Recent developments in microfluidic large scale integration.

In 2002, Thorsen et al. integrated thousands of micromechanical valves on a single microfluidic chip and demonstrated that the control of the fluidic networks can be simplified through multiplexors [1]. This enabled realization of highly parallel and automated fluidic processes with substantial sample economy advantage. Moreover, the fabrication of these devices by multilayer soft lithography was easy and reliable hence contributed to the power of the technology; microfluidic large scale integration (mLSI). Since then, mLSI has found use in wide variety of applications in biology and chemistry. In the meantime, efforts to improve the technology have been ongoing. These efforts mostly focus on; novel materials, components, micromechanical valve actuation methods, and chip architectures for mLSI. In this review, these technological advances are discussed and, recent examples of the mLSI applications are summarized.

[1]  S. Quake,et al.  Biocompatibility and reduced drug absorption of sol-gel-treated poly(dimethyl siloxane) for microfluidic cell culture applications. , 2010, Analytical chemistry.

[2]  Wei Wang,et al.  Studies on Parylene C-caulked PDMS (pcPDMS) for low permeability required microfluidics applications. , 2011, Lab on a chip.

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

[4]  J. Madsen,et al.  Synthesis of biochemical applications on flow-based microfluidic biochips using constraint programming , 2012, 2012 Symposium on Design, Test, Integration and Packaging of MEMS/MOEMS.

[5]  A. Neogi,et al.  Oscillating magnetic field-actuated microvalves for micro- and nanofluidics , 2009 .

[6]  Yanju Wang,et al.  An integrated microfluidic device for large-scale in situ click chemistry screening. , 2009, Lab on a chip.

[7]  Shuichi Takayama,et al.  High-density fabrication of normally closed microfluidic valves by patterned deactivation of oxidized polydimethylsiloxane. , 2011, Lab on a chip.

[8]  William H. Grover,et al.  Monolithic membrane valves and diaphragm pumps for practical large-scale integration into glass microfluidic devices , 2003 .

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

[10]  Seung-Yong Jung,et al.  Fast mixing and reaction initiation control of single-enzyme kinetics in confined volumes. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[11]  Niels W. Hanson,et al.  A programmable droplet-based microfluidic device applied to multiparameter analysis of single microbes and microbial communities , 2012, Proceedings of the National Academy of Sciences.

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

[13]  Sebastian J Maerkl,et al.  A software-programmable microfluidic device for automated biology. , 2011, Lab on a chip.

[14]  Ismail Emre Araci,et al.  Microfluidic very large scale integration (mVLSI) with integrated micromechanical valves. , 2012, Lab on a chip.

[15]  Rong Fan,et al.  A Clinical Microchip for Evaluation of Single Immune Cells Reveals High Functional Heterogeneity in Phenotypically Similar T Cells Nih Public Access Author Manuscript Design Rationale and Detection Limit of the Scbc Online Methods Microchip Fabrication On-chip Secretion Profiling Supplementary Mater , 2022 .

[16]  D. Marshall,et al.  Microfluidics for single cell analysis. , 2012, Current opinion in biotechnology.

[17]  C. Hansen,et al.  Microfluidic single cell analysis: from promise to practice. , 2012, Current opinion in chemical biology.

[18]  Marc Alexander Unger,et al.  Multilayer soft lithography of perfluoropolyether based elastomer for microfluidic device fabrication. , 2011, Lab on a chip.

[19]  S. Quake,et al.  Microfluidic Large-Scale Integration , 2002, Science.

[20]  Tsung-Yi Ho,et al.  A top-down synthesis methodology for flow-based microfluidic biochips considering valve-switching minimization , 2013, ISPD '13.

[21]  S. Quake,et al.  Dissecting biological “dark matter” with single-cell genetic analysis of rare and uncultivated TM7 microbes from the human mouth , 2007, Proceedings of the National Academy of Sciences.

[22]  Sujitha Martin,et al.  Electronic control of elastomeric microfluidic circuits with shape memory actuators. , 2008, Lab on a chip.

[23]  Numrin Thaitrong,et al.  Integrated microfluidic bioprocessor for single-cell gene expression analysis , 2008, Proceedings of the National Academy of Sciences.

[24]  Qin Tu,et al.  An integrated microfluidic system for studying cell-microenvironmental interactions versatilely and dynamically. , 2010, Lab on a chip.

[25]  Tsung-Yi Ho,et al.  A clique-based approach to find binding and scheduling result in flow-based microfluidic biochips , 2013, 2013 18th Asia and South Pacific Design Automation Conference (ASP-DAC).

[26]  J. Einasto Dark Matter , 2009, 0901.0632.

[27]  Axel Scherer,et al.  A microfluidic processor for gene expression profiling of single human embryonic stem cells. , 2008, Lab on a chip.

[28]  Paul Pop,et al.  Architectural synthesis of flow-based microfluidic large-scale integration biochips , 2012, CASES '12.

