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

小型企业创新研究(SBIR)第一阶段项目的广泛影响/商业潜力源于这样一个事实，即癌症每年导致全球约1000万人死亡，仅在美国，不包括生产力损失，癌症患者的经济负担估计每年约为210亿美元。在美国，每年有超过60万人死于癌症，年轻人口中的癌症病例正在上升。目前，只有少数癌症，如乳腺癌、结肠癌、宫颈癌和前列腺癌，建议进行早期筛查，遗憾的是，70%的癌症死亡是由没有建议筛查的癌症引起的。早期发现，在适当的情况下进行准确的监测和手术，似乎是改善结果和生活质量并降低医疗成本的理想策略。利用生物体液进行微创生物标志物分析的新诊断技术的可用性，将极大地帮助患者和临床医生对致命癌症的早期诊断和治疗。本文提出的技术的发展将在准确的早期检测和诊断、生活质量、死亡率和医疗负担方面对癌症诊断空间产生广泛影响。这个小型企业创新研究(SBIR)第一阶段项目旨在开发多标记诊断分析，以弥合从生物标记物发现到诊断分析翻译的关键差距。该项目利用合成化学、酶学、光谱学和工程学的原理，建立了一种新型的生物传感平台，将表面增强拉曼光谱(SERS)和蛋白酶周转分析结合起来，为生物标记物的检测提供了高精度的方法。该项目将导致开发下一代传感器，以满足从高粘性、蛋白质类临床样本中进行多分子蛋白酶活性分析的独特要求，并提供可堆叠的分析工作流程，使临床实验室工作人员能够快速周转。在第一阶段将解决的技术障碍将包括：1)合成开发超灵敏的SERS活性染料及其与与胰腺囊肿和其他癌症的高度不典型增生相关的蛋白酶底物的结合物，以及2)使用具有高通量能力的自动化SERS检测平台，开发和优化使用上述底物的多重多蛋白酶周转分析，最终在CLIA实验室环境中进行商业化。这项技术具有变革的潜力，因为它具有多路复用能力、高灵敏度和选择性、成本效益以及在复杂生物流体中的可靠性能。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.