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

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.

Soft bioreactor systems: a necessary step toward engineered MSK soft tissue?

“…Besides stresses and strains, soft sensors able to measure biochemical signals become increasingly attractive ( Brunner et al, 2021 ). Lee et al proposed a smart bioreactor equipped with fully integrated wireless multivariate sensors for real-time monitoring of stem cell cultures ( Jimin Lee et al, 2024 ). This system enabled continuous monitoring of pH, dissolved oxygen, glucose levels, and temperature in a soft culture chamber through the integration of soft sensors in its walls.…”

“…Integrating soft chambers with soft strain sensors would enable real time measurements and improved spatial resolution to uncover subtle local differences in strain distribution. Such combinations are already under development, although not yet in the context of TE ( Tric et al, 2017 ; Jimin Lee et al, 2024 ). Soft sensors embedded in soft actuators, would provide additional advantages, such as close monitoring of stresses and strains.…”

Integrated Mini-Pillar Platform for Wireless Real-Time Cell Monitoring

“…Real-time monitoring of cells is crucial as changes in cellular metabolism effectively reflect the progression of various cellular activities, such as cell growth, differentiation, and drug toxicity [ 5 – 7 ]. Long-term monitoring can effectively assess the evolution of cellular factors over time, reflecting cell vitality and growth dynamics [ 8 – 10 ]. The limited applicability of traditional methods and the demand for precise quantitative monitoring of cellular metabolism have spurred the development of various biosensing techniques [ 11 – 13 ].…”