Triboelectric Ambient Mass Spectrometry Imaging of Renal Cell Carcinomas

肾细胞癌的摩擦电环境质谱成像

• 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
• 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

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.

主要研究者：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 了解癌组织的分子组成以及这些改变的变化， 时间和干预措施。质谱成像（MSI）是探测薄 当需要毫微微至阿托摩尔的灵敏度时，组织切片具有同时精确的特异性。 在这个项目中，提出了开发基于摩擦电的概念验证MSI离子源。 纳米发电机（TENG），并将其性能与标准MSI技术进行基准测试，例如 基质辅助激光解吸/电离（MALDI）和解吸电喷雾电离（DESI） 使用去识别的透明细胞肾癌组织切片。这些是富含脂质的肿瘤 脂质代谢在疾病发展中起主要作用。当与MS耦合时，TENG已经显示出 比标准纳米电喷雾离子化更高的灵敏度，特别是对于难以分离、低 极性脂质和代谢物。TENG还可以用于产生关于重要的结构信息。 分子，如脂质，通过扩大TENG电极面积，这允许进行控制 气相离子分子反应，产生诊断碎片模式。组织切片 将从John彼得罗斯教授维护的生物库中选择TENG MSI检查的样本， 埃默里大学的长期合作者TENG MSI离子源将耦合到离子迁移率- 质谱仪，以便能够在成像实验期间区分脂质同量异位素， 仪器供应商（沃茨）。TENG图像与MALDI和DESI图像的配准 将与格鲁吉亚理工学院（肯普）的合作者开发的算法进行。改进 到TENG MSI离子源将实现使用符号回归的方法，这将使 同时优化多个定量性能指标，例如空间分辨率， 总体灵敏度、检测到的光谱特征的数量、脂质/代谢物化学物质的数量 检测的类别和氧化脂质的数量。总的来说，这个项目将开发一种MSI技术， 这将成为研究癌症研究中重要的富脂组织的宝贵工具。