MALDI TOF/TOF Mass Spectrometer for Imaging Thin Tissue Sections

描述（由申请人提供）： 我们正在申请资助最先进的基质辅助激光解吸电离飞行时间/飞行时间（MALDI-TOF/TOF）质谱仪，用于薄组织切片的质谱成像（ImMS）。蛋白质组学技术的一个令人兴奋的新应用是通过MALDI-TOF/TOF质谱（MS）进行组织的分子成像。直接组织分析和成像质谱提供了对组织样本内复杂蛋白质模式的详细评估，允许可视化组织切片中蛋白质/肽和其他分析物的空间分布，并洞察特定细胞和组织生物学和病理学。这种新开发的技术需要高灵敏度质谱，我们将利用质谱仪的能力，以线性模式操作灵敏度和反射模式的高分辨率和质量精度。该仪器的MS/MS测序能力将允许直接从组织中鉴定临床相关肽，而无需进一步分级分离或分离。MALDI的组织成像允许以高通量方式自动处理临床标本，并扩大了临床蛋白质组学核心，组织采购核心实验室和加州大学洛杉矶分校分子仪器中心的研究能力。MALDI-TOF/TOF成像系统将成为加州大学洛杉矶分校10多个不同NIH资助项目的重要组成部分。资助的研究将影响许多生物医学导向的研究，包括癌症（前列腺癌，脑癌，皮肤癌和肺癌），免疫/炎症性疾病（炎症性肠病），代谢疾病（糖尿病和代谢综合征）和心血管疾病（动脉粥样硬化）。 公共卫生相关性：新仪器将有利于广泛的临床研究，特别是在转化医学领域。我们将在一系列重要的人类疾病中寻找新的生物标志物，包括前列腺癌和肺癌，胶质母细胞瘤，黑色素瘤和炎症性肠病。我们的研究将寻求确定新的生物标志物候选者，以及更好地了解疾病进展的病因和病理。

DESCRIPTION (provided by applicant): We are requesting funding for a state-of-the-art matrix-assisted laser desorption ionization time-of-flight/time- of-flight (MALDI-TOF/TOF) mass spectrometer to be utilized for imaging by mass spectrometry (ImMS) of thin tissue sections. An exciting new application of proteomics technology is molecular imaging of tissues by MALDI-TOF/TOF mass spectrometry (MS). Direct tissue profiling and imaging mass spectrometry provide a detailed assessment of the complex protein pattern within a tissue sample, allows visualization of the spatial distribution of proteins/peptides and other analytes in tissue sections, and insight into specific cell and tissue biology and pathology. This newly developed technique requires high sensitivity mass spectrometry and we will be taking advantage of the ability of the mass spectrometer to operate in both linear mode for sensitivity and reflectron mode for high resolution and mass accuracy. The MS/MS sequencing capabilities of the instrument will allow the identification of clinically relevant peptides directly from the tissues without further fractionation or isolation. Tissue imaging by MALDI allows for automated processing of clinical specimens in a high-throughput fashion and expands the research capacity of the Clinical Proteomics Core, the Tissue Procurement Core Laboratory, and the Molecular Instrumentation Center at UCLA. The MALDI-TOF/TOF imaging system will be an important part of over 10 different NIH-funded projects at UCLA. The funded research will impact a number of biomedically-oriented studies including cancer (prostate, brain, skin, and lung cancers), immune/inflammatory disorders (inflammatory bowel disease), metabolic disease (diabetes and metabolic syndrome), and cardiovascular disease (atherosclerosis). PUBLIC HEALTH RELEVANCE: The new instrumentation will benefit a wide range of clinically-oriented studies, particularly in the field of translational medicine. We will be seeking new biomarkers in an array of important human conditions including prostate and lung cancer, glioblastoma, melanoma, and inflammatory bowel disease. Our studies will seek both to identify new biomarker candidates as well as to better understand the etiology and pathology of disease progression.