Soft wireless multimodal cardiac implantable devices for long-term investigating heart failure pathogenesis

项目摘要 这份R01提案的目标是开发一种超软、完全可植入、无线无标签的心脏标测 和调制系统，并应用它来识别慢性电生理和代谢变化及其联系 在自由意识动物心力衰竭的发展、进展和起搏治疗过程中 细胞水平和整个心脏水平。为了实现这一点，一种小型化、机械兼容的平台 高密度、高分辨率的传感和调制通道，具有无线能量采集、存储、控制 提出了数据通信模块的设计方案。由此产生的系统将极大地减少运动伪影和 允许在活体动物中进行双向高含量的电和代谢标测和起搏。这些设备是 创新，因为它们直接解决了目前在长期量化个人角色和 在心脏病发病机制中重要的心脏生物物理参数之间的相互作用 从根本上研究与病理生理条件有关的复杂疾病机制 致死性心力衰竭及其治疗。一旦实现，这项技术将对心脏具有很高的价值 研究社区。从长远来看，这项工作将使闭环多参数心脏标测和 起搏系统，并提供了新的方法来研究精确的机制和优化诊断和 心衰以外其他危及生命的心脏病的治疗策略。这三个具体目标是： AIM 1将建立超软多模式心脏系统，用于无标记细胞分辨率标测 兴奋-收缩-代谢波和心脏起搏。机械柔顺的高度可伸缩 系统由(1)透明微电极组成的高密度阵列(总共约300个通道)组成，用于电 测绘和刺激；(2)多色微发光二极管，以及用于激发和刺激的微型光电探测器 测定细胞能量代谢的主要内源性荧光标记物的自发荧光。 Aim 2将开发完全可植入的无线方案，用于电力采集、存储、控制和数据 用于在封闭的胸腔内自由活动地长期操作目标1中的平台的通信 小动物，这是目前技术所不能支持的。图形用户界面将是 专为设备配置、实时双向控制、数据采集和处理而开发。这个 集成系统将通过反复的台式测量进行表征、验证和优化。 Aim 3将系统地研究HF的确切发病机制和使用电池进行治疗 在心力衰竭大鼠模型上的测试。建议的系统的功能将在体外和体内进行评估。 学习。植入式心脏装置将识别局部代谢和局部代谢之间的个体作用和联系。 在不同时间点和不同阶段的高频发展和进展期间的电学特性 评价心脏再同步化治疗的效果。

Project Summary The goal of this R01 proposal is to develop an ultra-soft, fully implantable, wireless label-free cardiac mapping and modulation system and apply it to identify chronic electrophysiological and metabolic changes and their links during heart failure (HF) development, progression, and pacing treatment in unrestrained conscious animals at cellular and whole heart levels. To achieve this, a miniaturized, mechanically compliant platform that integrates high-density, high-resolution sensing and modulation channels with wireless energy harvesting, storage, control, and data communication module is proposed. The resulting systems will greatly reduce motion artifacts and allow bidirectional high-content electrical and metabolic mapping and pacing in live animals. Those devices are innovative because they directly address the current limitations in chronically quantifying the individual roles and interplay between vital cardiac biophysical parameters during heart disease pathogenesis and will be used to fundamentally investigate the complex disease mechanisms involved in pathophysiological conditions leading to lethal HF and its therapeutic treatment. Once realized, this technology will be highly valuable to the cardiac research community. In the long term this work will enable closed-loop multiparametric cardiac mapping and pacing systems and offer new approaches to study the precise mechanisms and optimize the diagnostic and therapeutic strategies of other life-threatening heart diseases beyond HF. The three specific aims are: Aim 1 will establish ultra-soft multimodal cardiac systems for label-free cellular-resolution mapping of the excitation-contraction-metabolic waves and cardiac pacing. The mechanically compliant highly stretchable systems consist of high-density arrays (~300 channels in total) of (1) transparent microelectrodes for electrical mapping and stimulation; (2) multicolor micro-light-emitting diodes, and micro-photodetectors to excite and measure the autofluorescence of major endogenous fluorescent markers of cellular energy metabolism. Aim 2 will develop fully implantable wireless schemes for power harvesting, storage, control, and data communication to chronically operate the platforms in Aim 1 within a closed thoracic cavity in freely behaving small animals, which is beyond any possibility supported by current techniques. Graphical user interfaces will be developed for device configuration, real-time bidirectional control, data acquisition and processing. The integrated systems will be characterized, validated, and optimized by iterative benchtop measurements. Aim 3 will systematically investigate the precise mechanisms of HF pathogenesis and therapy using a battery of tests in rat models of HF. The functions of the proposed systems will be assessed in both ex vivo and in vivo studies. The implantable cardiac devices will identify the individual roles and links between local metabolic and electrical properties during different time points and stages of HF development and progression, and thoroughly evaluate the effects of cardiac-resynchronization therapy.