[29]  Stephen R Quake,et al.  Whole-genome molecular haplotyping of single cells , 2011, Nature Biotechnology.

[30]  D. Kent,et al.  High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays , 2011, Nature Methods.

[31]  Shuichi Takayama,et al.  Microfluidic automation using elastomeric valves and droplets: reducing reliance on external controllers. , 2012, Small.

[32]  Jiashu Sun,et al.  Microfluidics for manipulating cells. , 2013, Small.

[33]  Timothy K Lee,et al.  Single-cell NF-κB dynamics reveal digital activation and analogue information processing , 2010, Nature.

[34]  Philip Brisk,et al.  Design and verification tools for continuous fluid flow-based microfluidic devices , 2013, 2013 18th Asia and South Pacific Design Automation Conference (ASP-DAC).

[35]  Carl L Hansen,et al.  Microfluidic integration of parallel solid-phase liquid chromatography. , 2013, Analytical chemistry.

[36]  Naga Sai Gopi K Devaraju,et al.  Pressure driven digital logic in PDMS based microfluidic devices fabricated by multilayer soft lithography. , 2012, Lab on a chip.

[37]  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.

[38]  Lynn Conway,et al.  Introduction to VLSI systems , 1978 .

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

[40]  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.

[41]  Tsung-Yi Ho,et al.  A network-flow based valve-switching aware binding algorithm for flow-based microfluidic biochips , 2013, 2013 18th Asia and South Pacific Design Automation Conference (ASP-DAC).

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

[43]  Stephen R Quake,et al.  Microfluidic serial digital to analog pressure converter for arbitrary pressure generation and contamination-free flow control. , 2013, Lab on a chip.

[44]  Frieder Mugele,et al.  Microfluidic valves with integrated structured elastomeric membranes for reversible fluidic entrapment and in situ channel functionalization. , 2009, Lab on a chip.

[45]  S. Quake,et al.  Solvent-Resistant Photocurable “Liquid Teflon” for Microfluidic Device Fabrication , 2004 .

[46]  M. Mowlem,et al.  Chemically resistant microfluidic valves from Viton® membranes bonded to COC and PMMA. , 2011, Lab on a chip.

[47]  Bastian E. Rapp,et al.  Design and characterization of a platform for thermal actuation of up to 588 microfluidic valves , 2013 .

[48]  Tsung-Yi Ho,et al.  Control synthesis for the flow-based microfluidic large-scale integration biochips , 2013, 2013 18th Asia and South Pacific Design Automation Conference (ASP-DAC).

[49]  I. Shmulevich,et al.  Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform , 2009, Proceedings of the National Academy of Sciences.

[50]  Carl L Hansen,et al.  Three-dimensional large-scale microfluidic integration by laser ablation of interlayer connections. , 2010, Lab on a chip.

[51]  Sebastian J Maerkl,et al.  Next generation microfluidic platforms for high-throughput protein biochemistry. , 2011, Current opinion in biotechnology.

[52]  Mark Horowitz,et al.  Static control logic for microfluidic devices using pressure-gain valves , 2010 .

[53]  Jungkyu Kim,et al.  Digitally programmable microfluidic automaton for multiscale combinatorial mixing and sample processing. , 2013, Lab on a chip.

[54]  Samuel Aparicio,et al.  High-throughput microfluidic single-cell RT-qPCR , 2011, Proceedings of the National Academy of Sciences.

[55]  Meng-Ping Chang,et al.  Electrostatically-driven elastomer components for user-reconfigurable high density microfluidics. , 2009, Lab on a chip.

[56]  S. Tay,et al.  Flow-switching allows independently programmable, extremely stable, high-throughput diffusion-based gradients. , 2013, Lab on a chip.

[57]  Shuichi Takayama,et al.  Next-generation integrated microfluidic circuits. , 2011, Lab on a chip.

[58]  Frantisek Svec,et al.  Light-actuated high pressure-resisting microvalve for on-chip flow control based on thermo-responsive nanostructured polymer. , 2008, Lab on a chip.

[59]  S Elizabeth Hulme,et al.  Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices. , 2009, Lab on a chip.

[60]  Nada Amin,et al.  Computer-aided design for microfluidic chips based on multilayer soft lithography , 2009, 2009 IEEE International Conference on Computer Design.

[61]  Erik C Jensen,et al.  A digital microfluidic platform for the automation of quantitative biomolecular assays. , 2010, Lab on a chip.

[62]  I. Shmulevich,et al.  High-throughput tracking of single yeast cells in a microfluidic imaging matrix. , 2011, Lab on a chip.

[63]  Paul Pop,et al.  System-level modeling and synthesis of flow-based microfluidic biochips , 2011, 2011 Proceedings of the 14th International Conference on Compilers, Architectures and Synthesis for Embedded Systems (CASES).