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

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.

[1]  B. Finlayson,et al.  Combinatorial mixing of microfluidic streams. , 2004, Lab on a chip.

[2]  B. Lin,et al.  Parallel microfluidic networks for studying cellular response to chemical modulation. , 2007, Journal of biotechnology.

[3]  Mark A Burns,et al.  Analysis of non-Newtonian liquids using a microfluidic capillary viscometer. , 2006, Analytical chemistry.

[4]  H. El-Samad,et al.  Bound attractant at the leading vs. the trailing edge determines chemotactic prowess , 2007, Proceedings of the National Academy of Sciences.

[5]  A. Valero,et al.  Optimization of microfluidic single cell trapping for long-term on-chip culture. , 2010, Lab on a chip.

[6]  Chong H. Ahn,et al.  An on-chip air-bursting detonator for driving fluids on disposable lab-on-a-chip systems , 2007 .

[7]  D T Chiu,et al.  Using three-dimensional microfluidic networks for solving computationally hard problems , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Mohr,et al.  Systematic linearisation of a microfluidic gradient network with unequal solution inlet viscosities demonstrated using glycerol , 2010 .

[9]  Hanry Yu,et al.  A practical guide to microfluidic perfusion culture of adherent mammalian cells. , 2007, Lab on a chip.

[10]  M. Tokeshi,et al.  Glass microchip with three-dimensional microchannel network for 2 x 2 parallel synthesis. , 2002, Lab on a chip.

[11]  Guoping Lian,et al.  Compact model for multi-phase liquid-liquid flows in micro-fluidic devices. , 2005, Lab on a chip.

[12]  Alex Groisman,et al.  An easy to assemble microfluidic perfusion device with a magnetic clamp. , 2009, Lab on a chip.

[13]  P. Cremer,et al.  Generating fixed concentration arrays in a microfluidic device , 2003 .

[14]  Luis F. Olguin,et al.  Simultaneous measurement of reactions in microdroplets filled by concentration gradients. , 2009, Lab on a chip.

[15]  A. B. Frazier,et al.  Reliability aspects of packaging and integration technology for microfluidic systems , 2005, IEEE Transactions on Device and Materials Reliability.

[16]  Sergey S Shevkoplyas,et al.  Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device. , 2006, Lab on a chip.

[17]  F. Okkels,et al.  A generalized theoretical model for "continuous particle separation in a microchannel having asymmetrically arranged multiple branches". , 2009, Lab on a chip.

[18]  Kae Sato,et al.  Power-free poly(dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis. , 2004, Lab on a chip.

[19]  B. Chung,et al.  Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. , 2005, Lab on a chip.

[20]  Y. Tai,et al.  Monolithic fabrication of three-dimensional microfluidic networks for constructing cell culture array with an integrated combinatorial mixer , 2008 .

[21]  Jean-Louis Viovy,et al.  Design, modeling and characterization of microfluidic architectures for high flow rate, small footprint microfluidic systems. , 2011, Lab on a chip.

[22]  S. Quake,et al.  Microfluidics: Fluid physics at the nanoliter scale , 2005 .

[23]  Dongqing Li,et al.  Analysis of electrokinetic flow in microfluidic networks , 2004 .

[24]  G. Whitesides,et al.  Generation of Solution and Surface Gradients Using Microfluidic Systems , 2000 .

[25]  D. Webster Combinatorial and High‐Throughput Methods in Macromolecular Materials Research and Development , 2008 .

[26]  Jintae Kim,et al.  Centrifugal microfluidics for biomedical applications. , 2010, Lab on a chip.

[27]  P. Yager,et al.  A rapid diffusion immunoassay in a T-sensor , 2001, Nature Biotechnology.

[28]  J. Wikswo,et al.  Effects of flow and diffusion on chemotaxis studies in a microfabricated gradient generator. , 2005, Lab on a chip.

[29]  Jingjun Xu,et al.  A multishear microfluidic device for quantitative analysis of calcium dynamics in osteoblasts. , 2011, Biochemical and biophysical research communications.

[30]  Raymond H. W. Lam,et al.  Culturing Aerobic and Anaerobic Bacteria and Mammalian Cells with a Microfluidic Differential Oxygenator , 2009, Analytical chemistry.

[31]  M. Gad-el-Hak The MEMS Handbook , 2001 .

[32]  Erik K. Bassett,et al.  Lung assist device technology with physiologic blood flow developed on a tissue engineered scaffold platform. , 2011, Lab on a chip.

[33]  Andreas Manz,et al.  Latest developments in micro total analysis systems. , 2010, Analytical chemistry.

[34]  J. Koo,et al.  Liquid flow in microchannels: experimental observations and computational analyses of microfluidics effects , 2003 .

[35]  Alex Groisman,et al.  Quantitative measurements of the strength of adhesion of human neutrophils to a substratum in a microfluidic device. , 2007, Analytical chemistry.

[36]  B. Kirby Micro- and nanoscale fluid mechanics : transport in microfluidic devices , 2010 .

[37]  강지윤,et al.  Hydrodynamically Focused Particle Filtration Using an Island Structure , 2009 .

