Abstract

The Biological and Technical Challenges of MicroPhysiological Systems: Past, Present, and Future

John Wikswo, A.B. Learned Professor of Living State Physics; Founding Director, Vanderbilt Institute for Integrative Biosystems, Vanderbilt University

We must celebrate a decade of microphysiological systems (MPS) research in the US that began with the 2010 papers on Shuler’s and Esch’s body on a chip and the Huh’s, Ingber’s, and colleagues’ lung on a chip, received critical funding impulses from FDA, DARPA, NIH, and DTRA, and was forged by NIH/NCATS into a large, functional community. NASA, EPA, and other agencies are expanding the scope of research. Academic groups are publishing more than a thousand papers a year and there are more than a dozen companies in the US and Europe offering single- and multiple-organ chips and platforms. Now would be a good time to assess how well MPS researchers have addressed the engineering challenges for instrumenting and controlling integrated organ-on-chip systems that I enumerated in 2013, compare the capabilities and weaknesses of organoids and tissue chips, and assess the current and future value of coupled organ systems. As we address the early challenges, some remain and new ones appear: How do we obtain or create the appropriate cells? How do we build low-cost, disposable pumps and valves to perfuse and couple organ chips? What are our alternatives to PDMS? How do we acquire and analyze the data required for quantitative characterization of our MPS models? How do we recapitulate the adaptive immune system? What are our capabilities to control, rather than just observe, MPS models? How do we address the complexity, for example, of the neurohumeral connections between the microbiome-gut-immune-liver-brain axis in development, health, aging, and disease and with exposure to pathogens and toxins? All of these technologies should help us close the hermeneutic circle of biology, particularly now that we are within striking distance of being able to create robot scientists that can operate 10,000 independent, parallel MPS models and use optimum design-of-experiment techniques to generate and test hypotheses about biological regulation. The second MPS decade should be productive and exciting.