Highly sensitive immunoassay for determination of biomarkers for neurodegenerative diseases

用于测定神经退行性疾病生物标志物的高灵敏度免疫测定

基本信息

批准号：
10698757
负责人：
Simon Bystryak
金额：
$ 97.77万
依托单位：
ALLIED INNOVATIVE SYSTEMS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10698757
关键词：
Achievement Affect Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer’s disease biomarker Amyloid beta-42 Amyloid beta-Protein Antibodies Bacteria Binding Biochemical Reaction Biological Assay Biological Markers Biology Blood Blood specimen Brain-Derived Neurotrophic Factor Businesses Cerebrospinal Fluid Clinical Complex Coronavirus Detection Development Devices Diagnosis Diagnostic Diagnostic Reagent Kits Disease Drug Screening Enzyme-Linked Immunosorbent Assay Enzymes European Evaluation Studies Goals Horseradish Peroxidase Immune System Diseases Immunoassay Interleukins Label Legal patent Licensing Lighting Malignant Neoplasms Manuals Measures Mediating Medicine Methods Monitor Neurodegenerative Disorders Neurofibrillary Tangles Peptides Performance Phase Plasma Process Production Property Proteins Public Health Reaction Reagent Research Sampling Secure Serum Signal Transduction Solid System Technology Testing Time Visible Radiation analytical method antibody detection brain-derived neurotrophic factor precursor cost cost effective cytokine design detection assay detection method detection platform detection test early detection biomarkers improved innovation interest laboratory equipment manufacture new technology success tau Proteins tau-1 viral detection

项目摘要

Abstract The long-term objective of this proposal is to further develop a photochemical signal amplification method (PSAM) for increasing the sensitivity of conventional enzyme-linked immunosorbent assays (ELISA) for determination of biomarkers for various neurodegenerative diseases, such as Alzheimer’s Disease (AD). Immunoenzymatic methods such as ELISA are widely used in biology and medicine for drug screening, for detecting viruses (including coronaviruses), bacteria, and biomarkers, particularly cytokines and interleukins for cancer and immunological disorders, and biomarkers for neurodegenerative diseases. They are routinely used in manual, semi-automated, and automated systems where high volumes of tests are performed. However, in many cases the sensitivity of ELISA is inadequate. Some of the key biomarkers for early diagnosis of AD include three cerebrospinal fluid (CSF) biomarkers: amyloid ß-42 (Aß-42), which causes formation of oligomeric plaques, total tau (t-tau), and phosphorylated tau (p-tau) (which increases intracellular neurofibrillary tangles (NFTs). To date, there is no sensitive and cost- effective method for the quantification of these three proteins, hindering the diagnosis and progression monitoring of AD. Existing highly sensitive methods are cumbersome and expensive. Therefore, there is an increased necessity for a common ELISA platform to detect low levels of Aß-42, t-tau, p-tau and other biomarkers for various neurodegenerative diseases that is both inexpensive and simple enough to not require specialized laboratory equipment. In our Phase II project, we propose to further develop a very sensitive and inexpensive immunoassay platform for detection of biomarkers for various neurodegenerative diseases. In particular, we will 1) design and manufacture a pre-production PSAM illumination device; 2) design and develop a PSAM detection system kit, ELISA + PSAM kits for detection of Aß-42, t-tau, p-tau, BDNF and proBDNF; 3) conduct extensive performance evaluation studies towards Research Use Only applications of the PSAM products.

抽象的该提案的长期目标是进一步开发光化学信号放大方法 (PSAM) 用于提高传统酶联免疫吸附测定 (ELISA) 的灵敏度测定各种神经退行性疾病的生物标志物，例如阿尔茨海默病 (AD)。 ELISA等免疫酶方法广泛应用于生物学和医学领域的药物筛选、检测病毒（包括冠状病毒）、细菌和生物标志物，特别是细胞因子和白细胞介素癌症和免疫性疾病以及神经退行性疾病的生物标志物它们被常规使用。在执行大量测试的手动、半自动和自动化系统中。许多情况下 ELISA 的灵敏度不够。 AD 早期诊断的一些关键生物标志物包括三种脑脊液 (CSF) 生物标志物：淀粉样蛋白 ß-42 (Aß-42)，导致寡聚斑块、总 tau (t-tau) 和磷酸化 tau 蛋白的形成（p-tau）（它会增加细胞内神经原纤维缠结（NFT）。迄今为止，还没有敏感且成本高的方法定量这三种蛋白质的有效方法，阻碍了诊断和进展 AD 监测。现有的高灵敏度方法既麻烦又昂贵，因此越来越多。需要一个通用的 ELISA 平台来检测低水平的 Aß-42、t-tau、p-tau 和其他生物标志物各种神经退行性疾病既便宜又简单，不需要专门的治疗在我们的第二阶段项目中，我们建议进一步开发一种非常灵敏且廉价的实验室设备。特别是，我们将用于检测各种神经退行性疾病的生物标志物的免疫测定平台。 1) 设计和制造预生产的 PSAM 照明装置 2) 设计和开发 PSAM 检测；系统试剂盒、ELISA + PSAM 试剂盒用于检测 Aß-42、t-tau、p-tau、BDNF 和 proBDNF 3) 进行广泛的检测；针对 PSAM 产品仅供研究使用的应用的性能评估研究。