High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry
Abstract
Mass spectrometry imaging (MSI) enables label-free spatial mapping of hundreds of biomolecules in tissue sections. This capability provides valuable information on tissue heterogeneity that is difficult to obtain using population-averaged assays. Despite substantial developments in both instrumentation and methodology, MSI of tissue samples at single-cell resolution remains challenging. In our research, we describe a protocol for robust imaging of tissue sections with a high (better than 10-μm) spatial resolution using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry, an ambient ionization technique that does not require sample pretreatment before analysis. In this protocol, mouse uterine tissue is used as a model system to illustrate both the workflow and data obtained in these experiments. We provide a detailed description of the nano-DESI MSI platform, fabrication of the nano-DESI and shear force probes, shear force microscopy experiments, spectral acquisition, and data processing. A properly trained researcher (e.g., technician, graduate student, or postdoc) can complete all the steps from probe fabrication to data acquisition and processing within a single day. We further describe a new strategy for acquiring both positive- and negative-mode imaging data in the same experiment. This is achieved by alternating between positive and negative data acquisition modes during consecutive line scans.more »
- Authors:
-
- Purdue Univ., West Lafayette, IN (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Univ. of Cincinnati, OH (United States)
- Purdue Univ., West Lafayette, IN (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1608770
- Report Number(s):
- PNNL-SA-142602
Journal ID: ISSN 1754-2189
- Grant/Contract Number:
- AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Protocols
- Additional Journal Information:
- Journal Volume: 14; Journal Issue: 12; Journal ID: ISSN 1754-2189
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Yin, Ruichuan, Burnum-Johnson, Kristin E., Sun, Xiaofei, Dey, Sudhansu K., and Laskin, Julia. High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry. United States: N. p., 2019.
Web. doi:10.1038/s41596-019-0237-4.
Yin, Ruichuan, Burnum-Johnson, Kristin E., Sun, Xiaofei, Dey, Sudhansu K., & Laskin, Julia. High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry. United States. https://doi.org/10.1038/s41596-019-0237-4
Yin, Ruichuan, Burnum-Johnson, Kristin E., Sun, Xiaofei, Dey, Sudhansu K., and Laskin, Julia. Wed .
"High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry". United States. https://doi.org/10.1038/s41596-019-0237-4. https://www.osti.gov/servlets/purl/1608770.
@article{osti_1608770,
title = {High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry},
author = {Yin, Ruichuan and Burnum-Johnson, Kristin E. and Sun, Xiaofei and Dey, Sudhansu K. and Laskin, Julia},
abstractNote = {Mass spectrometry imaging (MSI) enables label-free spatial mapping of hundreds of biomolecules in tissue sections. This capability provides valuable information on tissue heterogeneity that is difficult to obtain using population-averaged assays. Despite substantial developments in both instrumentation and methodology, MSI of tissue samples at single-cell resolution remains challenging. In our research, we describe a protocol for robust imaging of tissue sections with a high (better than 10-μm) spatial resolution using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry, an ambient ionization technique that does not require sample pretreatment before analysis. In this protocol, mouse uterine tissue is used as a model system to illustrate both the workflow and data obtained in these experiments. We provide a detailed description of the nano-DESI MSI platform, fabrication of the nano-DESI and shear force probes, shear force microscopy experiments, spectral acquisition, and data processing. A properly trained researcher (e.g., technician, graduate student, or postdoc) can complete all the steps from probe fabrication to data acquisition and processing within a single day. We further describe a new strategy for acquiring both positive- and negative-mode imaging data in the same experiment. This is achieved by alternating between positive and negative data acquisition modes during consecutive line scans. Using our imaging approach, hundreds of high-quality ion images were obtained from a single uterine section. This protocol enables sensitive and quantitative imaging of lipids and metabolites in heterogeneous tissue sections with high spatial resolution, which is critical to understanding biochemical processes occurring in biological tissues.},
doi = {10.1038/s41596-019-0237-4},
journal = {Nature Protocols},
number = 12,
volume = 14,
place = {United States},
year = {2019},
month = {11}
}
Web of Science
Works referenced in this record:
Roadmap to embryo implantation: clues from mouse models
journal, March 2006
- Wang, Haibin; Dey, Sudhansu K.
