Light-directed chemical synthesis has been used to generate miniaturized, high-density arrays of oligonucleotide probes. These probe arrays, or DNA chips, are then used for parallel DNA hybridization analysis, directly yielding sequence information from genomic DNA. Successful implementation of the DNA chip technology requires development of methods for fabrication of the probe arrays, detection of target hybridization, resolution of the thermodynamic parameters affecting hybridization, and algorithms to analyze hybridization and reconstruct target sequence. The results of recent experiments addressing each of these methods will be discussed. Application specific oligonucleotide probe array designs will be presented. These designed arrays have been used to demonstrate direct reading of genomic sequence. This method is proving to be a powerful tool for rapid investigations in DNA sequencing, human genetics and diagnostics, pathogen detection, and DNA molecular recognition.

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