[38]  Susan E. Abbatiello,et al.  Erratum: Synergistic drug combinations tend to improve therapeutically relevant selectivity , 2009, Nature Biotechnology.

[39]  Frédéric Clerc,et al.  Optimisation methodologies and algorithms for research on catalysis employing high-throughput methods: comparison using the Selox benchmark. , 2007, Combinatorial chemistry & high throughput screening.

[40]  Craig A Simmons,et al.  Macro- and microscale fluid flow systems for endothelial cell biology. , 2010, Lab on a chip.

[41]  Daniel Rothbart Explaining the Growth of Scientific Knowledge: Metaphors, Models, and Meanings , 1997 .

[42]  George M. Whitesides,et al.  Coding/Decoding and Reversibility of Droplet Trains in Microfluidic Networks , 2007, Science.

[43]  N. Mortensen,et al.  Reexamination of Hagen-Poiseuille flow: shape dependence of the hydraulic resistance in microchannels. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[44]  A. Bhagat,et al.  Continuous particle separation in spiral microchannels using Dean flows and differential migration. , 2008, Lab on a chip.

[45]  M. Yamada,et al.  Continuous particle separation in a microchannel having asymmetrically arranged multiple branches. , 2005, Lab on a chip.

[46]  G. Ming,et al.  A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues. , 2008, Lab on a chip.

[47]  Mann A. Shoffner,et al.  Integrated cell isolation and polymerase chain reaction analysis using silicon microfilter chambers. , 1998, Analytical biochemistry.

[48]  K. Oh,et al.  3-Dimensional cell culture for on-chip differentiation of stem cells in embryoid body. , 2011, Lab on a chip.

[49]  Andreas Schmid,et al.  A rapid, reliable, and automatable lab-on-a-chip interface. , 2009, Lab on a chip.

[50]  Eun Kyu Lee,et al.  On-chip immunoassay using surface-enhanced Raman scattering of hollow gold nanospheres. , 2010, Analytical chemistry.

[51]  Xiaoju Tang,et al.  A PDMS viscometer for microliter Newtonian fluid , 2007 .

[52]  P. Kenis,et al.  Active control of the depletion boundary layers in microfluidic electrochemical reactors. , 2006, Lab on a chip.

[53]  T. Floyd-Smith,et al.  Patterned dispersion of nanoparticles in hydrogels using microfluidics , 2008 .

[54]  Ahmad S. Khalil,et al.  Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate , 2010, Biomedical microdevices.

[55]  Luke P. Lee,et al.  Tunable liquid-filled microlens array integrated with microfluidic network. , 2003, Optics express.

[56]  C Gärtner,et al.  Polymer microfabrication methods for microfluidic analytical applications , 2000, Electrophoresis.

[57]  Tingrui Pan,et al.  Fit-to-Flow (F2F) interconnects: universal reversible adhesive-free microfluidic adaptors for lab-on-a-chip systems. , 2011, Lab on a chip.

[58]  Thomas Laurell,et al.  Buffer medium exchange in continuous cell and particle streams using ultrasonic standing wave focusing , 2009 .

[59]  David W Inglis,et al.  Critical particle size for fractionation by deterministic lateral displacement. , 2006, Lab on a chip.

[60]  Bingcheng Lin,et al.  Droplet-based microfluidic system for individual Caenorhabditis elegans assay. , 2008, Lab on a chip.

[61]  Jan Eijkel,et al.  Evaporation driven pumping for chromatography application. , 2002, Lab on a chip.

[62]  H. Morgan,et al.  Integrated systems for rapid point of care (PoC) blood cell analysis. , 2011, Lab on a chip.

[63]  A. Folch,et al.  A multi-purpose microfluidic perfusion system with combinatorial choice of inputs, mixtures, gradient patterns, and flow rates. , 2009, Lab on a chip.

[64]  S. Takayama,et al.  Gravity-driven microfluidic particle sorting device with hydrodynamic separation amplification. , 2007, Analytical chemistry.

[65]  Bradford J. Smith,et al.  Agent-based simulations of complex droplet pattern formation in a two-branch microfluidic network. , 2010, Lab on a chip.

[66]  S. Takayama,et al.  Arrays of horizontally-oriented mini-reservoirs generate steady microfluidic flows for continuous perfusion cell culture and gradient generation. , 2004, The Analyst.

[67]  K. Oh,et al.  Generalized serial dilution module for monotonic and arbitrary microfluidic gradient generators. , 2009, Lab on a chip.

[68]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.

[69]  O. Orwar,et al.  Microfluidic gradient-generating device for pharmacological profiling. , 2005, Analytical chemistry.

[70]  J. Voldman,et al.  Microfluidic arrays for logarithmically perfused embryonic stem cell culture. , 2006, Lab on a chip.

[71]  Po Ki Yuen,et al.  Multidimensional modular microfluidic system. , 2009, Lab on a chip.

[72]  Armand Ajdari,et al.  Steady flows in networks of microfluidic channels: building on the analogy with electrical circuits , 2004 .

[73]  Robert H. Austin,et al.  Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials , 2008, Proceedings of the National Academy of Sciences.

[74]  G. Whitesides,et al.  Microfluidic arrays of fluid-fluid diffusional contacts as detection elements and combinatorial tools. , 2001, Analytical chemistry.

