Quantitative evaluation of flow inside an Organ-on-Chip model using optical coherence tomography

Abstract

Organ-on-chip (OoC) systems combine the advantages of well-characterised human cells with the benefits of engineered, physiological-like microenvironments. The extracellular matrix is the natural microenvironment of cells in the human body responsible for providing the appropriate stimuli to cells to control cell processes such as morphogenesis. OoCs can mimic the ECM, via biomaterials, fluid channels and porous membranes, to provide the cells with (patho)physiological stimuli governed by the fluid dynamics in the system. Resolving fluid behaviour in OoC systems can not only aid in fine tuning the stimuli sensed by the cultured cells and control cell fate, but also perform quantitative OoC system inspections. The current state-of-the-art methods for evaluating fluid flow in the OoC systems are simulations, theoretical calculations, and empirical observations, however a real-time quantitative characterization is lacking.
In this study, we use optical coherence tomography (OCT) for measuring both the flow in different regions of the Bi/ond inCHIPit microfluidic OoC and also simultaneously obtain structural information of the OoC system. We used a commercially available high resolution (3 microns in air) spectral domain OCT system. We made quantitative 1D and 2D flow measurements using phase-resolved Doppler-OCT and number fluctuation dynamic light scattering OCT to measure the flow under realistic use scenarios in the supply flow channels and, in the tissue supporting culture well where perfusion flow occurs. The results were compared to computational fluid dynamic simulations, and found to be in partial agreement. Moreover, we investigated the effects of fixed cells on the flow behaviour demonstrating real-time biologically relevant flow information and extended the work to qualitatively evaluate the perfusion flow in the presence of a liver sample in the culture well. The results of the study pave the way for further studies that determine the shear stress forces experienced by the cells in the OoC system.