Research and Teaching Interests
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An array of 15 DNA primer-template duplexes sequentially probed with the four dNTPs. Predicted readout patterns are shown in the inset. |
In my research group we divide the material world into two parts – “rocks” and “goo” – and develop and exploit novel analytical methods targeted to these disparate materials types. “Rocks” constitute the hard, mostly inorganic world of metals, semiconductors and minerals. Here the information needed is mostly elemental and/or isotopic composition, usually spatially resolved to within a few micrometers or less, and for this we utilize the technique of secondary ion mass spectrometry. Our interests lie in understanding the complex phenomena underlying secondary ion formation and in developing novel instrumentation, for example a novel electrometer array detector to determine the isotopic composition of oxygen in the sun, as reflected in solar wind samples from the Genesis satellite. Our workhorse instrument is a Cameca IMS 3f; we also use a Cameca IMS 6f and will add a time-of-flight SIMS instrument (TRIFT 1) in 2004.The “goo” side of the world consists of biomolecules, e.g. proteins and DNA; here the analytical challenge is to obtain structural and/or sequence information that both identifies the molecules and rapidly detects potentially hazardous mutations. For proteins, we are developing new applications of matrix-assisted laser desorption/ionization (MALDI) time of flight mass spectrometry. For DNA we are developing a new approach to DNA sequencing. We use DNA polymerase together with single, fluorescently-labeled deoxyribonucleotide triphosphates (dNTPs) to probe the template sequences of a surface-immobilized array of DNA primer/template duplexes. The primers with appropriate template sequence are extended and those spots fluoresce. After destroying the fluorescent label the process is cyclically repeated with the four species of dNTP. The projected information rate is > 10,000 bases/minute on an array of 10,000 or more DNA samples.
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| Representative Publications
"Multiplexed DNA sequencing-by-synthesis," S.A. Aksyonov, M. Bittner, L.B. Bloom, L.J. Reha-Krantz, I.R. Gould, M.A. Hayes, U.A. Kiernan, E.E. Niederkofler, V. Pizzicone, R.S. Rivera, D.J.B. Williams and P. Williams, Anal. Biochem. In press, (2006).
"Quantitative study of oxygen enhancement of sputtered ion yields. I: Argon ion bombardment of a silicon surface with O2 flood," K. Franzreb, J. Lorincik and P. Williams, Surf. Sci. 573, 291-309 (2004).
"Inert gas clusters ejected from bursting bubbles during sputtering," K. Franzreb and P. Williams, Phys. Rev. Letters 91, 15501 (2003).
"Mass-resolved low-energy back-scattering of alkali ions," K. Franzreb and P. Williams, Applied Surface Science 203-204, 98-101 (2003).
"High-throughput protein characterization using mass spectrometric immunoassay," U.A. Kiernan, K.A. Tubbs, K. Gruber, D. Nedelkov, E.E. Niederkofler, P. Williams and R.W. Nelson, Analytical Biochemistry 301, 49-56 (2002).
"Impact desolvation of electrosprayed microdroplets: a new ionization method for mass spectrometry of large biomolecules," S.A. Aksyonov and P. Williams, Mass Spectrom. 15, 2001-2006 (2001).
"Electrical Deflection of Polar Liquid Streams: A Misunderstood Demonstration," M. Ziaei-Moayyed, E. Goodman and P. Williams, J. Chem. Ed. 77, 1520-1524 (2000).
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