[75]  A. Undar,et al.  A microfluidic device for continuous, real time blood plasma separation. , 2006, Lab on a chip.

[76]  Richard B. Fair,et al.  Digital microfluidics: is a true lab-on-a-chip possible? , 2007 .

[77]  Ximin He,et al.  A double droplet trap system for studying mass transport across a droplet-droplet interface. , 2010, Lab on a chip.

[78]  D. Beebe,et al.  Cell infection within a microfluidic device using virus gradients , 2004 .

[79]  R. Zengerle,et al.  Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications. , 2010, Chemical Society reviews.

[80]  Chong H. Ahn,et al.  Miniaturization of pinch-type valves and pumps for practical micro total analysis system integration , 2005 .

[81]  J. Eijkel,et al.  Energy conversion in microsystems: is there a role for micro/nanofluidics? , 2007, Lab on a chip.

[82]  M. S. Practical Electricity , 2022, Nature.

[83]  M. Kersaudy-Kerhoas,et al.  Hydrodynamic blood plasma separation in microfluidic channels , 2009 .

[84]  S. Cho,et al.  Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits , 2003 .

[85]  Sindy K. Y. Tang,et al.  Dynamically reconfigurable liquid-core liquid-cladding lens in a microfluidic channel. , 2008, Lab on a chip.

[86]  Hyoung J. Cho,et al.  Droplet actuation on a liquid layer due to thermocapillary motion: Shape effect , 2010 .

[87]  M. Tokeshi,et al.  Continuous‐Flow Chemical Processing in Three‐Dimensional Microchannel Network for On‐Chip Integration of Multiple Reactions in a Combinatorial Mode , 2005 .

[88]  Qiaobing Xu,et al.  A general method for patterning gradients of biomolecules on surfaces using microfluidic networks. , 2005, Analytical chemistry.

[89]  Yeshaiahu Fainman,et al.  On-chip microfluidic tuning of an optical microring resonator , 2006 .

[90]  Albert Folch,et al.  Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies. , 2005, Lab on a chip.

[91]  S. Sugiura,et al.  Microenvironment array chip for cell culture environment screening. , 2011, Lab on a chip.

[92]  R. Austin,et al.  Hydrodynamic Focusing on a Silicon Chip: Mixing Nanoliters in Microseconds , 1998 .

[93]  Jeffrey T Borenstein,et al.  Branched vascular network architecture: a new approach to lung assist device technology. , 2010, The Journal of thoracic and cardiovascular surgery.

[94]  N. Monteiro-Riviere,et al.  A linear dilution microfluidic device for cytotoxicity assays. , 2007, Lab on a chip.

[95]  W. Messner,et al.  Pressure-driven spatiotemporal control of the laminar flow interface in a microfluidic network. , 2007, Lab on a chip.

[96]  A. Manz,et al.  Micro total analysis systems. Latest advancements and trends. , 2006, Analytical chemistry.

[97]  M. Toner,et al.  Universal microfluidic gradient generator. , 2006, Analytical chemistry.

[98]  Chien-Cheng Chang,et al.  High-pressure needle interface for thermoplastic microfluidics. , 2009, Lab on a chip.

[99]  M. S. Levy,et al.  Framework for the Rapid Optimization of Soluble Protein Expression in Escherichia coli Combining Microscale Experiments and Statistical Experimental Design , 2007, Biotechnology progress.

[100]  Philippe Renaud,et al.  A simple pneumatic setup for driving microfluidics. , 2007, Lab on a chip.

[101]  Yu-Chong Tai,et al.  A 3-D microfluidic combinatorial cell array , 2011, Biomedical microdevices.

[102]  N. Gershenfeld,et al.  Microfluidic Bubble Logic , 2006, Science.

[103]  Sung-Jin Park,et al.  Fabrication of the PDMS microchip for serially diluting sample with buffer , 2003 .

[104]  G. Whitesides,et al.  Dynamic control of liquid-core/liquid-cladding optical waveguides , 2004, (CLEO). Conference on Lasers and Electro-Optics, 2005..

[105]  N. D. de Rooij,et al.  A novel microfluidic concept for bioanalysis using freely moving beads trapped in recirculating flows. , 2003, Lab on a chip.

[106]  M. Yamada,et al.  Microfluidic particle sorter employing flow splitting and recombining. , 2006, Analytical chemistry.

[107]  H. Tseng,et al.  A dynamic micromixer for arbitrary control of disguised chemical selectivity. , 2008, Chemical communications.

[108]  S. Shoji Micro Total Analysis Systems , 1999 .

[109]  D. Bartholomeusz,et al.  Xurography: rapid prototyping of microstructures using a cutting plotter , 2005, Journal of Microelectromechanical Systems.

[110]  Luke P. Lee,et al.  A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array. , 2005, Lab on a chip.

[111]  R. J. Cornish,et al.  Flow in a Pipe of Rectangular Cross-Section , 1928 .

[112]  Yu Tian,et al.  Comparison of inlet geometry in microfluidic cell affinity chromatography. , 2011, Analytical chemistry.

