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：智能样本简介系统的质谱系统的开发迫切需要新技术，该系统可以快速测量，而不会对分析数据进行重大损害。本文中，我们建议开发出强大的质谱（MS）表面采样装置，该设备可以直接分析各种材料，包括生物组织和活微生物，有望在该目标上传递。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，被泵泵和吸气，以使溶剂脱离感兴趣的表面，其中微萃取发生在探针和样品之间的界面上。 Prosolia已从AB Sciex获得了LMJSSP技术的许可，并将通过NIH实验室与Marketplace计划与Oak Ridge国家实验室的原始发明者合作，以使技术在各种BIO分析工作中的应用更强大，并用户友好，从而为商业上可行的产品创建先进的原型。该项目的任务可以分为三个目标。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探索一些有前途的方法，以自动控制连续的提取连接处所需的匹配液体流，以持续探针和表面之间。另外，建立一种保持探针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生产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。具体而言，将创建标准，以确定在各种条件下（包括在不同的实验室内）中提取的概况和效率。这些将确定潜在使用，维护和支持的预期限制，以确保对各种方法进行校准的强大操作。在这一工作部分中，将对通过较小变体进行对标准探测布置的分辨率增加的研究，以确定在组织学相关的采样大小的诊断和生物标志物研究人员中的分析指标。使用另一种基于MS的表面采样技术的早期实验，解吸电喷雾电离，用于直接生物分析活体微生物，能够生成细菌菌落的光谱谱。但是，生成这些结果的过程需要经常清洁和交换仪器毛细血管，这是由于与细菌的结垢而被吹出并进入仪器入口。使用我们的原型LMJSSP系统获得的初步光谱已经以更加简单的方式收集，并显示出一些特别有趣的特征，以区分和表征不同种类和细菌的菌株。但是，必须获得更多的指纹，以确定这些数据的统计显着性和适用性。此外，我们还将建立在各种生长点和压力条件下采样的效果，以生成潜在的自动分类库。在实施自动化和优化的更改之后，我们用于直接分析表面的原型将是一个简单的示例简介系统，从少数几个使用的学术原型过渡到可以部署到许多人的商业原型。通过访问我们提出的里程碑：进行适当的硬件更改，确定与溶剂和探针大小相对应的分析指标，并收集与细菌分析的统计相关数量的概况数量，将评估手动微生物分析的能力。因此，我们的第二阶段建议将包括进一步的硬件改进，更广泛的样本选择，增强的数据集成和处理软件。