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Imaging mass cytometry-elemental immunohistochemistry for multiparametric imaging and quantitation
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摘要
Background:Pathology assessment of tissue sections provides prognostic evaluation and helps select optimum treatment regimens.Digital pathology has made significant strides in the analysis of several markers.There is a growing understanding of cell heterogeneity within tumor tissue,role of microenvironment,and the impact of immune cells on cancer development.Sophisticated tools are needed to provide quantitative information for a large number of biomarkers,lowabundance small molecules and chemotherapeutic drugs,while retaining spatial resolution of cells and tissue architecture.Methods:Imaging mass cytometry(IMC) is a novel multiparametric,quantitative technique for phenotypical and functional analysis of cells and tissue sections.It can measure more than 50 metal-containing reagents in tissues at 1μm X-Y spatial resolution.IMC combines laser ablation with mass cytometry.Stained tissue sections(FFPE or cryosections) or cells attached to glass slides are inserted into the laser ablation chamber,where a deep UV pulsed laser ablates the tissue.Results:IMC provides a specially designed laser beam optical path,visualization optics,and careful treatment of gas dynamics of the ablation chamber to achieve optimal performance.The system allows interrogation of tumor tissue sections with a 1 μm spot size,at 100 Hz laser repetition frequency,creating Individual plumes of particles from each spot.Individual isotopes are detected and indexed against the source location,yielding an intensity and spatial map of biomarker distribution in tissue or glass-plated cells using multiparametric visualization software.Conclusion:Precision medicine is based on access to high-density data(proteomics and genomics) which provides accurate diagnosis and information on the best therapeutic approach.IMC is a highly multiparametric,quantitative method for phenotypic,signaling pathway,and cell state protein identification together with spatial information within tissue sections.
Background:Pathology assessment of tissue sections provides prognostic evaluation and helps select optimum treatment regimens.Digital pathology has made significant strides in the analysis of several markers.There is a growing understanding of cell heterogeneity within tumor tissue,role of microenvironment,and the impact of immune cells on cancer development.Sophisticated tools are needed to provide quantitative information for a large number of biomarkers,lowabundance small molecules and chemotherapeutic drugs,while retaining spatial resolution of cells and tissue architecture.Methods:Imaging mass cytometry(IMC) is a novel multiparametric,quantitative technique for phenotypical and functional analysis of cells and tissue sections.It can measure more than 50 metal-containing reagents in tissues at 1μm X-Y spatial resolution.IMC combines laser ablation with mass cytometry.Stained tissue sections(FFPE or cryosections) or cells attached to glass slides are inserted into the laser ablation chamber,where a deep UV pulsed laser ablates the tissue.Results:IMC provides a specially designed laser beam optical path,visualization optics,and careful treatment of gas dynamics of the ablation chamber to achieve optimal performance.The system allows interrogation of tumor tissue sections with a 1 μm spot size,at 100 Hz laser repetition frequency,creating Individual plumes of particles from each spot.Individual isotopes are detected and indexed against the source location,yielding an intensity and spatial map of biomarker distribution in tissue or glass-plated cells using multiparametric visualization software.Conclusion:Precision medicine is based on access to high-density data(proteomics and genomics) which provides accurate diagnosis and information on the best therapeutic approach.IMC is a highly multiparametric,quantitative method for phenotypic,signaling pathway,and cell state protein identification together with spatial information within tissue sections.
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