SBIR Phase I: Proteomic-Based Detection Technology

这个小型企业创新研究(SBIR)第一阶段项目将开发基于蛋白质组学的安全技术，其中将包括基于亲和力的质谱分析和用于检测生物防御剂的软件。现有的用于特定微生物病原体的蛋白质组检测的免疫分析方法对可能由自发或故意的生物毒素修饰而引起的结构偏差不敏感。这些检测方法可能无法检测到基因工程生物毒素，也无法描绘出可能显著影响体内蛋白质功能的蛋白质结构异质性。该项目旨在开发用于检测生物战剂的基于质谱学检测方法的软件和生物检测方法，以解决商业免疫检测方法的缺点。为了便于生物毒素亚型的检测和描述，数据评估软件将被整合到为检测特定生物防御剂而设计的基于MS的分析中。将创建特定生物毒素异构体的库，并将其用于生成软件开发和验证的数据。将创建数据评估软件，该软件能够快速识别注册质量值与根据氨基酸序列预测的值不同的生物毒素亚型。该项目的技术可行性将通过数据评估软件在特定生物毒素亚型结构变化的检测和描绘中的成功演示来确定。这些检测和软件将创新检测生物制剂的方式，并提供其他商业检测无法提供的结构信息。该项目更广泛的价值是通过最终创建包含质谱学和数据评估软件的分析来实现的，这些软件可用于分析被归类为生物防御剂的生物病原体。关键的技术改进是从各种样本中快速筛选这些病原体特有的蛋白质生物标记物，以及检测结构修饰的病原体毒素。在生物有机体的筛选中，MSIA分析作为直接读数工具的推广所产生的商业影响可能是显著的。这些化验方法和附带的平台可用于处于生物和化学恐怖主义防御前沿的实验室网络(疾控中心实验室响应网络的成员)。这些基于MS的免疫分析和软件将补充那些实验室已经在使用的基于PCR的检测方法，并将改进(并进一步使)生物威胁物质的检测和表征。

This Small Business Innovation Research (SBIR) Phase I project will develop proteomic-based security technology that will incorporate affinity-based mass spectrometry assays and software for the detection of Biodefense Agents. Existing immunoassay methods for proteomic detection of specific microorganism pathogens are insensitive to structural deviations that might arise as a result of spontaneous or deliberate biotoxin modifications. These methods of detection can fail to detect genetically engineered biotoxins, and cannot delineate protein structural heterogeneities that can significantly affect protein functionality in vivo. This project aims to develop software and bioassays based on mass spectrometric methods of detection for assaying biological warfare agents that will address the shortcomings of the commercially available immunoassays. To facilitate detection and delineation of biotoxin isoforms, data evaluation software will be integrated into the MS-based assays designed for detection of specific biodefense agents. A library of specific biotoxin isoforms will be created and used in the generation of data for the software development and validation. Data evaluation software will be created that is capable of rapidly identifying biotoxin isoforms that register at different mass values from those predicted from the amino acid sequence. The technical feasibility of the project will be established by the successful demonstration of the data evaluation software in the detection and delineation of specific biotoxin isoforms structural changes.These assays and software will innovate the ways biological agents are detected, and provide structural information that no other commercially available assays can. The broader value of the project is realized by the ultimate creation of assays that encompass mass spectrometry and data evaluation software that can be employed to analyze biological pathogens classified as Biodefense Agents. The key technological enhancements are the rapid screening of protein biomarkers characteristic of these pathogens, from a variety of samples, and the detection of structurally modified pathogen toxins. The commercial impact from the propagation of the MSIA assays as direct reading instruments in screening for biological organisms can be significant. These assays and the accompanying platform can be used in a network of Laboratories (members of the CDC.s Laboratory Response Network) that are at the forefront of the biological and chemical terrorism defense. These MS-based immunoassays and software will complement the PCR-based methods of detections already in use in those Laboratories, and will improve (and further enable) the detection and characterization of the bio-threat agents.