Abstract

Towards High Content & High Throughput Screening Platforms: Enabling Technologies to Advance Organ-on-a-Chip Systems

Peter Loskill, Attract Group Manager Organ-on-a-Chip, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB

Drug discovery and development to date has relied on animal models, which are useful, but fail to resemble human physiology. The discovery of human induced pluripotent stem (iPS) cells has led to the emergence of a new paradigm of drug screening using human patient- and disease-specific organ/tissue-models. One promising approach to generate these models is by combining the iPS technology with microfluidic devices tailored to create microphysiological environments and recapitulate 3D tissue structure and function. Such microphysiological organ-on-a-chip systems (OoCs) combine human genetic background, in vivo-like tissue structure, physiological functionality, and “vasculature-like” perfusion. Using microfabrication techniques, we have developed multiple OoCs that incorporate complex human 3D tissues and keep them viable and functional over multiple weeks, including a “Retina-on-a-chip”, a “Heart-on-a-chip” and a “White adipose tissue (WAT)-on-a-chip”. The OoCs generally consist of three functional components: organ-specific tissue chambers mimicking in vivo structure and microenvironment of the respective tissues; “vasculature-like” media channels enabling a precise and computationally predictable delivery of soluble compounds (nutrients, drugs, hormones); “endothelial-like” barriers protecting the tissues from shear forces while allowing diffusive transport. The small scale and accessibility for in situ analysis makes our OoCs amenable for both massive parallelization and integration into a high-content-screening approach. The adoption of OoCs in industrial and non-specialized laboratories requires enabling technology that is user-friendly and compatible with automated workflows. We have developed technologies for automated 3D tissue generation as well as flexible plug&play connection of individual OoCs into multi-organ-chips. These technologies paired with the versatility of our OoCs pave the way for applications in drug development, personalized medicine, toxicity screening, and mechanistic research.