CiteULike: Tag microfluidics

Continuous Particle Separation Through Deterministic Lateral Displacement

Lotien Huang — 2007-11-30T17:48:27-00:00

Science, Vol. 304, No. 5673. (14 May 2004), pp. 987-990.

We report on a microfluidic particle-separation device that makes use of the asymmetric bifurcation of laminar flow around obstacles. A particle chooses its path deterministically on the basis of its size. All particles of a given size follow equivalent migration paths, leading to high resolution. The microspheres of 0.8, 0.9, and 1.0 micrometers that were used to characterize the device were sorted in 40seconds with a resolution of [~]10nanometers, which was better than the time and resolution of conventional flow techniques. Bacterial artificial chromosomes could be separated in 10 minutes with a resolution of [~]12%. 10.1126/science.1094567

Mechanism for clogging of microchannels

Hans Wyss — 2007-09-22T19:57:03-00:00

Physical Review E (Statistical, Nonlinear, and Soft Matter Physics), Vol. 74, No. 6. (2006)

We investigate clogging of microchannels at the single-pore level using microfluidic devices as model porous media. The process of clogging is studied at low volume fractions and high flow rates, a technologically important regime. We show that clogging is independent of particle flow rate and volume fraction, indicating that collective effects do not play an important role. Instead, the average number of particles that can pass through a pore before it clogs scales with the ratio of pore to particle size. We present a simple model that accounts for the data.

Jamming, Two-Fluid Behavior, and “Self-Filtration” in Concentrated Particulate Suspensions

MD Haw — 2007-09-22T19:54:19-00:00

Physical Review Letters, Vol. 92, No. 18. (2004), pp. 185506-185506.

We study the flow of model hard-sphere colloidal suspensions at high volume fraction driven through a constriction by a pressure gradient. Above a particle-size dependent limit 0, direct microscopic observations demonstrate jamming and unjamming—conversion of fluid to solid and vice versa—during flow. We show that such a jamming flow produces a reduction in colloid concentration x downstream of the constriction. We propose that this "self-filtration" effect is due to a combination of jamming of the particulate part of the system and continuing flow of the liquid part, i.e., the solvent, through the pores of the jammed solid. Thus we link jamming in colloidal and granular media with a "two-fluid-like" picture of the flow of concentrated suspensions. Results are also discussed in the light of the original experiments of Reynolds on dilation in granular materials.

Experimental studies of the flow of concentrated hard sphere suspensions into a constriction

L Isa — 2006-06-07T11:46:33-00:00

Journal of Physics: Conference Series, Vol. 40, No. 1. (2006), pp. 124-132.

Interesting flow properties are observed when a concentrated suspension of colloidal particles flows into a geometrical constriction. We present here a description of two different experimental techniques used to study the pressure driven flow of dense suspensions of micron-sized hard spheres into glass capillaries. The first one involves the analysis of the driving pressure during the flow, the other one is based on fast confocal microscopy. Technical details are given, together with a selection of preliminary results.

From Micro- to Nanofabrication with Soft Materials

Stephen Quake — 2007-09-27T08:45:33-00:00

Science, Vol. 290, No. 5496. (24 November 2000), pp. 1536-1540.

Soft materials are finding applications in areas ranging from microfluidic device technology to nanofabrication. We review recent work in these areas, discuss the motivation for device fabrication with soft materials, and describe applications of soft materials. In particular, we discuss active microfluidic devices for cell sorting and biochemical assays, replication-molded optics with subdiffraction limit features, and nanometer-scale resonators and wires formed from single-molecule DNA templates as examples of how the special properties of soft materials address outstanding problems in device fabrication.

Microfluidics: Fluid physics at the nanoliter scale

Todd Squires — 2006-01-16T15:14:37-00:00

Reviews of Modern Physics, Vol. 77, No. 3. (2005)

Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Péclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

Numerical investigation of mixing in microchannels with patterned grooves

H Wang — 2008-03-11T01:51:39-00:00

Journal of Micromechanics and Microengineering, Vol. 13, No. 6. (2003), pp. 801-808.

Mixing in microchannels with patterned grooves was studied numerically by CFD simulations and particle tracking technique. Point location, velocity interpolation and a fourth-order adaptive Runge-Kutta integration scheme were applied in the particle tracking algorithms. Using these algorithms, Poincare maps were calculated from the 3D velocity field exported from a CFD package for microfluidics (MemCFD). For small aspect ratio (a = 0.05) grooves, the results showed that there was no significant irregularity in the Poincare map, and indicated little chaotic effect. For high aspect ratio (a = 0.30) grooves, the flow pattern became more jumbled, but there was no apparent evidence that indicated the flow was chaotic, for Reynolds numbers up to five. However, Poincare maps could still be used to evaluate the performance of this type of micro-mixer. The particle trajectories recorded in the Poincare maps were circular-like patterns. By counting the number of dots to form one circle in the Poincare maps, the length of the channel to enable one recirculation could be calculated. The results indicated that this length had an exponential relation to the aspect ratio of grooves, and it was independent of the flow velocity. The CFD simulation showed that the transverse motion could fold and stretch fluids to increase their interfacial area. The results showed that micro-mixers with patterned grooves caused rotation of the fluid streams. This rotation can reorient the folding in the depth direction, and can enhance passive mixing in microfluidic devices with shallow channels.

