The Australian Centre for Blood Diseases , Monash University , 99 Commercial Road , Melbourne , Victoria 3004 , Australia.
School of Engineering , RMIT University , 124 La Trobe Street , Melbourne , Victoria 3000 , Australia.
Anal Chem. 2019 Aug 20;91(16):10830-10839. doi: 10.1021/acs.analchem.9b02486. Epub 2019 Aug 6.
There is a need for scalable automated lab-on-chip systems incorporating precise hemodynamic control that can be applied to high-content screening of new more efficacious antiplatelet therapies. This paper reports on the development and characterization of a novel active micropump-mixer microfluidic to address this need. Using a novel reciprocating elastomeric micropump design, we take advantage of the flexible structural and actuation properties of this framework to manage the hemodynamics for on-chip platelet thrombosis assay on type 1 fibrillar collagen, using whole blood. By characterizing and harnessing the complex three-dimensional hemodynamics of the micropump operation in conjunction with a microvalve controlled reagent injection system we demonstrate that this prototype can act as a real-time assay of antiplatelet drug pharmacokinetics. In a proof-of-concept preclinical application, we utilize this system to investigate the way in which rapid dosing of human whole blood with isoform selective inhibitors of phosphatidylinositol 3-kinase dose dependently modulate platelet thrombus dynamics. This modular system exhibits utility as an automated multiplexable assay system with applications to high-content chemical library screening of new antiplatelet therapies.
需要开发可扩展的自动化芯片实验室系统，该系统将精确的血液动力学控制与高通量筛选新的、更有效的抗血小板治疗方法相结合。本文报告了一种新型主动式微泵-混合器微流控芯片的开发和特性研究，以满足这一需求。我们采用新颖的往复式弹性体微泵设计，利用这种结构的灵活结构和致动特性，在 1 型纤维状胶原蛋白上，使用全血进行芯片血小板血栓形成分析，以管理血液动力学。通过对微泵操作的复杂三维血液动力学进行表征和利用，以及微阀控制的试剂注入系统，我们证明了该原型可以实时检测抗血小板药物药代动力学。在概念验证的临床前应用中，我们利用该系统研究了快速向人全血中注入同工型选择性磷脂酰肌醇 3-激酶抑制剂的方式，剂量依赖性地调节血小板血栓动力学。该模块化系统作为一种自动化的可复用分析系统具有应用价值，可用于高通量筛选新的抗血小板治疗方法的化学文库。
