Microcirculation On A Chip

Abstract: The primary physiological function of the cardiovascular system, i.e. the delivery of oxygen and nutrients to and the removal of metabolic waste products from living tissues, is performed by the microcirculation. It is also where key events of the immune response such as leukocyte margination, rolling and subsequent diapedesis take place. Microvascular blood flow dynamics have a major impact on all of these vital processes. We used silicon micromachining and polydimethylsiloxane replica molding to create microchannel networks with dimensions and topology similar to the real microcirculation. These networks provide high quality of imaging and unprecedented control over all hemodynamically relevant parameters. We reproduced and documented a number of key blood flow dynamics and phenomena characteristic of the microcirculation in vivo using whole blood and blood cell suspensions of varying composition. This suggests the possibility to use this system as a convenient microfluidic platform for experimental studies of the mechanics of the microcirculation. The impact of blood cell rheology and interactions, plasma composition, network architecture and channel wall surface properties on microvascular network blood flow dynamics can now be addressed without interference from active biological regulation. This system will, for the first time, provide a viable bridge between computer simulations and experiments in vivo. Finally, we created a simple microfluidic device that takes advantage of plasma skimming and leukocyte margination to provide positive, continuous flow selection of leukocytes directly from microliter samples of whole blood. It produces a 34-fold enrichment of the leukocyte-to-erythrocyte ratio and requires no preliminary labeling of cells. This effortless, efficient and inexpensive technology can be used as a lab-on-a-chip component for initial whole blood sample preparation. Its integration into microanalytical devices that require leukocyte enrichment will enable accelerated transition of these devices into the field for point-of-care clinical testing.