Integrated genetic analysis microsystems

The advent of integrated microsystems for genetic analysis allows the acquisition of information at unprecedented length and time scales. The convergence of molecular biology, chemistry, physics, and materials science is required for their design and construction. The utility of the microsystems originates from increased analysis speed, lower analysis cost, and higher parallelism leading to increased assay throughput. In addition, when fully integrated, this technology will enable portable systems for high-speed in situ analyses, permitting a new standard in disciplines such as clinical chemistry, personalized medicine, forensics, biowarfare detection, and epidemiology. This article presents an overview of the recent history of integrated genetic analysis microsystems with an emphasis on materials aspects, and provides a perspective on current developments and future prospects.

[1]  F F Becker,et al.  Cell separation on microfabricated electrodes using dielectrophoretic/gravitational field-flow fractionation. , 1999, Analytical chemistry.

[2]  N. Manaresi,et al.  A CMOS chip for individual cell manipulation and detection , 2003, 2003 IEEE International Solid-State Circuits Conference, 2003. Digest of Technical Papers. ISSCC..

[3]  R. Abramson,et al.  Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. A. Northrup,et al.  Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. , 1996, Analytical chemistry.

[5]  Russell Higuchi,et al.  Kinetic PCR Analysis: Real-time Monitoring of DNA Amplification Reactions , 1993, Bio/Technology.

[6]  Richard A Mathies,et al.  High throughput DNA sequencing with a microfabricated 96-lane capillary array electrophoresis bioprocessor , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  W. Bishai,et al.  Mechanisms of latency in Mycobacterium tuberculosis. , 1998, Trends in microbiology.

[8]  K. R. Williams,et al.  Novel interconnection technologies for integrated microfluidic systems , 1998 .

[9]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[10]  Hans Peter Herzig,et al.  Performance of an integrated microoptical system for fluorescence detection in microfluidic systems. , 2002, Analytical chemistry.

[11]  James S. Wilkinson,et al.  Design and theoretical evaluation of a novel microfluidic device to be used for PCR , 2003 .

[12]  George F. Sensabaugh,et al.  DNA typing from single hairs , 1988, Nature.

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

[14]  J P Landers,et al.  Towards dynamic coating of glass microchip chambers for amplifying DNA via the polymerase chain reaction , 2001, Electrophoresis.

[15]  Yong-Sang Kim,et al.  A disposable capillary electrophoresis microchip with an indium tin oxide decoupler/amperometric detector , 2005 .

[16]  C. Cerniglia,et al.  A universal protocol for PCR detection of 13 species of foodborne pathogens in foods , 1997, Journal of applied microbiology.

[17]  S. Spearing,et al.  Mechanics of wafer bonding: effect of clamping , 2004 .

[18]  R A Mathies,et al.  Loss of heterozygosity assay for molecular detection of cancer using energy-transfer primers and capillary array electrophoresis. , 2000, Genome research.

[19]  W. Al-Soud,et al.  Purification and Characterization of PCR-Inhibitory Components in Blood Cells , 2001, Journal of Clinical Microbiology.

[20]  R. Pethig Dielectrophoresis: Using Inhomogeneous AC Electrical Fields to Separate and Manipulate Cells , 1996 .

[21]  Osamu Tabata,et al.  High-performance genetic analysis on microfabricated capillary array electrophoresis plastic chips fabricated by injection molding. , 2005, Analytical chemistry.

[22]  Robin H. Liu,et al.  Fabrication and characterization of hydrogel-based microvalves , 2002 .

[23]  Chunhai Fan,et al.  Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection of DNA , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  S. Farrah,et al.  Presence of human immunodeficiency virus nucleic acids in wastewater and their detection by polymerase chain reaction , 1992, Applied and environmental microbiology.

[25]  Richard A Mathies,et al.  Microchip bioprocessor for integrated nanovolume sample purification and DNA sequencing. , 2002, Analytical chemistry.

[26]  Zhao-Lun Fang,et al.  DNA separation with low-viscosity sieving matrix on microfabricated polycarbonate microfluidic chips , 2005, Analytical and bioanalytical chemistry.

[27]  G. Whitesides,et al.  Microfluidic devices fabricated in Poly(dimethylsiloxane) for biological studies , 2003, Electrophoresis.

[28]  K. Roux,et al.  High and low annealing temperatures increase both specificity and yield in touchdown and stepdown PCR. , 1996, BioTechniques.

[29]  Ian L. Pepper,et al.  Fecal Coliforms in Soil Detected by Polymerase Chain Reaction and DNA-DNA Hybridizations , 1991 .

[30]  Stellan Hjertén,et al.  High-performance electrophoresis : Elimination of electroendosmosis and solute adsorption , 1985 .

[31]  L J Kricka,et al.  PCR in a silicon microstructure. , 1994, Clinical chemistry.

[32]  S. Schnell,et al.  Enzymological considerations for a theoretical description of the quantitative competitive polymerase chain reaction (QC-PCR). , 1997, Journal of theoretical biology.

[33]  T. B. Taylor,et al.  Optimization of the performance of the polymerase chain reaction in silicon-based microstructures. , 1997, Nucleic acids research.

[34]  D. J. Harrison,et al.  Immunomagnetic T cell capture from blood for PCR analysis using microfluidic systems. , 2004, Lab on a chip.

[35]  D. Mccormick Sequence the Human Genome , 1986, Bio/Technology.

[36]  Mark A Burns,et al.  Polymerase chain reaction in high surface-to-volume ratio SiO2 microstructures. , 2004, Analytical chemistry.

[37]  C. Hackbarth,et al.  Methicillin-resistant staphylococci: genetics and mechanisms of resistance , 1989, Antimicrobial Agents and Chemotherapy.

[38]  Teruo Fujii,et al.  A plug and play microfluidic device. , 2003, Lab on a chip.

[39]  Dong-Chul Han,et al.  PDMS-based micro PCR chip with Parylene coating , 2003 .

[40]  Robin H. Liu,et al.  Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection. , 2004, Analytical chemistry.

[41]  L J Kricka,et al.  Chip PCR. II. Investigation of different PCR amplification systems in microbabricated silicon-glass chips. , 1996, Nucleic acids research.

[42]  Peter Ertl,et al.  Capillary electrophoresis chips with a sheath-flow supported electrochemical detection system. , 2004, Analytical chemistry.

[43]  B. Vogelstein,et al.  Preparative and analytical purification of DNA from agarose. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Timothy J. Johnson,et al.  Chemical mapping of hot-embossed and UV-laser-ablated microchannels in poly(methyl methacrylate) using carboxylate specific fluorescent probes , 2001 .

[45]  V. Studer,et al.  An integrated AC electrokinetic pump in a microfluidic loop for fast and tunable flow control. , 2004, The Analyst.

[46]  R. L. Guerrant,et al.  Escherichia coli O157:H7. , 1995, The New England journal of medicine.

[47]  Christopher Dye,et al.  Global Burden of Tuberculosis: Estimated Incidence, Prevalence, and Mortality by Country , 1999 .

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

[49]  Igor L. Medintz,et al.  Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis. , 2002, Analytical chemistry.

[50]  A. Paulus,et al.  Rapid separation and purification of oligonucleotides by high-performance capillary gel electrophoresis. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Luke P. Lee,et al.  Micromachined transmissive scanning confocal microscope. , 2004, Optics letters.

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

[53]  P. Grodzinski,et al.  A Modular Microfluidic System for Cell Pre-concentration and Genetic Sample Preparation , 2003 .

[54]  T. Kamei,et al.  Microfluidic Genetic Analysis with an Integrated a-Si:H Detector , 2005, Biomedical microdevices.

[55]  Z Hugh Fan,et al.  Integrating polymerase chain reaction, valving, and electrophoresis in a plastic device for bacterial detection. , 2003, Analytical chemistry.

[56]  Hiroaki Misawa,et al.  A heater-integrated transparent microchannel chip for continuous-flow PCR , 2002 .

[57]  J. Karns,et al.  A handheld real time thermal cycler for bacterial pathogen detection. , 2003, Biosensors & bioelectronics.

[58]  M. Owen,et al.  Hydrophobic Recovery of Plasma-Treated Polydimethylsiloxane , 1995 .

