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.

项目概述：本提案描述了一个为期五年的研究和职业发展计划， 博士Razieh Khalifehzadeh作为独立调查员的职业生涯。该计划将建立在博士。 Khalifehzadeh作为生物工程科学家的多学科背景，在生物电子学，生物材料 和基础癌症研究，通过提供设计灵活和高灵敏度压力传感器的专业知识， 与脑肿瘤相关的颅内压（ICP）的连续无线监测。PI将 曾在斯坦福大学工程与医学学院接受鲍哲南博士（主要导师，灵活， 可穿戴生物电子学），Sanjiv S. Gambhir（癌症诊断、癌症生物工程和癌症联合导师 Heike Daldrup-Link（脑癌成像和治疗的共同导师，以及促进纳米技术的领导者） 多样性），Ada Poon（合作者，无线生物电子学），Melanie Hayden（合作者，神经外科和 神经学）和Eric阿佩尔（合作者，生物材料和生物相容性）。 脑肿瘤通常与颅内压升高有关。高血压的延误诊断和治疗 ICP常导致不可逆的神经损伤甚至死亡。拟议的总体目标 研究是设计高灵敏度和大脑兼容的压力传感器，可以无线检测ICP 变异，作为脑肿瘤患者中通常被忽视的神经学标志物。最近，我开发了超小型 （3×3×0.1 mm 3）、柔性和植入式压力传感器，可有效无线监测ICP U87脑肿瘤生长小鼠模型在30天生存期内的变化。的关键部件 这些压力传感器是具有特定压力响应微图案的中间弹性体层， 定义了这些设备在大脑中长期精确测量的一致灵敏度。目标1， 在这个项目中，我将研究这种弹性体层的新设计，以进一步提高灵敏度和长期- 我的压力传感器的长期机电稳定性。此外，我将使用实验和模拟， 找到用于更有效的无线信号传输的替代设计（即，更高的信噪比） 传感器.我还将开发一个手持无线信号记录设置，使记录和快速分析， 使用智能手机的无线压力数据，更容易在体内测量和未来的护理点 应用.目标2的重点是延长传感器的植入后寿命和大脑兼容性 用聚对二甲苯（厚度约1-4 µm）涂覆。聚对二甲苯已被广泛用作保护涂层， 神经接口和心脏辅助装置，以提高其植入后寿命。最后，我将使用这些 用于连续无线监测不同小鼠脑肿瘤模型中ICP变化的传感器， 生存期，取决于肿瘤的侵袭性（目的3）。将使用MRI、模拟和组织学 以验证ICP测量结果。这些传感器在临床上需要用于监测不同脑部疾病中的ICP， 包括肿瘤，我们设想它们的多功能设计将促进它们的临床应用。