data System (ADS)

Jiemsakul, Thanakorn; Manakasettharn, Supone; Kanharattanachai, Sivakorn; Wanna, Yongyuth; Wangsuya, Sujint; Pratontep, Sirapat

2017-01-01

We demonstrate microfluidic switching valves using magnetic nanoparticles blended within the working fluid as an alternative microfluidic flow control in microchannels. Y-shaped microchannels have been fabricated by using a CO2 laser cutter to pattern microchannels on transparent poly(methyl methacrylate) (PMMA) sheets covered with thermally bonded transparent polyvinyl chloride (PVC) sheets. To examine the performance of the microfluidic magnetic switching valves, an aqueous magnetic nanoparticle suspension was injected into the microchannels by a syringe pump. Neodymium magnets were then employed to attract magnetic nanoparticles and form an aggregate that blocked the microchannels at a required position. We have found that the maximum volumetric flow rate of the syringe pump that the magnetic nanoparticle aggregate can withstand scales with the square of the external magnetic flux density. The viscosity of the fluid exhibits dependent on the aggregate length and the size of the magnetic nanoparticles. This microfluidic switching valve based on aggregates of magnetic nanoparticles has strong potentials as an on-demand flow control, which may help simplifying microfluidic channel designs.

Simulation analysis of rectifying microfluidic mixing with field-effect-tunable electrothermal induced flow.

PubMed

Liu, Weiyu; Ren, Yukun; Tao, Ye; Yao, Bobin; Li, You

2018-03-01

We report herein field-effect control on in-phase electrothermal streaming from a theoretical point of view, a phenomenon termed "alternating-current electrothermal-flow field effect transistor" (ACET-FFET), in the context of a new technology for handing analytes in microfluidics. Field-effect control through a gate terminal endows ACET-FFET the ability to generate arbitrary symmetry breaking in the transverse vortex flow pattern, which makes it attractive for mixing microfluidic samples. A computational model is developed to study the feasibility of this new microfluidic device design for micromixing. The influence of various parameters on developing an efficient mixer is investigated, and an integrated layout of discrete electrode array is suggested for achieving high-throughput mixing. Our physical demonstration with field-effect electrothermal flow control using a simple electrode structure proves invaluable for designing active micromixers for modern micro total analytical system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of Electrically Induced Swirling Flow of Isotonic Saline in a Mixing Microchannel

NASA Astrophysics Data System (ADS)

Hirahara, Shuzo; Tsuruta, Tomoyuki; Matsumoto, Yoshinori; Minamitani, Haruyuki

We have designed a prototype microfluidic device to mix suspended particles with isotonic saline by use of electrically induced swirling flow in the microchannel. However, the principles underlying microfluidic rotation induced by AC electrodes are not well understood, and the characteristics of the rotation velocity are unpredictable. Furthermore, these properties have not been studied using a highly conductive liquid like isotonic saline, which is an important fluid in the medical and biological fields. The lack of such studies causes uncertainty in the design required for high-performance microfluidic devices. We have examined the electrical rotational properties of the microfluid at an isotonic concentration of saline using computer simulation, and here we show that buoyant flow, which has previously been largely ignored, has a significant effect in channels of 100-μm depth or deeper, and that AC electroosmotic flow is not induced at isotonic saline concentrations.

A Gravity-Driven Microfluidic Particle Sorting Device with Hydrodynamic Separation Amplification

PubMed Central

Huh, Dongeun; Bahng, Joong Hwan; Ling, Yibo; Wei, Hsien-Hung; Kripfgans, Oliver D.; Fowlkes, J. Brian; Grotberg, James B.; Takayama, Shuichi

2008-01-01

This paper describes a simple microfluidic sorting system that can perform size-profiling and continuous mass-dependent separation of particles through combined use of gravity (1g) and hydrodynamic flows capable of rapidly amplifying sedimentation-based separation between particles. Operation of the device relies on two microfluidic transport processes: i) initial hydrodynamic focusing of particles in a microchannel oriented parallel to gravity, ii) subsequent sample separation where positional difference between particles with different mass generated by sedimentation is further amplified by hydrodynamic flows whose streamlines gradually widen out due to the geometry of a widening microchannel oriented perpendicular to gravity. The microfluidic sorting device was fabricated in poly(dimethylsiloxane) (PDMS), and hydrodynamic flows in microchannels were driven by gravity without using external pumps. We conducted theoretical and experimental studies on fluid dynamic characteristics of laminar flows in widening microchannels and hydrodynamic amplification of particle separation. Direct trajectory monitoring, collection, and post-analysis of separated particles were performed using polystyrene microbeads with different sizes to demonstrate rapid (< 1 min) and high-purity (> 99.9 %) separation. Finally, we demonstrated biomedical applications of our system by isolating small-sized (diameter < 6 μm) perfluorocarbon liquid droplets from polydisperse droplet emulsions, which is crucial in preparing contrast agents for safe, reliable ultrasound medical imaging, tracers for magnetic resonance imaging, or transpulmonary droplets used in ultrasound-based occlusion therapy for cancer treatment. Our method enables straightforward, rapid real-time size-monitoring and continuous separation of particles in simple stand-alone microfabricated devices without the need for bulky and complex external power sources. We believe that this system will provide a useful tool o separate colloids and particles for various analytical and preparative applications, and may hold 3 potential for separation of cells or development of diagnostic tools requiring point-of-care sample preparation or testing. PMID:17297936

A hard-soft microfluidic-based biosensor flow cell for SPR imaging application.

PubMed

Liu, Changchun; Cui, Dafu; Li, Hui

2010-09-15

An ideal microfluidic-based biosensor flow cell should have not only a "soft" interface for high strength sealing with biosensing chips, but also "hard" macro-to-micro interface for tubing connection. Since these properties are exclusive of each other, no one material can provide the advantages of both. In this paper, we explore the application of a SiO(2) thin film, deposited by plasma-enhanced chemical vapor deposition (PECVD) technology, as an intermediate layer for irreversibly adhering polydimethylsiloxane (PDMS) to plastic substrate, and develop a hard-soft, compact, robust microfluidic-based biosensor flow cell for the multi-array immunoassay application of surface plasmon resonance (SPR) imaging. This hard-soft biosensor flow cell consists of one rigid, computer numerically controlled (CNC)-machined poly(methyl methacrylate) (PMMA) base coated with a 200 nm thick SiO(2) thin film, and one soft PDMS microfluidic layer. This novel microfluidic-based biosensor flow cell does not only keep the original advantage of conventional PDMS-based biosensor flow cell such as the intrinsically soft interface, easy-to-fabrication, and low cost, but also has a rigid, robust, easy-to-use interface to tubing connection and can be operated up to 185 kPa in aqueous environments without failure. Its application was successfully demonstrated with two types of experiments by coupling with SPR imaging biosensor: the real-time monitoring of the immunoglobulin G (IgG) interaction, as well as the detection of sulfamethoxazole (SMOZ) and sulfamethazine (SMZ) with the sensitivity of 3.5 and 0.6 ng/mL, respectively. This novel hard-soft microfluidic device is also useful for a variety of other biosensor flow cells. Copyright 2010 Elsevier B.V. All rights reserved.

Karst-on-a-chip: microfluidic studies of dissolution of a gypsum fracture

NASA Astrophysics Data System (ADS)

Szymczak, Piotr; Dutka, Filip; Osselin, Florian

2017-04-01

Dissolution of fractured and porous media introduces a positive feedback between fluid transport and chemical reactions at mineral surfaces leading to self-focusing of the flow in pronounced wormhole-like channels [1,2]. We study the flow-induced dissolution in a simple microfluidic setup, with a gypsum block inserted in between two polycarbonate plates, which is the simplest model of a fracture [3]. This gives us a unique opportunity to observe the evolution of the dissolution patterns in-situ and in real-time. By changing the flow rate and the aperture of the fracture we can scan a relatively wide range of Peclet and Damkohler numbers, characterizing the relative magnitude of advection, diffusion and reaction in the system. Additionally, as the aperture is increased, a transition is observed between the fractal and regular dissolution patterns. For small gaps, the patterns are ramified fractals. For larger gaps, the dissolution fingers are found to have regular forms of two different kinds: either linear (for high flow rates) or parabolic (for lower flow rates). The experiments are supplemented with numerical simulations and analytical modeling which allow for a better understanding of evolving flow patterns. In particular, we find the shapes and propagation velocities of dominant fingers for different widths of the system, flow rates and reaction rates. Finally, we comment on the link between the experimentally observed patterns and the natural karst systems - both cave conduits and epikarst solution pipes. [1] Hoefner, M. L. and Fogler, H. S. Pore evolution and channel formation during flow and reaction in porous media. AIChE J. 34, 45-54, 1988 [2] P. Szymczak, A. J. C. Ladd, Wormhole formation in dissolving fractures, J. Geophys. Res., 114, B06203, 2009 [3] F. Osselin, P. Kondratiuk, A Budek, O. Cybulski, P. Garstecki, P. Szymczak Microfluidic observation of the onset of reactive infiltration instability in an analog fracture, Geophys. Res. Lett., 43, 6907-6915, 2016

Slopes To Prevent Trapping of Bubbles in Microfluidic Channels

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

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

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

Pereira, Candido; Nichols, Kevin

2013-11-27

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

[Synthesis of hollow titania microspheres by using microfluidic droplet-template].

PubMed

Ma, Jingyun; Jiang, Lei; Qin, Jianhu

2011-09-01

Droplet-based microfluidics is of great interest due to its particular characteristics compared with the conventional methods, such as reduced reagent consumption, rapid mixing, high-throughput, shape controlled, etc. A novel method using microfluidic droplet as soft template for the synthesis of hollow titania microspheres was developed. A typical polydimethylsiloxane (PDMS) microfluidic device containing "flow-focusing" geometry was used to generate water/oil (W/O) droplet. The mechanism for the hollow structure formation was based on the interfacial hydrolysis reaction between the continuous phase containing titanium butoxide precursor and the dispersed containing water. The continuous phase mixed with butanol was added in the downstream of the channel after the hydrolysis reaction. This step was used for drawing the water out of the microgels for further hydrolysis. The microgels obtained through a glass pipe integrated were washed, dried under vacuum and calcined after aging for a certain time. The fluorescence and scanning electron microscope (SEM) image of the microspheres indicated the hollow structure and the thickness of the shell. In addition, these microspheres with thin shell (about 2 microm) were apt to rupture and collapse. Droplet-based microfluidic offered a gentle and size-controllable manner to moderate this problem. Moreover, it has potential applications in photocatalysis combined with some modification realized on the chip simultaneously.

Student-Fabricated Microfluidic Devices as Flow Reactors for Organic and Inorganic Synthesis

ERIC Educational Resources Information Center

Feng, Z. Vivian; Edelman, Kate R.; Swanson, Benjamin P.

2015-01-01

Flow synthesis in microfluidic devices has been rapidly adapted in the pharmaceutical industry and in many research laboratories. Yet, the cost of commercial flow reactors is a major factor limiting the dissemination of this technology in the undergraduate curriculum. Here, we present a laboratory activity where students design and fabricate…

Controlling the trajectories of bubble trains at a microfluidic junction

NASA Astrophysics Data System (ADS)

Parthiban, Pravien; Khan, Saif

2011-11-01

The increasing number of applications facilitated by digital microfluidic flows has resulted in a sustained interest in not only understanding the diverse, interesting and often complex dynamics associated with such flows in microchannel networks but also in developing facile strategies to control them. We find that there are readily accessible flow speeds wherein resistance to flow in microchannels decreases with an increase in the number of confined bubbles present, and exploit this intriguing phenomenon to sort all bubble of a train exclusively into one of the arms of a nominally symmetric microfluidic loop. We also demonstrate how the arm into which the train filters into can be chosen by applying a temporary external stimulus by means of an additional flow of the continuous liquid into one the arms of the loop. Furthermore, we show how by tuning the magnitude and period of this temporary stimulus we can switch controllably, the traffic of bubbles between both arms of the loop even when the loop is asymmetric. The results of this work should aid in developing viable methods to regulate traffic of digital flows in microfluidic networks.

Patterned-wettability-induced alteration of electro-osmosis over charge-modulated surfaces in narrow confinements.

PubMed

Ghosh, Uddipta; Chakraborty, Suman

2012-04-01

In the present study, we focus on alterations in flow physics as a consequence of interactions between patterned-wettability gradients on microfluidic substrates with modulated surface charge distributions, giving rise to an intricate electrohydrodynamic coupling over small scales. We demonstrate that by exploiting such intricate coupling, it may be possible to pattern vortices occurring in the fluidic confinement by exploiting an interplay between the Navier slip and electro-osmotic transport. Our studies do reveal that the resultant flow structure originating out of the spatially periodic variations in the surface charge and surface wettability may depend critically on several independently tunable controlling parameters, such as the amplitudes and frequencies of the respective patterning functions, the phase shift between the two, an asymmetry factor, and the channel height to Debye length ratio. We show that judicious choices with regard to the combinations of these parameters may result in significant augmentations in the corresponding mixing efficiency without any appreciable compromise in the net microfluidic throughput. Furthermore, our studies reveal an optimum patterning frequency, which results in the most efficient microfluidic mixing within the constraints of achieving a desired volumetric flow rate. Our results also demonstrate that the net flow rate is maximized when the surface wettability variation functions and surface charge-density functions are in phase, whereas mixing is best facilitated when they are in opposite phase. In practice, therefore, one may select an intermediate value of the phase angle depending on the extent of compromise necessary between flow rate and mixing characteristics, yielding far-ranging scientific and technological advances toward an improved design of miniaturized fluidic devices of practical relevance.

Microfluidic "Pouch" Chips for Immunoassays and Nucleic Acid Amplification Tests.

PubMed

Mauk, Michael G; Liu, Changchun; Qiu, Xianbo; Chen, Dafeng; Song, Jinzhao; Bau, Haim H

2017-01-01

Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.

An easy to assemble microfluidic perfusion device with a magnetic clamp

PubMed Central

Tkachenko, Eugene; Gutierrez, Edgar; Ginsberg, Mark H.; Groisman, Alex

2009-01-01

We have built and characterized a magnetic clamp for reversible sealing of PDMS microfluidic chips against cover glasses with cell cultures and a microfluidic chip for experiments on shear stress response of endothelial cells. The magnetic clamp exerts a reproducible uniform pressure on the microfluidic chip, achieving fast and reliable sealing for liquid pressures up to 40 kPa inside the chip with <10% deformations of microchannels and minimal variations of the substrate shear stress in perfusion flow. The microfluidic chip has 8 test regions with the substrate shear stress varying by a factor of 2 between each region, thus covering a 128-fold range from low venous to arterial. The perfusion is driven by differential pressure, which makes it possible to create pulsatile flows mimicking pulsing in the vasculature. The setup is tested by 15 – 40 hours perfusions over endothelial monolayers with shear stress in the range of 0.07 - 9 dyn/cm2. Excellent cell viability at all shear stresses and alignment of cells along the flow at high shear stresses are repeatedly observed. A scratch wound healing assay under a shear flow is demonstrated and cell migration velocities are measured. Transfection of cells with a fluorescent protein is performed, and migrating fluorescent cells are imaged at a high resolution under shear flow in real time. The magnetic clamp can be closed with minimal mechanical perturbation to cells on the substrate and used with a variety of microfluidic chips for experiments with adherent and non-adherent cells. PMID:19350090

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

Yang, Li; Zhu, Zihua; Yu, Xiao-Ying

In this study, we report new results of in situ study of 5 nm goat anti-mouse IgG gold nanoparticles in a novel portable vacuum compatible microfluidic device using scanning electron microscope (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The unique feature of the liquid flow cell is that the detection window is open to the vacuum allowing direct probing of the liquid surface. The flow cell is composed of a silicon nitride (SiN) membrane and polydimethylsiloxane (PDMS), and it is fully compatible with vacuum operations for surface analysis. The aperture can be drilled through the 100 nm SiN membranemore » using a focused ion beam. Characteristic signals of the conjugated gold nanoparticles were successfully observed through the aperture by both energy-dispersive X-ray spectroscopy (EDX) in SEM and ToF-SIMS. Comparison was also made among wet samples, dry samples, and liquid sample in the flow cell using SEM/EDX. Stronger gold signal can be observed in our novel portable device by SEM/EDX compared with the wet or dry samples, respectively. Our results indicate that analyses of the nanoparticle components are better made in their native liquid environment. This is made possible using our unique microfluidic flow cell.« less

Double Emulsion Generation Using a Polydimethylsiloxane (PDMS) Co-axial Flow Focus Device.

PubMed

Cole, Russell H; Tran, Tuan M; Abate, Adam R

2015-12-25

Double emulsions are useful in a number of biological and industrial applications in which it is important to have an aqueous carrier fluid. This paper presents a polydimethylsiloxane (PDMS) microfluidic device capable of generating water/oil/water double emulsions using a coaxial flow focusing geometry that can be fabricated entirely using soft lithography. Similar to emulsion devices using glass capillaries, double emulsions can be formed in channels with uniform wettability and with dimensions much smaller than the channel sizes. Three dimensional flow focusing geometry is achieved by casting a pair of PDMS slabs using two layer soft lithography, then mating the slabs together in a clamshell configuration. Complementary locking features molded into the PDMS slabs enable the accurate registration of features on each of the slab surfaces. Device testing demonstrates formation of double emulsions from 14 µm to 50 µm in diameter while using large channels that are robust against fouling and clogging.

Double Emulsion Generation Using a Polydimethylsiloxane (PDMS) Co-axial Flow Focus Device

PubMed Central

Cole, Russell H.; Tran, Tuan M.; Abate, Adam R.

2015-01-01

Double emulsions are useful in a number of biological and industrial applications in which it is important to have an aqueous carrier fluid. This paper presents a polydimethylsiloxane (PDMS) microfluidic device capable of generating water/oil/water double emulsions using a coaxial flow focusing geometry that can be fabricated entirely using soft lithography. Similar to emulsion devices using glass capillaries, double emulsions can be formed in channels with uniform wettability and with dimensions much smaller than the channel sizes. Three dimensional flow focusing geometry is achieved by casting a pair of PDMS slabs using two layer soft lithography, then mating the slabs together in a clamshell configuration. Complementary locking features molded into the PDMS slabs enable the accurate registration of features on each of the slab surfaces. Device testing demonstrates formation of double emulsions from 14 µm to 50 µm in diameter while using large channels that are robust against fouling and clogging. PMID:26780079

On-demand control of microfluidic flow via capillary-tuned solenoid microvalve suction.

PubMed

Zhang, Qiang; Zhang, Peiran; Su, Yetian; Mou, Chunbo; Zhou, Teng; Yang, Menglong; Xu, Jian; Ma, Bo

2014-12-21

A simple, low-cost and on-demand microfluidic flow controlling platform was developed based on a unique capillary-tuned solenoid microvalve suction effect without any outer pressure source. The suction effect was innovatively employed as a stable and controllable driving force for the manipulation of the microfluidic system by connecting a piece of capillary between the microvalve and the microfluidic chip, which caused significant hydrodynamic resistance differences among the solenoid valve ports and changed the flowing mode inside the valve. The volume of sucked liquid could be controlled from microliters even down to picoliters either by decreasing the valve energized duration (from a maximum energized duration to the valve response time of 20 ms) or by increasing the inserted capillary length (i.e., its hydrodynamic resistance). Several important microfluidic unit operations such as cell/droplet sorting and on-demand size-controllable droplet generation have been demonstrated on the developed platform and both simulations and experiments confirmed that this platform has good controllability and stability.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Conductivity detection for monitoring mixing reactions in microfluidic devices.

PubMed

Liu, Y; Wipf, D O; Henry, C S

2001-08-01

A conductivity detector was coupled to poly(dimethylsiloxane)-glass capillary electrophoresis microchips to monitor microfluidic flow. Electroosmotic flow was investigated with both conductivity detection (CD) and the current monitoring method. No significant variation was observed between these methods, but CD showed a lower relative standard deviation. Gradient mixing experiments were employed to investigate the relationship between the electrolyte conductivity and the electrolyte concentration. A good linear response of conductivity to concentration was obtained for solutions whose difference in concentrations were less than 27 mM. The new system holds great promise for precision mixing in microfluidic devices using electrically driven flows.

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.

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.

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

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

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

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.

Microfluidics-based microbubbles in methylene blue solution for photoacoustic and ultrasound imaging

NASA Astrophysics Data System (ADS)

Das, Dhiman; Sivasubramanian, Kathyayini; Yang, Chun; Pramanik, Manojit

2018-02-01

Contrast agents which can be used for more than one bio-imaging technique has gained a lot of attention from researchers in recent years. In this work, a microfluidic device employing a flow-focusing junction, is used for the continuous generation of monodisperse nitrogen microbubbles in methylene blue, an optically absorbing organic dye, for dual-modal photoacoustic and ultrasound imaging. Using an external phase of polyoxyethylene glycol 40 stearate (PEG 40), a non-ionic surfactant, and 50% glycerol solution at a flow rate of 1 ml/hr and gas pressure at 1.75 bar, monodisperse nitrogen microbubbles of diameter 7 microns were obtained. The external phase also contained methylene blue hydrate at a concentration of 1 gm/litre. The monodisperse microbubbles produced a strong ultrasound signal as expected. It was observed that the signal-to-noise (SNR) ratio of the photoacoustic signal for the methylene blue solution in the presence of the monodisperse microbubbles was 68.6% lower than that of methylene blue solution in the absence of microbubbles. This work is of significance because using microfluidics, we can precisely control the bubbles' production rate and bubble size which increases ultrasound imaging efficiency. A uniform size distribution of the bubbles will have narrower resonance frequency bandwidth which will respond well to specific ultrasound frequencies.

Integrated Microfluidic Flow-Through Microbial Fuel Cells

PubMed Central

Jiang, Huawei; Ali, Md. Azahar; Xu, Zhen; Halverson, Larry J.; Dong, Liang

2017-01-01

This paper reports on a miniaturized microbial fuel cell with a microfluidic flow-through configuration: a porous anolyte chamber is formed by filling a microfluidic chamber with three-dimensional graphene foam as anode, allowing nutritional medium to flow through the chamber to intimately interact with the colonized microbes on the scaffolds of the anode. No nutritional media flow over the anode. This allows sustaining high levels of nutrient utilization, minimizing consumption of nutritional substrates, and reducing response time of electricity generation owing to fast mass transport through pressure-driven flow and rapid diffusion of nutrients within the anode. The device provides a volume power density of 745 μW/cm3 and a surface power density of 89.4 μW/cm2 using Shewanella oneidensis as a model biocatalyst without any optimization of bacterial culture. The medium consumption and the response time of the flow-through device are reduced by 16.4 times and 4.2 times, respectively, compared to the non-flow-through counterpart with its freeway space volume six times the volume of graphene foam anode. The graphene foam enabled microfluidic flow-through approach will allow efficient microbial conversion of carbon-containing bioconvertible substrates to electricity with smaller space, less medium consumption, and shorter start-up time. PMID:28120875

Integrated Microfluidic Flow-Through Microbial Fuel Cells

NASA Astrophysics Data System (ADS)

Jiang, Huawei; Ali, Md. Azahar; Xu, Zhen; Halverson, Larry J.; Dong, Liang

2017-01-01

This paper reports on a miniaturized microbial fuel cell with a microfluidic flow-through configuration: a porous anolyte chamber is formed by filling a microfluidic chamber with three-dimensional graphene foam as anode, allowing nutritional medium to flow through the chamber to intimately interact with the colonized microbes on the scaffolds of the anode. No nutritional media flow over the anode. This allows sustaining high levels of nutrient utilization, minimizing consumption of nutritional substrates, and reducing response time of electricity generation owing to fast mass transport through pressure-driven flow and rapid diffusion of nutrients within the anode. The device provides a volume power density of 745 μW/cm3 and a surface power density of 89.4 μW/cm2 using Shewanella oneidensis as a model biocatalyst without any optimization of bacterial culture. The medium consumption and the response time of the flow-through device are reduced by 16.4 times and 4.2 times, respectively, compared to the non-flow-through counterpart with its freeway space volume six times the volume of graphene foam anode. The graphene foam enabled microfluidic flow-through approach will allow efficient microbial conversion of carbon-containing bioconvertible substrates to electricity with smaller space, less medium consumption, and shorter start-up time.

Characterization of electrokinetic gating valve in microfluidic channels.

PubMed

Zhang, Guiseng; Du, Wei; Liu, Bi-Feng; Hisamoto, Hideaki; Terabe, Shigeru

2007-02-12

Electrokinetic gating, functioning as a micro-valve, has been widely employed in microfluidic chips for sample injection and flow switch. Investigating its valving performance is fundamentally vital for microfluidics and microfluidics-based chemical analysis. In this paper, electrokinetic gating valve in microchannels was evaluated using optical imaging technique. Microflow profiles at channels junction were examined, revealing that molecular diffusion played a significant role in the valving disable; which could cause analyte leakage in sample injection. Due to diffusion, the analyte crossed the interface of the analyte flow and gating flow, and then formed a cometic tail-like diffusion area at channels junction. From theoretical calculation and some experimental evidences, the size of the area was related to the diffusion coefficient and the velocity of analytes. Additionally, molecular diffusion was also believed to be another reason of sampling bias in gated injection.

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.

Microfluidic co-flow of Newtonian and viscoelastic fluids for high-resolution separation of microparticles.

PubMed

Tian, Fei; Zhang, Wei; Cai, Lili; Li, Shanshan; Hu, Guoqing; Cong, Yulong; Liu, Chao; Li, Tiejun; Sun, Jiashu

2017-09-12

The microfluidic passive control of microparticles largely relies on the hydrodynamic effects of the carrier media such as Newtonian fluids and viscoelastic fluids. Yet the viscoelastic/Newtonian interfacial effect has been scarcely investigated, especially for high-resolution particle separation. Here we report a microfluidic co-flow of Newtonian (water or PBS) and viscoelastic fluids (PEO) for the size-dependent separation of microparticles. The co-flow condition generates a stable viscoelastic/Newtonian interface, giving rise to the wall-directed elastic lift forces that compete with the center-directed lift forces, and efficiently hinders the migration of microparticles from the Newtonian to the viscoelastic fluid in a size-dependent manner. An almost complete separation of a binary mixture of 1 μm and 2 μm polystyrene particles is achieved by the co-flow of water and a very dilute PEO solution (100 ppm), whereas the sole use of water or PEO could not lead to an efficient separation. This co-flow microfluidic system is also applied for the separation of Staphylococcus aureus (1 μm) from platelets (2-3 μm) with >90% efficiencies and purities.

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.

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).

Microfluidic setup for on-line SERS monitoring using laser induced nanoparticle spots as SERS active substrate.

PubMed

Buja, Oana-M; Gordan, Ovidiu D; Leopold, Nicolae; Morschhauser, Andreas; Nestler, Jörg; Zahn, Dietrich R T

2017-01-01

A microfluidic setup which enables on-line monitoring of residues of malachite green (MG) using surface-enhanced Raman scattering (SERS) is reported. The SERS active substrate was prepared via laser induced synthesis of silver or gold nanoparticles spot on the bottom of a 200 μm inner dimension glass capillary, by focusing the laser beam during a continuous flow of a mixture of silver nitrate or gold chloride and sodium citrate. The described microfluidic setup enables within a few minutes the monitoring of several processes: the synthesis of the SERS active spot, MG adsorption to the metal surface, detection of the analyte when saturation of the SERS signal is reached, and finally, the desorption of MG from the spot. Moreover, after MG complete desorption, the regeneration of the SERS active spot was achieved. The detection of MG was possible down to 10 -7 M concentration with a good reproducibility when using silver or gold spots as SERS substrate.

Nitrate measurement in droplet flow: gas-mediated crosstalk and correction.

PubMed

Nightingale, Adrian M; Hassan, Sammer-Ul; Evans, Gareth W H; Coleman, Sharon M; Niu, Xize

2018-06-07

In droplet microfluidics, droplets have traditionally been considered discrete self-contained reaction chambers, however recent work has shown that dissolved solutes can transfer into the oil phase and migrate into neighbouring droplets under certain conditions. The majority of reports on such inter-droplet "crosstalk" have focused on surfactant-driven mechanisms, such as transport within micelles. While trialling a droplet-based system for quantifying nitrate in water, we encountered crosstalk driven by a very different mechanism: conversion of the analyte to a gaseous intermediate which subsequently diffused between droplets. Importantly we found that the crosstalk occurred predictably, could be experimentally quantified, and measurements rationally post-corrected. This showed that droplet microfluidic systems susceptible to crosstalk such as this can nonetheless be used for quantitative analysis.

Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials

PubMed Central

Morton, Keith J.; Loutherback, Kevin; Inglis, David W.; Tsui, Ophelia K.; Sturm, James C.; Chou, Stephen Y.; Austin, Robert H.

2008-01-01

We show that it is possible to direct particles entrained in a fluid along trajectories much like rays of light in classical optics. A microstructured, asymmetric post array forms the core hydrodynamic element and is used as a building block to construct microfluidic metamaterials and to demonstrate refractive, focusing, and dispersive pathways for flowing beads and cells. The core element is based on the concept of deterministic lateral displacement where particles choose different paths through the asymmetric array based on their size: Particles larger than a critical size are displaced laterally at each row by a post and move along the asymmetric axis at an angle to the flow, while smaller particles move along streamline paths. We create compound elements with complex particle handling modes by tiling this core element using multiple transformation operations; we show that particle trajectories can be bent at an interface between two elements and that particles can be focused into hydrodynamic jets by using a single inlet port. Although particles propagate through these elements in a way that strongly resembles light rays propagating through optical elements, there are unique differences in the paths of our particles as compared with photons. The unusual aspects of these modular, microfluidic metamaterials form a rich design toolkit for mixing, separating, and analyzing cells and functional beads on-chip. PMID:18495920

Generation of Microbubbles with Applications to Industry and Medicine

NASA Astrophysics Data System (ADS)

Rodríguez-Rodríguez, Javier; Sevilla, Alejandro; Martínez-Bazán, Carlos; Gordillo, José Manuel

2015-01-01

We provide a comprehensive and systematic description of the diverse microbubble generation methods recently developed to satisfy emerging technological, pharmaceutical, and medical demands. We first introduce a theoretical framework unifying the physics of bubble formation in the wide variety of existing types of generators. These devices are then classified according to the way the bubbling process is controlled: outer liquid flows (e.g., coflows, cross flows, and flow-focusing flows), acoustic forcing, and electric fields. We also address modern techniques developed to produce bubbles coated with surfactants and liquid shells. The stringent requirements to precisely control the bubbling frequency, the bubble size, and the properties of the coating make microfluidics the natural choice to implement such techniques.

Fluid flows and forces in development: functions, features and biophysical principles

PubMed Central

Freund, Jonathan B.; Goetz, Jacky G.; Hill, Kent L.; Vermot, Julien

2012-01-01

Throughout morphogenesis, cells experience intracellular tensile and contractile forces on microscopic scales. Cells also experience extracellular forces, such as static forces mediated by the extracellular matrix and forces resulting from microscopic fluid flow. Although the biological ramifications of static forces have received much attention, little is known about the roles of fluid flows and forces during embryogenesis. Here, we focus on the microfluidic forces generated by cilia-driven fluid flow and heart-driven hemodynamics, as well as on the signaling pathways involved in flow sensing. We discuss recent studies that describe the functions and the biomechanical features of these fluid flows. These insights suggest that biological flow determines many aspects of cell behavior and identity through a specific set of physical stimuli and signaling pathways. PMID:22395739

On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging

PubMed Central

Hettiarachchi, Kanaka; Talu, Esra; Longo, Marjorie L.; Dayton, Paul A.; Lee, Abraham P.

