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

我的总体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满足的需求。本提案描述了一种基于激光的传感分子分析平台的工程发展，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。该平台将包括法医和食品科学快速病理学领域的广泛应用，后者是本文提出验证的重点，因为它解决了一个明显未满足的需求。传感是通过质谱（MS）实现的，它可以提供样品的分子复杂性概况，结合复杂性概况库，可以用MS明确而快速地识别，能够解吸提取样品分子含量到气相的烧蚀激光系统目前用于许多基于MS的分子分析平台。本提案探讨了一种专门的脉冲中红外（IR）激光系统的实用性，该系统将脉冲沉积的振动能量转化为分子振动。对于富含水的样品，如生物组织，皮秒红外激光（PIRL）的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的强耦合。沉积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，释放水和组织成分分子，将它们喷射到气相。这个过程比过热的水分子到周围样品分子的热量传递更快，使它们保持完整。本提案描述了一种手持PIRL-MS探针的工程、开发和集成，用于生物组织的快速分子指纹识别和加速决策；一种基于实时分析激光释放的组织化学成分含量，快速传递组织类型、组织化学、代谢状态、肿瘤类型、亚型和疾病部位边缘等疾病状态信息的探针。相关的工程原理将用于开发优化的收集和电离界面，进一步增强统计分析方法，并与跟踪和定位技术集成，以实现手持式分子分析工具。将统计分析的输出与3D定位系统相结合，可以通过增强现实显示平台将空间编码质谱结果（即分类器）可视化。捆绑解决方案包括激光器、质谱分析仪、分子指纹库、统计分析平台和用于空间编码质谱结果的导航显示，将使用现实世界的样品进行验证。

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.