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: 10002217
• 负责人: Jennifer M Blain Christen
• 金额: $ 17.84万
• 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 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002217
• 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 尽管过去十年的起搏器技术取得了重大进步，但目前的起搏器系统仍在 受到一些关键局限性。首先，需要植入起搏器引导在心脏室内 可能导致许多并发症，例如感染，血栓形成，三尖瓣和心室穿孔， 以及需要在需要时提取铅的并发症。此外，与 传统的起搏器，步调可进入的心脏区域仅限于右心室（RV，通常在 顶点），偶尔会在双室起搏的情况下进行冠状动脉鼻窦分布。 RV起搏创造 异常左心室（LV）收缩，泵功能降低，肥大，超微结构异常和 增加心房颤动，心室心律不齐以及最终心力衰竭和死亡的风险。无铅 起搏器解决了与血管内导线相关的问题，但仅在RV上进行起搏时仍然有限 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波 与传统的双室起搏器结合使用的无线LV起搏电极是 从技术上讲，由于需要一个没有肋骨笼的声窗口，在传播路径上进行肺 电极和高密度超声会迅速排出电池。克服当前的局限 可用的起搏器，我们建议开发由 无线，微型，无电池，射频（RF）微波激活传感器/刺激器 可以由远程脉冲发生器植入和控制的电极。在AIM 1中，我们将追求 微型无线传感器/刺激器电极的技术开发，以独立的方式运行 平台和远程脉冲发电机控制器，以监视模拟心脏信号并提供起搏信号 使用有机幻像模型上的微电动机械系统（MEMS）和RF技术 通过测量热量产生和无关的RF干扰来测试安全性。在AIM 2中，我们将测试无线 在我们经过验证的 使用人类诱导的多能干细胞得出的CMS（HIPSCS-CMS），仿生心脏微组织模型， 以及使用啮齿动物胸切开术模型的体内。我们设想提出的创新无线 起搏器系统可以通过加快精确的能力来引发起搏器疗法的范式转移 心脏区域导致更多的生理起搏和心脏表现优化。 呢