Abstract

Pumps, Valves, and Fluidic Connectors for Automating and Integrating Microphysiological Systems

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

Much of the organ-on-chip and tissue-chip research to date has relied on very simple perfusion schemes that include surface tension, hydrostatic pressure, rocking plates, syringe pumps, pressurized reservoirs, and on-chip pneumatic or electromagnetic peristaltic pumps. A number of commercial microphysiological systems are moving towards high-throughput well-plate formats. Each of these fluid handling technologies presents different advantages in cost, convenience, and simplicity, and disadvantages regarding reservoir filling, media change, recirculation and volume minimization, organ-organ integration, bubble- and microbe-free addition and removal of chips from multi-organ microphysiological systems, temporal control of drug concentrations, adjusting/balancing flow rates, and controlling sensors for long-term use. While a common trend is towards high throughput and low cost, there are critical applications where high content is more important than high throughput, particularly those requiring multi-omic characterization of physiological responses over time to drugs and toxins for both single and multiple organs. We review how our computer controlled, modular, rotary planar peristaltic micropumps and twenty-five port rotary planar valves can be used to create autocalibrating electrochemical MicroClinical Analyzers, multi-well MicroFormulators that can create in vivo the pharmacokinetics observed in animals and humans, and perfusion controllers for multiple NeuroVascular Unit, Gut-in-a Puck, and Thick Tissue Mammary Bioreactors. Pumps and valves are useful for compact perfusion controllers that operate in microgravity environments. Miniature rotary valves will enable bubble-free, sterile connection and disconnection of individual organ chips to other organs and analyzers. Ongoing and future applications include 100-port valves and systems for optimizing the differentiation of induced pluripotent stem cells, a 10,000 channel yeast MicroChemostat, and a MicroDialysis imager, all with direct injection into a mass spectrometer. The cost and complexity of these systems over present technologies is balanced by sophisticated computer control and sensor integration, reduced technician effort, high content results, and parallelization.