[113]  M. Yamada,et al.  In-channel focusing of flowing microparticles utilizing hydrodynamic filtration , 2009 .

[114]  G. Whitesides,et al.  Gradients of substrate-bound laminin orient axonal specification of neurons , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[115]  George M. Whitesides,et al.  Solving Mazes Using Microfluidic Networks , 2003 .

[116]  J. Friend,et al.  Fabrication of microfluidic devices using polydimethylsiloxane. , 2010, Biomicrofluidics.

[117]  S. Vanapalli,et al.  Behavior of a train of droplets in a fluidic network with hydrodynamic traps. , 2010, Biomicrofluidics.

[118]  C. Simmons,et al.  Matrix-dependent adhesion of vascular and valvular endothelial cells in microfluidic channels. , 2007, Lab on a chip.

[119]  Anne L Plant,et al.  A vacuum manifold for rapid world-to-chip connectivity of complex PDMS microdevices. , 2009, Lab on a chip.

[120]  W. Maier,et al.  Combinatorial and high-throughput materials science. , 2007, Angewandte Chemie.

[121]  Minoru Seki,et al.  Microfluidic devices for size-dependent separation of liver cells , 2007, Biomedical microdevices.

[122]  Kangsun Lee,et al.  Parallel synchronization of two trains of droplets using a railroad-like channel network. , 2011, Lab on a chip.

[123]  Cheuk-Wing Li,et al.  Generation of linear and non-linear concentration gradients along microfluidic channel by microtunnel controlled stepwise addition of sample solution. , 2007, Lab on a chip.

[124]  Darko Stefanovic,et al.  Characterization of transverse channel concentration profiles obtainable with a class of microfluidic networks. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[125]  Darwin R. Reyes,et al.  Micro total analysis systems. 1. Introduction, theory, and technology. , 2002, Analytical chemistry.

[126]  Shinji Sugiura,et al.  Pressure‐driven perfusion culture microchamber array for a parallel drug cytotoxicity assay , 2008, Biotechnology and bioengineering.

[127]  L. Hood,et al.  Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood , 2008, Nature Biotechnology.

[128]  Jian Shi,et al.  Characterization of microfluidic fuel cell based on multiple laminar flow , 2007 .

[129]  D. Inglis A method for reducing pressure-induced deformation in silicone microfluidics. , 2010, Biomicrofluidics.

[130]  Luke P. Lee,et al.  Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays. , 2006, Analytical chemistry.

[131]  J. Kang,et al.  A serial dilution microfluidic device using a ladder network generating logarithmic or linear concentrations. , 2008, Lab on a chip.

[132]  Frantisek Svec,et al.  Flow control valves for analytical microfluidic chips without mechanical parts based on thermally responsive monolithic polymers. , 2003, Analytical chemistry.

[133]  J. Lewis,et al.  Direct-write assembly of biomimetic microvascular networks for efficient fluid transport , 2010 .

[134]  Mark A. Burns,et al.  Acoustically driven programmable liquid motion using resonance cavities , 2009, Proceedings of the National Academy of Sciences.

[135]  Je-Kyun Park,et al.  Microfluidic parallel circuit for measurement of hydraulic resistance. , 2010, Biomicrofluidics.

[136]  Jun Yang,et al.  Controllable positioning and alignment of silver nanowires by tunable hydrodynamic focusing , 2011, Nanotechnology.

[137]  Jian-Bin Bao,et al.  Measurement of flow in microfluidic networks with micrometer‐sized flow restrictors , 2006 .

[138]  Milica Radisic,et al.  Deterministic lateral displacement as a means to enrich large cells for tissue engineering. , 2009, Analytical chemistry.

[139]  Adrien Plecis,et al.  Fabrication of microfluidic devices based on glass-PDMS-glass technology , 2007 .

[140]  Shuichi Takayama,et al.  Computerized microfluidic cell culture using elastomeric channels and Braille displays. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[141]  Willem Verboom,et al.  Multichannel quench-flow microreactor chip for parallel reaction monitoring. , 2007, Lab on a chip.

[142]  Bong-Kee Lee,et al.  A novel monolithic fabrication method for a plastic microfluidic chip with liquid interconnecting ports , 2010 .

[143]  Jing-Tang Yang,et al.  Characterization of microfluidic mixing and reaction in microchannels via analysis of cross-sectional patterns. , 2011, Biomicrofluidics.

[144]  Robert W Barber,et al.  Biomimetic design of microfluidic manifolds based on a generalised Murray's law. , 2006, Lab on a chip.

[145]  A. Groisman,et al.  Generation of complex concentration profiles in microchannels in a logarithmically small number of steps. , 2007, Lab on a chip.

[146]  Roland Zengerle,et al.  Microfluidic platforms for lab-on-a-chip applications. , 2007, Lab on a chip.

[147]  A. Jayaraman,et al.  Dynamic gene expression profiling using a microfabricated living cell array. , 2004, Analytical chemistry.

[148]  Shoji Takeuchi,et al.  A trap-and-release integrated microfluidic system for dynamic microarray applications , 2007, Proceedings of the National Academy of Sciences.

[149]  B. Lin,et al.  Cell-based high content screening using an integrated microfluidic device. , 2007, Lab on a chip.

