STTR Phase I: Standardized and reproducible culture and activation of endothelial cells in microfluidic devices for drug screening applications

这个小企业技术转移计划(STTR)第一阶段项目的更广泛的影响/商业潜力是开发一种微流控分析，用于与药物发现/筛选、个性化药物、药物毒性评估、患者临床状态评估以及预测患者对某些治疗的特定反应相关的应用。拟议的平台允许在特定生理条件下进行药物测试，以调查某些药物或药物组合可能如何影响特定细胞。目前可用的平台极其复杂，依赖于昂贵、劳动密集型、耗时和低产量的制造方法，阻碍了此类系统转化为商业环境的潜力。此外，需要对这些平台进行标准化和分析验证，以便进行可重复和可靠的样本测试，从而促进监管部门的批准过程。该项目将极大地帮助标准化和验证用于大规模部署的高吞吐量平台。该项目将有助于降低临床前药物发现/筛选研究的运营成本，并降低药物失败率，因为将可能进行针对患者的测试。这个小企业技术转移计划(STTR)第一阶段项目建议开发一个标准化的、经过验证的微流控平台，与人类内皮细胞集成，用于药物发现/筛选目的。由于在药物开发的临床前阶段采用的传统体内和体外技术极其昂贵、劳动强度大、耗时长，并且仍然可能导致高失败率，因此迫切需要用于新药候选的临床前评估的生理学相关的体外分析，特别是在心血管疾病和血液疾病领域。微流控平台允许精确控制气体和流动条件，其大小相当于人体微血管，并为体外测试提供生理上相关的血管环境。为了确保测定的准确性、可靠性和稳健性，研究目标包括一种全面和系统的方法，以标准化生理流动条件下内皮细胞的培养和激活。此外，通过疾病特异性激活剂(例如，血红素、肿瘤坏死因子-α等)使内皮细胞的短期和长期激活标准化。这一奖项反映了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 Technology Transfer Program (STTR) Phase I project is to develop a microfluidic assay for applications related to drug discovery/screening, personalized medicine, drug toxicity assessment, evaluation of patient clinical status, and predicting patient-specific responses to certain therapies. The proposed platforms allow drug testing under specific physiological conditions to investigate how certain drugs or drug combinations might affect specific cells. Currently available platforms are extremely complex and rely on costly, labor-intensive, time-consuming, and low-throughput fabrication methods, hampering the translation potential of such systems into a commercial setting. Moreover, standardization and analytic validation of such platforms are needed for reproducible and reliable sample testing, facilitating the process of regulatory approval. This project will significantly help standardize and validate a high-throughput platform for deployment at scale. This project will help reduce operational costs for preclinical drug discovery/screening studies and lower the drug failure rate, as patient-specific testing will be possible.This Small Business Technology Transfer Program (STTR) Phase I project proposes to develop a standardized and validated microfluidic platform integrated with human endothelial cells for drug discovery/screening purposes. Since the traditional in vivo and in vitro techniques that are employed in the preclinical stage of drug development are extremely costly, labor intensive, time-consuming, and can still lead to high failure rates, there is an urgent need for physiologically relevant in vitro assays for preclinical assessment of new drug candidates, particularly in the cardiovascular disease and blood disorders spaces. Microfluidic platforms allow for precise control of gas and flow conditions at a size scale equivalent to that of human microvasculature and offer physiologically relevant vascularized environments for in vitro testing. To ensure accuracy, reliability, and robustness of the assay, research objectives include a comprehensive and systematic approach to standardize the culture and activation of endothelial cells under physiologic flow conditions. Furthermore, standardized both short-term and long-term activation of endothelial cells via disease specific activators (e.g., heme, TNF-α, etc.) will be established to better mimic in vivo conditions.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.