Topographical Scanning Spectroscopy of Gene Markers

The investigators state improving the efficiency and accuracy of DNA sequencing methods is essentiasuccess of the Human Genome Program. The instrumentation will result in new forms of scanning-probespectroscopies (SPMOS) which will permit the topographical chemical mapping of DNA samples with unprlateral and normal resolution. The microscope detects a change in signal intensity and in spectral wapproaches an emission site. Due to the higher strength of radiation in the near zone, and due to tisignals are observed. Low resolution physical mapping has recently been improved due to fluorescence(FISH) and the use of interphase chromosomes. They claim SPMOS should resolve neighboring markers muconventional optical methods. Effects to be studied for SPMOS include quenching, stimulated emissionfluorescence due to the probe tip. In Phase II, optically induced repulsive forces in chromatin willattempt to physically improve marker separations by using the high energy density of evanescent waveenhancements due to artificial microstructures. The applicant intends to demonstrate physical mappininterphase chromosomes with specification of actual spatial coordinates at a resolution of 1-100kbpinstrument that has both imaging zoom and spectroscopic zoom capabilities. During Phase I of this prdevelop a hybrid scanning probe fiber optic scan head which will be mounted on a conventional microswill be demonstrated by imaging fluorescently labelled probes on selected mouse and human chromosome