Optically driven viscous micropump using a rotating microdisk

Shoji Maruo — 2008-03-14T02:38:37-00:00

Applied Physics Letters, Vol. 91, No. 8. (2007)

An optically driven micropump using viscous drag exerted on a rotating disk microrotor was developed. The disk microrotor (diameter of 10 µm), which has three columns as targets for the optical trap, is confined to a U-shaped microchannel. To pump fluid, the disk microrotor is rotated by a time-shared optical trapping technique. The flow field inside the U-shaped microchannel was analyzed using finite element method (FEM) based on the Navier-Stokes equation. The optimized micropump was fabricated using a two-photon microfabrication technique. The flow rate of the micropump agreed with simulation result obtained by FEM analysis.

Chaotic Mixing in a Steady Flow in a Microchannel

Claire Simonnet — 2008-03-11T19:37:05-00:00

Physical Review Letters, Vol. 94, No. 13. (2005)

We report experiments on mixing of a passively advected fluorescent dye in a low Reynolds number flow in a microscopic channel. The channel is a chain of repeating segments with a custom designed profile that generates a steady three-dimensional flow with stretching and folding, and chaotic mixing. A few statistical characteristics of mixing in the flow are studied and are all found to agree with theoretical and experimental results for the flows in the Batchelor regime of mixing that are chaotic in time. The proposed microchannel provides fast and efficient mixing and is simple to fabricate.

Chaotic mixing using periodic and aperiodic sequences of mixing protocols in a micromixer

Tae Kang — 2008-03-11T19:28:52-00:00

Microfluidics and Nanofluidics

Abstract We conducted a numerical study on mixing in a barrier embedded micromixer with an emphasis on the effect of periodic and aperiodic sequences of mixing protocols on mixing performance. A mapping method was employed to investigate mixing in various sequences, enabling us to qualitatively observe the progress of mixing and also to quantify both the rate and the final state of mixing. First, we introduce the design concept of the four mixing protocols and the route to achieve chaotic mixing of the mixer. Then, several periodic sequences consisting of the four mixing protocols are used to investigate the mixing performance depending on the sequence. Chaotic mixing was observed, but with different mixing rates and different final mixing states significantly influenced by the specific sequence of mixing protocols and inertia. As for the effect of inertia, the higher the Reynolds number the larger the rotational motion of the fluid leading to faster mixing. We found that a sequence showing the best mixing performance at a certain Reynolds number is not always superior to other sequences in a different Reynolds number regime. A properly chosen aperiodic sequence results in faster and more uniform mixing than periodic sequences.

Chaotic mixing in microfluidic devices driven by oscillatory cross flow

Jr Phelan — 2008-03-11T19:16:10-00:00

Physics of Fluids, Vol. 20, No. 2. (2008)

Shear-induced particle migration in one-, two-, and three-dimensional flows

C Gao — 2008-03-11T19:14:44-00:00

Physical Review E (Statistical, Nonlinear, and Soft Matter Physics), Vol. 77, No. 2. (2008)

We investigate the segregation resulting from the competition between advection and shear-induced migration of suspensions in steady open flows. Herringbone channels form a concentration profile deviating from the particle focusing found in straight channels. Transients can result from a buckling instability during the onset of migration when particle-depleted fluid is injected into particle-rich fluid. In chaotic flows, the better mixing found at low bulk volume fraction is not seen at higher bulk volume fraction. Thus, the ability of static mixers to reduce the effects of shear-induced migration is significantly limited.

Multivortex micromixing

Arjun Sudarsan — 2008-03-11T03:43:00-00:00

Proceedings of the National Academy of Sciences, Vol. 103, No. 19. (9 May 2006), pp. 7228-7233.

