Label-free assessment of a microfluidic vessel-on-chip model with visible-light optical tomography reveals structural changes in vascular networks

Abstract

Microvascular dysfunction is characterized by impaired structure and function of small blood vessels, contributing to disease-related tissue and organ damage, such as in the retina. Optical coherence tomography is a widely used clinical technology to detect, monitor and diagnose disorders of the retina and choroid, such as diabetic retinopathy, macular degeneration, and various inherited retinal diseases. Currently, there are limited experimental platforms that correlate observed changes in clinical metrics with underlying mechanisms of disease progression. Organ-on-chips have the potential to offer a platform for correlative studies. Previous studies have demonstrated that the three-dimensional complexity of the microvasculature can be captured in a vessel-on-chip. Yet, current vessel-on-chip imaging analysis is based on end-point read-outs that provide limited dynamic information and do not have direct correlation with imaging techniques used in the clinic. Therefore, there is a need for clinically relevant, label-free, real-time imaging technologies. In this work, we show that optical coherence tomography can fulfill this need by providing non-invasive, label-free imaging of vascular networks-on-chip. We show that optical coherence tomography can detect and can be used to quantify changes in vascular network structures over multiple days, both during vascular network development and in response to disease-associated conditions. Our results indicate that optical coherence tomography has the potential to become a standard read-out for monitoring dynamic processes in organ-on-chips. In the future, these read-outs may enable the correlation of clinical metrics, thereby providing deeper insights in the pathophysiology of diseases, for example of the retina.