SBIR Phase I: Proteomic-Based Detection Technology

这项小企业创新研究（SBIR）第一阶段项目将开发基于蛋白质组学的安全技术，该技术将结合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蛋白质组学检测的免疫分析方法对自发或故意的生物毒素修饰可能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，也无法描述在体内显著影响蛋白质功能的蛋白质结构异质性。该项目旨在开发基于质谱检测方法的软件和生物分析，用于分析生物战剂，以解决市售免疫分析的缺点。为了便于生物毒素亚型的检测和描述，数据评估软件将被集成到基于ms的检测中，用于检测特定的生物防御剂。将创建一个特定生物毒素异构体库，并用于软件开发和验证的数据生成。将创建数据评估软件，能够快速识别生物毒素同种异构体，这些同种异构体与氨基酸序列预测的质量值不同。该项目的技术可行性将通过数据评估软件在检测和描述特定生物毒素同种异构体结构变化方面的成功示范来确定。这些检测方法和软件将创新检测生物制剂的方法，并提供其他市售检测方法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法和数据评估软件的分析来实现的，这些软件可用于分析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品中快速筛选这些病原体特征的蛋白质生物标志物，以及检测结构修饰的病原体毒素。作为筛选生物有机体的直接读取仪器，MSIA测定法的传播对商业的影响可能是显著的。这些检测方法和附带的平台可在实验室网络（CDC成员）中使用。美国的实验室反应网络（Laboratory Response Network）处于生化恐怖主义防御的前沿。这些基于质谱的免疫分析和软件将补充这些实验室已经使用的基于聚合酶链反应的检测方法，并将改进（并进一步使之成为可能）生物威胁因子的检测和表征。

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.