Extra-Corporeal Oxygenator with Minimal Blood Surface Contact

与血液表面接触最少的体外氧合器

• 批准号: 10760184
• 负责人: Andrew Jones
• 金额: $ 29.89万
• 依托单位: BOUNDLESS SCIENCE, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2024-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760184
• 关键词: Acute; Acute Respiratory Distress Syndrome; Adsorption; Alveolar; Animals; Anticoagulants; Anticoagulation; Area; Asthma; Blood; Blood Platelets; Blood Substitutes; Blood Tests; Blood coagulation; Blood flow; COVID-19; Carbon Dioxide; Characteristics; Childhood; Chronic Obstructive Pulmonary Disease; Circulation; Clinical; Coagulation Process; Complement Activation; Consumption; Deposition; Development; Devices; Diameter; Diffuse; Disease; Excision; Extracorporeal Membrane Oxygenation; Family suidae; Feedback; Fiber; Fibrin; Fluorocarbons; Frequencies; Gases; Geometry; Goals; Guidelines; Hemolysis; Hemorrhage; Heparin; Hour; Human body; In Vitro; Incidence; Inflammation Mediators; Injury; Interview; Liquid substance; Lung; Lung Transplantation; Marketing; Medical Device; Membrane; Modeling; Operative Surgical Procedures; Orphan; Oxygen; Oxygenators; Patients; Performance; Phase; Physiological; Platelet Activation; Pneumonectomy; Proteins; Respiratory Failure; Risk; Science; Small Business Innovation Research Grant; Structure; Surface; System; Testing; Therapeutic; Thrombosis; Thrombus; Venous; Weight; Work; biomaterial compatibility; blood damage; commercialization; density; design; experience; good laboratory practice; graft dysfunction; heart function; improved outcome; in silico; leukocyte activation; lung failure; mortality; novel; pressure; prevent; prototype; pulmonary function

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.

项目概要 全球约 20,317 名患者通过体外膜接受人工肺支持 2021 年进行氧合 (ECMO)。在 ECMO 期间，中空纤维膜 (HFM) 气体交换器需要一个表面 约 2 m2 的面积以实现治疗气体传输；然而，这种与血液的大接触面积会激活 需要全身抗凝来抑制的凝血级联反应，通常使用肝素。虽然 肝素会降低凝血频率，不能有效抑制血小板表面沉积， 蛋白质。这些关键凝血成分的消耗以及全身性的持续给药 抗凝剂，导致 ECMO 期间出血的风险增加，并增加并发症的风险 死亡。我们建议用液体全氟化碳血氧替代HFM气体交换器 系统将导致较少的凝血并需要较少的抗凝剂使用，从而降低血栓形成的发生率 和出血。全氟萘烷 (PFD) 等液体全氟化碳具有多种特性 这样的系统可行：（1）它们与血液完全不混溶，可以轻松地将两者分离 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，从而形成 流动系统通过自然循环工作； (3) 它们携带约 40% 重量的氧气和 >160% 的重量 二氧化碳重量（均在 STP 下），可实现血液中气体的有效传输； (4) PFD 对人体是安全的 1989 年，Boundless 被批准作为血液替代品。Boundless 将制造一种装置，一种全氟化碳 血液氧合系统 (PBOS) 将含氧 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、溶血或 血小板活化。小血滴在 PFD 中快速获得氧气并释放二氧化碳 在 PBOS 顶部重新聚集。新含氧的血液返回体内。 PFD 移动 进入一个室，在那里它被重新充氧并去除二氧化碳。该提案旨在确定一个 最佳流量系统，可优化体外血液氧合（和二氧化碳去除），同时 防止血液活化、血液损伤或向体内添加 PFD。在减少 PB​​OS 中的血液剪切力时， 我们将最大限度地减少溶血和血液活化。我们将通过以下几方面的努力来实现这一目标 具体目标： 目标 1：通过结合计算机建模来优化 VDG 几何结构和流量 和原型。目标 2：量化血液氧合和二氧化碳去除量与液滴大小和 PFD 流量。目标 3：演示 2 L/min 系统，具有临床上有用的氧合、CO2 去除、 和溶血。目标 4：为 PBOS 制定初步营销和监管计划。成功的 结果不仅将展示 PBOS 的潜力，还将提供必要的设计指南来推动 开发临床上可行的 PBOS 系统。