A Bipolar Electrochemical Single Entity Bioanalyzer

双极电化学单一实体生物分析仪

• 批准号: 10644615
• 负责人: Bo Zhang
• 金额: $ 17.95万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644615
• 关键词: Address; Adsorption; Biological; Biological Process; Biomedical Research; Blood; Cell Extracts; Chemicals; Coupled; Development; Diagnosis; Diagnostic; Electrochemistry; Electrodes; Elements; Film; Future; Geometry; Individual; Knowledge; Label; Lead; Learning; Ligands; Liquid substance; Magnetism; Metals; Methods; Microelectrodes; Microfabrication; Microscope; Microscopy; Microspheres; Mission; National Institute of General Medical Sciences; Nucleic Acids; Optics; Oxidation-Reduction; Oxygen; Performance; Reaction; Research; Risk; Role; Saliva; Side; Signal Transduction; Silicon Dioxide; Speed; Surface; Testing; Tissue Extracts; United States National Institutes of Health; Virus; Work; amplification detection; analytical method; cancer biomarkers; charge coupled device camera; clinically relevant; cost; design; detection platform; exosome; experience; indium tin oxide; innovation; innovative technologies; instrument; instrumentation; light transmission; magnetic beads; magnetic field; meter; nanofabrication; nanoparticle; operation; oxidation; particle; parylene; receptor; response; sensor; success; tool; tumor; voltage

Abstract This proposal is in response to NIH FOA (PAR-22-126), which “supports exploratory research leading to the development of innovative technologies for biomedical research...” This R21 project aims to harness the high sensitivity and resolving power of optical microscopy and asymmetric bipolar microelectrode arrays to develop a low-cost, highly sensitive bipolar electrochemical array platform for detecting and counting individual biological target species. Many biologically or clinically relevant species, such as certain cancer biomarkers, present at very low concentrations, sometimes down to a few copies. These species have been difficult to detect and quantify with existing bioanalytical methods due to their insufficient sensitivity, selectivity, and response speed. To address this challenge, we propose to develop a bipolar electrochemical single entity bioanalyzer, which will allow us to analyze individual biological species, such as single viruses and circulating tumor exosomes. The success of this project builds upon the strong expertise of the PI’s group in bipolar electrochemical arrays, microfabricated sensors, and single entity electroanalysis and has three specific aims. Aim 1 builds the asymmetric bipolar microelectrode arrays containing 250,000 electrodes and characterizes and optimizes them for single entity analysis. Aim 2 will synthesize and characterize Janus Pt/silica nanoparticles (NPs) and use them to label analyte species pre-concentrated onto magnetic microbeads. Aim 3 will build an integrated analytical platform by combining the bipolar microelectrode array with optical microscopy, characterize and optimize its analytical performance for single entity bioanalysis of pseudovirus particles and exosomes. The proposed analytical platform is innovative and powerful for single entity bioanalysis due to the use of an optical signal to amplify and read a small electrochemical signal. The use of a large array of 250,000 bipolar microelectrodes and magnetic beads for pre-concentration further enhances the sensitivity, selectivity, and throughput. Future work will develop a standalone benchtop analytical instrument, which will be useful for their general use in research and diagnosis involving single entity bioanalysis.

抽象的 该提案是对 NIH FOA (PAR-22-126) 的回应，该提案“支持探索性研究，以实现 开发生物医学研究的创新技术......”这个 R21 项目旨在利用高 光学显微镜和非对称双极微电极阵列的灵敏度和分辨率，以开发 用于检测和计数个体的低成本、高灵敏度双极电化学阵列平台 生物目标物种。 许多生物学或临床相关的物种，例如某些癌症生物标志物，其含量非常低 浓度，有时低至几个副本，这些物种很难检测和量化。 现有的生物分析方法由于其灵敏度、选择性和响应速度不足。 为了应对这一挑战，我们建议开发一种双极电化学单一实体生物分析仪， 将使我们能够分析单个生物物种，例如单个病毒和循环肿瘤外泌体。 该项目的成功建立在 PI 团队在双极电化学阵列方面的强大专业知识的基础上， 目标 1 构建了微制造传感器和单一实体电分析，并具有三个具体目标。 包含 250,000 个电极的非对称双极微电极阵列及其特性和优化 Aim 2 将合成并表征 Janus Pt/二氧化硅纳米粒子 (NP) 和 使用它们来标记预浓缩到磁性微珠上的分析物种类，Aim 3 将构建一个集成的。 通过将双极微电极阵列与光学显微镜相结合的分析平台，表征和 优化其对假病毒颗粒和外泌体的单一实体生物分析的分析性能。 所提出的分析平台对于单一实体生物分析来说是创新且强大的，因为使用 使用 250,000 个大阵列来放大和读取小型电化学信号。 双极微电极和磁珠预浓缩进一步提高了灵敏度、选择性、 未来的工作将开发一种独立的台式分析仪器，这将是有用的。 它们在涉及单一实体生物分析的研究和诊断中的一般用途。