Triboelectric Ambient Mass Spectrometry Imaging of Renal Cell Carcinomas

肾细胞癌的摩擦电环境质谱成像

基本信息

批准号：
10707686
负责人：
Facundo Martin Fernandez
金额：
$ 21.51万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707686
关键词：
Ablation Academia Algorithms Appearance Area Benchmarking Biological Biological Markers Bladder Cancer Biology Characteristics Charge Chemicals Clear cell renal cell carcinoma Collaborations Colon Complex Conventional (Clear Cell) Renal Cell Carcinoma Coupled Data Development Devices Diagnosis Diagnostic Disease Early Diagnosis Electrodes Electrospray Ionization Electrostatics Environment Feces Gases Generations Histologic Image Imaging Techniques Imaging technology Industry Inflammatory Response Intervention Ions Irrigation Isomerism Kidney Knowledge Lasers Lipids Liquid Chromatography Lung MRI Scans Malignant Epithelial Cell Malignant Neoplasms Measures Metabolism Microscope Molecular Names Neoplasm Metastasis Noise Ovarian Pathway Analysis Pathway interactions Pattern Performance Pharmaceutical Preparations Phase Physical condensation Physiologic pulse Play Positioning Attribute Principal Investigator Process Proteomics Reaction Renal Cell Carcinoma Renal carcinoma Renal pelvis Reproducibility Research Resolution Role Sampling Signal Transduction Source Specificity Spectrometry, Mass, Electrospray Ionization Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stream Survival Rate Symptoms Techniques Technology Testing Thinness Time Tissue Sample Tissues Tumor Tissue United States Universities Urine Uterus Vendor Water X-Ray Computed Tomography anticancer research biobank biomarker discovery cancer cell cancer imaging cancer therapy detection limit electric field experimental study imaging approach improved inflammatory marker instrument ion mobility ion source ionization kidney biopsy lipid metabolism lipid structure lipidome lipidomics mass spectrometer mass spectrometric imaging metabolic phenotype metabolome metabolomics nano nano-electrospray oxidized lipid pi bond prevent tandem mass spectrometry tool transcriptomics tumor tumor growth tumor progression urinary voltage

项目摘要

Principal Investigator: FM Fernández – Triboelectric Ambient Mass Spectrometry Imaging of Renal Cell Carcinomas Understanding complex chemical and biological alterations in cancer requires detailed knowledge of the molecular composition of cancer tissues and the changes in these alterations over time, and following interventions. Mass spectrometry imaging (MSI) is the tool of choice for probing thin tissue sections when femto- to attomole sensitivity is required with simultaneous exquisite specificity. In this project it is proposed to develop a proof-of-concept MSI ion source based on a triboelectric nanogenerator (TENG), and benchmark it’s performance against standard MSI techniques such as matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI) using de-identified clear cell renal carcinoma tissue sections. These are lipid-rich cancer tumors where lipid metabolism plays a major role in disease development. TENG, when coupled to MS, have shown higher sensitivity than standard nanoelectrospray ionization, particularly for difficult to ionize, low polarity lipids and metabolites. TENG can also be used to yield structural information about important molecules such as lipids, by enlarging the TENG electrode area, which allows to carry out controlled gas-phase ion molecule reactions that yield diagnostic fragmentation patterns. Tissue sections to be examined by TENG MSI will be selected from the biobank maintained by Prof. John Petros, a long- standing collaborator at Emory University. The TENG MSI ion source will be coupled to an ion mobility- mass spectrometer to enable distinguishing lipid isobars during imaging experiments, in collaboration with the instrument vendor (Waters). Co-registration of TENG images with MALDI and DESI images will be conducted with algorithms developed with collaborators at Georgia Tech (Kemp). Improvements to the TENG MSI ion source will be achieved using a symbolic regression approach that will enable the simultaneous optimization of several quantitative performance metrics such as spatial resolution, overall sensitivity, the number of detected spectral features, the number of lipid/metabolite chemical classes detected, and the number of oxidized lipids. Overall, this project will develop an MSI technology that will become an invaluable tool for investigating lipid-rich tissues of importance in cancer research.

首席研究员：FM Fernández – 肾细胞癌的摩擦电环境质谱成像了解癌症中复杂的化学和生物学变化需要详细的了解癌症组织的分子组成以及这些变化的变化质谱成像 (MSI) 是探测薄层的首选工具。当需要飞秒到阿托摩尔的灵敏度同时具有精确的特异性时，组织切片。在该项目中，建议开发一种基于摩擦电的概念验证 MSI 离子源纳米发电机（TENG），并根据标准 MSI 技术对其性能进行基准测试，例如基质辅助激光解吸/电离 (MALDI) 和解吸电喷雾电离 (DESI) 使用未鉴定的透明细胞肾癌组织切片。这些是富含脂质的癌症肿瘤。研究表明，当 TENG 与 MS 结合时，脂质代谢在疾病发展中发挥着重要作用。比标准纳电喷雾电离具有更高的灵敏度，特别是对于难以电离、低极性脂质和代谢物也可用于产生重要的结构信息。通过扩大 TENG 电极面积，可以控制脂质等分子产生诊断性碎片模式的气相离子分子反应。由 TENG MSI 检查的 MSI 将从 John Petros 教授维护的生物库中选择，John Petros 是一位长期从事埃默里大学的长期合作者 TENG MSI 离子源将与离子淌度耦合。合作使用质谱仪在成像实验期间区分脂质同工酶与仪器供应商 (Waters) 共同配准 TENG 图像与 MALDI 和 DESI 图像。将使用与佐治亚理工学院（Kemp）的合作者开发的算法进行。 TENG MSI 离子源将使用符号回归方法来实现，该方法将使同时优化多个定量性能指标，例如空间分辨率，总体灵敏度、检测到的光谱特征数量、脂质/代谢物化学物质的数量总体而言，该项目将开发 MSI 技术。这将成为研究癌症研究中重要的富含脂质的组织的宝贵工具。