Surface Plasmon Resonance Protein Array Phenotyping

提出了一种基于微阵列的系统，用于在非常小体积的组织或血液（约10 mL）中分析无标记，高通量蛋白质表达。该系统将由一个仪器和一个集成在流体盒中的蛋白质组生物传感器芯片组成。它采用了一种新型的光栅耦合表面等离子体共振（GC-SPR）成像技术，可以同时测量数千种分析物，而不受报告分子的限制。我们将使用细胞培养中细胞激活的快速评估作为模型系统来开发和评估基于GC-SPR芯片的技术。我们期望这项技术将为实验动物的代谢和生理表型分析以及研究人类遗传变异的代谢结果提供一个新的有力工具。它将适用于广泛的代谢产物、信号分子、激素、酶、受体和其他蛋白质的检测。例子包括细胞因子谱的快速测量，组织样品中多种激素浓度的同时测量，以及细胞内信号转导级联的评估。该技术也适用于临床环境中的微创微阵列，在这种环境中，诊断资料可以从一滴血中测量，而不是从静脉中采集大量样本。建议的商业应用：潜在的应用范围从基础研究到药物靶点发现到临床诊断。具体的例子包括蛋白质表达谱；高通量配体捕捞，鉴定新的受体和天然配体，免疫反应表征，蛋白质家族同源性研究，鉴定疾病标志物等。

A microarray-based system for label-free, high throughput protein expression in profiling in very small volumes of tissue or blood (approximately 10 mL) is proposed. The system will consist of an instrument, and a proteomic biosensor chip integrated into a fluidics cartridge. It utilizes a novel grating-coupled surface plasmon resonance (GC-SPR) imaging technology that will enable measurement of thousands of analytes simultaneously without the limitations of reporter molecules. We will use rapid assessment of cellular activation in cell cultures as a model system to develop and evaluate the GC-SPR chip- based technology. We expect that this technology will provide a new powerful tool for metabolic and physiologic phenotyping of laboratory animals as well as for investigating the metabolic outcome of genetic variation in humans. It will be applicable to the detection of a broad range of metabolic products, signaling molecules, hormones, enzymes, receptors and other proteins. Examples include rapid measurement of cytokine profiles, simultaneous measurement of many hormone concentrations in tissue samples, and assessment of intracellular signal transduction cascades. The technology is also suitable for minimally invasive microarrays in clinical settings where diagnostic profiles could be measured from a drop of blood instead of a large sample from a vein. PROPOSED COMMERCIAL APPLICATIONS: Potential applications range from basic research to drug target discovery to clinical diagnostics. Specific examples include protein expression profiling; high-throughput ligand fishing, identifying new receptors and natural ligands, immune response characterization, homology studies on protein families, identifying disease markers and others.