Solvent effects on differentiation of mouse brain tissue using laser microdissection ‘cut and drop’ sampling with direct mass spectral analysis

Cahill, John F.; Kertesz, Vilmos; Porta, Tiffany; LeBlanc, J. C.  Yves; Heeren, Ron M. A.; Van Berkel, Gary J.

doi:10.1002/rcm.8053

Solvent effects on differentiation of mouse brain tissue using laser microdissection ‘cut and drop’ sampling with direct mass spectral analysis

Journal Article · Thu Feb 08 00:00:00 EST 2018 · Rapid Communications in Mass Spectrometry

DOI:https://doi.org/10.1002/rcm.8053· OSTI ID:1436950

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Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division, Mass Spectrometry and Laser Spectroscopy Group
Maastricht Univ., Maastricht (The Netherlands). Maastricht MultiModal Molecular Imaging (M4I) inst., Division of Imaging Mass Spectrometry
Sciex, Concord, ON (Canada)

Rationale: Laser microdissection-liquid vortex capture/electrospray ionization mass spectrometry (LMD-LVC/ESI-MS) has potential for on-line classification of tissue but an investigation into what analytical conditions provide best spectral differentiation has not been conducted. The effects of solvent, ionization polarity, and spectral acquisition parameters on differentiation of mouse brain tissue regions are described.Methods: Individual 40 × 40 μm microdissections from cortex, white, grey, granular, and nucleus regions of mouse brain tissue were analyzed using different capture/ESI solvents, in positive and negative ion mode ESI, using time-of-flight (TOF)-MS and sequential window acquisitions of all theoretical spectra (SWATH)-MS (a permutation of tandem-MS), and combinations thereof. Principal component analysis-linear discriminant analysis (PCA-LDA), applied to each mass spectral dataset, was used to determine the accuracy of differentiation of mouse brain tissue regions. Results: Mass spectral differences associated with capture/ESI solvent composition manifested as altered relative distributions of ions rather than the presence or absence of unique ions. In negative ion mode ESI, 80/20 (v/v) methanol/water yielded spectra with low signal/noise ratios relative to other solvents. PCA-LDA models acquired using 90/10 (v/v) methanol/chloroform differentiated tissue regions with 100% accuracy while data collected using methanol misclassified some samples. The combination of SWATH-MS and TOF-MS data improved differentiation accuracy.Conclusions: Combined TOF-MS and SWATH-MS data differentiated white, grey, granular, and nucleus mouse tissue regions with greater accuracy than when solely using TOF-MS data. Using 90/10 (v/v) methanol/chloroform, tissue regions were perfectly differentiated. Lastly, these results will guide future studies looking to utilize the potential of LMD-LVC/ESI-MS for tissue and disease differentiation.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1436950

Alternate ID(s):: OSTI ID: 1419991

Journal Information:: Rapid Communications in Mass Spectrometry, Journal Name: Rapid Communications in Mass Spectrometry Journal Issue: 5 Vol. 32; ISSN 0951-4198

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (55)

