MRI-Controllable Microscale Electronics for Minimally-Invasive Wireless Bio-Sensors and Bio-Actuators

项目摘要 过去几十年来生物医学设备的进步正在改变我们对诊断的看法 和治疗学。如今，小型医疗设备可以从身体内部诊断和治疗疾病 靶向神经和自身免疫性疾病、心血管疾病、癌症和其他疾病。为 例如，智能药丸被用于胃肠道成像，分布式传感器正在开发中， 来绘制大脑的功能，微型机器人被设计成通过血液进入器官 源源不断的然而，这些设备与外界通信的方式仍然是一个重大挑战。 现有的基于电磁、声学和成像的方法用于定位此类对象并与其通信， 具有空间选择性的装置受到组织的物理性质或成像性能的限制 模态类似地，目前用于监测不透明环境中的生物物理电磁信号的大多数方法都是不透明的。 组织遭受差的空间分辨率或其它技术相关的限制（例如，系留装置，差 敏感性，高度侵入性）。 在这里，我们建议通过开发一种替代方法来解决这两个挑战， 使用高精度和高分辨率侵入式监测和控制生物物理过程 微型仿生装置具体来说，我们将调整磁共振中核自旋的行为， 成像（MRI）来设计基于MRI可控谐振电路的微系统，其谐振频率 和调谐分别取决于局部磁场和生物电磁信号。的应用 然后，磁场梯度和射频信号（在MRI中可用）允许局部的成像， 生物物理过程这些无线电子MRI代理（WEMA）将使用集成电路开发 (IC)技术，并将与MRI仪器兼容。我们将使用小动物7T MRI仪器 （可在USC获得）作为我们的初始系统。作为一个概念验证，我们将针对检测克伦氏病 使用光致发光的WEMA设备，解决了准确和早期诊断的需要， 炎症性小肠疾病。如果成功，这种变革性的技术将提供一种新的仿生 能够无线、分布式、微创感测和控制生物物理过程的平台 磁共振成像，并将加强发展广泛的生物医学应用，从分布式监测 相关生物标志物的靶向释放治疗剂和用于疾病诊断的组织成像。 我们会透过以下主要目标，达致建议的整体目标： 具体目标1：通过IC设计开发微型WEMA器件。 具体目标2：开发与WEMA器械接口的MRI方法。 具体目标3：WEMA技术在体内的实验验证。

Project Summary The progress of biomedical devices over the past decades is changing how we think about diagnostics and therapeutics. Nowadays, small medical devices can diagnose and treat disease from inside the body targeting neurological and autoimmune disorders, cardiovascular conditions, cancer, and other diseases. For instance, smart pills are being used to image the gastrointestinal tract, distributed sensors are being developed to map the function of the brain, and microscale robots are being designed to access organs through the blood stream. However, a major challenge remains in the way these devices communicate with the outside world. Existing electromagnetic, acoustic, and imaging-based methods for localizing and communicating with such devices with spatial selectivity are limited by the physical properties of tissue or the performance of the imaging modality. Similarly, most of the current methods for monitoring biophysical electromagnetic signals in opaque tissue suffer from poor spatial resolution or other technology-dependent limitations (e.g., tethered devices, poor sensitivity, highly invasive). Here, we propose to address both challenges by developing an alternative approach for the minimally invasive monitoring and control of biophysical processes with high-precision and high-resolution using microscale biomimetic devices. Specifically, we will adapt the behavior of nuclear spins in magnetic resonance imaging (MRI) to engineer MRI-controllable resonant-circuit-based microsystems whose resonance frequency and tuning depend on the local magnetic field and bio-electromagnetic signal, respectively. The application of magnetic field gradients and radio-frequency signals (available in MRI) then allows the imaging of localized biophysical processes. These Wireless Electronic MRI Agents (WEMA) will be developed using integrated circuit (IC) technology and will be compatible with MRI-instrumentation. We will use a small animal 7 T MRI instrument (available at USC) as our initial system. As a proof-of-concept, we will target the detection of Chron’s disease using photoluminescence-enabled WEMA devices, addressing the need for accurate and early diagnosis in inflammatory small bowel disorders. If successful, this transformative technology will provide a new biomimetic platform capable of wireless, distributed, minimally-invasive sensing and control of biophysical processes using MRI, and will enhance the development of a wide range of biomedical applications, from distributed monitoring of relevant biomarkers to targeted release of therapeutic agents and tissue imaging for disease diagnosis. We will achieve the proposed overall goals by pursuing the following major aims: Specific Aim 1: Develop miniature WEMA devices via IC design. Specific Aim 2: Develop MRI methods to interface with WEMA devices. Specific Aim 3: Experimental validation of WEMA technology in vivo.