Protein microarray technology.

Microarray technology allows the simultaneous analysis of thousands of parameters within a single experiment. Microspots of capture molecules are immobilised in rows and columns onto a solid support and exposed to samples containing the corresponding binding molecules. Readout systems based on fluorescence, chemiluminescence, mass spectrometry, radioactivity or electrochemistry can be used to detect complex formation within each microspot. Such miniaturised and parallelised binding assays can be highly sensitive, and the extraordinary power of the method is exemplified by array-based gene expression analysis. In these systems, arrays containing immobilised DNA probes are exposed to complementary targets and the degree of hybridisation is measured. Recent developments in the field of protein microarrays show applications for enzyme-substrate, DNA-protein and different types of protein-protein interactions. This article discusses theoretical advantages and limitations of any miniaturised capture-molecule-ligand assay system and discusses how the use of protein microarrays will change diagnostic methods and genome and proteome research.

[1]  H. Davies,et al.  Tissue-specific microdissection coupled with ProteinChip array technologies: applications in cancer research. , 2000, BioTechniques.

[2]  Martha L. Bulyk,et al.  Quantifying DNA–protein interactions by double-stranded DNA arrays , 1999, Nature Biotechnology.

[3]  S. P. Fodor,et al.  Multiplexed biochemical assays with biological chips , 1993, Nature.

[4]  Patrik Samuelson,et al.  Staphylococcal Surface Display of Immunoglobulin A (IgA)- and IgE-Specific In Vitro-Selected Binding Proteins (Affibodies) Based on Staphylococcus aureus Protein A , 1999, Applied and Environmental Microbiology.

[5]  H. Ge,et al.  UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions. , 2000, Nucleic acids research.

[6]  H. Lehrach,et al.  Protein microarrays for gene expression and antibody screening. , 1999, Analytical biochemistry.

[7]  Anthony D. Keefe,et al.  The use of mRNA display to select high-affinity protein-binding peptides , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Y. Baba Development of novel biomedicine based on genome science. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[9]  I. Tomlinson,et al.  Antibody arrays for high-throughput screening of antibody–antigen interactions , 2000, Nature Biotechnology.

[10]  H. Lehrach,et al.  Protein arrays for gene expression and molecular interaction screening. , 2000, Current opinion in microbiology.

[11]  N. Anderson,et al.  Proteome and proteomics: New technologies, new concepts, and new words , 1998, Electrophoresis.

[12]  Manqiu Cao,et al.  High-throughput generation and engineering of recombinant human antibodies. , 2001, Journal of immunological methods.

[13]  B. Bruce,et al.  Organelle isolation by magnetic immunoabsorption. , 1999, BioTechniques.

[14]  G. Cagney,et al.  Large-scale functional analysis using peptide or protein arrays , 2000, Nature Biotechnology.

[15]  Dolores J. Cahill,et al.  Protein arrays: a high-throughput solution for proteomics research? , 2000 .

[16]  Stuart L. Schreiber,et al.  Printing Small Molecules as Microarrays and Detecting Protein−Ligand Interactions en Masse , 1999 .

[17]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[18]  H. Lehrach,et al.  A method for global protein expression and antibody screening on high-density filters of an arrayed cDNA library. , 1998, Nucleic acids research.

[19]  P. Brown,et al.  Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions , 2001, Genome Biology.

[20]  Dieter Stoll,et al.  A microarray enzyme‐linked immunosorbent assay for autoimmune diagnostics , 2000, Electrophoresis.

[21]  M. Gerstein,et al.  Analysis of yeast protein kinases using protein chips , 2000, Nature Genetics.

[22]  I Humphery-Smith,et al.  Array-based proteomics: high-throughput expression and purification of IMAGE consortium cDNA clones. , 1999, Current opinion in molecular therapeutics.

[23]  P. Kufer,et al.  Anti-self antibodies selected from a human IgD heavy chain repertoire: a novel approach to generate therapeutic human antibodies against tumor-associated differentiation antigens , 2001, Cancer Immunology, Immunotherapy.

[24]  A. Plückthun,et al.  Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. , 2000, Journal of molecular biology.

[25]  S. Weinberger,et al.  Recent trends in protein biochip technology. , 2000, Pharmacogenomics.

[26]  T. Logtenberg,et al.  Tumor cell killing by in vitro affinity-matured recombinant human monoclonal antibodies , 2001, Cancer Immunology and Immunotherapy.

[27]  D. Walt,et al.  A fiber-optic microarray biosensor using aptamers as receptors. , 2000, Analytical biochemistry.

[28]  F. Müller,et al.  Messenger RNA expression and immunological quantification of phospholamban and SR-Ca(2+)-ATPase in failing and nonfailing human hearts. , 1996, Cardiovascular research.

[29]  B. Kreider PROfusion™: Genetically Tagged Proteins for Functional Proteomics and Beyond , 2000, Medicinal research reviews.

[30]  L. G. Mendoza,et al.  High-throughput microarray-based enzyme-linked immunosorbent assay (ELISA). , 1999, BioTechniques.

[31]  R. Goldman,et al.  Antibodies: indispensable tools for biomedical research. , 2000, Trends in biochemical sciences.

[32]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[33]  Ű. Langel,et al.  Antisense properties of peptide nucleic acids. , 1999, Frontiers in bioscience : a journal and virtual library.

[34]  L. Gold,et al.  Aptamers as therapeutic and diagnostic agents. , 2000, Journal of biotechnology.

[35]  Ruo-Pan Huang,et al.  Simultaneous Detection of Multiple Proteins with an Array-Based Enzyme-Linked Immunosorbent Assay (ELISA) and Enhanced Chemiluminescence (ECL) , 2001, Clinical chemistry and laboratory medicine.

[36]  D. Housman,et al.  Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Uhlén,et al.  Affinity maturation of a Taq DNA polymerase specific affibody by helix shuffling. , 1999, Protein engineering.

[38]  R. Lerner,et al.  Making artificial antibodies: a format for phage display of combinatorial heterodimeric arrays. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Voorberg,et al.  Multiple VH genes are used to assemble human antibodies directed toward the A3-C1 domains of factor VIII. , 2001, Blood.

[40]  D. Corey,et al.  Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA. , 2001, Chemistry & biology.

[41]  Lohse Pa,et al.  In vitro protein display in drug discovery. , 2001 .

[42]  R. Ekins,et al.  Multi-analyte immunoassay. , 1989, Journal of pharmaceutical and biomedical analysis.

[43]  S. Schreiber,et al.  Printing proteins as microarrays for high-throughput function determination. , 2000, Science.

[44]  F W Chu,et al.  Multianalyte microspot immunoassay--microanalytical "compact disk" of the future. , 1991, Clinical chemistry.

[45]  S. Jayasena Aptamers: an emerging class of molecules that rival antibodies in diagnostics. , 1999, Clinical chemistry.

[46]  S. Kingsmore,et al.  Immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[47]  R Ekins,et al.  Multispot, multianalyte, immunoassay. , 1990, Annales de biologie clinique.

[48]  D. Ryu,et al.  Recent Progress in Biomolecular Engineering , 2000, Biotechnology progress.

[49]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[50]  A. Mirzabekov,et al.  Protein microchips: use for immunoassay and enzymatic reactions. , 2000, Analytical biochemistry.