Circulating DNA in blood is a strong diagnostic and prognostic indicator, making blood a valuable solid tumor surrogate for preventive cancer diagnostics as well as a noninvasive monitoring of patients who are actively under cancer therapy. Unfortunately, current nucleic-acid-based technologies are not sensitive enough to detect the circulating DNA fragments carrying rare allele mutations (associated with cancer) in the background of a higher load of normal genomic DNA (range: 10-3 to 10-6). MSI proposes to develop the automated microfluidic MutaSorter-Chip system for the enrichment of circulating DNA fragments with mutations associated with various cancer types. The system uniquely combines bar-coded bead technology to capture rare mutant alleles via hybridization on digitally encoded micro-particles with 1 x N microfluidic sorting to subsequently enrich the captured DNA segments, followed by PCR-based screens. The platform is amenable to scale and allows thousands of different DNA segments to be screened for specific mutations (including sequence alterations as well as epigenetic alterations) with high sensitivity and specificity. Phase I will be dedicated to the fabrication and feasibility testing of the bead-based microfluidic chip system for a panel of different types of mutations. ? ?
