Biosensing for organ-on-a-chip platforms

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Recent advances in tissue engineering and microfluidics have enabled the creation of “organ-on-a-chip” platforms that mimic the functions of human organs and tissues better than conventional Petri dish-based cell culture systems. These technologies hold great promise for disease modeling, drug discovery, and as bioreactor test beds to develop engineered tissues. Despite their great potential, a persistent limitation of organ-on-a-chip and microfluidic cell culture platforms is that they rely on manual, off-chip analytical methods, which creates an analysis bottleneck and limits the value of these platforms. Integration of on-chip sensing could enable higher-throughput and higher-content analyses, real-time measurement of cell and tissue function, and even feedback control of dynamic culture microsystems. Strikingly, while there have been significant advances in incorporating biosensors into point-of-care microfluidic devices, biosensors have not been integrated into microtissue and organ-on-a-chip platforms largely because of the engineering challenges involved. Here, we propose a research program to directly address these limitations by leveraging our novel microfluidic and microtissues technologies to engineer organ-on-a-chip platforms with on-chip biosensing capabilities. To do so, we investigate fundamental aspects of biotransport and biosensing to enable biomolecule detection in dynamic microfluidic environments; develop sensitive on-chip strain sensors to measure cell contraction forces; and identify process control strategies to engineer mechanically robust tissues. This knowledge will be applied to generate novel organ-on-a-chip models for monitoring transport across the blood-brain-barrier; for measuring heart muscle contraction on-chip; and for optimizing protocols for mechanical stimulation of engineered tissues. The graduate and undergraduate students trained in this research program will be equipped with the scientific and professional skills required to apply the knowledge generated by their research for long-term impact and to lead bold new initiatives in biosensing, biomicrofluidics, and biotechnology in the future.