Advanced Development of a Multiplexed SERS-based Biomarker Detection Platform: A

基于多重 SERS 的生物标志物检测平台的高级开发：A

• 批准号: 8336835
• 负责人: SEAN J MULVIHILL
• 金额: $ 33.44万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8336835
• 关键词: Address; Adsorption; Advanced Development; Aliquot; Antigens; Architecture; Attention; Benchmarking; Benign; Biological Assay; Biological Markers; Blood; Cancer Detection; Clinical; Clinical Sensitivity; Complex; Coupling; Detection; Development; Diagnosis; Diagnostic; Disease; Disease model; Disease susceptibility; Dose; Drops; Early Diagnosis; Effectiveness; Electrodes; Enzymes; Exhibits; Future; General Population; Goals; Gold; Grant; Health; Immunoassay; Individual; Label; Laboratories; Link; Malignant Neoplasms; Maps; Measures; Medicine; Methodology; Methods; Metric; Monoclonal Antibodies; Mutation; Neoplasms; Optics; Outcome; Pancreatic Adenocarcinoma; Patients; Performance; Phase; Physicians' Offices; Preparation; Primary Care Physician; Procedures; Proteins; Protocols documentation; Research; Research Infrastructure; Risk; Risk Assessment; Sampling; Screening for cancer; Screening procedure; Sensitivity and Specificity; Serum; Serum Markers; Speed; Staging; Surface; System; Technology; Testing; Treatment Efficacy; Tumor Markers; United States National Institutes of Health; Validation; Work; advanced disease; base; biochip; cancer risk; chronic pancreatitis; cohort; combat; cost; cost effective; design; diagnostic accuracy; improved; innovation; internal control; nanoparticle; prognostic; research study; response; trait

DESCRIPTION (provided by applicant): This proposed research focuses on the advanced development and validation of an innovative, extensible diagnostics platform to markedly improve early cancer detection and cancer risk assessment through the ultrasensitive readout of biomarker panels. The creation of a surface-enhanced Raman scattering (SERS) immunoassay diagnostic platform, realized by coupling sensitive SERS detection with nanoparticle labels, enhanced analyte delivery, and immunoassay architectures, will result in a simple platform capable of multiplexed biomarker detection. This intelligent use of a panel of biomarkers will serve as the cornerstone in making subclinical cancer detection a reality. Integral to this work is the use of pancreatic adenocarcinoma (PA) as a disease model to validate the platform. PA exhibits traits common to most diseases that progress asymptomatically, including the unavailability of one ideal tumor marker with high clinical sensitivity and specificity. Since development of PA arises from a range of causative mutations in individuals, a panel of multiple biomarkers with overlapping detection capabilities is likely to provide improved accuracy. Assembly of such a panel from markers that have demonstrated limited correlative value individually provides a vehicle to assess the figures of merit and multiplexing ability of the SERS platform. Currently, our ability to identify health risk, disease susceptibility, and response to therapy remains unreachable due in part to our technical inability to easily screen a single sample for the large number of biomarkers that potentially make up a "disease map" and to do so at costs that enable routine testing for everyone. The SERS platform is designed to remove this hurdle. Once validated, the platform could also be used for marker and marker panel discovery and is uniquely suited for rapid deployment as a cost-effective, portable, and robust system for multiplexed diagnostic assays in a clinical setting or to form an essential part of the personalized medicine infrastructure.

描述（由申请人提供）：这项拟议的研究重点介绍了创新的，可扩展的诊断平台的高级开发和验证，可通过对生物标志物面板的超敏感读数明显改善早期癌症检测和癌症风险评估。创建表面增强的拉曼散射（SERS）免疫测定诊断平台，该平台通过将敏感的SERS检测与纳米颗粒标签耦合，增强的分析物和免疫测定结构来实现，将导致一个简单的平台，该平台能够通过多路生生物标记的检测来实现。这种智能使用一组生物标志物将是使亚临床癌症检测成为现实的基石。这项工作不可或缺的是将胰腺腺癌（PA）用作验证平台的疾病模型。 PA表现出对大多数疾病的共同性状，这些疾病无症状，包括一个具有高临床敏感性和特异性的理想肿瘤标记物的不可用。由于PA的发展源于个体中的一系列致病突变，因此具有重叠检测能力的多个生物标志物的小组可能会提供提高的准确性。来自标记的这样一个面板的组装分别显示出有限的相关值，这提供了一种评估SERS平台的功绩和多路复用能力数字的工具。当前，我们鉴定健康风险，疾病敏感性和对治疗的反应的能力部分是由于我们的技术无法轻松筛选一个样本的大量生物标志物，这些生物标志物可能构成了“疾病图”，并以此为代价而造成常规测试。 SERS平台旨在消除此障碍。一旦得到验证，该平台也可以用于标记和标记面板发现，并且非常适合快速部署，作为一种具有成本效益，便携式且健壮的系统，用于在临床环境中用于多重诊断测定法，或者构成个性化医学基础设施的重要组成部分。