Biomicrofluidics

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

Xu Li, David R. Ballerini, and Wei Shen

Biomicrofluidics 6, 011301 (2012); http://dx.doi.org/10.1063/1.3687398 (13 pages)

Online Publication Date: 2 March 2012

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“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.

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87.85.Ox	Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
47.85.Np	Fluidics
81.16.-c	Methods of micro- and nanofabrication and processing
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.80.Ek	Mechanical and micromechanical techniques

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Preface to Special Topic: Selected Papers from the Second Conference on Advances in Microfluidics and Nanofluidics and Asia-Pacific International Symposium on Lab on Chip

Z. P. Wang and C. Yang

Biomicrofluidics 6, 012701 (2012); http://dx.doi.org/10.1063/1.3692256 (2 pages)

Online Publication Date: 20 March 2012

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87.80.Ek	Mechanical and micromechanical techniques
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices

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Efficient manipulation of microparticles in bubble streaming flows

Cheng Wang, Shreyas V. Jalikop, and Sascha Hilgenfeldt

Biomicrofluidics 6, 012801 (2012); http://dx.doi.org/10.1063/1.3654949 (11 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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Oscillating microbubbles of radius 20–100 μm driven by ultrasound initiate a steady streaming flow around the bubbles. In such flows, microparticles of even smaller sizes (radius 1–5 μm) exhibit size-dependent behaviors: particles of different sizes follow different characteristic trajectories despite density-matching. Adjusting the relative strengths of the streaming flow and a superimposed Poiseuille flow allows for a simple tuning of particle behavior, separating the trajectories of particles with a size resolution on the order of 1 μm. Selective trapping, accumulation, and release of particles can be achieved. We show here how to design bubble microfluidic devices that use these concepts to filter, enrich, and preconcentrate particles of selected sizes, either by concentrating them in discrete clusters (localized both stream- and spanwise) or by forcing them into narrow, continuous trajectory bundles of strong spanwise localization.

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87.80.Ek	Mechanical and micromechanical techniques
87.85.Ox	Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
47.15.Rq	Laminar flows in cavities, channels, ducts, and conduits
47.85.Np	Fluidics
87.17.-d	Cell processes
47.60.Dx	Flows in ducts and channels

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Cell separation and transportation between two miscible fluid streams using ultrasound

Yang Liu, Deny Hartono, and Kian-Meng Lim

Biomicrofluidics 6, 012802 (2012); http://dx.doi.org/10.1063/1.3671062 (14 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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This paper presents a two-stream microfluidic system for transporting cells or micro-sized particles from one fluid stream to another by acoustophoresis. The two fluid streams, one being the original suspension and the other being the destination fluid, flow parallel to each other in a microchannel. Using a half-wave acoustic standing wave across the channel width, cells or particles with positive acoustic contrast factors are moved to the destination fluid where the pressure nodal line lies. By controlling the relative flow rate of the two fluid streams, the pressure nodal line can be maintained at a specific offset from the fluid interface within the destination fluid. Using this transportation method, particles or cells of different sizes and mechanical properties can be separated. The cells experiencing a larger acoustic radiation force are separated and transported from the original suspension to the destination fluid stream. The other particles or cells experiencing a smaller acoustic radiation force continue flowing in the original solution. Experiments were conducted to demonstrate the effective separation of polystyrene microbeads of different sizes (3 μm and 10 μm) and waterborne parasites (Giardia lamblia and Cryptosporidium parvum). Diffusion occurs between the two miscible fluids, but it was found to have little effects on the transport and separation process, even when the two fluids have different density and speed of sound.

