The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL. Red blood cells and platelets were assumed to be non-interacting spherical particles transported by the bulk fluid flow, and convection of the activated coagulation factor II, thrombin, was assumed to be governed by mass transfer. This model served as the basis for predicting formation of local shear rate gradients, stagnation points and recirculation zones as dictated by the bypass geometry. Based on the insights from these models, we were able to predict the patterns of blood clot formation at specific locations in the device. Our experimental data was then used to adjust the model to account for the dynamical presence of thrombus formation in the biorheology of blood flow. The model predictions were then compared to results from experiments using recalcified whole human blood. Microfluidic devices were coated with the extracellular matrix protein, fibrillar collagen, and the initiator of the extrinsic pathway of coagulation, tissue factor. Blood was perfused through the devices at a flow rate of 2 µL/min, translating to physiologically relevant initial shear rates of 300 and 700 s−1 for main channels and bypasses, respectively. Using fluorescent and light microscopy, we observed distinct flow and thrombus formation patterns near channel intersections at bypass points, within recirculation zones and at stagnation points. Findings from this proof-of-principle ladder network model suggest a specific correlation between microvascular geometry and thrombus formation dynamics under shear. This model holds potential for use as an integrative approach to identify regions susceptible to intravascular thrombus formation within the microvasculature as well as extravascular devices such as ECMO.

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in Wiley Online Library (wileyonlinelibrary.com).The transport of confined droplets in fluidic networks can lead to complex spatiotemporal dynamics, precluding full control of the position of droplets in the network. Here, we report the design of a model-based feedback controller that can actively regulate droplet positions in a network. We specifically consider droplet dynamics in a microfluidic loop where a main channel splits into two and recombines. Consistent with previous studies, we find that without active control, the dynamics of droplets in the loop can range from periodic to chaotic behaviors. However, by implementing the model-based feedback controller, we show that the droplets can be made to sort alternately into the branches of the loop as well as to synchronize the times at which pairs of droplets exit the loop. In particular, our computations demonstrate that the controller is capable of executing remarkable droplet sort-synchronization tasks in the otherwise chaotic dynamics in the loop. The design of our controller incorporates a hydrodynamic network model, that is, capable of predicting droplet positions and subsequently delivering an actuation to the branches in the loop through elastomeric valves. Efficacy of the controller is discussed in terms of actuation characteristics and constraints imposed by elastomeric valves. The model-based feedback controller framework presented in this study is likely to promote the development of lab-on-chip technologies in which droplet manipulation tasks are executed with active control.The periodic dips in the actuation are shown in the inset. (f) Actuation frequency as a ratio of number of actuations at a particular value to the total number of actuations for synchronizing 35 pairs of droplets. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]The periodic dips in the actuation are seen in the inset. Interestingly in this case the upper branch also gets actuated consistently (f) Actuation frequency as a ratio of number of actuations at a particular value to the total number of actuations for synchronizing 35 pairs of droplets. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Droplets moving in a microfluidic loop device exhibit both periodic and chaotic behaviors based on the inlet droplet spacing. We observe that the periodic behavior is an outcome of carrier phase mass conservation principle, which translates into a droplet spacing quantization rule. This rule implies that the summation of exit spacing is equal to an integral multiple of inlet spacing. This principle also enables identification of periodicity in experimental systems with input scatter. We find that the origin of chaotic behavior is through intermittency, which arises when drops enter and leave the junctions at the same time. We derive an analytical expression to estimate the occurrence of these chaotic regions as a function of system parameters. We provide experimental, simulation, and analytical results to validate the origin of periodic and chaotic behavior.