Flexible and Wireless Bioelectronics for Continuous Monitoring of Intracranial Pressure

用于连续监测颅内压的灵活无线生物电子学

• 批准号: 10427358
• 负责人: Layla Khalifehzadeh
• 金额: $ 9.53万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-09-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427358
• 关键词: Award; Basic Cancer Research; Biocompatible Materials; Biomedical Engineering; Brain; Brain Diseases; Brain Neoplasms; Butadiene; Cancer Patient; Cardiovascular system; Cellular Phone; Cerebrospinal Fluid; Cessation of life; Clinical; Data; Detection; Devices; Diagnosis; Disease; Doctor of Philosophy; Elastomers; Electric Capacitance; Elements; Emergency Situation; Engineering; Environment; Frequencies; Future; Goals; Growth; Heart-Assist Devices; Histology; Hospitals; Hydrocephalus; Immune response; Immunohistochemistry; Implant; Individual; Intervention; Intracranial Hypertension; Intracranial Pressure; Kinetics; Left; Life; Link; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Measurement; Measures; Medicine; Mentors; Monitor; Morphology; Mus; Nanotechnology; Nervous System Trauma; Neurologic; Neurology; Noise; Operative Surgical Procedures; Patients; Pattern; Performance; Polymers; Procedures; Program Development; Research; Research Personnel; Rights; Schools; Scientist; Signal Transduction; Stents; Stroke; Structure; Styrenes; System; Technology; Testing; Therapeutic; Thick; Thinness; Time; Training; Tumor Cell Line; Tumor Volume; Urinary system; Variant; base; bioelectronics; biomaterial compatibility; brain magnetic resonance imaging; brain tissue; cancer diagnosis; cancer imaging; cancer therapy; career; career development; clinical application; cost; design; diagnostic technologies; elastomeric; experience; experimental study; flexibility; implantable device; implantation; improved; in vivo; light weight; model design; mouse model; multidisciplinary; neglect; neurosurgery; optical imaging; parylene; point of care; pressure; pressure sensor; prevent; programs; relating to nervous system; research and development; response; sensor; simulation; temporal measurement; tumor; tumor growth; water diffusion; wireless; wireless communication; wireless sensor

Project Summary: This proposal describes a five-year research and career development program to prepare Dr. Razieh Khalifehzadeh for a career as an independent investigator. This program will build upon Dr. Khalifehzadeh’s multidisciplinary background as a bioengineer scientist, trained in bioelectronics, biomaterials and basic cancer research, by providing expertise in designing flexible and highly sensitive pressure sensors for continuous wireless monitoring of intracranial pressure (ICP) associated with brain tumors. The PI will be mentored at Stanford Schools of Engineering and Medicine by Drs. Zhenan Bao (Main mentor, flexible and wearable bioelectronics), Sanjiv S. Gambhir (co-mentor, cancer diagnosis, cancer bioengineering and cancer nanotechnology), Heike Daldrup-Link (co-mentor, brain cancer imaging and therapy, and a leader in promoting diversity), Ada Poon (collaborator, wireless bioelectronics), Melanie Hayden (collaborator, neurosurgery and neurology) and Eric Appel (collaborator, biomaterials and biocompatibility). Brain tumors are usually associated with increased ICP. Delayed diagnosis and treatment of the elevated ICP often results in irreversible neurological damage and even death. The overall goal of the proposed research is to design highly sensitive and brain compatible pressure sensors that can wirelessly detect ICP variations, as a generally neglected neurological marker in brain tumor patients. Recently, I developed ultrasmall (3×3×0.1 mm3), flexible, and implantable pressure sensors that were effective for wireless monitoring of the ICP variations in mice models of growing U87 brain tumor over their 30 day survival period. The key component of these pressure sensors is an intermediate elastomer layer with a specific pressure-responsive micropattern that defines the consistent sensitivity of these devices for long-term accurate measurements in the brain. In Aim 1 of this project, I will study new designs for this elastomer layer, in order to further improve the sensitivity and long- term electro-mechanical stability of my pressure sensors. Additionally, I will use experiments and simulations to find alternative designs for more efficient wireless signal transfer (i.e., higher signal-to-noise ratios) from these sensors. I will also develop a handheld wireless signal recording setup to enable recording and rapid analysis of the wireless pressure data using a smartphone, for easier in vivo measurements and future point-of-care applications. Aim 2 is focused on extending the post-implantation lifetime and brain compatibility of the sensors by coating them with parylene (thickness ~ 1-4 µm). Parylene has been broadly used as a protective coating for neuro-interface and cardiac assist devices to enhance their post-implantation lifetime. Finally, I will use these sensors for continuous wireless monitoring of ICP variations in different mice models of brain tumors, with various survival periods, depending on invasiveness of the tumor (Aim 3). MRI, simulations and histology will be used to verify ICP measurements. These sensors are clinically needed for monitoring ICP in different brain diseases, including tumors, and we envision that their versatile design will facilitate their clinical applications.

项目摘要：该提案描述了一项为期五年的研究和职业发展计划 Razieh Khalifehzadeh博士从事独立调查员的职业。该计划将基于博士。 Khalifehzadeh作为生物工程学的多学科背景，接受过生物材料的培训 和基本的癌症研究，通过在设计灵活且高度敏感的压力传感器方面提供专业知识 连续无线监测与脑肿瘤相关的颅内压（ICP）。 PI将是 博士在斯坦福大学工程和医学学校的指导。 Zhenan Bao（灵活和 可穿戴生物电子学），Sanjiv S. Gambhir（癌症诊断，癌症生物工程和癌症 纳米技术），Heike daldrup-link（脑癌成像和疗法的同事，以及促进的领导者 多样性），Ada Poon（无线生物电子学合作者），Melanie Hayden（神经外科合作者和 神经病学）和Eric Appel（合作者，生物材料和生物相容性）。 脑肿瘤通常与ICP增加有关。升高的诊断和升高治疗 ICP通常会导致不可逆的神经系统损害甚至死亡。拟议的总体目标 研究是设计高度敏感和大脑兼容的压力传感器，可以无线检测ICP 变异是脑肿瘤患者中普遍忽视的神经系统标记。最近，我开发了Ultrasmall （3×3×0.1 mm3），柔性和可植入压力传感器，可有效地监测ICP 在其30天生存期内，小鼠模型中U87脑肿瘤的变化。一个关键组成部分 这些压力传感器是具有特定压力响应微图案的中间弹性层 定义这些设备对大脑长期准确测量的一致灵敏度。在目标1中 这个项目，我将研究该弹性体层的新设计，以进一步提高灵敏度和长期。 我的压力传感器的术语电力稳定性。此外，我将使用实验和模拟进行 从这些寻找更有效的无线信号传输（即较高的信噪比）的替代设计 传感器。我还将开发手持无线信号记录设置，以启用记录和快速分析 使用智能手机的无线压力数据，以便于体内测量和未来的护理点 申请。 AIM 2专注于扩展传感器的植入后寿命和大脑兼容性 通过将它们涂有parylene（厚度〜1-4 µm）。 Parylene已广泛用作保护性涂层 神经界面和心脏辅助设备，以增强其植入后寿命。最后，我将使用这些 用于连续无线监测ICP变化的传感器，不同小鼠的脑肿瘤模型 生存期，具体取决于肿瘤的侵入性（AIM 3）。 MRI，模拟和组织学将使用 验证ICP测量值。这些传感器在临床上需要监测不同脑部疾病的ICP， 包括肿瘤在内，我们设想它们的多功能设计将促进其临床应用。