Microfluidic Bioreactor for High Throughput Hepatotoxicity Screening

描述(申请人提供)：第二阶段提案的主要目标是将第一阶段开发的SBS标准格式微流控生物反应器阵列商业化，用于制药和生物技术行业的高通量生理细胞筛查，特别关注预测性肝毒性筛查，自2005年以来，FDA已将其列为关键路径举措之一，以提供除动物模型之外更好的临床前药物筛选工具。这一命题的价值在于，在昂贵和耗时的人体临床试验之前，使用更具生理性的体外人体肝脏培养模型来改进药物毒性的预测。第二阶段的奖励将使我们能够优化生物反应器的设计，并与制药公司一起对通过动物试验但在人体临床试验中仍造成肝脏损伤的药物化合物进行产品贝塔测试。第二阶段的建议是继续计划公告PA-06-019分子文库筛选仪器的第一阶段获奖项目(1R43DK076325-01)，更具体地说，是将SBS标准微流控生物反应器阵列商业化，以提供更好的体外人体模型来预测临床试验中的药物毒性效应，特别是肝脏毒性。该项目的成功完成将为制药和生物科技行业提供一个更好和更具成本效益的高通量肝毒性筛查平台。

DESCRIPTION (provided by applicant): The main objective of the Phase II proposal is to commercialize the SBS standard format microfluidic bioreactor array developed in Phase I for high throughput physiologic cell-based screening in the pharmaceutical and biotechnology industry, with special focus on predictive hepatotoxicity screening, which has been included as one of the Critical Path Initiatives by the FDA since 2005 in order to provide better pre-clinical drug screening tools other than animal models. The value of this proposition is to improve prediction of drug toxicity before the expensive and time consuming human clinical trials using a more physiological in vitro human liver culture model. The Phase II award will enable us to optimize the bioreactor design and initiate the product beta testing with pharmaceutical companies on drug compounds that passed animal studies yet still caused liver injuries during human clinical trials. The Phase II proposal is to continue the awarded Phase I project (1R43DK076325-01) under program announcement PA-06-019 Molecular Libraries Screening Instrumentation , more specifically, to the commercialization of an SBS standard microfluidic bioreactor array to provide a better in vitro human model to predict drug toxicity effect during clinical trials, especially liver toxicity. The successful completion of the project will provide the pharmaceutical and biotechnology industry a better and more cost-effective platform on high throughput liver toxicity screening.