Mass Spectrometric Profiling of Intact Biological Tissue by Using Desorption Electrospray Ionization Wiseman, Justin M.; Puolitaival, Satu M.; Takáts, Zoltán Angewandte Chemie, Vol. 117, Issue 43 https://doi.org/10.1002/ange.200502362	journal	November 2005
Discrimination of Human Astrocytoma Subtypes by Lipid Analysis Using Desorption Electrospray Ionization Imaging Mass Spectrometry Eberlin, Livia S.; Dill, Allison L.; Golby, Alexandra J. Angewandte Chemie, Vol. 122, Issue 34 https://doi.org/10.1002/ange.201001452	journal	July 2010
Mass Spectrometric Profiling of Intact Biological Tissue by Using Desorption Electrospray Ionization Wiseman, Justin M.; Puolitaival, Satu M.; Takáts, Zoltán Angewandte Chemie International Edition, Vol. 44, Issue 43 https://doi.org/10.1002/anie.200502362	journal	November 2005
Discrimination of Human Astrocytoma Subtypes by Lipid Analysis Using Desorption Electrospray Ionization Imaging Mass Spectrometry Eberlin, Livia S.; Dill, Allison L.; Golby, Alexandra J. Angewandte Chemie International Edition, Vol. 49, Issue 34 https://doi.org/10.1002/anie.201001452	journal	July 2010
Multivariate Statistical Identification of Human Bladder Carcinomas Using Ambient Ionization Imaging Mass Spectrometry Dill, Allison L.; Eberlin, Livia S.; Costa, Anthony B. Chemistry - A European Journal, Vol. 17, Issue 10 https://doi.org/10.1002/chem.201001692	journal	January 2011
Mass spectrometry imaging as a tool for surgical decision-making Calligaris, D.; Norton, I.; Feldman, D. R. Journal of Mass Spectrometry, Vol. 48, Issue 11 https://doi.org/10.1002/jms.3194	journal	November 2013
Mass spectrometry imaging as a tool for surgical decision-making: Intraoperative mass spectrometry Calligaris, David; Norton, Isaiah; Feldman, Daniel R. Journal of Mass Spectrometry, Vol. 48, Issue 11 https://doi.org/10.1002/jms.3295	journal	November 2013
Phospholipids in liquid chromatography/mass spectrometry bioanalysis: comparison of three tandem mass spectrometric techniques for monitoring plasma phospholipids, the effect of mobile phase composition on phospholipids elution and the association of phospholipids with matrix effects Xia, Yuan-Qing; Jemal, Mohammed Rapid Communications in Mass Spectrometry, Vol. 23, Issue 14 https://doi.org/10.1002/rcm.4121	journal	July 2009
An open port sampling interface for liquid introduction atmospheric pressure ionization mass spectrometry: Open port sampling interface Van Berkel, Gary J.; Kertesz, Vilmos Rapid Communications in Mass Spectrometry, Vol. 29, Issue 19 https://doi.org/10.1002/rcm.7274	journal	August 2015
Laser dissection sampling modes for direct mass spectral analysis: Laser dissection sampling modes for mass spectral analysis Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J. Rapid Communications in Mass Spectrometry, Vol. 30, Issue 5 https://doi.org/10.1002/rcm.7477	journal	February 2016
Rapid sample classification using an open port sampling interface coupled with liquid introduction atmospheric pressure ionization mass spectrometry: Sample classification using an open port sampling interface Van Berkel, Gary J.; Kertesz, Vilmos Rapid Communications in Mass Spectrometry, Vol. 31, Issue 3 https://doi.org/10.1002/rcm.7792	journal	January 2017
Feasibility of desorption electrospray ionization mass spectrometry for diagnosis of oral tongue squamous cell carcinoma D'Hue, Cedric; Moore, Michael; Summerlin, Don-John Rapid Communications in Mass Spectrometry, Vol. 32, Issue 2 https://doi.org/10.1002/rcm.8019	journal	December 2017
Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry Dill, Allison L.; Eberlin, Livia S.; Zheng, Cheng Analytical and Bioanalytical Chemistry, Vol. 398, Issue 7-8 https://doi.org/10.1007/s00216-010-4259-6	journal	October 2010
Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging Gerbig, Stefanie; Golf, Ottmar; Balog, Julia Analytical and Bioanalytical Chemistry, Vol. 403, Issue 8 https://doi.org/10.1007/s00216-012-5841-x	journal	March 2012
Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S. Journal of The American Society for Mass Spectrometry, Vol. 22, Issue 8 https://doi.org/10.1007/s13361-011-0134-8	journal	April 2011
Application of Probe Electrospray Ionization Mass Spectrometry (PESI-MS) to Clinical Diagnosis: Solvent Effect on Lipid Analysis Mandal, Mridul Kanti; Yoshimura, Kentaro; Chen, Lee Chuin Journal of The American Society for Mass Spectrometry, Vol. 23, Issue 11 https://doi.org/10.1007/s13361-012-0462-3	journal	August 2012
Desorption electrospray ionization mass spectrometry for lipid characterization and biological tissue imaging Eberlin, Livia S.; Ferreira, Christina R.; Dill, Allison L. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1811, Issue 11 https://doi.org/10.1016/j.bbalip.2011.05.006	journal	November 2011