[150]  Sung Yang,et al.  A microfluidic device for continuous white blood cell separation and lysis from whole blood. , 2010, Artificial organs.

[151]  David W. M. Marr,et al.  Hydrodynamic focusing for vacuum-pumped microfluidics , 2005 .

[152]  Adrien Plecis,et al.  Microfluidic analogy of the wheatstone bridge for systematic investigations of electro-osmotic flows. , 2008, Analytical chemistry.

[153]  R. Jaenisch,et al.  Microfluidic Control of Cell Pairing and Fusion , 2009, Nature Methods.

[154]  Larry J. Markoski,et al.  Microfluidic fuel cell based on laminar flow , 2004 .

[155]  Sergey S Shevkoplyas,et al.  Biomimetic autoseparation of leukocytes from whole blood in a microfluidic device. , 2005, Analytical chemistry.

[156]  Chong H. Ahn,et al.  Institute of Physics Publishing Journal of Micromechanics and Microengineering a Review of Microvalves , 2022 .

[157]  Masahito Hosokawa,et al.  Microfluidic device with chemical gradient for single-cell cytotoxicity assays. , 2011, Analytical chemistry.

[158]  S. Gurrum,et al.  Thermal issues in next-generation integrated circuits , 2004, IEEE Transactions on Device and Materials Reliability.

[159]  J. Rossier,et al.  Injection and flow control system for microchannels. , 2004, Lab on a chip.

[160]  J. Chang,et al.  Serial dilution microchip for cytotoxicity test , 2004 .

[161]  G. Whitesides,et al.  Three-dimensional microfluidic devices fabricated in layered paper and tape , 2008, Proceedings of the National Academy of Sciences.

[162]  Andreas Manz,et al.  Micro total analysis systems: latest achievements. , 2008, Analytical chemistry.

[163]  L Chen,et al.  Generation of dynamic chemical signals with microfluidic C-DACs. , 2007, Lab on a chip.

[164]  Roland Zengerle,et al.  Lab-on-a-Foil: microfluidics on thin and flexible films. , 2010, Lab on a chip.

[165]  Matthew Tirrell,et al.  Cell adhesion and growth to Peptide-patterned supported lipid membranes. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[166]  G. Whitesides,et al.  Polymer microstructures formed by moulding in capillaries , 1995, Nature.

[167]  Patrick S Doyle,et al.  Permeation-driven flow in poly(dimethylsiloxane) microfluidic devices. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[168]  S. Bhatia,et al.  An extracellular matrix microarray for probing cellular differentiation , 2005, Nature Methods.

[169]  S. Siddhaye,et al.  System-level modeling and simulation of biochemical assays in lab-on-a-chip devices , 2007 .

[170]  Howard A. Stone,et al.  ENGINEERING FLOWS IN SMALL DEVICES , 2004 .

[171]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[172]  Kevin Loutherback,et al.  Improved performance of deterministic lateral displacement arrays with triangular posts , 2010 .

[173]  George M Whitesides,et al.  The pressure drop along rectangular microchannels containing bubbles. , 2007, Lab on a chip.

[174]  L. Yobas,et al.  Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip. , 2007, Lab on a chip.

[175]  Klavs F Jensen,et al.  Solder-based chip-to-tube and chip-to-chip packaging for microfluidic devices. , 2007, Lab on a chip.

[176]  S. Quake,et al.  Versatile, fully automated, microfluidic cell culture system. , 2007, Analytical chemistry.

[177]  Giovanni Vozzi,et al.  Finite element modelling and design of a concentration gradient generating bioreactor: application to biological pattern formation and toxicology. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[178]  M. Yamada,et al.  Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. , 2005, Lab on a chip.

[179]  Luke P. Lee,et al.  Dynamic single cell culture array. , 2006, Lab on a chip.

[180]  Frederick Sachs,et al.  Microfluidic actuation using electrochemically generated bubbles. , 2002, Analytical chemistry.

[181]  Armand Ajdari,et al.  Microfluidic bypass for efficient passive regulation of droplet traffic at a junction , 2006 .

[182]  Chang Liu,et al.  Re-configurable fluid circuits by PDMS elastomer micromachining , 1999, Technical Digest. IEEE International MEMS 99 Conference. Twelfth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.99CH36291).

[183]  Shuichi Takayama,et al.  Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method. , 2003, Lab on a chip.

[184]  Hongjun Song,et al.  System-level simulation of liquid filling in microfluidic chips. , 2011, Biomicrofluidics.

[185]  A. Levchenko,et al.  Microengineered platforms for cell mechanobiology. , 2009, Annual review of biomedical engineering.

[186]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[187]  Y. Tai,et al.  A 3-D Microfluidic Combinatorial Cell Culture Array , 2009, 2009 IEEE 22nd International Conference on Micro Electro Mechanical Systems.

[188]  Dhananjay Dendukuri,et al.  Controlled synthesis of nonspherical microparticles using microfluidics. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[189]  A. Manz,et al.  Micro total analysis systems. Recent developments. , 2004, Analytical chemistry.

[190]  Francis Lin,et al.  Generation of dynamic temporal and spatial concentration gradients using microfluidic devices. , 2004, Lab on a chip.