2007-01-01

This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (σ) values of <2% through microfluidic flow-focusing. Micron-sized lipid shell-based perfluorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method. The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 μm orifice width, and are robust enough for consistent production of microbubbles with runtimes lasting several hours. With high-speed imaging, we characterized relationships between channel geometry, liquid flow rate Q, and gas pressure P in controlling bubble sizes. By a simple optimization of the channel geometry and Q and P, bubbles with a mean diameter of <5 μm can be obtained, ideal for various ultrasonic imaging applications. This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions, different gas compositions and new shell materials for stabilization, and for future targeted imaging and therapeutic applications. PMID:17389962

Parametric study of fluid flow manipulation with piezoelectric macrofiber composite flaps

NASA Astrophysics Data System (ADS)

Sadeghi, O.; Tarazaga, P.; Stremler, M.; Shahab, S.

2017-04-01

Active Fluid Flow Control (AFFC) has received great research attention due to its significant potential in engineering applications. It is known that drag reduction, turbulence management, flow separation delay and noise suppression through active control can result in significantly increased efficiency of future commercial transport vehicles and gas turbine engines. In microfluidics systems, AFFC has mainly been used to manipulate fluid passing through the microfluidic device. We put forward a conceptual approach for fluid flow manipulation by coupling multiple vibrating structures through flow interactions in an otherwise quiescent fluid. Previous investigations of piezoelectric flaps interacting with a fluid have focused on a single flap. In this work, arrays of closely-spaced, free-standing piezoelectric flaps are attached perpendicular to the bottom surface of a tank. The coupling of vibrating flaps due to their interacting with the surrounding fluid is investigated in air (for calibration) and under water. Actuated flaps are driven with a harmonic input voltage, which results in bending vibration of the flaps that can work with or against the flow-induced bending. The size and spatial distribution of the attached flaps, and the phase and frequency of the input actuation voltage are the key parameters to be investigated in this work. Our analysis will characterize the electrohydroelastic dynamics of active, interacting flaps and the fluid motion induced by the system.

Understanding cell passage through constricted microfluidic channels

NASA Astrophysics Data System (ADS)

Cartas-Ayala, Marco A.; Karnik, Rohit

2012-11-01

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

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.

Sample to answer visualization pipeline for low-cost point-of-care blood cell counting

NASA Astrophysics Data System (ADS)

Smith, Suzanne; Naidoo, Thegaran; Davies, Emlyn; Fourie, Louis; Nxumalo, Zandile; Swart, Hein; Marais, Philip; Land, Kevin; Roux, Pieter

2015-03-01

We present a visualization pipeline from sample to answer for point-of-care blood cell counting applications. Effective and low-cost point-of-care medical diagnostic tests provide developing countries and rural communities with accessible healthcare solutions [1], and can be particularly beneficial for blood cell count tests, which are often the starting point in the process of diagnosing a patient [2]. The initial focus of this work is on total white and red blood cell counts, using a microfluidic cartridge [3] for sample processing. Analysis of the processed samples has been implemented by means of two main optical visualization systems developed in-house: 1) a fluidic operation analysis system using high speed video data to determine volumes, mixing efficiency and flow rates, and 2) a microscopy analysis system to investigate homogeneity and concentration of blood cells. Fluidic parameters were derived from the optical flow [4] as well as color-based segmentation of the different fluids using a hue-saturation-value (HSV) color space. Cell count estimates were obtained using automated microscopy analysis and were compared to a widely accepted manual method for cell counting using a hemocytometer [5]. The results using the first iteration microfluidic device [3] showed that the most simple - and thus low-cost - approach for microfluidic component implementation was not adequate as compared to techniques based on manual cell counting principles. An improved microfluidic design has been developed to incorporate enhanced mixing and metering components, which together with this work provides the foundation on which to successfully implement automated, rapid and low-cost blood cell counting tests.

Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

NASA Astrophysics Data System (ADS)

Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

2015-11-01

Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery.

PubMed

Zhao, Chun-Xia

2013-11-01

Considerable effort has been directed towards developing novel drug delivery systems. Microfluidics, capable of generating monodisperse single and multiple emulsion droplets, executing precise control and operations on these droplets, is a powerful tool for fabricating complex systems (microparticles, microcapsules, microgels) with uniform size, narrow size distribution and desired properties, which have great potential in drug delivery applications. This review presents an overview of the state-of-the-art multiphase flow microfluidics for the production of single emulsions or multiple emulsions for drug delivery. The review starts with a brief introduction of the approaches for making single and multiple emulsions, followed by presentation of some potential drug delivery systems (microparticles, microcapsules and microgels) fabricated in microfluidic devices using single or multiple emulsions as templates. The design principles, manufacturing processes and properties of these drug delivery systems are also discussed and compared. Furthermore, drug encapsulation and drug release (including passive and active controlled release) are provided and compared highlighting some key findings and insights. Finally, site-targeting delivery using multiphase flow microfluidics is also briefly introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Experimental Investigations on the Surface-Driven Capillary Flow of Aqueous Microparticle Suspensions in the Microfluidic Laboratory-On Systems

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Subhadeep

In this work, total 1592 individual leakage-free polymethylmethacrylate (PMMA) microfluidic devices as laboratory-on-a-chip systems are fabricated by maskless lithography, hot embossing lithography, and direct bonding technique. Total 1094 individual Audio Video Interleave Files as experimental outputs related to the surface-driven capillary flow have been recorded and analyzed. The influence of effective viscosity, effect of surface wettability, effect of channel aspect ratio, and effect of centrifugal force on the surface-driven microfluidic flow of aqueous microparticle suspensions have been successfully and individually investigated in these laboratory-on-a-chip systems. Also, 5 micron polystyrene particles have been separated from the aqueous microparticle suspensions in the microfluidic lab-on-a-chip systems of modified design with 98% separation efficiency, and 10 micron polystyrene particles have been separated with 100% separation efficiency. About the novelty of this work, the experimental investigations have been performed on the surface-driven microfluidic flow of aqueous microparticle suspensions with the investigations on the separation time in particle-size based separation mechanism to control these suspensions in the microfluidic lab-on-a-chip systems. This research work contains a total of 10,112 individual experimental outputs obtained using total 30 individual instruments by author’s own hands-on completely during more than three years continuously. Author has performed the experimental investigations on both the fluid statics and fluid dynamics to develop an automated fluid machine.

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.

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization.

PubMed

Kastner, Elisabeth; Kaur, Randip; Lowry, Deborah; Moghaddam, Behfar; Wilkinson, Alexander; Perrie, Yvonne

2014-12-30

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

A small-scale, rolled-membrane microfluidic artificial lung designed towards future large area manufacturing.

PubMed

Thompson, A J; Marks, L H; Goudie, M J; Rojas-Pena, A; Handa, H; Potkay, J A

2017-03-01

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μ l/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10  μ m tall artificial capillaries, and a 66  μ m thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O 2 , atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO 2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.

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

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.

Tunable two-dimensional liquid gradient refractive index (L-GRIN) lens for variable light focusing.

PubMed

Huang, Hua; Mao, Xiaole; Lin, Sz-Chin Steven; Kiraly, Brian; Huang, Yiping; Huang, Tony Jun

2010-09-21

We report a two-dimensional (2D) tunable liquid gradient refractive index (L-GRIN) lens for variable focusing of light in the out-of-plane direction. This lens focuses a light beam through a liquid medium with a 2D hyperbolic secant (HS) refractive index gradient. The refractive index gradient is established in a microfluidic chamber through the diffusion between two fluids with different refractive indices, i.e. CaCl(2) solution and deionized (DI) water. The 2D HS refractive index profile and subsequently the focal length of the L-GRIN lens can be tuned by changing the ratio of the flow rates of the CaCl(2) solution and DI water. The focusing effect is experimentally characterized through side-view and top-view image analysis, and the experimental data match well with the results from ray-tracing optical simulations. Advantages of the 2D L-GRIN lens include simple device fabrication procedure, low fluid consumption rate, convenient lens-tuning mechanism, and compatibility with existing microfluidic devices. We expect that with further optimizations, this 2D L-GRIN lens can be used in many optics-based lab-on-a-chip applications.

Classification of biological cells using a sound wave based flow cytometer

NASA Astrophysics Data System (ADS)

Strohm, Eric M.; Gnyawali, Vaskar; Van De Vondervoort, Mia; Daghighi, Yasaman; Tsai, Scott S. H.; Kolios, Michael C.

2016-03-01

A flow cytometer that uses sound waves to determine the size of biological cells is presented. In this system, a microfluidic device made of polydimethylsiloxane (PDMS) was developed to hydrodynamically flow focus cells in a single file through a target area. Integrated into the microfluidic device was an ultrasound transducer with a 375 MHz center frequency, aligned opposite the transducer was a pulsed 532 nm laser focused into the device by a 10x objective. Each passing cell was insonfied with a high frequency ultrasound pulse, and irradiated with the laser. The resulting ultrasound and photoacoustic waves from each cell were analyzed using signal processing methods, where features in the power spectra were compared to theoretical models to calculate the cell size. Two cell lines with different size distributions were used to test the system: acute myeloid leukemia cells (AML) and melanoma cells. Over 200 cells were measured using this system. The average calculated diameter of the AML cells was 10.4 +/- 2.5 μm using ultrasound, and 11.4 +/- 2.3 μm using photoacoustics. The average diameter of the melanoma cells was 16.2 +/- 2.9 μm using ultrasound, and 18.9 +/- 3.5 μm using photoacoustics. The cell sizes calculated using ultrasound and photoacoustic methods agreed with measurements using a Coulter Counter, where the AML cells were 9.8 +/- 1.8 μm and the melanoma cells were 16.0 +/- 2.5 μm. These results demonstrate a high speed method of assessing cell size using sound waves, which is an alternative method to traditional flow cytometry techniques.

Flow of wormlike micellar solutions around confined microfluidic cylinders.

PubMed

Zhao, Ya; Shen, Amy Q; Haward, Simon J

2016-10-26

Wormlike micellar (WLM) solutions are frequently used in enhanced oil and gas recovery applications in porous rock beds where complex microscopic geometries result in mixed flow kinematics with strong shear and extensional components. Experiments with WLM solutions through model microfluidic porous media have revealed a variety of complex flow phenomena, including the formation of stable gel-like structures known as a Flow-Induced Structured Phase (FISP), which undoubtedly play an important role in applications of WLM fluids, but are still poorly understood. A first step in understanding flows of WLM fluids through porous media can be made by examining the flow around a single micro-scale cylinder aligned on the flow axis. Here we study flow behavior of an aqueous WLM solution consisting of cationic surfactant cetyltrimethylammonium bromide (CTAB) and a stable hydrotropic salt 3-hydroxy naphthalene-2-carboxylate (SHNC) in microfluidic devices with three different cylinder blockage ratios, β. We observe a rich sequence of flow instabilities depending on β as the Weissenberg number (Wi) is increased to large values while the Reynolds number (Re) remains low. Instabilities upstream of the cylinder are associated with high stresses in fluid that accelerates into the narrow gap between the cylinder and the channel wall; vortex growth upstream is reminiscent of that seen in microfluidic contraction geometries. Instability downstream of the cylinder is associated with stresses generated at the trailing stagnation point and the resulting flow modification in the wake, coupled with the onset of time-dependent flow upstream and the asymmetric division of flow around the cylinder.

Red blood cell (RBC) suspensions in confined microflows: Pressure-flow relationship.

PubMed

Stauber, Hagit; Waisman, Dan; Korin, Netanel; Sznitman, Josué

2017-10-01

Microfluidic-based assays have become increasingly popular to explore microcirculation in vitro. In these experiments, blood is resuspended to a desired haematocrit level in a buffer solution, where frequent choices for preparing RBC suspensions comprise notably Dextran and physiological buffer. Yet, the rational for selecting one buffer versus another is often ill-defined and lacks detailed quantification, including ensuing changes in RBC flow characteristics. Here, we revisit RBC suspensions in microflows and attempt to quantify systematically some of the differences emanating between buffers. We measure bulk flow rate (Q) of RBC suspensions, using PBS- and Dextran-40, as a function of the applied pressure drop (ΔP) for two hematocrits (∼0% and 23%). Two distinct microfluidic designs of varying dimensions are employed: a straight channel larger than and a network array similar to the size of individual RBCs. Using the resulting pressure-flow curves, we extract the equivalent hydrodynamic resistances and estimate the relative viscosities. These efforts are a first step in rigorously quantifying the influence of the 'background' buffer on RBC flows within microfluidic devices and thereby underline the importance of purposefully selecting buffer suspensions for microfluidic in vitro assays. Copyright © 2017. Published by Elsevier Ltd.

[Design and Optimization of Microfluidic Chips Used for Mixing Cryoprotectants].

PubMed

Zhou, Xinli; Yi, Xingyue; Zhou, Nanfeng; Yang, Yun

2016-06-01

Microfluidic chips can be used to realize continuous cryoprotectants(CPA)loading/unloading for oocytes,reducing osmotic damage and chemical toxicity of CPA.In this study,five different Y-shape microfluidic chips were fabricated to realize the continuous CPA loading/unloading.The effects of flow rate,entrance angle,aspect ratio and turning radius of microchannels on the mixing efficiency of microfluidic chips were analyzed quantitatively.The experimental results showed that with the decrease of flow rates,the increase of aspect ratios and the decrease of turning raradius of microchannel,the mixing length decreased and the mixing velocity was promoted,while the entrance angle had little effect on the mixing efficiency.However,the operating conditions and structural parameters of the chips in practical application should be determined based on an overall consideration of CPA loading/unloading time and machining accuracy.These results would provide a reference to the application of microfluidic chip in CPA mixing.

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.

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

An organic self-regulating microfluidic system.

PubMed

Eddington, D T; Liu, R H; Moore, J S; Beebe, D J

2001-12-01

In this paper we present an organic feedback scheme that merges microfluidics and responsive materials to address several limitations of current microfluidic systems. By using in situ fabrication and by taking advantage of microscale phenomena (e.g., laminar flow, short diffusion times), we have demonstrated feedback control of the output pH in a completely organic system. The system autonomously regulates an output stream at pH 7 under a range of input flow conditions. A single responsive hydrogel component performs the functionality of traditional feedback system components. Vertically stacked laminar flow is used to improve the time response of the hydrogel actuator. A star shaped orifice is utilized to improve the flow characteristics of the membrane/orifice valve. By changing the chemistry of the hydrogel component, the system can be altered to regulate flow based on hydrogels sensitive to temperature, light, biological/molecular, and others.

Compressed-air flow control system.

PubMed

Bong, Ki Wan; Chapin, Stephen C; Pregibon, Daniel C; Baah, David; Floyd-Smith, Tamara M; Doyle, Patrick S

2011-02-21

We present the construction and operation of a compressed-air driven flow system that can be used for a variety of microfluidic applications that require rapid dynamic response and precise control of multiple inlet streams. With the use of inexpensive and readily available parts, we describe how to assemble this versatile control system and further explore its utility in continuous- and pulsed-flow microfluidic procedures for the synthesis and analysis of microparticles.

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

PubMed Central

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

2013-01-01

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis. PMID:24404074

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

PubMed

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

2013-01-01

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis.

A novel microfluidic model can mimic organ-specific metastasis of circulating tumor cells.

PubMed

Kong, Jing; Luo, Yong; Jin, Dong; An, Fan; Zhang, Wenyuan; Liu, Lilu; Li, Jiao; Fang, Shimeng; Li, Xiaojie; Yang, Xuesong; Lin, Bingcheng; Liu, Tingjiao

2016-11-29

A biomimetic microsystem might compensate costly and time-consuming animal metastatic models. Herein we developed a biomimetic microfluidic model to study cancer metastasis. Primary cells isolated from different organs were cultured on the microlfuidic model to represent individual organs. Breast and salivary gland cancer cells were driven to flow over primary cell culture chambers, mimicking dynamic adhesion of circulating tumor cells (CTCs) to endothelium in vivo. These flowing artificial CTCs showed different metastatic potentials to lung on the microfluidic model. The traditional nude mouse model of lung metastasis was performed to investigate the physiological similarity of the microfluidic model to animal models. It was found that the metastatic potential of different cancer cells assessed by the microfluidic model was in agreement with that assessed by the nude mouse model. Furthermore, it was demonstrated that the metastatic inhibitor AMD3100 inhibited lung metastasis effectively in both the microfluidic model and the nude mouse model. Then the microfluidic model was used to mimick liver and bone metastasis of CTCs and confirm the potential for research of multiple-organ metastasis. Thus, the metastasis of CTCs to different organs was reconstituted on the microfluidic model. It may expand the capabilities of traditional cell culture models, providing a low-cost, time-saving, and rapid alternative to animal models.

High-throughput optofluidic system for the laser microsurgery of oocytes

NASA Astrophysics Data System (ADS)

Chandsawangbhuwana, Charlie; Shi, Linda Z.; Zhu, Qingyuan; Alliegro, Mark C.; Berns, Michael W.

2012-01-01

This study combines microfluidics with optical microablation in a microscopy system that allows for high-throughput manipulation of oocytes, automated media exchange, and long-term oocyte observation. The microfluidic component of the system transports oocytes from an inlet port into multiple flow channels. Within each channel, oocytes are confined against a microfluidic barrier using a steady fluid flow provided by an external computer-controlled syringe pump. This allows for easy media replacement without disturbing the oocyte location. The microfluidic and optical-laser microbeam ablation capabilities of the system were validated using surf clam (Spisula solidissima) oocytes that were immobilized in order to permit ablation of the 5 μm diameter nucleolinus within the oocyte nucleolus. Oocytes were the followed and assayed for polar body ejection.

Microfluidic point-of-care blood panel based on a novel technique: Reversible electroosmotic flow

PubMed Central

Mohammadi, Mahdi; Madadi, Hojjat; Casals-Terré, Jasmina

2015-01-01

A wide range of diseases and conditions are monitored or diagnosed from blood plasma, but the ability to analyze a whole blood sample with the requirements for a point-of-care device, such as robustness, user-friendliness, and simple handling, remains unmet. Microfluidics technology offers the possibility not only to work fresh thumb-pricked whole blood but also to maximize the amount of the obtained plasma from the initial sample and therefore the possibility to implement multiple tests in a single cartridge. The microfluidic design presented in this paper is a combination of cross-flow filtration with a reversible electroosmotic flow that prevents clogging at the filter entrance and maximizes the amount of separated plasma. The main advantage of this design is its efficiency, since from a small amount of sample (a single droplet ∼10 μl) almost 10% of this (approx 1 μl) is extracted and collected with high purity (more than 99%) in a reasonable time (5–8 min). To validate the quality and quantity of the separated plasma and to show its potential as a clinical tool, the microfluidic chip has been combined with lateral flow immunochromatography technology to perform a qualitative detection of the thyroid-stimulating hormone and a blood panel for measuring cardiac Troponin and Creatine Kinase MB. The results from the microfluidic system are comparable to previous commercial lateral flow assays that required more sample for implementing fewer tests. PMID:26396660

Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation.

PubMed

Bhagat, Ali Asgar S; Hou, Han Wei; Li, Leon D; Lim, Chwee Teck; Han, Jongyoon

2011-06-07

Blood is a highly complex bio-fluid with cellular components making up >40% of the total volume, thus making its analysis challenging and time-consuming. In this work, we introduce a high-throughput size-based separation method for processing diluted blood using inertial microfluidics. The technique takes advantage of the preferential cell focusing in high aspect-ratio microchannels coupled with pinched flow dynamics for isolating low abundance cells from blood. As an application of the developed technique, we demonstrate the isolation of cancer cells (circulating tumor cells (CTCs)) spiked in blood by exploiting the difference in size between CTCs and hematologic cells. The microchannel dimensions and processing parameters were optimized to enable high throughput and high resolution separation, comparable to existing CTC isolation technologies. Results from experiments conducted with MCF-7 cells spiked into whole blood indicate >80% cell recovery with an impressive 3.25 × 10(5) fold enrichment over red blood cells (RBCs) and 1.2 × 10(4) fold enrichment over peripheral blood leukocytes (PBL). In spite of a 20× sample dilution, the fast operating flow rate allows the processing of ∼10(8) cells min(-1) through a single microfluidic device. The device design can be easily customized for isolating other rare cells from blood including peripheral blood leukocytes and fetal nucleated red blood cells by simply varying the 'pinching' width. The advantage of simple label-free separation, combined with the ability to retrieve viable cells post enrichment and minimal sample pre-processing presents numerous applications for use in clinical diagnosis and conducting fundamental studies.

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.

Dynamics of blood flow in a microfluidic ladder network

NASA Astrophysics Data System (ADS)

Maddala, Jeevan; Zilberman-Rudenko, Jevgenia; McCarty, Owen

The dynamics of a complex mixture of cells and proteins, such as blood, in perturbed shear flow remains ill-defined. Microfluidics is a promising technology for improving the understanding of blood flow under complex conditions of shear; as found in stent implants and in tortuous blood vessels. We model the fluid dynamics of blood flow in a microfluidic ladder network with dimensions mimicking venules. Interaction of blood cells was modeled using multiagent framework, where cells of different diameters were treated as spheres. This model served as the basis for predicting transition regions, collision pathways, re-circulation zones and residence times of cells dependent on their diameters and device architecture. Based on these insights from the model, we were able to predict the clot formation configurations at various locations in the device. These predictions were supported by the experiments using whole blood. To facilitate platelet aggregation, the devices were coated with fibrillar collagen and tissue factor. Blood was perfused through the microfluidic device for 9 min at a physiologically relevant venous shear rate of 600 s-1. Using fluorescent microscopy, we observed flow transitions near the channel intersections and at the areas of blood flow obstruction, which promoted larger thrombus formation. This study of integrating model predictions with experimental design, aids in defining the dynamics of blood flow in microvasculature and in development of novel biomedical devices.

Collective oscillations and coupled modes in confined microfluidic droplet arrays

NASA Astrophysics Data System (ADS)

Schiller, Ulf D.; Fleury, Jean-Baptiste; Seemann, Ralf; Gompper, Gerhard

Microfluidic droplets have a wide range of applications ranging from analytic assays in cellular biology to controlled mixing in chemical engineering. Ensembles of microfluidic droplets are interesting model systems for non-equilibrium many-body phenomena. When flowing in a microchannel, trains of droplets can form microfluidic crystals whose dynamics are governed by long-range hydrodynamic interactions and boundary effects. In this contribution, excitation mechanisms for collective waves in dense and confined microfluidic droplet arrays are investigated by experiments and computer simulations. We demonstrate that distinct modes can be excited by creating specific `defect' patterns in flowing droplet trains. While longitudinal modes exhibit a short-lived cascade of pairs of laterally displacing droplets, transversely excited modes form propagating waves that behave like microfluidic phonons. We show that the confinement induces a coupling between longitudinal and transverse modes. We also investigate the life time of the collective oscillations and discuss possible mechanisms for the onset of instabilities. Our results demonstrate that microfluidic phonons can exhibit effects beyond the linear theory, which can be studied particularly well in dense and confined systems. This work was supported by Deutsche Forschungsgemeinschaft under Grant No. SE 1118/4.

Sheathless focusing and separation of microparticles using tilted angle travelling surface acoustic waves.

PubMed

Ahmed, Husnain; Destgeer, Ghulam; Park, Jinsoo; Afzal, Muhammad; Sung, Hyung Jin

2018-06-18

The sheathless focusing and separation of microparticles is an important pre-processing step in various biochemical assays in which enriched sample isolation is critical. Most previous microfluidic particle separation techniques have used a sheath flow to achieve efficient sample focusing. The sheath flow diluted the analyte, and required additional microchannels and accurate flow control. We demonstrated a tilted angle travelling surface acoustic wave (taTSAW)-based sheathless focusing and separation of particles in a continuous flow. The proposed device consisted of a piezoelectric substrate with a pair of interdigitated transducers (IDTs) deposited at two different angles relative to the flow direction. A Y-shaped polydimethylsiloxane (PDMS) microchannel having one inlet and two outlet ports was positioned on top of the IDTs such that the acoustic energy coupling into the fluid was maximized and wave attenuation by the PDMS walls was minimized. The two IDTs independently produced high-frequency taTSAWs, which propagated at ±30° with respect to the flow direction and imparted a direct acoustic radiation force onto the target particles. A sample mixture containing 4.8 and 3.2 µm particles was focused and then separated by the actuation of the IDTs at 194 and 136 MHz frequencies, respectively, without using an additional sheath flow. The proposed taTSAW-based particle separation device offered a high purity > 99% at the both outlets over a wide range of flow speeds (up to 83.3 mm/s).

Recent advancements in chemical luminescence-based lab-on-chip and microfluidic platforms for bioanalysis.

PubMed

Mirasoli, Mara; Guardigli, Massimo; Michelini, Elisa; Roda, Aldo

2014-01-01

Miniaturization of analytical procedures through microchips, lab-on-a-chip or micro total analysis systems is one of the most recent trends in chemical and biological analysis. These systems are designed to perform all the steps in an analytical procedure, with the advantages of low sample and reagent consumption, fast analysis, reduced costs, possibility of extra-laboratory application. A range of detection technologies have been employed in miniaturized analytical systems, but most applications relied on fluorescence and electrochemical detection. Chemical luminescence (which includes chemiluminescence, bioluminescence, and electrogenerated chemiluminescence) represents an alternative detection principle that offered comparable (or better) analytical performance and easier implementation in miniaturized analytical devices. Nevertheless, chemical luminescence-based ones represents only a small fraction of the microfluidic devices reported in the literature, and until now no review has been focused on these devices. Here we review the most relevant applications (since 2009) of miniaturized analytical devices based on chemical luminescence detection. After a brief overview of the main chemical luminescence systems and of the recent technological advancements regarding their implementation in miniaturized analytical devices, analytical applications are reviewed according to the nature of the device (microfluidic chips, microchip electrophoresis, lateral flow- and paper-based devices) and the type of application (micro-flow injection assays, enzyme assays, immunoassays, gene probe hybridization assays, cell assays, whole-cell biosensors). Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2018-06-13

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

miRNA detection at single-cell resolution using microfluidic LNA flow-FISH

DOE PAGES

Wu, Meiye; Piccini, Matthew Ernest; Koh, Chung -Yan; ...

2014-08-20

Flow cytometry in combination with fluorescent in situ hybridization (flow-FISH) is a powerful technique that can be utilized to rapidly detect nucleic acids at single-cell resolution without the need for homogenization or nucleic acid extraction. Here, we describe a microfluidic-based method which enables the detection of microRNAs or miRNAs in single intact cells by flow-FISH using locked nucleic acid (LNA)-containing probes. Our method can be applied to all RNA species including mRNA and small noncoding RNA and is suitable for multiplexing with protein immunostaining in the same cell. For demonstration of our method, this chapter details the detection of miR155more » and CD69 protein in PMA and ionomycin-stimulated Jurkat cells. Here, we also include instructions on how to set up a microfluidic chip sample preparation station to prepare cells for imaging and analysis on a commercial flow cytometer or a custom-built micro-flow cytometer.« less

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

PubMed

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

2018-01-29

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

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.

Inventions Utilizing Microfluidics and Colloidal Particles

NASA Technical Reports Server (NTRS)

Marr, David W.; Gong, Tieying; Oakey, John; Terray, Alexander V.; Wu, David T.

2009-01-01

Several related inventions pertain to families of devices that utilize microfluidics and/or colloidal particles to obtain useful physical effects. The families of devices can be summarized as follows: (1) Microfluidic pumps and/or valves wherein colloidal-size particles driven by electrical, magnetic, or optical fields serve as the principal moving parts that propel and/or direct the affected flows. (2) Devices that are similar to the aforementioned pumps and/or valves except that they are used to manipulate light instead of fluids. The colloidal particles in these devices are substantially constrained to move in a plane and are driven to spatially order them into arrays that function, variously, as waveguides, filters, or switches for optical signals. (3) Devices wherein the ultra-laminar nature of microfluidic flows is exploited to effect separation, sorting, or filtering of colloidal particles or biological cells in suspension. (4) Devices wherein a combination of confinement and applied electrical and/or optical fields forces the colloidal particles to become arranged into three-dimensional crystal lattices. Control of the colloidal crystalline structures could be exploited to control diffraction of light. (5) Microfluidic devices, incorporating fluid waveguides, wherein switching of flows among different paths would be accompanied by switching of optical signals.

Paper pump for passive and programmable transport

PubMed Central

Wang, Xiao; Hagen, Joshua A.; Papautsky, Ian

2013-01-01

In microfluidic systems, a pump for fluid-driving is often necessary. To keep the size of microfluidic systems small, a pump that is small in size, light-weight and needs no external power source is advantageous. In this work, we present a passive, simple, ultra-low-cost, and easily controlled pumping method based on capillary action of paper that pumps fluid through conventional polymer-based microfluidic channels with steady flow rate. By using inexpensive cutting tools, paper can be shaped and placed at the outlet port of a conventional microfluidic channel, providing a wide range of pumping rates. A theoretical model was developed to describe the pumping mechanism and aid in the design of paper pumps. As we show, paper pumps can provide steady flow rates from 0.3 μl/s to 1.7 μl/s and can be cascaded to achieve programmable flow-rate tuning during the pumping process. We also successfully demonstrate transport of the most common biofluids (urine, serum, and blood). With these capabilities, the paper pump has the potential to become a powerful fluid-driving approach that will benefit the fielding of microfluidic systems for point-of-care applications. PMID:24403999

Highly Permeable Silicon Membranes for Shear Free Chemotaxis and Rapid Cell Labeling

PubMed Central

Chung, Henry H.; Chan, Charles K.; Khire, Tejas S.; Marsh, Graham A.; Clark, Alfred; Waugh, Richard E.; McGrath, James L.

2015-01-01

Microfluidic systems are powerful tools for cell biology studies because they enable the precise addition and removal of solutes in small volumes. However, the fluid forces inherent in the use of microfluidics for cell cultures are sometimes undesirable. An important example is chemotaxis systems where fluid flow creates well-defined and steady chemotactic gradients but also pushes cells downstream. Here we demonstrate a chemotaxis system in which two chambers are separated by a molecularly thin (15 nm), transparent, and nanoporous silicon membrane. One chamber is a microfluidic channel that carries a flow-generated gradient while the other chamber is a shear-free environment for cell observation. The molecularly thin membranes provide effectively no resistance to molecular diffusion between the two chambers, making them ideal elements for creating flow-free chambers in microfluidic systems. Analytical and computational flow models that account for membrane and chamber geometry, predict shear reduction of more than five orders of magnitude. This prediction is confirmed by observing the pure diffusion of nanoparticles in the cell-hosting chamber despite high input flow (Q = 10 µL min−1; vavg ~45 mm min−1) in the flow chamber only 15 nm away. Using total internal reflection fluorescence (TIRF) microscopy, we show that a flow-generated molecular gradient will pass through the membrane into the quiescent cell chamber. Finally we demonstrate that our device allows us to expose migrating neutrophils to a chemotactic gradient or fluorescent label without any influence from flow. PMID:24850320

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.

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.

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

PubMed

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

2014-09-21

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

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.

Successes and future outlook for microfluidics-based cardiovascular drug discovery.

PubMed

Skommer, Joanna; Wlodkowic, Donald

2015-03-01

The greatest advantage of using microfluidics as a platform for the assessment of cardiovascular drug action is its ability to finely regulate fluid flow conditions, including flow rate, shear stress and pulsatile flow. At the same time, microfluidics provide means for modifying the vessel geometry (bifurcations, stenoses, complex networks), the type of surface of the vessel walls, and for patterning cells in 3D tissue-like architecture, including generation of lumen walls lined with cells and heart-on-a-chip structures for mimicking ventricular cardiomyocyte physiology. In addition, owing to the small volume of required specimens, microfluidics is ideally suited to clinical situations whereby monitoring of drug dosing or efficacy needs to be coupled with minimal phlebotomy-related drug loss. In this review, the authors highlight potential applications for the currently existing and emerging technologies and offer several suggestions on how to close the development cycle of microfluidic devices for cardiovascular drug discovery. The ultimate goal in microfluidics research for drug discovery is to develop 'human-on-a-chip' systems, whereby several organ cultures, including the vasculature and the heart, can mimic complex interactions between the organs and body systems. This would provide in vivo-like pharmacokinetics and pharmacodynamics for drug ADMET assessment. At present, however, the great variety of available designs does not go hand in hand with their use by the pharmaceutical community.

