SBIR Phase I: Advanced microfluidic systems enabling development of novel circulating tumor cell diagnostics

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是改善癌症的诊断，风险评估和监测。近40%的美国人在一生中会被诊断出患有癌症。晚期癌症的诊断大大减少了治疗选择，导致预后不良和生存率低。此外，由于可能需要多轮昂贵的治疗，晚期患者的平均治疗费用可能比早期患者高3-5倍。这些多轮治疗导致癌症的高经济负担。因此，早期发现癌症不仅会改善患者的预后，而且可能会降低癌症治疗的总成本。此外，可以广泛地进行微创和高度准确的诊断，以有效地识别患有各种癌症的人，进一步提高商业潜力。该小型企业创新研究（SBIR）第一阶段项目旨在开发一种先进的微流体系统，用于分离和评估循环肿瘤细胞（CTC）和CTC簇（CTCC），用于癌症诊断和监测。已经开发了各种形式的微流体装置以从数十亿血细胞中分离极其罕见的CTC群体，但是这些技术存在三个主要问题：1）低样品纯度，2）分离的CTC/CTCC的数量少，和3）CTC/CTCC异质性。为了克服这些局限性，该项目将开发一种创新设备，用于同时分离和评估单个和集群CTC及其分子特征，从而实现新的、高度敏感和准确的癌症液体活检。该项目的主要目标是：1）设计和开发一种混合微流控系统，用于同时分离和浓缩高纯度的CTC和CTCC，2）开发和优化两种用于单一CTC和CTCC分析的设备，3）使用前列腺癌患者标本进行测试和验证。该研究将导致开发一种新的癌症诊断平台，该平台具有微创性，比现有方法更敏感和准确，扩大治疗选择并改善患者结局。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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 is to improve the diagnosis, risk assessment, and monitoring of cancer. Nearly 40% of Americans will be diagnosed with cancer in their lifetime. Diagnosis of cancer in later stages dramatically reduces treatment options, leading to poor prognosis and low survival rates. In addition, the average cost of treatment for late-stage patients can be 3–5 times higher than that for early-stage patients due to the potential need for multiple rounds of expensive therapies. These multiple rounds of treatment contribute to the high economic burden of cancer. Thus, detecting cancer earlier will not only lead to improved patient outcomes but will likely reduce the overall costs of cancer treatment. Moreover, a minimally invasive and highly accurate diagnostic could be broadly administered to effectively identify those with various cancers, enhancing the commercial potential further. This Small Business Innovation Research (SBIR) Phase I project seeks to develop an advanced microfluidic system for the isolation and assessment of circulating tumor cells (CTCs) and CTC clusters (CTCCs) for cancer diagnosis and monitoring. Microfluidic devices in various forms have been developed to isolate the extremely rare CTC population from billions of blood cells, but these technologies suffer from three major problems: 1) low sample purity, 2) low numbers of isolated CTCs/CTCCs, and 3) CTC/CTCC heterogeneity. To overcome these limitations, this project will develop an innovative device for the simultaneous isolation and assessment of single and clustered CTCs and their molecular signatures, enabling the implementation of new, highly sensitive and accurate liquid biopsies for cancer. The key objectives for this project are: 1) Design and develop a hybrid microfluidic system for simultaneous isolation and concentration of CTCs and CTCCs with high purity, 2) Develop and optimize two devices for single CTC and CTCC analysis, and 3) Testing and validation using prostate cancer patient specimens. This research will lead to the development of a new cancer diagnostics platform that is minimally invasive and more sensitive and accurate than current methods, expanding treatment options and improving patient outcomes.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.