Development of a microfluidic 3D vascularized tissue model with integrated electric cell-layer impendance sensing

疗效差和不可预测的效果是药物从市场上撤下的主要原因，制药公司浪费了数十亿美元，并将患者置于危险之中。药物在人体中的表现不佳，主要是因为药物是在实验室中进行测试的，这些实验室要么在二维（2D）塑料培养皿上培养细胞，要么使用动物模型，这些模型很难模拟人类药物反应。因此，需要改进的基于细胞的模型，其可以在药物发现过程的早期识别和消除无效和危险的药物，这可能具有巨大的健康和经济效益。 为了满足这一需求，我们开发了一种系统，能够重现复杂的三维结构和血管化组织的功能，如大脑，肝脏和心脏。通过将微流体通道阵列（模拟血管）与单个设备上的3D细胞培养（器官组织）相结合，我们能够重新创建人工人类微组织，用于快速和低成本的早期药物筛选。该技术的潜在最终用户，包括辉瑞公司和3D-Biotek，有兴趣使用它来模拟血脑屏障，但需要方法来验证在我们的设备内培养的组织是生理性的。为此，我们计划在现有平台中实现细胞层电阻抗传感，以评估我们系统中创建的人工血管的质量。最终的结果将是一个系统，预计将在发现过程中更早地识别无效药物，从而节省时间和金钱。 与大多数市售的微流体平台不同，我们的发明在与标准实验室设备和中高通量工作流程的兼容性方面是独特的，从而确保易于实施到药物发现管道中。易于采用将使我们能够在项目完成后不久直接接触到目标最终用户（制药、生物技术和生命科学公司和研究实验室）。为了满足潜在客户的巨大需求，我们将成立一家初创公司，直接向客户销售微流控平台。

Poor efficacy and unpredictable effects are the leading causes of drug removal from the market, costing pharmaceutical companies billions of wasted dollars and putting patients at risk. Poor drug performance in humans is largely because drugs are tested in labs that either grow cells on two dimensional (2D) plastic dishes or use animal models, which poorly mimic human drug responses. Therefore, there is a need for improved cell-based models that could identify and eliminate ineffective and dangerous drugs early in the drug discovery process could have enormous health and economic benefits. To meet this need, we have developed a system capable of recapitulating the complex, three-dimensional structure and function of vascularized tissues, like the brain, liver, and heart. By combining arrays of microfludic channels (to mimic blood vessels) with 3D cell culture (organ tissue) on a single device we are able to recreate artificial human microtissues for quick and low cost early stage drug screening. Potential end-users of this technology, including Pfizer and 3D-Biotek, are interested in using it to model the blood-brain barrier, but require methods to validate that the tissues cultured within our device are physiological. To that end, we plan to implement electrical cell-layer impedance sensing into the existing platform to assess the quality of the artificial blood vessels created within our system. The end result will be a system that is expected to identify ineffective drugs much earlier in the discovery process, thereby saving time and money. Unlike the majority of commercially available microfludic platforms, our invention is unique in its compatibility with standard laboratory equipment and medium- to high-throughput workflow, ensuring ease of implementation into the drug discovery pipeline. The ease of adoption will allow us to directly reach our target end-users (pharmaceutical, biotechnology, and life science companies and research labs) shortly after completion of this project. To meet the significant demand from potential customers, we will form a start-up company to sell the microfludic platform directly to the customers.