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From Single Cells to Tissues: a Novel Mass Spectrometry Approach for Bioanalysis

从单细胞到组织：一种新颖的生物分析质谱方法

基本信息

批准号：
9767790
负责人：
Zhibo Yang
金额：
$ 29.7万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767790
关键词：
3-Dimensional Animals Antineoplastic Agents Atlas of Cancer Mortality in the United States Biological Biology Biomedical Research Biomimetics Breast Cancer Cell Cell Line Cell physiology Cells Cellular Spheroids Cellular biology Ceramides Chemicals Cholesterol Clinical Research Cultured Cells Detection Devices Doxorubicin Eukaryotic Cell Fiber Goals Image Imaging Techniques In Situ In Vitro Individual Investigation Knowledge Lipids Location Malignant Neoplasms Mammary Neoplasms Maps Mass Spectrum Analysis Measurement Measures Medical Research Methods Microscopy Modeling Molecular Molecular Analysis Motion Mus Organism Paclitaxel Peptides Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacotherapy Population Population Heterogeneity Preparation Research Resolution Sampling Science Silicon Dioxide Slice Software Engineering Spatial Distribution Stable Isotope Labeling Structure System Techniques Technology Time Tissue Sample Tissue imaging Tissues Tumor Biology Tumor Tissue Tumor-Derived analytical method animal tissue anti-cancer base biological research cancer cell experimental study human disease imaging modality imaging study improved innovative technologies instrumentation ionization miniaturize neoplastic cell novel public health relevance scaffold single cell analysis tool tumor

项目摘要

DESCRIPTION (provided by applicant): There is a fundamental lack of understanding in biology on the single cell level, especially in human disease biology. This gap in knowledge encompasses both how individual cells function and also how single cells combine and collaborate to construct multi-cellular creations, such as how many cancer cells associate to form a tumor. Traditionally, bioanalysis has largely been conducted through large numbers (i.e. thousands or millions) of cells being destroyed and mixed together to form a completely artificial construct: the cell lysate. Cell lysates are prepared from a large number of heterogeneous cells, either present in tissue samples or grown in culture. Bioanalysis of lysates are an amalgamated average of many heterogeneous cells subjected to artificial sample preparation, and therefore, standard bioanalytical methods have been largely unable to define single cell biology. Recently, single cell analysis (SCA) has become possible through advancements in many experimental methods. Due to its unparalleled detection sensitivity, mass spectrometry (MS) is one of the most promising analytical methods to be deployed for single cell analysis. Single-cell mass spectrometry (SCMS) and mass spectrometry imaging (MSI) are emerging techniques that could potentially revolutionize bioanalytical science in basic scientific and biomedical research. We have developed a miniaturized sampling and ionization device, the Single-probe, capable of performing single cell mass spectrometry (SCMS) in real time under ambient conditions. The Single-probe, with a sampling tip smaller than eukaryotic cells (<10 µm), can be inserted into individual living cells to sample the intracellular compounds for immediate MS analysis. The Single-probe SCMS technique has produced highly sensitive detection of intracellular compounds, including cell metabolites, lipids and anticancer compounds, inside living single cells. The Single-probe has also been used successfully in MSI experiments to reconstruct the spatial distribution of species (e.g. lipids and cell metabolites) from sections of animal tissue. Our long-term research goal is to fully establish the Single- probe based techniques in SCMS and MSI for broad utilization in bioanalysis. The objective of this application is to develop the Single-probe MS technology as a first-in-class tool for quantitative SCMS (qSCMS) in cells and for MSI-based investigation of tumors. This research objective will be accomplished through completing the following three Specific Aims: 1) create quantitative single cell mass spectrometry (qSCMS) for compounds inside of single cells from cultured cell lines; 2) use the Single-probe MS to analyze single cells in in vitro tumors; and, 3) perform Single-probe MSI measurements of the in vitro and animal-derived tumors. The Single-probe MS is an innovative technology in that it provides new experimental capabilities for single cell analysis and tissue imaging. The proposed research is significant because the Single-probe MS experimental applications (i.e. qSCMS and MSI), once developed, will allow new understandings in single cell and tumor biology that are not currently possible.

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions.

DOI：
10.3791/53911
发表时间：
2016-06-14
期刊：
Journal of visualized experiments : JoVE
影响因子：
0
作者：
Rao W;Pan N;Yang Z
通讯作者：
Yang Z

Using Dicationic Ion-Pairing Compounds To Enhance the Single Cell Mass Spectrometry Analysis Using the Single-Probe: A Microscale Sampling and Ionization Device.

DOI：
10.1021/acs.analchem.6b01284
发表时间：
2016-07-05
期刊：
Analytical chemistry
影响因子：
7.4
作者：
Pan N;Rao W;Standke SJ;Yang Z
通讯作者：
Yang Z

Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds.

DOI：
10.1016/j.antiviral.2019.104548
发表时间：
2019-07
期刊：
Antiviral research
影响因子：
7.6
作者：
B. L. Roberts;Zachary C Severance;Ryan C. Bensen;Anh T. Le;Cori A Malinky;Evan M Mettenbrink;J. Núñez;William J Reddig;E. Blewett;Anthony W. G. Burgett
通讯作者：
B. L. Roberts;Zachary C Severance;Ryan C. Bensen;Anh T. Le;Cori A Malinky;Evan M Mettenbrink;J. Núñez;William J Reddig;E. Blewett;Anthony W. G. Burgett

ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3β1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells.

DOI：
10.1053/j.gastro.2019.10.038
发表时间：
2020-02
期刊：
Gastroenterology
影响因子：
29.4
作者：
Liu M;Zhang Y;Yang J;Cui X;Zhou Z;Zhan H;Ding K;Tian X;Yang Z;Fung KA;Edil BH;Postier RG;Bronze MS;Fernandez-Zapico ME;Stemmler MP;Brabletz T;Li YP;Houchen CW;Li M
通讯作者：
Li M

Enhancement of photodynamic cancer therapy by physical and chemical factors.