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87.80.Ek	Mechanical and micromechanical techniques
07.10.Cm	Micromechanical devices and systems
82.70.Kj	Emulsions and suspensions
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.17.Uv	Biotechnology of cell processes
87.50.yg	Biophysical mechanisms of interaction

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Studying enzymatic bioreactions in a millisecond microfluidic flow mixer

Wolfgang Buchegger, Anna Haller, Sander van den Driesche, Martin Kraft, Bernhard Lendl, and Michael Vellekoop

Biomicrofluidics 6, 012803 (2012); http://dx.doi.org/10.1063/1.3665717 (9 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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In this study, the pre-steady state development of enzymatic bioreactions using a microfluidic mixer is presented. To follow such reactions fast mixing of reagents (enzyme and substrate) is crucial. By using a highly efficient passive micromixer based on multilaminar flow, mixing times in the low millisecond range are reached. Four lamination layers in a shallow channel reduce the diffusion lengths to a few micrometers only, enabling very fast mixing. This was proven by confocal fluorescence measurements in the channel’s cross sectional area. Adjusting the overall flow rate in the 200 μm wide and 900 μm long mixing and observation channel makes it possible to investigate enzyme reactions over several seconds. Further, the device enables changing the enzyme/substrate ratio from 1:1 up to 3:1, while still providing high mixing efficiency, as shown for the enzymatic hydrolysis using β-galactosidase. This way, the early kinetics of the enzyme reaction at multiple enzyme/substrate concentrations can be collected in a very short time (minutes). The fast and easy handling of the mixing device makes it a very powerful and convenient instrument for millisecond temporal analysis of bioreactions.

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87.80.Ek	Mechanical and micromechanical techniques
87.15.Vv	Diffusion
87.14.ej	Enzymes
87.15.R-	Reactions and kinetics

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Development and validation of a low cost blood filtration element separating plasma from undiluted whole blood

Alexandra Homsy, Peter D. van der Wal, Werner Doll, Roland Schaller, Stefan Korsatko, Maria Ratzer, Martin Ellmerer, Thomas R. Pieber, Andreas Nicol, and Nico F. de Rooij

Biomicrofluidics 6, 012804 (2012); http://dx.doi.org/10.1063/1.3672188 (9 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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Clinical point of care testing often needs plasma instead of whole blood. As centrifugation is labor intensive and not always accessible, filtration is a more appropriate separation technique. The complexity of whole blood is such that there is still no commercially available filtration system capable of separating small sample volumes (10-100 μl) at the point of care. The microfluidics research in blood filtration is very active but to date nobody has validated a low cost device that simultaneously filtrates small samples of whole blood and reproducibly recovers clinically relevant biomarkers, and all this in a limited amount of time with undiluted raw samples. In this paper, we show first that plasma filtration from undiluted whole blood is feasible and reproducible in a low-cost microfluidic device. This novel microfluidic blood filtration element (BFE) extracts 12 μl of plasma from 100 μl of whole blood in less than 10 min. Then, we demonstrate that our device is valid for clinical studies by measuring the adsorption of interleukins through our system. This adsorption is reproducible for interleukins IL6, IL8, and IL10 but not for TNFα. Hence, our BFE is valid for clinical diagnostics with simple calibration prior to performing any measurement.

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87.85.Ox	Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
47.85.Np	Fluidics

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Characterization and separation of Cryptosporidium and Giardia cells using on-chip dielectrophoresis

Harikrishnan Narayanan Unni, Deny Hartono, Lin Yue Lanry Yung, Mary Mah-Lee Ng, Heow Pueh Lee, Boo Cheong Khoo, and Kian-Meng Lim

Biomicrofluidics 6, 012805 (2012); http://dx.doi.org/10.1063/1.3671065 (14 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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Dielectrophoresis (DEP) has been shown to have significant potential for the characterization of cells and could become an efficient tool for rapid identification and assessment of microorganisms. The present work is focused on the trapping, characterization, and separation of two species of Cryptosporidium (C. parvum and C. muris) and Giardia lambia (G. lambia) using a microfluidic experimental setup. Cryptosporidium oocysts, which are 2-4 μm in size and nearly spherical in shape, are used for the preliminary stage of prototype development and testing. G. lambia cysts are 8–12 μm in size. In order to facilitate effective trapping, simulations were performed to study the effects of buffer conductivity and applied voltage on the flow and cell transport inside the DEP chip. Microscopic experiments were performed using the fabricated device and the real part of Clausius—Mossotti factor of the cells was estimated from critical voltages for particle trapping at the electrodes under steady fluid flow. The dielectric properties of the cell compartments (cytoplasm and membrane) were calculated based on a single shell model of the cells. The separation of C. muris and G. lambia is achieved successfully at a frequency of 10 MHz and a voltage of 3 Vpp (peak to peak voltage).

