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

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.

Microfluidic study of fast gas-liquid reactions.

We present a new concept for studies of the kinetics of fast gas-liquid reactions. The strategy relies on the microfluidic generation of highly monodisperse gas bubbles in the liquid reaction medium and subsequent analysis of time-dependent changes in bubble dimensions. Using reactions of CO(2) with secondary amines as an exemplary system, we demonstrate that the method enables rapid determination of reaction rate constant and conversion, and comparison of various binding agents. The proposed approach addresses two challenges in studies of gas-liquid reactions: a mass-transfer limitation and a poorly defined gas-liquid interface. The proposed strategy offers new possibilities in studies of the fundamental aspects of rapid multiphase reactions, and can be combined with throughput optimization of reaction conditions.

A microfluidic platform for probing small artery structure and function.

Although pathologic changes to the structure and function of small blood vessels are hallmarks of various cardiovascular diseases, limitations of conventional investigation methods (i.e. pressure myography) have prohibited a comprehensive understanding of the underlying mechanisms. We developed a microfluidic device to facilitate assessment of resistance artery structure and function under physiological conditions (37 degrees C, 45 mmHg transmural pressure). The platform allows for on-chip fixation, long-term culture and fully automated acquisition of up to ten dose-response sequences of intact mouse mesenteric artery segments (diameter approximately 250 micrometres and length approximately 1.5 mm) in a well-defined microenvironment. Even abluminal application of phenylephrine or acetylcholine (homogeneous condition) yielded dose-response relationships virtually identical to conventional myography. Unilateral application of phenylephrine (heterogeneous condition) limited constriction to the drug-exposed side, suggesting a lack of circumferential communication. The microfluidic platform allows us to address new fundamental biological questions, replaces a manually demanding procedure with a scalable approach and may enable organ-based screens to be routinely performed during drug development.