SBIR Topic 238 - Development of Clinical Automated Multiplex Affinity Capture Te

预计2006年将有200多万新的癌症病例。早期诊断以改善预后的必要性已得到充分证明。研究表明，在临床环境中，单分子标记物不能准确地诊断个体。常见的蛋白质发现技术缺乏在一次分析中定量测量多种生物标志物的能力，而较新的技术则缺乏灵敏度、精度和自动化。基于规则的医学（RBM）已经开发出基于头部的多重免疫测定法，用于执行生物标志物的多分析物谱（MAPs），解决了这些局限性。在第一阶段，将开发一种定量、自动化、5-plex免疫分析法，用于快速检测低丰度癌症相关蛋白。为了进一步增加该平台上内容的广度，需要开发和筛选数百到数千个配体结合分子的新方法。因此，在第一阶段，将开发一种创新的方法来快速筛选多个配体结合分子，以确定那些提供最佳MAP性能的分子。在第二阶段，我们建议通过筛选配体结合分子来验证第一阶段开发的筛选平台，以额外筛选45个靶点。在此过程中，将开发一种低丰度癌症相关蛋白的50倍免疫测定法（即肿瘤学MAP）。如果成功，该筛选平台和50层肿瘤MAP都将作为服务于制药、生物技术、医学和基础研究界的商业应用。

Over 2 million new cancer cases are expected in 2006. The need for early diagnostics that improve prognosis is well documented. Studies have shown that single molecular markers are not able to accurately diagnose individuals in the clinical setting. Common protein discovery technologies lack the ability to quantitatively measure multiple biomarkers in a single assay, while newer technologies suffer from a lack of sensitivity, precision and automation. Rules-Based Medicine (RBM) has developed bead-based multiplex immunoassays for performing Multi-Analyte Profiles (MAPs) of biomarkers that has addressed these limitations. In Phase I, a quantitative, automated, 5-plex immunoassay for the rapid detection of low abundance cancer-related proteins will be developed. To further increase the breadth of the content on this platform, new methods to both develop and screen hundreds to thousands of ligand binding molecules are needed. Thus, in Phase I, an innovative approach for the rapid screening of multiple ligand binding molecules to identify those providing optimal MAP performance will be developed. During Phase II, we propose to validate the screening platform developed in Phase I by screening ligand binding molecules for an additional forty-five targets. In doing this, a 50-plex immunoassay for low abundance cancer-related proteins (i.e., an Oncology MAP) will be developed. If successful, both the screening platform and the 50-plex Oncology MAP will have commercial application as a service to pharmaceutical, biotechnological, medical and basic research communities.