Evaluation of Organ-on-Chip Microfluidic Flows Using Optical Coherence Tomography

Abstract

Isolation of specific biological phenomena in vitro is critical to understanding living systems, due to cells’ innate capacity to integrate and respond to a wide range of signals simultaneously. Concomitantly, advances in micromanufacturing techniques overlap with progress in tissue engineering to produce microenvironments that better mimic in vivo systems. The convergence of these fields has given rise to microfluidic 3D culture platforms which have resulted in a large shift in the understanding of how many biological processes unfold due the platform’s ability to highly control microarchitectures, biochemical gradients, co-culture conditions, and mechanical stimuli. So-called Organ on Chip’s (OOCs) have been instrumental in shifting the paradigm in which cell culturing is carried out and in which ways scientists think about testing potential drug therapeutics.
The microfluidic OOC platform, inCHIPitTM, by BIOND Solutions, B.V. is a versatile tool designed for co-culture with a variety of macroscopic tissue types, such as organoids, explants, spheroids, and microtissues. It is a silicone (a.k.a. PDMS) and silicon-based platform that has the capacity for pneumatically controlled flexions and monitoring bioelectrical potentials. The inCHIPitTM model has already be implemented to model various organs, including midbrain organoids and induced pluripotent stem cells (iPSCs). The purpose of this study, however, is to further characterize the laboratory tool itself rather than the potential biological applications. Here, optical coherence tomography (OCT) is used to interrogate the OOC device’s construction and culture capability by making use of properties of interfering waves and backscattering light. Furthermore, the microfluidic fluid flows and diffusion events in an OOC were characterized with OCT for the first time. And, as proof of concept, organoid-like bodies (OLBs) and their impact on flows in culture were examined.
inCHIPitTM consists of two microcompartments – a straight microfluidic channel and a culture well separated by a microporous PDMS membrane – which are supported by a series of interlocking plates and a culture lid, all composed of different materials. In terms of imaging quality, the plate material choice and lid optical traits played a key role by limiting background noise, yet, for instance, the culture lid qualities would prove inhibiting to OCT measurements during actual cell culture experiments. Moreover, the fluid velocity profiles within in inCHIPitTM microfluidics were observed and were demonstrated to exhibit characteristic velocity profiles. It was also shown that mass transport phenomenon across the porous membrane in the cell culture well occur and follow typical diffusive mechanisms. Further, initial observations as to the effects of OLBs on fluid flow characteristics in the inCHIPitTM platform were reported. The compilation of OCT and OLB measurements and observations make a strong argument for the potential of inCHIPitTM system as a staple of biomedical applications.