The ability to mix liquids in microchannel networks is fundamentally important in the design of nearly every miniaturized chemical and biochemical analysis system. Here, we show that enhanced micromixing can be achieved in topologically simple and easily fabricated planar 2D microchannels by simply introducing curvature and changes in width in a prescribed manner. This goal is accomplished by harnessing a synergistic combination of (i) Dean vortices that arise in the vertical plane of curved channels as a consequence of an interplay between inertial, centrifugal, and viscous effects, and (ii) expansion vortices that arise in the horizontal plane due to an abrupt increase in a conduit's cross-sectional area. We characterize these effects by using confocal microscopy of aqueous fluorescent dye streams and by observing binding interactions between an intercalating dye and double-stranded DNA. These mixing approaches are versatile and scalable and can be straightforwardly integrated as generic components in a variety of lab-on-a-chip systems. 10.1073/pnas.0507976103

Microscale flow visualization

Sinton — 2006-05-18T17:45:40-00:00

Microfluidics and Nanofluidics, Vol. 1, No. 1. (November 2004), pp. 2-21.

Microfluidics-a review

P Gravesen — 2007-02-12T18:58:36-00:00

Journal of Micromechanics and Microengineering, Vol. 3, No. 4. (1993), pp. 168-182.

An overview is given of research activities in the field of fluid components or systems built with microfabrication technologies. This review focuses on the fluidic behaviour of the various devices, such as valves, pumps and flow sensors as well as the possibilities and pitfalls related to the modelling of these devices using simple flow theory. Finally, a number of microfluidic systems are described and comments on future trends are given.

Departure from Navier-Stokes hydrodynamics in confined liquids

Karl Travis — 2006-03-27T09:30:15-00:00

Physical Review E (Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics), Vol. 55, No. 4. (1997), pp. 4288-4295.

In this work we use nonequilibrium molecular dynamics (NEMD) to simulate an atomic liquid undergoing gravity-fed flow down a narrow channel. We compare the simulation results against the predictions of classical Navier-Stokes theory for two different channel widths. For a channel width of 5.1 molecular diameters, we find that the velocity profile deviates significantly from the hydrodynamic prediction. The shape of this velocity profile is found to be independent of the applied field (pressure gradient). We find that the heat flux profile does not agree with the cubic profile predicted by Navier-Stokes hydrodynamics, but shows significant oscillations located about one molecular diameter from the walls. This result differs from the earlier work of Todd and Evans [B. D. Todd and D. J. Evans, J. Chem. Phys. 103, 9804 (1995)], in which an assumption of a purely quadratic velocity profile resulted in very weak oscillations in the heat flux. We find that in narrow channels the viscosity cannot be described by a linear, local constitutive relation. However, classical Navier-Stokes behavior is approached for a channel width of > ~ 10 molecular diameters.

Patterning Flows Using Grooved Surfaces

AD Stroock — 2008-03-11T03:17:03-00:00

Anal. Chem., Vol. 74, No. 20. (15 October 2002), pp. 5306-5312.

Abstract: Through a simple analytical description we quantify how pressure-driven flows over grooved surfaces develop transverse components, which, for shallow grooves, can be modeled with simple anisotropic effective boundary conditions. Helical recirculation results in channels or capillaries with grooved walls. An experimental validation of our model is presented. Our analysis provides a workable guide for the design of 3D flows with simple patterns of grooved regions, e.g., to control the position of streams in the cross section of a channel or to promote mixing. Potential applications in microfluidics are outlined.

The centrifugal microfluidic Bio-Disk platform

Jens Ducrée — 2007-12-11T16:35:45-00:00

Journal of Micromechanics and Microengineering, Vol. 17, No. 7. (2007), pp. S103-S115.

This paper reviews the centrifugal 'Bio-Disk' platform which is based on rotationally controlled, multi-scale liquid handling to fully integrate and automate complex analysis and synthesis protocols in the life sciences. The platform offers the crucial ingredients for a rapid development of applications: a coherent library of fluidic unit operations, a device technology for actuation, liquid interfacing and detection as well as a developer toolbox providing experimental testing, rapid prototyping and simulation capabilities. Various applications in the fields of life science, in vitro diagnostics and micro-process engineering are demonstrated.

Micromixers—a review

Nam-Trung Nguyen — 2007-12-28T23:53:09-00:00

Journal of Micromechanics and Microengineering, Vol. 15, No. 2. (2005), pp. R1-R16.

This review reports the progress on the recent development of micromixers. The review first presents the different micromixer types and designs. Micromixers in this review are categorized as passive micromixers and active micromixers. Due to the simple fabrication technology and the easy implementation in a complex microfluidic system, passive micromixers will be the focus of this review. Next, the review discusses the operation points of the micromixers based on characteristic dimensionless numbers such as Reynolds number Re, Peclet number Pe, and in dynamic cases the Strouhal number St. The fabrication technologies for different mixer types are also analysed. Quantification techniques for evaluation of the performance of micromixers are discussed. Finally, the review addresses typical applications of micromixers.

