Droplet microfluidics for high-throughput biological assays.

Droplet microfluidics offers significant advantages for performing high-throughput screens and sensitive assays. Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost. Manipulation and measurement at kilohertz speeds enable up to 10(8) samples to be screened in one day. Compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds. Droplet microfluidics combines these powerful features to enable currently inaccessible high-throughput screening applications, including single-cell and single-molecule assays.

[1]  Andrew D Griffiths,et al.  Droplet-based microfluidic systems for high-throughput single DNA molecule isothermal amplification and analysis. , 2009, Analytical chemistry.

[2]  R. Daniel,et al.  Rapid Identification of Genes Encoding DNA Polymerases by Function-Based Screening of Metagenomic Libraries Derived from Glacial Ice , 2009, Applied and Environmental Microbiology.

[3]  Alexander Sczyrba,et al.  Decontamination of MDA Reagents for Single Cell Whole Genome Amplification , 2011, PloS one.

[4]  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.

[5]  Timothy B. Stockwell,et al.  Nanoliter Reactors Improve Multiple Displacement Amplification of Genomes from Single Cells , 2007, PLoS genetics.

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

[7]  Rohit Sharma,et al.  Directed Evolution: An Approach to Engineer Enzymes , 2006, Critical reviews in biotechnology.

[8]  E. Coligan.  Current protocols in immunology , 1991 .

[9]  D. Dressman,et al.  Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Weitz,et al.  Geometrically mediated breakup of drops in microfluidic devices. , 2003, Physical review letters.

[11]  James E. Crowe,et al.  Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors , 2008, Nature.

[12]  J. S. Johnson,et al.  Biocompatible surfactants for water-in-fluorocarbon emulsions. , 2008, Lab on a chip.

[13]  V. Torsvik,et al.  High diversity in DNA of soil bacteria , 1990, Applied and environmental microbiology.

[14]  Andrew D Griffiths,et al.  Miniaturizing chemistry and biology in microdroplets. , 2007, Chemical communications.

[15]  R. Quatrano.  Genomics , 1998, Plant Cell.

[16]  Peter G. Schultz,et al.  Identification of small-molecule inducers of pancreatic β-cell expansion , 2009, Proceedings of the National Academy of Sciences.

[17]  S. Quake,et al.  Dynamic pattern formation in a vesicle-generating microfluidic device. , 2001, Physical review letters.

[18]  Tanja Woyke,et al.  Genomic sequencing of single microbial cells from environmental samples. , 2008, Current opinion in microbiology.

[19]  H. Morgan,et al.  Removal of contaminating DNA from polymerase chain reaction using ethidium monoazide. , 2007, Journal of microbiological methods.

[20]  S. Leibler,et al.  Bacterial Persistence as a Phenotypic Switch , 2004, Science.

[21]  Larissa B. Thackray,et al.  Replication of Norovirus in Cell Culture Reveals a Tropism for Dendritic Cells and Macrophages , 2004, PLoS biology.

[22]  P. Umbanhowar,et al.  Monodisperse Emulsion Generation via Drop Break Off in a Coflowing Stream , 2000 .

[23]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[24]  Bill W Colston,et al.  High-throughput quantitative polymerase chain reaction in picoliter droplets. , 2008, Analytical chemistry.

[25]  Richard Novak,et al.  High-performance single cell genetic analysis using microfluidic emulsion generator arrays. , 2010, Analytical chemistry.

[26]  Christoph A. Merten,et al.  Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms. , 2008, Chemistry & biology.

[27]  G. Church,et al.  Bacteria Subsisting on Antibiotics , 2007, Science.

[28]  Adam D. Wier,et al.  Raw Sewage Harbors Diverse Viral Populations , 2011, mBio.

[29]  Peter Rådström,et al.  Pre-PCR processing , 2004, Molecular biotechnology.

[30]  AC Tose.  Cell , 1993, Cell.

[31]  Sallie W. Chisholm,et al.  Whole Genome Amplification and De novo Assembly of Single Bacterial Cells , 2009, PloS one.

[32]  J. C. Love,et al.  A microengraving method for rapid selection of single cells producing antigen-specific antibodies , 2006, Nature Biotechnology.

[33]  P. Turnbaugh,et al.  An Invitation to the Marriage of Metagenomics and Metabolomics , 2008, Cell.