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87.85.Ox	Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
87.80.Ek	Mechanical and micromechanical techniques
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.16.dp	Transport, including channels, pores, and lateral diffusion
87.85.jc	Electrical, thermal, and mechanical properties of biological matter

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Floating-electrode enhanced constriction dielectrophoresis for biomolecular trapping in physiological media of high conductivity

Vasudha Chaurey, Carlos Polanco, Chia-Fu Chou, and Nathan S. Swami

Biomicrofluidics 6, 012806 (2012); http://dx.doi.org/10.1063/1.3676069 (14 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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We present an electrokinetic framework for designing insulator constriction-based dielectrophoresis devices with enhanced ability to trap nanoscale biomolecules in physiological media of high conductivity, through coupling short-range dielectrophoresis forces with long-range electrothermal flow. While a 500-fold constriction enables field focusing sufficient to trap nanoscale biomolecules by dielectrophoresis, the extent of this high-field region is enhanced through coupling the constriction to an electrically floating sensor electrode at the constriction floor. However, the enhanced localized fields due to the constriction and enhanced current within saline media of high conductivity (1 S/m) cause a rise in temperature due to Joule heating, resulting in a hotspot region midway within the channel depth at the constriction center, with temperatures of ∼8°–10°K above the ambient. While the resulting vortices from electrothermal flow are directed away from the hotspot region to oppose dielectrophoretic trapping, they also cause a downward and inward flow towards the electrode edges at the constriction floor. This assists biomolecular trapping at the sensor electrode through enabling long-range fluid sampling as well as through localized stirring by fluid circulation in its vicinity.

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87.80.-y	Biophysical techniques (research methods)
82.45.-h	Electrochemistry and electrophoresis
87.15.Tt	Electrophoresis

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AC-dielectrophoretic characterization and separation of submicron and micron particles using sidewall AgPDMS electrodes

Nuttawut Lewpiriyawong and Chun Yang

Biomicrofluidics 6, 012807 (2012); http://dx.doi.org/10.1063/1.3682049 (9 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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The recent development of microfluidic “lab on a chip” devices requires the need to continuously separate submicron particles. Here, we present a PDMS microfluidic device with sidewall conducting PDMS (AgPDMS) composite electrodes capable of separating submicron particles in hydrodynamic flow. In particular, the device can service dual functions. First, the AgPDMS composite electrodes embedded in a sidewall of the device channel allow for performing AC-dielectrophoretic (DEP) characterization through direct microscopic observation of particle behavior. Characterization experiments are carried out for numerous parameters including particle size, medium conductivity, and AC field frequency to reveal important dielectrophoresis DEP information in terms of the crossover frequency and positive/negative DEP behavior under specific frequencies. Second, the device offers an advantage that sidewall AgPDMS composite electrodes can produce strong DEP effects throughout the entire channel height, and thus the robustness of the on-chip particle separation is demonstrated for continuous separation in a flowing mixture of 0.5 and 5 μm particles with 100% separation efficiency.

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87.80.Kc	Electrochemical techniques
82.47.Rs	Electrochemical sensors
87.80.Ek	Mechanical and micromechanical techniques
07.07.Df	Sensors (chemical, optical, electrical, movement, gas, etc.); remote sensing
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
07.10.Cm	Micromechanical devices and systems

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Microfluidic fabrication of water-in-water (w/w) jets and emulsions

Ho Cheung Shum (岑浩璋), Jason Varnell, and David A. Weitz

Biomicrofluidics 6, 012808 (2012); http://dx.doi.org/10.1063/1.3670365 (9 pages) | Cited 2 times

Online Publication Date: 15 March 2012

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We demonstrate the generation of water-in-water (w/w) jets and emulsions by combining droplet microfluidics and aqueous two-phase systems (ATPS). The application of ATPS in microfluidics has been hampered by the low interfacial tension between typical aqueous phases. The low tension makes it difficult to form w/w droplets with conventional droplet microfluidic approaches. We show that by mechanically perturbing a stable w/w jet, w/w emulsions can be prepared in a controlled and reproducible fashion. We also characterize the encapsulation ability of w/w emulsions and demonstrate that their encapsulation efficiency can be significantly enhanced by inducing formation of precipitates and gels at the w/w interfaces. Our work suggests a biologically and environmentally friendly platform for droplet microfluidics and establishes the potential of w/w droplet microfluidics for encapsulation-related applications.

