Nanoporous semiconductor-enabled multi-site photostimulation for cardiac resynchronization therapy

项目摘要 各种各样的可变形生物界面装置被用于诊断、治疗和监测。 通过测量生理参数，应用生物电调制，或 运送毒品尽管生物技术如光遗传学和基于细胞的生物学在临床前取得了进展， 起搏、非遗传电子方法仍然是治疗心律紊乱的主要方法。 特别是半导体，已经成为非遗传性心血管研究的潜在有用工具， 包括基于场效应晶体管的电生理学感测、光驱动的心脏群体激活，以及 电子集成心脏组织工程。 我们最近发表了几种光电化学方法，用于光学调制心脏活动， 培养的细胞以及离体成年啮齿动物模型。使用光来调制心脏组织， 已经证明了与光遗传学中使用的强度相当的强度。在这项工作中，田将密切合作， 与日比野扩大和加强我们最新的光电化学生物调节系统，孔隙为基础的 硅异质结，用于心脏组织的多位点、无铅、非遗传和光电调制。 具体来说，我们将设计，构建和测试一个选择的异质结的基础上孔隙率的光学 心脏组织的调节。我们将合成核/壳纳米线、核/壳微粒和双层膜 包含无孔/纳米孔异质结的膜。为了提高异质结的稳定性， 在生理条件下，我们将应用原子层沉积来钝化硅表面。我们将 用金属或金属氧化物催化剂修饰材料表面以增强信号转导。支持 硅异质结，我们计划使用软基质，如聚合物和水凝胶，这将提高 生物相容性和生物界面的信号转导。我们还将制造生物相容的光纤 用于体内光刺激实验。为了实现多部位光学起搏，我们将开发， 组装和测试软件、机械、电气和光学组件。之后，我们计划验证 扫描仪的性能，如其准确性，扫描速度和功率输送，其次是 离体光刺激试验。然后将在大鼠模型中测试该装置以确定其生物相容性， 随后使用单腔、双腔和多腔起搏器在急性和慢性环境中测试心脏起搏， 在猪模型中的位点刺激。我们将测试我们的假设，可变形和生物相容的异质结， 装置可用于由光信号触发的多部位心脏栓塞治疗。 拟议的研究可以为心脏调节定义一种新的治疗选择。独立式 光敏半导体与可兴奋的细胞和组织将产生生物界面， 由光线控制。基于生物传感器的生物界面的新设计将允许无线的，非遗传的， 多尺度和随机存取光调制。

Project Summary A wide range of deformable biointerface devices are employed for the diagnosis, treatment, and monitoring of cardiovascular diseases by measuring physiological parameters, applying bioelectrical modulation, or delivering drugs. Despite preclinical advances in biotechnology such as optogenetics and cell-based biological pacing, non-genetic electronic methods remain the dominant method for treating cardiac rhythm disorders. Semiconductors, in particular, have emerged as a potentially useful tool for non-genetic cardiovascular research, including field effect transistor-based electrophysiology sensing, light-driven cardiac population activation, and electronics-integrated cardiac tissue engineering. We recently published several photoelectrochemical methods for optically modulating cardiac activity in cultured cells as well as in adult rodent models ex vivo. The use of light to modulate cardiac tissue with an intensity comparable to that used in optogenetics has been demonstrated. In this work, Tian will work closely with Hibino to expand and strengthen our newest photoelectrochemical biomodulation system, porosity-based silicon heterojunctions, for multi-site, leadless, nongenetic, and optoelectronic modulation of cardiac tissues. Specifically, we will design, construct, and test a selection of heterojunctions based on porosity for optical modulation of cardiac tissues. We will synthesize core/shell nanowires, core/shell microparticles, and bilayer membranes that contain non-porous/nanoporous heterojunctions. To improve the stability of the heterojunctions under physiological conditions, we will apply atomic layer deposition to passivate the silicon surfaces. We will modify the material surface with metal or metal-oxide catalysts to enhance signal transduction. To support the silicon heterojunctions, we plan to use soft matrices such as polymers and hydrogels, which will enhance biocompatibility and signal transduction at the biointerfaces. We will also fabricate biocompatible optical fibers for use in in vivo photostimulation experiments. In order to enable multi-site optical pacing, we will develop, assemble, and test the software, mechanical, electrical, and optical components. Afterwards, we plan to validate the scanner's performance, such as its accuracy, scanning speed, and power delivery, followed by the photostimulation tests ex vivo. The device will then be tested to determine its biocompatibility in a rat model, followed by testing heart pacing in acute and chronic settings using single-chamber, dual-chamber, and multi- site stimulations in a pig model. We will test our hypothesis that deformable and biocompatible heterojunction devices can be used for multi-site cardiac resynchronization therapy triggered by optical signals. The proposed research can define a new treatment option for cardiac modulation. Incorporating freestanding and photosensitive semiconductors with excitable cells and tissues will result in biointerfaces that can be controlled by light. The new designs for semiconductor-based biointerfaces would allow for wireless, nongenetic, multiscale, and random access photomodulation.