[59]  A D Stroock,et al.  An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications. , 2001, Analytical chemistry.

[60]  M. Heller,et al.  Preparation and hybridization analysis of DNA/RNA from E. coli on microfabricated bioelectronic chips , 1998, Nature Biotechnology.

[61]  C. Cantor,et al.  Pulsed-field gel electrophoresis of large DNA molecules , 1986, Nature.

[62]  J.S. Harris,et al.  Integrated semiconductor vertical-cavity surface-emitting lasers and PIN photodetectors for biomedical fluorescence sensing , 2004, IEEE Journal of Quantum Electronics.

[63]  S. Quake,et al.  An Integrated Microfabricated Cell Sorter , 2022 .

[64]  L J Kricka,et al.  Chip PCR. I. Surface passivation of microfabricated silicon-glass chips for PCR. , 1996, Nucleic acids research.

[65]  Richard A Mathies,et al.  Microfluidic devices for DNA sequencing: sample preparation and electrophoretic analysis. , 2003, Current opinion in biotechnology.

[66]  A. Woolley,et al.  Ultra-high-speed DNA sequencing using capillary electrophoresis chips. , 1995, Analytical chemistry.

[67]  Lloyd M. Smith,et al.  Analysis of resolution in DNA sequencing by capillary gel electrophoresis , 1993 .

[68]  H. Brunner Annual Review of Genomics and Human Genetics , 2001, European Journal of Human Genetics.

[69]  P. Gascoyne,et al.  Particle separation by dielectrophoresis , 2002, Electrophoresis.

[70]  R. Mathies,et al.  Fully integrated PCR-capillary electrophoresis microsystem for DNA analysis. , 2001, Lab on a chip.

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

[72]  D. J. Harrison,et al.  Capillary electrophoresis and sample injection systems integrated on a planar glass chip , 1992 .

[73]  E. Cummings,et al.  Insulator‐based dielectrophoresis for the selective concentration and separation of live bacteria in water , 2004, Electrophoresis.

[74]  D J Harrison,et al.  mRNA isolation in a microfluidic device for eventual integration of cDNA library construction. , 2000, The Analyst.

[75]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[76]  Mario Cabodi,et al.  Entropic recoil separation of long DNA molecules. , 2002, Analytical chemistry.

[77]  Y. Huang,et al.  Cell separation by dielectrophoretic field-flow-fractionation. , 2000, Analytical chemistry.

[78]  M. Tarlov,et al.  Surface characterization of laser-ablated polymers used for microfluidics. , 2002, Analytical chemistry.

[79]  P. Sarro,et al.  Polyimide sacrificial layer and novel materials for post-processing surface micromachining , 2002 .

[80]  Vijay Namasivayam,et al.  Advances in on-chip photodetection for applications in miniaturized genetic analysis systems , 2004 .

[81]  R. Hölzel,et al.  Non-invasive determination of bacterial single cell properties by electrorotation. , 1999, Biochimica et biophysica acta.

[82]  Peter R. C. Gascoyne,et al.  Dielectrophoresis-based sample handling in general-purpose programmable diagnostic instruments , 2004, Proceedings of the IEEE.

[83]  Zachary Shriver,et al.  Glycomics: a pathway to a class of new and improved therapeutics , 2004, Nature Reviews Drug Discovery.

[84]  Joseph Wang,et al.  Silver-Enhanced Colloidal Gold Electrochemical Stripping Detection of DNA Hybridization , 2001 .

[85]  B. Lin,et al.  Modification of a poly(methyl methacrylate) injection-molded microchip and its use for high performance analysis of DNA. , 2005, Journal of separation science.

[86]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[87]  P Belgrader,et al.  A battery-powered notebook thermal cycler for rapid multiplex real-time PCR analysis. , 2001, Analytical chemistry.

[88]  R. Wilson,et al.  Complete genome sequence of Salmonella enterica serovar Typhimurium LT2 , 2001, Nature.

[89]  E. Cummings,et al.  Dielectrophoretic concentration and separation of live and dead bacteria in an array of insulators. , 2004, Analytical chemistry.

[90]  Harold G. Craighead,et al.  Entropic trapping and sieving of long DNA molecules in a nanofluidic channel , 1999 .

