Light-generated oligonucleotide arrays for rapid DNA sequence analysis

Journal Article · Tue May 24 04:00:00 EDT 1994 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.91.11.5022· OSTI ID:6853784

Pease, A C; Solas, D; Sullivan, E J; Holmes, C P ^[1]; Cronin, M T ^[2]; Fodor, S P.A. ^[3]

---

1. Affymax, Palo Alto, CA (United States)
2. Affymetrix, Santa Clara, CA (United States)
3. Affymetrix, Palo Alto, CA (United States) Affymetrix, Santa Clara, CA (United States)

In many areas of molecular biology there is a need to rapidly extract and analyze genetic information; however, current technologies for DNA sequence analysis are slow and labor intensive. The authors report here how modern photolithographic techniques can be used to facilitate sequence analysis by generating miniaturized arrays of densely packed oligonucleotide probes. These probe arrays, or DNA chips, can then be applied to parallel DNA hybridization analysis, directly yielding sequence information. In a preliminary experiment, a 1.28 [times] 1.28 cm array of 256 different octanucleotides was produced in 16 chemical reaction cycles, requiring 4 hr to complete. The hybridization pattern of fluorescently labeled oligonucleotide targets was then detected by epifluorescene microscopy. The fluorescence signals from complementary probes were 5-35 times stronger than those with single or double base-pair hybridization mismatches, demonstrating specificity in the identification of complementary sequences. This method should prove to be a powerful tool for rapid investigations in human genetics and diagnostics, pathogen detection, and DNA molecular recognition.

• OSTI ID: 6853784
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 91:11; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550400 -- Genetics
59 BASIC BIOLOGICAL SCIENCES
DNA SEQUENCING
OPTIMIZATION
STRUCTURAL CHEMICAL ANALYSIS