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

项目摘要/摘要 为全球超过70万名患者提供必要的生命维持氧气和二氧化碳气体交换 呼吸衰竭或接受心脏/肺手术是通过血液流经含有 体外氧合器。商用氧合器使用中空纤维(HF)作为气体交换 组件。血液在这些HFs的外面湍急地流动，而一股扫射气体流过它们的 中空通道。通过微孔的HF壁，O2扩散到血液中，CO2扩散出去， 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、起爆体积、湍流和高压流动条件以及累积剪应力，姿势 影响治疗和康复的持续健康风险(即暂时性认知障碍等)和 导致严重的发病率和死亡率(即多器官衰竭等)，并进一步加剧 经久耐用。高频氧合器技术在过去十年中只是逐步改进， 可以显著提高性能和/或安全性的替代技术仍处于初级阶段(低 流量)级。这项SBIR建议的目标是首先开发一种儿科，然后是一种成人更安全的FAB- 氧气机。FAB氧合器结合了新的气体交换组件(流体通道阵列砖， 在这里被称为“FAB”)具有直的和层流的血流路径、低的压力降和较高的O2和 二氧化碳气体传输效率。这些FAB氧合器提供所需的O2和CO2气体传输率 较低水平的多种关键止血并发症风险因素，即(I)血液接触面积，(Ii)预充 体积、(Iii)压降和(Iv)累积压力，从而提高患者的安全性。这些风险因素 影响血液损伤和丧失、血小板激活、凝血风险、血液制品需求和气体转移 速率稳定。这项SBIR提案的长期目标是开发一种更安全的氧合器家族，最好是 为每个患者类别(新生儿、儿科、小型和大型成人)配置。FAB-制氧器放大到 成人患者类别，加上经过充分优化的FAB，在未来的发展中可能会导致 体外人工肺。在第一阶段，我们将开发一种更安全的儿科FAB氧合器。可行性将是 通过体外评估与市售的儿童HF氧合器进行比较而建立 根据FDA推荐的AAMI7199测试协议，并具有建模和安全优点函数值 比较一下。如果获得批准，第二阶段将足以完成最多 成人大小的FAB氧合器，进行第一次体内测试，开始批量生产，以及 为FDA的提交做好准备。我们计划建立FAB氧合器设计许可/技术转让和 FABS/FAB-组件与多家氧气机制造商建立合作伙伴关系并组建团队 由专家、临床医生、营销人员、制造商和工程师组成，他们可以共同将脂肪氧合器带入 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.