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Non-invasive Monitoring of Subcellular Morphology

$415,000R33FY2004RRNIH

Beth Israel Deaconess Medical Center, Boston MA

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Abstract

DESCRIPTION (provided by applicant): The overall objective of this project is to develop and test a novel technique for non-invasive dynamic monitoring of subcellular structure, which can be used in multiple areas of biomedical research. Based on the technique, we will develop an instrument to scan biological cells with focused laser beams at multiple wavelengths and collect elastically scattered light using a confocal arrangement. Collected light, elastically scattered by various subcellular organelles and structures, will provide real time information about morphological, biochemical and physical properties of various regions of the living cell and their function. To extract this information we will combine the principals of light scattering spectroscopy (LSS) with confocal laser scanning microscopy (CLSM). LSS is an optical technique, which relates spectroscopic properties of light elastically scattered by small particles to their physical properties, such as size, refractive index and shape. CLSM is an optical technique developed to resolve biological structures within a translucent object with micron resolution. LSS was recently applied to biological problems by this investigator and his colleagues primarily to detect early cancer. The multispectral nature of LSS enables this technique to achieve a resolving power beyond the Rayleigh limit by combining the information obtained at many different wavelengths. The new technique will be capable of determining quantitative parameters of microscopic biological structures, such as, for example, characteristics of embryo morphology and stage of development as a function of time or morphological properties related to early precancerous changes on subcellular scale.

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