[191]  M. Bayindir,et al.  Microfluidics for reconfigurable electromagnetic metamaterials , 2009 .

[192]  Caglar Elbuken,et al.  Microfluidic system with integrated electroosmotic pumps, concentration gradient generator and fish cell line (RTgill-W1)--towards water toxicity testing. , 2009, Lab on a chip.

[193]  Gwo-Bin Lee,et al.  The hydrodynamic focusing effect inside rectangular microchannels , 2006 .

[194]  Howard A. Stone,et al.  Microfluidics: Tuned-in flow control , 2009 .

[195]  Ian Papautsky,et al.  Virtual electrowetting channels: electronic liquid transport with continuous channel functionality. , 2010, Lab on a chip.

[196]  Daniel C Leslie,et al.  Frequency-specific flow control in microfluidic circuits with passive elastomeric features , 2009 .

[197]  Mark E. Polinkovsky,et al.  Fine temporal control of the medium gas content and acidity and on-chip generation of series of oxygen concentrations for cell cultures. , 2009, Lab on a chip.

[198]  Juan G. Santiago,et al.  A review of micropumps , 2004 .

[199]  Luke P. Lee,et al.  Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. , 2005, Biotechnology and bioengineering.

[200]  Andreas Manz,et al.  Latest developments in microfluidic cell biology and analysis systems. , 2010, Analytical chemistry.

[201]  M. Yamada,et al.  Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. , 2004, Analytical chemistry.

[202]  H. Becker,et al.  Polymer microfluidic devices. , 2002, Talanta.

[203]  G. Whitesides,et al.  Generation of Gradients Having Complex Shapes Using Microfluidic Networks , 2001 .

[204]  Xingyu Jiang,et al.  Modular microfluidics for gradient generation. , 2008, Lab on a chip.

[205]  Youngeun Kim,et al.  2-layer based microfluidic concentration generator by hybrid serial and volumetric dilutions , 2010, Biomedical microdevices.

[206]  Michela Matteoli,et al.  Controlled deposition of cells in sealed microfluidics using flow velocity boundaries. , 2009, Lab on a chip.

[207]  Douglas A Lauffenburger,et al.  Microfluidic shear devices for quantitative analysis of cell adhesion. , 2004, Analytical chemistry.

[208]  N.R. Aluru,et al.  Combined circuit/device modeling and simulation of integrated microfluidic systems , 2005, Journal of Microelectromechanical Systems.

[209]  N. Jeon,et al.  Biological applications of microfluidic gradient devices. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[210]  Jin-Woo Choi,et al.  Disposable smart lab on a chip for point-of-care clinical diagnostics , 2004, Proceedings of the IEEE.

[211]  Paul Yager,et al.  Cell lysis and protein extraction in a microfluidic device with detection by a fluorogenic enzyme assay. , 2002, Analytical chemistry.

[212]  Dan Bratton,et al.  Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays. , 2009, Lab on a chip.

[213]  Nancy A. Monteiro-Riviere,et al.  Microfabricated curtains for controlled cell seeding in high throughput microfluidic systems. , 2009, Lab on a chip.

[214]  Rajiv Kumar,et al.  Optimizing drug delivery systems using systematic "design of experiments." Part I: fundamental aspects. , 2005, Critical reviews in therapeutic drug carrier systems.

[215]  Justin Cooper-White,et al.  Microbioreactor array for full-factorial analysis of provision of multiple soluble factors in cellular microenvironments. , 2009, Biotechnology and bioengineering.

[216]  W. Maier,et al.  Strategies for the discovery of new catalysts with combinatorial chemistry , 2004 .

[217]  J. Sturm,et al.  Continuous Particle Separation Through Deterministic Lateral Displacement , 2004, Science.

[218]  Luke P. Lee,et al.  Systematic characterization of degas-driven flow for poly(dimethylsiloxane) microfluidic devices. , 2011, Biomicrofluidics.

[219]  Eli J. Weinberg,et al.  In vitro analysis of a hepatic device with intrinsic microvascular-based channels , 2008, Biomedical microdevices.

[220]  Thomas Gervais,et al.  Flow-induced deformation of shallow microfluidic channels. , 2006, Lab on a chip.

[221]  P. Pittet,et al.  Amperometric quantification based on serial dilution microfluidic systems. , 2009, The Analyst.

[222]  Shih-hui Chao,et al.  Rapid fabrication of microchannels using microscale plasma activated templating (microPLAT) generated water molds. , 2007, Lab on a chip.

[223]  Joo H. Kang,et al.  Analysis of pressure-driven air bubble elimination in a microfluidic device. , 2008, Lab on a chip.

[224]  R. Nuzzo,et al.  A method for filling complex polymeric microfluidic devices and arrays. , 2001, Analytical chemistry.

[225]  Dongshin Kim,et al.  A method for dynamic system characterization using hydraulic series resistance. , 2006, Lab on a chip.

[226]  A. Bhagat,et al.  Inertial microfluidics for continuous particle separation in spiral microchannels. , 2009, Lab on a chip.

[227]  Tae Song Kim,et al.  Rapid exchange of oil-phase in microencapsulation chip to enhance cell viability. , 2009, Lab on a chip.