An Optimized Micromixer with Patterned Grooves

Yanghua Tang — 2008-03-11T02:05:24-00:00

MEMS, NANO and Smart Systems, 2004. ICMENS 2004. Proceedings. 2004 International Conference on (2004), pp. 300-305.

With the development of microfluidic systems, there is a growing interest in micro scale laminar flow mixing. In this work, the fluid rotating angle and mixing efficiency in a micromixer with patterned grooves are studied as a function of the dimensions of the microstructure by numerical simulation. We found that mixing efficiency does not always increase with higher fluid stream rotation in the microchannel. High groove aspect ratios are not advantageous to fluid rotation. Experiments on mixture of two fluids were done on a micromixer fabricated in PDMS by replica molding. An 85% mixing efficiency was obtained in a 30mm long mixing channel with two dyed liquids.

Flexible polyimide probes with microelectrodes and embedded microfluidic channels for simultaneous drug delivery and multi-channel monitoring of bioelectric activity

S Metz — 2006-02-16T23:45:13-00:00

Biosensors and Bioelectronics, Vol. 19, No. 10. (15 May 2004), pp. 1309-1318.

The study of intracellular communication requires devices that can not only monitor the bioelectric activity, but also control and observe the biochemical environment at the cellular level. This paper reports on the development and characterisation of implantable polyimide microprobes that allow simultaneous, selective chemical delivery/probing and multi-channel recording/stimulation of bioelectric activity. The key component of the system is a flexible polyimide substrate with embedded microchannels that is batch-fabricated combining polyimide micromachining and a lamination technique. The devices provide platinum microelectrodes on both sides of the polyimide substrate with an active surface between 20 [mu]m x 20 [mu]m and 50 [mu]m x 50 [mu]m. The embedded microchannels permit highly localised drug delivery or probing at the tip of the device via channel outlets adjacent to the microelectrodes. The microelectrodes were characterised by electrical impedance spectroscopy and the microchannels were studied in microflow experiments. Two different fluid delivery schemes were explored in two different designs. The first device type consists of a simple combination of microchannels and microelectrodes on one substrate. Liquids are ejected at the tip of the device by pressure injection techniques. The second device was inspired by the so-called U-tube concept allowing for highly localised delivery of controlled amounts of liquids in the picoliters range. Thus, the influence of chemical compounds on the electrical activity of cells can be studied with high temporal and spatial resolution. The flexible, implantable devices can be used for studying the chemical and electrical information exchange and communication of cells in in vivo and in vitro experiments.

Zeta potential of microfluidic substrates: 2. Data for polymers.

BJ Kirby — 2006-04-06T17:23:11-00:00

Electrophoresis, Vol. 25, No. 2. (January 2004), pp. 203-213.

Zeta potential data are reviewed for a variety of polymeric microfluidic substrate materials. Many of these materials currently used for microchip fabrication have only recently been employed for generation of electroosmotic flow. Despite their recent history, polymeric microfluidic substrates are currently used extensively for microchip separations and other techniques, and understanding of the surface zeta potential is crucial for experimental design. This paper proposes the use of pC (the negative logarithm of the counterion concentration) as a useful normalization for the zeta potential on polymer substrates in contact with indifferent univalent counterions. Normalizing zeta by pC facilitates comparison of results from many investigators. The sparseness of available data for polymeric substrates prevents complete and rigorous justification for this normalization; however, it is consistent with double layer and adsorption theory. For buffers with indifferent univalent cations, normalization with the logarithm of the counterion concentration in general collapses data onto a single zeta/pC vs. pH curve, and (with the exception of PMMA) the repeatability of the data is quite encouraging. Normalization techniques should allow improved ability to predict zeta potential performance on microfluidic substrates and compare results observed with different parameters.

Zeta potential of microfluidic substrates: 1. Theory, experimental techniques, and effects on separations.

BJ Kirby — 2006-04-06T17:21:07-00:00

Electrophoresis, Vol. 25, No. 2. (January 2004), pp. 187-202.

This paper summarizes theory, experimental techniques, and the reported data pertaining to the zeta potential of silica and silicon with attention to use as microfluidic substrate materials, particularly for microchip chemical separations. Dependence on cation concentration, buffer and cation type, pH, cation valency, and temperature are discussed. The Debye-Hückel limit, which is often correctly treated as a good approximation for describing the ion concentration in the double layer, can lead to serious errors if it is extended to predict the dependence of zeta potential on the counterion concentration. For indifferent univalent electrolytes (e.g., sodium and potassium), two simple scalings for the dependence of zeta potential on counterion concentration can be derived in high- and low-zeta limits of the nonlinear Poisson-Boltzman equation solution in the double layer. It is shown that for most situations relevant to microchip separations, the high-zeta limit is most applicable, leading to the conclusion that the zeta potential on silica substrates is approximately proportional to the logarithm of the molar counterion concentration. The zeta vs. pH dependence measurements from several experiments are compared by normalizing the zeta based on concentration.