Molecular typing of meningiomas by desorption electrospray ionization mass spectrometry imaging for surgical decision-making Calligaris, David; Feldman, Daniel R.; Norton, Isaiah International Journal of Mass Spectrometry, Vol. 377 https://doi.org/10.1016/j.ijms.2014.06.024	journal	February 2015
Total structure characterization of unsaturated acidic phospholipids provided by vicinal di-hydroxylation of fatty acid double bonds and negative electrospray ionization mass spectrometry Moe, Morten K.; Anderssen, Trude; Strøm, Morten B. Journal of the American Society for Mass Spectrometry, Vol. 16, Issue 1 https://doi.org/10.1016/j.jasms.2004.09.014	journal	January 2005
Mass spectrometric imaging of lipids using desorption electrospray ionization Dill, Allison L.; Ifa, Demian R.; Manicke, Nicholas E. Journal of Chromatography B, Vol. 877, Issue 26 https://doi.org/10.1016/j.jchromb.2008.12.058	journal	September 2009
In Situ, Real-Time Identification of Biological Tissues by Ultraviolet and Infrared Laser Desorption Ionization Mass Spectrometry Schäfer, Karl-Christian; Szaniszló, Tamás; Günther, Sabine Analytical Chemistry, Vol. 83, Issue 5 https://doi.org/10.1021/ac102613m	journal	March 2011
Real Time Analysis of Brain Tissue by Direct Combination of Ultrasonic Surgical Aspiration and Sonic Spray Mass Spectrometry Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás Analytical Chemistry, Vol. 83, Issue 20 https://doi.org/10.1021/ac201251s	journal	October 2011
Quantitative Spatial Analysis of the Mouse Brain Lipidome by Pressurized Liquid Extraction Surface Analysis Almeida, Reinaldo; Berzina, Zane; Arnspang, Eva C. Analytical Chemistry, Vol. 87, Issue 3 https://doi.org/10.1021/ac503627z	journal	January 2015
Rapid Evaporative Ionization Mass Spectrometry Imaging Platform for Direct Mapping from Bulk Tissue and Bacterial Growth Media Golf, Ottmar; Strittmatter, Nicole; Karancsi, Tamas Analytical Chemistry, Vol. 87, Issue 5 https://doi.org/10.1021/ac5046752	journal	February 2015
Simultaneous Imaging of Small Metabolites and Lipids in Rat Brain Tissues at Atmospheric Pressure by Laser Ablation Electrospray Ionization Mass Spectrometry Nemes, Peter; Woods, Amina S.; Vertes, Akos Analytical Chemistry, Vol. 82, Issue 3 https://doi.org/10.1021/ac902245p	journal	February 2010
Cholesterol Sulfate Imaging in Human Prostate Cancer Tissue by Desorption Electrospray Ionization Mass Spectrometry Eberlin, Livia S.; Dill, Allison L.; Costa, Anthony B. Analytical Chemistry, Vol. 82, Issue 9 https://doi.org/10.1021/ac9029482	journal	May 2010
Characterization and Application of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging with Sub-micrometer Spatial Resolution Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J. Analytical Chemistry, Vol. 87, Issue 21 https://doi.org/10.1021/acs.analchem.5b03293	journal	July 2015
Online, Absolute Quantitation of Propranolol from Spatially Distinct 20- and 40-μm Dissections of Brain, Liver, and Kidney Thin Tissue Sections by Laser Microdissection–Liquid Vortex Capture–Mass Spectrometry Cahill, John F.; Kertesz, Vilmos; Weiskittel, Taylor M. Analytical Chemistry, Vol. 88, Issue 11 https://doi.org/10.1021/acs.analchem.6b01155	journal	May 2016
Identification of expressed genes by laser-mediated manipulation of single cells Schüitze, Karin; Lahr, Georgia Nature Biotechnology, Vol. 16, Issue 8 https://doi.org/10.1038/nbt0898-737	journal	August 1998
In vivo Real-Time Mass Spectrometry for Guided Surgery Application Fatou, Benoit; Saudemont, Philippe; Leblanc, Eric Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep25919	journal	May 2016
Imaging mass spectrometry of a mouse brain by tapping-mode scanning probe electrospray ionization Otsuka, Yoichi; Naito, Junpei; Satoh, Shuya The Analyst, Vol. 139, Issue 10 https://doi.org/10.1039/C3AN02340K	journal	January 2014
Discrimination of lymph node metastases using desorption electrospray ionisation-mass spectrometry imaging Abbassi-Ghadi, N.; Veselkov, K.; Kumar, S. Chem. Commun., Vol. 50, Issue 28 https://doi.org/10.1039/C3CC48927B	journal	January 2014
Touch spray mass spectrometry for in situ analysis of complex samples Kerian, Kevin S.; Jarmusch, Alan K.; Cooks, R. Graham The Analyst, Vol. 139, Issue 11 https://doi.org/10.1039/C4AN00548A	journal	January 2014
Differentiation of prostate cancer from normal tissue in radical prostatectomy specimens by desorption electrospray ionization and touch spray ionization mass spectrometry Kerian, K. S.; Jarmusch, A. K.; Pirro, V. The Analyst, Vol. 140, Issue 4 https://doi.org/10.1039/C4AN02039A	journal	January 2015
Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration Woolman, Michael; Tata, Alessandra; Dara, Delaram The Analyst, Vol. 142, Issue 17 https://doi.org/10.1039/C7AN00830A	journal	January 2017
