Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists.

High-density arrays of oligonucleotide probes are proving to be powerful new tools for large-scale DNA and RNA sequence analysis. A method for constructing these arrays, using light-directed DNA synthesis with photo-activatable monomers, can currently achieve densities on the order of 10(6) sequences/cm2. One of the challenges facing this technology is to further increase the volume, complexity, and density of sequence information encoded in these arrays. Here we demonstrate a new approach for synthesizing DNA probe arrays that combines standard solid-phase oligonucleotide synthesis with polymeric photoresist films serving as the photoimageable component. This opens the way to exploiting high-resolution imaging materials and processes from the microelectronics industry for the fabrication of DNA probe arrays with substantially higher densities than are currently available.

[1]  W. Bains,et al.  A novel method for nucleic acid sequence determination. , 1988, Journal of theoretical biology.

[2]  Arnost Reiser,et al.  Photoreactive Polymers: The Science and Technology of Resists , 1989 .

[3]  Simple negative resist for deep ultraviolet, electron beam, and x‐ray lithography , 1989 .

[4]  R. Drmanac,et al.  Sequencing of megabase plus DNA by hybridization: theory of the method. , 1989, Genomics.

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

[6]  Lysov YuP,et al.  A method for DNA sequencing by hybridization with oligonucleotide matrix. , 1991, DNA sequence : the journal of DNA sequencing and mapping.

[7]  L. Hood,et al.  Large-scale and automated DNA sequence determination. , 1991, Science.

[8]  E. Southern,et al.  Parallel analysis of oligodeoxyribonucleotide (oligonucleotide) interactions. I. Analysis of factors influencing oligonucleotide duplex formation. , 1992, Nucleic acids research.

[9]  S. Beaucage,et al.  Advances in the Synthesis of Oligonucleotides by the Phosphoramidite Approach , 1992 .

[10]  E. Southern,et al.  Analyzing and comparing nucleic acid sequences by hybridization to arrays of oligonucleotides: evaluation using experimental models. , 1992, Genomics.

[11]  D. J. Harrison,et al.  Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip , 1993, Science.

[12]  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.

[13]  Robert J. Lipshutz,et al.  Advanced DNA sequencing technologies , 1994 .

[14]  C. Grant Willson,et al.  Chemical Amplification in High-Resolution Imaging Systems , 1994 .

[15]  S. P. Fodor,et al.  Light-generated oligonucleotide arrays for rapid DNA sequence analysis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. G. Willson,et al.  Introduction to microlithography , 1994 .

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

[18]  M Eggers,et al.  A review of microfabricated devices for gene-based diagnostics. , 1995, Hematologic pathology.

[19]  S. P. Fodor,et al.  Using oligonucleotide probe arrays to access genetic diversity. , 1995, BioTechniques.

[20]  A. R. Kaiser,et al.  Microfabricated structures for integrated DNA analysis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[21]  N. Shen,et al.  Extensive polymorphisms observed in HIV–1 clade B protease gene using high–density oligonucleotide arrays , 1996, Nature Medicine.

[22]  S. M. Kim,et al.  Cystic fibrosis mutation detection by hybridization to light‐generated DNA probe arrays , 1996, Human mutation.

[23]  R. Sapolsky,et al.  Mapping genomic library clones using oligonucleotide arrays. , 1996, Genomics.

[24]  A. Blanchard,et al.  High-density oligonucleotide arrays , 1996 .

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

[26]  J. Badge.  DNA sequencing. , 1998, Methods in molecular biology.