Development of higher efficiency and safer Oxygenators for Critical Respiratory Failure Treatment and Heart/Lung Surgery Assist

项目概要/摘要 为全球超过700，000名重症患者提供维持生命的必要氧气和二氧化碳气体交换 呼吸衰竭或进行心脏/肺手术的患者通过使血液流过回路来提供，该回路包含 体外氧合器。市售氧合器使用中空纤维（HF）作为气体交换 件.血液在这些HF的外部周围流动，而吹扫气体流过它们的HF。 中空通道通过微孔HF壁，O2扩散到血液中，CO2扩散出来， 将静脉血转化为动脉血然而，关键的止血并发症风险因素，如血液- 接触面积、预充体积、湍流和高压流动条件以及累积剪切应力、姿态 影响治疗和康复的持续健康风险（即，暂时性认知障碍等）和 导致显著的发病率和死亡率（即，多器官衰竭等），这进一步加剧了 长期使用。HF氧合器技术在过去十年中仅逐步改进， 能够显著提高性能和/或安全性的替代技术仍处于初期阶段（低 流量）阶段。该SBIR提案的目标是首先开发儿科FAB，然后开发成人更安全的FAB- 氧合器FAB-氧合器结合了新型气体交换部件（流体通道阵列砖， 本文称为“FAB”）具有直线和层流的血液流动路径、低压降和较高的O2， CO2气体传输效率。这些FAB氧合器提供所需的O2和CO2气体传输速率， 多个关键止血并发症风险因素水平较低，即（i）血液接触表面积，（ii）预充 体积、（iii）压降和（iv）累积应力，从而提高患者安全性。这些风险因素 影响血液损伤和流失、血小板活化、凝血风险、血液制品需求和气体输送 速率稳定性SBIR提案的长期目标是开发一系列更安全的氧合器， 为每个患者类别（新生儿、儿科、小型和大型成人）配置。FAB-氧合器放大至 在未来的发展中，成人患者类别，以及完全优化的FAB，可能会导致 体外人工肺在第一阶段，我们将开发更安全的儿科FAB氧合器。可行性将是 通过体外评价与市售儿科HF氧合器进行比较而确立 根据FDA推荐的AAMI 7199测试方案，并使用建模和安全优值函数值 对比如果获得批准，第二阶段将足以完成最多 成人尺寸FAB氧合器，进行首次体内试验，开始批量生产，以及 准备FDA提交。我们计划建立FAB-氧合器设计许可/技术转让， FAB/FAB-子组件供应商与多家氧合器制造商建立合作伙伴关系，并组建团队 专家，临床医生，营销人员，制造商和工程师，他们可以共同将FAB氧合器带入 市场

Project Summary/Abstract Essential life-maintaining O2 and CO2 gas exchanges for over 700,000 patients worldwide with critical respiratory failure or undergoing heart/lung surgery are provided by flowing blood through an circuit containing an extracorporeal oxygenator. Commercially available oxygenators use hollow fibers (HF) as gas exchange components. Blood flows turbulently around the outside of these HFs while a sweep gas flows through their hollow channels. Through the microporous HF walls, O2 diffuses into the blood, and CO2 diffuses out, converting venous blood into arterial blood. However, key hemostatic complication risk factors, like blood- contact area, priming volume, turbulent and high-pressure flow conditions, and accumulated shear stress, pose continuous health risks that affect treatment and recovery (i.e., temporary cognitive impairment, etc.) and contribute to significant morbidity and mortality (i.e., multiple organ failures, etc.), which are further aggravated with prolonged use. HF oxygenator technology has only incrementally improved over the last decade and alternative technologies that could significantly improve performance and/or safety are still in their infant (low flow capacity) stage. The goal of this SBIR proposal is to develop first a pediatric and then an adult safer FAB- Oxygenator. FAB-Oxygenators incorporate novel gas exchange components (Fluid channel Array Bricks, herein called “FABs”) having a straight and laminar blood flow path, low-pressure drop, and a higher O2 and CO2 gas transfer efficiency. These FAB-Oxygenators provide the required O2 and CO2 gas transfer rates with lower levels of multiple key hemostatic complication risk factors, i.e. (i) blood contact surface area, (ii) priming volume, (iii) pressure drop, and (iv) accumulated stress, thereby improving patient safety. These risk factors affect blood damage and loss, platelet activation, coagulation risk, demand for blood products, and gas transfer rate stability. The long-term goal of this SBIR proposal is to develop a family of safer oxygenators, optimally configured for each patient class (neonatal, pediatric, small, and large adults). FAB-Oxygenator scale-up to adult patient class, together with fully optimized FABs, under a future development, could lead to an extracorporeal artificial lung. In Phase I, we will develop a safer pediatric FAB-Oxygenator. Feasibility will be established by comparison to commercially available pediatric HF oxygenators through in vitro evaluation under the FDA-recommended AAMI 7199 test protocol, and with modeling and a safety merit function value comparison. Phase II, if granted, will be sufficient to complete extended in vitro verification/validation of up to adult size FAB-Oxygenators, perform the first in vivo tests, begin the transfer to volume manufacturing, and prepare for FDA submission. We plan to establish FAB-Oxygenator design licensing/technology transfer and FABs/FAB-SubAssembly supply partnerships with multiple oxygenator manufacturers and to assemble a team of experts, clinicians, marketers, manufacturers, and engineers who can jointly bring FAB-Oxygenators into the market.