Microfluidic analysis of electrokinetic streaming potential induced by microflows of monovalent electrolyte solution

Myung-Suk Chun — 2005-02-05T14:41:31-00:00

Journal of Micromechanics and Microengineering, Vol. 15, No. 4. (April 2005), 710.

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

MS Chun — 2006-04-06T19:50:37-00:00

Lab Chip, Vol. 6, No. 2. (February 2006), pp. 302-309.

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

A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors

Sebastian Maerkl — 2007-01-12T15:17:06-00:00

Science, Vol. 315, No. 5809. (12 January 2007), pp. 233-237.

A major goal of systems biology is to predict the function of biological networks. Although network topologies have been successfully determined in many cases, the quantitative parameters governing these networks generally have not. Measuring affinities of molecular interactions in high-throughput format remains problematic, especially for transient and low-affinity interactions. We describe a high-throughput microfluidic platform that measures such properties on the basis of mechanical trapping of molecular interactions. With this platform we characterized DNA binding energy landscapes for four eukaryotic transcription factors; these landscapes were used to test basic assumptions about transcription factor binding and to predict their in vivo function. 10.1126/science.1131007

Microfluidic devices for cellomics: a review

Helene Andersson — 2008-01-15T23:21:16-00:00

Sensors and Actuators B: Chemical, Vol. 92, No. 3. (15 July 2003), pp. 315-325.

A review of microfluidic devices for cellomics is presented. After a brief description of the historical background of Lab-on-Chip (LOC) devices, different areas are reviewed. Devices for cell sampling are presented, followed by cell trapping and cell sorting devices based upon mechanical and electrical principles. Subsequently, a popular type of cell sorters, flow cytometers, is considered, followed by a chapter describing devices for cell treatment: cell lysis, poration/gene transfection and cell fusion devices. Finally a number of microfluidic devices for cellular studies are reviewed. The large amount of very recent publications treated in this review indicates the rapidly growing interest in this exciting application area of LOC.

Developing optofluidic technology through the fusion of microfluidics and optics

Demetri Psaltis — 2006-07-28T05:50:51-00:00

Nature, Vol. 442, No. 7101. (26 July 2006), pp. 381-386.

Stability analysis of optofluidic transport on solid-core waveguiding structures

Allen Yang — 2008-01-13T11:22:35-00:00

Nanotechnology, Vol. 19, No. 4. (30 January 2008), pp. 45704-45714.

Optical tweezers applied to a microfluidic system.

J Enger — 2007-08-06T19:06:31-00:00

Lab Chip, Vol. 4, No. 3. (June 2004), pp. 196-200.

We will demonstrate how optical tweezers can be combined with a microfluidic system to create a versatile microlaboratory. Cells are moved between reservoirs filled with different media by means of optical tweezers. We show that the cells, on a timescale of a few seconds, can be moved from one reservoir to another without the media being dragged along with them. The system is demonstrated with an experiment where we expose E. coli bacteria to different fluorescent markers. We will also discuss how the system can be used as an advanced cell sorter. It can favorably be used to sort out a small fraction of cells from a large population, in particular when advanced microscopic techniques are required to distinguish various cells. Patterns of channels and reservoirs were generated in a computer and transferred to a mask using either a sophisticated electron beam technique or a standard laser printer. Lithographic methods were applied to create microchannels in rubber silicon (PDMS). Media were transported in the channels using electroosmotic flow. The optical system consisted of a combined confocal and epi-fluorescence microscope, dual optical tweezers and a laser scalpel.

Microfluidics: Sorting particles with light

Jesper Gluckstad — 2007-10-26T18:16:22-00:00

Nat Mater, Vol. 3, No. 1. (January 2004), pp. 9-10.

Long-term monitoring of bacteria undergoing programmed population control in a microchemostat.

FK Balagaddé — 2005-07-26T03:11:04-00:00

Science, Vol. 309, No. 5731. (1 July 2005), pp. 137-140.

Using an active approach to preventing biofilm formation, we implemented a microfluidic bioreactor that enables long-term culture and monitoring of extremely small populations of bacteria with single-cell resolution. We used this device to observe the dynamics of Escherichia coli carrying a synthetic "population control" circuit that regulates cell density through a feedback mechanism based on quorum sensing. The microfluidic bioreactor enabled long-term monitoring of unnatural behavior programmed by the synthetic circuit, which included sustained oscillations in cell density and associated morphological changes, over hundreds of hours.

A chemical waveform synthesizer.

