Integration of Compliance Chambers into Diaphragm Displacement Pump to Double the Pumping Flow of Pediatric Paracorporeal Pulsatile Ventricular Assist Device

将顺应室集成到隔膜排量泵中，使儿科体外脉动心室辅助装置的泵流量加倍

• 批准号: 10761399
• 负责人: Stephen R Topaz
• 金额: $ 29.59万
• 依托单位: W-Z BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761399
• 关键词: Adult; Aorta; Apical; Berlin; Biotechnology; Blood; Blood flow; Cannulas; Cardiac; Cardiogenic Shock; Cardiomyopathies; Child; Childhood; Complex; Coupled; Data; Devices; Diastole; Drainage procedure; Engineering; FDA approved; Frequencies; Glycerol; Goals; Head; Heart; Heart Transplantation; Heart failure; Housing; Implant; Infusion procedures; Interruption; Kentucky; Laboratory Animal Production and Facilities; Lung; Membrane; Molds; Motor; Movement; Myocarditis; Patients; Performance; Phase; Polyurethanes; Publications; Pulsatile Flow; Pump; Research Support; Respiratory Diaphragm; Scientist; Silicones; Small Business Innovation Research Grant; Stress; Surgeon; System; Systole; Technology; Testing; Thrombosis; Time; Trauma; Tricuspid valve structure; Universities; Vacuum; Weight; Withdrawal; biomaterial compatibility; blood damage; blood pump; commercialization; congenital heart disorder; design; experience; fabrication; flexibility; hemocompatibility; improved; improved outcome; in vivo; innovation; invention; left ventricular assist device; light weight; minimally invasive; multidisciplinary; neonate; novel; pediatric heart failure; pediatric patients; polycarbonate; pressure; prototype; research and development; shear stress; ventricular assist device

The paracorporeal Berlin Heart EXCOR is the only FDA-approved ventricular assist device (VAD) for pediatric patients. This pulsatile diaphragm displacement pump (DDP) is small/light weight to facilitate pediatric patient ambulation. However, EXCOR efficiency is only 50% since it withdraws and pumps blood at different times (interrupted pulsatile flow). This generates a high peak blood flow rate, which may cause blood damage. A paracorporeal continuous flow PediMag VAD has also been used in smaller children. This centrifugal pump is highly efficient due to the constant flow through the drainage/infusion cannulas, but the PediMag pump head must be attached to a bulky/heavy motor, which hinders ambulation. We previously developed a transapical to aorta (TAA) double lumen cannula (DLC) for a minimally invasive ambulatory LVAD, which showed excellent 96 hr performance/hemocompatibility in neonate lambs. Our ultimate goal is to develop an efficient, minimally invasive, paracorporeal LVAD system for pediatric patients, which combines the small size/weight (ambulation potential) of current interrupted pulsatile flow pump (e.g EXCOR) and the current high efficiency of a continuous flow pump (e.g PediMag). The enabling technology is a compliant diaphragm displacement pump (cDDP), which has compliance chambers integrated into the drainage and infusion outlets to double blood flow. The cDDP will be high performing due to: 1) noninterrupted/continuous blood flow; 2) infusion/drainage compliance chambers that decrease cDDP afterload/increase cDDP preload. The lower peak drainage/infusion flow of the cDDP will also reduce blood trauma. Preliminary data showed that adding compliance chambers increased pumping flow from 1.1 to 2.6 L/min and decreased peak flow rate. The Phase I SBIR objective is to design and fabricate a cDDP working prototype with optimal compliance chambers size. This cDDP will be tested in lambs with our previously developed TAA DLC. Specific Aim 1: To design, fabricate, and bench test a cDDP. Compliance chambers will be integrated into the cDDP drainage and infusion outlets. The cDDP will be made of polycarbonate housing with a polyurethane diaphragm in the middle. A tricuspid valve will connect the cDDP housing to the two small silicone compliance chambers. The final prototype will be tested for 1 week in a 37% glycerin mock loop for performance/reliability/durability. Specific Aim 2: To test the cDDP working prototype in lambs. The cDDP will be combined with the TAA DLC to form a less invasive, ambulatory LVAD, which will be tested in 10-15 kg lambs (n=9) to evaluate 6 hr performance/reliability and initial biocompatibility. Prototype design/fabrication/bench testing will be done at W-Z Biotech, and the lamb studies will be done at the University of Kentucky. Rather than fine-tuning existing technology, our cDDP is a novel invention, which will enable a pulsatile paracorporeal VAD with doubled efficiency. This technology can also be used in adults and may significantly impact cardiogenic shock/bridge to heart transplant management.

柏林多人心脏的excor是唯一的FDA批准心室辅助装置（VAD） 小儿患者。这种脉动隔膜位移泵（DDP）很小/轻巧，可促进小儿 病人的行动。但是，Excor效率仅为50％，因为它会退出并在不同的 时间（脉冲流中断）。这会产生高峰值流量，这可能会导致血液损伤。 较小的儿童也已使用了型体体连续流pedimag VAD。这个离心泵 由于恒定流经排水/输注插管的恒定流动，效率很高，但是Pedimag泵头 必须附着在笨重/重型电机上，这会阻碍行动。我们以前开发了一种经济 主动脉（TAA）双管子套管（DLC），用于微创的非卧床LVAD，显示出极好的 新生儿羔羊中的96个小时性能/血流相容性。我们的最终目标是开发一个有效的，最小的 针对小儿患者的侵入性，型体体LVAD系统，结合了较小的体重/体重 电流中断的脉冲流动泵（例如Excor）和A的电流高效率 连续流动泵（例如pedimag）。促成技术是符合符合的膜片位移泵 （CDDP），其合规室集成到排水和输液出口中，以双流动流动。 由于：1）非中断/连续的血流，CDDP的性能很高； 2）输液/排水 降低CDDP后载/增加CDDP预紧盘的合规室。较低的峰值排水/输液 CDDP的流量也会减少血液创伤。初步数据表明，添加合规室 泵送流量从1.1增加到2.6 l/min，峰值流速降低。 I阶段SBIR目标是 设计和制造具有最佳合规室尺寸的CDDP工作原型。这个CDDP将是 用我们先前开发的TAA DLC在羔羊中测试。特定目的1：设计，捏造和长凳 测试CDDP。合规室将集成到CDDP排水和输液出口中。 CDDP 将由中间有聚氨酯隔膜的聚碳酸酯外壳制成。三尖瓣会 将CDDP外壳连接到两个小硅酮合规室。最终原型将进行测试 在37％的甘油模拟环中进行1周的性能/可靠性/耐用性。特定目标2：测试CDDP 羔羊的工作原型。 CDDP将与TAA DLC结合起来，形成较小的侵入性， 卧床LVAD，将在10-15千克羔羊（n = 9）中进行测试，以评估6个小时的性能/可靠性和 初始生物相容性。原型设计/制造/台式测试将在W-Z Biotech和羔羊上进行 研究将在肯塔基大学进行。我们的CDDP不是微调现有技术，而是 新颖的发明，这将使效率增加一倍的脉动parac体体VAD。这项技术可以 还可以在成人中使用，并可能会显着影响心脏源性休克/桥梁对心脏移植管理。