CAREER: Self-Clearing Glutamate Biosensor Towards Chronic Neurodegeneration Monitoring

职业：用于慢性神经退行性变监测的自清除谷氨酸生物传感器

• 批准号: 1944480
• 负责人: Hyowon Lee
• 金额: $ 50万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1944480&HistoricalAwards=false
• 关键词: CAREER; Self; Clearing; Glutamate; Biosensor

Enabling continuous monitoring of how our bodies change with age can significantly enhance our understanding of how many chronic illnesses progress and provide new opportunities for novel preventative treatments. However, even the state-of-the-art implantable biosensors currently have a limited lifetime of 14 days largely due to the body’s immune response, which continuously fouls the sensor surface. This CAREER project is aimed on creating a new class of implantable biosensors that can self-clear its sensing elements to allow truly longitudinal monitoring of various biomarkers for chronic neurodegenerative diseases. By utilizing a combination of active and passive anti-biofouling measures on printable biosensors, this work aims to improve the functional lifetime of these implantable biochemical sensors by an order of magnitude. Post-doctoral, graduate and undergraduate students working on this truly multidisciplinary project will receive a world-class training in biosensor development and learn fundamental skills in microfabrication, electrochemistry, and biosensor physics. The proposed research will also lead to complementary educational and outreach activities as a part the CAREER project. For example, in collaboration with the nationally recognized Purdue Engineering Projects in Community Service (EPICS), this program will increase adolescent (K–8) awareness of biomedical research within the context of the future medical devices using game-based learning. Biofouling is a significant challenge in the development of chronically reliable implantable biosensors. To minimize the immunogenic biofouling, various biomaterials have already been explored. However, most passive anti-biofouling approaches can only delay, not eliminate biofouling to extend the lifetime of these implantable biosensors. Building upon successful preliminary studies using active anti-biofouling magnetic microactuators and nanocomposite-based electrochemical biosensors, this CAREER proposal seeks to develop self-clearing biosensors that can be implanted for months and potentially years by passively preventing biofilm formation and actively clearing biofilm from the sensor surface. This novel microscale sensing platform will serve as the launchpad for a new class of implantable biosensors that can enable truly longitudinal in vivo monitoring of multiple analytes over the lifetime of patients. Using a combination of in vitro and in vivo models, the proposed research seeks to evaluate the chronic functional efficacy of this self-clearing biosensing platform to measure changes in glutamate, a key inflammatory biomarker in the brain that is linked to a number of neurodegenerative disorders. The results of this proposal will significantly advance our understanding on the limits of implantable microscale biosensors towards personalized continuous monitoring of chronic illnesses. Furthermore, the knowledge gained from this work will support the PI’s educational objectives to improve STEM pipeline for multidisciplinary biomedical engineering research by increasing the awareness of implantable microdevices in K-8 students and early career engineering students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

能够持续监测我们的身体如何随着年龄的增长而变化，可以显着提高我们对有多少慢性疾病进展的理解，并为新的预防性治疗提供新的机会。然而，即使是最先进的可植入生物传感器目前也只有14天的有限寿命，这主要是由于身体的免疫反应，这会持续污染传感器表面。该CAREER项目旨在创建一类新的可植入生物传感器，可以自清除其传感元件，从而真正纵向监测慢性神经退行性疾病的各种生物标志物。通过在可打印生物传感器上利用主动和被动抗生物污染措施的组合，这项工作旨在将这些可植入生化传感器的功能寿命提高一个数量级。从事这一真正多学科项目的博士后，研究生和本科生将接受生物传感器开发方面的世界级培训，并学习微细加工，电化学和生物传感器物理学方面的基本技能。拟议的研究还将导致补充教育和推广活动，作为职业生涯项目的一部分。例如，与国家认可的普渡大学社区服务工程项目（EPICS）合作，该计划将提高青少年（K-8）在未来医疗器械背景下使用基于游戏的学习对生物医学研究的认识。生物污染是长期可靠的植入式生物传感器开发中的一个重大挑战。为了使免疫原性生物污损最小化，已经探索了各种生物材料。然而，大多数被动抗生物污染方法只能延迟生物污染，而不能消除生物污染以延长这些可植入生物传感器的寿命。基于使用主动抗生物污染磁性微致动器和基于纳米复合材料的电化学生物传感器的成功初步研究，该CAREER提案旨在开发自清洁生物传感器，通过被动防止生物膜形成和主动清除传感器表面的生物膜，可以植入数月甚至数年。这种新型的微尺度传感平台将作为一类新的可植入生物传感器的发射台，可以在患者的一生中对多种分析物进行真正的纵向体内监测。使用体外和体内模型的组合，拟议的研究旨在评估这种自清除生物传感平台的慢性功能功效，以测量谷氨酸的变化，谷氨酸是大脑中与许多神经退行性疾病相关的关键炎症生物标志物。这项提案的结果将大大推进我们对植入式微型生物传感器的局限性的理解，以实现对慢性疾病的个性化连续监测。此外，从这项工作中获得的知识将支持PI的教育目标，通过提高K-8学生和早期职业工程学生对植入式微型设备的认识，改善多学科生物医学工程研究的STEM管道。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Wearable Glucose Monitoring and Implantable Drug Delivery Systems for Diabetes Management

• DOI: 10.1002/adhm.202100194
• 发表时间: 2021-04
• 期刊: Advanced Healthcare Materials
• 影响因子: 10
• 作者: Jinyuan Zhang;Jian Xu;Jongcheon Lim;James K. Nolan;Hyowon Lee;Chi Hwan Lee