DEVELOPMENT OF AN INTELLIGENT SAMPLE INTRODUCTION SYSTEM FOR MASS SPECTROMETRY

质谱智能进样系统的开发

• 批准号: 8590085
• 负责人: Justin Michael Wiseman
• 金额: $ 35万
• 依托单位: PROSOLIA, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8590085
• 关键词: Adoption; Affect; Area; Aspirate substance; Automation; Bacteria; Biological; Biological Markers; Blood capillaries; Classification; Computer software; Data; Detection; Development; Devices; Diagnostic; Digestion; Electrospray Ionization; Ensure; Fingerprint; Gases; Government; Growth; Hand; Height; Histologic; Image; In Situ; Investigation; Ions; Laboratories; Lasers; Libraries; Licensing; Life; Liquid substance; Literature; Maintenance; Marketing; Mass Spectrum Analysis; Measurement; Methodology; Methods; Metric; Microfluidics; Modeling; Modification; Organism; Performance; Phase; Plant Roots; Positioning Attribute; Process; Proteomics; Pump; Relative (related person); Reproducibility; Research; Research Personnel; Resolution; Sample Size; Sampling; Solid; Solutions; Solvents; Spottings; Stress; Surface; System; Systems Development; Techniques; Technology; Time; Tissues; United States National Institutes of Health; Variant; Vision; Work; base; capillary; data integration; in vivo; innovation; instrument; interest; microorganism; new technology; operation; programs; prototype; public health relevance; research study; sensor; user-friendly

DESCRIPTION: Development of an Intelligent Sample Introduction System for Mass Spectrometry There is a pressing need for new technologies that enable rapid measurements without significant compromise to the analytical data. Herein, we propose to develop a robust mass spectrometry (MS) based surface sampling device that enables direct analysis of a variety of materials including biological tissue and live microorganisms that promises to deliver on this objective. The basis for this device is the Liquid Micro junction Surface Sampling Probe (LMJSSP), a set of coaxial microfluidic capillaries that are pumped and aspirated to bring solvent to and away from a surface of interest, where micro extraction takes place at the interface between the probe and the sample. Prosolia has licensed the LMJSSP technology from AB Sciex and will partner with the original inventor at Oak Ridge National Laboratory via the NIH Lab to Marketplace program to create an advanced prototype towards a commercially viable product by making the technology more robust and user-friendly for applications in various bio analytical workflows. The tasks of this project can be divided into three Aims. The first and second Aims are to ensure that the hardware of the device is sufficiently easy to use for commercial viability. This includes characterization of the present prototype and exploration of a few promising methods for automatic control of matched liquid flows required for a continuous extractive junction to persist between probe and surface. Additionally, establishing a mechanism for maintaining an ideal distance between the probe and surface will be critical for successful implementation. Upon establishing methods for flow and height management with optimized control and reasonable potential for manufacture, these hardware modifications will be used to determine the analytical conditions for instrument operation. Specifically, standards will be created to determine the profile and efficiency of extraction under a variety of conditions (including within different laboratories). These will determine the expected limits for potential use, maintenance, and support to ensure robust operations calibrated for a variety of methodologies. During this section of work, investigations into potential increases in resolution from the standard probing arrangement via smaller variants will be performed to identify analytical metrics at histologically relevant sampling sizes of interest to diagnostic and biomarker researchers. Early experiments using another MS-based surface sampling technique, Desorption Electrospray Ionization, for direct bio analysis of live microorganisms were able to generate spectral profiles for bacterial colonies; however, the process to generate these results required frequent cleaning and exchanging of instrument capillaries due to fouling with bacteria that were blown off the surface and into the instrument inlet. Preliminary spectra obtained using our prototype LMJSSP system have been collected in a much more facile manner, and have shown some particularly interesting features for distinguishing and characterizing different species and strains of bacteria. However, more fingerprints must be acquired in order to determine statistical significance and applicability of these data. In addition, we will establish he effects of sampling at various growth points and stress conditions in order to generate a potential library for automated classification. After implementing changes for automation and optimization, our prototype for direct analysis of surfaces, will be a simple sample introduction system transitioning from an academic prototype used by a few to a commercial prototype that can be deployed to many. By hewing to the milestones we propose: making appropriate hardware changes, determining analytical metrics corresponding to solvents and probe sizes, and gathering a statistically relevant number of profiles for bacterial analysis, the capacity for hands-off microorganism profiling will have been assessed. As such our phase II proposal will include further hardware refinements, a broader selection of samples, enhanced data integration, and processing software.

描述：开发用于质谱分析的智能样品引入系统迫切需要能够快速测量而不会对分析数据造成重大影响的新技术。在此，我们建议开发一种基于质谱（MS）的强大表面采样装置，能够直接分析包括生物组织和活微生物在内的各种材料，有望实现这一目标。该设备的基础是液体微连接表面采样探针 (LMJSSP)，这是一组同轴微流体毛细管，通过泵送和抽吸将溶剂带入或带离感兴趣的表面，其中微萃取发生在表面之间的界面处。探针和样品。 Prosolia 已获得 AB Sciex 的 LMJSSP 技术许可，并将通过 NIH 实验室到市场计划与橡树岭国家实验室的原始发明人合作，通过使该技术更加强大和用户友好，创建一个先进的原型，实现商业上可行的产品在各种生物分析工作流程中。该项目的任务可分为三个目标。第一个和第二个目标是确保设备的硬件足够易于使用 商业可行性。这包括对当前原型的表征以及对一些有前途的方法的探索，这些方法用于自动控制在探针和表面之间持续存在的连续提取连接所需的匹配液体流。此外，建立一种保持探头和表面之间理想距离的机制对于成功实施至关重要。在建立具有优化控制和合理制造潜力的流量和高度管理方法后，这些硬件修改将用于确定仪器操作的分析条件。具体来说，将制定标准来确定各种条件下（包括不同实验室内）的提取概况和效率。这些将确定潜在使用、维护和支持的预期限制，以确保针对各种方法进行校准的稳健操作。在这部分工作中，将通过较小的变体对标准探测布置分辨率的潜在增加进行调查，以确定诊断和生物标志物研究人员感兴趣的组织学相关采样大小的分析指标。早期实验使用另一种基于 MS 的表面采样技术解吸电喷雾电离对活微生物进行直接生物分析，能够生成细菌菌落的光谱图；然而，产生这些结果的过程需要经常清洁和更换仪器毛细管，因为细菌会从表面吹落并进入仪器入口。使用我们的原型 LMJSSP 系统获得的初步光谱以更容易的方式收集，并且显示出一些特别有趣的特征，用于区分和表征不同的细菌物种和菌株。然而，必须获取更多的指纹才能确定这些数据的统计意义和适用性。此外，我们将建立在不同生长点和应力条件下采样的效果，以便生成用于自动分类的潜在库。在实施自动化和优化的更改后，我们用于直接分析表面的原型将是一个简单的样品引入系统，从少数人使用的学术原型转变为可以部署到许多人的商业原型。通过遵守我们建议的里程碑：进行适当的硬件更改，确定与溶剂和探针尺寸相对应的分析指标，并收集统计上相关数量的细菌分析图谱，从而评估不干涉微生物分析的能力。因此，我们的第二阶段提案将包括进一步改进硬件、更广泛的样本选择、增强的数据集成和处理软件。