Recent advances in microfluidic technologies for biochemistry and molecular biologys.

Advances in the fields of proteomics and genomics have necessitated the development of high-throughput screening methods (HTS) for the systematic transformation of large amounts of biological chemical data into an organized database of knowledge. Microfluidic systems are ideally suited for high-throughput biochemical experimentation since they offer high analytical throughput, consume minute quantities of expensive biological reagents, exhibit superior sensitivity and functionality compared to traditional micro-array techniques and can be integrated within complex experimental work flows. A range of basic biochemical and molecular biological operations have been transferred to chip-based microfluidic formats over the last decade, including gene sequencing, emulsion PCR, immunoassays, electrophoresis, cell-based assays, expression cloning and macromolecule blotting. In this review, we highlight some of the recent advances in the application of microfluidics to biochemistry and molecular biology.

[1]  Stephen R Quake,et al.  An in vitro microfluidic approach to generating protein-interaction networks , 2009, Nature Methods.

[2]  M. Bowser,et al.  Fast determination of mitochondria electrophoretic mobility using micro free-flow electrophoresis. , 2009, Analytical chemistry.

[3]  J Taylor,et al.  Development of a multichannel microfluidic analysis system employing affinity capillary electrophoresis for immunoassay. , 2001, Analytical chemistry.

[4]  Detection of single nucleotide polymorphism using tension-dependent stochastic behavior of a single-molecule template. , 2011, Journal of the American Chemical Society.

[5]  Terence G. Henares,et al.  Current development in microfluidic immunosensing chip. , 2008, Analytica chimica acta.

[6]  Amy E Herr,et al.  Microfluidic immunoassays as rapid saliva-based clinical diagnostics , 2007, Proceedings of the National Academy of Sciences.

[7]  A. Abate,et al.  Ultrahigh-throughput screening in drop-based microfluidics for directed evolution , 2010, Proceedings of the National Academy of Sciences.

[8]  Wilhelm T S Huck,et al.  Simultaneous determination of gene expression and enzymatic activity in individual bacterial cells in microdroplet compartments. , 2009, Journal of the American Chemical Society.

[9]  Christoph A. Merten,et al.  High-throughput screening of enzymes by retroviral display using droplet-based microfluidics. , 2010, Chemistry and Biology.

[10]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[11]  D. J. Harrison,et al.  Integrated self‐calibration via electrokinetic solvent proportioning for microfluidic immunoassays , 2001, Electrophoresis.

[12]  K. Mullis,et al.  Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. , 1986, Cold Spring Harbor symposia on quantitative biology.

[13]  Paul Matsudaira,et al.  A 768-lane microfabricated system for high-throughput DNA sequencing. , 2005, Lab on a chip.

[14]  D. Weitz,et al.  Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. , 2009, Lab on a chip.

[15]  Polyacrylamide gel photopatterning enables automated protein immunoblotting in a two-dimensional microdevice. , 2010, Journal of the American Chemical Society.

[16]  Michael T Bowser,et al.  Fast electrophoretic separation optimization using gradient micro free-flow electrophoresis. , 2008, Analytical chemistry.

[17]  David S. Kong,et al.  Parallel gene synthesis in a microfluidic device , 2007, Nucleic acids research.

[18]  Rustem F Ismagilov,et al.  Time-controlled microfluidic seeding in nL-volume droplets to separate nucleation and growth stages of protein crystallization. , 2006, Angewandte Chemie.

[19]  A. deMello,et al.  Non-emissive colour filters for fluorescence detection. , 2011, Lab on a chip.

[20]  Aaron R Wheeler,et al.  Immunoassays in microfluidic systems , 2010, Analytical and bioanalytical chemistry.

[21]  Ren Sun,et al.  Genetic analysis of H1N1 influenza virus from throat swab samples in a microfluidic system for point-of-care diagnostics. , 2011, Journal of the American Chemical Society.

