Democratization of Mass Spectrometry Through Simplified Sample Preparation/Ionization for High Impact Applications

化学分析是各种学科(如环境、医学和“组学”相关研究领域)发现的基础。开发速度更快、需要的样品更少、灵敏度更高、与各种基质兼容的分析系统，对于探测生物和化学系统至关重要。我的研究计划提案利用了我们在微流体、质谱学和分离科学方面的专业知识，并将重点放在新方法上，以增强、简化和加固样品制备和质谱学引入，并将其应用于高影响应用。拟议的计划将涉及四项研究推动力。第一个重点是使用自湿的疏水/亲水图案化表面来快速产生微滴阵列，以进行快速样品制备(组织成像、液相色谱存档和预浓缩)。第二个重点是增强一种新颖的质谱学环境电离界面(液体微连接表面采样探头，LMJ-SSP)，以使用“尖端梯度法”快速采样复杂生物样品的更广泛的化学空间。第一个和第二个推进器都寻求进一步民主化质谱学，将其从专业的、训练有素的操作员带到公共卫生和医院环境中更常规的现场使用。第三个推进器将利用LMJ SSP来表征不同相关表面上形成的生物膜。生物膜保护微生物群落免受外部压力的影响，包括抗生素、免疫细胞和饮用水消毒。学员将在女王医院的饮用水分配实验室(DWDL)和新成立的卫生创新中心(金斯敦综合医院)工作，以评估相关表面的生物膜生长。相比之下，构成生物膜的微生物产生许多生物活性化合物，以实现互惠互利和/或作为生存工具。在与Avena博士的合作下，罗斯在女王医院的团队将使用新型的MS工具来检查生长在不同支架上的不同种类的假交替单胞菌，以寻找新的生物合成化合物。第四个推力涉及与美国哈佛医学院的Natalie Agar博士(癌症)、荷兰格罗宁根的sElizabeth Verpoorte博士(肝脏)和女王医院的分子导航小组合作开发LMJ-SSP，作为术中肿瘤边缘和肝功能的快速组织成像工具。公平、多样性和包容性将继续是我研究计划的优先事项。HQP将被要求参加通过大学人权和平等办公室组织的正式EDI培训计划。HQP将受益于在学科接口工作，在那里研究人员将接受组织准备、化学/生化安全以及最先进的电化学、质谱学、微生物学和微制造技术方面的培训。

Chemical analysis forms the basis for discovery in a wide variety of disciplines (e.g. environmental, medical and "omics" related research areas). The development of analysis systems that are faster, require less sample, and offer increased sensitivity and compatibility with a variety of matrices are critical to probing e.g. biological and chemical systems. My research program proposal leverages our expertise in microfluidics, mass spectrometry, and separation science and will focus on novel methods to enhance, simplify and ruggedise both sample preparation and introduction for mass spectrometry, and apply them to high impact applications. The proposed program will involve four research thrusts. The first will focus on the use of hydrophobic/hydrophilic patterned surfaces that self-wet to quickly yield micro-droplet arrays to carry out rapid sample preparation (tissue imaging, liquid chromatographic archiving and preconcentration). The second will focus on enhancing a novel mass spectrometric ambient ionization interface (liquid micro-junction surface sampling probe, LMJ-SSP) to rapidly sample the broader chemical space of complex biological samples using a "gradient at the tip approach". Both thrusts one and two seek to further democratise mass spectrometry, taking it from specialised, well-trained operators to more routine field use in public health, and hospital settings.  The third thrust will utilise the LMJ SSP to characterise biofilms formed on different relevant surfaces. Biofilms protect the microbial community from external pressures, including antibiotics, immune cells and drinking water disinfection. Trainees will work in the Drinking Water Distribution Laboratory (DWDL) at Queen's and at the newly minted Centre for Health Innovation (Kingston General Hospital) to assess biofilm growth on relevant surfaces. Contrastingly, the microbes that make up biofilms produce a number of bioactive compounds for mutualistic benefit and/or as a survival tool. In collaboration with Dr. Avena Ross's group at Queen's will be using novel MS tools to examine different species of Psuedoalteromonas grown on different scaffolds to search for novel biosynthetic compounds. The fourth thrust  involves working with Dr. Natalie Agar, Harvard School of Medicine, USA (Cancer) and Dr. Sabeth Verpoorte, Groningen, The Netherlands (Liver) and the Molecular Navigation Group at Queen's to develop LMJ-SSP and) as a rapid tissue imaging tool for intra-operative assessment of tumour margins and liver function. Equity, Diversity, and Inclusion will continue to be a priority of my research program. HQP will be required to participate in formal EDI training programs organised through the University Human Rights and Equity Office. HQP will benefit from working at discipline interfaces where researchers will be trained on tissue preparation, chemical/biochemical safety, and state-of-the-art electrochemical, mass spectrometric, microbiological and microfabrication techniques.