Extra-Corporeal Oxygenator with Minimal Blood Surface Contact

项目摘要 全球约有20，317例患者通过皮质外膜接受人工肺支持 ECMO（ECMO）2021年在ECMO期间，中空纤维膜（HFM）气体交换器需要表面 面积约为2 m2，以实现治疗气体输送;然而，与血液的这种大接触面积激活了 需要全身抗凝抑制的凝血级联反应，通常使用肝素。虽然 肝素降低了凝血的频率，它不能有效地抑制血小板的表面沉积， proteins.这些关键凝血成分的消耗，以及持续全身给药， 抗凝剂，导致ECMO期间出血风险增加，并发症风险增加， mortality.我们建议用液体全氟化碳血液氧合代替HFM气体交换器， 系统将导致更少的凝血，需要更少的抗凝剂使用，降低血栓形成的发生率 和出血。液体全氟化碳如全氟萘烷（PFD）具有几个特性， 这样的系统可行：（1）它们与血液完全不混溶，使得两者之间容易分离 液体;（2）它们的密度是血液的两倍，因此血液通过全氟化碳向上流动， 流动系统通过自然循环工作;（3）它们携带约40%的氧气和>160%的 二氧化碳重量，均在STP下，能够有效地与血液进行气体转移;以及（4）PFD对人体安全 1989年被批准为血液替代品。无限将创建一个设备，一个氟碳化合物 血液氧合系统（PBOS），将氧合PFD与血液一起流入腔室， 文丘里血滴发生器，喷嘴，以最小的剪切力，溶血，或 血小板活化小血滴获得氧气并释放二氧化碳到PFD中， 在PBOS的顶部重新聚集。新充氧的血液返回到身体。PFD移动 进入一个腔室，在那里它被重新氧化并除去二氧化碳。这项建议旨在确定一个 优化体外血液氧合（和二氧化碳清除）的最佳流量系统， 防止血液激活、血液损伤或将PFD添加到身体中。在减少PBOS中的血液剪切中， 我们会尽量减少溶血和血液激活我们将通过以下方式实现这一目标 具体目标：目标1：通过计算机模拟建模的组合优化VDG几何形状和流速 和原型。目的2：量化血液氧合和CO2清除作为液滴大小的函数， PFD流速。目标3：证明一个2 L/min的系统，具有临床有用的氧合、CO2去除， 和溶血。目标4：为PBOS制定初步的营销和监管计划。成功 研究结果不仅将显示PBOS的潜力，而且将提供必要的设计指导方针，以推动 开发临床可行的PBOS系统。

PROJECT SUMMARY Approximately 20,317 patients globally received artificial pulmonary support via extra-corporeal membrane oxygenation (ECMO) in 2021. During ECMO, hollow fiber membrane (HFM) gas exchangers require a surface area of ~2 m2 to achieve therapeutic gas transfer; however, this large contact area with the blood activates the coagulation cascade that requires systemic anticoagulation for suppression, usually with heparin. Although heparin reduces the frequency of clotting, it does not effectively inhibit the surface deposition of platelets and proteins. The consumption of these critical clotting components, as well as continuous administration of systemic anticoagulant, results in an increased risk of bleeding during ECMO and increases the risk of complications and mortality. We propose that replacing the HFM gas exchanger with a liquid perfluorocarbon blood oxygenation system will lead to less clotting and require less anticoagulant use, reducing the incidence of both thrombosis and hemorrhage. Liquid perfluorocarbons such as perfluorodecalin (PFD) have several characteristics to make such a system viable: (1) They are completely immiscible with blood, allowing easy separation between the two liquids; (2) They have ~twice the density of blood, such that blood flows up through perfluorocarbons, making a flow system work through natural circulation; (3) They carry ~40% of their weight in oxygen and >160% of their weight in carbon dioxide, both at STP, enabling efficient gas transfer with blood; and (4) PFD is safe in the human body having been approved as a blood substitute in 1989. Boundless will create a device, a Perfluorocarbon Blood Oxygenation System (PBOS) that flows oxygenated PFD into a chamber in combination with blood using Venturi Blood Droplet generators, nozzles that create small droplets of blood with minimal shear, hemolysis, or platelet activation. The small blood droplets gain oxygen and release carbon dioxide into the PFD quickly before reagglomerating at the top of the PBOS. The newly oxygenated blood is returned to the body. The PFD moves into a chamber where it is re-oxygenated and carbon dioxide is removed. This proposal seeks to identify an optimal flow system that optimizes extracorporeal blood oxygenation (and carbon dioxide removal) while preventing blood activation, blood damage, or adding PFD to the body. In reducing blood shear in the PBOS, we will minimize hemolysis and blood activation. We will progress toward this objective through the following Specific Aims: Aim 1: Optimize VDG geometry and flow rates through a combination of in-silico modeling and prototypes. Aim 2: Quantify blood oxygenation and CO2 removal as a function of droplet sizes and PFD flow rates. Aim 3: Demonstrate a 2 L/min system with clinically useful oxygenation, CO2 removal, and hemolysis. Aim 4: Develop preliminary marketing and regulatory plans for the PBOS. Successful results will not only show the potential of PBOS but will provide the necessary design guidelines to drive the development of a clinically viable PBOS system.