SBIR Phase I: Vertical Perfusion System for Cell Culture and Monitoring

这个小型企业创新研究(SBIR)第一阶段项目将尝试展示垂直灌注盒系统的可行性，以改进对不同细胞类型的体外研究，包括朗格汉斯的胰岛素分泌胰岛。随着所提出的灌流系统的发展，细胞生理学的基础和应用研究将会得到进一步的发展。其目的是开发一种方便、批量生产和易于使用的包含四到十六个腔室的灌注柱。组件的模块化结构便于加载胰岛，控制和维持灌流，并响应生理扰动通过吸收/荧光光谱实时测量氧耗率(OCR)、细胞色素-c氧化状态、NADH和其他分子。拟议的设计将允许方便的灭菌，可选择重复使用或一次性组件，内置氧气传感器和相关仪器，用于实时监测和记录数据。在第一阶段，计划使用非活细胞复制和活岛来设计、建造和评估一个或多个盒式系统。拟议技术的三个重要商业市场与胰岛移植、基础胰岛研究和药物发现有关，这些行业价值数十亿美元，需要为能够降低开发和运营风险的方法支付溢价。最近的两篇论文估计，胰岛移植手术的总实际成本为每个患者10万至15万美元，但随着程序的完善，成本将随着时间的推移而下降。尽管如此，识别可存活的胰岛或协助开发此类方法的设备，或加快研究替代移植方法(如封装)的设备，将很快在成本节约方面收回成本。与胰岛相关的应用包括对生理和功能的基础研究，针对胰岛的药物的开发和验证，以及移植前胰岛生存能力的评估。研究胰岛基本功能和生物学的研究人员会发现这个系统很有用，因为它可以同时检查多组胰岛，从而提高他们研究结果的统计学意义。

This Small Business Innovation Research (SBIR) Phase I project will attempt to show feasibility of a Vertical Perfusion Cartridge system to improve in vitro studies of diverse cell types, including insulin-producing Islets of Langerhans. Basic and applied cell physiology research could be advanced with the development of the proposed perfusion system. The aim is to develop a convenient, mass produced and easily used perfusion column cartridge that contains four to sixteen chambers. Modular construction of the assembly facilitates loading of the islets, controlling and maintain perfusion and performing real-time measurement of oxygen consumption rate (OCR), cytochrome-c oxidative state, NADH and other molecules via absorption/fluorescence spectroscopy in response to physiological perturbations. The proposed design will allow convenient sterilization, optionally reusable or disposable components, built-in oxygen sensors and associated instrumentation for real-time monitoring and recording of data. During Phase I, the plan is to design, build and evaluate one or more cartridge systems, using non-living cell-replicates and using live islets.Three significant commercial markets for the proposed technology are related to islet transplantation, basic islet research, and drug discovery, multi-billion dollar industries that pay a premium for methods capable of reducing development and operational risks. Two recent publications estimated the total real cost of islet transplantation procedures at $100,000 to $150,000 per patient, though the cost will fall over time as the procedures are refined. Nonetheless devices that either identify viable islets or assist in the development of such methods, or that speed research into alternative transplant methods, such as encapsulation, would quickly pay for themselves in cost savings. Applications related to islets include basic research into physiology and function, development and validation of drugs targeting islets, and assessment of islet viability prior to transplantation. Researchers who work on basic function and biology of islets will find this system useful because it enables the examination of multiple sets of islets simultaneously, thus improving statistical significance of their findings.