- Nature Reviews Genetics, Vol. 7, Issue 3
Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections
journal, February 2007
- Stoeckli, Markus; Staab, Dieter; Schweitzer, Alain
- International Journal of Mass Spectrometry, Vol. 260, Issue 2-3
Imaging mass spectrometry: Instrumentation, applications, and combination with other visualization techniques: IMAGING MASS SPECTROMETRY
journal, May 2015
- Bodzon-Kulakowska, Anna; Suder, Piotr
- Mass Spectrometry Reviews, Vol. 35, Issue 1
Quantitative Mass Spectrometry Imaging of Prostaglandins as Silver Ion Adducts with Nanospray Desorption Electrospray Ionization
journal, April 2018
- Duncan, Kyle D.; Fang, Ru; Yuan, Jia
- Analytical Chemistry, Vol. 90, Issue 12
Constant-Distance Mode Scanning Electrochemical Microscopy (SECM)—Part I: Adaptation of a Non-Optical Shear-Force-Based Positioning Mode for SECM Tips
journal, May 2003
- Ballesteros Katemann, Bernardo; Schulte, Albert; Schuhmann, Wolfgang
- Chemistry - A European Journal, Vol. 9, Issue 9
Evidence for 5-Hydroxyeicosatetraenoic Acid (5-HETE) and Leukotriene C 4 (LTC 4 ) in the Onset of Labor b
journal, May 1991
- Walsh, Scott W.
- Annals of the New York Academy of Sciences, Vol. 622, Issue 1 The Primate E
Mass spectrometry imaging under ambient conditions
journal, September 2012
- Wu, Chunping; Dill, Allison L.; Eberlin, Livia S.
- Mass Spectrometry Reviews, Vol. 32, Issue 3
Oversampling To Improve Spatial Resolution for Liquid Extraction Mass Spectrometry Imaging
journal, January 2018
- Duncan, Kyle D.; Lanekoff, Ingela
- Analytical Chemistry, Vol. 90, Issue 4
Improved spatial resolution in the imaging of biological tissue using desorption electrospray ionization
journal, June 2012
- Campbell, Dahlia I.; Ferreira, Christina R.; Eberlin, Livia S.
- Analytical and Bioanalytical Chemistry, Vol. 404, Issue 2
Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site
journal, September 2016
- Lanekoff, Ingela; Cha, Jeeyeon; Kyle, Jennifer E.
- Scientific Reports, Vol. 6, Issue 1
Gas Cluster Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry High-Resolution Imaging of Cardiolipin Speciation in the Brain: Identification of Molecular Losses after Traumatic Injury
journal, March 2017
- Tian, Hua; Sparvero, Louis J.; Amoscato, Andrew A.
- Analytical Chemistry, Vol. 89, Issue 8
Ambient Ionization Mass Spectrometry: Recent Developments and Applications
journal, February 2019
- Feider, Clara L.; Krieger, Anna; DeHoog, Rachel J.
- Analytical Chemistry, Vol. 91, Issue 7
Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy
journal, July 2017
- Nguyen, Son N.; Sontag, Ryan L.; Carson, James P.
- Journal of The American Society for Mass Spectrometry, Vol. 29, Issue 2
Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization
journal, January 2016
- Bergman, Hilde-Marléne; Lundin, Erik; Andersson, Malin
- The Analyst, Vol. 141, Issue 12
Rapid, Direct Analysis of Cholesterol by Charge Labeling in Reactive Desorption Electrospray Ionization
journal, September 2009
- Wu, Chunping; Ifa, Demian R.; Manicke, Nicholas E.
