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）中进行无标记、高通量蛋白表达谱分析。该系统将由一个仪器和一个集成到射流盒中的蛋白质组生物传感器芯片组成。它利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。我们将使用快速评估细胞培养物中的细胞活化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以及研究人类遗传变异的代谢结果提供一个新的强大工具。它将适用于检测广泛的代谢产物、信号分子、激素、酶、受体和其他蛋白质。例如，快速测量细胞因子谱，同时测量组织样品中的许多激素浓度，以及评估细胞内信号转导级联。该技术也适用于临床环境中的微创微阵列，其中诊断谱可以从一滴血而不是静脉的大样本中测量。拟议的商业应用：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，识别新的受体和天然配体，免疫反应表征，蛋白质家族的同源性研究，识别疾病标志物等。

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.