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Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array

Nature Biotechnology volume 17, pages 974–978 (1999)Cite this article

Abstract

Oligonucleotide microarrays, also called "DNA chips," are currently made by a light-directed chemistry that requires a large number of photolithographic masks for each chip. Here we describe a maskless array synthesizer (MAS) that replaces the chrome masks with virtual masks generated on a computer, which are relayed to a digital micromirror array. A 1:1 reflective imaging system forms an ultraviolet image of the virtual mask on the active surface of the glass substrate, which is mounted in a flow cell reaction chamber connected to a DNA synthesizer. Programmed chemical coupling cycles follow light exposure, and these steps are repeated with different virtual masks to grow desired oligonucleotides in a selected pattern. This instrument has been used to synthesize oligonucleotide microarrays containing more than 76,000 features measuring 16 μm2. The oligonucleotides were synthesized at high repetitive yield and, after hybridization, could readily discriminate single-base pair mismatches. The MAS is adaptable to the fabrication of DNA chips containing probes for thousands of genes, as well as any other solid-phase combinatorial chemistry to be performed in high-density microarrays.

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Figure 1: Schematic of the maskless array synthesizer (MAS).
Figure 2: Optical performance of the MAS optical system.
Figure 3: High-resolution patterning of MeNPOC using MAS.
Figure 4: Repetitive yield of MeNPOC-bases.
Figure 5: Hybridization specificity.
Figure 6: Hybridization of different length oligonucleotides.

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Acknowledgements

We thank the University of Wisconsin's University/Industry Relations Board, the UW Graduate School, and the UW NIH Biotechnology Training Grant (RDG) for funding, the Keck Neural Imaging Laboratory of the University of Wisconsin for use of their confocal microscope, ModularIS, Inc. for donating MAS control software, and Craig Richmond for helpful discussions.

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Author notes

  1. Sangeet Singh-Gasson

    Present address: Department of Bioengineering (MC 063), University of Illinois at Chicago, Chicago, IL, 60607

  2. Sangeet Singh-Gasson and Roland D. Green: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, Center for NanoTechnology, University of Wisconsin, Madison, 53706, WI

    Sangeet Singh-Gasson, Yongjian Yue & Franco Cerrina

  2. Environmental Toxicology Center, University of Wisconsin , Madison, 53706, WI

    Roland D. Green

  3. Program in Cellular and Molecular Biology, University of Wisconsin, Madison, 53706, WI

    Clark Nelson

  4. Department of Genetics, University of Wisconsin, Madison, 53706, WI

    Fred Blattner

  5. Biotechnology Center, University of Wisconsin, Madison, 53706, WI

    Michael R. Sussman

Authors
  1. Sangeet Singh-Gasson
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  2. Roland D. Green
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  3. Yongjian Yue
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  4. Clark Nelson
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  5. Fred Blattner
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  6. Michael R. Sussman
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  7. Franco Cerrina
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Corresponding author

Correspondence to Michael R. Sussman.

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Singh-Gasson, S., Green, R., Yue, Y. et al. Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nat Biotechnol 17, 974–978 (1999). https://doi.org/10.1038/13664

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