[91]  J R Scherer,et al.  Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. , 2004, Analytical chemistry.

[92]  G. Whitesides,et al.  Patterning Thin Films of Poly(ethylene imine) on a Reactive SAM Using Microcontact Printing , 1999 .

[93]  O. Tabata,et al.  Replica multichannel polymer chips with a network of sacrificial channels sealed by adhesive printing method. , 2005, Lab on a chip.

[94]  Christopher R. Lowe,et al.  Silicon microchambers for DNA amplification , 1998 .

[95]  H T Soh,et al.  Integrated microsystem for dielectrophoretic cell concentration and genetic detection. , 2005, Lab on a chip.

[96]  J P Landers,et al.  Polymerase chain reaction in polymeric microchips: DNA amplification in less than 240 seconds. , 2001, Analytical biochemistry.

[97]  Jan Bressler,et al.  Epigenetics and human disease. , 2004, Annual review of genomics and human genetics.

[98]  R A Mathies,et al.  Capillary electrophoresis chips with integrated electrochemical detection. , 1998, Analytical chemistry.

[99]  Theodore K. Christopoulos,et al.  Continuous-flow DNA and RNA amplification chip combined with laser-induced fluorescence detection , 2003 .

[100]  T. R. Anthony Anodic bonding of imperfect surfaces , 1983 .

[101]  T. Dawes,et al.  Microfluidic bischemical analysis system , 1997, Proceedings of International Solid State Sensors and Actuators Conference (Transducers '97).

[102]  Igor L. Medintz,et al.  High speed single nucleotide polymorphism typing of a hereditary haemochromatosis mutation with capillary array electrophoresis microplates , 2000, Electrophoresis.

[103]  K. Jakobsen,et al.  Purification of mRNA directly from crude plant tissues in 15 minutes using magnetic oligo dT microspheres. , 1990, Nucleic acids research.

[104]  R S Foote,et al.  Microchip device for cell lysis, multiplex PCR amplification, and electrophoretic sizing. , 1998, Analytical chemistry.

[105]  Kevin T. Turner,et al.  Modeling of direct wafer bonding: effect of wafer bow and etch patterns , 2002 .

[106]  C. Kvam,et al.  Application of Magnetic Beads in Bioassays , 1993, Bio/Technology.

[107]  I-Ming Hsing,et al.  Sequence-specific electrochemical detection of asymmetric PCR amplicons of traditional Chinese medicinal plant DNA. , 2002, Analytical chemistry.

[108]  Robin H. Liu,et al.  An organic self-regulating microfluidic system. , 2001, Lab on a chip.

[109]  K. Goodson,et al.  Transient liquid crystal thermometry of microfabricated PCR vessel arrays , 1998 .

[110]  Ulrich Dillner,et al.  Chip elements for fast thermocycling , 1997 .

[111]  Brian N. Johnson,et al.  An integrated nanoliter DNA analysis device. , 1998, Science.

[112]  Marc Madou,et al.  MEMS-based sample preparation for molecular diagnostics , 2002, Analytical and bioanalytical chemistry.

[113]  M. Enright,et al.  Molecular Typing of Bacteria Directly from Cerebrospinal Fluid , 2000, European Journal of Clinical Microbiology and Infectious Diseases.

[114]  D. Stevens,et al.  Community-acquired Staphylococcus aureus infections: Increasing virulence and emerging methicillin resistance in the new millennium. , 2003, Current Opinion in Infectious Diseases.

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

[116]  D. Swerdlow,et al.  Escherichia coli O157:H7 and the hemolytic-uremic syndrome. , 1995, The New England journal of medicine.

[117]  S. Hjertén,et al.  Free zone electrophoresis. , 1967, Chromatographic reviews.

[118]  Jutamaad Satayavivad,et al.  Microfluidic approaches to malaria detection. , 2004, Acta tropica.

[119]  Vincent Studer,et al.  A nanoliter-scale nucleic acid processor with parallel architecture , 2004, Nature Biotechnology.

[120]  I-Ming Hsing,et al.  Microfabricated PCR-electrochemical device for simultaneous DNA amplification and detection. , 2003, Lab on a chip.

