PumpKIN PreClinical

Ension儿科心肺辅助系统(PCAS)被设计和开发为下一代体外膜氧合(ECMO)-也称为体外生命支持(ECLS)-系统，提供更多的功能和血液兼容性。PCAS的预期用途是使用单一的一次性血液接触式泵-氧合器，为2公斤至25公斤的患者提供部分或全部心肺支持，最长可达两周。该系统经过专门设计，可在不到五分钟内完成的程序中快速更换泵-氧合器，以适应这两周后的延长支持。与目前可用的系统相比，该系统具有关键的优势，特别是改善了血液兼容性，更小的表面积和引爆量，快速部署，以及便于亲子结合和患者运输的紧凑配置。 PCAS系统由泵-氧合器、控制台和包括静脉和动脉插管以及气泡捕集器在内的辅助部件组成。PCAS泵-氧合器是一种紧凑型装置，由离心式叶轮通过旋转扩散器直接与血液氧合器集成在一起。氧合器由中空纤维膜(Celgard PP微孔针织阵列)组成，其中包含专门为增强血液相容性而设计的基于肝素的工程表面。PCAS控制台功能包括调节泵速、显示所有运行参数、监测故障状况、显示报警以及控制供应给血封的清洗液。控制台集成了一个内部备用电池，能够在交流电源丢失或病人运送过程中提供超过两个小时的连续操作。 在PCAS项目的开发阶段(主要由NIH儿科循环系统支持)，已经制造并广泛测试了PCAS泵-氧合器和控制台的原型 支持合同HHSN268200448189C从2004年4月开始并正在进行)。集成泵-氧合器和控制台的候选设计以及随后的改进以功能性、生物兼容性、临床和成本要求以及测试数据、正式危害分析、人为因素评估、计算流体动力学(CFD)分析和可靠性考虑为指导。制造过程已作为产品开发和原型生产过程的一部分进行了建立、改进和验证。Ension准备在符合国际标准化组织13485和21 CFR 820.30中阐明的设计控制规定的质量体系下组装和测试所有必要的PCAS系统组件。这包括继续使用深入的风险和可靠性分析、管理和缓解。 Ension的PCAS系统在开发过程中已在体外和体内进行了广泛的测试。体外数据已经证明，PCAS泵-氧合器能够达到所需的血流速度和压力，并交换氧气和二氧化碳。更多的体外数据证实，血液损伤最小，红细胞、白细胞和血小板消耗水平较低，血浆渗漏较目前可用的中空纤维膜氧合器显著改善，血液相容性得到改善。Ension在仔猪身上进行了体内系统测试，证明PCAS系统为目标人群中的小患者和小牛提供了适当的血流动力学支持，展示了更长期的设备功能和血液兼容性。

The Ension pediatric cardiopulmonary assist system (pCAS) has been designed and developed as a next-generation extracorporeal membrane oxygenation (ECMO) - also called extracorporeal life support (ECLS) - system that provides increased functionality and blood compatibility. The intended use of the pCAS is to provide partial or complete cardiopulmonary support to patients from 2 kg to 25 kg for periods of up to two weeks using a single disposable blood-contacting pump-oxygenator. The system has been specifically designed to accommodate extended support beyond this two-week period by rapid change-out of the pump-oxygenator in a procedure that can be completed in less than five minutes. The system offers key advantages over currently available systems, specifically improved blood compatibility, smaller surface area and priming volume, rapid deployment, and a compact configuration that facilitates parent-child bonding and patient transport. The pCAS system consists of a pump-oxygenator, a control console, and ancillary components that include venous and arterial cannulae and a bubble trap. The pCAS pump-oxygenator is a compact device consisting of a centrifugal impeller directly integrated with a blood oxygenator via a turning diffuser. The oxygenator is comprised of hollow fiber membranes (Celgard polypropylene microporous knitted array) incorporating a heparin-based engineered surface specifically designed to enhance blood compatibility. The pCAS control console functionality includes regulation of pump speed, display of all operational parameters, monitoring for fault conditions, display of alarms, and control of purge fluid supplied to the blood seal. The control console incorporates an internal backup battery capable of providing over two hours of continuous operation should AC power be lost or during patient transport. Prototype pCAS pump-oxygenators and control consoles have been fabricated and tested extensively during the development phase of the pCAS project (primarily supported by NIH Pediatric Circulatory Support contract HHSN268200448189C beginning in April 2004 and ongoing). Candidate designs for the integrated pump-oxygenator and control console, as well as subsequent refinements, were guided by functionality, biocompatibility, clinical, and cost requirements as well as test data, formal hazards analysis, human factors evaluations, computational fluid dynamics (CFD) analyses, and reliability considerations. Manufacturing processes have been established, refined, and validated as part of the product development and prototype production processes. Ension is prepared to assemble and test all necessary pCAS system components under a Quality System compliant with ISO 13485 as well as the design control regulations articulated in 21 CFR 820.30. This includes the continued use of in-depth risk and reliability analysis, management, and mitigation. Ension's pCAS system has been extensively tested in vitro and in vivo during development. In vitro data have demonstrated the pCAS pump-oxygenator's ability to achieve required blood flow rates and pressures and to exchange oxygen and carbon dioxide. Additional in vitro data have confirmed minimal blood damage as evidenced by low levels of red cell, white cell, and platelet consumption, significant improvement in plasma leakage over currently available hollow fiber membrane oxygenators, and improvement in blood compatibility. Ension has conducted in vivo system testing in piglets demonstrating that the pCAS system provides appropriate hemodynamic support for the small patients in the target population and in calves demonstrating longer-term device functionality and blood compatibility.