Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders

Schoeman, Rogier M.; Lehmann, Marcus; Neeves, Keith B.

doi:10.1080/09537104.2017.1306042

Cited by 24 publications

(16 citation statements)

References 96 publications

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“…Microfluidic flow chambers (MFCs) designed to observe platelet adhesion and thrombus formation on surfaces coated with adhesive proteins, such as collagen, have become a valuable tool for research in hemostasis and thrombosis [7][8][9]. These devices can characterize platelet function under flow with low blood volume requirements and controlled conditions.…”

Section: Introductionmentioning

confidence: 99%

Platelet Adhesion and Thrombus Formation in Microchannels: The Effect of Assay-Dependent Variables

Scavone

Bozzi

Mencarini

et al. 2020

IJMS

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Microfluidic flow chambers (MFCs) allow the study of platelet adhesion and thrombus formation under flow, which may be influenced by several variables. We developed a new MFC, with which we tested the effects of different variables on the results of platelet deposition and thrombus formation on a collagen-coated surface. Methods: Whole blood was perfused in the MFC over collagen Type I for 4 min at different wall shear rates (WSR) and different concentrations of collagen-coating solutions, keeping blood samples at room temperature or 37 °C before starting the experiments. In addition, we tested the effects of the antiplatelet agent acetylsalicylic acid (ASA) (antagonist of cyclooxygenase-1, 100 µM) and cangrelor (antagonist of P2Y12, 1 µM). Results: Platelet deposition on collagen (I) was not affected by the storage temperature of the blood before perfusion (room temperature vs. 37 °C); (II) was dependent on a shear rate in the range between 300/s and 1700/s; and (III) was influenced by the collagen concentration used to coat the microchannels up to a value of 10 µg/mL. ASA and cangrelor did not cause statistically significant inhibition of platelet accumulation, except for ASA at low collagen concentrations. Conclusions: Platelet deposition on collagen-coated surfaces is a shear-dependent process, not influenced by the collagen concentration beyond a value of 10 µg/mL. However, the inhibitory effect of antiplatelet drugs is better observed using low concentrations of collagen.

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Section: Introductionmentioning

confidence: 99%

Platelet Adhesion and Thrombus Formation in Microchannels: The Effect of Assay-Dependent Variables

Scavone

Bozzi

Mencarini

et al. 2020

IJMS

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“…Many laboratories have used microfluidic systems to monitor thrombus formation, demonstrate the effects of fluid shear stress and define molecular events involved (110)(111)(112)(113)(114). Microfluidic studies have assessed thrombus formation in healthy donors (50, 115) and patients afflicted with von Willebrand disease, hemophilia, or thrombocytopenia (114,116), and used to tease out points of difference between immobilized ligands. De Witt and colleagues ranked 52 different adhesive surfaces for thrombus formation at arterial and venous shear rates (104) and others have studied thrombus formation in blood from mice with genetically engineered deficiencies in platelet receptors or signaling proteins (50).…”

Section: Laboratory Research and Extending To The Clinical Sectormentioning

confidence: 99%

Imaging Platelet Processes and Function—Current and Emerging Approaches for Imaging in vitro and in vivo

et al. 2020

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Platelets are small anucleate cells that are essential for many biological processes including hemostasis, thrombosis, inflammation, innate immunity, tumor metastasis, and wound healing. Platelets circulate in the blood and in order to perform all of their biological roles, platelets must be able to arrest their movement at an appropriate site and time. Our knowledge of how platelets achieve this has expanded as our ability to visualize and quantify discreet platelet events has improved. Platelets are exquisitely sensitive to changes in blood flow parameters and so the visualization of rapid intricate platelet processes under conditions found in flowing blood provides a substantial challenge to the platelet imaging field. The platelet's size (∼2 µm), rapid activation (milliseconds), and unsuitability for genetic manipulation, means that appropriate imaging tools are limited. However, with the application of modern imaging systems to study platelet function, our understanding of molecular events mediating platelet adhesion from a single-cell perspective, to platelet recruitment and activation, leading to thrombus (clot) formation has expanded dramatically. This review will discuss current platelet imaging techniques in vitro and in vivo, describing how the advancements in imaging have helped answer/expand on platelet biology with a particular focus on hemostasis. We will focus on platelet aggregation and thrombus formation, and how platelet imaging has enhanced our understanding of key events, highlighting the knowledge gained through the application of imaging modalities to experimental models in vitro and in vivo. Furthermore, we will review the limitations of current imaging techniques, and questions in thrombosis research that remain to be addressed. Finally, we will speculate how the same imaging advancements might be applied to the imaging of other vascular cell biological functions and visualization of dynamic cell-cell interactions.

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“…12 These aggregation events can be observed and quantified using fluorescent microscopy, and various microfluidic technologies have been developed to utilize shear stress-induced platelet aggregation as a diagnostic tool. 225,[227][228][229][230][231][232] Release of Platelet Constituents Various compounds are released or secreted by platelets during activation. 233 Soluble agonists released or produced on the surface of adherent platelets such as adenosine diphosphate (ADP), Thromboxane A2, and thrombin are responsible for the recruitment of further platelets and propagation of thrombi.…”

Section: Assessing Hemocompatibility In the Platelet Contextmentioning

confidence: 99%

A Review of Design Considerations for Hemocompatibility within Microfluidic Systems

Szydzik

Brazilek

Nesbitt

2020

Semin Thromb Hemost

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The manipulation of blood within in vitro environments presents a persistent challenge, due to the highly reactive nature of blood, and its multifaceted response to material contact, changes in environmental conditions, and stimulation during handling. Microfluidic Lab-on-Chip systems offer the promise of robust point-of-care diagnostic tools and sophisticated research platforms. The capacity for precise control of environmental and experimental conditions afforded by microfluidic technologies presents unique opportunities that are particularly relevant to research and clinical applications requiring the controlled manipulation of blood. A critical bottleneck impeding the translation of existing Lab-on-Chip technology from laboratory bench to the clinic is the ability to reliably handle relatively small blood samples without negatively impacting blood composition or function. This review explores design considerations critical to the development of microfluidic systems intended for use with whole blood from an engineering perspective. Material hemocompatibility is briefly explored, encompassing common microfluidic device materials, as well as surface modification strategies intended to improve hemocompatibility. Operational hemocompatibility, including shear-induced effects, temperature dependence, and gas interactions are explored, microfluidic sample preparation methodologies are introduced, as well as current techniques for on-chip manipulation of the whole blood. Finally, methods of assessing hemocompatibility are briefly introduced, with an emphasis on primary hemostasis and platelet function.

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Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders

Cited by 24 publications

References 96 publications

Platelet Adhesion and Thrombus Formation in Microchannels: The Effect of Assay-Dependent Variables

Platelet Adhesion and Thrombus Formation in Microchannels: The Effect of Assay-Dependent Variables

Imaging Platelet Processes and Function—Current and Emerging Approaches for Imaging in vitro and in vivo

A Review of Design Considerations for Hemocompatibility within Microfluidic Systems

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