[22]  T Kitamori,et al.  Integration of an immunosorbent assay system: analysis of secretory human immunoglobulin A on polystyrene beads in a microchip. , 2000, Analytical chemistry.

[23]  K. Frazer,et al.  Microdroplet-based PCR amplification for large scale targeted sequencing , 2009, Nature Biotechnology.

[24]  R. Kostiainen,et al.  Fully microfabricated and integrated SU-8-based capillary electrophoresis-electrospray ionization microchips for mass spectrometry. , 2007, Analytical Chemistry.

[25]  Darshana Dadhania,et al.  MicroRNA expression profiles predictive of human renal allograft status , 2009, Proceedings of the National Academy of Sciences.

[26]  A. deMello,et al.  Droplet-based compartmentalization of chemically separated components in two-dimensional separations. , 2009, Chemical communications.

[27]  Antoine Pallandre,et al.  Recent innovations in protein separation on microchips by electrophoretic methods: An update , 2010, Electrophoresis.

[28]  T Kitamori,et al.  Determination of carcinoembryonic antigen in human sera by integrated bead-bed immunoassay in a microchip for cancer diagnosis. , 2001, Analytical chemistry.

[29]  Anupam Singhal,et al.  Megapixel digital PCR , 2011, Nature Methods.

[30]  Rustem F Ismagilov,et al.  A droplet-based, composite PDMS/glass capillary microfluidic system for evaluating protein crystallization conditions by microbatch and vapor-diffusion methods with on-chip X-ray diffraction. , 2004, Angewandte Chemie.

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

[32]  Amy E Herr,et al.  Automated microfluidic protein immunoblotting , 2010, Nature Protocols.

[33]  Daniel Bratton,et al.  Development of quantitative cell-based enzyme assays in microdroplets. , 2008, Analytical chemistry.

[34]  Andrew J deMello,et al.  Micro- and nanofluidic systems for high-throughput biological screening. , 2009, Drug discovery today.

[35]  Improving sensitivity in micro‐free flow electrophoresis using signal averaging , 2009, Electrophoresis.

[36]  Todd Thorsen,et al.  Noninvasive metabolic profiling using microfluidics for analysis of single preimplantation embryos. , 2008, Analytical chemistry.

[37]  Marin Sigurdson,et al.  AC electrothermal enhancement of heterogeneous assays in microfluidics. , 2007, Lab on a chip.

[38]  Xuhua Wang,et al.  Towards microalbuminuria determination on a disposable diagnostic microchip with integrated fluorescence detection based on thin-film organic light emitting diodes. , 2005, Lab on a chip.

[39]  D. Bradley,et al.  Thin-film organic photodiodes for integrated on-chip chemiluminescence detection – application to antioxidant capacity screening , 2009 .

[40]  Robert T Kennedy,et al.  Continuous-flow enzyme assay on a microfluidic chip for monitoring glycerol secretion from cultured adipocytes. , 2009, Analytical chemistry.

[41]  Rustem F Ismagilov,et al.  Using nanoliter plugs in microfluidics to facilitate and understand protein crystallization. , 2005, Current opinion in structural biology.

[42]  D. Beebe,et al.  Cell culture models in microfluidic systems. , 2008, Annual review of analytical chemistry.

[43]  Takehiko Kitamori,et al.  Microchip‐based immunoassay system with branching multichannels for simultaneous determination of interferon‐γ , 2002, Electrophoresis.

[44]  Ke Liu,et al.  Thermoplastic microfluidic devices and their applications in protein and DNA analysis. , 2011, The Analyst.

[45]  Richard A Mathies,et al.  Microfabricated bioprocessor for integrated nanoliter-scale Sanger DNA sequencing. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Stephen R Quake,et al.  Microfluidic device reads up to four consecutive base pairs in DNA sequencing-by-synthesis. , 2004, Nucleic acids research.

