A microfluidic blood-brain barrier model with on-chip cell barrier biosensing

我们正在开发一种高通量，易于使用的微流体系统，用于模拟血管和组织之间的界面，用于药物筛选，运输研究和基础研究，首次应用于血脑屏障（BBB）建模。药物通过血脑屏障的运输是制药和生物技术行业的主要兴趣，因为血脑屏障对许多药物是不可渗透的，这使得神经系统疾病难以治疗。不良的模型系统阻碍了神经学药物的开发，因为动物模型往往无法复制人类生物学，而目前的血脑屏障实验室模型无法充分复制体内环境，导致预测能力较差。我们开发了一种微流体细胞培养系统，解决了对先进细胞培养系统的未满足需求，该系统可以更好地复制药物开发中的人类生物学。本提案的重点是通过集成电子传感器来直接在平台上监测BBB模型的质量，从而改善我们系统的功能。这是BBB模型的基本功能，但没有纳入任何商业上可用的器官芯片平台。通过与CellScale Biomaterials（一家位于安大略省的生物技术制造公司）合作，我们将优化电极和传感系统的设计，将其集成到我们的微流体平台中，验证其在BBB建模中的应用，并开发可扩展的制造工艺用于商业翻译。CellScale通过现金和实物捐助大力支持该项目。他们在加拿大具有独特的地位，可以利用该项目的研究成果开发出将在两年内上市的产品，有助于培养高素质人才，创造新的就业机会，并为加拿大作为先进细胞培养生物技术的新研发和制造中心的经济增长做出贡献。

We are developing a high throughput, easy-to-use microfluidic system, used to model the interface between blood vessels and tissues for drug screening, transport studies and basic research, with a first application in blood brain barrier (BBB) modelling. Transport of drugs across the BBB is of prime interest to the pharmaceutical and biotechnology industries because the BBB is impermeable to many drugs, making neurological diseases difficult to treat. Development of neurological drugs is hampered by poor model systems, as animal models often fail to replicate human biology and current laboratory models of the BBB inadequately replicate the environment in the body, leading to poor predictive power. We have developed a microfluidic cell culture system that addresses the unmet need for advanced cell culture systems that better replicate human biology for drug development. The focus of this proposal is to improve the functionality of our system by integrating electrical sensors to monitor the quality of the BBB model directly on the platform. This is an essential feature of BBB models, but is not incorporated into any commercially-available organ-on-a-chip platform. In partnership with CellScale Biomaterials, an Ontario-based biotechnology manufacturing company, we will optimize the design of the electrodes and sensing system, integrate it into our microfluidic platform, validate its application for BBB modeling, and develop scalable manufacturing processes for commercial translation. CellScale is strongly supporting this project through both cash and in-kind contributions. They are uniquely positioned in Canada to leverage the research outputs of this project to develop products that will be market-ready within two years, contribute to the development of highly qualified personnel, generate new jobs, and contribute to economic growth in Canada as a new R&D and manufacturing centre for advanced cell culture biotechnologies.