title: A microfluidics device to monitor platelet aggregation dynamics in response to strain rate micro-gradients in flowing blood.
abstract: This paper reports the development of a platform technology for measuring platelet function and aggregation based on localized strain rate micro-gradients. Recent experimental findings within our laboratories have identified a key role for strain rate micro-gradients in focally triggering initial recruitment and subsequent aggregation of discoid platelets at sites of blood vessel injury. We present the design justification, hydrodynamic characterization and experimental validation of a microfluidic device incorporating contraction-expansion geometries that generate strain rate conditions mimicking the effects of pathological changes in blood vessel geometry. Blood perfusion through this device supports our published findings of both in vivo and in vitro platelet aggregation and confirms a critical requirement for the coupling of blood flow acceleration to downstream deceleration for the initiation and stabilization of platelet aggregation, in the absence of soluble platelet agonists. The microfluidics platform presented will facilitate the detailed analysis of the effects of hemodynamic parameters on the rate and extent of platelet aggregation and will be a useful tool to elucidate the hemodynamic and platelet mechano-transduction mechanisms, underlying this shear-dependent process.
authors.affiliation: School of Electrical and Computer Engineering, RMIT University, Melbourne, Victoria, Australia. tovar.lopez.fj@gmail.com
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Tovar-Lopez
authors.forename: Gary
authors.initials: G
authors.lastname: Rosengarten
authors.forename: Erik
authors.initials: E
authors.lastname: Westein
authors.forename: Khashayar
authors.initials: K
authors.lastname: Khoshmanesh
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Jackson
authors.forename: Arnan
authors.initials: A
authors.lastname: Mitchell
authors.forename: Warwick S
authors.initials: WS
authors.lastname: Nesbitt
mesh_terms: D040761:Biomimetic Materials; D001783:Blood Flow Velocity / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D017076:Computer-Aided Design; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D015539:Platelet Activation / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity