C. difficile Toxin Membrane Test with Magnetic Particles

描述(由申请人提供)：顺磁颗粒(PMP)的使用及其在磁性分析读取器(MAR)中的检测代表了一种适用于横向流动膜系统的新的“平台”技术。在初步研究中，这项新技术能够提供3到4个对数，比使用免疫金或酶标记抗体的现有横向流动技术更敏感。我们建议开发一种新的快速横向流动系统，用于艰难梭菌毒素A和B的快速侧向流动。艰难梭菌是评估这项技术的一个很好的候选者。这种厌氧菌是工业化国家医院内腹泻和结肠炎的主要原因。尽管目前基于抗体的艰难梭菌检测比被认为是金标准的组织培养检测更快，但它们提供的敏感度不同。在第一阶段，我们将优化开发艰难梭菌毒素PMP测试所需的条件。我们将优化PMP的连接过程，用分离膜和捕捉线过程测试格式化，评估稳定性，并开发粪便样本稀释剂。将开发一个原型装置，我们将开始研究以评估性能特征。此外，我们还将开发检测IOTA毒素的抗体，IOTA毒素是一种新发现的艰难梭菌毒素。第二阶段将是第一阶段的自然延伸，生产设备的技术将转移到GMP设施，我们将通过内部和现场研究来评估GMP生产的设备。将收集和汇编数据，并编写510(K)文件。利用我们将在第一阶段评估的PMP横向流动技术平台，我们还将开发艰难梭菌的诊断小组测试，这将对艰难梭菌疾病的流行病学和监测研究有用。此外，我们将开发抗生素相关性腹泻(AAD)的临床诊断小组测试，包括基于PMP的产气荚膜梭菌肠毒素测试，这是AAD的另一个原因。该项目开发的技术将广泛应用于新的高灵敏度粪便抗原检测的开发。

DESCRIPTION (provided by applicant): The use of paramagnetic particles (PMP) and their detection in a magnetic assay reader (MAR) represent a new "platform" technology that is adaptable to lateral flow membrane systems. In preliminary studies, the new technology is capable of delivering 3 to 4 logs increased sensitivity over existing lateral flow technologies that use immunogold or enzyme-tagged antibodies. We propose to develop a new rapid lateral flow system for Clostridium difficile toxins A and B using this technology. C. difficile is an excellent candidate to evaluate the technology. This anaerobic pathogen is the leading cause of nosocomial diarrhea and colitis in industrialized countries. Although the current antibody-based tests for C. difficile are more rapid than the tissue culture assay, which is considered the gold standard, they do not offer the same level of sensitivity. In Phase I, we will optimize the conditions needed to develop a PMP test for the toxins of C. difficile. We will optimize the PMP conjugation process, test formatting with separation membrane and capture line processes, evaluate stability, and develop a fecal sample diluent. A prototype device will be developed and we will initiate studies to evaluate performance characteristics. In addition, we will develop antibodies for the detection of iota toxin, a newly recognized C. difficile toxin. Phase II will be a natural extension of Phase I. The technology for producing the device will be transferred to a GMP facility, and we will evaluate GMP produced devices through in-house and on-site studies. Data will be collected and compiled, and 510(k) documents will be prepared. Using the PMP lateral flow technology platform that we will evaluate in Phase I, we will also develop a diagnostic C. difficile panel test, which will be useful for epidemiological and surveillance studies of C. difficile disease. In addition, we will develop a clinical diagnostic panel test for antibiotic associated diarrhea (AAD), including a PMP-based test for C. perfringens enterotoxin, another cause of AAD. The technology developed in this project will be widely applicable for the development of new highly sensitive stool antigen tests.