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

项目摘要 广泛的可变形生物接口设备被用于诊断、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。尽管在光遗传学和细胞生物学等生物技术方面取得了临床前的进展 起搏，非遗传的电子方法仍然是治疗心律失常的主要方法。 特别是，半导体已经成为非遗传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传感，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用于光调制心脏活动的光电化学方法 在体外培养的细胞以及成年啮齿动物模型中。利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 与日野一起扩展和加强我们最新的基于孔隙率的光电化学生物调节系统 硅异质结，用于心脏组织的多位点、无铅、非遗传和光电调制。 具体地说，我们将设计、构建和测试一系列基于光学材料孔隙度的异质结 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 含有非多孔/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，我们将采用原子层沉积的方法对硅表面进行钝化。我们会 用金属或金属氧化物催化剂对材料表面进行修饰，以增强信号转导。为了支持 硅异质结，我们计划使用软基质，如聚合物和水凝胶，这将增强 生物界面的生物相容性和信号转导。我们还将制造生物兼容光纤 用于体内光刺激实验。为了实现多点光学起搏，我们将开发， 组装并测试软件、机械、电气和光学组件。之后，我们计划验证 扫描仪的性能，如其精度、扫描速度和功率传输，然后是 体外光刺激试验。然后，该设备将在大鼠模型中进行测试，以确定其生物兼容性， 然后使用单腔、双腔和多腔心脏起搏测试急性和慢性环境下的心脏起搏 猪模型中的现场刺激。我们将验证我们的假设，即可变形和生物兼容的异质结 该装置可用于由光信号触发的多部位心脏再同步治疗。 这项拟议的研究可以为心脏调制定义一种新的治疗选择。结合独立式 而具有可兴奋细胞和组织的光敏半导体将产生可以 受光控制。基于半导体的生物接口的新设计将允许无线、非遗传、 多尺度和随机访问光调制。

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.