Project Summary: Lung cancer is the leading cause of cancer-related deaths in the United States. Low dose chest computed tomography (CT) screening programs that target high-risk individuals can reduce lung cancer-specific mortality by 20% and overall mortality by 6.9%. There is a growing movement to implement this life saving screening into routine practice, with endorsements from the U.S. Preventive Services Task Force, the American Thoracic Society, and the American College of Chest Physicians, and a willingness from payers to provide reimbursement. Yet, numerous challenges still exist to realize early detection and improved outcomes for lung cancer, including: a) how to diagnosis lung cancer patients with indeterminate pulmonary nodules (IPNs); b) how to determine recurrence after therapy; and c) how to position biomarker use prior or alongside chest CT screening to decrease the cost and rates of false positive tests. The availability of a rapid, high sensitivity detection method to improve the quantification of biomarkers has the potential to revolutionize management of patients with IPNs. Under this Phase I STTR, we propose to take the next logical steps toward commercial translation of our novel and patented technologies, the free-solution assay (FSA) and the compensated interferometric reader (CIR) that has been shown to potentially improve IPN diagnosis. The FSA-CIR methodology is potentially transformative with respect to biomedical research and medicine, representing the only solution-phase, label-free molecular interaction measurement methodology with sensitivity comparable to, or better than, fluorescence, and compatible with a wide range of complex matrices. These properties have enabled FSA-CIR to be used to address previously challenging or intractable applications ranging from enhanced lung cancer detection, as proposed here, to improved in-vitro in-vivo correlations for first in human dosing, to the rapid quantification of low abundance chemicals in human samples, including neonatal opioids in urine and chemical nerve agents in urine and serum.