Jessica Olofsson — 2005-06-07T16:14:02-00:00

Proc Natl Acad Sci U S A (31 May 2005)

Algorithms and methods were developed to synthesize complex chemical waveforms in open volumes by using a scanning-probe microfluidic platform. Time-dependent variations and oscillations of one or several chemical species around the scanning probe, such as formation of sine waves, damped oscillations, and generation of more complex patterns, are demonstrated. Furthermore, we show that intricate bursting and chaotic calcium oscillations found in biological microdomains can be reproduced and that a biological cell can be used as a probe to study receptor functionalities as a function of exposure to time-dependent variations of receptor activators and inhibitors. Thus, the method allows for studies of biologically important oscillatory reactions. More generally, the system allows for detailed studies of complex time-varying chemical and physical phenomena in solution or at solution/surface interfaces.

Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics

Elena Lucchetta — 2005-04-27T18:51:12-00:00

Nature, Vol. 434, No. 7037., pp. 1134-1138.

Monitoring dynamics of single-cell gene expression over multiple cell cycles

Scott Cookson — 2005-11-23T02:38:38-00:00

Molecular Systems Biology, Vol. 1, No. 1. (22 November 2005), pp. msb4100032-E1-msb4100032-E6.

Nonlithographic Fabrication of Microfluidic Devices

VI Vullev — 2008-07-09T10:07:41-00:00

J. Am. Chem. Soc., Vol. 128, No. 50. (20 December 2006), pp. 16062-16072.

Abstract: A facile nonlithographic method for expedient fabrication of microfluidic devices of poly(dimethylsiloxane) is described. Positive-relief masters for the molds are directly printed on smooth substrates. For the formation of connecting channels and chambers inside the polymer components of the microfluidic devices, cavity-forming elements are adhered to the surfaces of the masters. Using this nonlithographic approach, we fabricated microfluidic devices for detection of bacterial spores on the basis of enhancement of the emission of terbium (III) ions.

Micro total analysis systems. 1. Introduction, theory, and technology.

DR Reyes — 2008-07-09T11:18:53-00:00

Analytical chemistry, Vol. 74, No. 12. (15 June 2002), pp. 2623-2636.

Micro total analysis systems. 2. Analytical standard operations and applications.

PA Auroux — 2008-07-09T11:17:31-00:00

Analytical chemistry, Vol. 74, No. 12. (15 June 2002), pp. 2637-2652.

Generation of Gradients Having Complex Shapes Using Microfluidic Networks

SKW Dertinger — 2008-07-09T10:24:31-00:00

Anal. Chem., Vol. 73, No. 6. (15 March 2001), pp. 1240-1246.

Abstract: This paper describes the generation of gradients having complex shapes in solution using microfluidic networks. Flowing multiple streams of fluid each carrying different concentrations of substances laminarly and side-by-side generated step concentration gradients perpendicular to the direction of the flow. Appropriately designed networks of microchannels for controlled diffusive mixing of substances generated a range of shapes for the gradients, including linear, parabolic, and periodic. The lateral dimensions of the gradients ranged from 900 to 2200 m. This paper also demonstrates the generation of overlapping gradients composed of different species. Since solutions in the microfluidic network exist as steady states and are continuously renewed, the gradients established in the capillaries are spatially and temporally constant and can be maintained easily for periods of hours. Using laminar flow to generate gradients should be useful in both biological and nonbiological research.

Human neural stem cell growth and differentiation in a gradient-generating microfluidic device

Bong Chung — 2008-07-09T10:18:32-00:00

Lab Chip, Vol. 5, No. 4. (2005), pp. 401-406.

This paper describes a gradient-generating microfluidic platform for optimizing proliferation and differentiation of neural stem cells (NSCs) in culture. Microfluidic technology has great potential to improve stem cell (SC) cultures, whose promise in cell-based therapies is limited by the inability to precisely control their behavior in culture. Compared to traditional culture tools, microfluidic platforms should provide much greater control over cell microenvironment and rapid optimization of media composition using relatively small numbers of cells. Our platform exposes cells to a concentration gradient of growth factors under continuous flow, thus minimizing autocrine and paracrine signaling. Human NSCs (hNSCs) from the developing cerebral cortex were cultured for more than 1 week in the microfluidic device while constantly exposed to a continuous gradient of a growth factor (GF) mixture containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2) and platelet-derived growth factor (PDGF). Proliferation and differentiation of NSCs into astrocytes were monitored by time-lapse microscopy and immunocytochemistry. The NSCs remained healthy throughout the entire culture period, and importantly, proliferated and differentiated in a graded and proportional fashion that varied directly with GF concentration. These concentration-dependent cellular responses were quantitatively similar to those measured in control chambers built into the device and in parallel cultures using traditional 6-well plates. This gradient-generating microfluidic platform should be useful for a wide range of basic and applied studies on cultured cells, including SCs.

