AVS 47th International Symposium
    Surface Science Monday Sessions
       Session SS3-MoM

Paper SS3-MoM8
DNA Sequence Information Obtained by TOF-SIMS Analysis

Monday, October 2, 2000, 10:40 am, Room 210

Session: Surface Science Opportunities and New Applications
Presenter: K.F. Willey, Atom Sciences, Inc.
Authors: K.F. Willey, Atom Sciences, Inc.
W.L.B. White, Atom Sciences, Inc.
T.J. Whitaker, Atom Sciences, Inc.
Correspondent: Click to Email
A high-speed DNA screening technology is currently being developed at Atom Sciences. Our approach utilizes gene chip technology, which has paved the way for widespread DNA diagnostics. Current technology utilizes DNA hybridization to complementary oligonucleotides of known sequence immobilized to a surface. Unknown DNA is typically labeled with radioisotopes, stable isotopes, or fluorescent tags in order to detect hybridization sites. This labeling is costly and can be an impediment to the widespread use of gene chips. We are developing a new technology that requires no labeling. In this technique, target DNA hybridizes to an array of known sequences of peptide nucleic acid (PNA) probes attached to a silicon substrate. The naturally occurring phosphate groups in DNA provide an ideal intrinsic label because PNA contains no phosphorous. PNA is an analog of DNA in which the sugar/phosphate backbone of DNA is replaced by a peptide backbone. Target DNA and PNA probes undergo hydrogen bonding of AT and GC base pairs (Watson-Crick rules). Diagnostic information is obtained by identifying DNA hybridization sites within the array using negative SIMS detection of phosphate fragments. The sensitivity of SIMS detection and use of PNA probes gives our technology distinct advantages over existing diagnostic techniques (e.g. fluorescence). The major drawback, however, is the cost of commercial SIMS instrumentation. Therefore, at Atom Sciences, we have developed an inexpensive TOF-SIMS instrument. We will discuss the advantages of using a DNA/PNA hybridization scheme and its application to identifying single base mismatches. We will also discuss the current SIMS instrument used for technology development and how it could be simplified for a clinical diagnostic setting.