Artery-on-a-chip platform for automated, multimodal assessment of cerebral blood vessel structure and function

Abstract

We present a compact microfluidic platform for the automated, multimodal assessment of intact small blood vessels. Mouse olfactory artery segments were reversibly loaded onto a microfluidic device and kept under physiological (i.e., close to in vivo) environmental conditions. For immunohistochemical endpoint protein analysis, automated on chip fixation and staining of the artery eliminated the need for any subsequent tissue sectioning or processing outside the chip. In a first case study, we demonstrate the blood vessel abluminal structure based on the positions of smooth muscle cell nuclei, actin filaments and voltage gated calcium channels. In a second case study we incubated smooth muscle cells (SMCs) with a calcium-sensitive dye to simultaneously assess time-dependent, agonist-induced calcium and diameter changes of pressurized resistance arteries. We expect the presented microfluidic platform to promote routine on-chip staining and quantitative fluorescence imaging of intact blood vessels from different vascular beds, tissue engineered vascular constructs and vascularized microtissues. The at least tenfold reduction in required aliquot volumes for functional assessment and staining was achieved by on-board fluid manipulation of the syringe-pump free platform and may promote its applications for screening of newly synthesized compounds.