Extra-Corporeal Oxygenator with Minimal Blood Surface Contact

项目总结 全球约有20,317名患者通过体外膜接受人工肺支持 2021年的氧合(ECMO)。在ECMO过程中，中空纤维膜(HFM)气体交换器需要表面 面积~2平方米以实现治疗性气体转移；然而，这种与血液的大接触面积激活了 需要全身抗凝才能抑制的凝血级联反应，通常使用肝素。虽然 肝素降低凝血频率，它不能有效地抑制血小板的表面沉积和 蛋白质。这些关键的凝血成分的消耗，以及持续的全身给药 抗凝剂，导致ECMO中出血的风险增加，并增加并发症和 死亡率。我们建议用液体全氟碳血液氧合取代HFM气体交换器 系统将导致较少的凝血和需要较少的抗凝剂的使用，减少血栓的发生率 还有大出血。液体全氟碳化合物，如全氟碳氢化合物(PFD)，有几个特点需要制造 这样的系统是可行的：(1)它们与血液完全不相容，使两者很容易分离 液体；(2)它们的密度是血液的两倍，这样血液就会通过全氟碳化合物向上流动，从而产生 流动系统通过自然循环工作；(3)它们携带约40%的重量的氧气和160%的 二氧化碳的重量，两者都在STP，使气体能够有效地与血液转移；以及(4)PFD在人体内是安全的 人体在1989年被批准为血液替代品。无界将创造一种装置，一种全氟化碳 血液充氧系统(PBOS)，将含氧的PFD与血液一起流入室内，使用 文丘里血滴发生器，喷嘴，以最小的剪切力产生小的血滴，溶血或 血小板被激活。在此之前，小的血滴获得氧气并迅速释放二氧化碳到PFD中 在PBOS的顶部重新凝聚。新产生的含氧量的血液被送回体内。PFD的行动 进入一个房间，在那里它被重新氧化，二氧化碳被去除。这项提案旨在确定一种 最佳流动系统，优化体外血液氧合(和二氧化碳清除)，同时 防止血液活化、血液损伤或在体内添加PFD。在降低PBOS中的血液切变方面， 我们将最大限度地减少溶血和血液活化。我们会透过以下工作，朝这个目标迈进 具体目标：目标1：通过结合硅内建模优化VDG几何形状和流量 和原型。目标2：量化血液氧合和二氧化碳清除作为液滴大小和 PFD流量。目的3：演示一种2 L/分钟的临床有用的氧合、二氧化碳清除、 还有溶血。目标4：为PBOS制定初步的营销和监管计划。成功 结果将不仅显示PBOS的潜力，而且将提供必要的设计指南，以推动 临床可行的PBOS系统的开发。

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.