Picosecond Infrared Laser Ablation Mass Spectrometry for Rapid Characterization of Biological Tissues

用于快速表征生物组织的皮秒红外激光烧蚀质谱法

• 批准号: RGPIN-2018-04611
• 负责人: ZarrineAfsar, Arash
• 金额: $ 1.75万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=679930
• 关键词: Picosecond; Infrared; Laser; Ablation; Mass

***My overall research program aims to develop needs driven' enabling sensing' technologies to address unmet needs in the biomedical domain. This proposal describes engineering developments of a laser-based sensing molecular analysis platform capable of characterizing organic matter in a few seconds of laser interrogation and analysis time. The platform will include a wide array of applications in the areas of forensic and food science to rapid pathology, the latter being the focus of proposed validation herein as it addresses a clear unmet need. Sensing is achieved with Mass Spectrometry (MS) that can deliver a molecular complexity profile of the sample which, in combination with a library of complexity profiles, can be identified unambiguously and rapidly with MS. ******Ablative laser systems capable of desorptive extraction, to the gas phase, of sample molecular content are currently used in a number of MS based molecular analysis platforms. This proposal explores the utility of a specialized, pulsed mid-infrared (IR) laser system that harbours the most optimal conversion of the impulsively deposited vibrational energy to molecular libration. ******For water-rich samples such as biological tissues, molecular desorption with a Picosecond InfraRed Laser (PIRL) is a highly efficient process due to the strong coupling between libration and vibrational modes of water on this timescale. The bulk of the impulsive energy deposited into the vibrational mode of tissue water molecules is converted into desorption, liberating water and tissue constituent molecules, ejecting them to the gas phase. The process takes place faster than heat transfer from superheated water molecules to the surrounding sample molecules, leaving them intact. ******This proposal describes engineering, development and the integration of a hand held PIRL-MS probe for the specific purpose of rapid molecular fingerprinting of biological tissues and accelerated decision making; a probe that delivers rapidly information regarding tissue type, tissue chemistry, metabolic state, disease state such tumor type, subtype and disease site margins, based on real time analysis of laser liberated tissue chemical content.******Relevant engineering principles will be leveraged to develop an optimized collection and ionization interface, further augmented with statistical analysis methods, and integration with tracking and positioning technologies towards a hand-held molecular profiling tool. Coupling the output of the statistical analysis with 3D positioning systems allows spatially encoded mass spectrometry results (i.e. classifiers) to visualize pathology through an augmented reality display platform. The bundled solution comprising the laser, MS analyzer, molecular fingerprint library, statistical analysis platform and navigation display for spatially encoded MS results will be validated using real world samples.

*我的整个研究计划旨在开发需求驱动的“使能传感”技术，以解决生物医学领域未得到满足的需求。这项提案描述了基于激光的传感分子分析平台的工程开发，该平台能够在几秒钟的激光询问和分析时间内表征有机物。该平台将包括在法医和食品科学领域的广泛应用，包括快速病理学，后者是本文拟议验证的重点，因为它解决了一个明显未得到满足的需求。传感是通过质谱学(MS)实现的，它可以提供样品的分子复杂性简档，与复杂性简档库相结合，可以利用MS明确和快速地识别能够解吸提取样品分子内容物到气相的消融激光系统。目前，许多基于MS的分子分析平台使用了这种系统。这项建议探索了一种特殊的脉冲中红外(IR)激光系统的用途，该系统包含了脉冲沉积的振动能量到分子振动的最佳转换。*对于富含水的样品，如生物组织，利用皮秒红外激光(PIRL)进行分子解吸是一个高效的过程，因为在这个时间尺度上，水的振动和振动模式之间存在强烈的耦合。储存在组织水分子振动模式中的大部分脉冲能量被转化为解吸，释放出水和组织组成分子，将它们喷射到气相。这个过程比从过热的水分子到周围的样品分子的热传递更快，保持它们的完好无损。*本提案描述了手持式PIRL-MS探头的设计、开发和集成，该探头用于生物组织的快速分子指纹识别和加速决策的特定目的；探头基于对激光释放的组织化学成分的实时分析，快速提供关于组织类型、组织化学、代谢状态、疾病状态(如肿瘤类型、亚型和疾病部位边缘)的信息。*将利用相关的工程原理来开发优化的收集和电离界面，并通过统计分析方法进一步增强，并与跟踪和定位技术集成，从而形成手持式分子图谱工具。将统计分析的输出与3D定位系统相结合，允许空间编码的质谱分析结果(即分类器)通过增强现实显示平台可视化病理。捆绑的解决方案包括激光、MS分析器、分子指纹库、统计分析平台和用于空间编码MS结果的导航显示，将使用真实世界的样本进行验证。