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

描述(申请人提供)：这项拟议的研究侧重于创新的、可扩展的诊断平台的高级开发和验证，以通过生物标志物面板的超灵敏读数显著改进癌症早期检测和癌症风险评估。通过将敏感的表面增强拉曼散射(SERS)检测与纳米颗粒标记、增强的分析物传递和免疫分析体系相结合来实现表面增强拉曼散射(SERS)免疫分析诊断平台的创建，将产生一个能够进行多路生物标志物检测的简单平台。这种生物标志物面板的智能使用将成为实现亚临床癌症检测的基石。这项工作的一个组成部分是使用胰腺癌(PA)作为疾病模型来验证该平台。PA表现出大多数疾病无症状进展的共同特征，包括缺乏一种具有高临床敏感度和特异度的理想肿瘤标志物。由于PA的发展是由个体的一系列致病突变引起的，具有重叠检测能力的多个生物标记物的组合可能提供更高的准确性。将已分别显示出有限相关价值的标记组装成这样一个面板，为评估SERS平台的优劣系数和多路复用能力提供了一种工具。目前，我们识别健康风险、疾病易感性和对治疗的反应的能力仍然无法实现，部分原因是我们在技术上无法轻松地对单个样本进行筛选，以大量生物标记物潜在地构成“疾病地图”，并以使每个人都能进行常规检测的成本做到这一点。SERS平台旨在消除这一障碍。经过验证后，该平台还可用于标记和标记面板发现，特别适合作为一种经济高效、便携且功能强大的系统快速部署，用于临床环境中的多路诊断分析，或构成个性化医疗基础设施的重要组成部分。

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.