SmartBuild-A truly plug-n-play modular microfluidic system

Po Yuen — 2008-07-18T04:42:14-00:00

Lab Chip (2008)

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

Novel inorganic polymer derived microreactors for organic microchemistry applications

Tae-Ho Yoon — 2008-07-18T04:40:16-00:00

Lab Chip (2008)

Microreactors fabricated with optically transparent inorganic polymers from two types of precursors using a UV-microimprinting process demonstrated reliable solvent resistance and capability for performing three model organic synthetic reactions, which were compared with batch systems and glass based microreactors.

Ultraviolet-based bonding for perfluoropolyether low aspect-ratio microchannels and hybrid devices

Carmela Marco — 2008-07-18T04:32:27-00:00

Lab Chip (2008)

Producing solvent-resistant microfluidic devices is a challenge for analytical chemistry and biochemistry. We demonstrate a simple and low-cost fabrication approach for the realization of solvent-resistant microchannels based on perfluoropolyether elastomers, exhibiting very low aspect ratios (0.01). The strength of the microchannels sealing is evaluated through the maximum internal pressure (1.52 MPa) prior to device failure, due to delamination at the bonded interface. This approach allows the elastic properties of silicone elastomers, suitable for high quality external connections, to be combined with the non-swelling character of perfluoropolyethers.

Disposable integrated microfluidics with self-aligned planar microlenses

Jeonggi Seo — 2007-07-26T19:18:33-00:00

Sensors and Actuators B: Chemical, Vol. 99, No. 2-3. (1 May 2004), pp. 615-622.

Design, fabrication, and characterization of the disposable integrated microfluidic devices with self-aligned planar microlenses for the applications of bioanalytical system are described. The development of the polydimethylsiloxane (PDMS)-based disposable integrated microfluidics is realized by the monolithic integration of self-aligned two-dimensional (2D) planar micro-optics with microfluidic chips. The disposable integrated microfluidics with self-aligned planar microlenses allows increasing sensitivity of the device and reducing time-consuming optical alignments. The optical detection of the chips is based on the orthogonal arrangement of excitation light source via integrated 2D planar microlens onto the microfluidic channel and the collection of fluorescent emission. It provides an effective detection mechanism with increased signal-to-noise ratio and a simple `lab-on-a-chip' platform with light emitting diodes (LEDs) as excitation sources and photodiodes as detectors. The 2D compound microlenses of the disposable integrated microfluidic devices promise minimized optical aberration, amplified fluorescence, and self-alignment of the micro-optical components of the bioanalysis systems. The disposable integrated microfluidic devices with self-aligned planar microlenses can be used effectively as low-cost, rapid, and sensitive diagnostic chips.

Simulating the dynamic behavior of immiscible binary fluids in three-dimensional chemically patterned microchannels

Olga Kuksenok — 2007-11-21T05:04:00-00:00

Physical Review E, Vol. 68, No. 1. (11 July 2003), 011502.

Using computer simulations; we investigate the behavior of an immiscible binary AB fluid that is driven to flow through a microchannel; which is decorated with a checkerboard pattern of chemically distinct A - and B -like patches on the top and bottom walls. We isolate conditions where the coupling between the imposed flow field and thermodynamic interactions yields a rich interfacial behavior between the A and B fluids and complex velocity patterns over the checkerboard domains. In effect; the A and B fluids undergo extensive mixing in specific regions of the channel; even for low Reynolds number flow. Decreasing the height-to-width ratio of the patterned microchannel enhances the extent of mixing between these two components. On the other hand; the length of the A / B interfaces is optimized in microchannels that have a square cross section. The results provide guidelines for designing microfluidic devices that can be used to effectively intermix multicomponent fluids.

A low temperature biochemically compatible bonding technique using fluoropolymers for biochemical microfluidic systems

A Han — 2006-02-09T03:20:17-00:00

Micro Electro Mechanical Systems, 2000. MEMS 2000. The Thirteenth Annual International Conference on (2000), pp. 414-418.

A new low temperature biochemically compatible bonding technique using fluoropolymers has been developed in this work and characterized in terms of mechanical bonding strength and biochemical resistance. This bonding technique uses a spin-on Teflon-like amorphous fluorocarbon polymer (CYTOP<sup>TM</sup>) as a bonding interface layer. The developed bonding process requires a bonding temperature of 160°C and the bonding strength attained from the process shows 4.3 Mpa in silicon-to-silicon. Furthermore, the bonding technique achieves reliable and leak-proof bonding in various substrates and provides excellent chemical resistance and biocompatibility for some specific immunoassays. The bonding technique developed in this work has been successfully applied to the development of a microfluidic motherboard system with surface mountable microfluidic components

Darwinian Evolution on a Chip

Brian Paegel — 2008-04-08T18:05:48-00:00

PLoS Biology, Vol. 6, No. 4. (1 April 2008), e85.

