A rapid solution-phase immunoassay for proteomics

蛋白质组学的快速溶液相免疫分析

• 批准号: 7435119
• 负责人: Steven Patrick Tyrrell
• 金额: $ 9.98万
• 依托单位: CONTROLLED PROCESS TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2008-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7435119
• 关键词: Antibodies; Antigen-Antibody Complex; Applications Grants; Area; Authorship; Basic Science; Binding; Biological Assay; Biological Markers; Biotin; Buffers; Clinical; Clinical Medicine; Complex; Concentration measurement; Condition; Costs and Benefits; Depth; Detection; Development; Device or Instrument Development; Dextrans; Diagnosis; Diagnostic; Disease; Dose; Electrophoresis; Enzyme-Linked Immunosorbent Assay; Exhibits; Goals; Healthcare; Heart; Human; Human Chorionic Gonadotropin; Human Genome Project; Human body; Immunoassay; Interleukin-6; Investigation; Laboratories; Lead; Legal patent; Malignant Neoplasms; Marketing; Measurement; Measures; Medical; Modern Medicine; Monitor; Numbers; Peer Review; Performance; Persons; Phase; Plasma; Polymers; Population; Problem Solving; Process; Protein Binding; Proteins; Proteomics; Publications; Range; Reaction; Relative (related person); Reproducibility; Research; Saliva; Sampling; Sensitivity and Specificity; Solutions; Speed; Techniques; Technology; Time; Transferrin; Validation; Work; antibody conjugate; antigen binding; assay development; base; clinically relevant; cost; dextran; experience; fluorophore; instrument; instrumentation; neutravidin; polyacrylamide; pressure; prototype; response; self assembly; success; voltage

DESCRIPTION (provided by applicant): Described herein is the development of the "EVEIA" immunoassay that has the potential to supplant existing techniques for the validation of low-abundance biomarkers. Protein assays are a core technology of modern medicine, as nearly all diseases (including cancer) can be detected by monitoring protein concentrations in the human body (e.g. PSA, BRAC-1&2). However, the validation of newly identified low-abundance biomarkers (a rapidly growing list due to the Human Genome Project) is an area that is not well-served by current technology. EVEIA will become the platform of choice for biomarker validation mainly by displaying the superior sensitivity necessary for meaningful measurements of low-abundance proteins, but also by providing simpler assay development and being easier to use than other "high sensitivity" assay platforms. Success in the validation arena should also lead to opportunities in the diagnostics market. Low-abundance proteins are hard to measure, especially in clinically relevant contexts such as plasma or saliva. This difficulty leads to a non-productive cycle in the research and clinical arenas in regards to such proteins. Since it is difficult to determine the clinical relevance of a protein that is difficult to measure, there is little demand for instruments to measure such proteins in the clinical laboratories. Conversely, with little clinical demand, there is little pressure to determine the clinical relevance of these low-abundance proteins. Unfortunately, most new protein discoveries can be expected to be found in low abundance. An instrument or assay that would make the measurement of such proteins easier would speed research and enhance clinical medicine. This application describes the basic, ongoing development of EVEIA, including comparisons with existing high-sensitivity assays. Controlled Process Technologies (CPT) has assembled a team with over 80 person-years of laboratory and instrument development experience, with authorship of nearly one hundred peer-reviewed publications and more than 15 issued patents. This team has the expertise to bring the EVEIA assay to the point that its applications in both the research and clinical laboratory are readily apparent. As specifically applied to cancer health-care, the EVEIA technology has the potential to greatly expand the population of available biomarkers by allowing the validation and analysis of low-abundance proteins that can be used for the diagnosis, monitoring, and basic research of human cancer. CPT is developing a protein immunoassay and instrumentation that is expected to have a level of sensitivity two to three orders of magnitude better than existing commercial instruments, while maintaining ease-of-use and cost benefits. Such an instrument will allow the study and detection of protein biomarkers discovered by the Human Genome Project that are normally found in concentrations too low for easy detection by current technology. Biomarkers that might be otherwise ignored could therefore become generally available for medical diagnosis and research.

描述（由申请人提供）：本文描述的是“EVEIA”免疫测定法的开发，该方法有可能取代现有的低丰度生物标志物验证技术。蛋白质检测是现代医学的核心技术，因为几乎所有疾病（包括癌症）都可以通过监测人体内的蛋白质浓度来检测（例如PSA， brac -1和2）。然而，新发现的低丰度生物标志物（由于人类基因组计划而快速增长的列表）的验证是当前技术无法很好地服务的领域。EVEIA将成为生物标志物验证的首选平台，主要是因为它具有对低丰度蛋白质进行有意义测量所必需的卓越灵敏度，而且还提供了比其他“高灵敏度”分析平台更简单的分析开发和更容易使用。验证领域的成功也会带来诊断市场的机会。低丰度蛋白质很难测量，特别是在临床相关的情况下，如血浆或唾液。这一困难导致了这类蛋白质在研究和临床领域的非生产性循环。由于难以确定难以测量的蛋白质的临床相关性，因此临床实验室对测量此类蛋白质的仪器的需求很少。相反，由于临床需求很少，因此确定这些低丰度蛋白的临床相关性的压力很小。不幸的是，大多数新发现的蛋白质都是低丰度的。如果有一种仪器或检测方法能使这类蛋白质的测量变得更容易，将会加快研究速度，提高临床医学水平。本申请描述了EVEIA的基本、正在进行的发展，包括与现有高灵敏度分析的比较。控制过程技术（CPT）组建了一支拥有超过80人年的实验室和仪器开发经验的团队，拥有近百篇同行评审出版物的作者和超过15项专利。该团队拥有专业知识，可以将EVEIA检测方法应用于研究和临床实验室。由于EVEIA技术专门应用于癌症医疗保健，因此可以对可用于诊断、监测和人类癌症基础研究的低丰度蛋白质进行验证和分析，从而有可能大大扩大可用生物标志物的数量。CPT正在开发一种蛋白质免疫测定和仪器，预计其灵敏度水平比现有的商业仪器高2到3个数量级，同时保持易用性和成本效益。这种仪器将允许研究和检测人类基因组计划发现的蛋白质生物标记物，这些标记物通常在浓度过低的情况下被现有技术容易检测到。因此，可能被忽视的生物标记物可以普遍用于医学诊断和研究。