Background Supraphysiological hemodynamics are a recognized driver of platelet activation and thrombosis at high-grade stenosis and in blood contacting circulatory support devices. However, whether platelets mechano-sense hemodynamic parameters directly in free flow (in the absence of adhesion receptor engagement), the specific hemodynamic parameters at play, the precise timing of activation, and the signaling mechanism(s) involved remain poorly elucidated. Results Using a generalized Newtonian computational model in combination with microfluidic models of flow acceleration and quasi-homogenous extensional strain, we demonstrate that platelets directly mechano-sense acute changes in free-flow extensional strain independent of shear strain, platelet amplification loops, von Willebrand factor, and canonical adhesion receptor engagement. We define an extensional strain sensing “mechanosome” in platelets involving cooperative Ca2+ signaling driven by the mechanosensitive channel Piezo1 (as the primary strain sensor) and the fast ATP gated channel P2X1 (as the secondary signal amplifier). We demonstrate that type II PI3 kinase C2α activity (acting as a “clutch”) couples extensional strain to the mechanosome. Conclusions Our findings suggest that platelets are adapted to rapidly respond to supraphysiological extensional strain dynamics, rather than the peak magnitude of imposed wall shear stress. In the context of overall platelet activation and thrombosis, we posit that “extensional strain sensing” acts as a priming mechanism in response to threshold levels of extensional strain allowing platelets to form downstream adhesive interactions more rapidly under the limiting effects of supraphysiological hemodynamics.

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Stagnation point flows have been widely used to study the deformation and break-up of objects in two-dimensional pure straining flows. Here, we report a systematic study of the characterisation of stagnation point flows in two devices, a miniature Taylor's four-roll mill and a cross-slot microchannel. The aim of the study is to find the best platform suitable for investigating the effect of strain rate on the mechanical properties of waterborne microorganisms. Using micro-PIV, the velocity field and the strain rates in both devices were measured at different flow rates and compared with an ideal hyperbolic stagnation point flow. The cross-slot microchannel was found to be a better experimental device than the miniature four-roll mill for the purpose of confining micron-sized objects in a controlled stagnation point flow. This is mainly due to the difficulty of maintaining a fixed location for the stagnation point within one micron in the miniature four-roll mill and achieving high strain rates beyond 10 s-1. However, with no moving parts, the cross-slot microchannel was found to maintain a steady flow with the stagnation point varying less than one micron at a cross-junction of 400 × 400 µm 2 , and was able to reach uniform strain rates up to 140 s-1 .

Here we report novel micro-PIV measurements around micron-sized objects that are trapped at the centre of a stagnation point flow generated in a cross-slow microchannel using real-time control. The method enables one to obtain accurate velocity and strain rate fields around the trapped objects under straining flows. In previous works, it has been assumed that the flow field measured in the absence of the object is the one experienced by the object in the stagnation point flow. However, the results reveal that this need not be the case and typically the strain rates experienced by the objects are higher. Therefore, simultaneously measuring the flow field around a trapped object is needed to accurately estimate the undisturbed strain rate (away from the trapped object). By combining the micro-PIV measurements with an analytical solution by Jeffery (1922), we are able to estimate the velocity and strain rate around the trapped object, thus providing a potential fluidic method for characterising mechanical

This paper reports on the parameters that determine the haemocompatibility of elastomeric microvalves for blood handling in microfluidic systems. Using a comprehensive investigation of blood function, we describe a hierarchy of haemocompatibility as a function of microvalve geometry and identify a "normally-closed" v-gate pneumatic microvalve design that minimally affects blood plasma fibrinogen and von Willebrand factor composition, minimises effects on erythrocyte structure and function, and limits effects on platelet activation and aggregation, while facilitating rapid switching control for blood sample delivery. We propose that the haemodynamic profile of valve gate geometries is a significant determinant of platelet-dependent biofouling and haemocompatibility. Overall our findings suggest that modification of microvalve gate geometry and consequently haemodynamic profile can improve haemocompatibility, while minimising the requirement for chemical or protein modification of microfluidic surfaces. This biological insight and approach may be harnessed to inform future haemocompatible microfluidic valve and component design, and is an advance towards lab-on-chip automation for blood based diagnostic systems.