An Electro-Mechanical Perspective for Microphysiological Systems

Microphysiological systems (MPS) aim to capture in-vitro the native (patho)physiology of living tissues and organs. They stand out from traditional cell cultures thanks to the provision of tailored topography, multi-physical stimulation and dynamic cues to synthetially recapitulate a realistic microenvironment. Additionally, MPS should enable continous and potentially real-time monitoring of cell and tissue conditions to facilitate long-term culturing and track responses to endogenous (e.g., phenotypical maturation) and exogenous processes (e.g., drug administration). Whereas the current main driving force behind the development of MPS is the potential of improving the quality and speeding up the conclusion of drug development processes, the longer-term promise lies in more comprehensive, bottom-up understanding of organismal physiology alongside personalized medicine.<br/>Here we argue that an electro-mechanical perspective is particularly convenient to address standing technological challenges in the way of further development of MPS. These challenges include integrated stimulation and sensing of cell and tissue cultures, convenient and industrially-compliant upscaling of device fabrication, and co-existence of partly-conflicting requirements from fit-for-purposeness and standardization - traits which recent MPS developmental roadmaps have indicated as critical. To articulate the feasibility and benefits of the proposed perspective, we present a set of MPS fabricated using a consistent toolbox of multi-material, wafer-level microfabrication technologies and addressing a variety of microphysiological purposes: MPS for engineered heart tissues with integrated microelectrodes for electric pacing and capacitive recording of cardiac contractile dynamics; MPS with integrated charge and field-potential sensing of cell electrophysiology; MPS with arrays of three-dimensionally stacked and electrically-addressable microelectrodes for spatial tracking of inter-neuronal signaling; a microfluidic MPS with integrated electrodes for 4-point transendothelial electrical resistance sensing. Furthermore, the concept of the smart mutli-well plate is introduced to demonstrate how fit-for-purpose MPS can be subsumed into a standardized, modular and easy-to-use technology platform compatible with existing microfluidic standards and laboratory workflows and suitable for large-volume industrial production. Grounded in decades of technological advancements and informed by mature experience in the microelectronic domain, the electro-mechanical perspective may deliver comparable benefits and outlines of progress to bring MPS to the widest adoption.