- Analytical Chemistry, Vol. 81, Issue 18
Mass spectrometry imaging for drugs and metabolites
journal, November 2011
- Greer, Tyler; Sturm, Robert; Li, Lingjun
- Journal of Proteomics, Vol. 74, Issue 12
Three-dimensional imaging of lipids and metabolites in tissues by nanospray desorption electrospray ionization mass spectrometry
journal, November 2014
- Lanekoff, Ingela; Burnum-Johnson, Kristin; Thomas, Mathew
- Analytical and Bioanalytical Chemistry, Vol. 407, Issue 8
Imaging of Proteins in Tissue Samples Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, October 2015
- Hsu, Cheng-Chih; Chou, Pi-Tai; Zare, Richard N.
- Analytical Chemistry, Vol. 87, Issue 22
Secondary‐Ion Mass Spectrometry Images Cardiolipins and Phosphatidylethanolamines at the Subcellular Level
journal, January 2019
- Tian, Hua; Sparvero, Louis J.; Blenkinsopp, Paul
- Angewandte Chemie, Vol. 131, Issue 10
Shotgun Approach for Quantitative Imaging of Phospholipids Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, January 2014
- Lanekoff, Ingela; Thomas, Mathew; Laskin, Julia
- Analytical Chemistry, Vol. 86, Issue 3
Tissue protein imaging at 1 μm laser spot diameter for high spatial resolution and high imaging speed using transmission geometry MALDI TOF MS
journal, February 2015
- Zavalin, Andre; Yang, Junhai; Hayden, Kevin
- Analytical and Bioanalytical Chemistry, Vol. 407, Issue 8
Constant-Distance Mode Nanospray Desorption Electrospray Ionization Mass Spectrometry Imaging of Biological Samples with Complex Topography
journal, December 2016
- Nguyen, Son N.; Liyu, Andrey V.; Chu, Rosalie K.
- Analytical Chemistry, Vol. 89, Issue 2
Discovery of a second 15S-lipoxygenase in humans
journal, June 1997
- Brash, A. R.; Boeglin, W. E.; Chang, M. S.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 12
Imaging mass spectrometry: fundamentals and applications to drug discovery
journal, June 2005
- Rubakhin, Stanislav S.; Jurchen, John C.; Monroe, Eric B.
- Drug Discovery Today, Vol. 10, Issue 12
Shear force microscopy with a nanoscale resolution
journal, June 2005
- Ndobo-Epoy, J. -P.; Lesniewska, E.; Guicquero, J. -P.
- Ultramicroscopy, Vol. 103, Issue 3
Imaging mass spectrometry of thin tissue sections: A decade of collective efforts
journal, August 2012
- Chaurand, Pierre
- Journal of Proteomics, Vol. 75, Issue 16
Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, December 2011
- Laskin, Julia; Heath, Brandi S.; Roach, Patrick J.
- Analytical Chemistry, Vol. 84, Issue 1
Lipid Coverage in Nanospray Desorption Electrospray Ionization Mass Spectrometry Imaging of Mouse Lung Tissues
journal, August 2019
- Nguyen, Son N.; Kyle, Jennifer E.; Dautel, Sydney E.
- Analytical Chemistry, Vol. 91, Issue 18
High Spatial Resolution Imaging of Mouse Pancreatic Islets Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, April 2018
- Yin, Ruichuan; Kyle, Jennifer; Burnum-Johnson, Kristin
- Analytical Chemistry, Vol. 90, Issue 11
High-Spatial Resolution Mass Spectrometric Imaging of Peptide and Protein Distributions on a Surface
journal, September 2004
- Luxembourg, Stefan L.; Mize, Todd H.; McDonnell, Liam A.
- Analytical Chemistry, Vol. 76, Issue 18
Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS: Single-cell imaging with transmission geometry
journal, November 2012
- Zavalin, Andre; Todd, Erik M.; Rawhouser, Patrick D.
