A wireless fully-passive miniaturized patient-tailored pacemaker

无线全无源微型患者定制起搏器

• 批准号: 9809482
• 负责人: Jennifer M Blain Christen
• 金额: $ 18.18万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9809482
• 关键词: Acoustics; Address; Anisotropy; Architecture; Atrial Fibrillation; Biocompatible Materials; Biomimetics; Caliber; Cardiac; Cardiac Myocytes; Cardiomyopathies; Cardiovascular Physiology; Cessation of life; Coronary; Coronary sinus structure; Data; Detection; Development; Electric Conductivity; Electrical Engineering; Electrocardiogram; Electrodes; Electronics; Freedom; Functional disorder; Generations; Goals; Gold; Heart; Heart failure; Heterogeneity; Histology; Human; Hydrogels; Hypertrophy; Impairment; Implant; In Vitro; Infection; Lead; Left; Location; Lung; Measures; Mechanics; Metals; Modeling; Monitor; Morphology; Myocardial Infarction; Myocardium; Pacemakers; Patients; Perforation; Performance; Physiologic pulse; Physiological; Pump; Rattus; Right ventricular structure; Risk; Rodent; Rodent Model; Safety; Signal Transduction; Site; Sprague-Dawley Rats; System; Technology; Telemetry; Testing; Therapeutic; Thoracotomy; Thrombosis; Tissue Model; Tissues; Tricuspid valve structure; Ultrasonography; Ventricular; Ventricular Arrhythmia; Wireless Technology; Work; absorption; base; biomaterial compatibility; cardiac tissue engineering; density; design; efficacy testing; flexibility; heart function; hemodynamics; human stem cells; implantation; improved; in vivo; in vivo evaluation; induced pluripotent stem cell; innovation; microwave electromagnetic radiation; miniaturize; minimally invasive; multidisciplinary; nanorod; nanoscale; next generation; personalized approach; phantom model; prototype; radio frequency; release of sequestered calcium ion into cytoplasm; response; rib bone structure; safety testing; sensor; transmission process

Summary Despite major advances in pacemaker technologies during the past decade, current pacemaker systems still suffer from several critical limitations. Primarily, the need to implant pacemaker leads within cardiac chambers could lead to a host of complications such as infection, thrombosis, tricuspid valve and ventricular perforation, along with the complications associated with the extraction of the lead when required. Furthermore, with traditional pacemakers, the cardiac regions accessible to pacing are restricted to right ventricle (RV, typically at the apex) and occasionally, coronary sinus distribution in cases of biventricular pacing. RV pacing creates abnormal left ventricular (LV) contraction, reduced pump function, hypertrophy, ultrastructural abnormalities and increases risk of atrial fibrillation, ventricular arrhythmias and ultimately heart failure and death. Leadless pacemakers address the issue associated with intravascular leads, but they remain limited in pacing only the RV and require placement of a new pacemaker after battery depletion. The recently developed remote ultrasound- powered wireless LV pacing electrode in conjunction with traditional pacemaker for biventricular pacing is technically limited by need for an acoustic window free of rib cage and lung on the transmission path to the electrode and the high density ultrasound drains battery quickly. To overcome the limitations of currently available pacemakers, we propose to develop the next generation of pacemaker system composed of wireless, miniaturized, battery-free, radiofrequency (RF) microwave activated sensor/stimulator electrodes that could be implantable and controlled by a remote pulse generator. In Aim 1, we will pursue technical development of miniaturized wireless sensor/stimulator electrodes, operating as a stand-alone platform, and remote pulse generator controller to monitor simulated cardiac signals and provide pacing signals using Micro-Electro-Mechanical-Systems (MEMS) and RF technologies on an organic phantom model while testing safety by measuring heat generation and extraneous RF interference. In Aim 2, we will test the wireless pacemaker system in vitro by measuring signal detection, pacing stimulation and tissue safety on our validated biomimetic cardiac micro-tissue model, using human induced pluripotent stem cell derived CMs (hiPSCs-CMs), as well as in vivo using a rodent thoracotomy model. We envision that the proposed innovative wireless pacemaker system could usher a paradigm shift in pacemaker therapeutics through the ability to pace precise regions of the heart resulting in more physiologic pacing and optimization of cardiac performance. !

概括 尽管起搏器技术在过去十年中取得了重大进步，但当前的起搏器系统仍然 受到几个关键的限制。主要是需要在心室内植入起搏器导线 可能导致一系列并发症，如感染、血栓形成、三尖瓣和心室穿孔， 以及在需要时与拔出引线相关的并发症。此外，与 传统的起搏器，可进行起搏的心脏区域仅限于右心室（RV，通常位于 心尖），偶尔，双心室起搏情况下的冠状窦分布。 RV 起搏会产生 左心室 (LV) 收缩异常、泵功能降低、肥大、超微结构异常和 增加心房颤动、室性心律失常以及最终心力衰竭和死亡的风险。无引线 起搏器解决了与血管内导线相关的问题，但它们仅在右心室起搏方面受到限制 并需要在电池耗尽后放置新的起搏器。最近开发的远程超声- 供电无线左心室起搏电极与传统起搏器相结合进行双心室起搏 技术上的限制是需要在传输路径上没有肋骨和肺部的声窗 电极和高密度超声波会快速耗尽电池电量。为克服目前的局限性 可用的起搏器，我们建议开发下一代起搏器系统，包括 无线、小型、无电池、射频 (RF) 微波激活传感器/刺激器 可以植入并由远程脉冲发生器控制的电极。在目标1中，我们将追求 小型化无线传感器/刺激器电极的技术开发，作为独立操作 平台和远程脉冲发生器控制器，用于监测模拟心脏信号并提供起搏信号 在有机体模模型上使用微机电系统 (MEMS) 和射频技术，同时 通过测量热量产生和外部射频干扰来测试安全性。在目标 2 中，我们将测试无线 通过在我们经过验证的设备上测量信号检测、起搏刺激和组织安全性来体外起搏器系统 仿生心脏微组织模型，使用人类诱导多能干细胞衍生的 CM（hiPSC-CM）， 以及使用啮齿动物开胸手术模型进行体内实验。我们预计所提议的创新无线 起搏器系统可以通过精确起搏的能力引领起搏器治疗的范式转变 心脏区域导致更多的生理起搏和心脏性能的优化。 ！