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Session LC31 - Imaging and Spectroscopy: Scanning Microscopy and Biomagnetic Probes.
ORAL session, Tuesday afternoon, March 23
Room 164W, GWCC

[LC31.04] Discrimination of DNA Hybridization Using Chemical Force Microscopy

L. Mazzola (Stanford University, Stanford, CA 94305), S.P.A. Fodor (Affymetrix, Inc., Santa Clara, CA 95051), C.W. Frank (Stanford University, Stanford, CA 94305)

Atomic force microscopy (AFM) can be used to probe the mechanics of molecular recognition. In the application known as "chemical force" microscopy, the AFM tip can be chemically modified and then used to probe surfaces through chemical recognition. When modified with a biological ligand or receptor, the AFM tip can differentiate the biological binding partner from a surface array. The strength of the interaction between the modified tip and the substrate is mediated by the chemical affinity of the molecular pair. In this work we use chemical force microscopy (CFM) to probe the interaction of short segments of DNA (oligonucleotides). A standard AFM cantilever was modified with the sequence 3'-CAGTTCTACGATGGCAAGTC and then used to scan substrates containing the complementary sequence 5*-GTCAAGATGCTACCGTTCAG. The substrates consisted of micron-scale, patterned arrays of one or more distinct oligonucleotides. When in sliding contact with the substrate, the modified tips exhibit a strong frictional interaction with the surface-bound DNA. The friction force is linear with the applied load and is shown to be proportional to the molecular adhesion. Through friction force imaging, the DNA-modified tips clearly distinguish the complementary oligonucleotide from non-complementary sequences within the patterned array.

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