Rare aging-related mutagenic processes are associated with diseasesm and while the identification of these events has the potential to aid in early diagnosis, these events are often undetected due to a variety of reasons, most notably cost and technical difficulties in the abilitying to detect these low abundance events from minute quantities of biological specimens. An example is Lynch syndrome (LS), a hereditary cancer predisposition syndrome caused by the breakdown of the DNA mismatch repair machinery. Despite that MMR deficiency can be detected by the presence of microsatellite instability markers, most of the current technologies require biopsy specimens to do so. Another example is hepatocellular carcinoma (HCC), in which the presence of low-abundance hepatitis B virus may be detected as the sequence is integrated in the genome. Methods such as single molecule molecular inversion probe-based sequencing (smMIP-seq) and N-methylpyrrole-N-methylimidazole polyamide (PIP)-assisted droplet digital polymerase chain reaction (PDPCR) have been considered to provide the resolution needed to characterize low-level genomic aberrations in blood or saliva samples, and a platform utilizing these techniques may be able to achieve accurate and multiplexed target capture, and subsequently the goal of ultrasensitive characterization of rare somatic mutations at a relatively low cost. This proposal aims to develop development of a novel ultra-sensitive, low-cost and high-throughput detection platform, using technologies such as smMIP-seq and PDPCR for the detection of low-abundance genomic aberrations.