[228]  Sung-Dong Yang,et al.  Blood Plasma Separation in Microfluidic Channels Using Flow Rate Control , 2005, ASAIO journal.

[229]  Heinz Schmid,et al.  Siloxane Polymers for High-Resolution, High-Accuracy Soft Lithography , 2000 .

[230]  K. Oh,et al.  Microfluidic concentration-on-demand combinatorial dilutions , 2011 .

[231]  D. Beebe,et al.  Controlled microfluidic interfaces , 2005, Nature.

[232]  Darwin R. Reyes,et al.  Micro total analysis systems. 2. Analytical standard operations and applications. , 2002, Analytical chemistry.

[233]  J. Apfeld,et al.  A microfabricated array of clamps for immobilizing and imaging C. elegans. , 2007, Lab on a chip.

[234]  D J Beebe,et al.  Microfabricated elastomeric stencils for micropatterning cell cultures. , 2000, Journal of biomedical materials research.

[235]  Tza-Huei Wang,et al.  DNA methylation analysis on a droplet-in-oil PCR array. , 2009, Lab on a chip.

[236]  Jeffrey D Zahn,et al.  Continuous cytometric bead processing within a microfluidic device for bead based sensing platforms. , 2007, Lab on a chip.

[237]  Ming C. Wu,et al.  Massively parallel manipulation of single cells and microparticles using optical images , 2005, Nature.

[238]  Tingrui Pan,et al.  Three-dimensional surface microfluidics enabled by spatiotemporal control of elastic fluidic interface. , 2010, Lab on a chip.

[239]  Z Hugh Fan,et al.  Macro-to-micro interfaces for microfluidic devices. , 2004, Lab on a chip.

[240]  A. Manz,et al.  Miniaturized total chemical analysis systems: A novel concept for chemical sensing , 1990 .

[241]  Mohamed Abdelgawad,et al.  Soft lithography: masters on demand. , 2008, Lab on a chip.

[242]  Lidong Qin,et al.  Self-powered microfluidic chips for multiplexed protein assays from whole blood. , 2009, Lab on a chip.

[243]  Xingyu Jiang,et al.  A miniaturized, parallel, serially diluted immunoassay for analyzing multiple antigens. , 2003, Journal of the American Chemical Society.

[244]  Rui Qiao,et al.  A compact model for electroosmotic flows in microfluidic devices , 2002 .

[245]  K. Oh,et al.  Microfluidic network-based combinatorial dilution device for high throughput screening and optimization , 2010 .

[246]  Yu-Cheng Lin,et al.  Use of a gradient-generating microfluidic device to rapidly determine a suitable glucose concentration for cell viability test , 2011 .

[247]  Jaephil Do,et al.  Maskless writing of microfluidics: Rapid prototyping of 3D microfluidics using scratch on a polymer substrate , 2011 .

[248]  Stephan Mohr,et al.  Optimisation and analysis of microreactor designs for microfluidic gradient generation using a purpose built optical detection system for entire chip imaging. , 2009, Lab on a chip.

[249]  Yanwei Jia,et al.  Simple, robust storage of drops and fluids in a microfluidic device. , 2009, Lab on a chip.

[250]  T. Mukherjee,et al.  Institute of Physics Publishing Journal of Micromechanics and Microengineering Systematic Modeling of Microfluidic Concentration Gradient Generators , 2022 .

[251]  H. Mao,et al.  A sensitive, versatile microfluidic assay for bacterial chemotaxis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[252]  Hyoung J. Cho,et al.  Diffusive mixing through velocity profile variation in microchannels , 2011 .

[253]  Oliver Lodge LIGHTNING-CONDUCTORS FROM A MODERN POINT OF VIEW. , 1890, Science.

[254]  M. Yamada,et al.  A microfluidic flow distributor generating stepwise concentrations for high-throughput biochemical processing. , 2006, Lab on a chip.

[255]  Valentina Preziosi,et al.  Microfluidics analysis of red blood cell membrane viscoelasticity. , 2011, Lab on a chip.

[256]  Brian N. Johnson,et al.  Flexible casting of modular self-aligning microfluidic assembly blocks. , 2011, Lab on a chip.

[257]  A. Groisman,et al.  Microfluidic devices for studies of shear-dependent platelet adhesion. , 2008, Lab on a chip.

[258]  S. Sugiura,et al.  Microfluidic serial dilution cell-based assay for analyzing drug dose response over a wide concentration range. , 2010, Analytical chemistry.

[259]  J. Wikswo,et al.  Characterization of transport in microfluidic gradient generators , 2008 .

[260]  M Roche,et al.  Droplet motion in microfluidic networks: Hydrodynamic interactions and pressure-drop measurements. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[261]  Jintae Kim,et al.  World-to-chip microfluidic interface with built-in valves for multichamber chip-based PCR assays. , 2005, Lab on a chip.

[262]  S. Jacobson,et al.  Microfluidic devices for electrokinetically driven parallel and serial mixing , 1999 .

[263]  Peter R. Fielden,et al.  Novel microsystems for concentration gradient generation through computer optimization with validation using optical instrumentation , 2008 .