Microfluidic Mixing Technology for a Universal Health Sensor

NASA Technical Reports Server (NTRS)

Chan, Eugene Y.; Bae, Candice

2009-01-01

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

Electropermanent magnet actuation for droplet ferromicrofluidics

PubMed Central

Padovani, José I.; Jeffrey, Stefanie S.; Howe, Roger T.

2016-01-01

Droplet actuation is an essential mechanism for droplet-based microfluidic systems. On-demand electromagnetic actuation is used in a ferrofluid-based microfluidic system for water droplet displacement. Electropermanent magnets (EPMs) are used to induce 50 mT magnetic fields in a ferrofluid filled microchannel with gradients up to 6.4 × 104 kA/m2. Short 50 µs current pulses activate the electropermanent magnets and generate negative magnetophoretic forces that range from 10 to 70 nN on 40 to 80 µm water-in-ferrofluid droplets. Maximum droplet displacement velocities of up to 300 µm/s are obtained under flow and no-flow conditions. Electropermanent magnet-activated droplet sorting under continuous flow is demonstrated using a split-junction microfluidic design. PMID:27583301

Multiple independent autonomous hydraulic oscillators driven by a common gravity head.

PubMed

Kim, Sung-Jin; Yokokawa, Ryuji; Lesher-Perez, Sasha Cai; Takayama, Shuichi

2015-06-15

Self-switching microfluidic circuits that are able to perform biochemical experiments in a parallel and autonomous manner, similar to instruction-embedded electronics, are rarely implemented. Here, we present design principles and demonstrations for gravity-driven, integrated, microfluidic pulsatile flow circuits. With a common gravity head as the only driving force, these fluidic oscillator arrays realize a wide range of periods (0.4 s-2 h) and flow rates (0.10-63 μl min(-1)) with completely independent timing between the multiple oscillator sub-circuits connected in parallel. As a model application, we perform systematic, parallel analysis of endothelial cell elongation response to different fluidic shearing patterns generated by the autonomous microfluidic pulsed flow generation system.

Microfluidic assembly blocks.

PubMed

Rhee, Minsoung; Burns, Mark A

2008-08-01

An assembly approach for microdevice construction using prefabricated microfluidic components is presented. Although microfluidic systems are convenient platforms for biological assays, their use in the life sciences is still limited mainly due to the high-level fabrication expertise required for construction. This approach involves prefabrication of individual microfluidic assembly blocks (MABs) in PDMS that can be readily assembled to form microfluidic systems. Non-expert users can assemble the blocks on glass slides to build their devices in minutes without any fabrication steps. In this paper, we describe the construction and assembly of the devices using the MAB methodology, and demonstrate common microfluidic applications including laminar flow development, valve control, and cell culture.

Continuous flow microfluidic separation and processing of rare cells and bioparticles found in blood - A review.

PubMed

Antfolk, Maria; Laurell, Thomas

2017-05-01

Rare cells in blood, such as circulating tumor cells or fetal cells in the maternal circulation, posses a great prognostic or diagnostic value, or for the development of personalized medicine, where the study of rare cells could provide information to more specifically targeted treatments. When conventional cell separation methods, such as flow cytometry or magnetic activated cell sorting, have fallen short other methods are desperately sought for. Microfluidics have been extensively used towards isolating and processing rare cells as it offers possibilities not present in the conventional systems. Furthermore, microfluidic methods offer new possibilities for cell separation as they often rely on non-traditional biomarkers and intrinsic cell properties. This offers the possibility to isolate cell populations that would otherwise not be targeted using conventional methods. Here, we provide an extensive review of the latest advances in continuous flow microfluidic rare cell separation and processing with each cell's specific characteristics and separation challenges as a point of view. Copyright © 2017 Elsevier B.V. All rights reserved.

Generation of microfluidic flow using an optically assembled and magnetically driven microrotor

NASA Astrophysics Data System (ADS)

Köhler, J.; Ghadiri, R.; Ksouri, S. I.; Guo, Q.; Gurevich, E. L.; Ostendorf, A.

2014-12-01

The key components in microfluidic systems are micropumps, valves and mixers. Depending on the chosen technology, the realization of these microsystems often requires rotational and translational control of subcomponents. The manufacturing of such active components as well as the driving principle are still challenging tasks. A promising all-optical approach could be the combination of laser direct writing and actuation based on optical forces. However, when higher actuation velocities are required, optical driving might be too slow. Hence, a novel approach based on optical assembling of microfluidic structures and subsequent magnetic actuation is proposed. By applying the optical assembly of microspherical building blocks as the manufacturing method and magnetic actuation, a microrotor was successfully fabricated and tested within a microfluidic channel. The resulting fluid flow was characterized by introducing an optically levitated measuring probe particle. Finally, a freely moving tracer particle visualizes the generated flow. The tracer particle analysis shows average velocities of 0.4-0.5 µm s-1 achieved with the presented technology.

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.

Culture and Sampling of Primary Adipose Tissue in Practical Microfluidic Systems.

PubMed

Brooks, Jessica C; Judd, Robert L; Easley, Christopher J

2017-01-01

Microfluidic culture of primary adipose tissue allows for reduced sample and reagent volumes as well as constant media perfusion of the cells. By continuously flowing media over the tissue, microfluidic sampling systems can more accurately mimic vascular flow in vivo. Quantitative measurements can be performed on or off chip to provide time-resolved secretion data, furthering insight into the dynamics of the function of adipose tissue. Buoyancy resulting from the large lipid storage capacity in this tissue presents a unique challenge for culture, and it is important to account for this buoyancy during microdevice design. Herein, we describe approaches for microfluidic device fabrication that utilize 3D-printed interface templating to help counteract cell buoyancy. We apply such methods to the culture of both isolated, dispersed primary adipocytes and epididymal adipose explants. To facilitate more widespread adoption of the methodology, the devices presented here are designed for user-friendly operation. Only handheld syringes are needed to control flow, and devices are inexpensive and disposable.

A high-throughput flow cytometry-on-a-CMOS platform for single-cell dielectric spectroscopy at microwave frequencies.

PubMed

Chien, Jun-Chau; Ameri, Ali; Yeh, Erh-Chia; Killilea, Alison N; Anwar, Mekhail; Niknejad, Ali M

2018-06-06

This work presents a microfluidics-integrated label-free flow cytometry-on-a-CMOS platform for the characterization of the cytoplasm dielectric properties at microwave frequencies. Compared with MHz impedance cytometers, operating at GHz frequencies offers direct intracellular permittivity probing due to electric fields penetrating through the cellular membrane. To overcome the detection challenges at high frequencies, the spectrometer employs on-chip oscillator-based sensors, which embeds simultaneous frequency generation, electrode excitation, and signal detection capabilities. By employing an injection-locking phase-detection technique, the spectrometer offers state-of-the-art sensitivity, achieving a less than 1 aFrms capacitance detection limit (or 5 ppm in frequency-shift) at a 100 kHz noise filtering bandwidth, enabling high throughput (>1k cells per s), with a measured cellular SNR of more than 28 dB. With CMOS/microfluidics co-design, we distribute four sensing channels at 6.5, 11, 17.5, and 30 GHz in an arrayed format whereas the frequencies are selected to center around the water relaxation frequency at 18 GHz. An issue in the integration of CMOS and microfluidics due to size mismatch is also addressed through introducing a cost-efficient epoxy-molding technique. With 3-D hydrodynamic focusing microfluidics, we perform characterization on four different cell lines including two breast cell lines (MCF-10A and MDA-MB-231) and two leukocyte cell lines (K-562 and THP-1). After normalizing the higher frequency signals to the 6.5 GHz ones, the size-independent dielectric opacity shows a differentiable distribution at 17.5 GHz between normal (0.905 ± 0.160, mean ± std.) and highly metastatic (1.033 ± 0.107) breast cells with p ≪ 0.001.

Acoustically and Electrokinetically Driven Transport in Microfluidic Devices

NASA Astrophysics Data System (ADS)

Sayar, Ersin

Electrokinetically driven flows are widely employed as a primary method for liquid pumping in micro-electromechanical systems. Mixing of analytes and reagents is limited in microfluidic devices due to the low Reynolds number of the flows. Acoustic excitations have recently been suggested to promote mixing in the microscale flow systems. Electrokinetic flows through straight microchannels were investigated using the Poisson-Boltzmann and Nernst-Planck models. The acoustic wave/fluid flow interactions in a microchannel were investigated via the development of two and three-dimensional dynamic predictive models for flows with field couplings of the electrical, mechanical and fluid flow quantities. The effectiveness and applicability of electrokinetic augmentation in flexural plate wave micropumps for enhanced capabilities were explored. The proposed concept can be exploited to integrate micropumps into complex microfluidic chips improving the portability of micro-total-analysis systems along with the capabilities of actively controlling acoustics and electrokinetics for micro-mixer applications. Acoustically excited flows in microchannels consisting of flexural plate wave devices and thin film resonators were considered. Compressible flow fields were considered to accommodate the acoustic excitations produced by a vibrating wall. The velocity and pressure profiles for different parameters including frequency, channel height, wave amplitude and length were investigated. Coupled electrokinetics and acoustics cases were investigated while the electric field intensity of the electrokinetic body forces and actuation frequency of acoustic excitations were varied. Multifield analysis of a piezoelectrically actuated valveless micropump was also presented. The effect of voltage and frequency on membrane deflection and flow rate were investigated. Detailed fluid/solid deformation coupled simulations of piezoelectric valveless micropump have been conducted to predict the generated time averaged flow rates. Developed coupled solid and fluid mechanics models can be utilized to integrate flow-through sensors with microfluidic chips.

Unconventional microfluidics: expanding the discipline.

PubMed

Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S; Huang, Tony Jun

2013-04-21

Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields-and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such "unconventional" microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline.

Membraneless seawater desalination

DOEpatents

Crooks, Richard A.; Knust, Kyle N.; Perdue, Robbyn K.

2018-04-03

Disclosed are microfluidic devices and systems for the desalination of water. The devices and systems can include an electrode configured to generate an electric field gradient in proximity to an intersection formed by the divergence of two microfluidic channels from an inlet channel. Under an applied bias and in the presence of a pressure driven flow of saltwater, the electric field gradient can preferentially direct ions in saltwater into one of the diverging microfluidic channels, while desalted water flows into second diverging channel. Also provided are methods of using the devices and systems described herein to decrease the salinity of water.

Recent advances in engineering microparticles and their nascent utilization in biomedical delivery and diagnostic applications.

PubMed

Choi, Andrew; Seo, Kyoung Duck; Kim, Do Wan; Kim, Bum Chang; Kim, Dong Sung

2017-02-14

Complex microparticles (MPs) bearing unique characteristics such as well-tailored sizes, various morphologies, and multi-compartments have been attempted to be produced by many researchers in the past decades. However, a conventionally used method of fabricating MPs, emulsion polymerization, has a limitation in achieving the aforementioned characteristics and several approaches such as the microfluidics-assisted (droplet-based microfluidics and flow lithography-based microfluidics), electrohydrodynamics (EHD)-based, centrifugation-based, and template-based methods have been recently suggested to overcome this limitation. The outstanding features of complex MPs engineered through these suggested methods have provided new opportunities for MPs to be applied in a wider range of applications including cell carriers, drug delivery agents, active pigments for display, microsensors, interface stabilizers, and catalyst substrates. Overall, the engineered MPs expose their potential particularly in the field of biomedical engineering as the increased complexity in the engineered MPs fulfills well the requirements of the high-end applications. This review outlines the current trends of newly developed techniques used for engineered MPs fabrication and focuses on the current state of engineered MPs in biomedical applications.

Three-dimensional parallelization of microfluidic droplet generators for a litre per hour volume production of single emulsions.

PubMed

Conchouso, D; Castro, D; Khan, S A; Foulds, I G

2014-08-21

This paper looks at the design, fabrication and characterization of stackable microfluidic emulsion generators, with coefficients of variation as low as ~6% and with production rates as high as ~1 L h(-1). This work reports the highest throughput reported in the literature for a microfluidic device with simultaneous operation of liquid-liquid droplet generators. The device was achieved by stacking several layers of 128 flow-focusing droplet generators, organized in a circular array. These layers are interconnected via through-holes and fed with designated fractal distribution networks. The proposed layers were milled on poly(methylmethacrylate) (PMMA) sheets and the stack was thermo-compression bonded to create a three-dimensional device with a high density of generators and an integrated hydraulic manifold. The effect of stacking multiple layers was studied and the results show that fabrication accuracy has a greater impact on the dispersity of the emulsion than the addition of more layers to the stack. Particle crystallization of drugs was also demonstrated as a possible application of this technology in industry.

Tuning-free controller to accurately regulate flow rates in a microfluidic network

NASA Astrophysics Data System (ADS)

Heo, Young Jin; Kang, Junsu; Kim, Min Jun; Chung, Wan Kyun

2016-03-01

We describe a control algorithm that can improve accuracy and stability of flow regulation in a microfluidic network that uses a conventional pressure pump system. The algorithm enables simultaneous and independent control of fluid flows in multiple micro-channels of a microfluidic network, but does not require any model parameters or tuning process. We investigate robustness and optimality of the proposed control algorithm and those are verified by simulations and experiments. In addition, the control algorithm is compared with a conventional PID controller to show that the proposed control algorithm resolves critical problems induced by the PID control. The capability of the control algorithm can be used not only in high-precision flow regulation in the presence of disturbance, but in some useful functions for lab-on-a-chip devices such as regulation of volumetric flow rate, interface position control of two laminar flows, valveless flow switching, droplet generation and particle manipulation. We demonstrate those functions and also suggest further potential biological applications which can be accomplished by the proposed control framework.

Tuning-free controller to accurately regulate flow rates in a microfluidic network

PubMed Central

Heo, Young Jin; Kang, Junsu; Kim, Min Jun; Chung, Wan Kyun

2016-01-01

We describe a control algorithm that can improve accuracy and stability of flow regulation in a microfluidic network that uses a conventional pressure pump system. The algorithm enables simultaneous and independent control of fluid flows in multiple micro-channels of a microfluidic network, but does not require any model parameters or tuning process. We investigate robustness and optimality of the proposed control algorithm and those are verified by simulations and experiments. In addition, the control algorithm is compared with a conventional PID controller to show that the proposed control algorithm resolves critical problems induced by the PID control. The capability of the control algorithm can be used not only in high-precision flow regulation in the presence of disturbance, but in some useful functions for lab-on-a-chip devices such as regulation of volumetric flow rate, interface position control of two laminar flows, valveless flow switching, droplet generation and particle manipulation. We demonstrate those functions and also suggest further potential biological applications which can be accomplished by the proposed control framework. PMID:26987587

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

A novel 3D micron-scale DPTV (Defocused Particle Tracking Velocimetry) and its applications in microfluidic devices

NASA Astrophysics Data System (ADS)

Roberts, John

2005-11-01

The rapid advancements in micro/nano biotechnology demand quantitative tools for characterizing microfluidic flows in lab-on-a-chip applications, validation of computational results for fully 3D flows in complex micro-devices, and efficient observation of cellular dynamics in 3D. We present a novel 3D micron-scale DPTV (defocused particle tracking velocimetry) that is capable of mapping out 3D Lagrangian, as well as 3D Eulerian velocity flow fields at sub-micron resolution and with one camera. The main part of the imaging system is an epi-fluorescent microscope (Olympus IX 51), and the seeding particles are fluorescent particles with diameter range 300nm - 10um. A software package has been developed for identifying (x,y,z,t) coordinates of the particles using the defocused images. Using the imaging system, we successfully mapped the pressure driven flow fields in microfluidic channels. In particular, we measured the Laglangian flow fields in a microfluidic channel with a herring bone pattern at the bottom, the later is used to enhance fluid mixing in lateral directions. The 3D particle tracks revealed the flow structure that has only been seen in numerical computation. This work is supported by the National Science Foundation (CTS - 0514443), the Nanobiotechnology Center at Cornell, and The New York State Center for Life Science Enterprise.

A radial flow microfluidic device for ultra-high-throughput affinity-based isolation of circulating tumor cells.

PubMed

Murlidhar, Vasudha; Zeinali, Mina; Grabauskiene, Svetlana; Ghannad-Rezaie, Mostafa; Wicha, Max S; Simeone, Diane M; Ramnath, Nithya; Reddy, Rishindra M; Nagrath, Sunitha

2014-12-10

Circulating tumor cells (CTCs) are believed to play an important role in metastasis, a process responsible for the majority of cancer-related deaths. But their rarity in the bloodstream makes microfluidic isolation complex and time-consuming. Additionally the low processing speeds can be a hindrance to obtaining higher yields of CTCs, limiting their potential use as biomarkers for early diagnosis. Here, a high throughput microfluidic technology, the OncoBean Chip, is reported. It employs radial flow that introduces a varying shear profile across the device, enabling efficient cell capture by affinity at high flow rates. The recovery from whole blood is validated with cancer cell lines H1650 and MCF7, achieving a mean efficiency >80% at a throughput of 10 mL h(-1) in contrast to a flow rate of 1 mL h(-1) standardly reported with other microfluidic devices. Cells are recovered with a viability rate of 93% at these high speeds, increasing the ability to use captured CTCs for downstream analysis. Broad clinical application is demonstrated using comparable flow rates from blood specimens obtained from breast, pancreatic, and lung cancer patients. Comparable CTC numbers are recovered in all the samples at the two flow rates, demonstrating the ability of the technology to perform at high throughputs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mobile monolithic polymer elements for flow control in microfluidic devices

DOEpatents

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

2004-08-31

A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by either fluid or gas pressure against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

Mobile Monolith Polymer Elements For Flow Control In Microfluidic Systems

DOEpatents

Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.; Kirby, Brian J.

2006-01-24

A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

Mobile monolithic polymer elements for flow control in microfluidic devices

DOEpatents

Hasselbrink, Jr., Ernest F.; Rehm, Jason E [Alameda, CA; Shepodd, Timothy J [Livermore, CA; Kirby, Brian J [San Francisco, CA

2005-11-11

A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

Constant flow-driven microfluidic oscillator for different duty cycles

PubMed Central

Kim, Sung-Jin; Yokokawa, Ryuji; Lesher-Perez, Sasha Cai; Takayama, Shuichi

2012-01-01

This paper presents microfluidic devices that autonomously convert two constant flow inputs into an alternating oscillatory flow output. We accomplish this hardware embedded self-control programming using normally closed membrane valves that have an inlet, an outlet, and a membrane-pressurization chamber connected to a third terminal. Adjustment of threshold opening pressures in these 3-terminal flow switching valves enabled adjustment of oscillation periods to between 57–360 s with duty cycles of 0.2–0.5. These values are in relatively good agreement with theoretical values, providing the way for rational design of an even wider range of different waveform oscillations. We also demonstrate the ability to use these oscillators to perform temporally patterned delivery of chemicals to living cells. The device only needs a syringe pump, thus removing the use of complex, expensive external actuators. These tunable waveform microfluidic oscillators are envisioned to facilitate cell-based studies that require temporal stimulation. PMID:22206453

Electrowetting (EW)-based valve combined with hydrophilic teflon microfluidic guidance in controlling continuous fluid flow.

PubMed

Cheng, Ji-Yen; Hsiung, Lo-Chang

2004-12-01

Electrowetting (EW)-based techniques have been widely used in manipulating discrete liquid. However, few articles discussed the controlling of continuous fluid flow by using EW-based techniques. In this paper, an EW-based valve combined with plasma-modified Teflon surface, which serves as a microfluidic guidance, in controlling continuous fluid flow has been demonstrated. The plasma-modified Teflon surface is firstly demonstrated for confining continuous fluid flow. The EW-based microfluidic device possesses the functions of a valve and a microchannel without complex moving parts and grooved microchannels. The quantitative characteristics of the EW-based valve are also studied. Propylene carbonate (PC) is firstly demonstrated as the working liquid in the EW-based device because of its applications in parallel oligonucleotide synthesis. It is found that lower valve actuation voltage reduces the deterioration of the valve and improves the valve stability.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

NASA Astrophysics Data System (ADS)

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

PubMed Central

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-01-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. PMID:21974603

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins.

PubMed

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. © 2011 American Institute of Physics

Morphology-Patterned Anisotropic Wetting Surface for Fluid Control and Gas-Liquid Separation in Microfluidics.

PubMed

Wang, Shuli; Yu, Nianzuo; Wang, Tieqiang; Ge, Peng; Ye, Shunsheng; Xue, Peihong; Liu, Wendong; Shen, Huaizhong; Zhang, Junhu; Yang, Bai

2016-05-25

This article shows morphology-patterned stripes as a new platform for directing flow guidance of the fluid in microfluidic devices. Anisotropic (even unidirectional) spreading behavior due to anisotropic wetting of the underlying surface is observed after integrating morphology-patterned stripes with a Y-shaped microchannel. The anisotropic wetting flow of the fluid is influenced by the applied pressure, dimensions of the patterns, including the period and depth of the structure, and size of the channels. Fluids with different surface tensions show different flowing anisotropy in our microdevice. Moreover, the morphology-patterned surfaces could be used as a microvalve, and gas-water separation in the microchannel was realized using the unidirectional flow of water. Therefore, benefiting from their good performance and simple fabrication process, morphology-patterned surfaces are good candidates to be applied in controlling the fluid behavior in microfluidics.

Fabrication and Operation of Microfluidic Hanging-Drop Networks.

PubMed

Misun, Patrick M; Birchler, Axel K; Lang, Moritz; Hierlemann, Andreas; Frey, Olivier

2018-01-01

The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks.

Simple, robust storage of drops and fluids in a microfluidic device.

PubMed

Boukellal, Hakim; Selimović, Seila; Jia, Yanwei; Cristobal, Galder; Fraden, Seth

2009-01-21

We describe a single microfluidic device and two methods for the passive storage of aqueous drops in a continuous stream of oil without any external control but hydrodynamic flow. Advantages of this device are that it is simple to manufacture, robust under operation, and drops never come into contact with each other, making it unnecessary to stabilize drops against coalescence. In one method the device can be used to store drops that are created upstream from the storage zone. In the second method the same device can be used to simultaneously create and store drops from a single large continuous fluid stream without resorting to the usual flow focusing or T-junction drop generation processes. Additionally, this device stores all the fluid introduced, including the first amount, with zero waste. Transport of drops in this device depends, however, on whether or not the aqueous drops wet the device walls. Analysis of drop transport in these two cases is presented. Finally, a method for extraction of the drops from the device is also presented, which works best when drops do not wet the walls of the chip.

Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

PubMed

Mawad, Damia; Figtree, Gemma; Gentile, Carmine

2017-01-01

The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

Development of a microfluidics model for studying migration of sperm in the female reproductive tract

NASA Astrophysics Data System (ADS)

Tung, Chih-Kuan; Ardón, Florencia; Wu, Mingming; Suárez, Susan

2013-03-01

Infertility is a significant issue, both for humans and dairy cattle. In order for fertilization to happen, sperm must migrate through the female reproductive tract to reach the egg in the oviduct (fallopian tube). There is strong evidence that sperm interact with the female tract via both chemical and physical mechanisms. In this work, we focus on how the physical environment of the female tract influences the migration of bull sperm, which also serve as models for human sperm. In order for bull and human sperm to pass from the vagina into the uterus, they must swim through the cervical canal, which is lined by microchannels. Then, sperm must swim through the uterotubal junction, which also contains microchannels, in order to reach the oviduct. In both passageways, sperm must swim against a fluid flow, which would be less in the microchannels than in the central passageways. We have developed a microfluidic model for studying the sperm migration effects of the geometry of the cervix and uterotubal junction and the fluid flow within. Supported by NIH grant 1R01HD070038.

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.

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.

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

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.

A microfluidic direct formate fuel cell on paper.

PubMed

Copenhaver, Thomas S; Purohit, Krutarth H; Domalaon, Kryls; Pham, Linda; Burgess, Brianna J; Manorothkul, Natalie; Galvan, Vicente; Sotez, Samantha; Gomez, Frank A; Haan, John L

2015-08-01

We describe the first direct formate fuel cell on a paper microfluidic platform. In traditional membrane-less microfluidic fuel cells (MFCs), external pumping consumes power produced by the fuel cell in order to maintain co-laminar flow of the anode stream and oxidant stream to prevent mixing. However, in paper microfluidics, capillary action drives flow while minimizing stream mixing. In this work, we demonstrate a paper MFC that uses formate and hydrogen peroxide as the anode fuel and cathode oxidant, respectively. Using these materials we achieve a maximum power density of nearly 2.5 mW/mg Pd. In a series configuration, our MFC achieves an open circuit voltage just over 1 V, and in a parallel configuration, short circuit of 20 mA absolute current. We also demonstrate that the MFC does not require continuous flow of fuel and oxidant to produce power. We found that we can pre-saturate the materials on the paper, stop the electrolyte flow, and still produce approximately 0.5 V for 15 min. This type of paper MFC has potential applications in point-of-care diagnostic devices and other electrochemical sensors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Reversible thermo-pneumatic valves on centrifugal microfluidic platforms.

PubMed

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

2015-08-21

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

Biochemical analysis with microfluidic systems.

PubMed

Bilitewski, Ursula; Genrich, Meike; Kadow, Sabine; Mersal, Gaber

2003-10-01

Microfluidic systems are capillary networks of varying complexity fabricated originally in silicon, but nowadays in glass and polymeric substrates. Flow of liquid is mainly controlled by use of electroosmotic effects, i.e. application of electric fields, in addition to pressurized flow, i.e. application of pressure or vacuum. Because electroosmotic flow rates depend on the charge densities on the walls of capillaries, they are influenced by substrate material, fabrication processes, surface pretreatment procedures, and buffer additives. Microfluidic systems combine the properties of capillary electrophoretic systems and flow-through analytical systems, and thus biochemical analytical assays have been developed utilizing and integrating both aspects. Proteins, peptides, and nucleic acids can be separated because of their different electrophoretic mobility; detection is achieved with fluorescence detectors. For protein analysis, in particular, interfaces between microfluidic chips and mass spectrometers were developed. Further levels of integration of required sample-treatment steps were achieved by integration of protein digestion by immobilized trypsin and amplification of nucleic acids by the polymerase chain reaction. Kinetic constants of enzyme reactions were determined by adjusting different degrees of dilution of enzyme substrates or inhibitors within a single chip utilizing mainly the properties of controlled dosing and mixing liquids within a chip. For analysis of kinase reactions, however, a combination of a reaction step (enzyme with substrate and inhibitor) and a separation step (enzyme substrate and reaction product) was required. Microfluidic chips also enable separation of analytes from sample matrix constituents, which can interfere with quantitative determination, if they have different electrophoretic mobilities. In addition to analysis of nucleic acids and enzymes, immunoassays are the third group of analytical assays performed in microfluidic chips. They utilize either affinity capillary electrophoresis as a homogeneous assay format, or immobilized antigens or antibodies in heterogeneous assays with serial supply of reagents and washing solutions.

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

Magnetic manipulation of particles and cells in ferrofluid flow through straight microchannels using two magnets

NASA Astrophysics Data System (ADS)

Zeng, Jian

Microfluidic devices have been increasingly used in the past two decades for particle and cell manipulations in many chemical and biomedical applications. A variety of force fields have been demonstrated to control particle and cell transport in these devices including electric, magnetic, acoustic, and optical forces etc. Among these particle handling techniques, the magnetic approach provides clear advantages over others such as low cost, noninvasive, and free of fluid heating issues. However, the current knowledge of magnetic control of particle transport is still very limited, especially lacking is the handling of diamagnetic particle. This thesis is focused on the magnetic manipulation of diamagnetic particles and cells in ferrofluid flow through the use of a pair of permanent magnets. By varying the configuration of the two magnets, diverse operations of particles and cells is implemented in a straight microchannel that can potentially be integrated into lab-on-a-chip devices for various applications. First, an approach for embedding two, symmetrically positioned, repulsive permanent magnets about a straight rectangular microchannel in a PDMS-based microfluidic device is developed for particle focusing. Focusing particles and cells into a tight stream is often required in order for continuous detection, counting, and sorting. The closest distance between the magnets is limited only by the size of the magnets involved in the fabrication process. The device is used to implement and investigate the three-dimensional magnetic focusing of polystyrene particles in ferrofluid microflow with both top-view and side-view visualizations. The effects of flow speed and particle size on the particle focusing effectiveness are studied. This device is also applied to magnetically focus yeast cells in ferrofluid, which proves to be biocompatible as verified by cell viability test. In addition, an analytical model is developed and found to be able to predict the experimentally observed particle and cell focusing behaviors with reasonable agreement. Next, a simple magnetic technique to concentrate polystyrene particles and live yeast cells in ferrofluid flow through a straight rectangular microchannel is developed. Concentrating particles to a detectable level is often necessary in many applications. The magnetic field gradient is created by two attracting permanent magnets that are placed on the top and bottom of the planar microfluidic device and held in position by their natural attractive force. The effects of flow speed and magnet-magnet distance are studied and the device was applied for use for concentrating live yeast cells. The magnet-magnet distance is mainly controlled by the thickness of the device substrate and can be made small, providing a locally strengthened magnetic field as well as allowing for the use of dilute ferrofluid in the developed magnetic concentration technique. This advantage not only enables a magnetic/fluorescent label-free handling of diamagnetic particles but also renders such handling biocompatible. Lastly, a device is presented for a size-based continuous separation of particles through a straight rectangular microchannel. Particle separation is critical in many applications involving the sorting of cells. A first magnet is used for focusing the particle mixture into a single stream due to its relative close positioning with respect to the channel, thus creating a greater magnetic field magnitude. Then, a following magnet is used to displace the aligned particles to dissimilar flow paths by placing it farther away compared the first magnet, which provides a weaker magnetic field, therefore more sensitive towards the deflection of particles based on their size. The effects of both flow speed and separator magnet position are examined. The experimental data are found to fit well with analytical model predictions. This is followed by a study replacing the particles which are closely sized to that of live yeast cells and observe the separation of the cells from larger particles. Afterwards, a test for biocompatibility is confirmed.

SIMULATION AND VISUALIZATION OF FLOW PATTERN IN MICROARRAYS FOR LIQUID PHASE OLIGONUCLEOTIDE AND PEPTIDE SYNTHESIS

PubMed Central

O-Charoen, Sirimon; Srivannavit, Onnop; Gulari, Erdogan

2008-01-01

Microfluidic microarrays have been developed for economical and rapid parallel synthesis of oligonucleotide and peptide libraries. For a synthesis system to be reproducible and uniform, it is crucial to have a uniform reagent delivery throughout the system. Computational fluid dynamics (CFD) is used to model and simulate the microfluidic microarrays to study geometrical effects on flow patterns. By proper design geometry, flow uniformity could be obtained in every microreactor in the microarrays. PMID:17480053

Frequency tuning allows flow direction control in microfluidic networks with passive features.

