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 该建议是对NIH FOA（PAR-22-126）的回应，该提案“支持探索性研究，导致 开发生物医学研究的创新技术...“这个R21项目旨在利用高 光学显微镜和不对称双极微电极阵列的灵敏度和解决能力 一个低成本，高度敏感的双极电化学阵列平台，用于检测和计数个体 生物靶物种。 许多生物学或临床相关的物种，例如某些癌症生物标志物，以非常低 浓度，有时会降低几份。这些物种很难检测和量化 由于其敏感性，选择性和响应速度不足，现有的生物分析方法。到 应对这一挑战，我们建议开发一种双极电化学单实体生物分析仪，该分析仪 将使我们能够分析单个生物学物种，例如单个病毒和循环肿瘤外泌体。 该项目的成功建立在双极电化学阵列中PI小组的强大专业知识上， 微生物传感器和单实体电分析，具有三个特定的目的。 AIM 1构建 不对称的双极微电极阵列，包含250,000个电子和特征，并优化 它们用于单个实体分析。 AIM 2将合成并表征Janus PT/二氧化硅纳米颗粒（NP）和 使用它们将预核化的分析物物种标记在磁微珠上。 AIM 3将建立一个集成的 分析平台通过将双极微电极阵列与光学显微镜相结合，表征和 优化对假病毒颗粒和外泌体的单一实体生物分析的分析性能。 提出的分析平台具有创新性和强大的对单实体生物分析的功能 光学信号的放大和读取小的电化学信号。使用250,000的大阵列 双极微电极和用于预浓缩的磁珠进一步提高了灵敏度，选择性， 和吞吐量。未来的工作将开发独立的台式分析工具，这将很有用 为了在研究和诊断参与单实体生物分析中的一般使用。