scholarly journals High Spatial Resolution Ambient Ionization Mass Spectrometry Imaging Using Microscopy Image Fusion Determines Tumor Margins

2019 ◽  
Author(s):  
Li-En Lin ◽  
Chih-Lin Chen ◽  
Ying-Chen Huang ◽  
Hsin-Hsiang Chung ◽  
Chiao-Wei Lin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Imaging ◽  
Image Fusion ◽  
Electrospray Ionization ◽  
Spatial Resolution ◽  
Mass Spectrometry Imaging ◽  
Desorption Electrospray Ionization ◽  
Ambient Ionization ◽  
Tumor Margins ◽  
Tissue Sections

AbstractMass spectrometry imaging (MSI) using ambient ionization technique enables a direct chemical investigation of biological samples with minimal sample pretreatment. However, detailed morphological information of the sample is often lost due to its limited spatial resolution. In this study, predictive high-resolution molecular imaging was produced by the fusion of ambient ionization MSI with optical microscopy of routine hematoxylin and eosin (H&E) staining produces. Specifically, desorption electrospray ionization (DESI) and nanospray desorption electrospray ionization (nanoDESI) mass spectrometry are employed to visualize lipid and protein species on mice tissue sections. The resulting molecular distributions obtained by ambient ionization MSI-microscopy fusion are verified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI and immunohistochemistry (IHC) staining. Label-free molecular imaging with 5-μm spatial resolution can be acquired using DESI and nanoDESI, whereas the typical spatial resolution of ambient ionization MSI is ~100 μm. In this regard, sharpened molecular histology of tissue sections is achieved, providing complementary references to the pathology. Such a multimodality integration enables the discovery of potential tumor biomarkers. After image fusion, more than a dozen of potential biomarkers that could be used to determine the tumor margins on a metastatic mouse lung tissue section and Luminal B breast tumor tissue section are identified.

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples

2020 ◽  
Author(s):  
Xiangtang Li ◽  
ruichuan yin ◽  
hang hu ◽  
Yingju Li ◽  
Xiaofei Sun ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spatial Resolution ◽  
Biological Samples ◽  
Desorption Electrospray Ionization ◽  
Ambient Ionization ◽  
Liquid Extraction ◽  
Biological Research ◽  
Tissue Sections ◽  
Comparable Performance ◽  
And Performance

Ambient ionization based on liquid extraction is widely used in mass spectrometry<br>imaging (MSI) of molecules in biological samples. The development of nanospray desorption electrospray ionization (nano-DESI) has enabled the robust imaging of tissue sections with high spatial resolution. However, the fabrication of the nano-DESI probe is challenging, which limits its dissemination to the broader scientific community. Herein, we describe the design and performance of an integrated microfluidic probe (iMFP) for nano-DESI MSI. The glass iMFP fabricated using photolithography, wet etching, and polishing shows comparable performance to the capillary-based nano-DESI MSI in terms of stability and sensitivity; the spatial resolution of better than 25 μm was obtained in these first proof-of-principle experiments. The iMFP is easy to operate and align in front of a mass spectrometer, which will facilitate broader use of liquid extraction-based MSI in biological research, drug discovery, and clinical studies.

scholarly journals Nanospray Desorption Electrospray Ionization (nano-DESI) Mass Spectrometry Imaging of Drift Time-Separated Ions

2020 ◽  
Author(s):  
Daisy Unsihuay ◽  
ruichuan yin ◽  
Daniela Mesa Sanchez ◽  
Yingju Li ◽  
Xiaofei Sun ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Spatial Resolution ◽  
Ion Mobility ◽  
Mass Spectrometry Imaging ◽  
Structural Information ◽  
Biological Systems ◽  
Drift Time ◽  
Desorption Electrospray Ionization ◽  
Chemical Information

Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility spectrometer-mass spectrometer (IM-MS). Separation of biomolecules observed in MSI experiments based on their drift times provides unique molecular descriptors necessary for their identification by comparison with databases. Furthermore, it enables isomer-specific imaging, which is particularly important for unraveling the complexity of biological systems. Imaging of day 4 pregnant mouse uterine sections using the newly developed nano-DESI-IM-MSI system demonstrates rapid isobaric and isomeric separation and reduced chemical noise in MSI experiments. A direct comparison of the performance of the new nano-DESI-MSI platform operated in the MS mode with the more established nano-DESI-Orbitrap platform indicates a comparable performance of these two systems. A spatial resolution of better than ~16 µm and similar molecular coverage was obtained using both platforms. The structural information provided by the ion mobility separation expands the molecular specificity of high-resolution MSI necessary for the detailed understanding of biological systems.