[264]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[265]  Young-Ho Cho,et al.  A pumpless cell culture chip with the constant medium perfusion-rate maintained by balanced droplet dispensing. , 2010, Lab on a chip.

[266]  Charles-Henri Bruneau,et al.  Viscosimeter on a microfluidic chip. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[267]  Armand Ajdari,et al.  Droplet traffic in microfluidic networks: a simple model for understanding and designing. , 2007, Physical review letters.

[268]  A. Hierlemann,et al.  A hybrid microsystem for parallel perfusion experiments on living cells , 2007 .

[269]  Yusuke Arima,et al.  Combinatorial protein display for the cell-based screening of biomaterials that direct neural stem cell differentiation. , 2007, Biomaterials.

[270]  Minoru Seki,et al.  Millisecond treatment of cells using microfluidic devices via two-step carrier-medium exchange. , 2008, Lab on a chip.

[271]  Robert Langer,et al.  Combinatorial extracellular matrices for human embryonic stem cell differentiation in 3D. , 2010, Biomacromolecules.

[272]  Mark A Burns,et al.  Microfluidic pneumatic logic circuits and digital pneumatic microprocessors for integrated microfluidic systems. , 2009, Lab on a chip.

[273]  A. Ahluwalia,et al.  A microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine. , 2008, Toxicology in vitro : an international journal published in association with BIBRA.

[274]  R. Shah,et al.  Laminar Flow Forced Convection in Ducts: A Source Book for Compact Heat Exchanger Analytical Data , 2014 .

[275]  J. Macgregor,et al.  Mixture designs and models for the simultaneous selection of ingredients and their ratios , 2007 .

[276]  Michela Matteoli,et al.  A microfluidic device for depositing and addressing two cell populations with intercellular population communication capability , 2010, Biomedical microdevices.

[277]  I. Takeuchi,et al.  Role of high-throughput characterization tools in combinatorial materials science , 2004 .

[278]  N Scott Lynn,et al.  Passive microfluidic pumping using coupled capillary/evaporation effects. , 2009, Lab on a chip.

[279]  Gwo-Bin Lee,et al.  A fast prototyping process for fabrication of microfluidic systems on soda-lime glass , 2001 .

[280]  Shoji Takeuchi,et al.  A dynamic microarray device for paired bead-based analysis. , 2010, Lab on a chip.

[281]  Xiaoju Tang,et al.  A PDMS viscometer for assaying endoglucanase activity. , 2011, The Analyst.

[282]  Andreas Manz,et al.  Phaseguides: a paradigm shift in microfluidic priming and emptying. , 2011, Lab on a chip.

[283]  R. Tompkins,et al.  Continuous inertial focusing, ordering, and separation of particles in microchannels , 2007, Proceedings of the National Academy of Sciences.

[284]  H. Tseng,et al.  Integrated microfluidic devices for combinatorial cell-based assays , 2009, Biomedical microdevices.

[285]  G. Whitesides,et al.  Flexible Methods for Microfluidics , 2001 .

[286]  Shur-Jen Wang,et al.  A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis , 2006, Biomedical microdevices.

[287]  David R. Emerson,et al.  Optimal design of microfluidic networks using biologically inspired principles , 2008 .

[288]  Joseph Turner MAXWELL ON THE METHOD OF PHYSICAL ANALOGY* , 1955, The British Journal for the Philosophy of Science.

[289]  Nam-Trung Nguyen,et al.  Micromixers?a review , 2005 .

[290]  Heather Tye Application of statistical 'design of experiments' methods in drug discovery. , 2004, Drug discovery today.

[291]  Mehmet Toner,et al.  Microfluidic flow-encoded switching for parallel control of dynamic cellular microenvironments. , 2008, Lab on a chip.

[292]  Ann-Shyn Chiang,et al.  Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[293]  Charles J. Choi,et al.  Microfluidic chip for combinatorial mixing and screening of assays. , 2009, Lab on a Chip.

[294]  L. Gervais,et al.  Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates. , 2009, Lab on a chip.

[295]  S. Sugiura,et al.  Generation of arbitrary monotonic concentration profiles by a serial dilution microfluidic network composed of microchannels with a high fluidic-resistance ratio. , 2009, Lab on a chip.

[296]  Brandon Kuczenski,et al.  Modulation of fluidic resistance and capacitance for long-term, high-speed feedback control of a microfluidic interface. , 2009, Lab on a chip.

[297]  G. Whitesides,et al.  Components for integrated poly(dimethylsiloxane) microfluidic systems , 2002, Electrophoresis.

[298]  Piotr Garstecki,et al.  Dynamic memory in a microfluidic system of droplets traveling through a simple network of microchannels. , 2010, Lab on a chip.

[299]  Paul A. Luker,et al.  Qualitative Simulation Modeling and Analysis , 1991, Advances in Simulation.

[300]  G. Kovacs Micromachined Transducers Sourcebook , 1998 .

[301]  D. Leckband,et al.  Cell migration and polarity on microfabricated gradients of extracellular matrix proteins. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[302]  Jessica Melin,et al.  Microfluidic large-scale integration: the evolution of design rules for biological automation. , 2007, Annual review of biophysics and biomolecular structure.