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87.80.Ek	Mechanical and micromechanical techniques
82.70.Kj	Emulsions and suspensions
82.70.Gg	Gels and sols
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
07.10.Cm	Micromechanical devices and systems

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Effect of slippage on the thermocapillary migration of a small droplet

Huy-Bich Nguyen and Jyh-Chen Chen

Biomicrofluidics 6, 012809 (2012); http://dx.doi.org/10.1063/1.3644382 (13 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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We conduct a numerical investigation and analytical analysis of the effect of slippage on the thermocapillary migration of a small liquid droplet on a horizontal solid surface. The finite element method is employed to solve the Navier-Stokes equations coupled with the energy equation. The effect of the slip behavior on the droplet migration is determined by using the Navier slip condition at the solid-liquid boundary. The results indicate that the dynamic contact angles and the contact angle hysteresis of the droplet are strictly correlated to the slip coefficient. The enhancement of the slip length leads to an increase in the droplet migration velocity due to the enhancement of the net momentum of thermocapillary convection vortices inside the droplet. A larger contact angle leads to an increase in the migration velocity which in turn enlarges the rate of the droplet migration velocity to the slip length. There is good agreement between the analytical and the numerical results when the dynamic contact angle utilizes in the analytical approach obtained from the results of the numerical computation, and the static contact angle is smaller than 50°.

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47.45.Gx	Slip flows and accommodation
47.55.dm	Thermocapillary effects
47.55.P-	Buoyancy-driven flows; convection
47.10.ad	Navier-Stokes equations
47.11.Fg	Finite element methods
47.32.-y	Vortex dynamics; rotating fluids

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Visualizing millisecond chaotic mixing dynamics in microdroplets: A direct comparison of experiment and simulation

Liguo Jiang, Yan Zeng, Hongbo Zhou, Jianan Y. Qu, and Shuhuai Yao

Biomicrofluidics 6, 012810 (2012); http://dx.doi.org/10.1063/1.3673254 (12 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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In order to fully explore and utilize the advantages of droplet-based microfluidics, fast, sensitive, and quantitative measurements are indispensable for the diagnosis of biochemical reactions in microdroplets. Here, we report an optical detection technique using two-photon fluorescence lifetime imaging microscopy, with an aligning-summing and non-fitting division method, to depict two-dimensional (2D) maps of mixing dynamics by chaotic advection in microdroplets with high temporal and spatial resolution. The mixing patterns of two dye solutions inside droplets were quantitatively and accurately measured. The mixing efficiency in a serpentine droplet mixer was also quantified and compared with the simulation data. The mapped chaotic mixing dynamics agree well with the numerical simulation and theoretical prediction. This quantitative characterization is potentially applicable to the real-time kinetic study of biological and chemical reactions in droplet-based microfluidic systems.

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87.80.Ek	Mechanical and micromechanical techniques
02.60.-x	Numerical approximation and analysis
07.10.Cm	Micromechanical devices and systems
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.15.mq	Luminescence
87.15.R-	Reactions and kinetics

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Temperature-induced droplet coalescence in microchannels

Bin Xu, Nam-Trung Nguyen, and Teck Neng Wong

Biomicrofluidics 6, 012811 (2012); http://dx.doi.org/10.1063/1.3630124 (8 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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This paper reports a technique for temperature-induced merging of droplets in a microchannel. The multiphase system consists of water droplet and oil as the dispersed phase and the carrying continuous phase. A resistive heater provides heating in a rectangular merging chamber. The temperature of the chamber is controlled by the voltage applied to the heater. The merging process of two neighboring droplets was investigated with different applied voltage, flow rate ratio between water and oil and total flowrate. Merging is found to be effective at high flow rate ratio, high temperature, and low total flowrate. The presented technique could be used for merging and mixing in droplet-based lab-on-a-chip platforms

