Lateral Flow Based Nanoelectronic Sensing Array for Detection of Chronic Cerebral Hypoperfusion Biomarkers

基于横向流动的纳米电子传感阵列用于检测慢性脑灌注不足生物标志物

• 批准号: 1916894
• 负责人: Yuxin Liu
• 金额: $ 40万
• 依托单位: West Virginia University Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1916894&HistoricalAwards=false
• 关键词: Lateral; Flow; Based; Nanoelectronic; Sensing

Ability to understand and diagnose disease has experienced considerable progress over the past decades due to the advances in quantifications of molecular biomarkers. Commonly used methods for quantifying protein markers in a clinical setting are immunonephelometry or enzyme-linked immunosorbent assay. Both require a centralized lab to separate whole blood and to perform multiple strict washing steps over several hours. Also, proper infrastructure and a higher degree of training are required, and therefore expensive. This project aims to develop an enabling technology by integrating highly sensitive nanoelectronic immunoassay arrays and lateral flow devices for detecting protein biomarkers with improved diagnostic modalities, capable of using minimal amounts of blood and of returning rapid results. The results from this project can lead to the development of a generic platform for detecting a broad range of molecular biomarkers in assisting earlier disease diagnostics and assessment and monitoring treatment outcome. The applied technologies built from low-cost microfabrication and nanoelectronic detection would significantly reduce the costs for healthcare delivery, and be especially beneficial for regions with limited access to healthcare. Additionally, this project offers opportunities for integrating students' educational experience across interdisciplinary areas, stimulates students' interests in the fields of science, technology, engineering, and mathematics, encourages the participation of underrepresented groups, develops curriculum with new resources, and boosts the biomedical engineering program at West Virginia University.Chronic cerebral hypoperfusion has been considered a significant cause for vascular dementia and Alzheimer's disease associated with reduced blood supply and gradually damaged regions of the brain which are responsible for memory, cognition, and behavior. It is vital to diagnose chronic cerebral hypoperfusion as early as possible because the prompt institution of drugs for increasing cerebral blood flow improves outcomes and delays the onset of advanced dementia. The objective of the research is to develop an integrated multiplexed detection immunoassay for rapid-detecting chronic cerebral hypoperfusion biomarkers. Three research tasks have been proposed to accomplish the study. First, a nanoelectronic immunoassay array will be developed, fabricated, and optimized. The nanoelectronic immunoassay array will allow well regulation of matrix effects of electrolytes and statistical validation of measured results. Second, the nanoelectronic immunoassay array will be integrated with a lateral flow device to realize a portable and capillary driven platform with minimizing the need for off-chip equipment. The integrated device is capable of real-world sample pretreatment, fluid transport, and single biomarker detection. Third, multiplexed detection of biomarkers will be conducted and corroborated by a clinically relevant chronic cerebral hypoperfusion model to determine the most informative combinations of biomarkers. By accomplishing the proposed tasks, the integrated device will allow generation of more meaningful and conclusive information for clinical diagnosis. This project is jointly supported by the Electronics, Photonics and Magnetic Devices (EPMD) Program of the Electrical, Communications and Cyber Systems (ECCS) Division and the Established Program to Stimulate Competitive Research (EPSCoR).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.

在过去的几十年里，由于分子生物标志物定量的进步，理解和诊断疾病的能力已经经历了相当大的进步。在临床环境中用于定量蛋白质标志物的常用方法是免疫比浊法或酶联免疫吸附测定法。两者都需要一个集中的实验室来分离全血，并在几个小时内执行多个严格的洗涤步骤。此外，还需要适当的基础设施和更高程度的培训，因此费用昂贵。该项目旨在开发一种使能技术，将高灵敏度的纳米电子免疫测定阵列和侧流装置结合起来，以改进的诊断方式检测蛋白质生物标志物，能够使用最少量的血液并快速返回结果。该项目的结果可以导致开发一个通用平台，用于检测广泛的分子生物标志物，以协助早期疾病诊断和评估以及监测治疗结果。从低成本微制造和纳米电子检测构建的应用技术将大大降低医疗保健提供的成本，特别有利于医疗保健有限的地区。此外，该项目还提供了整合学生跨学科领域教育经验的机会，激发学生对科学、技术、工程和数学领域的兴趣，鼓励代表性不足的群体参与，利用新资源开发课程，并促进了西弗吉尼亚大学的生物医学工程项目。慢性脑灌注不足被认为是血管性脑损伤的重要原因。痴呆症和阿尔茨海默氏病与血液供应减少和负责记忆、认知和行为的大脑区域逐渐受损有关。尽早诊断慢性脑灌注不足是至关重要的，因为及时使用增加脑血流量的药物可以改善预后并延迟晚期痴呆的发作。本研究的目的是建立一种快速检测慢性脑灌注不足生物标志物的综合多重检测免疫分析方法。为了完成这项研究，提出了三项研究任务。首先，将开发、制造和优化纳米电子免疫分析阵列。纳米电子免疫分析阵列将允许很好地调节电解质的基质效应和测量结果的统计验证。其次，纳米电子免疫分析阵列将与侧流装置集成，以实现便携式和毛细管驱动的平台，最大限度地减少对芯片外设备的需求。该集成设备能够进行真实世界的样品预处理、流体输送和单一生物标志物检测。第三，将进行生物标志物的多重检测，并通过临床相关的慢性脑灌注不足模型进行证实，以确定信息量最大的生物标志物组合。通过完成所提出的任务，集成设备将允许生成用于临床诊断的更有意义和结论性的信息。 该项目由电气、通信和网络系统（ECCS）部门的电子、光子和磁器件（EPMD）项目以及刺激竞争性研究的既定项目（EPSCoR）联合支持。该奖项反映了NSF的法定使命，并通过使用基金会的知识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

Role of B cells and the aging brain in stroke recovery and treatment

• DOI: 10.1007/s11357-020-00242-9
• 发表时间: 2020-08-07
• 期刊: GEROSCIENCE
• 影响因子: 5.6
• 作者: Engler-Chiurazz, E. B.;Monaghan, K. L.;Ren, X.
• 通讯作者: Ren, X.