I-CORPS: VASCULARIZED ORGAN-ON-A-CHIP PLATFORM FOR BIOPHARMACEUTICAL TESTING

生物制药使癌症、免疫、炎症和神经疾病的治疗发生了革命性变化。由于这些药物是通过静脉给药，然后通过血管系统分配到靶组织，它们的体外试验还不够具有预测性。其次，因为这些药物是人性化的，从动物研究中预测安全危险一直是具有挑战性的，志愿者们遭受了严重的反应。由于这些原因，与药物开发相关的经济和时间表，生物制药行业寻求人类芯片上的器官平台，以进行更具预测性的药物测试。不幸的是，还没有一个足够简单的系统供研究人员使用，在足够的吞吐量下，并且足够标准化，以适应药物筛选工作流程。这个项目的目标是帮助研究人员解决这个问题，为开发一个易于使用、高通量的芯片上人体器官平台奠定基础，并以标准格式随时整合到他们的测试程序中。拟议的创新是一个中等吞吐量的简单工具，任何研究人员都可以使用，并能够回答复杂的商业灌流系统所做的所有问题(如果服务他们的所有硬件都可以放在一个实验室，研究人员接受如何使用它的培训)。拟议的血管化芯片上器官平台(PerfusionPal)将是标准格式、高吞吐量、易于使用并适合常规制药工作流程。它将是诊断和预后的；评估靶标特异性、与靶外组织的交叉反应并识别生物标志物的诊断；以及预测或能够预测临床试验中的严重反应，如细胞因子风暴、输液反应、免疫抑制和靶外器官责任。PerfusionPal的商业化将对危险药物线索进行分类，并使安全药物从工作台到床边的开发速度更快、成本更低，从而造福于患者、医疗保健行业和社会。

Biopharmaceuticals have revolutionized treatment of cancer, immune, inflammatory and neurological diseases. As these drugs are administered to patients intravenously and then distributed by vasculature to target tissues, their testing in vitro has not been predictive enough. Next, because these drugs are humanized, predicting safety hazards from animal studies has been challenging and volunteers suffered from severe reactions. For these reasons, economics and timeline associated with drug development, biopharmaceutical industry seeks human organ-on-a-chip platforms for more predictive drug testing. Unfortunately, there has not yet been a system that is simple enough for researchers to use, in adequate throughput, and standardized enough to fit into drug screening workflows. The goal of this project is to help solve this problem for researchers by setting a foothold for development of a human organ-on-a-chip platform that is easy for them to use, high-throughput, and in a standard format to readily integrate into their testing routine.The proposed innovation is a simple tool in a medium throughput, a tool that any researcher can use and be able to answer all the questions that complex commercial perfusion systems do (if all the hardware that services them could be put in one lab and researchers trained on how to use it all). The proposed vascularized organ-on-a-chip platform (PerfusionPal) will be in standard format, high throughput, easy to use and fit into routine pharmaceutical workflows. It will be diagnostic and prognostic; diagnostic to assess target specificity, cross-reactivity with off-target tissues and to identify biomarkers; and prognostic or capable of predicting severe reactions in clinical trials such as cytokine storms, infusion reactions, immune suppression and off-target organ liabilities. PerfusionPal commercialization will triage dangerous drug leads and enable faster and cheaper development of safe drugs from bench to bedside for the benefit of patients, healthcare industry and society.