Computer control of Darwinian evolution has been demonstrated by propagating a population of RNA enzymes in a microfluidic device. The RNA population was challenged to catalyze the ligation of an oligonucleotide substrate under conditions of progressively lower substrate concentrations. A microchip-based serial dilution circuit automated an exponential growth phase followed by a 10-fold dilution, which was repeated for 500 log-growth iterations. Evolution was observed in real time as the population adapted and achieved progressively faster growth rates over time. The final evolved enzyme contained a set of 11 mutations that conferred a 90-fold improvement in substrate utilization, coinciding with the applied selective pressure. This system reduces evolution to a microfluidic algorithm, allowing the experimenter to observe and manipulate adaptation.

“Bottleneck Effect” in Two-Dimensional Microfluidics

Patricia Burriel — 2008-04-04T18:09:50-00:00

Physical Review Letters, Vol. 100, No. 13. (2008)

An anomalously long transient is needed to achieve a steady pressurization of a fluid when forced to flow through micronarrowed channels under constant mechanical driving. This phenomenon, known as the “bottleneck effect” is here revisited from a different perspective, by using confined displacements of interfacial fluids. Compared to standard microfluidics, such effect admits in this case a neat quantitative characterization, which reveals intrinsic material characteristics of flowing monolayers and permits to envisage strategies for their controlled micromanipulation.

A microfluidic flow-through device for high throughput electrical lysis of bacterial cells based on continuous dc voltage

HY Wang — 2007-08-17T16:40:13-00:00

Biosensors and Bioelectronics, Vol. 22, No. 5. (2006), pp. 582-588.

Interest in electrical lysis of biological cells on a microfludic platform has increased because it allows for the rapid recovery of intracellular contents without introducing lytic agents. In this study we demonstrated a simple microfluidic flow-through device which lysed Escherichia coli cells under a continuous dc voltage. The E. coli cells had previously been modified to express green fluorescent protein (GFP). In our design, the cell lysis only happened in a defined section of a microfluidic channel due to the local field amplification by geometric modification. The geometric modification also effectively decreased the required voltage for lysis by several folds. We found that local field strength of 1000-1500 V/cm was required for nearly 100% cell death. This threshold field strength was considerably lower than the value reported in the literature, possibly due to the longer duration of the field [Lee, S.W., Tai, Y.C., 1999. Sens. Actuators A: Phys. 73, 74-79]. Cell lysis was detected by both plate count and fluorescence spectroscopy. The cell membrane was completely disintegrated in the lysis section of the microfluidic device, when the field strength was higher than 2000 V/cm. The devices were fabricated using low-cost soft lithography with channel widths considerably larger than the cell size to avoid clogging and ensure stable performance. Our tool will be ideal for high throughput processing of bacterial cells for chemical analysis of intracellular contents such as DNA and proteins. The application of continuous dc voltage greatly simplified the instrumentation compared to devices using electrical pulses for similar purposes. In principle, the same approach can also be applied for lysis of mammalian cells and electroporative transfection. © 2006 Elsevier B.V. All rights reserved.

A continuous electrical cell lysis device using a low dc voltage for a cell transport and rupture

DW Lee — 2007-08-17T16:35:07-00:00

Sens Actuators, B Chem, Vol. 124, No. 1. (2007), pp. 84-89.

We present a continuous and low voltage cell lysis device in which a width and length of a channel change to generate focused the high electric field strength for cell lysis and the low electric field strength for a transport of samples. The previous cell lysis devices acquire the high electric field strength for a cell lysis by applying an ac voltage to a micro-gap between electrodes and require additional pumps or valves for a sample transport. However, when we change the width and length of the channel between a pair of external electrodes attached to a dc voltage, we generate both the high electric field strength for a cell lysis and the low electric field strength for an electroosmotic flow. The present device therefore performs continuous cell lysis and a sample transport without needing either an additional flow source or an additional process fabricating the electrodes for the micro-gap. The experimental study features an orifice whose width and length is 20 times narrower and 175 times shorter than the width and length of a microchannel. With an operational voltage of 50 V, the present device generates high electric field strength of 1.2 kV/cm at the orifice to disrupt cells with 100% lysis rate of red blood cells and low electric field strength of 60 V/cm at the microchannel to generate an electroosmotic flow of 30 ± 9 ?m/s. In conclusion, the present device is capable of continuous self-pumping cell lysis at a low voltage; thus, it is suitable for a sample pretreatment component of a micro total analysis system or lab-on-a-chip. © 2006 Elsevier B.V. All rights reserved.