SENSITIVE, MULTIPLEXED ANALYSIS OF BREAST CANCER MARKERS

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This proposal describes the development of semi-conductor nanocrystals (quantum dots) as probes for the specific detection of multiple markers of breast cell transformation simultaneously. Quantum dots are novel luminescent probes that are photo-stable, easily multiplexed and can be sensitively detected with simple, inexpensive optical systems. In phase I of the project we will use conjugated quantum dots to detect three selected breast cancer markers in sections of well-characterized breast cancer cell lines to demonstrate their specificity in a simple model system. In phase II we will multiplex this system, incorporate a fourth marker and develop it for use on tissues and tissue micro-arrays. We will detect the expression of three protein markers (p53, estrogen receptor and progesterone receptor). Initially we will characterize the assay specificity and performance of the probes individually. We will use this model to compare the stability and sensitivity of quantum dots with conventional fluorescent dyes. It is anticipated that this technology will allow the use of these probes to characterize breast tumor biopsies and ultimately quantum dots could be used to more confidently phenotype any disease for which multiple markers exist. PROPOSED COMMERCIAL APPLICATIONS: This research could directly lead to a novel product that allows more sensitive, quicker and more informative diagnostic and prognostic evaluation of breast cancer tissue sections. The technology is also directly applicable to many different kinds of tumor analysis and could be used on tissue microarrays to vastly increase the throughput and aid the archiving of tissue section analysis.