Introduction

Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited in vitro methods exist for assessing the effects of anticoagulants on hemostasis, the development of novel therapies to safely prevent thrombosis in COVID-19 patients relies on preclinical animal models and early phase human trials. Herein we present the design of a microfluidic “bleeding chip” to evaluate the effects of antithrombotic therapies on hemostatic plug formation in vitro.

Methods

The design of the microfluidic device consists of two orthogonal channels: an inlet that serves as a model blood vessel, and a bleeding channel to model hemostatic plug formation at sites of compromised endothelial barrier function. This is achieved by placing a series of 3 pillars spaced 10 μm apart at the intersection of the two channels. The pillars and bleeding channel are coated with the extracellular matrix protein collagen.

Results

Perfusion of human whole blood through the microfluidic bleeding chip led to initial platelet adhesion and aggregation at the pillars followed by hemostatic plug formation and occlusion of the bleeding channel.

Conclusions

Safe and effective mitigating agents are needed for treatment and prevention of thrombotic complications in COVID-19 patients. This simple microfluidic device holds potential to be developed into a tool for assessing the effects of anticoagulant therapy on hemostasis.

中文翻译：

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设计用于评估用于 COVID-19 患者的抗血栓药物的微流控出血芯片。

介绍

可以预防新型冠状病毒病 (COVID-19) 患者血栓形成、临床失代偿和呼吸损害的干预措施是降低死亡率的关键。研究表明，细胞因子的大量释放和凝血的过度激活似乎是 COVID-19 相关死亡率的关键驱动因素。由于评估抗凝剂对止血作用的体外方法有限，开发新疗法以安全预防 COVID-19 患者血栓形成依赖于临床前动物模型和早期人体试验。在这里，我们提出了一种微流控“出血芯片”的设计，以评估抗血栓治疗对体外止血栓形成的影响。

方法

微流体装置的设计由两个正交通道组成：一个用作模型血管的入口，一个用于模拟内皮屏障功能受损部位的止血栓形成的出血通道。这是通过在两个通道的交叉处放置一系列间隔 10 μ m 的 3 个柱子来实现的。柱子和出血通道涂有细胞外基质蛋白胶原蛋白。

结果

通过微流控出血芯片灌注人全血导致血小板在柱子上的初始粘附和聚集，然后形成止血栓并阻塞出血通道。

结论

需要安全有效的缓解剂来治疗和预防 COVID-19 患者的血栓并发症。这种简单的微流体装置有可能被开发成一种评估抗凝治疗对止血效果的工具。