scholarly journals Desorption Electrospray Ionization then MALDI Mass Spectrometry Imaging of Lipid and Protein Distributions in Single Tissue Sections

2011 ◽  
Vol 83 (22) ◽  
pp. 8366-8371 ◽  
Author(s):  
Livia S. Eberlin ◽  
Xiaohui Liu ◽  
Christina R. Ferreira ◽  
Sandro Santagata ◽  
Nathalie Y.R. Agar ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Mass Spectrometry Imaging ◽  
Desorption Electrospray Ionization ◽  
Maldi Mass Spectrometry ◽  
Tissue Sections ◽  
Maldi Mass Spectrometry Imaging

scholarly journals Nanospray Desorption Electrospray Ionization (nano-DESI) Mass Spectrometry Imaging of Drift Time-Separated Ions

2020 ◽  
Author(s):  
Daisy Unsihuay ◽  
ruichuan yin ◽  
Daniela Mesa Sanchez ◽  
Yingju Li ◽  
Xiaofei Sun ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Spatial Resolution ◽  
Ion Mobility ◽  
Mass Spectrometry Imaging ◽  
Structural Information ◽  
Biological Systems ◽  
Drift Time ◽  
Desorption Electrospray Ionization ◽  
Chemical Information

Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility spectrometer-mass spectrometer (IM-MS). Separation of biomolecules observed in MSI experiments based on their drift times provides unique molecular descriptors necessary for their identification by comparison with databases. Furthermore, it enables isomer-specific imaging, which is particularly important for unraveling the complexity of biological systems. Imaging of day 4 pregnant mouse uterine sections using the newly developed nano-DESI-IM-MSI system demonstrates rapid isobaric and isomeric separation and reduced chemical noise in MSI experiments. A direct comparison of the performance of the new nano-DESI-MSI platform operated in the MS mode with the more established nano-DESI-Orbitrap platform indicates a comparable performance of these two systems. A spatial resolution of better than ~16 µm and similar molecular coverage was obtained using both platforms. The structural information provided by the ion mobility separation expands the molecular specificity of high-resolution MSI necessary for the detailed understanding of biological systems.

scholarly journals Quantitative mass spectrometry imaging of glutathione in healthy and cancerous hen ovarian tissue sections by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)

The Analyst ◽  
2018 ◽  
Vol 143 (3) ◽  
pp. 654-661 ◽  
Author(s):  
Milad Nazari ◽  
Mark T. Bokhart ◽  
Philip L. Loziuk ◽  
David C. Muddiman
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Mass Spectrometry Imaging ◽  
Ovarian Tissue ◽  
Desorption Electrospray Ionization ◽  
Laser Desorption ◽  
Quantitative Mass Spectrometry ◽  
Tissue Sections ◽  
Matrix Assisted Laser ◽  
Matrix Assisted Laser Desorption

IR-MALDESI quantitative mass spectrometry imaging of glutathione in healthy and cancerous hen ovarian tissues.

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples

2020 ◽  
Author(s):  
Xiangtang Li ◽  
ruichuan yin ◽  
hang hu ◽  
Yingju Li ◽  
Xiaofei Sun ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spatial Resolution ◽  
Biological Samples ◽  
Desorption Electrospray Ionization ◽  
Ambient Ionization ◽  
Liquid Extraction ◽  
Biological Research ◽  
Tissue Sections ◽  
Comparable Performance ◽  
And Performance

Ambient ionization based on liquid extraction is widely used in mass spectrometry<br>imaging (MSI) of molecules in biological samples. The development of nanospray desorption electrospray ionization (nano-DESI) has enabled the robust imaging of tissue sections with high spatial resolution. However, the fabrication of the nano-DESI probe is challenging, which limits its dissemination to the broader scientific community. Herein, we describe the design and performance of an integrated microfluidic probe (iMFP) for nano-DESI MSI. The glass iMFP fabricated using photolithography, wet etching, and polishing shows comparable performance to the capillary-based nano-DESI MSI in terms of stability and sensitivity; the spatial resolution of better than 25 μm was obtained in these first proof-of-principle experiments. The iMFP is easy to operate and align in front of a mass spectrometer, which will facilitate broader use of liquid extraction-based MSI in biological research, drug discovery, and clinical studies.

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