PubMed

Jain, Rahil; Lutz, Barry

2017-05-02

Frequency tuning has emerged as an attractive alternative to conventional pumping techniques in microfluidics. Oscillating (AC) flow driven through a passive valve can be rectified to create steady (DC) flow, and tuning the excitation frequency to the characteristic (resonance) frequency of the underlying microfluidic network allows control of flow magnitude using simple hardware, such as an on-chip piezo buzzer. In this paper, we report that frequency tuning can also be used to control the direction (forward or backward) of the rectified DC flow in a single device. Initially, we observed that certain devices provided DC flow in the "forward" direction expected from previous work with a similar valve geometry, and the maximum DC flow occurred at the same frequency as a prominent peak in the AC flow magnitude, as expected. However, devices of a slightly different geometry provided the DC flow in the opposite direction and at a frequency well below the peak AC flow. Using an equivalent electrical circuit model, we found that the "forward" DC flow occurred at the series resonance frequency (with large AC flow peak), while the "backward" DC flow occurred at a less obvious parallel resonance (a valley in AC flow magnitude). We also observed that the DC flow occurred only when there was a measurable differential in the AC flow magnitude across the valve, and the DC flow direction was from the channel with large AC flow magnitude to that with small AC flow magnitude. Using these observations and the AC flow predictions from the equivalent circuit model, we designed a device with an AC flowrate frequency profile that was expected to allow the DC flow in opposite directions at two distinct frequencies. The fabricated device showed the expected flow reversal at the expected frequencies. This approach expands the flow control toolkit to include both magnitude and direction control in frequency-tuned microfluidic pumps. The work also raises interesting questions about the origin of flow reversal behavior that may be addressed by the further study of the circuit model behavior or dynamic modeling of the fluid-solid mechanics of the valve under the AC flow.

Microfluidics to Mimic Blood Flow in Health and Disease

NASA Astrophysics Data System (ADS)

Sebastian, Bernhard; Dittrich, Petra S.

2018-01-01

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

Development of Droplet Microfluidics Enabling High-Throughput Single-Cell Analysis.

PubMed

Wen, Na; Zhao, Zhan; Fan, Beiyuan; Chen, Deyong; Men, Dong; Wang, Junbo; Chen, Jian

2016-07-05

This article reviews recent developments in droplet microfluidics enabling high-throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic droplets enabling single-cell proteomic analysis; (4) microfluidic droplets enabling single-cell genomic analysis; and (5) integrated microfluidic droplet systems enabling single-cell screening. We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on key performances of throughput, multifunctionality, and absolute quantification.

Optofluidic control of axonal guidance

NASA Astrophysics Data System (ADS)

Gu, Ling; Ordonez, Simon; Black, Bryan; Mohanty, Samarendra K.

2013-03-01

Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

Capillarics: pre-programmed, self-powered microfluidic circuits built from capillary elements.

PubMed

Safavieh, Roozbeh; Juncker, David

2013-11-07

Microfluidic capillary systems employ surface tension effects to manipulate liquids, and are thus self-powered and self-regulated as liquid handling is structurally and chemically encoded in microscale conduits. However, capillary systems have been limited to perform simple fluidic operations. Here, we introduce complex capillary flow circuits that encode sequential flow of multiple liquids with distinct flow rates and flow reversal. We first introduce two novel microfluidic capillary elements including (i) retention burst valves and (ii) robust low aspect ratio trigger valves. These elements are combined with flow resistors, capillary retention valves, capillary pumps, and open and closed reservoirs to build a capillary circuit that, following sample addition, autonomously delivers a defined sequence of multiple chemicals according to a preprogrammed and predetermined flow rate and time. Such a circuit was used to measure the concentration of C-reactive protein. This work illustrates that as in electronics, complex capillary circuits may be built by combining simple capillary elements. We define such circuits as "capillarics", and introduce symbolic representations. We believe that more complex circuits will become possible by expanding the library of building elements and formulating abstract design rules.

Microfluidic Fabrication of Cell Adhesive Chitosan Microtubes

PubMed Central

Oh, Jonghyun; Kim, Keekyoung; Won, Sung Wook; Cha, Chaenyung; Gaharwar, Akhilesh; Selimović, Šeila; Bae, Hojae; Lee, Kwang Ho; Lee, Dong Hwan; Lee, Sang-Hoon; Khademhosseini, Ali

2013-01-01

Chitosan has been used as a scaffolding material in tissue engineering due to its mechanical properties and biocompatibility. With increased appreciation of the effect of micro- and nanoscale environments on cellular behavior, there is increased emphasis on generating microfabricated chitosan structures. Here we employed a microfluidic coaxial flow-focusing system to generate cell adhesive chitosan microtubes of controlled sizes by modifying the flow rates of a chitosan pre-polymer solution and phosphate buffered saline (PBS). The microtubes were extruded from a glass capillary with a 300 μm inner diameter. After ionic crosslinking with sodium tripolyphosphate (TPP), fabricated microtubes had inner and outer diameter ranges of 70-150 μm and 120-185 μm. Computational simulation validated the controlled size of microtubes and cell attachment. To enhance cell adhesiveness on the microtubes, we mixed gelatin with the chitosan pre-polymer solution and adjusted the pH values of the chitosan pre-polymer solution with gelatin and TPP. During the fabrication of microtubes, fibroblasts suspended in core PBS flow adhered to the inner surface of chitosan-gelatin microtubes. To achieve physiological pH values, we adjusted pH values of chiotsan pre-polymer solution and TPP. In particular, we were able to improve cell viability to 92% with pH values of 5.8 and 7.4 for chitosan and TPP solution respectively. Cell culturing for three days showed that the addition of the gelatin enhanced cell spreading and proliferation inside the chitosan-gelatin microtubes. The microfluidic fabrication method for ionically crosslinked chitosan microtubes at physiological pH can be compatible with a variety of cells and used as a versatile platform for microengineered tissue engineering. PMID:23355068

Magnetohydrodynamic pump with a system for promoting flow of fluid in one direction

DOEpatents

Lemoff, Asuncion V [Union City, CA; Lee, Abraham P [Irvine, CA

2010-07-13

A magnetohydrodynamic pump for pumping a fluid. The pump includes a microfluidic channel for channeling the fluid, a MHD electrode/magnet system operatively connected to the microfluidic channel, and a system for promoting flow of the fluid in one direction in the microfluidic channel. The pump has uses in the medical and biotechnology industries for blood-cell-separation equipment, biochemical assays, chemical synthesis, genetic analysis, drug screening, an array of antigen-antibody reactions, combinatorial chemistry, drug testing, medical and biological diagnostics, and combinatorial chemistry. The pump also has uses in electrochromatography, surface micromachining, laser ablation, inkjet printers, and mechanical micromilling.

Micro-Fluidic Device for Drug Delivery

NASA Technical Reports Server (NTRS)

Beebe, David J. (Inventor); Eddington, David T. (Inventor); MacDonald, Michael J. (Inventor); Mensing, Glennys A. (Inventor)

2014-01-01

A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

Microfluidic device for drug delivery

NASA Technical Reports Server (NTRS)

MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Beebe, David J. (Inventor); Mensing, Glennys A. (Inventor)

2010-01-01

A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

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 Droplet Sorting with a High Frequency Ultrasound Beam

PubMed Central

Lee, Changyang; Lee, Jungwoo; Kim, Hyung Ham; Teh, Shia-Yen; Lee, Abraham; Chung, In-Young; Park, Jae Yeong; Shung, K. Kirk

2012-01-01

This paper presents experimental results demonstrating the feasibility of high frequency ultrasonic sensing and sorting for screening single oleic acid (lipid or oil) droplets under continuous flow in a microfluidic channel. In these experiments, hydrodynamically focused lipid droplets of two different diameters (50 μm and 100 μm) are centered along the middle of the channel that is filled with deionized (DI) water. A 30 MHz lithium niobate (LiNbO3) transducer, placed outside the channel, first transmits short sensing pulses to non-invasively determine acoustic scattering properties of individual droplets that are passing through the beam’s focus. Integrated backscatter (IB) coefficients, utilized as a sorting criterion, are measured by analyzing received echo signals from each droplet. When the IB values corresponding to 100 μm droplets are obtained, a custom-built LabVIEW panel commands the transducer to emit sinusoidal burst signals to commence the sorting operation. The number of droplets tested for the sorting is 139 for 50 μm droplets and 95 for 100 μm droplets. The sensing efficiencies are estimated to be 98.6 % and 99.0 %, respectively. The sorting is carried out by applying acoustic radiation forces to 100 μm droplets to direct them towards the upper sheath flow, thus separating them from the centered droplet flow. The sorting efficiencies are 99.3 % for 50 μm droplets and 85.3 % for 100 μm droplets. The results suggest that this proposed technique has the potential to be further developed into a cost-effective and efficient cell/microparticle sorting instrument. PMID:22643737

A flux monitoring method for easy and accurate flow rate measurement in pressure-driven flows.

PubMed

Siria, Alessandro; Biance, Anne-Laure; Ybert, Christophe; Bocquet, Lydéric

2012-03-07

We propose a low-cost and versatile method to measure flow rate in microfluidic channels under pressure-driven flows, thereby providing a simple characterization of the hydrodynamic permeability of the system. The technique is inspired by the current monitoring method usually employed to characterize electro-osmotic flows, and makes use of the measurement of the time-dependent electric resistance inside the channel associated with a moving salt front. We have successfully tested the method in a micrometer-size channel, as well as in a complex microfluidic channel with a varying cross-section, demonstrating its ability in detecting internal shape variations.

Flexible particle flow-focusing in microchannel driven by droplet-directed induced-charge electroosmosis.

PubMed

Ren, Yukun; Liu, Xianyu; Liu, Weiyu; Tao, Ye; Jia, Yankai; Hou, Likai; Li, Wenying; Jiang, Hongyuan

2018-02-01

We report herein a novel microfluidic particle concentrator that utilizes constriction microchannels to enhance the flow-focusing performance of induced-charge electroosmosis (ICEO), where viscous hemi-spherical oil droplets are embedded within the mainchannel to form deformable converging-diverging constriction structures. The constriction region between symmetric oil droplets partially coated on the electrode strips can improve the focusing performance by inducing a granular wake flow area at the diverging channel, which makes almost all of the scattered sample particles trapped within a narrow stream on the floating electrode. Another asymmetric droplet pair arranged near the outlets can further direct the trajectory of focused particle stream to one specified outlet port depending on the symmetry breaking in the shape of opposing phase interfaces. By fully exploiting rectification properties of induced-charge electrokinetic phenomena at immiscible water/oil interfaces of tunable geometry, the expected function of continuous and switchable flow-focusing is demonstrated by preconcentrating both inorganic silica particles and biological yeast cells. Physical mechanisms responsible for particle focusing and locus deflection in the droplet-assisted concentrentor are analyzed in detail, and simulation results are in good accordance with experimental observations. Our work provides new routes to construct flexible electrokinetic framework for preprocessing on-chip biological samples before performing subsequent analysis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 chamber. PMID:26487905

Whole cell quenched flow analysis.

PubMed

Chiang, Ya-Yu; Haeri, Sina; Gizewski, Carsten; Stewart, Joanna D; Ehrhard, Peter; Shrimpton, John; Janasek, Dirk; West, Jonathan

2013-12-03

This paper describes a microfluidic quenched flow platform for the investigation of ligand-mediated cell surface processes with unprecedented temporal resolution. A roll-slip behavior caused by cell-wall-fluid coupling was documented and acts to minimize the compression and shear stresses experienced by the cell. This feature enables high-velocity (100-400 mm/s) operation without impacting the integrity of the cell membrane. In addition, rotation generates localized convection paths. This cell-driven micromixing effect causes the cell to become rapidly enveloped with ligands to saturate the surface receptors. High-speed imaging of the transport of a Janus particle and fictitious domain numerical simulations were used to predict millisecond-scale biochemical switching times. Dispersion in the incubation channel was characterized by microparticle image velocimetry and minimized by using a horizontal Hele-Shaw velocity profile in combination with vertical hydrodynamic focusing to achieve highly reproducible incubation times (CV = 3.6%). Microfluidic quenched flow was used to investigate the pY1131 autophosphorylation transition in the type I insulin-like growth factor receptor (IGF-1R). This predimerized receptor undergoes autophosphorylation within 100 ms of stimulation. Beyond this demonstration, the extreme temporal resolution can be used to gain new insights into the mechanisms underpinning a tremendous variety of important cell surface events.

Direct numerical simulations of three-dimensional electrokinetic flows

NASA Astrophysics Data System (ADS)

Chiam, Keng-Hwee

2006-11-01

We discuss direct numerical simulations of three-dimensional electrokinetic flows in microfluidic devices. In particular, we focus on the study of the electrokinetic instability that develops when two solutions with different electrical conductivities are coupled to an external electric field. We characterize this ``mixing'' instability as a function of the parameters of the model, namely the Reynolds number of the flow, the electric Peclet number of the electrolyte solution, and the ratio of the electroosmotic to the electroviscous time scales. Finally, we describe how this model breaks down when the length scale of the device approaches the nanoscale, where the width of the electric Debye layer is comparable to the width of the channel, and discuss solutions to overcome this.

Fabrication and Operation of Paper-Based Analytical Devices

NASA Astrophysics Data System (ADS)

Jiang, Xiao; Fan, Z. Hugh

2016-06-01

This review focuses on the fabrication techniques and operational components of microfluidic paper-based analytical devices (μPADs). Being low-cost, user-friendly, fast, and simple, μPADs have seen explosive growth in the literature in the last decade. Many different materials and technologies have been employed to fabricate μPADs for various applications, including those that employ patterning, the creation of physical boundaries, and three-dimensional structures. In addition to fabrication techniques, flow control and other operational components in μPADs are of great interest. These components enable μPADs to control flow rates, direct flow paths via valves, sequentially deliver reagents automatically, and display test results, all of which will make μPADs more suitable for point-of-care applications.

Self-Powered Viscosity and Pressure Sensing in Microfluidic Systems Based on the Piezoelectric Energy Harvesting of Flowing Droplets.

PubMed

Wang, Zhao; Tan, Lun; Pan, Xumin; Liu, Gao; He, Yahua; Jin, Wenchao; Li, Meng; Hu, Yongming; Gu, Haoshuang

2017-08-30

The rapid development of microscaled piezoelectric energy harvesters has provided a simple and highly efficient way for building self-powered sensor systems through harvesting the mechanical energy from the ambient environment. In this work, a self-powered microfluidic sensor that can harvest the mechanical energy of the fluid and simultaneously monitor their characteristics was fabricated by integrating the flexible piezoelectric poly(vinylidene fluoride) (PVDF) nanofibers with the well-designed microfluidic chips. Those devices could generate open-circuit high output voltage up to 1.8 V when a droplet of water is flowing past the suspended PVDF nanofibers and result in their periodical deformations. The impulsive output voltage signal allowed them to be utilized for droplets or bubbles counting in the microfluidic systems. Furthermore, the devices also exhibited self-powered sensing behavior due to the decreased voltage amplitude with increasing input pressure and liquid viscosity. The drop of output voltage could be attributed to the variation of flow condition and velocity of the droplets, leading to the reduced deformation of the piezoelectric PVDF layer and the decrease of the generated piezoelectric potential.

Microfluidic based high throughput synthesis of lipid-polymer hybrid nanoparticles with tunable diameters

PubMed Central

Feng, Qiang; Zhang, Lu; Liu, Chao; Li, Xuanyu; Hu, Guoqing; Sun, Jiashu; Jiang, Xingyu

2015-01-01

Core-shell hybrid nanoparticles (NPs) for drug delivery have attracted numerous attentions due to their enhanced therapeutic efficacy and good biocompatibility. In this work, we fabricate a two-stage microfluidic chip to implement a high-throughput, one-step, and size-tunable synthesis of mono-disperse lipid-poly (lactic-co-glycolic acid) NPs. The size of hybrid NPs is tunable by varying the flow rates inside the two-stage microfluidic chip. To elucidate the mechanism of size-controllable generation of hybrid NPs, we observe the flow field in the microchannel with confocal microscope and perform the simulation by a numerical model. Both the experimental and numerical results indicate an enhanced mixing effect at high flow rate, thus resulting in the assembly of small and mono-disperse hybrid NPs. In vitro experiments show that the large hybrid NPs are more likely to be aggregated in serum and exhibit a lower cellular uptake efficacy than the small ones. This microfluidic chip shows great promise as a robust platform for optimization of nano drug delivery system. PMID:26180574

[Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

PubMed

Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

2010-06-01

With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

Partial wetting gas-liquid segmented flow microreactor.

PubMed

Kazemi Oskooei, S Ali; Sinton, David

2010-07-07

A microfluidic reactor strategy for reducing plug-to-plug transport in gas-liquid segmented flow microfluidic reactors is presented. The segmented flow is generated in a wetting portion of the chip that transitions downstream to a partially wetting reaction channel that serves to disconnect the liquid plugs. The resulting residence time distributions show little dependence on channel length, and over 60% narrowing in residence time distribution as compared to an otherwise similar reactor. This partial wetting strategy mitigates a central limitation (plug-to-plug dispersion) while preserving the many attractive features of gas-liquid segmented flow reactors.

Size-sensitive sorting of microparticles through control of flow geometry

NASA Astrophysics Data System (ADS)

Wang, Cheng; Jalikop, Shreyas V.; Hilgenfeldt, Sascha

2011-07-01

We demonstrate a general concept of flow manipulation in microfluidic environments, based on controlling the shape and position of flow domains in order to force switching and sorting of microparticles without moving parts or changes in design geometry. Using microbubble acoustic streaming, we show that regulation of the relative strength of streaming and a superimposed Poiseuille flow allows for size-selective trapping and releasing of particles, with particle size sensitivity much greater than what is imposed by the length scales of microfabrication. A simple criterion allows for quantitative tuning of microfluidic devices for switching and sorting of particles of desired size.

Jetting of a shear banding fluid in rectangular ducts

PubMed Central

Salipante, Paul F.; Little, Charles A. E.; Hudson, Steven D.

2017-01-01

Non-Newtonian fluids are susceptible to flow instabilities such as shear banding, in which the fluid may exhibit a markedly discontinuous viscosity at a critical stress. Here we report the characteristics and causes of a jetting flow instability of shear banding wormlike micelle solutions in microfluidic channels with rectangular cross sections over an intermediate volumetric flow regime. Particle-tracking methods are used to measure the three-dimensional flow field in channels of differing aspect ratios, sizes, and wall materials. When jetting occurs, it is self-contained within a portion of the channel where the flow velocity is greater than the surroundings. We observe that the instability forms in channels with aspect ratio greater than 5, and that the location of the high-velocity jet appears to be sensitive to stress localizations. Jetting is not observed in a lower concentration solution without shear banding. Simulations using the Johnson-Segalman viscoelastic model show a qualitatively similar behavior to the experimental observations and indicate that compressive normal stresses in the cross-stream directions support the development of the jetting flow. Our results show that nonuniform flow of shear thinning fluids can develop across the wide dimension in rectangular microfluidic channels, with implications for microfluidic rheometry. PMID:28691108

A microfluidic fuel cell with flow-through porous electrodes.

PubMed

Kjeang, Erik; Michel, Raphaelle; Harrington, David A; Djilali, Ned; Sinton, David

2008-03-26

A microfluidic fuel cell architecture incorporating flow-through porous electrodes is demonstrated. The design is based on cross-flow of aqueous vanadium redox species through the electrodes into an orthogonally arranged co-laminar exit channel, where the waste solutions provide ionic charge transfer in a membraneless configuration. This flow-through architecture enables improved utilization of the three-dimensional active area inside the porous electrodes and provides enhanced rates of convective/diffusive transport without increasing the parasitic loss required to drive the flow. Prototype fuel cells are fabricated by rapid prototyping with total material cost estimated at 2 USD/unit. Improved performance as compared to previous microfluidic fuel cells is demonstrated, including power densities at room temperature up to 131 mW cm-2. In addition, high overall energy conversion efficiency is obtained through a combination of relatively high levels of fuel utilization and cell voltage. When operated at 1 microL min-1 flow rate, the fuel cell produced 20 mW cm-2 at 0.8 V combined with an active fuel utilization of 94%. Finally, we demonstrate in situ fuel and oxidant regeneration by running the flow-through architecture fuel cell in reverse.

Full-angle tomographic phase microscopy of flowing quasi-spherical cells.

PubMed

Villone, Massimiliano M; Memmolo, Pasquale; Merola, Francesco; Mugnano, Martina; Miccio, Lisa; Maffettone, Pier Luca; Ferraro, Pietro

2017-12-19

We report a reliable full-angle tomographic phase microscopy (FA-TPM) method for flowing quasi-spherical cells along microfluidic channels. This method lies in a completely passive optical system, i.e. mechanical scanning or multi-direction probing of the sample is avoided. It exploits the engineered rolling of cells while they are flowing along a microfluidic channel. Here we demonstrate significant progress with respect to the state of the art of in-flow TPM by showing a general extension to cells having almost spherical shapes while they are flowing in suspension. In fact, the adopted strategy allows the accurate retrieval of rotation angles through a theoretical model of the cells' rotation in a dynamic microfluidic flow by matching it with phase-contrast images resulting from holographic reconstructions. So far, the proposed method is the first and the only one that permits to get in-flow TPM by probing the cells with full-angle, achieving accurate 3D refractive index mapping and the simplest optical setup, simultaneously. Proof of concept experiments were performed successfully on human breast adenocarcinoma MCF-7 cells, opening the way for the full characterization of circulating tumor cells (CTCs) in the new paradigm of liquid biopsy.

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.

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.

Active porous transition towards spatiotemporal control of molecular flow in a crystal membrane

NASA Astrophysics Data System (ADS)

Takasaki, Yuichi; Takamizawa, Satoshi

2015-11-01

Fluidic control is an essential technology widely found in processes such as flood control in land irrigation and cell metabolism in biological tissues. In any fluidic control system, valve function is the key mechanism used to actively regulate flow and miniaturization of fluidic regulation with precise workability will be particularly vital in the development of microfluidic control. The concept of crystal engineering is alternative to processing technology in microstructure construction, as the ultimate microfluidic devices must provide molecular level control. Consequently, microporous crystals can instantly be converted to microfluidic devices if introduced in an active transformability of porous structure and geometry. Here we show that the introduction of a stress-induced martensitic transition mechanism converts a microporous molecular crystal into an active fluidic device with spatiotemporal molecular flow controllability through mechanical reorientation of subnanometre channels.

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

High-throughput microfluidic line scan imaging for cytological characterization

NASA Astrophysics Data System (ADS)

Hutcheson, Joshua A.; Powless, Amy J.; Majid, Aneeka A.; Claycomb, Adair; Fritsch, Ingrid; Balachandran, Kartik; Muldoon, Timothy J.

2015-03-01

Imaging cells in a microfluidic chamber with an area scan camera is difficult due to motion blur and data loss during frame readout causing discontinuity of data acquisition as cells move at relatively high speeds through the chamber. We have developed a method to continuously acquire high-resolution images of cells in motion through a microfluidics chamber using a high-speed line scan camera. The sensor acquires images in a line-by-line fashion in order to continuously image moving objects without motion blur. The optical setup comprises an epi-illuminated microscope with a 40X oil immersion, 1.4 NA objective and a 150 mm tube lens focused on a microfluidic channel. Samples containing suspended cells fluorescently stained with 0.01% (w/v) proflavine in saline are introduced into the microfluidics chamber via a syringe pump; illumination is provided by a blue LED (455 nm). Images were taken of samples at the focal plane using an ELiiXA+ 8k/4k monochrome line-scan camera at a line rate of up to 40 kHz. The system's line rate and fluid velocity are tightly controlled to reduce image distortion and are validated using fluorescent microspheres. Image acquisition was controlled via MATLAB's Image Acquisition toolbox. Data sets comprise discrete images of every detectable cell which may be subsequently mined for morphological statistics and definable features by a custom texture analysis algorithm. This high-throughput screening method, comparable to cell counting by flow cytometry, provided efficient examination including counting, classification, and differentiation of saliva, blood, and cultured human cancer cells.

Giant Volume Change of Active Gels under Continuous Flow

DTIC Science & Technology

2014-04-21

harnessing chemical energy to produce motion, for example, using the energy released by ATP hydrolysis to power the directed movement of muscle fibers or micro ...microfluidic systems to generate capsules of biopolymer hydrogels, Herr demonstrated the use of gels for automated microfluidic protein blotting,13 Wu...active gels driven by the Belousov−Zhabotinsky reaction. These results demon- strate that microfluidics offers a useful and facile experimental

Design and fabrication of uniquely shaped thiol-ene microfibers using a two-stage hydrodynamic focusing design.

PubMed

Boyd, Darryl A; Shields, Adam R; Howell, Peter B; Ligler, Frances S

2013-08-07

Microfluidic systems have advantages that are just starting to be realized for materials fabrication. In addition to the more common use for fabrication of particles, hydrodynamic focusing has been used to fabricate continuous polymer fibers. We have previously described such a microfluidics system which has the ability to generate fibers with controlled cross-sectional shapes locked in place by in situ photopolymerization. The previous fiber fabrication studies produced relatively simple round or ribbon shapes, demonstrated the use of a variety of polymers, and described the interaction between sheath-core flow-rate ratios used to control the fiber diameter and the impact on possible shapes. These papers documented the fact that no matter what the intended shape, higher flow-rate ratios produced rounder fibers, even in the absence of interfacial tension between the core and sheath fluids. This work describes how to fabricate the next generation of fibers predesigned to have a much more complex geometry, as exemplified by the "double anchor" shape. Critical to production of the pre-specified fibers with complex features was independent control over both the shape and the size of the fabricated microfibers using a two-stage hydrodynamic focusing system. Design and optimization of the channels was performed using finite element simulations and confocal imaging to characterize each of the two stages theoretically and experimentally. The resulting device design was then used to generate thiol-ene fibers with a unique double anchor shape. Finally, proof-of-principle functional experiments demonstrated the ability of the fibers to transport fluids and to interlock laterally.

Microfluidic method for measuring viscosity using images from smartphone

NASA Astrophysics Data System (ADS)

Kim, Sooyeong; Kim, Kyung Chun; Yeom, Eunseop

2018-05-01

The viscosity of a fluid is the most important characteristic in fluid rheology. Many microfluidic devices have been proposed for easily measuring the fluid viscosity of small samples. A hybrid system consisting of a smartphone and microfluidic device can offer a mobile laboratory for performing a wide range of detection and analysis functions related to healthcare. In this study, a new mobile sensing method based on a microfluidic device was proposed for fluid viscosity measurements. By separately delivering sample and reference fluids into the two inlets of a Y-shaped microfluidic device, an interfacial line is induced at downstream of the device. Because the interfacial width (W) between the sample and reference fluid flows was determined by their pressure ratio, the viscosity (μ) of the sample could be estimated by measuring the interfacial width. To distinguish the interfacial width of a sample, optical images of the flows at downstream of the Y-shaped microfluidic device were acquired using a smartphone. To check the measurement accuracy of the proposed method, the viscosities of glycerol mixtures were compared with those measured by a conventional viscometer. The proposed technique was applied to monitor the variations in blood and oil samples depending on storage or rancidity. We expect that this mobile sensing method based on a microfluidic device could be utilized as a viscometer with significant advantages in terms of mobility, ease-of-operation, and data management.

Electrostatic actuators for portable microfluidic systems

NASA Astrophysics Data System (ADS)

Tice, Joshua

Both developed and developing nations have an urgent need to diagnose disease cheaply, reliably, and independently of centralized facilities. Microfulidic platforms are well-positioned to address the need for portable diagnostics, mainly due to their obvious advantage in size. However, most microfluidic methods rely on equipment outside of the chip either for driving fluid flow (e.g., syringe pumps) or for taking measurements (e.g., lasers or microscopes). The energy and space requirements of the whole system inhibit portability and contribute to costs. To capitalize on the strengths of microfluidic platforms and address the serious needs of society, system components need to be miniaturized. Also, miniaturization should be accomplished as simply as possible, considering that simplicity is usually requisite for achieving truly transformative technology. Herein, I attempt to address the issue of controlling fluid flow in portable microfluidic systems. I focus on systems that are driven by elastomer-based membrane valves, since these valves are inherently simple, yet they are capable of sophisticated fluid manipulation. Others have attempted to modify pneumatic microvalves for portable applications, e.g., by transitioning to electromagnetic, thermopneumatic, or piezoelectric actuation principles. However, none of these strategies maintain the proper balance of simplicity, functionality, and ease of integration. My research centers on electrostatic actuators, due to their conceptual simplicity and the efficacy of electrostatic forces on the microscale. To ensure easy integration with polymer-based systems, and to maintain simplicity in the fabrication procedure, the actuators were constructed solely from poly(dimethylsiloxane) and multi-walled carbon nanotubes. In addition, the actuators were fabricated exclusively with soft-lithographic techniques. A mathematical model was developed to identify actuator parameters compatible with soft-lithography, and also to minimize actuation potentials while eliminating stiction. Two strategies were developed to overcome challenges with electrode screening in the presence of aqueous fluids. First, instead of using the electrostatic actuators to interact directly with aqueous solutions, the actuators were used to regulate pressurized control lines for pneumatic microvalves. Secondly, by adopting a normally-closed architecture, the actuators were converted into microvalves capable of directly interacting with aqueous solutions. The two strategies are complementary, and together should enable sophisticated microfluidic systems for applications ranging from point-of-care diagnostics to portable chemical detection. To conclude the dissertation, I demonstrate a proof-of-principle microfluidic system that contained sixteen independently-operated electrostatic valves, operated with battery-operated electrical ancillaries in a hand-held format.

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

Observation and experimental investigation of confinement effects on ion transport and electrokinetic flows at the microscale

PubMed Central

Benneker, Anne M.; Wood, Jeffery A.; Tsai, Peichun A.; Lammertink, Rob G. H.

2016-01-01

Electrokinetic effects adjacent to charge-selective interfaces (CSI) have been experimentally investigated in microfluidic platforms in order to gain understanding on underlying phenomena of ion transport at elevated applied voltages. We experimentally investigate the influence of geometry and multiple array densities of the CSI on concentration and flow profiles in a microfluidic set-up using nanochannels as the CSI. Particle tracking obtained under chronoamperometric measurements show the development of vortices in the microchannel adjacent to the nanochannels. We found that the direction of the electric field and the potential drop inside the microchannel has a large influence on the ion transport through the interface, for example by inducing immediate wall electroosmotic flow. In microfluidic devices, the electric field may not be directed normal to the interface, which can result in an inefficient use of the CSI. Multiple vortices are observed adjacent to the CSI, growing in size and velocity as a function of time and dependent on their location in the microfluidic device. Local velocities inside the vortices are measured to be more than 1.5 mm/s. Vortex speed, as well as flow speed in the channel, are dependent on the geometry of the CSI and the distance from the electrode. PMID:27853257

Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

NASA Astrophysics Data System (ADS)

Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

2016-02-01

Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

Microfluidic-SANS: flow processing of complex fluids

NASA Astrophysics Data System (ADS)

Lopez, Carlos G.; Watanabe, Takaichi; Martel, Anne; Porcar, Lionel; Cabral, João T.

2015-01-01

Understanding and engineering the flow-response of complex and non-Newtonian fluids at a molecular level is a key challenge for their practical utilisation. Here we demonstrate the coupling of microfluidics with small angle neutron scattering (SANS). Microdevices with high neutron transmission (up to 98%), low scattering background (), broad solvent compatibility and high pressure tolerance (~3-15 bar) are rapidly prototyped via frontal photo polymerisation. Scattering from single microchannels of widths down to 60 μm, with beam footprint of 500 μm diameter, was successfully obtained in the scattering vector range 0.01-0.3 Å-1, corresponding to real space dimensions of . We demonstrate our approach by investigating the molecular re-orientation and alignment underpinning the flow response of two model complex fluids, namely cetyl trimethylammonium chloride/pentanol/D2O and sodium lauryl sulfate/octanol/brine lamellar systems. Finally, we assess the applicability and outlook of microfluidic-SANS for high-throughput and flow processing studies, with emphasis of soft matter.

