Mera: A scalable high throughput automated micro-physiological system

Abstract

There is an urgent need for scalable Microphysiological Systems (MPSs) that can better predict drug efficacy and toxicity at the preclinical screening stage. Here we present Mera, an automated, modular and scalable system for culturing and assaying microtissues with inbuilt environment control and automated image capture. The paradigm presented involves culturing and maturing common microtissue types in rows (rows of e.g., liver, heart, gastro-intestinal or kidney microtissues) and then reorienting fluid flow to create a recirculating circuit composed of inter-connected columns containing distinct microtissues (e.g. individual fluidic circuits with liver, heart, gastrointestinal and kidney micro-tissues inter-connected) to allow drugging or staining. We present data demonstrating the prototype system using an Acetaminophen/HepG2 liver microtissue toxicity assay with Calcein AM and Ethidium Homodimer viability assays. We demonstrate the functionality of the automated image capture system. The prototype microtissue culture plate wells are laid out in a 3x3 or 4x10 grid with viability and toxicity assays demonstrated in both formats. In this paper we set the groundwork for the Mera system as a viable option for scalable microtissue culture and assay development.