Automated and high-volume wafer-scale microfabrication of organ-on-chip (OoC) polymer structures and components

Abstract

Organ-on-chip (OoC) technology is a promising improvement within in vitro cell culture, better mimicking functional units of human organs compared to conventional techniques. Current fabrication of three-Dimensional (3D) components in OoC, such as thin membranes and microfluidic structures, is often achieved via soft lithography, bonding, and punching of access holes of polymers, such as polymethylsiloxane (PDMS). However, these methods often suffer from the need of manual fabrication steps, drastically increasing production time and reducing yield due to handling errors and manual alignment of the layers. Consequently, the scalability is limited, which is a crucial aspect for a more widespread adaptation of OoC technology. In this work, we present a reproducible and scalable process for the direct patterning of various 3D polymer structures. The investigated process employs commercially available systems from IC packaging to mould pillars, membranes, and microfluidic channels with varying dimensions and thicknesses. Our process simultaneously improves the control over the thickness and dimensions of these structures in comparison to conventional fabrication techniques. Furthermore, proof of functionality is presented by adapting this technology to an existing OoC platform which incorporates integrated electrodes used for electrophysiological recording, stimulation, and TEER measurements. We demonstrate a complete process for wafer-scale microfabrication of OoCs, enabling low-cost, high-volume automated production. This is an important next step to large-scale manufacturing of OoCs, enabling more biologists and scientists to integrate OoCs into their workflow.