Microfluidic step-emulsification in a cylindrical geometry

NASA Astrophysics Data System (ADS)

Chakraborty, Indrajit; Leshansky, Alexander M.

2016-11-01

The model microfluidic device for high-throughput droplet generation in a confined cylindrical geometry is investigated numerically. The device comprises of core-annular pressure-driven flow of two immiscible viscous liquids through a cylindrical capillary connected co-axially to a tube of a larger diameter through a sudden expansion, mimicking the microfluidic step-emulsifier (1). To study this problem, the numerical simulations of axisymmetric Navier-Stokes equations have been carried out using an interface capturing procedure based on coupled level set and volume-of-fluid (CLSVOF) methods. The accuracy of the numerical method was favorably tested vs. the predictions of the linear stability analysis of core-annular two-phase flow in a cylindrical capillary. Three distinct flow regimes can be identified: the dripping (D) instability near the entrance to the capillary, the step- (S) and the balloon- (B) emulsification at the step-like expansion. Based on the simulation results we present the phase diagram quantifying transitions between various regimes in plane of the capillary number and the flow-rate ratio. MICROFLUSA EU H2020 project.

Microfluidic redox battery.

PubMed

Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

2013-07-07

A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

Adhesion and formation of microbial biofilms in complex microfluidic devices

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

Kumar, Aloke; Karig, David K; Neethirajan, Suresh

2012-01-01

Shewanella oneidensis is a metal reducing bacterium, which is of interest for bioremediation and clean energy applications. S. oneidensis biofilms play a critical role in several situations such as in microbial energy harvesting devices. Here, we use a microfluidic device to quantify the effects of hydrodynamics on the biofilm morphology of S. oneidensis. For different rates of fluid flow through a complex microfluidic device, we studied the spatiotemporal dynamics of biofilms, and we quantified several morphological features such as spatial distribution, cluster formation and surface coverage. We found that hydrodynamics resulted in significant differences in biofilm dynamics. The baffles inmore » the device created regions of low and high flow in the same device. At higher flow rates, a nonuniform biofilm develops, due to unequal advection in different regions of the microchannel. However, at lower flow rates, a more uniform biofilm evolved. This depicts competition between adhesion events, growth and fluid advection. Atomic force microscopy (AFM) revealed that higher production of extra-cellular polymeric substances (EPS) occurred at higher flow velocities.« less

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.

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.

Microfluidics and Raman microscopy: current applications and future challenges.

PubMed

Chrimes, Adam F; Khoshmanesh, Khashayar; Stoddart, Paul R; Mitchell, Arnan; Kalantar-Zadeh, Kourosh

2013-07-07

Raman microscopy systems are becoming increasingly widespread and accessible for characterising chemical species. Microfluidic systems are also progressively finding their way into real world applications. Therefore, it is anticipated that the integration of Raman systems with microfluidics will become increasingly attractive and practical. This review aims to provide an overview of Raman microscopy-microfluidics integrated systems for researchers who are actively interested in utilising these tools. The fundamental principles and application strengths of Raman microscopy are discussed in the context of microfluidics. Various configurations of microfluidics that incorporate Raman microscopy methods are presented, with applications highlighted. Data analysis methods are discussed, with a focus on assisting the interpretation of Raman-microfluidics data from complex samples. Finally, possible future directions of Raman-microfluidic systems are presented.

Microfluidics-Based in Vivo Mimetic Systems for the Study of Cellular Biology

PubMed Central

2015-01-01

Conspectus The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system’s components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years that focus on modeling both biophysical and biochemical interactions in cellular communication, such as flow and cell–cell networks. We also describe more advanced systems that mimic higher level biological networks, such as organ on-a-chip and animal on-a-chip models. Since the first papers in the early 1990s, interest in the bioanalytical use of microfluidics has grown significantly. Advances in micro-/nanofabrication technology have allowed researchers to produce miniaturized, biocompatible assay platforms suitable for microfluidic studies in biochemistry and chemical biology. Well-designed microfluidic platforms can achieve quick, in vitro analyses on pico- and femtoliter volume samples that are temporally, spatially, and chemically resolved. In addition, controlled cell culture techniques using a microfluidic platform have produced biomimetic systems that allow researchers to replicate and monitor physiological interactions. Pioneering work has successfully created cell–fluid, cell–cell, cell–tissue, tissue–tissue, even organ-like level interfaces. Researchers have monitored cellular behaviors in these biomimetic microfluidic environments, producing validated model systems to understand human pathophysiology and to support the development of new therapeutics. PMID:24555566

Microfluidics-based in vivo mimetic systems for the study of cellular biology.

PubMed

Kim, Donghyuk; Wu, Xiaojie; Young, Ashlyn T; Haynes, Christy L

2014-04-15

The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system's components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years that focus on modeling both biophysical and biochemical interactions in cellular communication, such as flow and cell-cell networks. We also describe more advanced systems that mimic higher level biological networks, such as organ on-a-chip and animal on-a-chip models. Since the first papers in the early 1990s, interest in the bioanalytical use of microfluidics has grown significantly. Advances in micro-/nanofabrication technology have allowed researchers to produce miniaturized, biocompatible assay platforms suitable for microfluidic studies in biochemistry and chemical biology. Well-designed microfluidic platforms can achieve quick, in vitro analyses on pico- and femtoliter volume samples that are temporally, spatially, and chemically resolved. In addition, controlled cell culture techniques using a microfluidic platform have produced biomimetic systems that allow researchers to replicate and monitor physiological interactions. Pioneering work has successfully created cell-fluid, cell-cell, cell-tissue, tissue-tissue, even organ-like level interfaces. Researchers have monitored cellular behaviors in these biomimetic microfluidic environments, producing validated model systems to understand human pathophysiology and to support the development of new therapeutics.

Commensurability-driven structural defects in double emulsions produced with two-step microfluidic techniques.

PubMed

Schmit, Alexandre; Salkin, Louis; Courbin, Laurent; Panizza, Pascal

2014-07-14

The combination of two drop makers such as flow focusing geometries or ┬ junctions is commonly used in microfluidics to fabricate monodisperse double emulsions and novel fluid-based materials. Here we investigate the physics of the encapsulation of small droplets inside large drops that is at the core of such processes. The number of droplets per drop studied over time for large sequences of consecutive drops reveals that the dynamics of these systems are complex: we find a succession of well-defined elementary patterns and defects. We present a simple model based on a discrete approach that predicts the nature of these patterns and their non-trivial scheme of arrangement in a sequence as a function of the ratio of the two timescales of the problem, the production times of droplets and drops. Experiments validate our model as they concur very well with predictions.

Rational selection of substrates to improve color intensity and uniformity on microfluidic paper-based analytical devices.

PubMed

Evans, Elizabeth; Gabriel, Ellen Flávia Moreira; Coltro, Wendell Karlos Tomazelli; Garcia, Carlos D

2014-05-07

A systematic investigation was conducted to study the effect of paper type on the analytical performance of a series of microfluidic paper-based analytical devices (μPADs) fabricated using a CO2 laser engraver. Samples included three different grades of Whatman chromatography paper, and three grades of Whatman filter paper. According to the data collected and the characterization performed, different papers offer a wide range of flow rate, thickness, and pore size. After optimizing the channel widths on the μPAD, the focus of this study was directed towards the color intensity and color uniformity formed during a colorimetric enzymatic reaction. According to the results herein described, the type of paper and the volume of reagents dispensed in each detection zone can determine the color intensity and uniformity. Therefore, the objective of this communication is to provide rational guidelines for the selection of paper substrates for the fabrication of μPADs.

Macro- and microscale fluid flow systems for endothelial cell biology.

PubMed

Young, Edmond W K; Simmons, Craig A

2010-01-21

Recent advances in microfluidics have brought forth new tools for studying flow-induced effects on mammalian cells, with important applications in cardiovascular, bone and cancer biology. The plethora of microscale systems developed to date demonstrate the flexibility of microfluidic designs, and showcase advantages of the microscale that are simply not available at the macroscale. However, the majority of these systems will likely not achieve widespread use in the biological laboratory due to their complexity and lack of user-friendliness. To gain widespread acceptance in the biological research community, microfluidics engineers must understand the needs of cell biologists, while biologists must be made aware of available technology. This review provides a critical evaluation of cell culture flow (CCF) systems used to study the effects of mechanical forces on endothelial cells (ECs) in vitro. To help understand the need for various designs of CCF systems, we first briefly summarize main properties of ECs and their native environments. Basic principles of various macro- and microscale systems are described and evaluated. New opportunities are uncovered for developing technologies that have potential to both improve efficiency of experimentation as well as answer important biological questions that otherwise cannot be tackled with existing systems. Finally, we discuss some of the unresolved issues related to microfluidic cell culture, suggest possible avenues of investigation that could resolve these issues, and provide an outlook for the future of microfluidics in biological research.

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 method was also successfully applied to measure viscosities of blood with varying hematocrits, chemically fixed RBCS, and channel sizes. Based on these experimental results, the proposed method can be effectively used to measure the viscosities of various fluids easily, without any fluorescent labeling and tedious calibration procedures. PMID:24404040

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.

Finger-Powered Electro-Digital-Microfluidics.

PubMed

Peng, Cheng; Ju, Y Sungtaek

2017-01-01

Portable microfluidic devices are promising for point-of-care (POC) diagnosis and bio- and environmental surveillance in resource-constrained or non-laboratory environments. Lateral-flow devices, some built off paper or strings, have been widely developed but the fixed layouts of their underlying wicking/microchannel structures limit their flexibility and present challenges in implementing multistep reactions. Digital microfluidics can circumvent these difficulties by addressing discrete droplets individually. Existing approaches to digital microfluidics, however, often require bulky power supplies/batteries and high voltage circuits. We present a scheme to drive digital microfluidic devices by converting mechanical energy of human fingers to electrical energy using an array of piezoelectric elements. We describe the integration our scheme into two promising digital microfluidics platforms: one based on the electro-wetting-on-dielectric (EWOD) phenomenon and the other on the electrophoretic control of droplet (EPD). Basic operations of droplet manipulations, such as droplet transport, merging and splitting, are demonstrated using the finger-powered digital-microfluidics.

Formation of Cucurbit[8]uril-Based Supramolecular Hydrogel Beads Using Droplet-Based Microfluidics.

PubMed

Xu, Xuejiao; Appel, Eric A; Liu, Xin; Parker, Richard M; Scherman, Oren A; Abell, Chris

2015-09-14

Herein we describe the use of microdroplets as templates for the fabrication of uniform-sized supramolecular hydrogel beads, assembled by supramolecular cross-linking of functional biopolymers with the macrocyclic host molecule, cucurbit[8]uril (CB[8]). The microdroplets were formed containing diluted hydrogel precursors in solution, including the functional polymers and CB[8], in a microfluidic device. Subsequent evaporation of water from collected microdroplets concentrated the contents, driving the formation of the CB[8]-mediated host-guest ternary complex interactions and leading to the assembly of condensed three-dimensional polymeric scaffolds. Rehydration of the dried particles gave monodisperse hydrogel beads. Their equilibrium size was shown to be dependent on both the quantity of material loaded and the dimensions of the microfluidic flow focus. Fluorescein-labeled dextran was used to evaluate the efficacy of the hydrogel beads as a vector for controlled cargo release. Both passive, sustained release (hours) and triggered, fast release (minutes) of the FITC-dextran was observed, with the rate of sustained release dependent on the formulation. The kinetics of release was fitted to the Ritger-Peppas controlled release equation and shown to follow an anomalous (non-Fickian) transport mechanism.

The importance of microfluidics for the preparation of nanoparticles as advanced drug delivery systems.

PubMed

Martins, João Pedro; Torrieri, Giulia; Santos, Hélder A

2018-05-01

Nanoparticles are anticipated to overcome persistent challenges in efficient drug delivery, but the limitations associated with conventional methods of preparation are resulting in slow translation from research to clinical applications. Due to their enormous potential, microfluidic technologies have emerged as an advanced approach for the development of drug delivery systems with well-defined physicochemical characteristics and in a reproducible manner. Areas covered: This review provides an overview of microfluidic devices and materials used for their manufacturing, together with the flow patterns and regimes commonly used for nanoparticle preparation. Additionally, the different geometries used in droplet microfluidics are reviewed, with particular attention to the co-flow geometry used for the production of nanoparticles. Finally, this review summarizes the main and most recent nanoparticulate systems prepared using microfluidics, including drug nanosuspensions, polymeric, lipid, structured, and theranostic nanoparticles. Expert opinion: The production of nanoparticles at industrial scale is still a challenge, but the microfluidic technologies bring exciting opportunities to develop drug delivery systems that can be engineered in an easy, cost-effective and reproducible manner. As a highly interdisciplinary research field, more efforts and general acceptance are needed to allow for the translation of nanoparticulate drug delivery systems from academic research to the clinical practice.

Engineering controllable architecture in matrigel for 3D cell alignment.

PubMed

Jang, Jae Myung; Tran, Si-Hoai-Trung; Na, Sang Cheol; Jeon, Noo Li

2015-02-04

We report a microfluidic approach to impart alignment in ECM components in 3D hydrogels by continuously applying fluid flow across the bulk gel during the gelation process. The microfluidic device where each channel can be independently filled was tilted at 90° to generate continuous flow across the Matrigel as it gelled. The presence of flow helped that more than 70% of ECM components were oriented along the direction of flow, compared with randomly cross-linked Matrigel. Following the oriented ECM components, primary rat cortical neurons and mouse neural stem cells showed oriented outgrowth of neuronal processes within the 3D Matrigel matrix.

Characterization of an induced pressure pumping force for microfluidics

NASA Astrophysics Data System (ADS)

Jiang, Hai; Fan, Na; Peng, Bei; Weng, Xuan

2017-05-01

The electro-osmotic pumping and pressure-driven manipulation of fluids are considered as the most common strategies in microfluidic devices. However, both of them exhibit major disadvantages such as hard integration and high reagent consumption, and they are destructive methods for detection and photo bleaching. In this paper, an electric field-effect flow control approach, combining the electro-osmotic pumping force and the pressure-driven pumping force, was developed to generate the induced pressure-driven flow in a T-shaped microfluidic chip. Electro-osmotic flow between the T-intersection and two reservoirs was demonstrated, and it provided a stable, continuous, and electric field-free flow in the section of the microchannel without the electrodes. The velocity of the induced pressure-driven flow was linearly proportional to the applied voltages. Both numerical and experimental investigations were conducted to prove the concept, and the experimental results showed good agreement with the numerical simulations. In comparison to other induced pressure pumping methods, this approach can induce a high and controllable pressure drop in the electric field-free segment, subsequently causing an induced pressure-driven flow for transporting particles or biological cells. In addition, the generation of bubbles and the blocking of the microchannel are avoided.

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

PubMed

Alapan, Yunus; Hasan, Muhammad Noman; Shen, Richang; Gurkan, Umut A

2015-05-01

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices

PubMed Central

Shen, Richang; Gurkan, Umut A.

2016-01-01

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing. PMID:27512530

Photoresponsive Passive Micromixers Based on Spiropyran Size-Tunable Hydrogels.

PubMed

Ter Schiphorst, Jeroen; Melpignano, Giuseppe G; Amirabadi, Hossein Eslami; Houben, Menno H J M; Bakker, Sterre; den Toonder, Jaap M J; Schenning, Albertus P H J

2018-01-01

Microfluidic devices allow the manipulation of fluids down to the micrometer scale and are receiving a lot of attention for applications where low volumes and high throughputs are required. In these micro channels, laminar flow usually dominates, which requires long residence times of the fluids, limiting the flow speed and throughput. Here a switchable passive mixer has been developed to control mixing and to easily clean microchannels. The mixer is based on a photoresponsive spiropyran based hydrogel of which the dimensions can be tuned by changing the intensity of the light. The size-tunable gels have been used to fabricate a passive slanted groove mixer that can be switched off by light allowing to change mixing of microfluidics to non-mixed flows. These findings open new possibilities for multi-purpose microfluidic devices where mixers and valves can be tuned by light. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

There can be turbulence in microfluidics at low Reynolds number.

PubMed

Wang, G R; Yang, Fang; Zhao, Wei

2014-04-21

Turbulence is commonly viewed as a type of macroflow, where the Reynolds number (Re) has to be sufficiently high. In microfluidics, when Re is below or on the order of 1 and fast mixing is required, so far only chaotic flow has been reported to enhance mixing based on previous publications since turbulence is believed not to be possible to generate in such a low Re microflow. There is even a lack of velocimeter that can measure turbulence in microchannels. In this work, we report a direct observation of the existence of turbulence in microfluidics with Re on the order of 1 in a pressure driven flow under electrokinetic forcing using a novel velocimeter having ultrahigh spatiotemporal resolution. The work could provide a new method to control flow and transport phenomena in lab-on-a-chip and a new perspective on turbulence.

Screw-actuated displacement micropumps for thermoplastic microfluidics.

PubMed

Han, J Y; Rahmanian, O D; Kendall, E L; Fleming, N; DeVoe, D L

2016-10-05

The fabrication of on-chip displacement pumps integrated into thermoplastic chips is explored as a simple and low cost method for achieving precise and programmable flow control for disposable microfluidic systems. The displacement pumps consist of stainless steel screws inserted into threaded ports machined into a thermoplastic substrate which also serve as on-chip reagent storage reservoirs. Three different methods for pump sealing are investigated to enable high pressure flows without leakage, and software-defined control of multiple pumps is demonstrated in a self-contained platform using a compact and self-contained microcontroller for operation. Using this system, flow rates ranging from 0.5-40 μl min -1 are demonstrated. The pumps are combined with on-chip burst valves to fully seal multiple reagents into fabricated chips while providing on-demand fluid distribution in a downstream microfluidic network, and demonstrated for the generation of size-tunable water-in-oil emulsions.

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.

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.

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.

Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels.

PubMed

Liu, Chao; Xue, Chundong; Chen, Xiaodong; Shan, Lei; Tian, Yu; Hu, Guoqing

2015-06-16

Viscoelasticity-induced particle migration has recently received increasing attention due to its ability to obtain high-quality focusing over a wide range of flow rates. However, its application is limited to low throughput regime since the particles can defocus as flow rate increases. Using an engineered carrier medium with constant and low viscosity and strong elasticity, the sample flow rates are improved to be 1 order of magnitude higher than those in existing studies. Utilizing differential focusing of particles of different sizes, here, we present sheathless particle/cell separation in simple straight microchannels that possess excellent parallelizability for further throughput enhancement. The present method can be implemented over a wide range of particle/cell sizes and flow rates. We successfully separate small particles from larger particles, MCF-7 cells from red blood cells (RBCs), and Escherichia coli (E. coli) bacteria from RBCs in different straight microchannels. The proposed method could broaden the applications of viscoelastic microfluidic devices to particle/cell separation due to the enhanced sample throughput and simple channel design.

Flow lithography in ultraviolet-curable polydimethylsiloxane microfluidic chips

PubMed Central

Kim, Junbeom; An, Heseong; Seo, Yoojin; Jung, Youngmee; Lee, Jong Suk; Bong, Ki Wan

2017-01-01

Flow Lithography (FL) is the technique used for the synthesis of hydrogel microparticles with various complex shapes and distinct chemical compositions by combining microfluidics with photolithography. Although polydimethylsiloxane (PDMS) has been used most widely as almost the sole material for FL, PDMS microfluidic chips have limitations: (1) undesired shrinkage due to the thermal expansion of masters used for replica molding and (2) interfacial delamination between two thermally cured PDMS layers. Here, we propose the utilization of ultraviolet (UV)-curable PDMS (X-34-4184) for FL as an excellent alternative material of the conventional PDMS. Our proposed utilization of the UV-curable PDMS offers three key advantages, observed in our study: (1) UV-curable PDMS exhibited almost the same oxygen permeability as the conventional PDMS. (2) The almost complete absence of shrinkage facilitated the fabrication of more precise reverse duplication of microstructures. (3) UV-cured PDMS microfluidic chips were capable of much stronger interfacial bonding so that the burst pressure increased to ∼0.9 MPa. Owing to these benefits, we demonstrated a substantial improvement of productivity in synthesizing polyethylene glycol diacrylate microparticles via stop flow lithography, by applying a flow time (40 ms) an order of magnitude shorter. Our results suggest that UV-cured PDMS chips can be used as a general platform for various types of flow lithography and also be employed readily in other applications where very precise replication of structures on micro- or sub-micrometer scales and/or strong interfacial bonding are desirable. PMID:28469763

Inexpensive, rapid fabrication of polymer-film microfluidic autoregulatory valve for disposable microfluidics.

PubMed

Zhang, Xinjie; Zhu, Zhixian; Ni, Zhonghua; Xiang, Nan; Yi, Hong

2017-06-01

This work presents the fabrication of a microfluidic autoregulatory valve which is composed of several layers of thin polymer films (i.e., polyvinyl chloride (PVC), polyethylene terephthalate (PET) double-sided tape, and polydimethylsiloxane (PDMS)). Briefly, pulsed UV laser is employed to cut the microstructures of through grooves or holes in the thermoplastic polymer films, and then the polymer-film valves are precisely assembled through laminating the PDMS membranes to the thermoplastic polymer films through the roll-lamination method. The effective bonding between the PVC film and the PDMS membrane is realized using the planar seal method, and the valve is sandwiched and compressed by a home-made housing to achieve the good seal effect. Then, the flow performances of the prototype valve are examined, and constant flow autoregulation is realized under the static or dynamic test pressures. The long-term response of the valve is also studied and minimum flow-rate decrements are found over a long actuation time. The fabrication method proposed in this work is successful for the low-cost and fast prototyping of the polymer-film valve. We believe our method will also be broadly applicable for fabrication of other low-cost and disposable polymer-film microfluidic devices.

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.

Direct 3D-printing of cell-laden constructs in microfluidic architectures.

PubMed

Liu, Justin; Hwang, Henry H; Wang, Pengrui; Whang, Grace; Chen, Shaochen

2016-04-21

Microfluidic platforms have greatly benefited the biological and medical fields, however standard practices require a high cost of entry in terms of time and energy. The utilization of three-dimensional (3D) printing technologies has greatly enhanced the ability to iterate and build functional devices with unique functions. However, their inability to fabricate within microfluidic devices greatly increases the cost of producing several different devices to examine different scientific questions. In this work, a variable height micromixer (VHM) is fabricated using projection 3D-printing combined with soft lithography. Theoretical and flow experiments demonstrate that altering the local z-heights of VHM improved mixing at lower flow rates than simple geometries. Mixing of two fluids occurs as low as 320 μL min(-1) in VHM whereas the planar zigzag region requires a flow rate of 2.4 mL min(-1) before full mixing occurred. Following device printing, to further demonstrate the ability of this projection-based method, complex, user-defined cell-laden scaffolds are directly printed inside the VHM. The utilization of this unique ability to produce 3D tissue models within a microfluidic system could offer a unique platform for medical diagnostics and disease modeling.

Geo-material microfluidics at reservoir conditions for subsurface energy resource applications.

PubMed

Porter, Mark L; Jiménez-Martínez, Joaquín; Martinez, Ricardo; McCulloch, Quinn; Carey, J William; Viswanathan, Hari S

2015-10-21

Microfluidic investigations of flow and transport in porous and fractured media have the potential to play a significant role in the development of future subsurface energy resource technologies. However, the majority of experimental systems to date are limited in applicability due to operating conditions and/or the use of engineered material micromodels. We have developed a high pressure and temperature microfluidic experimental system that allows for direct observations of flow and transport within geo-material micromodels (e.g. rock, cement) at reservoir conditions. In this manuscript, we describe the experimental system, including our novel micromodel fabrication method that works in both geo- and engineered materials and utilizes 3-D tomography images of real fractures as micromodel templates to better represent the pore space and fracture geometries expected in subsurface formations. We present experimental results that highlight the advantages of using real-rock micromodels and discuss potential areas of research that could benefit from geo-material microfluidic investigations. The experiments include fracture-matrix interaction in which water imbibes into the shale rock matrix from etched fractures, supercritical CO2 (scCO2) displacing brine in idealized and realistic fracture patterns, and three-phase flow involving scCO2-brine-oil.

Optical measurement of transverse molecular diffusion in a microchannel.

PubMed Central

Kamholz, A E; Schilling, E A; Yager, P

2001-01-01

Quantitative analysis of molecular diffusion is a necessity for the efficient design of most microfluidic devices as well as an important biophysical method in its own right. This study demonstrates the rapid measurement of diffusion coefficients of large and small molecules in a microfluidic device, the T-sensor, by means of conventional epifluorescence microscopy. Data were collected by monitoring the transverse flux of analyte from a sample stream into a second stream flowing alongside it. As indicated by the low Reynolds numbers of the system (< 1), flow is laminar, and molecular transport between streams occurs only by diffusion. Quantitative determinations were made by fitting data with predictions of a one-dimensional model. Analysis was made of the flow development and its effect on the distribution of diffusing analyte using a three-dimensional modeling software package. Diffusion coefficients were measured for four fluorescently labeled molecules: fluorescein-biotin, insulin, ovalbumin, and streptavidin. The resulting values differed from accepted results by an average of 2.4%. Microfluidic system parameters can be selected to achieve accurate diffusion coefficient measurements and to optimize other microfluidic devices that rely on precise transverse transport of molecules. PMID:11259309

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

PubMed Central

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

2012-01-01

The motion of a suspension of red blood cells (RBCs) flowing in a Y-shaped bifurcating microfluidic channel is investigated using a validated low-dimensional RBC (LD-RBC) model based on dissipative particle dynamics (DPD). Specifically, the RBC is represented as a closed torus-like ring of ten colloidal particles, which leads to efficient simulations of blood flow in microcirculation over a wide range of hematocrits. Adaptive no-slip wall boundary conditions were implemented to model hydrodynamic flow within a specific wall structure of diverging 3D microfluidic channels, paying attention to controlling density fluctuations. Plasma skimming and the all-or-nothing phenomenon of RBCs in a bifurcating microfluidic channel have been investigated in our simulations for healthy and diseased blood, including the size of cell-free layer on the daughter branches. The feed hematocrit level in the parent channel has considerable influence on blood-plasma separation. Compared to the blood-plasma separation efficiencies of healthy RBCs, malaria-infected stiff RBCs (iRBCs) have a tendency to travel into the low flowrate daughter branch because of their different initial distribution in the parent channel. Our simulation results are consistent with previously published experimental results and theoretical predictions. PMID:22476709

Advances in microfluidics for drug discovery.

PubMed

Lombardi, Dario; Dittrich, Petra S

2010-11-01

Microfluidics is considered as an enabling technology for the development of unconventional and innovative methods in the drug discovery process. The concept of micrometer-sized reaction systems in the form of continuous flow reactors, microdroplets or microchambers is intriguing, and the versatility of the technology perfectly fits with the requirements of drug synthesis, drug screening and drug testing. In this review article, we introduce key microfluidic approaches to the drug discovery process, highlighting the latest and promising achievements in this field, mainly from the years 2007 - 2010. Despite high expectations of microfluidic approaches to several stages of the drug discovery process, up to now microfluidic technology has not been able to significantly replace conventional drug discovery platforms. Our aim is to identify bottlenecks that have impeded the transfer of microfluidics into routine platforms for drug discovery and show some recent solutions to overcome these hurdles. Although most microfluidic approaches are still applied only for proof-of-concept studies, thanks to creative microfluidic research in the past years unprecedented novel capabilities of microdevices could be demonstrated, and general applicable, robust and reliable microfluidic platforms seem to be within reach.

Core-shell hydrogel beads with extracellular matrix for tumor spheroid formation.

PubMed

Yu, L; Grist, S M; Nasseri, S S; Cheng, E; Hwang, Y-C E; Ni, C; Cheung, K C

2015-03-01

Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since they may provide a better model of the tumor than conventional monolayer culture. Moreover, tumor cell interaction with the extracellular matrix can determine cell organization and behavior. In this work, a microfluidic system was used to form cell-laden core-shell beads which incorporate elements of the extracellular matrix and support the formation of multicellular spheroids. The bead core (comprising a mixture of alginate, collagen, and reconstituted basement membrane, with gelation by temperature control) and shell (comprising alginate hydrogel, with gelation by ionic crosslinking) were simultaneously formed through flow focusing using a cooled flow path into the microfluidic chip. During droplet gelation, the alginate acts as a fast-gelling shell which aids in preventing droplet coalescence and in maintaining spherical droplet geometry during the slower gelation of the collagen and reconstituted basement membrane components as the beads warm up. After droplet gelation, the encapsulated MCF-7 cells proliferated to form uniform spheroids when the beads contained all three components: alginate, collagen, and reconstituted basement membrane. The dose-dependent response of the MCF-7 cell tumor spheroids to two anticancer drugs, docetaxel and tamoxifen, was compared to conventional monolayer culture.

Microscale fluid transport using optically controlled marangoni effect

DOEpatents

Thundat, Thomas G [Knoxville, TN; Passian, Ali [Knoxville, TN; Farahi, Rubye H [Oak Ridge, TN

2011-05-10

Low energy light illumination and either a doped semiconductor surface or a surface-plasmon supporting surface are used in combination for manipulating a fluid on the surface in the absence of any applied electric fields or flow channels. Precise control of fluid flow is achieved by applying focused or tightly collimated low energy light to the surface-fluid interface. In the first embodiment, with an appropriate dopant level in the semiconductor substrate, optically excited charge carriers are made to move to the surface when illuminated. In a second embodiment, with a thin-film noble metal surface on a dispersive substrate, optically excited surface plasmons are created for fluid manipulation. This electrode-less optical control of the Marangoni effect provides re-configurable manipulations of fluid flow, thereby paving the way for reprogrammable microfluidic devices.

A simple method for the evaluation of microfluidic architecture using flow quantitation via a multiplexed fluidic resistance measurement.

PubMed

Leslie, Daniel C; Melnikoff, Brett A; Marchiarullo, Daniel J; Cash, Devin R; Ferrance, Jerome P; Landers, James P

2010-08-07

Quality control of microdevices adds significant costs, in time and money, to any fabrication process. A simple, rapid quantitative method for the post-fabrication characterization of microchannel architecture using the measurement of flow with volumes relevant to microfluidics is presented. By measuring the mass of a dye solution passed through the device, it circumvents traditional gravimetric and interface-tracking methods that suffer from variable evaporation rates and the increased error associated with smaller volumes. The multiplexed fluidic resistance (MFR) measurement method measures flow via stable visible-wavelength dyes, a standard spectrophotometer and common laboratory glassware. Individual dyes are used as molecular markers of flow for individual channels, and in channel architectures where multiple channels terminate at a common reservoir, spectral deconvolution reveals the individual flow contributions. On-chip, this method was found to maintain accurate flow measurement at lower flow rates than the gravimetric approach. Multiple dyes are shown to allow for independent measurement of multiple flows on the same device simultaneously. We demonstrate that this technique is applicable for measuring the fluidic resistance, which is dependent on channel dimensions, in four fluidically connected channels simultaneously, ultimately determining that one chip was partially collapsed and, therefore, unusable for its intended purpose. This method is thus shown to be widely useful in troubleshooting microfluidic flow characteristics.

Dispersion of a Nanoliter Bolus in Microfluidic Co-Flow.

