Presently, there are no FDA-approved, blood-based assays for either the detection of point mutations or gene fusions in cell-free DNA. We propose to develop a nanophotonic platform that is capable of detecting mutations in low numbers without the need for PCR. This diagnostic test will be applied in clinical laboratories that will help tailor therapies and positively impact the patient outcome. For our proof-of-concept studies with our platform, asssays will be developed for the detection of cfDNA containing point mutations in the KRAS and BRAF genes, and gene fusions involving the ALK gene. These genomic aberrations are both validated biomarkers and clinically actionable. For example, activating point mutations of KRAS occur in non small cell ling and colorectal cancer respectively, and are associated with lack of response to treatment with the anti-EGFR monoclonal antibody panitumumab and the kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Similarly, BRAF and gene fusions of ALK gene are selected as they are correlated with existing therapy. In phase I, we propose to validate clinically relevant consentrations of the proposed mutations in serum samples.