Enhanced operation of female reproductive microphysiological system (MPS) for rapid mechanistic study

Microphysiological systems (MPS) have shown their capabilities in mimicking in vivo-like structural and functional complexity and are seeing significant increase in their utilization in the field of drug discovery and toxicology. However, the major time-consuming steps in the fabrication, utilization, and analyses of MPS devices limit the throughput for broader adoption. Here, we advanced the previously developed two-chamber MPS model of the female reproductive tracts from a single unit chip to an array type chip that is compatible with multi-channel pipettor or automated liquid handling robot for rapid and more efficient operation. To enable this array model, a new microfabrication method was developed, incorporating a microplate holder, bonding guide plate, and soft lithography cassette to minimize device-to-device variation. To validate its compatibility with multi-channel pipettors in chemical toxicity testing, cadmium, a chemical previously shown to elicit cytotoxicity in the two-chamber feto-maternal interface MPS model, was utilized to demonstrate highly uniform cell loading (variance < 100 cells/mm2) and consistent dose-dependent cytotoxic response. Additionally, a liquid handling robotic system was also utilized, with no operational errors such as air bubble introduction (zero bubbles out of 100 devices) during cell/chemical loading process, and no unintended cytotoxic effects (> 97% viability). These results highlight that this automation-compatible array type MPS device can provide highly consistent cell culture performance and significantly reduced chip-to-chip and operation-to-operation variations, overcoming the limitations of typical MPS devices.