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.

项目摘要 大约有20,317名全球通过体外膜获得人造肺部支持 2021年的氧合（ECMO）。在ECMO期间，空心纤维膜（HFM）气体交换器需要表面 〜2 m2面积以实现治疗气体转移；但是，与血液的大型接触区域激活 凝血级联反应需要全身性抗凝治疗抑制，通常用肝素抑制。虽然 肝素降低了凝血的频率，它不会有效地抑制血小板的表面沉积 蛋白质。这些关键的凝结组件的消耗以及全身的连续给药 抗凝剂，导致ECMO期间出血的风险增加，并增加并发症和并发症的风险 死亡。我们建议用液体全氟碳血液氧合代替HFM气体交换器 系统将导致凝结较少，需要较少的抗凝剂使用，从而降低两个血栓形成的发生率 和出血。液体全氟化合物（如全氟甲林（PFD））具有多种特征 这样的系统可行：（1）它们完全与血液不混溶，可以轻松分离两者 液体； （2）它们的血液密度是两倍，使血液通过完整的氟化物流动，使得 流动系统通过自然循环工作； （3）他们的氧气含量约为40％，> 160％ 在STP处的二氧化碳的重量，可通过血液进行有效的气体转移； （4）PFD在人类中是安全的 身体已于1989年被批准为血液替代。 血液氧合系统（PBO），将氧化PFD与血液结合使用 文丘里血液液滴发生器，产生小滴血的喷嘴，剪切最小，溶血或 血小板激活。小血液滴获得氧气，然后在 在PBO的顶部重新胶片。新含氧的血液被返回到体内。 PFD移动 进入将其重新氧合并去除二氧化碳的腔室。该建议旨在确定 优化体外血液氧合（和二氧化碳去除）的最佳流动系统，而 防止血液激活，血液损伤或将PFD添加到体内。在减少PBO中的血液剪切时， 我们将最大程度地减少溶血和血液激活。我们将通过以下 特定目的：目标1：通过硅胶建模的组合优化VDG几何和流速 和原型。目标2：定量血液氧合和去除二氧化碳作为液滴尺寸的函数， PFD流速。 AIM 3：演示具有临床上有用的氧合的2 L/min系统，CO2去除， 和溶血。目标4：制定PBO的初步营销和监管计划。成功的 结果不仅将显示PBO的潜力，而且还将提供必要的设计指南来推动 开发临床可行的PBOS系统。