STTR Phase I: Resonant Sensors for Wireless Monitoring of Viable Cell Concentration in Small, Disposable Bioreactors

这项小型企业技术转让（STTR）第一阶段项目的更广泛影响/商业潜力是开发一种共振传感器系统，以监测小型生物反应器中的细胞活力。细胞工厂每年生产价值超过1500亿美元的细胞疗法、蛋白质疗法、工业酶和小分子。在开发阶段，很少有技术来监测活细胞浓度，而活细胞浓度是大量生物反应器的关键质量属性。目前监测细胞活力的方法是劳动密集型的，昂贵的，并且可能会影响质量。提出的技术可以嵌入到一次性烧瓶和生物反应器的壁上，以提供活细胞浓度的实时测量。这可以为生物工艺开发人员、克隆选择和小批量生产提供实质性的“大数据”改进。这个STTR第一期项目建议演示用共振传感器对活细胞浓度的无源无线传感。介电探针在工业中用于将培养容量与大培养体积中的活细胞浓度联系起来。在该方案中，可以通过嵌入作为一次性培养瓶或一次性生物反应器的一部分的无源传感器无线报告小培养皿中培养电容的变化。在这种形式下，它永远不会与单元产品接触，可以无线实现，并且有可能很容易实现多路复用。这项工作的技术目标是：1)确定运动、介质成分和温度对信号干扰的影响程度；2)构建一个支持蓝牙的读取板，并在孵化器中实现；3)开发一种算法，将复杂的谐振传感器振幅和相位数据转换为可用于跟踪活细胞浓度的简单参数。此外，计划是建模和测试谐振器几何形状，材料组成和传感器放置的影响。目标是生产一个强大的传感器系统，用于在实际培养条件下对许多细胞类型进行细胞活力测试。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to develop a resonant sensor system to monitor cell viability in small bioreactors. Cell factories are responsible for producing more than $150B worth of cell therapies, protein therapies, industrial enzymes, and small molecules each year. At the development phase, there are few technologies to monitor viable cell concentration, a critical quality attribute in a large array of bioreactors. Current methods to monitor cell viability are labor intensive, expensive, and can compromise quality. The proposed technology could be embedded into the walls of disposable flasks and bioreactors to provide real-time measurement of viable cell concentration. This could enable substantial "big data" improvements for bioprocess developers, clonal selection, and small batch production.This STTR Phase I project proposes to demonstrate passive, wireless sensing of viable cell concentration with resonant sensors. Dielectric probes are used in industry to correlate culture capacitance to viable cell concentration in large culture volumes. In this proposal, the change in culture capacitance in small culture volumes could be wireless reported with a passive sensor embedded as part of the disposable culture flask or single-use bioreactor. In this form factor, it would never make contact with the cell product, would be wirelessly implemented, and would have potential to be easily multiplexed. Technical objectives for this work are 1) determining the extent of confounding signal effects from movement, media composition and temperature; 2) building a Bluetooth enabled reader pad for implementation in an incubator; and 3) developing an algorithm that translates the complex resonant sensor amplitude and phase data into simple parameters that can be used to track viable cell concentration. In addition, the plan is to model and test the effect of resonator geometry, material composition, and sensor placement. The goal is to produce a robust sensor system for cell viability to test in real culture conditions on numerous cell types.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.