I-Corps Team: Ultra Dielectric Probes

生物制药公司需要在线过程分析技术（PAT）来显著提高药品质量和生产率。目前生产工厂和实验室的现场监测仍然主要基于测量温度、pH值、溶解氧、压力、气流和液体流量。这些参数不能提供关于细胞活力、周期、大小、自噬和凋亡的信息，而这些是指示生物过程可重复性的指标。FDA建议PAT的关键技术如近红外、中红外、拉曼光谱、荧光和成像、质谱等都在积极开发中，但存在灵敏度有限、使用困难、成本高等局限性。电介质光谱作为一种很有前途的方法也被研究，但由于灵敏度和信息量有限，尚不适合用于PAT。本项目涉及一种用于在线过程分析技术（PAT）仪器开发的新型射频（RF）干涉仪技术。所获得的射频（RF）探头利用新的干扰过程来提高灵敏度，同时应用新的调谐机制来覆盖更宽的频率范围和调谐灵敏度，以实现稳健的系统操作。RF探针有望具有前所未有的灵敏度和鲁棒性，以无标记和无创的方式分析细胞活力、自噬、凋亡和大小。这些细胞的许多特性在其他PAT方法中是不可用的。电子方法有望使大规模生产低成本和易于使用的PAT仪器成为可能。

On-line Process Analytical Technology (PAT) is needed in enabling biopharmaceutical companies to significantly improve drug quality and productivity. Current in-situ monitoring in production plants and laboratories is still mainly based on measuring temperature, pH, dissolved oxygen, pressure, airflow, and liquid flow. These parameters do not give information on cell viability, cycle, size, autophagy and apoptosis that are metrics to indicate reproducibility of the bioprocess. FDA suggested key PAT technologies such as near-infrared, mid-infrared, Raman spectroscopy, fluorescence and imaging, and mass spectroscopy, are all under active development, but with limitations of one kind or another, such as limited sensitivity, difficult to use, and high cost. Dielectric spectroscopy is also studied as a promising approach, but not yet appropriate for PAT due to limited sensitivity and information contents.This project involves a novel radio frequency (RF) interferometer technique for On-line Process Analytical Technology (PAT) instrument development. The obtained radio frequency (RF) probes exploit novel interference processes to enhance sensitivity while applying novel tuning mechanisms to cover broad frequency ranges and tune sensitivity for robust system operations. The RF probes are expected to have unprecedented sensitivity and robustness to analyze cell viability, autophagy, apoptosis, and size in a label-free and non-invasive manner. Many of these cell properties are not available in other PAT methods. The electronic approach is expected to enable mass produced low-cost and easy-to-use PAT instruments.