SBIR Phase I: Development of a SERS-based diagnostic platform for multiplexing ubiquitous inflammatory markers in cancer.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project stems from the fact that cancer causes approximately 10 million deaths yearly worldwide, and the economic burden on cancer patients in the United States alone is estimated to be around $21 billion/yr, excluding lost productivity. Over 600,000 people die from cancer in the United States each year, and cancer cases among the younger population are on the rise. Currently, only a handful of cancers, such as breast, colon, cervical, and prostate, have recommended early screening, and sadly, 70% of cancer deaths are caused by cancers without recommended screening. Early detection, coupled with accurate monitoring and surgery in appropriate cases, appears to be the ideal strategy to improve outcomes and quality of life and reduce healthcare costs. The availability of novel diagnostic technology for minimally invasive biomarker analysis using biofluids to accurately predict malignancy potential would greatly benefit patients and clinicians in the early diagnosis and management of deadly cancers. Development of the technology proposed herein would have a broad impact on the cancer diagnostic space in terms of accurate early detection and diagnosis, quality of life, mortality, and healthcare burden. This Small Business Innovation Research (SBIR) Phase I project aims to develop multi-marker diagnostic assays to bridge a critical gap from biomarker discovery to diagnostic assay translation. This project leverages principles from synthetic chemistry, enzymology, spectroscopy, and engineering, leading to a novel biosensing platform that couples Surface-Enhanced Raman Spectroscopy (SERS) and a protease turnover assay to provide highly accurate methods for biomarker detection. This project will lead to developing next-generation sensors to meet the unique requirements for a multi-molecular protease activity assay from highly viscous, proteinaceous clinical samples and deliver a stackable assay workflow readily accessible to clinical laboratory staff with rapid turnaround. The technological hurdles that will be addressed during Phase I will include: 1) synthetic development of ultrasensitive SERS-active dyes and their conjugates with substrates of proteases associated with high-grade dysplasia in pancreatic cysts and other cancers, and 2) development and optimization of a multiplexed multi-protease turnover assay employing the aforementioned substrates using an automated-SERS detection platform with high-throughput capability for eventual commercialization in a CLIA lab setting. This technology has the potential to be transformative due to its multiplexing capability, high sensitivity and selectivity, cost-effectiveness, and reliable performance in complex biological fluids. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.