Large-scale smart bioreactor with fully integrated wireless multivariate sensors and electronics for long-term in situ monitoring of stem cell culture

大型智能生物反应器,配备全集成无线多变量传感器和电子设备,可长期原位监测干细胞培养

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作者:Jimin Lee, Hojoong Kim, Hyo-Ryoung Lim, Yun Soung Kim, Thi Thai Thanh Hoang, Jeongmoon Choi, Gun-Jae Jeong, Hodam Kim, Robert Herbert, Ira Soltis, Ka Ram Kim, Sung Hoon Lee, Youngjin Kwon, Yunki Lee, Young Charles Jang, Woon-Hong Yeo1

Abstract

Achieving large-scale, cost-effective, and reproducible manufacturing of stem cells with the existing devices is challenging. Traditional single-use cell-bag bioreactors, limited by their rigid and single-point sensors, struggle with accuracy and scalability for high-quality cell manufacturing. Here, we introduce a smart bioreactor system that enables multi-spatial sensing for real-time, wireless culture monitoring. This scalable system includes a low-profile, label-free thin-film sensor array and electronics integrated with a flexible cell bag, allowing for simultaneous assessment of culture properties such as pH, dissolved oxygen, glucose, and temperature, to receive real-time feedback for up to 30 days. The experimental results show the accurate monitoring of time-dynamic and spatial variations of stem cells and myoblast cells with adjustable carriers from a plastic dish to a 2-liter cell bag. These advances open up the broad applicability of the smart sensing system for large-scale, lower-cost, reproducible, and high-quality engineered cell manufacturing for broad clinical use.

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