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

描述（由申请人提供）：这项拟议的研究重点是先进的开发和验证一个创新的，可扩展的诊断平台，以显着提高早期癌症检测和癌症风险评估通过超灵敏读出的生物标志物面板。通过将灵敏的Sers检测与纳米颗粒标记、增强的分析物递送和免疫测定体系结构耦合来实现的表面增强拉曼散射（Sers）免疫测定诊断平台的创建将导致能够进行多重生物标志物检测的简单平台。这种对一组生物标志物的智能使用将成为亚临床癌症检测成为现实的基石。这项工作的组成部分是使用胰腺癌（PA）作为疾病模型来验证平台。PA表现出与大多数无症状进展的疾病共同的特征，包括没有一个具有高临床敏感性和特异性的理想肿瘤标志物。由于PA的发生是由个体中的一系列致病突变引起的，因此具有重叠检测能力的多个生物标志物的面板可能提供更高的准确性。从已经单独证明有限相关值的标记物组装这样的面板提供了评估Sers平台的品质因数和多路复用能力的工具。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遥不可及，部分原因是我们在技术上无法轻松筛选单个样本中的大量生物标志物，这些生物标志物可能构成“疾病地图”，而且这样做的成本使每个人都能进行常规检测。Sers平台旨在消除这一障碍。一旦经过验证，该平台还可用于标记物和标记物组发现，并且独特地适合于快速部署，作为具有成本效益的便携式和强大的系统，用于临床环境中的多重诊断测定，或形成个性化医疗基础设施的重要组成部分。 公共卫生相关性：该提案旨在使公众能够获得早期癌症检测和相关的改善结果的承诺。目前的技术限制阻碍了从个体患者中快速筛选大量生物标志物的能力，该方法据称具有优于单一生物标志物的改善的诊断、预后和治疗功效。该项目建议开发一个平台，使用快速，具有成本效益的光学检测技术，同时测量一滴血中的数百种生物标志物。

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. PUBLIC HEALTH RELEVANCE: This proposal seeks to make early cancer detection and the associated promise of improved outcomes accessible to the general public. Current technical limitations have hindered the ability to rapidly screen large numbers of biomarkers from individual patients, a method purported to have improved diagnostic, prognostic, and therapeutic efficacy over a single biomarker. The project proposes developing a platform that uses a rapid, cost-effective optical detection technology to simultaneously measure hundreds of biomarkers in a single drop of blood.