Large-scale smart bioreactor with fully integrated wireless multivariate sensors and electronics for long-term in situ monitoring of stem cell culture
Jimin Lee, Hojoong Kim, Hojoong Kim, Hyo‐Ryoung Lim, Yun‐Soung Kim, Thai Thanh Hoang Thi, Jeongmoon J. Choi, Gun‐Jae Jeong, Hodam Kim, Hodam Kim, Robert Herbert, Ira Soltis, Ka Ram Kim, Sung Hoon Lee, Youngjin Kwon, Yunki Lee, Young C. Jang, Woon‐Hong Yeo
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.