Elmore Family School of Electrical and Computer Engineering, Purdue University, West Lafayette, 47907, USA.
School of Aeronautics and Astronautics, Purdue University, West Lafayette, IN, 47907, USA.
Sci Rep. 2022 Jul 14;12(1):12010. doi: 10.1038/s41598-022-16073-x.
Monitoring product temperature during lyophilization is critical, especially during the process development stage, as the final product may be jeopardized if its process temperature exceeds a threshold value. Also, in-situ temperature monitoring of the product gives the capability of creating an optimized closed-loop lyophilization process. While conventional thermocouples can track product temperature, they are invasive, limited to a single-point measurement, and can significantly alter the freezing and drying behavior of the product in the monitored vial. This work has developed a new methodology that combines non-invasive temperature monitoring and comprehensive modeling. It allows the accurate reconstruction of the complete temperature profile of the product inside the vial during the lyophilization process. The proposed methodology is experimentally validated by combining the sensors' wirelessly collected data with the advanced multiphysics simulations. The flexible wireless multi-point temperature sensing probe is produced using micro-manufacturing techniques and attached outside the vial, allowing for accurate extraction of the product temperature.
冻干过程中监测产品温度至关重要，特别是在工艺开发阶段，如果产品的工艺温度超过阈值，最终产品可能会受到影响。此外，产品的原位温度监测能够实现优化的闭环冻干工艺。虽然传统热电偶可以跟踪产品温度，但它们具有侵入性，仅限于单点测量，并且会显著改变监测小瓶中产品的冷冻和干燥行为。本工作结合了非侵入式温度监测和全面建模，开发了一种新方法，可准确重建冻干过程中小瓶内产品的完整温度曲线。所提出的方法通过将传感器无线采集的数据与先进的多物理场模拟相结合，进行了实验验证。使用微制造技术制作的灵活无线多点温度感应探头，附在小瓶外部，可准确提取产品温度。
