Monitoring of Microphysiological Systems: Integrating Sensors and Real-Time Data Analysis toward Autonomous Decision-Making

Abstract

Microphysiological systems replicate human organ function and are promising technologies for discovery of translatable biomarkers, pharmaceuticals, and regenerative therapies. Because microphysiological systems require complex microscale anatomical structures and heterogeneous cell populations, a major challenge remains to manufacture and operate these products with reproducible and standardized function. In this Perspective, three stages of microphysiological system monitoring, including process, development, and function, are assessed. The unique features and remaining technical challenges for the required sensors are discussed. Monitoring of microphysiological systems requires nondestructive, continuous biosensors and imaging techniques. With such tools, the extent of cellular and tissue development, as well as function, can be autonomously determined and optimized by correlating physical and chemical sensor outputs with markers of physiological performance. Ultimately, data fusion and analyses across process, development, and function monitors can be implemented to adopt microphysiological systems for broad research and commercial applications.

Impact of Culture Medium on Cellular Interactions in in vitro Co-culture Systems

“…For example, medium composition can be tracked for the CS as a stem cell differentiates to determine how differentiation is progressing. Accordingly, growth factors can be removed or added to encourage further differentiation (Young et al, 2019).…”

“…Addition of biosensors to cell cultures is one of these beneficial combinations. Biosensors show potential for monitoring of the microenvironments in in vitro systems and aim at providing real-time information regarding cell viability, growth and metabolism ( Pereira Rodrigues et al, 2008 ; Modarres et al, 2018 ; Young et al, 2019 ). For example, on-line measurement of dissolved oxygen was applied for medium optimization of mammalian cell cultures ( Deshpande et al, 2004 ).…”

“…For example, fluctuations in oxygen and glucose concentration can affect cell growth, differentiation and signaling ( Place et al, 2017 ). Multiplexed sensing, recording, and processing of real-time data could provide novel insights into the optimal nutrients and culture conditions needed to grow cells ( Young et al, 2019 ). Furthermore, real-time data analytics can be used to respond to changes in culture conditions in a closed feedback loop, adjusting inputs to obtain desired results ( Young et al, 2019 ).…”

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

“…As such, Kieninger et al reviewed electrochemical and optical microsensors to monitor the metabolic activity of microfluidic cultures, while Santbergen et al assembled an overview of real-time, automated platforms, specifically for OOAC models [80,81]. Young et al provided a perspective of integrated microfluidic sensors that would move toward autonomous decision-making, for example, to evaluate OOAC culture maturity for testing and quality control purposes [82]. Yet, while a variety of microfluidic sensor platforms are already in existence, more advanced closed-loop sensor control platforms would greatly reduce the monitoring and handling burden for laboratory scientists (end-users), aid quality control, and increase the potential for scale-up.…”

Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

“…Such systems should also provide real-time readout from integrated sensors 5,12,13 . Progress in combining various interfacing modalities in closedloop platforms is highlighted in recent reviews 14,15 .…”