[34]  B. Stevenson,et al.  Current Protocols in Microbiology , 2005 .

[35]  Byron F. Brehm-Stecher,et al.  Single-Cell Microbiology: Tools, Technologies, and Applications , 2004, Microbiology and Molecular Biology Reviews.

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

[37]  Frances S. House,et al.  An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies. , 2008, Journal of immunological methods.

[38]  Monya Baker,et al.  Clever PCR: more genotyping, smaller volumes , 2010, Nature Methods.

[39]  Christoph A. Merten,et al.  Drop-based microfluidic devices for encapsulation of single cells. , 2008, Lab on a chip.

[40]  Yuji Kikuchi,et al.  Regular-sized cell creation in microchannel emulsification by visual microprocessing method , 1997 .

[41]  Ruud H. Brakenhoff,et al.  Detection, clinical relevance and specific biological properties of disseminating tumour cells , 2008, Nature Reviews Cancer.

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

[43]  G. Church,et al.  Functional Characterization of the Antibiotic Resistance Reservoir in the Human Microflora , 2009, Science.

[44]  A. Moya,et al.  Evaluating the Fidelity of De Novo Short Read Metagenomic Assembly Using Simulated Data , 2011, PloS one.

[45]  P. Carter.  Potent antibody therapeutics by design , 2006, Nature Reviews Immunology.

[46]  Stephen R. Quake,et al.  Microfluidic Digital PCR Enables Multigene Analysis of Individual Environmental Bacteria , 2006, Science.

[47]  A. Abate,et al.  High-throughput injection with microfluidics using picoinjectors , 2010, Proceedings of the National Academy of Sciences.

[48]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[49]  Shanavaz Nasarabadi,et al.  On-chip single-copy real-time reverse-transcription PCR in isolated picoliter droplets. , 2007, Analytical chemistry.

[50]  Anna Whyatt,et al.  Notes and references , 1984, International Journal of Legal Information : Official Publication.

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

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

[53]  Rustem F Ismagilov,et al.  The chemistrode: A droplet-based microfluidic device for stimulation and recording with high temporal, spatial, and chemical resolution , 2008, Proceedings of the National Academy of Sciences.

[54]  S. Nie,et al.  Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules , 2001, Nature Biotechnology.

[55]  U. Stenzel,et al.  Targeted high-throughput sequencing of tagged nucleic acid samples , 2007, Nucleic acids research.

[56]  H. Moyed,et al.  hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis , 1983, Journal of bacteriology.

[57]  Rob Phillips,et al.  Probing Individual Environmental Bacteria for Viruses by Using Microfluidic Digital PCR , 2011, Science.

[58]  S. Koren,et al.  Assembly algorithms for next-generation sequencing data. , 2010, Genomics.

[59]  G. Whitesides,et al.  Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up. , 2006, Lab on a chip.

[60]  David A. Weitz,et al.  Electrocoalescence of drops synchronized by size-dependent flow in microfluidic channels , 2006 .

[61]  W Henke,et al.  Betaine improves the PCR amplification of GC-rich DNA sequences. , 1997, Nucleic acids research.

[62]  H. Stone,et al.  Formation of dispersions using “flow focusing” in microchannels , 2003 .

[63]  Jong Wook Hong,et al.  Integrated nanoliter systems , 2003, Nature Biotechnology.

[64]  F. Arnold,et al.  Designed evolution of enzymatic properties. , 2000, Current opinion in biotechnology.

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

[66]  Mehmet Toner,et al.  Controlled encapsulation of single-cells into monodisperse picolitre drops. , 2008, Lab on a chip.

[67]  Wendy S. Schackwitz,et al.  One Bacterial Cell, One Complete Genome , 2010, PloS one.

[68]  R. Westervelt,et al.  Dielectrophoretic manipulation of drops for high-speed microfluidic sorting devices , 2006 .

[69]  R D Morgan,et al.  Characterization of the Specific DNA Nicking Activity of Restriction Endonuclease N.BstNBI , 2000, Biological chemistry.

[70]  Dan S. Tawfik,et al.  Man-made cell-like compartments for molecular evolution , 1998, Nature Biotechnology.

[71]  M. Aoun,et al.  Rapid Detection of Candida albicans in Clinical Blood Samples by Using a TaqMan-Based PCR Assay , 2003, Journal of Clinical Microbiology.