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47.85.Np	Fluidics
47.60.Dx	Flows in ducts and channels
47.55.df	Breakup and coalescence
47.57.-s	Complex fluids and colloidal systems
47.61.Ne	Micromixing

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Integrated microfluidics system using surface acoustic wave and electrowetting on dielectrics technology

Y. Li, Y. Q. Fu, S. D. Brodie, M. Alghane, and A. J. Walton

Biomicrofluidics 6, 012812 (2012); http://dx.doi.org/10.1063/1.3660198 (9 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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This paper presents integrated microfluidic lab-on-a-chip technology combining surface acoustic wave (SAW) and electro-wetting on dielectric (EWOD). This combination has been designed to provide enhanced microfluidic functionality and the integrated devices have been fabricated using a single mask lithographic process. The integrated technology uses EWOD to guide and precisely position microdroplets which can then be actuated by SAW devices for particle concentration, acoustic streaming, mixing and ejection, as well as for sensing using a shear-horizontal wave SAW device. A SAW induced force has also been employed to enhance the EWOD droplet splitting function.

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85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
81.16.Nd	Micro- and nanolithography
47.85.Np	Fluidics
47.55.dr	Interactions with surfaces
43.25.Nm	Acoustic streaming
68.08.Bc	Wetting

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Handling of artificial membranes using electrowetting-actuated droplets on a microfluidic device combined with integrated pA-measurements

Anne Martel and Benjamin Cross

Biomicrofluidics 6, 012813 (2012); http://dx.doi.org/10.1063/1.3665719 (7 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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Artificial membranes, as a controllable environment, are an essential tool to study membrane proteins. Electrophysiology provides information about the ion transport mechanism across a membrane at the single-protein level. Unfortunately, high-throughput studies and screening are not accessible to electrophysiology because it is a set of not automated and technically delicate methods. Therefore, it is necessary to automate and parallelize electrophysiology measurement in artificial membranes. Here, we present a first step toward this goal: the fabrication and characterization of a microfluidic device integrating electrophysiology measurements and the handling of an artificial membrane which includes its formation, its displacement and the separation of its leaflets using electrowetting actuation of sub-μL droplets. To validate this device, we recorded the insertion of a model porin, α-hemolysin.

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87.14.ep	Membrane proteins
87.15.Pc	Electronic and electrical properties
87.16.D-	Membranes, bilayers, and vesicles
87.80.Ek	Mechanical and micromechanical techniques
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices

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Electrowetting on dielectric driven droplet resonance and mixing enhancement in parallel-plate configuration

Chiun-Peng Lee, Hsin-Chien Chen, and Mei-Feng Lai

Biomicrofluidics 6, 012814 (2012); http://dx.doi.org/10.1063/1.3673258 (8 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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This study experimentally verifies that the mixing process in a droplet can be enhanced by driving the droplet at resonant frequencies and at alternating driving frequencies using a parallel-plate electrowetting on dielectric device. The mixing time, which is defined as the time required for reaching the well-mixed state, in a resonant droplet is found to be significantly shorter than that in a non-resonant droplet. Besides, it is also found that a higher driving potential leads to a better mixing effect, especially at resonant frequencies. Furthermore, when a droplet is driven by alternating two driving frequencies, especially two resonant frequencies, the mixing efficiency is found to be significantly enhanced for a specific alternating duration of these two frequencies.

