All-in-one Device for Forensic Toxicology Drug Screening

项目概要/摘要 毒理学病例中的药物筛选主要使用免疫测定法、气体- 色谱-质谱（GC-MS）和液相色谱-质谱 （LC-MS）。免疫测定缺乏灵敏度、多重能力和响应的灵活性 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。气相色谱法 MS需要大量的样品制备，包括衍生化反应，以获得足够的 性能尽管LC-MS是一种成熟的技术，但大多数实验室仍然没有使用它来检测药物。 筛选由于是高成本和复杂性。因此，我们看到了技术和市场需求 更好的药物筛选技术，结合联合收割机的简单性和自动化， 免疫分析具有高灵敏度和特异性的质谱。在这个快速通道中， （结合第一阶段和第二阶段）的建议，我们寻求开发一种基于质谱的药物 利用纸喷雾质谱的筛选系统。该项目的成果将 包括两个一次性盒装置，其执行样品收集、存储、提取 和电离用于MS检测。除了一次性设备外，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， 在市售质谱仪上分析样品分析盒。最后， 我们将创建仪器控制和数据分析软件包，提供一个完整的，最终的， 用于药物筛选的全面解决方案。 在该提案的第一阶段，一次性纸喷雾分析盒的原型 并将开发和测试手动质谱接口。如果 分析盒和接口的性能足以筛选代表 如果我们没有一套合成药物，我们将进入第二阶段。在第二阶段，我们将改进样品 分析盒，开发一种样品收集装置，该装置将能够可靠地收集 从未指定的初始体积中提取已知体积的血液，开发自动MS界面， 开发所需的控制和数据分析软件，并测试方法的性能， 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.