Solid probe assisted nanoelectrospray ionization mass spectrometry for biological tissue diagnostics Mandal, Mridul Kanti; Yoshimura, Kentaro; Saha, Subhrakanti The Analyst, Vol. 137, Issue 20 https://doi.org/10.1039/c2an36006c	journal	January 2012
Biomolecular analysis and cancer diagnostics by negative mode probe electrospray ionization Mandal, Mridul Kanti; Saha, Subhrakanti; Yoshimura, Kentaro The Analyst, Vol. 138, Issue 6 https://doi.org/10.1039/c3an36554a	journal	January 2013
Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors Eberlin, L. S.; Norton, I.; Orringer, D. Proceedings of the National Academy of Sciences, Vol. 110, Issue 5 https://doi.org/10.1073/pnas.1215687110	journal	January 2013
Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging Eberlin, L. S.; Tibshirani, R. J.; Zhang, J. Proceedings of the National Academy of Sciences, Vol. 111, Issue 7 https://doi.org/10.1073/pnas.1400274111	journal	February 2014
Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery Santagata, S.; Eberlin, L. S.; Norton, I. Proceedings of the National Academy of Sciences, Vol. 111, Issue 30 https://doi.org/10.1073/pnas.1404724111	journal	June 2014
Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis Calligaris, David; Caragacianu, Diana; Liu, Xiaohui Proceedings of the National Academy of Sciences, Vol. 111, Issue 42 https://doi.org/10.1073/pnas.1408129111	journal	September 2014
Alteration of the lipid profile in lymphomas induced by MYC overexpression Eberlin, L. S.; Gabay, M.; Fan, A. C. Proceedings of the National Academy of Sciences, Vol. 111, Issue 29 https://doi.org/10.1073/pnas.1409778111	journal	July 2014
Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS Jarmusch, Alan K.; Pirro, Valentina; Baird, Zane Proceedings of the National Academy of Sciences, Vol. 113, Issue 6 https://doi.org/10.1073/pnas.1523306113	journal	January 2016
Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry Brugger, B.; Erben, G.; Sandhoff, R. Proceedings of the National Academy of Sciences, Vol. 94, Issue 6 https://doi.org/10.1073/pnas.94.6.2339	journal	March 1997
Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis Gillet, Ludovic C.; Navarro, Pedro; Tate, Stephen Molecular & Cellular Proteomics, Vol. 11, Issue 6 https://doi.org/10.1074/mcp.O111.016717	journal	January 2012
Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry Balog, J.; Sasi-Szabo, L.; Kinross, J. Science Translational Medicine, Vol. 5, Issue 194 https://doi.org/10.1126/scitranslmed.3005623	journal	July 2013
Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system Zhang, Jialing; Rector, John; Lin, John Q. Science Translational Medicine, Vol. 9, Issue 406 https://doi.org/10.1126/scitranslmed.aan3968	journal	September 2017
Chemical Aspects of the Extractive Methods of Ambient Ionization Mass Spectrometry Badu-Tawiah, Abraham K.; Eberlin, Livia S.; Ouyang, Zheng Annual Review of Physical Chemistry, Vol. 64, Issue 1 https://doi.org/10.1146/annurev-physchem-040412-110026	journal	April 2013
Classifying Human Brain Tumors by Lipid Imaging with Mass Spectrometry Eberlin, L. S.; Norton, I.; Dill, A. L. Cancer Research, Vol. 72, Issue 3 https://doi.org/10.1158/0008-5472.CAN-11-2465	journal	December 2011
Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry Guenther, S.; Muirhead, L. J.; Speller, A. V. M. Cancer Research, Vol. 75, Issue 9 https://doi.org/10.1158/0008-5472.CAN-14-2258	journal	February 2015
Imaging regiospecific lipid turnover in mouse brain with desorption electrospray ionization mass spectrometry Carson, Richard H.; Lewis, Charlotte R.; Erickson, Mercede N. Journal of Lipid Research, Vol. 58, Issue 9 https://doi.org/10.1194/jlr.M078170	journal	July 2017
Development of Stereotactic Mass Spectrometry for Brain Tumor Surgery Agar, Nathalie Y. R.; Golby, Alexandra J.; Ligon, Keith L. Neurosurgery, Vol. 68, Issue 2 https://doi.org/10.1227/NEU.0b013e3181ff9cbb	journal	February 2011
Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging Eberlin, Livia S.; Margulis, Katherine; Planell-Mendez, Ivette PLOS Medicine, Vol. 13, Issue 8 https://doi.org/10.1371/journal.pmed.1002108	journal	August 2016
Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization – Mass Spectrometry Imaging Jarmusch, Alan K.; Alfaro, Clint M.; Pirro, Valentina PLOS ONE, Vol. 11, Issue 9 https://doi.org/10.1371/journal.pone.0163180	journal	September 2016
Ambient Ionization Mass Spectrometry for Cancer Diagnosis and Surgical Margin Evaluation Ifa, D. R.; Eberlin, L. S. Clinical Chemistry, Vol. 62, Issue 1 https://doi.org/10.1373/clinchem.2014.237172	journal	November 2015

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