Direct Mass Spectrometry Innovations for Trace Level Measurements in Complex Samples

分析化学的最终目标是鉴定和测量现实世界样品中的痕量分子水平。不幸的是，在复杂的实际样品（非法街头毒品、城市废水、食品、血液、尿液、组织液等）中进行的痕量水平测量可能会被样品的其他主要成分（干扰物）混淆，从而对成功的结果产生不利影响。此外，进行这些确定的传统方法既昂贵又耗时。直接测定是可取的，因为它们简单、快速，并且可以减少由于污染或稀释而改变结果的风险。在实际样品（农药、激素、药物、代谢物等）中成功测量环境和人类健康的关键决定因素具有挑战性，因为许多当前的分析方法需要样品清理、浓缩和其他制备步骤，增加了时间和成本，以及潜在污染或稀释样品的风险。我的研究计划旨在开发新方法，用于直接，在线，“实时”测量复杂，真实样品中的痕量水平分子（分析物），具有重要的环境，生物分析（临床，制药），执法，法医，减少危害的药物测试和食品安全应用。我的研究基础是使用直接采样接口作为复杂样品和质谱仪之间的桥梁，用于后续痕量分析物的识别和测量。我们研究小组正在探索和开发的膜导入质谱（MIMS）和纸喷雾质谱（PS-MS）的直接质谱技术使用简单，省去了样品预处理步骤：可以使用这两种技术进行快速，定量，分子特异性的测量。这些方法非常适合在护理点或现场使用紧凑型质谱仪。潜在的应用将从医疗诊断到环境应急反应，我们目前正在开发有效的下一代减少危害的药物测试战略，用于阿片类药物过量危机。从长远来看，我们的研究成果将促进直接测量技术的发展，在需要的时间和地点进行实时测量，提供实验室外的高精度结果，在重大事件（环境泄漏）等事件中至关重要，并提供及时的医疗诊断，实现更优质的医疗保健，提高所有加拿大人的生活质量。

The identification and measurement of trace levels of molecules in real world samples is the ultimate goal of analytical chemistry. Unfortunately, trace level measurements made in complicated, real-world samples (illicit street drugs, municipal waste water, foodstuffs, blood, urine, tissue fluids, etc.) can be confounded by the other, major components of the samples (interferents), adversely affecting successful results. Further, conventional methods to make these determinations can be both costly and time consuming. Direct determinations are desirable because they are simple and fast, and can reduce the risk of altering the results through contamination or dilution. The successful measurement of key determinants of environmental and human health in real samples (pesticides, hormones, drugs, metabolites, etc.) is challenging because many current analysis methods require sample cleanup, concentration and other preparation steps, adding time and cost, as well as the risk of potential contamination or dilution of the samples. My research program is aimed at developing new approaches for the direct, online, `real-time' measurement of trace level molecules (analytes) in complex, real samples, with important environmental, bioanalytical (clinical, pharmaceutical), enforcement, forensic, harm reduction drug testing and food security applications. The basis for my research is to use direct sampling interfaces as a bridge between complex samples and mass spectrometers, which are used for the subsequent identification and measurement of trace level analytes. The direct mass spectrometry techniques of membrane introduction mass spectrometry (MIMS) and paper spray mass spectrometry (PS-MS) being explored and developed in our research group are simple to use and eliminate sample pretreatment steps: rapid, quantitative, molecularly specific measurements are possible with both. These methods are ideally suited for use with compact mass spectrometers at the point-of-care or on-site in the field. Potential applications will span from medical diagnostics to environmental emergency responses, and we are currently developing effective, next generation harm reduction drug testing strategies for use in the opioid overdose crisis. In the long term our research outcomes will enable the development of direct measurement technologies that produce real-time measurements when and where they are needed, providing high precision results out-of- the-lab, crucial in events such as critical incidents (environmental spills) as well as in providing timely medical diagnostics, enabling better quality health care, improving the quality of life for all Canadians.