Protein Microarray System for Rheumatiod Arthritis Diagnosis

描述(申请人提供)：类风湿性关节炎(RA)和其他自身免疫性疾病的诊断是一项复杂的挑战，它结合了一系列生理线索的解释和分子分析。传统上，放射摄影术一直被用来测量RA的进展。RA及相关疾病的体外诊断试验几乎完全由单标志物试验组成。在自身免疫性疾病中，有一个公认但尚未得到满足的需求，即基于生物标记物的改进诊断，以表征疾病类型、状态、进展和对治疗的反应。我们建议开发一个集成的生物分析平台和临床研究计划，以促进在并行检测多个生物标志物的基础上对患者样本进行全面的差异表型分析，当将其解释为一种模式时，将产生高度预测和准确的分析。通过这种先进的蛋白质分子诊断方法获得的整体临床图像将为临床医生在自身免疫性疾病的治疗中早期发现、分类和预后、评估治疗和监测复发提供强有力的工具。反过来，这应导致改善患者护理、改善结果和降低患者护理成本。拟议的系统将由三个关键要素组成：一个仪器、一个蛋白质芯片微阵列盒和用于分析的模式识别软件。目标蛋白质生物标记物的高度平行检测是基于一种先进的无标记检测技术，我们称之为光栅耦合表面等离子体共振成像(GCSPRI)。这种基于芯片的技术使以极小的样本量(~5-50？L)以接近实时的成本效益地同时测量成百上千种分析物成为可能。长期目标(在第二阶段结束时)是为能够迅速获得FDA批准奠定必要的基础。第一阶段(两年)的更有限的目标是开发一个由仪器和试剂盒组成的综合原型生物分析诊断平台，并开发和验证旨在分析人体样本中相关分析物存在的芯片。在第一阶段开发的平台将在第二阶段用于人体临床研究。7.项目简介拟议的研究旨在改进类风湿性关节炎和其他自身免疫性疾病的诊断方法，这些疾病影响着5000多万美国人，是导致死亡和残疾的主要原因。预期的产品有望改善治疗，减少发病率，并改善这些疾病患者的生活质量。

DESCRIPTION (provided by applicant): The diagnosis of rheumatoid arthritis (RA) and other autoimmune disease is a complex challenge that combines the interpretation of a range of physiological cues and molecular assays. Traditionally, radiography has been used to measure RA progression. In vitro diagnostic tests for RA and related diseases consist almost exclusively of single marker tests. There is a well-recognized but unmet need for improved diagnostics based on biological markers to characterize disease type, status, progression, and response to therapy in autoimmune diseases. We are proposing to develop an integrated bioanalytical platform and a clinical research program to facilitate comprehensive differential phenotyping of patient samples on the basis of parallel detection of multiple biomarkers, which when interpreted as a pattern will result in highly predictive and accurate assays. The holistic clinical picture obtained from this advanced protein molecular diagnostic approach will provide the clinician with a powerful tool for early detection, classification, and prognosis, assessment of therapy and monitoring of recurrence, in the treatment of autoimmune disease. This, in turn, should lead to improved patient care, better outcomes and reduced patient care costs. The proposed system will consist of three key elements: an instrument, a protein chip microarray cartridge, and pattern recognition software for analysis. Highly parallel detection of the targeted protein biomarkers is based on an advanced label-free detection technology that we refer to as Grating-Coupled Surface Plasmon Resonance Imaging (GCSPRI). This chip-based technology makes it possible to cost-effectively measure hundreds of analytes simultaneously in near-real time in minute sample volumes (~5 - 50 ¿L). The long-term goal (at the end of Phase II) is to have developed the necessary foundation to be able to proceed expeditiously with FDA approval. The more limited goals of the Phase I (two years) are to develop an integrated prototype bioanalytical diagnostic platform consisting of an instrument and reagent cartridge and to develop and validate a chip designed to assay the presence of relevant analytes in human samples. The platform developed in Phase I would be used in Phase II for human clinical studies. 7. Project Narrative The proposed research aims to develop improved diagnostic methods for rheumatoid arthritis and other autoimmune diseases which affect over 50 million Americans and are a leading cause of death and disability. Anticipated products are expected to improve treatment, reduce morbidity and improve the quality of life of patients suffering from these diseases.