- Journal of Mass Spectrometry, Vol. 47, Issue 11
Relationship between MALDI IMS Intensity and Measured Quantity of Selected Phospholipids in Rat Brain Sections
journal, October 2010
- Hankin, Joseph A.; Murphy, Robert C.
- Analytical Chemistry, Vol. 82, Issue 20
Mass spectrometry imaging for clinical research – latest developments, applications, and current limitations
journal, January 2017
- Vaysse, Pierre-Maxence; Heeren, Ron M. A.; Porta, Tiffany
- The Analyst, Vol. 142, Issue 15
Imaging mass spectrometry: Hype or hope?
journal, June 2009
- Heeren, Ron M. A.; Smith, Donald F.; Stauber, Jonathan
- Journal of the American Society for Mass Spectrometry, Vol. 20, Issue 6
Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation
journal, January 2003
- Schwartz, Sarah A.; Reyzer, Michelle L.; Caprioli, Richard M.
- Journal of Mass Spectrometry, Vol. 38, Issue 7
Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-μm lateral resolution
journal, November 2016
- Kompauer, Mario; Heiles, Sven; Spengler, Bernhard
- Nature Methods, Vol. 14, Issue 1
A pneumatically assisted nanospray desorption electrospray ionization source for increased solvent versatility and enhanced metabolite detection from tissue
journal, January 2017
- Duncan, Kyle D.; Bergman, Hilde-Marléne; Lanekoff, Ingela
- The Analyst, Vol. 142, Issue 18
Analysis of Tissue Specimens by Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry in Biological and Clinical Research
journal, February 2013
- Norris, Jeremy L.; Caprioli, Richard M.
- Chemical Reviews, Vol. 113, Issue 4
Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation
journal, May 2009
- Burnum, Kristin E.; Cornett, Dale S.; Puolitaival, Satu M.
- Journal of Lipid Research, Vol. 50, Issue 11
Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques
journal, November 2015
- Laskin, Julia; Lanekoff, Ingela
- Analytical Chemistry, Vol. 88, Issue 1
Multiple Female Reproductive Failures in Cyclooxygenase 2–Deficient Mice
journal, October 1997
- Lim, Hyunjung; Paria, Bibhash C.; Das, Sanjoy K.
- Cell, Vol. 91, Issue 2
Desorption Electrospray Ionization Mass Spectrometry Imaging of Proteins Directly from Biological Tissue Sections
journal, May 2018
- Garza, Kyana Y.; Feider, Clara L.; Klein, Dustin R.
- Analytical Chemistry, Vol. 90, Issue 13
Automated Platform for High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, September 2012
- Lanekoff, Ingela; Heath, Brandi S.; Liyu, Andrey
- Analytical Chemistry, Vol. 84, Issue 19
Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry
journal, December 2012
- Lanekoff, Ingela; Thomas, Mathew; Carson, James P.
- Analytical Chemistry, Vol. 85, Issue 2
Matrix effects in biological mass spectrometry imaging: identification and compensation
journal, January 2014
- Lanekoff, Ingela; Stevens, Susan L.; Stenzel-Poore, Mary P.
- The Analyst, Vol. 139, Issue 14
High Resolution Tissue Imaging Using the Single-probe Mass Spectrometry under Ambient Conditions
journal, March 2015
- Rao, Wei; Pan, Ning; Yang, Zhibo
- Journal of The American Society for Mass Spectrometry, Vol. 26, Issue 6
Secondary‐Ion Mass Spectrometry Images Cardiolipins and Phosphatidylethanolamines at the Subcellular Level
journal, March 2019
- Tian, Hua; Sparvero, Louis J.; Blenkinsopp, Paul
- Angewandte Chemie International Edition, Vol. 58, Issue 10
Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS
journal, November 2012
- Zavalin, Andre; Todd, Erik M.; Rawhouser, Patrick D.
- Journal of Mass Spectrometry, Vol. 47, Issue 11