All-in-one Device for Forensic Toxicology Drug Screening

项目摘要/摘要 毒理学病例中的药物筛选主要使用免疫分析，气体- 气相色谱-质谱法(GC-MS)和液质联用法(LC-MS) (LC-MS)。免疫分析缺乏敏感度、多重能力和反应灵活性 包括芬太尼类似物和合成大麻素在内的强效合成药物的兴起。GC- MS需要广泛的样品制备，包括衍生化反应，以实现足够的 性能。尽管LC-MS是一项成熟的技术，但大多数实验室仍未将其用于药物 筛查由于成本高，操作复杂。因此，我们认为技术和市场需求都很大 更好的药物筛选技术，结合了简单和自动化的 免疫分析具有质谱学的高灵敏度和特异度。在这条快速通道中 (合并第一阶段和第二阶段)提案，我们寻求开发一种基于质谱学的药物 利用纸喷雾质谱仪的筛选系统。该项目的成果将 包括两个一次性盒装置，其执行样品采集、存储、提取 和用于MS检测的电离。除了一次性设备，我们还将开发一种 简单的手动操作和第二个自动质谱仪接口，将使 对市售质谱仪上的样品分析柱进行分析。最后， 我们将创建仪器控制和数据分析软件包，以提供完整的、最终的 药物筛选的端到端解决方案。 在本提案的第一阶段，一次性纸雾分析试剂盒的原型 以及手动质谱学界面将被开发和测试。如果 分析柱和接口的性能足以筛查代表 一套合成药物，我们将进入第二阶段。在第二阶段，我们将改进样品 分析试剂盒，开发一种样本收集设备，该设备将能够可靠地收集 从未指明的初始体积中提取已知的血量，开发自动化MS界面， 开发所需的控制和数据分析软件，并在 包括高分辨率和低分辨率质谱仪。

Project Summary/Abstract Drug screening in toxicology cases is performed mainly using immunoassays, gas- chromatography mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). Immunoassays lack the sensitivity, multiplexing capability, and flexibility to respond to the rise of potent synthetic drugs including fentanyl analogs and synthetic cannabinoids. GC- MS requires extensive sample preparation including derivatization reactions to achieve adequate performance. LC-MS, despite being a mature technology, is still not used by most labs for drug screening due to is high cost and complexity. We therefore see a both a technical and market need for better drug screening technologies that combine the simplicity and automation of immunoassays with the high sensitivity and specificity of mass spectrometry. In this Fast-Track (combined phase I and phase II) proposal, we seek to develop a mass spectrometry-based drug screening system utilizing paper spray mass spectrometry. The outcomes of this project will include two disposable cartridge devices which perform sample collection, storage, extraction, and ionization for MS detection. In addition to the disposable devices, we will also develop a simple manually operated and a second automated mass spectrometer interface which will enable analysis of the sample analysis cartridge on commercially available mass spectrometers. Finally, we will create instrument control and data analysis software package to provide a complete, end- to-end solution for drug screening. In phase I of this proposal, a prototype for the disposable paper spray analysis cartridge as well as the manual mass spectrometry interface will be developed and tested. If the performance of the analysis cartridge and interface are adequate for screening a representative set of synthetic drugs, we will proceed to phase II. In the second phase, we will improve the sample analysis cartridge, develop a sample collection device which will enable robust collection of a known volume of blood from an unspecified initial volume, develop the automated MS interface, develop needed control and data analysis software, and test the performance of the approach on both high resolution and low resolution mass spectrometers.