[47]  Loïc Dayon,et al.  Microfluidic systems in proteomics , 2003, Electrophoresis.

[48]  Mark A Hayes,et al.  Recent developments in electrophoretic separations on microfluidic devices , 2011, Electrophoresis.

[49]  E. Delamarche,et al.  Patterned delivery of immunoglobulins to surfaces using microfluidic networks. , 1997, Science.

[50]  K. Khrapko,et al.  Single-molecule PCR: an artifact-free PCR approach for the analysis of somatic mutations , 2005, Expert review of molecular diagnostics.

[51]  Yi Zhang,et al.  Advances in microfluidic PCR for point-of-care infectious disease diagnostics. , 2011, Biotechnology advances.

[52]  J. Shuga,et al.  Single-cell multiplex gene detection and sequencing with microfluidically generated agarose emulsions. , 2011, Angewandte Chemie.

[53]  Akira Harada,et al.  Large‐scale microfabricated channel plates for high‐throughput, fully automated DNA sequencing , 2008, Electrophoresis.

[54]  A. deMello Control and detection of chemical reactions in microfluidic systems , 2006, Nature.

[55]  D. Beebe,et al.  Microfluidic based platform for characterization of protein interactions in hydrogel nanoenvironments. , 2007, Analytical chemistry.

[56]  Takehiko Kitamori,et al.  Development of a microchip-based bioassay system using cultured cells. , 2005, Analytical chemistry.

[57]  R. Ismagilov,et al.  Screening of protein crystallization conditions on a microfluidic chip using nanoliter-size droplets. , 2003, Journal of the American Chemical Society.

[58]  Liang Li,et al.  Laterally mobile, functionalized self-assembled monolayers at the fluorous-aqueous interface in a plug-based microfluidic system: characterization and testing with membrane protein crystallization. , 2009, Journal of the American Chemical Society.

[59]  Viktor Stein,et al.  Continuous-flow polymerase chain reaction of single-copy DNA in microfluidic microdroplets. , 2009, Analytical chemistry.

[60]  Sriram Kosuri,et al.  Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips , 2010, Nature Biotechnology.

[61]  Jingsong Huang,et al.  Highly sensitive fluorescence detection system for microfluidic lab-on-a-chip. , 2011, Lab on a chip.

[62]  Jongin Hong,et al.  Analysis of Protein–Protein Interactions by Using Droplet‐Based Microfluidics , 2009, Chembiochem : a European journal of chemical biology.

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

[64]  R. Mathies,et al.  Fluorescence energy transfer‐labeled primers for high‐performance forensic DNA profiling , 2008, Electrophoresis.

[65]  N. Lee,et al.  Superporous agarose beads as a solid support for microfluidic immunoassay. , 2008, Ultramicroscopy.

[66]  A Manz,et al.  Chemical amplification: continuous-flow PCR on a chip. , 1998, Science.

[67]  Thomas N. Chiesl,et al.  Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes , 2008, Proceedings of the National Academy of Sciences.

[68]  Takehiko Kitamori,et al.  Microchip-based enzyme-linked immunosorbent assay (microELISA) system with thermal lens detection. , 2004, Lab on a chip.

[69]  R. Mathies,et al.  Integrated microfluidic systems for high-performance genetic analysis. , 2009, Trends in biotechnology.

[70]  Stephen R. Quake,et al.  A microfluidic oligonucleotide synthesizer , 2010, Nucleic acids research.

[71]  Richard A Mathies,et al.  Inline injection microdevice for attomole-scale sanger DNA sequencing. , 2007, Analytical chemistry.

[72]  N. Perrimon,et al.  Droplet microfluidic technology for single-cell high-throughput screening , 2009, Proceedings of the National Academy of Sciences.

[73]  Amy E Herr,et al.  Microfluidic polyacrylamide gel electrophoresis with in situ immunoblotting for native protein analysis. , 2009, Analytical chemistry.

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

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