Advancing microfluidic point-of-care platelet function tests: opportunities and challenges from bench to market

Figures

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  FIGURE 1. Overview of Currently Used Platelet Function Testing POCs (A) Schematic of VerifyNow® and LTA working principles, demonstrating platelet aggregation detection in response to agonists. Reprinted from Yoon et al. (2024), Copyright 2024, with permission from MDPI. (B) Platelet aggregation data measured by the born PFA® in response to agonists. Reprinted from Van Oosterom et al. (2022), Copyright 2021, with permission from Taylor and Francis Group. (C) Working principle of T-TAS with microscopy images showing thrombus growth in microchannels. (D) Example T-TAS data plotting flow pressure versus time, with the endpoint marked by the Area Under the Curve (AUC) (OST: occlusion start time, OT: occlusion time). Reproduced with permission from Fujimori Kogyo, Co. Ltd., Tokyo, Japan.

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  FIGURE 2. Overview of microfluidic POC PFTs. (A) Schematic representation of arterial thrombosis driven by SIPA, illustrating the process of shear-induced platelet aggregation under high shear rates. (B) Photograph of a microfluidic device and its corresponding microchannel design, simulating thrombosis-on-a-chip for the study of platelet function and thrombus formation. Reprinted from Liu et al. (2022), Copyright 2022, with permission from American Society of Hematology (C) Graph showing thrombus volume as a function of time, highlighting the progression of SIPA and the resulting occlusion in the microchannel. Reproduced with permission from Casa et al. (2015), Copyright 2015, with permission from Elsevier. (D) Overview of potential clinical and research applications of microfluidic POC PFTs.

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  FIGURE 3. The principle and design of microfluidic POC PFTs. (A) Schematic illustrating the reproduction of high-shear thrombosis in in vitro microfluidic platforms, mimicking arterial conditions. (B) Optical microscopy images capturing SIPA-induced occlusion within microchannels, demonstrating the thrombus growth process. Reprinted from Rooij et al. (2020), Copyright 2020, with permission from the Royal Society. (C) Graph showing discharge mass over time as SIPA progresses, correlating with thrombus formation. Reprinted from Casa and Ku. (2014a), Copyright 2014, with permission from Springer Nature. (D, E) Application of hemodynamic microfluidic POC PFTs in the development of antiplatelet therapies: (D) Occlusion time at various NAC doses, demonstrating dose-dependent effects, and (E) Kaplan-Meier survival plot versus occlusion time, assessing the therapeutic efficacy of antiplatelet agents. Reprinted from Bresette et al. (2024), Copyright 2023, with permission from Wolters Kluwer Health.

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  FIGURE 4. Research progress in microfluidic PFTs. (A) Schematic of a hemostasis monitor device and its method of operation, designed to assess platelet function and thrombus formation. Reprinted from Jain et al. (2016), Copyright 2024, with permission from Springer Nature. (B) Schematic of a microfluidic device incorporating high shear rates with an array of microblocks to simulate arterial thrombus formation. (C) SEM image showing a platelet aggregate formed after 45 s at a shear rate of 8,000 s⁻1, alongside a computational fluid dynamics (CFD) simulation visualizing wall shear rates. Reprinted from Ting et al. (2019), Copyright 2024, with permission from Springer Nature. (D) Photograph, design diagram, and CFD simulation of an injection-molded, scalable, manufacturable microfluidic device, highlighting its potential for large-scale production. (E) Graph showing shear rate as a function of occlusion fraction, illustrating how shear conditions evolve during occlusion. (F) Fluorescent intensity of platelets plotted against whole blood perfusion time at day 1 and after 6 months post-manufacturing, assessing the device’s shelf life and performance stability over time. Reprinted from Rossi and…