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87.80.Ek	Mechanical and micromechanical techniques
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
68.08.Bc	Wetting
47.85.Np	Fluidics
47.65.-d	Magnetohydrodynamics and electrohydrodynamics
47.55.dr	Interactions with surfaces

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Manipulating liquid plugs in microchannel with controllable air vents

Hao-Bing Liu, Eng Kiat Ting, and Hai-Qing Gong

Biomicrofluidics 6, 012815 (2012); http://dx.doi.org/10.1063/1.3686878 (10 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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An air venting element on microchannel, which can be controlled externally and automatically, was demonstrated for manipulating liquid plugs in microfluidic systems. The element’s open and closed statuses correspond to the positioning and movement of a liquid plug in the microchannel. Positioning of multiple liquid plugs at an air venting element enabled the merging and mixing of the plugs. Besides these basic functions, other modes of liquid plug manipulations including plug partitioning, multiple plug mixing, and spacing adjustment between liquid plugs, were realized using combination of multiple elements. The structure, operation, and some functions of the element were demonstrated with a microfluidic chip application. The performances of the element including its failure modes, threshold flow rate, and structural optimization were also discussed.

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47.85.Np	Fluidics
47.51.+a	Mixing
47.60.Dx	Flows in ducts and channels

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Direction dependence of displacement time for two-fluid electroosmotic flow

Chun Yee Lim and Yee Cheong Lam

Biomicrofluidics 6, 012816 (2012); http://dx.doi.org/10.1063/1.3665721 (17 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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Electroosmotic flow that involves one fluid displacing another fluid is commonly encountered in various microfludic applications and experiments, for example, current monitoring technique to determine zeta potential of microchannel. There is experimentally observed anomaly in such flow, namely, the displacement time is flow direction dependent, i.e., it depends if it is a high concentration fluid displacing a low concentration fluid, or vice versa. Thus, this investigation focuses on the displacement flow of two fluids with various concentration differences. The displacement time was determined experimentally with current monitoring method. It is concluded that the time required for a high concentration solution to displace a low concentration solution is smaller than the time required for a low concentration solution to displace a high concentration solution. The percentage displacement time difference increases with increasing concentration difference and independent of the length or width of the channel and the voltage applied. Hitherto, no theoretical analysis or numerical simulation has been conducted to explain this phenomenon. A numerical model based on finite element method was developed to explain the experimental observations. Simulations showed that the velocity profile and ion distribution deviate significantly from a single fluid electroosmotic flow. The distortion of ion distribution near the electrical double layer is responsible for the displacement time difference for the two different flow directions. The trends obtained from simulations agree with the experimental findings.

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87.50.ch	Electrophoresis/dielectrophoresis and other mechanical effects
87.80.Ek	Mechanical and micromechanical techniques
47.85.Np	Fluidics
82.45.-h	Electrochemistry and electrophoresis
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
47.60.Dx	Flows in ducts and channels

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Numerical study of dc-biased ac-electrokinetic flow over symmetrical electrodes

Wee Yang Ng, Antonio Ramos, Yee Cheong Lam, and Isabel Rodriguez

Biomicrofluidics 6, 012817 (2012); http://dx.doi.org/10.1063/1.3668262 (10 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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This paper presents a numerical study of DC-biased AC-electrokinetic (DC-biased ACEK) flow over a pair of symmetrical electrodes. The flow mechanism is based on a transverse conductivity gradient created through incipient Faradaic reactions occurring at the electrodes when a DC-bias is applied. The DC biased AC electric field acting on this gradient generates a fluid flow in the form of vortexes. To understand more in depth the DC-biased ACEK flow mechanism, a phenomenological model is developed to study the effects of voltage, conductivity ratio, channel width, depth, and aspect ratio on the induced flow characteristics. It was found that flow velocity on the order of mm/s can be produced at higher voltage and conductivity ratio. Such rapid flow velocity is one of the highest reported in microsystems technology using electrokinetics.

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87.80.Ek	Mechanical and micromechanical techniques
02.60.-x	Numerical approximation and analysis
07.10.Cm	Micromechanical devices and systems
82.45.Fk	Electrodes
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices

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Integrated microfluidic chip for rapid DNA digestion and time-resolved capillary electrophoresis analysis

Che-Hsin Lin, Yao-Nan Wang, and Lung-Ming Fu

Biomicrofluidics 6, 012818 (2012); http://dx.doi.org/10.1063/1.3654950 (11 pages) | Cited 2 times