PubMed

Conway, A J; Saadi, W M; Sinatra, F L; Kowalski, G; Larson, D; Fiering, J

2014-03-01

Microfluidic systems enable reactions and assays on the scale of nanoliters. However, at this scale nonuniformities in sample delivery become significant. To determine the fundamental minimum sample volume required for a particular device, a detailed understanding of mass transport is required. Co-flowing laminar streams are widely used in many devices, but typically only in the steady-state. Because establishing the co-flow steady-state consumes excess sample volume and time, there is a benefit to operating devices in the transient state, which predominates as the volume of the co-flow reactor decreases. Analysis of the co-flow transient has been neglected thus far. In this work we describe the fabrication of a pneumatically controlled microfluidic injector constructed to inject a discrete 50nL bolus into one side of a two-stream co-flow reactor. Using dye for image analysis, injections were performed at a range of flow rates from 0.5-10μL/min, and for comparison we collected the co-flow steady-state data for this range. The results of the image analysis were also compared against theory and simulations for device validation. For evaluation, we established a metric that indicates how well the mass distribution in the bolus injection approximates steady-state co-flow. Using such analysis, transient-state injections can approximate steady-state conditions within predefined errors, allowing straight forward measurements to be performed with reduced reagent consumption.

Development of a microimpedance pump for pulsatile flow transport - Part : Flow characteristics of the microimpedance pump. Part 2: A systematic study of steady and pulsatile transport in microscale cavities

NASA Astrophysics Data System (ADS)

Rinderknecht, Derek

Microfluidics offers an effective means to carry out a wide range of transport processes within a controlled microenvironment by drawing on the benefits imparted by increasing surface area to volume ratio at the microscale. Critical to the impact of microfluidics on integrated devices in the fields of bioengineering and biomedicine is the ability to transport fluids and biomolecules effectively particularly at the size scales involved. In this context a bio-inspired pumping mechanism, the valveless impedance pump, was explored for applications in microfluidics ranging from micro total analysis systems to microchannel cooling. Adhering to the basic principles of the impedance pump mechanism, pumps have been constructed at a variety of size scales from a few centimeters to a few hundred microns. The micro impedance pump is valveless, bidirectional, and can be constructed simply from a wide range of materials. Depending on the size of the pump flow rates range from nL/min to mL/min and pressures can be generated that exceed 20 kPa. Another benefit of the impedance pump is the pulsatile flow output which can be used in the context of microfluidic applications to enhance transport at low Reynolds numbers as well as metering in drug delivery. Pulsatile flow was therefore investigated as a method of augmenting transport in microfluidic systems. Micro PIV was used to study the affect of both steady and pulsatile flows on transport at low Reynolds number was examined in microscale rectangular cavities. Ventilation of the cavity contents was examined in terms of the residence time or average time a particle remains in the cavity region. Lagrangian coherent structures (LCS) were applied to empirical velocity fields to determine the impact of unsteadiness on time dependent boundaries to fluid transport present in the flow. Experimental results show that there are both frequencies which are beneficial and detrimental to cavity ventilation as well as certain frequencies which more evenly distribute particles originating in the cavity throughout the freestream.

Discrete microfluidics: Reorganizing droplet arrays at a bend

NASA Astrophysics Data System (ADS)

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

2009-10-01

Microfluidic manipulation of densely packed droplet arrangements (i.e., gel emulsions) using sharp microchannel bends was studied as a function of bend angle, droplet volume fraction, droplet size, and flow velocity. Emulsion reorganization was found to be specifically dependent on the pathlength that the droplets are forced to travel as they navigate the bend under spatial confinement. We describe how bend-induced droplet displacements might be exploited in complex, droplet-based microfluidics.

Microfluidic inertial focusing fundamentals, limitations and applications for biomedical sample processing

NASA Astrophysics Data System (ADS)

Reece, Amy E.

The microfabrication of microfluidic control systems and advances in molecular amplification tools has enabled the miniaturization of single cell analytical platforms for the efficient, highly selective enumeration and molecular characterization of rare and diseased cells from clinical samples. In many cases, the high-throughput nature of microfluidic inertial focusing has enabled the popularization of this new class of Lab-on-a-Chip devices that exhibit numerous advantages over conventional methods as prognostic and diagnostic tools. Inertial focusing is the passive, sheathless alignment of particles and cells to precise spatiotemporal equilibrium positions that arise from a force balance between opposing inertial lift forces and hydrodynamic repulsions. The applicability of inertial focusing to a spectrum of filtration, separation and encapsulation challenges places heavy emphasis upon the accurate description of the hydrodynamic forces responsible for predictable inertial focusing behavior. These inertial focusing fundamentals, limitations and their applications are studied extensively throughout this work.

Easy monitoring of velocity fields in microfluidic devices using spatiotemporal image correlation spectroscopy.

PubMed

Travagliati, Marco; Girardo, Salvatore; Pisignano, Dario; Beltram, Fabio; Cecchini, Marco

2013-09-03

Spatiotemporal image correlation spectroscopy (STICS) is a simple and powerful technique, well established as a tool to probe protein dynamics in cells. Recently, its potential as a tool to map velocity fields in lab-on-a-chip systems was discussed. However, the lack of studies on its performance has prevented its use for microfluidics applications. Here, we systematically and quantitatively explore STICS microvelocimetry in microfluidic devices. We exploit a simple experimental setup, based on a standard bright-field inverted microscope (no fluorescence required) and a high-fps camera, and apply STICS to map liquid flow in polydimethylsiloxane (PDMS) microchannels. Our data demonstrates optimal 2D velocimetry up to 10 mm/s flow and spatial resolution down to 5 μm.

Ionic electroactive polymer actuators as active microfluidic mixers

DOE PAGES

Meis, Catherine; Montazami, Reza; Hashemi, Nastaran

2015-11-06

On-chip sample processing is integral to the continued development of lab-on-a-chip devices for various applications. An active microfluidic mixer prototype is proposed using ionic electroactive polymer actuators (IEAPAs) as artificial cilia. A proof-of-concept experiment was performed in which the actuators were shown to produce localized flow pattern disruptions in the laminar flow regime. Suggestions for further engineering and optimization of a scaled-down, complete device are provided. Furthermore, the device in its current state of development necessitates further engineering, the use of IEAPAs addresses issues currently associated with the use of electromechanical actuators as active microfluidic mixers and may prove tomore » be a useful alternative to other similar materials.« less

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

PubMed Central

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

2015-01-01

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

Single-cell trapping and selective treatment via co-flow within a microfluidic platform.

PubMed

Benavente-Babace, A; Gallego-Pérez, D; Hansford, D J; Arana, S; Pérez-Lorenzo, E; Mujika, M

2014-11-15

Lab on a chip (LOC) systems provide interesting and low-cost solutions for key studies and applications in the biomedical field. Along with microfluidics, these microdevices make single-cell manipulation possible with high spatial and temporal resolution. In this work we have designed, fabricated and characterized a versatile and inexpensive microfluidic platform for on-chip selective single-cell trapping and treatment using laminar co-flow. The combination of co-existing laminar flow manipulation and hydrodynamic single-cell trapping for selective treatment offers a cost-effective solution for studying the effect of novel drugs on single-cells. The operation of the whole system is experimentally simple, highly adaptable and requires no specific equipment. As a proof of concept, a cytotoxicity study of ethanol in isolated hepatocytes is presented. The developed microfluidic platform controlled by means of co-flow is an attractive and multipurpose solution for the study of new substances of high interest in cell biology research. In addition, this platform will pave the way for the study of cell behavior under dynamic and controllable fluidic conditions providing information at the individual cell level. Thus, this analysis device could also hold a great potential to easily use the trapped cells as sensing elements expanding its functionalities as a cell-based biosensor with single-cell resolution. Copyright © 2014 Elsevier B.V. All rights reserved.

The pumping lid: investigating multi-material 3D printing for equipment-free, programmable generation of positive and negative pressures for microfluidic applications.

PubMed

Begolo, Stefano; Zhukov, Dmitriy V; Selck, David A; Li, Liang; Ismagilov, Rustem F

2014-12-21

Equipment-free pumping is a challenging problem and an active area of research in microfluidics, with applications for both laboratory and limited-resource settings. This paper describes the pumping lid method, a strategy to achieve equipment-free pumping by controlled generation of pressure. Pressure was generated using portable, lightweight, and disposable parts that can be integrated with existing microfluidic devices to simplify workflow and eliminate the need for pumping equipment. The development of this method was enabled by multi-material 3D printing, which allows fast prototyping, including composite parts that combine materials with different mechanical properties (e.g. both rigid and elastic materials in the same part). The first type of pumping lid we describe was used to produce predictable positive or negative pressures via controlled compression or expansion of gases. A model was developed to describe the pressures and flow rates generated with this approach and it was validated experimentally. Pressures were pre-programmed by the geometry of the parts and could be tuned further even while the experiment was in progress. Using multiple lids or a composite lid with different inlets enabled several solutions to be pumped independently in a single device. The second type of pumping lid, which relied on vapor-liquid equilibrium to generate pressure, was designed, modeled, and experimentally characterized. The pumping lid method was validated by controlling flow in different types of microfluidic applications, including the production of droplets, control of laminar flow profiles, and loading of SlipChip devices. We believe that applying the pumping lid methodology to existing microfluidic devices will enhance their use as portable diagnostic tools in limited resource settings as well as accelerate adoption of microfluidics in laboratories.

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.

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

Hydrodynamic Assists Magnetophoreses Rare Cancer cells Separation in Microchannel Simulation and Experimental Verifications

NASA Astrophysics Data System (ADS)

Saeed, O.; Duru, L.; Yulin, D.

2018-05-01

A proposed microfluidic design has been fabricated and simulated using COMSOL Multiphysics software, based on two physical models included in this design. The device’s ability to create a narrow stream of the core sample by controlling the sheath flow rates Qs1 and Qs2 in both peripheral channels was investigated. The main target of this paper is to study the possibility of combing the hydrodynamic and magnetic techniques, in order to achieve a high rate of cancer cells separation from a cell mixture and/or buffer sample. The study has been conducted in two stages, firstly, the effects of the sheath flow rates (Qs1 and Qs2) on the sample stream focusing were studied, to find the proposed device effectiveness optimal conditions and its capability in cell focusing, and then the magnetic mechanism has been utilized to finalize the pre-labelled cells separation process.

A Multi-Phase Based Fluid-Structure-Microfluidic interaction sensor for Aerodynamic Shear Stress

NASA Astrophysics Data System (ADS)

Hughes, Christopher; Dutta, Diganta; Bashirzadeh, Yashar; Ahmed, Kareem; Qian, Shizhi

2014-11-01

A novel innovative microfluidic shear stress sensor is developed for measuring shear stress through multi-phase fluid-structure-microfluidic interaction. The device is composed of a microfluidic cavity filled with an electrolyte liquid. Inside the cavity, two electrodes make electrochemical velocimetry measurements of the induced convection. The cavity is sealed with a flexible superhydrophobic membrane. The membrane will dynamically stretch and flex as a result of direct shear cross-flow interaction with the seal structure, forming instability wave modes and inducing fluid motion within the microfluidic cavity. The shear stress on the membrane is measured by sensing the induced convection generated by membrane deflections. The advantages of the sensor over current MEMS based shear stress sensor technology are: a simplified design with no moving parts, optimum relationship between size and sensitivity, no gaps such as those created by micromachining sensors in MEMS processes. We present the findings of a feasibility study of the proposed sensor including wind-tunnel tests, microPIV measurements, electrochemical velocimetry, and simulation data results. The study investigates the sensor in the supersonic and subsonic flow regimes. Supported by a NASA SBIR phase 1 contract.

Foundations of chaotic mixing.

PubMed

Wiggins, Stephen; Ottino, Julio M

2004-05-15

The simplest mixing problem corresponds to the mixing of a fluid with itself; this case provides a foundation on which the subject rests. The objective here is to study mixing independently of the mechanisms used to create the motion and review elements of theory focusing mostly on mathematical foundations and minimal models. The flows under consideration will be of two types: two-dimensional (2D) 'blinking flows', or three-dimensional (3D) duct flows. Given that mixing in continuous 3D duct flows depends critically on cross-sectional mixing, and that many microfluidic applications involve continuous flows, we focus on the essential aspects of mixing in 2D flows, as they provide a foundation from which to base our understanding of more complex cases. The baker's transformation is taken as the centrepiece for describing the dynamical systems framework. In particular, a hierarchy of characterizations of mixing exist, Bernoulli --> mixing --> ergodic, ordered according to the quality of mixing (the strongest first). Most importantly for the design process, we show how the so-called linked twist maps function as a minimal picture of mixing, provide a mathematical structure for understanding the type of 2D flows that arise in many micromixers already built, and give conditions guaranteeing the best quality mixing. Extensions of these concepts lead to first-principle-based designs without resorting to lengthy computations.

Nematic director reorientation at solid and liquid interfaces under flow: SAXS studies in a microfluidic device

DOE PAGES

Silva, Bruno F. B.; Zepeda-Rosales, Miguel; Venkateswaran, Neeraja; ...

2014-10-30

In this work we investigate the interplay between flow and boundary condition effects on the orientation field of a thermotropic nematic liquid crystal under flow and confinement in a microfluidic device. Two types of experiments were performed using synchrotron small-angle X-ray-scattering (SAXS). In the first, a nematic liquid crystal flows through a square-channel cross section at varying flow rates, while the nematic director orientation projected onto the velocity/velocity gradient plane is measured using a 2D detector. At moderate-to-high flow rates, the nematic director is predominantly aligned in the flow direction, but with a small tilt angle of ~±11° in themore » velocity gradient direction. The director tilt angle is constant throughout most of the channel width but switches sign when crossing the center of the channel, in agreement with the Ericksen–Leslie–Parodi (ELP) theory. At low flow rates, boundary conditions begin to dominate, and a flow profile resembling the escaped radial director configuration is observed, where the director is seen to vary more smoothly from the edges (with homeotropic alignment) to the center of the channel. In the second experiment, hydrodynamic focusing is employed to confine the nematic phase into a sheet of liquid sandwiched between two layers of Triton X-100 aqueous solutions. The average nematic director orientation shifts to some extent from the flow direction toward the liquid boundaries, although it remains unclear if one tilt angle is dominant through most of the nematic sheet (with abrupt jumps near the boundaries) or if the tilt angle varies smoothly between two extreme values (~90 and 0°). Lastly, the technique presented here could be applied to perform high-throughput measurements for assessing the influence of different surfactants on the orientation of nematic phases and may lead to further improvements in areas such as boundary lubrication and clarifying the nature of defect structures in LC displays.« less

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.

Microfluidics for producing poly (lactic-co-glycolic acid)-based pharmaceutical nanoparticles.

PubMed

Li, Xuanyu; Jiang, Xingyu

2017-12-24

Microfluidic chips allow the rapid production of a library of nanoparticles (NPs) with distinct properties by changing the precursors and the flow rates, significantly decreasing the time for screening optimal formulation as carriers for drug delivery compared to conventional methods. The batch-to-batch reproducibility which is essential for clinical translation is achieved by precisely controlling the precursors and the flow rate, regardless of operators. Poly (lactic-co-glycolic acid) (PLGA) is the most widely used Food and Drug Administration (FDA)-approved biodegradable polymers. Researchers often combine PLGA with lipids or amphiphilic molecules to assemble into a core/shell structure to exploit the potential of PLGA-based NPs as powerful carriers for cancer-related drug delivery. In this review, we discuss the advantages associated with microfluidic chips for producing PLGA-based functional nanocomplexes for drug delivery. These laboratory-based methods can readily scale up to provide sufficient amount of PLGA-based NPs in microfluidic chips for clinical studies and industrial-scale production. Copyright © 2017. Published by Elsevier B.V.

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.

Compact electrochemical sensor system and method for field testing for metals in saliva or other fluids

DOEpatents

Lin, Yuehe; Bennett, Wendy D.; Timchalk, Charles; Thrall, Karla D.

2004-03-02

Microanalytical systems based on a microfluidics/electrochemical detection scheme are described. Individual modules, such as microfabricated piezoelectrically actuated pumps and a microelectrochemical cell were integrated onto portable platforms. This allowed rapid change-out and repair of individual components by incorporating "plug and play" concepts now standard in PC's. Different integration schemes were used for construction of the microanalytical systems based on microfluidics/electrochemical detection. In one scheme, all individual modules were integrated in the surface of the standard microfluidic platform based on a plug-and-play design. Microelectrochemical flow cell which integrated three electrodes based on a wall-jet design was fabricated on polymer substrate. The microelectrochemical flow cell was then plugged directly into the microfluidic platform. Another integration scheme was based on a multilayer lamination method utilizing stacking modules with different functionality to achieve a compact microanalytical device. Application of the microanalytical system for detection of lead in, for example, river water and saliva samples using stripping voltammetry is described.

Construction of microscale structures in enclosed microfluidic networks by using a magnetic beads based method.

PubMed

Wang, Zhenyu; Zhang, Xiaojuan; Yang, Jun; Yang, Zhong; Wan, Xiaoping; Hu, Ning; Zheng, Xiaolin

2013-08-20

A large number of microscale structures have been used to elaborate flowing control or complex biological and chemical reaction on microfluidic chips. However, it is still inconvenient to fabricate microstructures with different heights (or depths) on the same substrate. These kinds of microstructures can be fabricated by using the photolithography and wet-etching method step by step, but involves time-consuming design and fabrication process, as well as complicated alignment of different masters. In addition, few existing methods can be used to perform fabrication within enclosed microfluidic networks. It is also difficult to change or remove existing microstructures within these networks. In this study, a magnetic-beads-based approach is presented to build microstructures in enclosed microfluidic networks. Electromagnetic field generated by microfabricated conducting wires (coils) is used to manipulate and trap magnetic beads on the bottom surface of a microchannel. These trapped beads are accumulated to form a microscale pile with desired shape, which can adjust liquid flow, dock cells, modify surface, and do some other things as those fabricated microstructures. Once the electromagnetic field is changed, trapped beads may form new shapes or be removed by a liquid flow. Besides being used in microfabrication, this magnetic-beads-based method can be used for novel microfluidic manipulation. It has been validated by forming microscale dam structure for cell docking and modified surface for cell patterning, as well as guiding the growth of neurons. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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.

Microfluidic filtration and extraction of pathogens from food samples by hydrodynamic focusing and inertial lateral migration.

PubMed

Clime, Liviu; Hoa, Xuyen D; Corneau, Nathalie; Morton, Keith J; Luebbert, Christian; Mounier, Maxence; Brassard, Daniel; Geissler, Matthias; Bidawid, Sabah; Farber, Jeff; Veres, Teodor

2015-02-01

Detecting pathogenic bacteria in food or other biological samples with lab-on-a-chip (LOC) devices requires several sample preparation steps prior to analysis which commonly involves cleaning complex sample matrices of large debris. This often underestimated step is important to prevent these larger particles from clogging devices and to preserve initial concentrations when LOC techniques are used to concentrate or isolate smaller target microorganisms for downstream analysis. In this context, we developed a novel microfluidic system for membrane-free cleaning of biological samples from debris particles by combining hydrodynamic focusing and inertial lateral migration effects. The microfluidic device is fabricated using thermoplastic elastomers being compatible with thermoforming fabrication techniques leading to low-cost single-use devices. Microfluidic chip design and pumping protocols are optimized by investigating diffusive losses numerically with coupled Navier-Stokes and convective-diffusion theoretical models. Stability of inertial lateral migration and separation of debris is assessed through fluorescence microscopy measurements with labelled particles serving as a model system. Efficiency of debris cleaning is experimentally investigated by monitoring microchip outlets with in situ optical turbidity sensors, while retention of targeted pathogens (i.e., Listeria monocytogenes) within the sample stream is assessed through bacterial culture techniques. Optimized pumping protocols can remove up to 50 % of debris from ground beef samples while percentage for preserved microorganisms can account for 95 % in relatively clean samples. However, comparison between inoculated turbid and clean samples (i.e., with and without ground beef debris) indicate some degree of interference between debris inertial lateral migration and hydrodynamic focusing of small microorganisms. Although this interference can lead to significant decrease in chip performance through loss of target bacteria, it remains possible to reach 70 % for sample recovery and more than 50 % for debris removal even in the most turbid samples tested. Due to the relatively simple design, the robustness of the inertial migration effect itself, the high operational flow rates and fabrication methods that leverage low-cost materials, the proposed device can have an impact on a wide range of applications where high-throughput separation of particles and biological species is of interest.

"Connecting worlds - a view on microfluidics for a wider application".

PubMed

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

From its birth, microfluidics has been referenced as a revolutionary technology and the solution to long standing technological and sociological issues, such as detection of dilute compounds and personalized healthcare. Microfluidics has for example been envisioned as: (1) being capable of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient's skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However, the current state of microfluidics, although technologically advanced, has so far failed to reach the originally promised widespread use. In this paper, some of the aspects are identified and discussed that have prevented microfluidics from reaching its full potential, especially in the chemical engineering and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, "plug and play" approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates, reactions and operation conditions, and other microfluidic systems is indeed of surmount importance and current academic and industrial approaches to modular microfluidics are presented. Furthermore, two views on the commercialization of plug-and-play microfluidics systems, leading towards improved acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors in microfluidics. The proposed guidelines are then applied for the development of two different example platforms, and to three examples taken from literature. With this work, we aim to provide an interesting perspective on the field of microfluidics when applied to chemical engineering and biotechnology studies, as well as to contribute with potential solutions to some of its current challenges. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Computer design of microfluidic mixers for protein/RNA folding studies.

PubMed

Inguva, Venkatesh; Kathuria, Sagar V; Bilsel, Osman; Perot, Blair James

2018-01-01

Kinetic studies of biological macromolecules increasingly use microfluidic mixers to initiate and monitor reaction progress. A motivation for using microfluidic mixers is to reduce sample consumption and decrease mixing time to microseconds. Some applications, such as small-angle x-ray scattering, also require large (>10 micron) sampling areas to ensure high signal-to-noise ratios and to minimize parasitic scattering. Chaotic to marginally turbulent mixers are well suited for these applications because this class of mixers provides a good middle ground between existing laminar and turbulent mixers. In this study, we model various chaotic to marginally turbulent mixing concepts such as flow turning, flow splitting, and vortex generation using computational fluid dynamics for optimization of mixing efficiency and observation volume. Design iterations show flow turning to be the best candidate for chaotic/marginally turbulent mixing. A qualitative experimental test is performed on the finalized design with mixing of 10 M urea and water to validate the flow turning unsteady mixing concept as a viable option for RNA and protein folding studies. A comparison of direct numerical simulations (DNS) and turbulence models suggests that the applicability of turbulence models to these flow regimes may be limited.

Uniform, stable supply of medium for in vitro cell culture using a robust chamber

NASA Astrophysics Data System (ADS)

Wei, Juan; Liu, Chong; Jiang, Yang; Liu, Tao; Chen, Li; Liu, Bo; Li, Jingmin

2018-06-01

A uniform, stable supply of medium is important for in vitro cell culture. In this paper, a microfluidic device is presented for culturing cells inside a robust chamber with continuous perfusion of medium. The device consists of a main channel, two bifurcated channels and a culture chamber. The culture chamber connects to the bifurcated channels via multiple paths, and distributes symmetrically on the main channel, to improve the efficiency of medium exchange. Furthermore, regular polygonal chambers with various numbers of edges have been designed, to study the effects of chamber shape on flow fields. The finite element method has been employed to predict the effects of multiple paths on the uniformity and stability of flow fields in the culture chamber. Particle tracking technology has been used to evaluate the flow fields in the chambers, and PC-12 cells have been cultured using the microfluidic device, to test its validity. The results of simulation and experiment indicate that the microfluidic design could provide a continuous interstitial-like flow microenvironment, with a relatively stable and uniform supply of medium.

Integrated microfluidic flowmeter based on a micro-FBG inscribed in Co²⁺-doped optical fiber.

PubMed

Liu, Zhengyong; Tse, Ming-Leung Vincent; Zhang, A Ping; Tam, Hwa-Yaw

2014-10-15

A novel microfluidic flowmeter integrated with microfiber Bragg grating (µFBG) is presented. Two glass capillaries and a short length of high-light-absorption Co²⁺-doped optical fiber were stacked inside a larger outer capillary tube. The stack was then drawn into a tapered device. Two microchannels with the diameter of ~50  μm were formed inside the capillaries for flowing of microfluidics. An FBG was inscribed in the tapered Co²⁺-doped fiber with waist diameter of ~70  μm, and acts as a flow-rate sensor. A pump laser with wavelength of 1480 nm was utilized to locally heat the µFBG, rendering the µFBG as miniature "hot-wire" flowmeter. The flow rate of the liquid in the microchannels is determined by the induced wavelength shift of the µFBG. The experimental results achieve a minimum detectable change of ~16  nL/s in flow rate, which is very promising in the use as part of biochips.

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.

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

DOEpatents

Jacobson, Stephen C.; Ramsey, J. Michael

2010-06-01

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

Pulsed laser activated cell sorter (PLACS) for high-throughput fluorescent mammalian cell sorting

NASA Astrophysics Data System (ADS)

Chen, Yue; Wu, Ting-Hsiang; Chung, Aram; Kung, Yu-Chung; Teitell, Michael A.; Di Carlo, Dino; Chiou, Pei-Yu

2014-09-01

We present a Pulsed Laser Activated Cell Sorter (PLACS) realized by exciting laser induced cavitation bubbles in a PDMS microfluidic channel to create high speed liquid jets to deflect detected fluorescent samples for high speed sorting. Pulse laser triggered cavitation bubbles can expand in few microseconds and provide a pressure higher than tens of MPa for fluid perturbation near the focused spot. This ultrafast switching mechanism has a complete on-off cycle less than 20 μsec. Two approaches have been utilized to achieve 3D sample focusing in PLACS. One is relying on multilayer PDMS channels to provide 3D hydrodynamic sheath flows. It offers accurate timing control of fast (2 m sec-1) passing particles so that synchronization with laser bubble excitation is possible, an critically important factor for high purity and high throughput sorting. PLACS with 3D hydrodynamic focusing is capable of sorting at 11,000 cells/sec with >95% purity, and 45,000 cells/sec with 45% purity using a single channel in a single step. We have also demonstrated 3D focusing using inertial flows in PLACS. This sheathless focusing approach requires 10 times lower initial cell concentration than that in sheath-based focusing and avoids severe sample dilution from high volume sheath flows. Inertia PLACS is capable of sorting at 10,000 particles sec-1 with >90% sort purity.

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.

Quasi-stokeslet induced by thermoplasmonic Marangoni effect around a water vapor microbubble

PubMed Central

Namura, Kyoko; Nakajima, Kaoru; Suzuki, Motofumi

2017-01-01

Rapid Marangoni flows around a water vapor microbubble (WVMB) is investigated using the thermoplasmonic effect of a gold nanoisland film (GNF). By focusing a laser onto the GNF, a stable WVMB with a diameter of ~10 μm is generated in degassed water, while an air bubble generated in non-degassed water is larger than 40 μm. Under continuous heating, the WVMB involves significantly rapid Marangoni flow. This flow is well-described by a stokeslet sat ~10 μm above the surface of GNF, from which the maximum flow speed around the WVMB is estimated to exceed 1 m/s. This rapid flow generation is attributed to the small bubble size, over which the temperature is graded, and the superheat at the bubble surface in contact with the GNF. It is expected to be useful not only for microfluidic mixing but also for fundamental research on viscous flow induced by a single stokeslet. PMID:28361949

Chemistry in Microfluidic Channels

ERIC Educational Resources Information Center

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

2011-01-01

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

Thermal Blood Clot Formation and use in Microfluidic Device Valving Applications

NASA Technical Reports Server (NTRS)

Tai, Yu-Chong (Inventor); Shi, Wendian (Inventor); Guo, Luke (Inventor)

2014-01-01

The present invention provides a method of forming a blood-clot microvalve by heating blood in a capillary tube of a microfluidic device. Also described are methods of modulating liquid flow in a capillary tube by forming and removing a blood-clot microvalve.

Microfabrication and Applications of Opto-Microfluidic Sensors

PubMed Central

Zhang, Daiying; Men, Liqiu; Chen, Qiying

2011-01-01

A review of research activities on opto-microfluidic sensors carried out by the research groups in Canada is presented. After a brief introduction of this exciting research field, detailed discussion is focused on different techniques for the fabrication of opto-microfluidic sensors, and various applications of these devices for bioanalysis, chemical detection, and optical measurement. Our current research on femtosecond laser microfabrication of optofluidic devices is introduced and some experimental results are elaborated. The research on opto-microfluidics provides highly sensitive opto-microfluidic sensors for practical applications with significant advantages of portability, efficiency, sensitivity, versatility, and low cost. PMID:22163904

Diffusion phenomena of cells and biomolecules in microfluidic devices.

PubMed

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-09-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules.

Diffusion phenomena of cells and biomolecules in microfluidic devices

PubMed Central

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-01-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules. PMID:26180576

Microfluidic fuel cell systems

NASA Astrophysics Data System (ADS)

Ho, Bernard; Kjeang, Erik

2011-06-01

A microfluidic fuel cell is a microfabricated device that produces electrical power through electrochemical reactions involving a fuel and an oxidant. Microfluidic fuel cell systems exploit co-laminar flow on the microscale to separate the fuel and oxidant species, in contrast to conventional fuel cells employing an ion exchange membrane for this function. Since 2002 when the first microfluidic fuel cell was invented, many different fuels, oxidants, and architectures have been investigated conceptually and experimentally. In this mini-review article, recent advancements in the field of microfluidic fuel cell systems are documented, with particular emphasis on design, operation, and performance. The present microfluidic fuel cell systems are categorized by the fluidic phases of the fuel and oxidant streams, featuring gaseous/gaseous, liquid/gaseous, and liquid/liquid systems. The typical cell configurations and recent contributions in each category are analyzed. Key research challenges and opportunities are highlighted and recommendations for further work are provided.

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.

Gel integration for microfluidic applications.

PubMed

Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

2016-05-21

Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

Multiplex Particle Focusing via Hydrodynamic Force in Viscoelastic Fluids

NASA Astrophysics Data System (ADS)

Lee, Doo Jin; Brenner, Howard; Youn, Jae Ryoun; Song, Young Seok

2013-11-01

We introduce a multiplex particle focusing phenomenon that arises from the hydrodynamic interaction between the viscoelastic force and the Dean drag force in a microfluidic device. In a confined microchannel, the first normal stress difference of viscoelastic fluids results in a lateral migration of suspended particles. Such a viscoelastic force was harnessed to focus different sized particles in the middle of a microchannel, and spiral channel geometry was also considered in order to take advantage of the counteracting force, Dean drag force that induces particle migration in the outward direction. For theoretical understanding, we performed a numerical analysis of viscoelastic fluids in the spiral microfluidic channel. From these results, a concept of the `Dean-coupled Elasto-inertial Focusing band (DEF)' was proposed. This study provides in-depth physical insight into the multiplex focusing of particles that can open a new venue for microfluidic particle dynamics for a concrete high throughput platform at microscale.

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.

Microfluidic Automation using elastomeric valves and droplets: reducing reliance on external controllers

PubMed Central

Kim, Sung-Jin; Lai, David; Park, Joong Yull; Yokokawa, Ryuji

2012-01-01

This paper gives an overview of elastomeric valve- and droplet-based microfluidic systems designed to minimize the need of external pressure to control fluid flow. This concept article introduces the working principle of representative components in these devices along with relevant biochemical applications. This is followed by providing a perspective on the roles of different microfluidic valves and systems through comparison of their similarities and differences with transistors (valves) and systems in microelectronics. Despite some physical limitation of drawing analogies from electronic circuits, automated microfluidic circuit design can gain insights from electronic circuits to minimize external control units, while implementing high complexity and throughput analysis. PMID:22761019

Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel.

PubMed

Yaginuma, T; Oliveira, M S N; Lima, R; Ishikawa, T; Yamaguchi, T

2013-01-01

It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the centerline of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases.

Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel

PubMed Central

Yaginuma, T.; Oliveira, M. S. N.; Lima, R.; Ishikawa, T.; Yamaguchi, T.