[121]  S. P. Fodor,et al.  Light-directed, spatially addressable parallel chemical synthesis. , 1991, Science.

[122]  Qintao Zhang,et al.  Temperature analysis of continuous-flow micro-PCR based on FEA , 2002 .

[123]  Stephen Quake,et al.  A nanoliter rotary device for polymerase chain reaction , 2002, Electrophoresis.

[124]  P. He,et al.  Electrochemical detection of DNA hybridization based on silver-enhanced gold nanoparticle label , 2002 .

[125]  C. Dye,et al.  Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. , 1999, JAMA.

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

[127]  R. Mathies,et al.  Monolithic integrated microfluidic DNA amplification and capillary electrophoresis analysis system , 2000 .

[128]  Igor L. Medintz,et al.  Genotyping energy-transfer-cassette-labeled short-tandem-repeat amplicons with capillary array electrophoresis microchannel plates. , 2001, Clinical chemistry.

[129]  Igor L. Medintz,et al.  Single-molecule DNA amplification and analysis in an integrated microfluidic device. , 2001, Analytical chemistry.

[130]  D E Ingber,et al.  Controlling cell attachment on contoured surfaces with self-assembled monolayers of alkanethiolates on gold. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[131]  A. Heeger,et al.  Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor. , 2005, Angewandte Chemie.

[132]  R. Pal,et al.  Phase change microvalve for integrated devices. , 2004, Analytical chemistry.

[133]  H. Sambrook Molecular cloning : a laboratory manual. Cold Spring Harbor, NY , 1989 .

[134]  Masayoshi Esashi,et al.  Low-temperature silicon-to-silicon anodic bonding with intermediate low melting point glan , 1990 .

[135]  M. Skidmore,et al.  Microbial Life beneath a High Arctic Glacier , 2000, Applied and Environmental Microbiology.

[136]  F F Becker,et al.  Differential analysis of human leukocytes by dielectrophoretic field-flow-fractionation. , 2000, Biophysical journal.

[137]  F. Fellmann,et al.  Simplified protocol of solid-phase cDNA libraries for multiple PCR amplification. , 1996, BioTechniques.

[138]  M. A. Northrup,et al.  DNA Amplification with a Microfabricated Reaction Chamber , 1993 .

[139]  V. Venkataraman,et al.  A portable battery-operated chip thermocycler based on induction heating , 2002 .

[140]  V W Weedn,et al.  Rapid PCR for identity testing using a battery-powered miniature thermal cycler. , 1998, Journal of forensic sciences.

[141]  Juan G. Santiago,et al.  Fabrication and characterization of electroosmotic micropumps , 2001 .

[142]  Harold G. Craighead,et al.  ENTROPIC TRAPPING AND ESCAPE OF LONG DNA MOLECULES AT SUBMICRON SIZE CONSTRICTION , 1999 .

[143]  Jeffery H. Fenton,et al.  A miniature integrated device for automated multistep genetic assays. , 2000, Nucleic acids research.

[144]  D. Jed Harrison,et al.  Microfabricated electrolysis pump system for isolating rare cells in blood , 2003 .

[145]  Toshihiro Kamei,et al.  Integrated hydrogenated amorphous Si photodiode detector for microfluidic bioanalytical devices. , 2003, Analytical chemistry.

[146]  M. Roederer,et al.  The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. , 2002, Clinical chemistry.

[147]  R A Mathies,et al.  Turn geometry for minimizing band broadening in microfabricated capillary electrophoresis channels. , 2000, Analytical chemistry.

[148]  Steven A Soper,et al.  Electrokinetically synchronized polymerase chain reaction microchip fabricated in polycarbonate. , 2005, Analytical chemistry.

[149]  A. Woolley,et al.  Ultra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[150]  C. Wittwer,et al.  PCR amplification using electrolytic resistance for heating and temperature monitoring. , 2000, BioTechniques.

[151]  Igor L. Medintz,et al.  High-performance multiplex SNP analysis of three hemochromatosis-related mutations with capillary array electrophoresis microplates. , 2001, Genome research.

[152]  K. Mullis,et al.  Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. , 1985, Science.