Online Publication Date: 15 March 2012

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An integrated microfluidic chip is proposed for rapid DNA digestion and time-resolved capillary electrophoresis (CE) analysis. The chip comprises two gel-filled chambers for DNA enrichment and purification, respectively, a T-form micromixer for DNA/restriction enzyme mixing, a serpentine channel for DNA digestion reaction, and a CE channel for on-line capillary electrophoresis analysis. The DNA and restriction enzyme are mixed electroomostically using a pinched-switching DC field. The experimental and numerical results show that a mixing performance of 97% is achieved within a distance of 1 mm from the T-junction when a driving voltage of 90 V/cm and a switching frequency of 4 Hz are applied. Successive mixing digestion and capillary electrophoresis operation clearly present the changes on digesting φx-174 DNA in different CE runs. The time-resolved electropherograms show that the proposed device enables a φx-174 DNA sample comprising 11 fragments to be concentrated and analyzed within 24 min. Overall, the results presented in this study show that the proposed microfluidic chip provides a rapid and effective tool for DNA digestion and CE analysis applications.

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85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.14.gk	DNA
07.10.Cm	Micromechanical devices and systems
47.85.-g	Applied fluid mechanics

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Focused ion beam milling of microchannels in lithium niobate

Manoj Sridhar, Devendra K. Maurya, James R. Friend, and Leslie Y. Yeo

Biomicrofluidics 6, 012819 (2012); http://dx.doi.org/10.1063/1.3673260 (11 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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We present experimental and simulation results for focused ion beam (FIB) milling of microchannels in lithium niobate in this paper. We investigate two different cuts of lithium niobate, Y- and Z-cuts, and observe that the experimental material removal rate in the FIB for both Y-cut and Z-cut samples was 0.3 μm³/nC, roughly two times greater than the material removal rate previously reported in the literature but in good agreement with the value we obtain from stopping and range of ions in matter (SRIM) simulations. Further, we investigate the FIB milling rate and resultant cross-sectional profile of microchannels at various ion beam currents and find that the milling rate decreases as a function of ion dose and correspondingly, the cross-sectional profiles change from rectangular to V-shaped. This indicates that material redeposition plays an important role at high ion dose or equivalently, high aspect ratio. We find that the experimental material removal rate decreases as a function of aspect ratio of the milled structures, in good agreement with our simulation results at low aspect ratio and in good agreement with the material removal rates previously reported in the literature at high aspect ratios. Our results show that it is indeed easier than previously assumed to fabricate nanochannels with low aspect ratio directly on lithium niobate using the FIB milling technique.

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87.85.Qr	Nanotechnologies-design
81.15.Jj	Ion and electron beam-assisted deposition; ion plating
81.16.Mk	Laser-assisted deposition
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices

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Investigation on CO₂ laser irradiation inducing glass strip peeling for microchannel formation

Z. K. Wang and H. Y. Zheng

Biomicrofluidics 6, 012820 (2012); http://dx.doi.org/10.1063/1.3670362 (12 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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The study investigates the use of CO₂ laser to induce glass strip peeling off to form microchannels on soda lime gass substrate. The strip peeling exhibits a strong dependence on the energy deposition rate on the glass surface. In spite of the vast difference in the combination of laser power and scanning speed, when the ratio of the two makes the energy deposition rate in the range 3.0-6.0 J/(cm² s), the temperature rising inside glass will be above the strain point and reach the softening region of the glass. As a result, glass strip peeling is able to occur and form microchannels with dimensions of 20-40 μm in depth and 200-280 μm in width on the glass surface. Beyond this range, higher energy depsotion rate would lead to surface melting associated with solidification cracks and lower energy deposition rate causes the generation of fragment cracks.

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42.62.-b	Laser applications
81.40.Np	Fatigue, corrosion fatigue, embrittlement, cracking, fracture, and failure
81.30.Fb	Solidification
64.70.D-	Solid-liquid transitions
07.10.Cm	Micromechanical devices and systems

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Rapid and cost-effective fabrication of selectively permeable calcium-alginate microfluidic device using “modified” embedded template method

Amit Asthana, Kwang Ho Lee, Kyeong-Ohn Kim, Dong-Myung Kim, and Dong-Pyo Kim

Biomicrofluidics 6, 012821 (2012); http://dx.doi.org/10.1063/1.3672189 (9 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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In this paper, we have presented a non-lithographic embedded template method for rapid and cost-effective fabrication of a selectively permeable calcium-alginate (Ca-alginate) based microfluidic device with long serpentine delay channel. To demonstrate the versatility of the presented method, we have demonstrated two different strategies to fabricate serpentine long delay channels without using any sophisticated microfabrication techniques, in formal lab atmosphere. The procedure presented here, also, enables the preparation of a multilayered microfluidic device with channels of varying dimensions, in a single device without using any sophisticated micromachining instrumentation. In addition, we have also qualitatively studied the diffusion of small and large molecules from a Ca-alginate based microfluidic device and proposed a method to effectively control the out-flow of macro biomolecules from the crosslinked Ca-alginate matrix to create a selectively permeable matrix required for various biological and biomimetic applications, as mentioned in the Introduction section of this work.

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87.85.Ox	Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
87.85.Va	Micromachining
87.15.Vv	Diffusion
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
47.85.Np	Fluidics
47.60.Dx	Flows in ducts and channels

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Cyclic olefin copolymer based microfluidic devices for biochip applications: Ultraviolet surface grafting using 2-methacryloyloxyethyl phosphorylcholine

Rajeeb K. Jena and C. Y. Yue

Biomicrofluidics 6, 012822 (2012); http://dx.doi.org/10.1063/1.3682098 (12 pages) | Cited 1 time

Online Publication Date: 15 March 2012

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This report studies the surface modification of cyclic olefin copolymer (COC) by 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer using photografting technique for the purpose of biointerface applications, which demonstrate resistance to both protein adsorption and cell adhesion in COC-based microfluidic devices. This is essential because the hydrophobic nature of COC can lead to adsorption of specific compounds from biological fluids in the microchannel, which can affect the results during fluidic analysis and cause clogging inside the microchannel. A correlation was found between the irradiation time and hydrophobicity of the modified substrate. Static water contact angle results show that the hydrophilicity property of the MPC-grafted substrate improves with increasing irradiation time. The contact angle of the modified surface decreased to 20 ± 5° from 88 ± 3° for the untreated substrate. The surface characterization of the modified surface was evaluated using x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR spectroscopy). Attenuated total reflection-FTIR and XPS results show the presence of the phosphate group (P-O) on modified COC substrates, indicating that the hydrophilic MPC monomer has successfully grafted on COC. Finally, it was demonstrated that cell adhesion and protein adsorption on the MPC modified COC specimen has reduced significantly.

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87.80.Ek	Mechanical and micromechanical techniques
07.10.Cm	Micromechanical devices and systems
82.80.Pv	Electron spectroscopy (X-ray photoelectron (XPS), Auger electron spectroscopy (AES), etc.)
85.85.+j	Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.14.E-	Proteins
87.17.Rt	Cell adhesion and cell mechanics

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Resolution limit for DNA barcodes in the Odijk regime

Yanwei Wang, Wes F. Reinhart, Douglas R. Tree, and Kevin D. Dorfman

Biomicrofluidics 6, 014101 (2012); http://dx.doi.org/10.1063/1.3672691 (9 pages)

Online Publication Date: 3 January 2012

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We develop an approximation for the probability of optically resolving two fluorescent labels on the backbone of a DNA molecule confined in a nanochannel in the Odijk regime as a function of the fluorescence wavelength, channel size, and the properties of the DNA (persistence length and effective width). The theoretical predictions agree well with equivalent data produced by Monte Carlo simulations of a touching wormlike bead model of DNA in a high ionic strength buffer. Although the theory is only strictly valid in the limit where the effective width of the nanochannel is small compared with the persistence length of the DNA, simulations indicate that the theoretical predictions are reasonably accurate for channel widths up to two-thirds of the persistence length. Our results quantify the conjecture that DNA barcoding has kilobase pair resolution—provided the nanochannel lies in the Odijk regime.

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87.15.ak	Monte Carlo simulations
87.14.gk	DNA

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