2013-01-01

It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the centerline of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases. PMID:24404073

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

PubMed

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

2018-03-01

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

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.

Microfluidics-Enabled Diagnostic Systems: Markets, Challenges, and Examples.

PubMed

Becker, Holger; Gärtner, Claudia

2017-01-01

Microfluidics has become an important tool for the commercial product development in diagnostics. This article will focus on current technical demands during the development process such as material and integration challenges. Furthermore, we present data on the diagnostics market as well as examples of microfluidics-enabled systems currently under commercial development or already on the market.

Microfluidic free-flow electrophoresis for the discovery and characterisation of calmodulin binding partners

NASA Astrophysics Data System (ADS)

Herling, Therese; Linse, Sara; Knowles, Tuomas

2015-03-01

Non-covalent and transient protein-ligand interactions are integral to cellular function and malfunction. Key steps in signalling and regulatory pathways rely on reversible non-covalent protein-protein binding or ion chelation. Here we present a microfluidic free-flow electrophoresis method for detecting and characterising protein-ligand interactions in solution. We apply this method to probe the binding equilibria of calmodulin, a central protein to calcium signalling pathways. In this study we characterise the specific binding of calmodulin to phosphorylase kinase, a known target, and creatine kinase, which we identify as a putative binding partner through a protein array screen and surface plasmon resonance experiments. We verify the interaction between calmodulin and creatine kinase in solution using free-flow electrophoresis and investigate the effect of calcium and sodium chloride on the calmodulin-ligand binding affinity in free solution without the presence of a potentially interfering surface. Our results demonstrate the general applicability of quantitative microfluidic electrophoresis to characterise binding equilibria between biomolecules in solution.

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

Droplets Formation and Merging in Two-Phase Flow Microfluidics

PubMed Central

Gu, Hao; Duits, Michel H. G.; Mugele, Frieder

2011-01-01

Two-phase flow microfluidics is emerging as a popular technology for a wide range of applications involving high throughput such as encapsulation, chemical synthesis and biochemical assays. Within this platform, the formation and merging of droplets inside an immiscible carrier fluid are two key procedures: (i) the emulsification step should lead to a very well controlled drop size (distribution); and (ii) the use of droplet as micro-reactors requires a reliable merging. A novel trend within this field is the use of additional active means of control besides the commonly used hydrodynamic manipulation. Electric fields are especially suitable for this, due to quantitative control over the amplitude and time dependence of the signals, and the flexibility in designing micro-electrode geometries. With this, the formation and merging of droplets can be achieved on-demand and with high precision. In this review on two-phase flow microfluidics, particular emphasis is given on these aspects. Also recent innovations in microfabrication technologies used for this purpose will be discussed. PMID:21731459

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.

Laser-bulge based ultrasonic bonding method for fabricating multilayer thermoplastic microfluidic devices

NASA Astrophysics Data System (ADS)

Liang, Chao; Liu, Chong; Liu, Ziyang; Meng, Fanjian; Li, Jingmin

2017-11-01

Ultrasonic bonding is a commonly-used method for fabrication of thermoplastic microfluidic devices. However, due to the existence of the energy director (a convex structure to concentrate the ultrasonic energy), it is difficult to control its molten polymer flow, which may result in a small gap between the bonding interface or microchannel clogging. In this paper, we present an approach to address these issues. Firstly, the microchannels were patterned onto the PMMA sheets using hot embossing with the wire electrical discharge machined molds. Then, a small bulge, which was formed at the edge of the laser-ablated groove (LG), was generated around the microchannel using a CO2 laser ablation system. By using the bulge to concentrate the ultrasonic energy, there was no need for fabricating the complicated and customized energy director. When the bulge was melted, it was able to flow into the LG which overcame the ‘gap’ and ‘clogging’ problems. Here, two types of two-layer microfluidic devices and a five-layer micromixer were fabricated to validate its performance. Our results showed that these thermoplastic microdevices can be successfully bonded by using this method. The liquid leakage was not observed in both the capillary-driven flowing test and the pressure-driven mixing experiments. It is a potential method for bonding the thermoplastic microfluidic devices.

Geo-material microfluidics at reservoir conditions for subsurface energy resource applications

DOE PAGES

Porter, Mark L.; Jiménez-Martínez, Joaquín; Martinez, Ricardo Martin; ...

2015-08-20

Microfluidic investigations of flow and transport in porous and fractured media have the potential to play a significant role in the development of future subsurface energy resource technologies. However, the majority of experimental systems to date are limited in applicability due to operating conditions and/or the use of engineered material micromodels. In this paper, we have developed a high pressure and temperature microfluidic experimental system that allows for direct observations of flow and transport within geo-material micromodels (e.g. rock, cement) at reservoir conditions. In this manuscript, we describe the experimental system, including our novel micromodel fabrication method that works inmore » both geo- and engineered materials and utilizes 3-D tomography images of real fractures as micromodel templates to better represent the pore space and fracture geometries expected in subsurface formations. We present experimental results that highlight the advantages of using real-rock micromodels and discuss potential areas of research that could benefit from geo-material microfluidic investigations. Finally, the experiments include fracture–matrix interaction in which water imbibes into the shale rock matrix from etched fractures, supercritical CO 2 (scCO 2) displacing brine in idealized and realistic fracture patterns, and three-phase flow involving scCO 2–brine–oil.« less

Filling of high aspect ratio micro features of a microfluidic flow cytometer chip using micro injection moulding

NASA Astrophysics Data System (ADS)

Zhang, Haoyang; Fang, Fengzhou; Gilchrist, Michael D.; Zhang, Nan

2018-07-01

Micro injection moulding has been demonstrated as one of the most efficient mass production technologies for manufacturing polymeric microfluidic devices, which have been widely used in life sciences, environmental and analytical fields and agro-food industries. However, the filling of micro features for typical microfluidic devices is complicated and not yet fully understood, which consequently restricts the chip development. In the present work, a microfluidic flow cytometer chip with essential high aspect ratio micro features was used as a typical model to study their filling process. Short-shot experiments and single factor experiments were performed to examine the filling progress of such features during the injection and packing stages of the micro injection moulding process. The influence of process parameters such as shot size, packing pressure, packing time and mould temperature were systematically monitored, characterised and correlated with 3D measurements and real response of the machine such as screw velocity and screw position. A combined melt flow and creep deformation model was proposed to explain the complex influence of process on replication. An approach of over-shot micro injection moulding was proposed and was shown to be effective at improving the replication quality of high aspect ratio micro features.

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

PubMed

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

2017-04-01

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

Real-time detection and analysis of Whispering gallery mode resonance in high-throughput flowing monodisperse microdroplets

NASA Astrophysics Data System (ADS)

El Abed, Abdel I.; Taly, Valérie

2013-11-01

We investigate light coupling into highly monodisperse liquid microdroplets, which are produced and manipulated at kHz rates in a microfluidic device. We show that such coupling leads to Whispering gallery mode resonances (WGMs) which are detected and analyzed versus time during the fast displacement of microdroplets into the microfluidic channel. Our results show that droplet-based microfluidics may be applied advantageously in the promising field of high-throughput label-free biosensing.

DEPSCOR06: A Dispersed Monopropellant Microslug Approach for Discrete Satellite Micropropulsion

DTIC Science & Technology

2010-08-01

microfluidics , a controlled slug formation process represents a virtual ’self- valving ’ mechanism which affords finer resolution than a micro- valve for a... microfluidic flow system to study the effects of geometry and material properties on the microslug formation phenomena. The inspiration for this work is derived...the-shelf microfluidic chip, manufactured by Micralyne, Inc. was used as shown in Figure A-1.1. Figure 1.A.1: Geometry of the Micralyne 50 µm x 20 µm

A practical guide for the fabrication of microfluidic devices using glass and silicon

PubMed Central

Iliescu, Ciprian; Taylor, Hayden; Avram, Marioara; Miao, Jianmin; Franssila, Sami

2012-01-01

This paper describes the main protocols that are used for fabricating microfluidic devices from glass and silicon. Methods for micropatterning glass and silicon are surveyed, and their limitations are discussed. Bonding methods that can be used for joining these materials are summarized and key process parameters are indicated. The paper also outlines techniques for forming electrical connections between microfluidic devices and external circuits. A framework is proposed for the synthesis of a complete glass/silicon device fabrication flow. PMID:22662101

Liposome production by microfluidics: potential and limiting factors

PubMed Central

Carugo, Dario; Bottaro, Elisabetta; Owen, Joshua; Stride, Eleanor; Nastruzzi, Claudio

2016-01-01

This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology. PMID:27194474

Liposome production by microfluidics: potential and limiting factors.

PubMed

Carugo, Dario; Bottaro, Elisabetta; Owen, Joshua; Stride, Eleanor; Nastruzzi, Claudio

2016-05-19

This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology.

Microfluidic nitrogen-assisted nanoelectrospray emitter: A monolithic interface for accurate mass measurements based on a single nozzle.

PubMed

Wang, Lingling; Wang, Yujiao; Jiang, Shichang; Ye, Mingyue; Su, Ping; Xiong, Bo

2016-10-28

Nitrogen-assisted nanoelectrospray emitter (NANE) was developed to achieve accurate mass-to-charge ratio (m/z) measurements with a single monolithic nozzle. Deposition patterns of generated electrosprays from NANE confirmed their wrapped configurations. Additionally, the intensity of the sample ion and its ratio relative to a reference ion was inclined to focus on the central region of the spray; this trend further supported the existence of wrapped configurations. Further, the proposed NANE was fabricated from poly-(dimethylsiloxane) (PDMS) with octadecyltrichlorosilane modification to restrain the dissolution of PDMS monomers. Assist nitrogen flows were introduced to improve the ionization of reference ions. Moreover, the NANE could regulate the distribution of reference ions by microfluidic three dimensional hydrodynamic focusing. By regulating the distribution of reference ions, the ionization depression was reduced to some degree, and an improved sensitivity was accomplished compared with the mixing of sample and reference solutions. Achieved relative errors of m/z were between 0.2-4.5ppm and 5.2-9.2ppm for ten organic molecules and four biological macromolecules, respectively. Acceptable linear ranges were obtained in quantifications for rhodamine B and emamectin benzoate. Finally, the NANE was compatible with broad infusion rates (from 50nLmin -1 to 15μLmin -1 ) and solutions of different compositions (from 100% methanol to 100% water). Considering the comprehensive application of PDMS in microfluidics, the proposed NANE could be used as a compact and monolithic interface to achieve accurate m/z measurements. Copyright © 2016 Elsevier B.V. All rights reserved.

A simple microfluidic Coriolis effect flowmeter for operation at high pressure and high temperature.

PubMed

Harrison, Christopher; Jundt, Jacques

2016-08-01

We describe a microfluidic Coriolis effect flowmeter that is simple to assemble, operates at elevated temperature and pressure, and can be operated with a lock-in amplifier. The sensor has a flow rate sensitivity greater than 2° of phase shift per 1 g/min of mass flow and is benchmarked with flow rates ranging from 0.05 to 2.0 g/min. The internal volume is 15 μl and uses off-the-shelf optical components to measure the tube motion. We demonstrate that fluid density can be calculated from the frequency of the resonating element with proper calibration.

Material-Efficient Microfluidic Platform for Exploratory Studies of Visible-Light Photoredox Catalysis.

PubMed

Coley, Connor W; Abolhasani, Milad; Lin, Hongkun; Jensen, Klavs F

2017-08-07

We present an automated microfluidic platform for in-flow studies of visible-light photoredox catalysis in liquid or gas-liquid reactions at the 15 μL scale. An oscillatory flow strategy enables a flexible residence time while preserving the mixing and heat transfer advantages of flow systems. The adjustable photon flux made possible with the platform is characterized using actinometry. Case studies of oxidative hydroxylation of phenylboronic acids and dimerization of thiophenol demonstrate the capabilities and advantages of the system. Reaction conditions identified through droplet screening translate directly to continuous synthesis with minor platform modifications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfluidic opportunities in the field of nutrition

PubMed Central

Li, Sixing; Kiehne, Justin; Sinoway, Lawrence I.; Cameron, Craig E.

2013-01-01

Nutrition has always been closely related to human health, which is a constant motivational force driving research in a variety of disciplines. Over the years, the rapidly emerging field of microfluidics has been pushing forward the healthcare industry with the development of microfluidic-based, point-of-care (POC) diagnostic devices. Though a great deal of work has been done in developing microfluidic platforms for disease diagnoses, potential microfluidic applications in the field of nutrition remain largely unexplored. In this Focus article, we would like to investigate the potential chances for microfluidics in the field of nutrition. We will first highlight some of the recent advances in microfluidic blood analysis systems that have the capacity to detect biomarkers of nutrition. Then we will examine existing examples of microfluidic devices for the detection of specific biomarkers of nutrition or nutrient content in food. Finally, we will discuss the challenges in this field and provide some insight into the future of applied microfluidics in nutrition. PMID:24056522

Shape-tunable wax microparticle synthesis via microfluidics and droplet impact

PubMed Central

Lee, Doojin; Beesabathuni, Shilpa N.; Shen, Amy Q.

2015-01-01

Spherical and non-spherical wax microparticles are generated by employing a facile two-step droplet microfluidic process which consists of the formation of molten wax microdroplets in a flow-focusing microchannel and their subsequent off-chip crystallization and deformation via microdroplet impingement on an immiscible liquid interface. Key parameters on the formation of molten wax microdroplets in a microfluidic channel are the viscosity of the molten wax and the interfacial tension between the dispersed and continuous fluids. A cursory phase diagram of wax morphology transition is depicted depending on the Capillary number and the Stefan number during the impact process. A combination of numerical simulation and analytical modeling is carried out to understand the physics underlying the deformation and crystallization process of the molten wax. The deformation of wax microdroplets is dominated by the viscous and thermal effects rather than the gravitational and buoyancy effects. Non-isothermal crystallization kinetics of the wax illustrates the time dependent thermal effects on the droplet deformation and crystallization. The work presented here will benefit those interested in the design and production criteria of soft non-spherical particles (i.e., alginate gels, wax, and polymer particles) with the aid of time and temperature mediated solidification and off-chip crosslinking. PMID:26697124

Microfluidic magnetic fluidized bed for DNA analysis in continuous flow mode.

PubMed

Hernández-Neuta, Iván; Pereiro, Iago; Ahlford, Annika; Ferraro, Davide; Zhang, Qiongdi; Viovy, Jean-Louis; Descroix, Stéphanie; Nilsson, Mats

2018-04-15

Magnetic solid phase substrates for biomolecule manipulation have become a valuable tool for simplification and automation of molecular biology protocols. However, the handling of magnetic particles inside microfluidic chips for miniaturized assays is often challenging due to inefficient mixing, aggregation, and the advanced instrumentation required for effective actuation. Here, we describe the use of a microfluidic magnetic fluidized bed approach that enables dynamic, highly efficient and simplified magnetic bead actuation for DNA analysis in a continuous flow platform with minimal technical requirements. We evaluate the performance of this approach by testing the efficiency of individual steps of a DNA assay based on padlock probes and rolling circle amplification. This assay comprises common nucleic acid analysis principles, such as hybridization, ligation, amplification and restriction digestion. We obtained efficiencies of up to 90% for these reactions with high throughput processing up to 120μL of DNA dilution at flow rates ranging from 1 to 5μL/min without compromising performance. The fluidized bed was 20-50% more efficient than a commercially available solution for microfluidic manipulation of magnetic beads. Moreover, to demonstrate the potential of this approach for integration into micro-total analysis systems, we optimized the production of a low-cost polymer based microarray and tested its analytical performance for integrated single-molecule digital read-out. Finally, we provide the proof-of-concept for a single-chamber microfluidic chip that combines the fluidized bed with the polymer microarray for a highly simplified and integrated magnetic bead-based DNA analyzer, with potential applications in diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Modular microfluidic system for biological sample preparation

DOEpatents

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

2015-09-29

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

Fluid flow in a spiral microfluidic duct

NASA Astrophysics Data System (ADS)

Harding, Brendan; Stokes, Yvonne

2018-04-01

We consider the steady, pressure driven flow of a viscous fluid through a microfluidic device having the geometry of a planar spiral duct with a slowly varying curvature and height smaller than width. For this problem, it is convenient to express the Navier-Stokes equations in terms of a non-orthogonal coordinate system. Then, after applying appropriate scalings, the leading order equations admit a relatively simple solution in the central region of the duct cross section. First-order corrections with respect to the duct curvature and aspect ratio parameters are also obtained for this region. Additional correction terms are needed to ensure that no slip and no penetration conditions are satisfied on the side walls. Our solutions allow for a top wall shape that varies with respect to the radial coordinate which allows us to study the flow in a variety of cross-sectional shapes, including trapezoidal-shaped ducts that have been studied experimentally. At leading order, the flow is found to depend on the local height and slope of the top wall within the central region. The solutions are compared with numerical approximations of a classical Dean flow and are found to be in good agreement for a small duct aspect ratio and a slowly varying and small curvature. We conclude that the slowly varying curvature typical of spiral microfluidic devices has a negligible impact on the flow in the sense that locally the flow does not differ significantly from the classical Dean flow through a duct having the same curvature.

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing.

PubMed

Wardrip, Nathaniel C; Arnusch, Christopher J

2016-02-13

Minimization and management of membrane fouling is a formidable challenge in diverse industrial processes and other practices that utilize membrane technology. Understanding the fouling process could lead to optimization and higher efficiency of membrane based filtration. Here we show the design and fabrication of an automated three-dimensionally (3-D) printed microfluidic cross-flow filtration system that can test up to 4 membranes in parallel. The microfluidic cells were printed using multi-material photopolymer 3-D printing technology, which used a transparent hard polymer for the microfluidic cell body and incorporated a thin rubber-like polymer layer, which prevents leakages during operation. The performance of ultrafiltration (UF), and nanofiltration (NF) membranes were tested and membrane fouling could be observed with a model foulant bovine serum albumin (BSA). Feed solutions containing BSA showed flux decline of the membrane. This protocol may be extended to measure fouling or biofouling with many other organic, inorganic or microbial containing solutions. The microfluidic design is especially advantageous for testing materials that are costly or only available in small quantities, for example polysaccharides, proteins, or lipids due to the small surface area of the membrane being tested. This modular system may also be easily expanded for high throughput testing of membranes.

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing

PubMed Central

Wardrip, Nathaniel C.; Arnusch, Christopher J.

2016-01-01

Minimization and management of membrane fouling is a formidable challenge in diverse industrial processes and other practices that utilize membrane technology. Understanding the fouling process could lead to optimization and higher efficiency of membrane based filtration. Here we show the design and fabrication of an automated three-dimensionally (3-D) printed microfluidic cross-flow filtration system that can test up to 4 membranes in parallel. The microfluidic cells were printed using multi-material photopolymer 3-D printing technology, which used a transparent hard polymer for the microfluidic cell body and incorporated a thin rubber-like polymer layer, which prevents leakages during operation. The performance of ultrafiltration (UF), and nanofiltration (NF) membranes were tested and membrane fouling could be observed with a model foulant bovine serum albumin (BSA). Feed solutions containing BSA showed flux decline of the membrane. This protocol may be extended to measure fouling or biofouling with many other organic, inorganic or microbial containing solutions. The microfluidic design is especially advantageous for testing materials that are costly or only available in small quantities, for example polysaccharides, proteins, or lipids due to the small surface area of the membrane being tested. This modular system may also be easily expanded for high throughput testing of membranes.  PMID:26968008

Development of a Passive Liquid Valve (PLV) Utilizing a Pressure Equilibrium Phenomenon on the Centrifugal Microfluidic Platform

PubMed Central

Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Bahari, Norulain; Arof, Hamzah; Rothan, Hussin A.; Yusof, Rohana; Madou, Marc

2015-01-01

In this paper, we propose an easy-to-implement passive liquid valve (PLV) for the microfluidic compact-disc (CD). This valve can be implemented by introducing venting chambers to control the air flow of the source and destination chambers. The PLV mechanism is based on equalizing the main forces acting on the microfluidic CD (i.e., the centrifugal and capillary forces) to control the burst frequency of the source chamber liquid. For a better understanding of the physics behind the proposed PLV, an analytical model is described. Moreover, three parameters that control the effectiveness of the proposed valve, i.e., the liquid height, liquid density, and venting chamber position with respect to the CD center, are tested experimentally. To demonstrate the ability of the proposed PLV valve, microfluidic liquid switching and liquid metering are performed. In addition, a Bradford assay is performed to measure the protein concentration and evaluated in comparison to the benchtop procedure. The result shows that the proposed valve can be implemented in any microfluidic process that requires simplicity and accuracy. Moreover, the developed valve increases the flexibility of the centrifugal CD platform for passive control of the liquid flow without the need for an external force or trigger. PMID:25723143

Development of a passive liquid valve (PLV) utilizing a pressure equilibrium phenomenon on the centrifugal microfluidic platform.

PubMed

Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Bahari, Norulain; Arof, Hamzah; Rothan, Hussin A; Yusof, Rohana; Madou, Marc

2015-02-25

In this paper, we propose an easy-to-implement passive liquid valve (PLV) for the microfluidic compact-disc (CD). This valve can be implemented by introducing venting chambers to control the air flow of the source and destination chambers. The PLV mechanism is based on equalizing the main forces acting on the microfluidic CD (i.e., the centrifugal and capillary forces) to control the burst frequency of the source chamber liquid. For a better understanding of the physics behind the proposed PLV, an analytical model is described. Moreover, three parameters that control the effectiveness of the proposed valve, i.e., the liquid height, liquid density, and venting chamber position with respect to the CD center, are tested experimentally. To demonstrate the ability of the proposed PLV valve, microfluidic liquid switching and liquid metering are performed. In addition, a Bradford assay is performed to measure the protein concentration and evaluated in comparison to the benchtop procedure. The result shows that the proposed valve can be implemented in any microfluidic process that requires simplicity and accuracy. Moreover, the developed valve increases the flexibility of the centrifugal CD platform for passive control of the liquid flow without the need for an external force or trigger.

Automated microfluidic platform for systematic studies of colloidal perovskite nanocrystals: towards continuous nano-manufacturing.

PubMed

Epps, Robert W; Felton, Kobi C; Coley, Connor W; Abolhasani, Milad

2017-11-21

Colloidal organic/inorganic metal-halide perovskite nanocrystals have recently emerged as a potential low-cost replacement for the semiconductor materials in commercial photovoltaics and light emitting diodes. However, unlike III-V and IV-VI semiconductor nanocrystals, studies of colloidal perovskite nanocrystals have yet to develop a fundamental and comprehensive understanding of nucleation and growth kinetics. Here, we introduce a modular and automated microfluidic platform for the systematic studies of room-temperature synthesized cesium-lead halide perovskite nanocrystals. With abundant data collection across the entirety of four orders of magnitude reaction time span, we comprehensively characterize nanocrystal growth within a modular microfluidic reactor. The developed high-throughput screening platform features a custom-designed three-port flow cell with translational capability for in situ spectral characterization of the in-flow synthesized perovskite nanocrystals along a tubular microreactor with an adjustable length, ranging from 3 cm to 196 cm. The translational flow cell allows for sampling of twenty unique residence times at a single equilibrated flow rate. The developed technique requires an average total liquid consumption of 20 μL per spectra and as little as 2 μL at the time of sampling. It may continuously sample up to 30 000 unique spectra per day in both single and multi-phase flow formats. Using the developed plug-and-play microfluidic platform, we study the growth of cesium lead trihalide perovskite nanocrystals through in situ monitoring of their absorption and emission band-gaps at residence times ranging from 100 ms to 17 min. The automated microfluidic platform enables a systematic study of the effect of mixing enhancement on the quality of the synthesized nanocrystals through a direct comparison between single- and multi-phase flow systems at similar reaction time scales. The improved mixing characteristics of the multi-phase flow format results in high-quality perovskite nanocrystals with kinetically tunable emission wavelength, ranging as much as 25 nm at equivalent residence times. Further application of this unique platform would allow rapid parameter optimization in the colloidal synthesis of a wide range of nanomaterials (e.g., metal or semiconductor), that is directly transferable to continuous manufacturing in a numbered-up platform with a similar characteristic length scale.

Optimization and scale up of microfluidic nanolipomer production method for preclinical and potential clinical trials.

PubMed

Gdowski, Andrew; Johnson, Kaitlyn; Shah, Sunil; Gryczynski, Ignacy; Vishwanatha, Jamboor; Ranjan, Amalendu

2018-02-12

The process of optimization and fabrication of nanoparticle synthesis for preclinical studies can be challenging and time consuming. Traditional small scale laboratory synthesis techniques suffer from batch to batch variability. Additionally, the parameters used in the original formulation must be re-optimized due to differences in fabrication techniques for clinical production. Several low flow microfluidic synthesis processes have been reported in recent years for developing nanoparticles that are a hybrid between polymeric nanoparticles and liposomes. However, use of high flow microfluidic synthetic techniques has not been described for this type of nanoparticle system, which we will term as nanolipomer. In this manuscript, we describe the successful optimization and functional assessment of nanolipomers fabricated using a microfluidic synthesis method under high flow parameters. The optimal total flow rate for synthesis of these nanolipomers was found to be 12 ml/min and flow rate ratio 1:1 (organic phase: aqueous phase). The PLGA polymer concentration of 10 mg/ml and a DSPE-PEG lipid concentration of 10% w/v provided optimal size, PDI and stability. Drug loading and encapsulation of a representative hydrophobic small molecule drug, curcumin, was optimized and found that high encapsulation efficiency of 58.8% and drug loading of 4.4% was achieved at 7.5% w/w initial concentration of curcumin/PLGA polymer. The final size and polydispersity index of the optimized nanolipomer was 102.11 nm and 0.126, respectively. Functional assessment of uptake of the nanolipomers in C4-2B prostate cancer cells showed uptake at 1 h and increased uptake at 24 h. The nanolipomer was more effective in the cell viability assay compared to free drug. Finally, assessment of in vivo retention in mice of these nanolipomers revealed retention for up to 2 h and were completely cleared at 24 h. In this study, we have demonstrated that a nanolipomer formulation can be successfully synthesized and easily scaled up through a high flow microfluidic system with optimal characteristics. The process of developing nanolipomers using this methodology is significant as the same optimized parameters used for small batches could be translated into manufacturing large scale batches for clinical trials through parallel flow systems.

Positional dependence of particles in microfludic impedance cytometry.

PubMed

Spencer, Daniel; Morgan, Hywel

2011-04-07

Single cell impedance cytometry is a label-free electrical analysis method that requires minimal sample preparation and has been used to count and discriminate cells on the basis of their impedance properties. This paper shows experimental and numerically simulated impedance signals for test particles (6 μm diameter polystyrene) flowing through a microfluidic channel. The variation of impedance signal with particle position is mapped using numerical simulation and these results match closely with experimental data. We demonstrate that for a nominal 40 μm × 40 μm channel, the impedance signal is independent of position over the majority of the channel area, but shows large experimentally verifiable variation at extreme positions. The parabolic flow profile in the channel ensures that most of the sample flows through the area of uniform signal. At high flow rates inertial focusing is observed; the particles flow in equal numbers through two equilibrium positions reducing the coefficient of variance (CV) in the impedance signals to negligible values.

Bio-microfluidics: biomaterials and biomimetic designs.

PubMed

Domachuk, Peter; Tsioris, Konstantinos; Omenetto, Fiorenzo G; Kaplan, David L

2010-01-12

Bio-microfluidics applies biomaterials and biologically inspired structural designs (biomimetics) to microfluidic devices. Microfluidics, the techniques for constraining fluids on the micrometer and sub-micrometer scale, offer applications ranging from lab-on-a-chip to optofluidics. Despite this wealth of applications, the design of typical microfluidic devices imparts relatively simple, laminar behavior on fluids and is realized using materials and techniques from silicon planar fabrication. On the other hand, highly complex microfluidic behavior is commonplace in nature, where fluids with nonlinear rheology flow through chaotic vasculature composed from a range of biopolymers. In this Review, the current state of bio-microfluidic materials, designs and applications are examined. Biopolymers enable bio-microfluidic devices with versatile functionalization chemistries, flexibility in fabrication, and biocompatibility in vitro and in vivo. Polymeric materials such as alginate, collagen, chitosan, and silk are being explored as bulk and film materials for bio-microfluidics. Hydrogels offer options for mechanically functional devices for microfluidic systems such as self-regulating valves, microlens arrays and drug release systems, vital for integrated bio-microfluidic devices. These devices including growth factor gradients to study cell responses, blood analysis, biomimetic capillary designs, and blood vessel tissue culture systems, as some recent examples of inroads in the field that should lead the way in a new generation of microfluidic devices for bio-related needs and applications. Perhaps one of the most intriguing directions for the future will be fully implantable microfluidic devices that will also integrate with existing vasculature and slowly degrade to fully recapitulate native tissue structure and function, yet serve critical interim functions, such as tissue maintenance, drug release, mechanical support, and cell delivery.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Encapsulation of cell into monodispersed hydrogels on microfluidic device

NASA Astrophysics Data System (ADS)

Choi, Chang-Hyoung; Lee, Ji-Hye; Shim, Hyun-Woo; Lee, Nae-Rym; Jung, Jae-Hoon; Yoon, Tae-Ho; Kim, Dong-Pyo; Lee, Chang-Soo

2007-12-01

In here, we present the microfluidic approach to produce monodispersed microbeads that will contain viable cells. The utilization of microfludics is helpful to synthesize monodispersed alginate hydrogels and in situ encapsulate cell into the generating hydrogels in microfludic device. First, the condition of formation of hydrogels in multiphase flows including oil, CaCl II, and alginate was optimized. Based on the preliminary survey, microfludic device could easily manipulate the size of alginate beads having narrow size distribution. The microfluidic method manipulates the size of hydrogel microbeads from 30 to 200um with a variation less than 2%. For the proof of concept of cell entrapment, the live yeast expressing green fluorescence protein is successfully encapsulated in microfluidic device.

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.

Deep wells integrated with microfluidic valves for stable docking and storage of cells.

PubMed

Jang, Yun-Ho; Kwon, Cheong Hoon; Kim, Sang Bok; Selimović, Seila; Sim, Woo Young; Bae, Hojae; Khademhosseini, Ali

2011-02-01

In this paper, we describe a microfluidic mechanism that combines microfluidic valves and deep wells for cell localization and storage. Cells are first introduced into the device via externally controlled flow. Activating on-chip valves was used to interrupt the flow and to sediment the cells floating above the wells. Thus, valves could be used to localize the cells in the desired locations. We quantified the effect of valves in the cell storage process by comparing the total number of cells stored with and without valve activation. We hypothesized that in deep wells external flows generate low shear stress regions that enable stable, long-term docking of cells. To assess this hypothesis we conducted numerical calculations to understand the influence of well depth on the forces acting on cells. We verified those predictions experimentally by comparing the fraction of stored cells as a function of the well depth and input flow rate upon activation of the valves. As expected, upon reintroduction of the flow the cells in the deep wells were not moved whereas those in shallow wells were washed away. Taken together, our paper demonstrates that deep wells and valves can be combined to enable a broad range of cell studies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combined Microfluidic-Eectric Diffused Mixing of Living Cells in Continuous Flow

NASA Astrophysics Data System (ADS)

Ming-Wen Wang,

2010-02-01

The mixing process is a crucially important stage in the operation of biological and chemical microfluidic devices. If the mixing is inadequate, reactants do not fully interact with each other, and the device may not operate properly. This paper describes a simplified microfluidic mixer (different from a chaotic mixer) which can uniformly mix a buffer solution with living cells by applying an AC electric charge. Diffusion of the living cells into the buffer solution occurs rapidly following the interface of the flow stream with the electric charge; no further agitating step is needed. To accomplish this, an asymmetric pair of electrodes was integrated at the inlets of the buffer solution and the cells fluid. When the buffer solution and the cells fluid were introduced into one flow path, they remained limited to that flow stream. When the electrodes were charged, however, the cells in a short distance were efficiently moved into the solution flow, and the original fluids were mixed. The mixing efficiency depends on the polarizability of the cells, and this in turn is governed by the dielectric properties of the cells, the medium, and the solvent. This micro device, capable of efficiently mixing living cells with a buffer solution, may potentially allow biological mixing to be done outside of hospitals, in facilities without biological analyzing instruments.

Volumetric flow rate in simulations of microfluidic devices+

NASA Astrophysics Data System (ADS)

Kovalčíková, KristÍna; Slavík, Martin; Bachratá, Katarína; Bachratý, Hynek; Bohiniková, Alžbeta

2018-06-01

In this work, we examine the volumetric flow rate of microfluidic devices. The volumetric flow rate is a parameter which is necessary to correctly set up a simulation of a real device and to check the conformity of a simulation and a laboratory experiments [1]. Instead of defining the volumetric rate at the beginning as a simulation parameter, a parameter of external force is set. The proposed hypothesis is that for a fixed set of other parameters (topology, viscosity of the liquid, …) the volumetric flow rate is linearly dependent on external force in typical ranges of fluid velocity used in our simulations. To confirm this linearity hypothesis and to find numerical limits of this approach, we test several values of the external force parameter. The tests are designed for three different topologies of simulation box and for various haematocrits. The topologies of the microfluidic devices are inspired by existing laboratory experiments [3 - 6]. The linear relationship between the external force and the volumetric flow rate is verified in orders of magnitudes similar to the values obtained from laboratory experiments. Supported by the Slovak Research and Development Agency under the contract No. APVV-15-0751 and by the Ministry of Education, Science, Research and Sport of the Slovak Republic under the contract No. VEGA 1/0643/17.

Enhanced biofilm distribution and cell performance of microfluidic microbial fuel cells with multiple anolyte inlets.

PubMed

Yang, Yang; Ye, Dingding; Liao, Qiang; Zhang, Pengqing; Zhu, Xun; Li, Jun; Fu, Qian

2016-05-15

A laminar-flow controlled microfluidic microbial fuel cell (MMFC) is considered as a promising approach to be a bio-electrochemical system (BES). But poor bacterial colonization and low power generation are two severe bottlenecks to restrict its development. In this study, we reported a MMFC with multiple anolyte inlets (MMFC-MI) to enhance the biofilm formation and promote the power density of MMFCs. Voltage profiles during the inoculation process demonstrated MMFC-MI had a faster start-up process than the conventional microfluidic microbial fuel cell with one inlet (MMFC-OI). Meanwhile, benefited from the periodical replenishment of boundary layer near the electrode, a more densely-packed bacterial aggregation was observed along the flow direction and also the substantially low internal resistance for MMFC-MI. Most importantly, the output power density of MMFC-MI was the highest value among the reported µl-scale MFCs to our best knowledge. The presented MMFC-MI appears promising for bio-chip technology and extends the scope of microfluidic energy. Copyright © 2015 Elsevier B.V. All rights reserved.

Microfluidic Bioprinting for Engineering Vascularized Tissues and Organoids.

PubMed

Zhang, Yu Shrike; Pi, Qingmeng; van Genderen, Anne Metje

2017-08-11

Engineering vascularized tissue constructs and organoids has been historically challenging. Here we describe a novel method based on microfluidic bioprinting to generate a scaffold with multilayer interlacing hydrogel microfibers. To achieve smooth bioprinting, a core-sheath microfluidic printhead containing a composite bioink formulation extruded from the core flow and the crosslinking solution carried by the sheath flow, was designed and fitted onto the bioprinter. By blending gelatin methacryloyl (GelMA) with alginate, a polysaccharide that undergoes instantaneous ionic crosslinking in the presence of select divalent ions, followed by a secondary photocrosslinking of the GelMA component to achieve permanent stabilization, a microfibrous scaffold could be obtained using this bioprinting strategy. Importantly, the endothelial cells encapsulated inside the bioprinted microfibers can form the lumen-like structures resembling the vasculature over the course of culture for 16 days. The endothelialized microfibrous scaffold may be further used as a vascular bed to construct a vascularized tissue through subsequent seeding of the secondary cell type into the interstitial space of the microfibers. Microfluidic bioprinting provides a generalized strategy in convenient engineering of vascularized tissues at high fidelity.

A microfluidic separation platform using an array of slanted ramps

NASA Astrophysics Data System (ADS)

Risbud, Sumedh; Bernate, Jorge; Drazer, German

2013-03-01

The separation of the different components of a sample is a crucial step in many micro- and nano-fluidic applications, including the detection of infections, the capture of circulating tumor cells, the isolation of proteins, RNA and DNA, to mention but a few. Vector chromatography, in which different species migrate in different directions in a planar microfluidic device thus achieving spatial as well as temporal resolution, offers the promise of high selectivity along with high throughput. In this work, we present a microfluidic vector chromatography platform consisting of slanted ramps in a microfluidic channel for the separation of suspended particles. We construct these ramps using inclined UV lithography, such that the inclined portion of the ramps is upstream. We show that particles of different size displace laterally to a different extent when driven by a flow field over a slanted ramp. The flow close to the ramp reorients along the ramp, causing the size-dependent deflection of the particles. The cumulative effect of an array of these ramps would cause particles of different size to migrate in different directions, thus allowing their passive and continuous separation.

Capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection

NASA Astrophysics Data System (ADS)

Yang, Hao; Deng, Min; Ga, Shan; Chen, Shouhui; Kang, Lin; Wang, Junhong; Xin, Wenwen; Zhang, Tao; You, Zherong; An, Yuan; Wang, Jinglin; Cui, Daxiang

2014-03-01

Herein, we firstly demonstrate the design and the proof-of-concept use of a capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection. The micropillar array substrate was etched and coated with a gold film by microelectromechanical systems (MEMS) process to integrate into a lateral flow test strip. The detection of abrin solutions of various concentrations was performed by the as-prepared microfluidic chip. It was shown that the correlation between the abrin concentration and SERS signal was found to be linear within the range of 0.1 ng/mL to 1 μg/mL with a limit of detection of 0.1 ng/mL. Our microfluidic chip design enhanced the operability of SERS-based immunodiagnostic techniques, significantly reducing the complication and cost of preparation as compared to previous SERS-based works. Meanwhile, this design proved the superiority to conventional lateral flow test strips in respect of both sensitivity and quantitation and showed great potential in the diagnosis and treatment for abrin poisoning as well as on-site screening of abrin-spiked materials.

Combining Whispering-Gallery Mode Optical Biosensors with Microfluidics for Real-Time Detection of Protein Secretion from Living Cells in Complex Media.

PubMed

Chen, Ying-Jen; Schoeler, Ulrike; Huang, Chung-Hsuan Benjamin; Vollmer, Frank

2018-05-01

The noninvasive monitoring of protein secretion of cells responding to drug treatment is an effective and essential tool in latest drug development and for cytotoxicity assays. In this work, a surface functionalization method is demonstrated for specific detection of protein released from cells and a platform that integrates highly sensitive optical devices, called whispering-gallery mode biosensors, with precise microfluidics control to achieve label-free and real-time detection. Cell biomarker release is measured in real time and with nanomolar sensitivity. The surface functionalization method allows for antibodies to be immobilized on the surface for specific detection, while the microfluidics system enables detection in a continuous flow with a negligible compromise between sensitivity and flow control over stabilization and mixing. Cytochrome c detection is used to illustrate the merits of the system. Jurkat cells are treated with the toxin staurosporine to trigger cell apoptosis and cytochrome c released into the cell culture medium is monitored via the newly invented optical microfluidic platform. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

PubMed Central

Bower, Ruth; Green, Victoria L; Kuvshinova, Elena; Kuvshinov, Dmitriy; Karsai, Laszlo; Crank, Stephen T; Stafford, Nicholas D; Greenman, John

2017-01-01

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. PMID:28670466

Characterization of light-controlled Volvox as movable microvalve element assembled in multilayer microfluidic device

NASA Astrophysics Data System (ADS)

Nagai, Moeto; Oguri, Michihito; Shibata, Takayuki

2015-06-01

We report a model of a light-controlled microvalve driven by Volvox and characterization of Volvox as a movable microvalve element in a multilayer microfluidic device for development of the valve. First, a three-layer microfluidic device having a single through-hole was fabricated by a replica molding process. The fabricated devices met the requirements for experiments using Volvox. Second, we used the phototactic behavior of V. carteri and controlled its motions in a microchannel by illuminating light. V. carteri migrated to the light source in the channel. Third, a colony of V. carteri was placed on a microhole, and the colony was found to stop the flow compared to the flow without Volvox on the hole. The integration of all of the obtained findings is expected to lead to the fabrication of the proposed microvalve.

A microfluidic two-pump system inspired by liquid feeding in mosquitoes

NASA Astrophysics Data System (ADS)

Marino, Andrew; Goad, Angela; Stremler, Mark; Socha, John; Jung, Sunghwan

Mosquitoes feed on nectar and blood using a two-pump system in the head-a smaller cibarial pump in line with a larger a pharyngeal pump, with a valve in between. To suck, mosquitoes transport the liquid (which may be a multi-component viscous fluid, blood) through a long micro-channel, the proboscis. In the engineering realm, microfluidic devices in biomedical applications, such as lab-on-a-chip technology, necessitate implementing a robust pump design to handle clogging and increase flow control compared to a single-pump system. In this talk, we introduce a microfluidic pump design inspired by the mosquito's two-pump system. The pumping performance (flow rate) in presence of impurities (air bubbles, soft clogs) is quantified as a function of phase difference and volume expansion of the pumps, and the elasticity of the valve.

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model.

PubMed

Wang, Ying; You, Guoxing; Chen, Peipei; Li, Jianjun; Chen, Gan; Wang, Bo; Li, Penglong; Han, Dong; Zhou, Hong; Zhao, Lian

2016-03-01

The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs.

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.

Microelectrokinetic turbulence in microfluidics at low Reynolds number.

PubMed

Wang, Guiren; Yang, Fang; Zhao, Wei

2016-01-01

There is commonly no turbulence in microfluidics, and the flows are believed to be either laminar or chaotic, since Reynolds number (Re) in microflows is usually on the order of unity or lower. However, we recently demonstrated that it is possible to achieve turbulence with low Re (based on the measured flow velocity and the width of the channel entrance) when a pressure-driven flow is electrokinetically forced in a quasi T-microchannel. To be able to measure high frequency velocity fluctuations in microchannels, a velocimeter with submicrometer spatial resolution and microsecond temporal resolution, called a laser-induced fluorescence photobleaching anemometer, is developed. Here we characterize the microelectrokinetic turbulence and observe some typical and important features of high Re flows, such as Kolmogorov -5/3 spectrum of velocity fluctuation, which usually can be realized only at very high Re in macroturbulent flows.

Automated Microfluidic Instrument for Label-Free and High-Throughput Cell Separation.

PubMed

Zhang, Xinjie; Zhu, Zhixian; Xiang, Nan; Long, Feifei; Ni, Zhonghua

2018-03-20

Microfluidic technologies for cell separation were reported frequently in recent years. However, a compact microfluidic instrument enabling thoroughly automated cell separation is still rarely reported until today due to the difficult hybrid between the macrosized fluidic control system and the microsized microfluidic device. In this work, we propose a novel and automated microfluidic instrument to realize size-based separation of cancer cells in a label-free and high-throughput manner. Briefly, the instrument is equipped with a fully integrated microfluidic device and a set of robust fluid-driven and control units, and the instrument functions of precise fluid infusion and high-throughput cell separation are guaranteed by a flow regulatory chip and two cell separation chips which are the key components of the microfluidic device. With optimized control programs, the instrument is successfully applied to automatically sort human breast adenocarcinoma cell line MCF-7 from 5 mL of diluted human blood with a high recovery ratio of ∼85% within a rapid processing time of ∼23 min. We envision that our microfluidic instrument will be potentially useful in many biomedical applications, especially cell separation, enrichment, and concentration for the purpose of cell culture and analysis.

Electrochemical push-pull probe: from scanning electrochemical microscopy to multimodal altering of cell microenvironment.

PubMed

Bondarenko, Alexandra; Cortés-Salazar, Fernando; Gheorghiu, Mihaela; Gáspár, Szilveszter; Momotenko, Dmitry; Stanica, Luciana; Lesch, Andreas; Gheorghiu, Eugen; Girault, Hubert H

2015-04-21

To understand biological processes at the cellular level, a general approach is to alter the cells' environment and to study their chemical responses. Herein, we present the implementation of an electrochemical push-pull probe, which combines a microfluidic system with a microelectrode, as a tool for locally altering the microenvironment of few adherent living cells by working in two different perturbation modes, namely electrochemical (i.e., electrochemical generation of a chemical effector compound) and microfluidic (i.e., infusion of a chemical effector compound from the pushing microchannel, while simultaneously aspirating it through the pulling channel, thereby focusing the flow between the channels). The effect of several parameters such as flow rate, working distance, and probe inclination angle on the affected area of adherently growing cells was investigated both theoretically and experimentally. As a proof of concept, localized fluorescent labeling and pH changes were purposely introduced to validate the probe as a tool for studying adherent cancer cells through the control over the chemical composition of the extracellular space with high spatiotemporal resolution. A very good agreement between experimental and simulated results showed that the electrochemical perturbation mode enables to affect precisely only a few living cells localized in a high-density cell culture.

Fractionation of Magnetic Microspheres in a Microfluidic Spiral: Interplay between Magnetic and Hydrodynamic Forces

PubMed Central

Hayden, M. E.; Häfeli, U. O.

2017-01-01

Magnetic forces and curvature-induced hydrodynamic drag have both been studied and employed in continuous microfluidic particle separation and enrichment schemes. Here we combine the two. We investigate consequences of applying an outwardly directed magnetic force to a dilute suspension of magnetic microspheres circulating in a spiral microfluidic channel. This force is realized with an array of permanent magnets arranged to produce a magnetic field with octupolar symmetry about the spiral axis. At low flow rates particles cluster around an apparent streamline of the flow near the outer wall of the turn. At high flow rates this equilibrium is disrupted by the induced secondary (Dean) flow and a new equilibrium is established near the inner wall of the turn. A model incorporating key forces involved in establishing these equilibria is described, and is used to extract quantitative information about the magnitude of local Dean drag forces from experimental data. Steady-state fractionation of suspensions by particle size under the combined influence of magnetic and hydrodynamic forces is demonstrated. Extensions of this work could lead to new continuous microscale particle sorting and enrichment processes with improved fidelity and specificity. PMID:28107472

High content evaluation of shear dependent platelet function in a microfluidic flow assay

PubMed Central

Hansen, Ryan R.; Wufsus, Adam R.; Barton, Steven T.; Onasoga, Abimbola A.; Johnson-Paben, Rebecca M.; Neeves, Keith B.

2012-01-01

The high blood volume requirements and low throughput of conventional flow assays for measuring platelet function are unsuitable for drug screening and clinical applications. In this study, we describe a microfluidic flow assay that uses 50 μL of whole blood to measure platelet function on ~300 micropatterned spots of collagen over a range of physiologic shear rates (50–920 s−1). Patterning of collagen thin films (CTF) was achieved using a novel hydrated microcontact stamping method. CTF spots of 20, 50, and 100 μm were defined on glass substrates and consisted of a dense mat of nanoscale collagen fibers (3.74 ± 0.75 nm). We found that a spot size of greater than 20 μm was necessary to support platelet adhesion under flow, suggesting a threshold injury is necessary for stable platelet adhesion. Integrating 50 μm CTF microspots into a multishear microfluidic device yielded a high content assay from which we extracted platelet accumulation metrics (lag time, growth rate, total accumulation) on the spots using Hoffman modulation contrast microscopy. This method has potential broad application in identifying platelet function defects and screening, monitoring and dosing antiplatelet agents. PMID:23001359

Mass production of monodisperse microbubbles for real applications avoiding microfluidics

NASA Astrophysics Data System (ADS)

Sanchez Quintero, Enrique Jesus; Evangelio, Alvaro; Gordillo, Jose Manuel

2017-11-01

In this presentation we report experiments showing the effect on the controlled generation of microbubbles of the pressure gradient imposed by the relative flow of a liquid stream around an airfoil-shaped solid. Taking advantage of the conclusions in, where the local pressure gradient was identified as the mechanism responsible of the generation of microbubbles in microfluidic devices and, with the purpose of overcoming the low production rates associated with these kind of microdevices, we have used the same physical principle but have applied it to a totally different geometry: a rectangular planar wing composed by symmetrical airfoils. The relative velocity field is imposed either submerging the static wing within a flowing hydraulic channel or by rotating the wings within a reservoir containing the otherwise quiescent liquid mass. We provide physical insight on the bubbling process and deduce a scaling law which expresses the diameters of the bubbles formed as a function of the gas flow rate, relative liquid velocity and the angle of attack of the incident flow. In spite of the geometry is totally different, we recover the same results obtained using microfluidic devices but with much higher production rates.

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).

Research highlights: increasing paper possibilities.

PubMed

Wu, Chueh-Yu; Adeyiga, Oladunni; Lin, Jonathan; Di Carlo, Dino

2014-09-07

In this issue we highlight three recent papers that demonstrate new strategies to extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers) has a long history as a substrate to perform biomolecular assays. Traditional lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and perform well when a yes or no answer is required and the analyte of interest is at relatively high concentrations. High concentrations are required because usually only a small volume of analyte-containing fluid flows past the detection region, leading to a limited signal. Further, the small pores within paper matrices prevent the use of paper to control the flow of larger particles and cells, limiting the use of paper microfluidics for cell-based diagnostics. The work we highlight addresses these important unmet challenges in paper microfluidics: enriching low concentration analytes to a higher concentration in a smaller volume that can be processed effectively, and using paper to pump flows in larger channels amenable to cells. Applying these new approaches may allow diagnosis of disease states currently technically unachievable using current LFA systems, while maintaining many of the "un-instrumented" advantages of an assay on self-wicking paper.

Wettability control on fluid-fluid displacements in patterned microfluidics and porous media

NASA Astrophysics Data System (ADS)

Juanes, Ruben; Trojer, Mathias; Zhao, Benzhong

2014-11-01

While it is well known that the wetting properties are critical in two-phase flows in porous media, the effect of wettability on fluid displacement continues to challenge our microscopic and macroscopic descriptions. Here we study this problem experimentally, starting with the classic experiment of two-phase flow in a capillary tube. We image the shape of the meniscus and measure the associated capillary pressure for a wide range of capillary numbers. We synthesize new observations on the dependence of the dynamic capillary pressure on wetting properties (contact angle) and flow conditions (viscosity contrast and capillary number). We then conduct experiments on a planar microfluidic device patterned with vertical posts. We track the evolution of the fluid-fluid interface and elucidate the impact of wetting on the cooperative nature of fluid displacement during pore invasion events. We use the insights gained from the capillary tube and patterned microfluidics experiments to elucidate the effect of wetting properties on viscous fingering and capillary fingering in a Hele-Shaw cell filled with glass beads, where we observe a contact-angle-dependent stabilizing behavior for the emerging flow instabilities, as the system transitions from drainage to imbibition.

Integrated light-sheet imaging and flow-based enquiry (iLIFE) system for 3D in-vivo imaging of multicellular organism

NASA Astrophysics Data System (ADS)

Rasmi, Chelur K.; Padmanabhan, Sreedevi; Shirlekar, Kalyanee; Rajan, Kanhirodan; Manjithaya, Ravi; Singh, Varsha; Mondal, Partha Pratim

2017-12-01

We propose and demonstrate a light-sheet-based 3D interrogation system on a microfluidic platform for screening biological specimens during flow. To achieve this, a diffraction-limited light-sheet (with a large field-of-view) is employed to optically section the specimens flowing through the microfluidic channel. This necessitates optimization of the parameters for the illumination sub-system (illumination intensity, light-sheet width, and thickness), microfluidic specimen platform (channel-width and flow-rate), and detection sub-system (camera exposure time and frame rate). Once optimized, these parameters facilitate cross-sectional imaging and 3D reconstruction of biological specimens. The proposed integrated light-sheet imaging and flow-based enquiry (iLIFE) imaging technique enables single-shot sectional imaging of a range of specimens of varying dimensions, ranging from a single cell (HeLa cell) to a multicellular organism (C. elegans). 3D reconstruction of the entire C. elegans is achieved in real-time and with an exposure time of few hundred micro-seconds. A maximum likelihood technique is developed and optimized for the iLIFE imaging system. We observed an intracellular resolution for mitochondria-labeled HeLa cells, which demonstrates the dynamic resolution of the iLIFE system. The proposed technique is a step towards achieving flow-based 3D imaging. We expect potential applications in diverse fields such as structural biology and biophysics.

Reduced-gravity environment hardware demonstrations of a prototype miniaturized flow cytometer and companion microfluidic mixing technology.

PubMed

Phipps, William S; Yin, Zhizhong; Bae, Candice; Sharpe, Julia Z; Bishara, Andrew M; Nelson, Emily S; Weaver, Aaron S; Brown, Daniel; McKay, Terri L; Griffin, DeVon; Chan, Eugene Y

2014-11-13

Until recently, astronaut blood samples were collected in-flight, transported to earth on the Space Shuttle, and analyzed in terrestrial laboratories. If humans are to travel beyond low Earth orbit, a transition towards space-ready, point-of-care (POC) testing is required. Such testing needs to be comprehensive, easy to perform in a reduced-gravity environment, and unaffected by the stresses of launch and spaceflight. Countless POC devices have been developed to mimic laboratory scale counterparts, but most have narrow applications and few have demonstrable use in an in-flight, reduced-gravity environment. In fact, demonstrations of biomedical diagnostics in reduced gravity are limited altogether, making component choice and certain logistical challenges difficult to approach when seeking to test new technology. To help fill the void, we are presenting a modular method for the construction and operation of a prototype blood diagnostic device and its associated parabolic flight test rig that meet the standards for flight-testing onboard a parabolic flight, reduced-gravity aircraft. The method first focuses on rig assembly for in-flight, reduced-gravity testing of a flow cytometer and a companion microfluidic mixing chip. Components are adaptable to other designs and some custom components, such as a microvolume sample loader and the micromixer may be of particular interest. The method then shifts focus to flight preparation, by offering guidelines and suggestions to prepare for a successful flight test with regard to user training, development of a standard operating procedure (SOP), and other issues. Finally, in-flight experimental procedures specific to our demonstrations are described.

Reduced-gravity Environment Hardware Demonstrations of a Prototype Miniaturized Flow Cytometer and Companion Microfluidic Mixing Technology

PubMed Central

Bae, Candice; Sharpe, Julia Z.; Bishara, Andrew M.; Nelson, Emily S.; Weaver, Aaron S.; Brown, Daniel; McKay, Terri L.; Griffin, DeVon; Chan, Eugene Y.

2014-01-01

Until recently, astronaut blood samples were collected in-flight, transported to earth on the Space Shuttle, and analyzed in terrestrial laboratories. If humans are to travel beyond low Earth orbit, a transition towards space-ready, point-of-care (POC) testing is required. Such testing needs to be comprehensive, easy to perform in a reduced-gravity environment, and unaffected by the stresses of launch and spaceflight. Countless POC devices have been developed to mimic laboratory scale counterparts, but most have narrow applications and few have demonstrable use in an in-flight, reduced-gravity environment. In fact, demonstrations of biomedical diagnostics in reduced gravity are limited altogether, making component choice and certain logistical challenges difficult to approach when seeking to test new technology. To help fill the void, we are presenting a modular method for the construction and operation of a prototype blood diagnostic device and its associated parabolic flight test rig that meet the standards for flight-testing onboard a parabolic flight, reduced-gravity aircraft. The method first focuses on rig assembly for in-flight, reduced-gravity testing of a flow cytometer and a companion microfluidic mixing chip. Components are adaptable to other designs and some custom components, such as a microvolume sample loader and the micromixer may be of particular interest. The method then shifts focus to flight preparation, by offering guidelines and suggestions to prepare for a successful flight test with regard to user training, development of a standard operating procedure (SOP), and other issues. Finally, in-flight experimental procedures specific to our demonstrations are described. PMID:25490614

Multiphase flows with digital and traditional microfluidics

NASA Astrophysics Data System (ADS)

Nilsson, Michael A.

Multi-phase fluid systems are an important concept in fluid mechanics, seen every day in how fluids interact with solids, gases, and other fluids in many industrial, medical, agricultural, and other regimes. In this thesis, the development of a two-dimensional digital microfluidic device is presented, followed by the development of a two-phase microfluidic diagnostic tool designed to simulate sandstone geometries in oil reservoirs. In both instances, it is possible to take advantage of the physics involved in multiphase flows to affect positive outcomes in both. In order to make an effective droplet-based digital microfluidic device, one must be able to precisely control a number of key processes including droplet positioning, motion, coalescence, mixing, and sorting. For planar or open microfluidic devices, many of these processes have yet to be demonstrated. A suitable platform for an open system is a superhydrophobic surface, as suface characteristics are critical. Great efforts have been spent over the last decade developing hydrophobic surfaces exhibiting very large contact angles with water, and which allow for high droplet mobility. We demonstrate that sanding Teflon can produce superhydrophobic surfaces with advancing contact angles of up to 151° and contact angle hysteresis of less than 4°. We use these surfaces to characterize droplet coalescence, mixing, motion, deflection, positioning, and sorting. This research culminates with the presentation of two digital microfluidic devices: a droplet reactor/analyzer and a droplet sorter. As global energy usage increases, maximizing oil recovery from known reserves becomes a crucial multiphase challenge in order to meet the rising demand. This thesis presents the development of a microfluidic sandstone platform capable of quickly and inexpensively testing the performance of fluids with different rheological properties on the recovery of oil. Specifically, these microfluidic devices are utilized to examine how shear-thinning, shear-thickening, and viscoelastic fluids affect oil recovery. This work begins by looking at oil displacement from a microfluidic sandstone device, then investigates small-scale oil recovery from a single pore, and finally investigates oil displacement from larger scale, more complex microfluidic sandstone devices of varying permeability. The results demonstrate that with careful fluid design, it is possible to outperform current commercial additives using the patent-pending fluid we developed. Furthermore, the resulting microfluidic sandstone devices can reduce the time and cost of developing and testing of current and new enhanced oil recovery fluids.

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.

Microfluidic desalination techniques and their potential applications.

PubMed

Roelofs, S H; van den Berg, A; Odijk, M

2015-09-07

In this review we discuss recent developments in the emerging research field of miniaturized desalination. Traditionally desalination is performed to convert salt water into potable water and research is focused on improving performance of large-scale desalination plants. Microfluidic desalination offers several new opportunities in comparison to macro-scale desalination, such as providing a platform to increase fundamental knowledge of ion transport on the nano- and microfluidic scale and new microfluidic sample preparation methods. This approach has also lead to the development of new desalination techniques, based on micro/nanofluidic ion-transport phenomena, which are potential candidates for up-scaling to (portable) drinking water devices. This review assesses microfluidic desalination techniques on their applications and is meant to contribute to further implementation of microfluidic desalination techniques in the lab-on-chip community.

Combined SERS biotags (SBTs) and microfluidic platform for the quantitative ratiometric discrimination between noncancerous and cancerous cells in flow

NASA Astrophysics Data System (ADS)

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

2012-10-01

SERS biotags are made from polymer-encapsulated silver nanoparticle dimers infused with unique Raman reporter molecules, and carry peptides as cell recognition moieties. We demonstrate their potential use for early and rapid identification of malignant cells, a central goal in cancer research. SERS biotags (SBTs) can be routinely synthesized and simultaneously excited with a single, low intensity laser source, making the determination of the relative contribution of the individual SBTs to the overall spectrum tractable. Importantly for biomedical applications, SERS employs tissuepenetrating lasers in the red to near-infrared range resulting in low autofluorescence. We have previously described a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Here we present the progress towards the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to characterize the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension (simulating cells' capture from blood), then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We show that using SBTs ratiometrically can provide cell identification insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

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.

Microfluidics-assisted in vitro drug screening and carrier production

PubMed Central

Tsui, Jonathan H.; Lee, Woohyuk; Pun, Suzie H.; Kim, Jungkyu; Kim, Deok-Ho

2013-01-01

Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. PMID:23856409

Silicon micromachined pumps employing piezoelectric membrane actuation for microfluidic systems

NASA Astrophysics Data System (ADS)

Koch, Michael

Microsystems technology is a rapidly expanding area that comprises electronics, mechanics and optics. In this field, physical/chemical sensing, fluid handling and optical communication are emerging as potential markets. Microfluidic systems like an implantable insulin pump, a drug delivery system and a total chemical analysis system are currently being developed by academia and industry around the world. This project contributes to the area of microfluidics in that a novel thick-film-on-silicon membrane actuator has been developed to allow inexpensive mass production of micropumps. To date piezoelectric plates have been surface mounted onto a silicon membrane. This single chip fabrication method can now be replaced by screen printing thick piezoelectric layers onto 4 inch silicon substrates. Two different pump types have been developed. These are membrane pumps with either cantilever valves or diffuser/nozzle valves. Pump rates between 100 and 200 μl min-1 and backpressures up to 4 kPa have been achieved with these pumps. Along with the technology of micropumps, simulators have been developed. A novel coupled FEM-CFD solver was realised by a computer controlled coupling of two commercially available packages (ANSYS and CFX-Flow3D). The results of this simulator were in good agreement with measurements on micromachined cantilever valves. CFX- Flow3D was also used to successfully model the behaviour of the diffuser/nozzle valve. Finally, the pump has been simulated using a continuity equation. A behavioural dynamic extension of the cantilever valve was necessary to achieve better prediction of the pump rates for higher frequencies. As well, a common process has been developed for microfluidic devices like micromixers, particle counters and sorters as well as flow sensors. The micromixer has been tested already and achieves mixing for input pressures between 2 and 7 kPa. This agrees with simulations of the diffusive mixing with CFX-Flow3D. Together with the micropump, a combination of these devices allows future development of microfluidic systems for the medical and (bio)chemical market.

Fabrication and Evaluation of Microfluidic Immunoassay Devices with Antibody-Immobilized Microbeads Retained in Porous Hydrogel Micropillars.

PubMed

Kasama, Toshihiro; Kaji, Noritada; Tokeshi, Manabu; Baba, Yoshinobu

2017-01-01

Due to the inherent characteristics including confinement of molecular diffusion and high surface-to-volume ratio, microfluidic device-based immunoassay has great advantages in cost, speed, sensitivity, and so on, compared with conventional techniques such as microtiter plate-based ELISA, latex agglutination method, and lateral flow immunochromatography. In this paper, we explain the detection of C-reactive protein as a model antigen by using our microfluidic immunoassay device, so-called immuno-pillar device. We describe in detail how we fabricated and used the immuno-pillar devices.

Multichannel microfluidic chip for rapid and reliable trapping and imaging plant-parasitic nematodes

NASA Astrophysics Data System (ADS)

Amrit, Ratthasart; Sripumkhai, Witsaroot; Porntheeraphat, Supanit; Jeamsaksiri, Wutthinan; Tangchitsomkid, Nuchanart; Sutapun, Boonsong

2013-05-01

Faster and reliable testing technique to count and identify nematode species resided in plant roots is therefore essential for export control and certification. This work proposes utilizing a multichannel microfluidic chip with an integrated flow-through microfilter to retain the nematodes in a trapping chamber. When trapped, it is rather simple and convenient to capture images of the nematodes and later identify their species by a trained technician. Multiple samples can be tested in parallel using the proposed microfluidic chip therefore increasing number of samples tested per day.