Rapid Multi-Channel Serum Profiling for Liver Disease using Fluorescent Nanosensors

项目摘要/摘要 利用荧光纳米传感器快速检测肝病的多通道血清图谱 肝脏疾病的快速诊断对于优化患者预后和将经济影响降至最低至关重要。 目前检测肝损伤(纤维化/肝硬变)的策略使用昂贵的生物标记物策略 难以转化为适用于监测化疗患者的护理点(PoC)平台 以及发展中国家的诊断学。在初步研究中，我们已经证明了简单的聚合物- 基于传感器阵列的传感器可以产生可用于检测肝纤维化的临床 关联性。在我们提议的研究中，我们将： 目的1：制备发夹聚合物-荧光团偶联物，并将其用作传感器元件，以提供多个 通道输出血清传感。 目标2：将我们的聚合物固定在表面上，以提供适用于临床和 护理点使用。这些传感器将使用模型血清进行测试和优化。 目标3：应用我们的传感器系统，使用Rosenberg和 佩弗勒。这些研究将集中在肝纤维化的检测和分期上，使用统计学方法 由C.Rotello开发。 目的4：使用蛋白质组学和Vachet来表征与聚合物传感器结合的蛋白质，提供 机械论的洞察力和潜在的纤维化新生物标记物。 这项提议的目标是开发用于肝病诊断的原型传感器系统；有效 实现这一目标将提供可转化为许多其他疾病的战略 各州。

Project Summary/Abstract Rapid Multi-Channel Serum Profiling for Liver Disease using Fluorescent Nanosensors Rapid diagnosis of liver disease is crucial to optimizing patient outcome and minimizing economic impact. Current strategies for detecting liver damage (fibrosis/cirrhosis) use biomarker strategies that are expensive and difficult to translate into Point of Care (PoC) platforms suitable for monitoring of chemotherapy patients and diagnostics for the developing world. In preliminary studies we have demonstrated that simple polymer- based sensor arrays can generate serum ‘signatures’ that can be used to detect liver fibrosis with clinical relevance. In our proposed research we will: Aim 1: Fabricate hairpin polymer-fluorophore conjugates and use these as sensor elements to provide multi- channel outputs serum sensing. Aim 2: Immobilize our polymers onto surfaces to provide prototype sensing systems suitable for clinical and point-of-care use. These sensors will be tested and optimized using model sera. Aim 3: Apply our sensor systems to profile liver fibrosis using pathological samples provided by Rosenberg and Peveler. These studies will focus on detection and staging of liver fibrosis, using statistical methods developed by C. Rotello. Aim 4: Use proteomics with Vachet to characterize protein binding to the polymer sensors, providing mechanistic insight and potentially new biomarkers for fibrosis. The goal of this proposal is to develop prototype sensor systems for diagnosis of LIVER disease; effective achievement of this goal would provide strategies that could be translated to numerous additional disease states.