Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

Abstract

Platelet function tests are essential to profile platelet dysfunction and dysregulation in hemostasis and thrombosis. Clinically they provide critical guidance to the patient management and therapeutic evaluation. Recently, the biomechanical effects induced by hemodynamic and contractile forces on platelet functions attracted increasing attention. Unfortunately, the existing platelet function tests on the market do not sufficiently incorporate the topical platelet mechanobiology at play. Besides, they are often expensive and bulky systems that require large sample volumes and long processing time. To this end, numerous novel microfluidic technologies emerge to mimic vascular anatomies, incorporate hemodynamic parameters and recapitulate platelet mechanobiology. These miniaturized and cost-efficient microfluidic devices shed light on high-throughput, rapid and scalable platelet function testing, hematological disorder profiling and antiplatelet drug screening. Moreover, the existing antiplatelet drugs often have suboptimal efficacy while incurring several adverse bleeding side effects on certain individuals. Encouraged by a few microfluidic systems that are successfully commercialized and applied to clinical practices, the microfluidics that incorporate platelet mechanobiology hold great potential as handy, efficient, and inexpensive point-of-care tools for patient monitoring and therapeutic evaluation. Hereby, we first summarize the conventional and commercially available platelet function tests. Then we highlight the recent advances of platelet mechanobiology inspired microfluidic technologies. Last but not least, we discuss their future potential of microfluidics as point-of-care tools for platelet function test and antiplatelet drug screening.

Microfluidic post method for 3-dimensional modeling of platelet–leukocyte interactions

“…Advances in microspot and microstamping techniques have facilitated investigation of the impact of local flow changes on platelet adhesion and thrombus formation. 23,36–38 Microfluidic models with blocks and pillars have been particularly useful to investigate the effects of localized flow disturbances on the formation and contractility of platelet aggregates. 21,22 In general, stenosed microfluidic devices 39–41 are highly efficient at promoting platelet adhesion and aggregation, however these assay systems are not designed to control the extent of platelet coverage or aggregate size.…”

“…21,22 Existing microfluidic devices containing 3D micro-tissues or micropillars create a dense network of small thrombi that induce complex flow disturbances. 23 Forming highly reproducible thrombus geometries is also challenging with these assays, due to the variable nature of surface coating by fibrillar collagens and the heterogenous degree of platelet activation. As a result, these assays are not ideal for investigating neutrophil–3D platelet interactions.…”

An Aspirin a Day…

“…21 In addition, platelet transcriptomics requires further validation as a tool to reproducibly assess whether hyperactive platelet signatures are associated with an increased risk of cardiovascular events. In addition to the potential of platelet transcriptomics, the exciting emergence of bioengineering in the thrombosis field over the last decade 22,23 provides the hope that the development of a point-of-care device that can assess platelet function in the clinic can be realized. Thus, although a challenge, the possibility to assess platelet function (or surrogate biomarker) to guide antiplatelet therapy and potentially bleeding risk would offer the exciting possibility to robustly test whether personalized approach to aspirin is truly beneficial.…”

Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis

“…Cerebral thrombosis and its associated strokes ranks as the second leading cause of death and the primary cause of disability globally. [ 1 ] Unlike arterial thrombosis, which has been intensively studied and modeled, [ 2–5 ] venous thrombosis, particularly in the brain, such as cerebral venous sinus thrombosis (CVST), remains underexplored. The lack of emphasis on integrative research in CVST can partly be attributed to its rarity compared to arterial stroke, [ 6 ] nonspecific signs and symptoms in patients, [ 7 ] and highly heterogenous cerebral venous sinus (CVS) anatomy, [ 8 ] making clinical diagnoses and monitoring more challenging.…”

“…[21][22][23] Blood coagulation tests and platelet function analyses have been undertaken to predict thrombotic risk without vessel wall. [3,24,25] However, such methodologies are reliant on labor-intensive testing, bulky and costly equipment, and specialist interpretation [14,26] -all of which are poorly available in regional and rural health settings. Currently, there is no personalized and affordable point-of-care testing available that allows for tailored risk stratification as well as long-term monitoring.…”