118:
and thyroid tissues. The mass spectra obtained for each sample contained metabolites, lipids, and some proteins that were representative of the molecular composition of the tissue analyzed. The collected data for each tissue type was then used to develop statistical models that could discriminate between the normal and cancer samples of each tissue type. Leave-one-patient-out cross validation was used to evaluate the accuracy of the models for distinguishing the normal and cancer tissues based on their molecular profiles. The method allowed for diagnosis of the breast tissues with 95.6% accuracy, lung with 96.8% accuracy, and ovary with 94.7% accuracy. Statistical models also allowed for the discrimination of normal thyroid from papillary thyroid carcinomas with 97.8% accuracy and from follicular thyroid adenomas with 94.7% accuracy. The report also demonstrated the ability of the MasSpec Pen technology to detect cancer within regions of mixed tissue containing both normal and cancerous cells from an ovarian cancer sample. Finally, the authors demonstrated the use of this method for
87:(DESI) was the first liquid-based ambient ionization MS method. DESI employed a spray of charged solvent droplets to bombard a sample surface to desorb and ionize molecules from the sample surface, which are then directed towards and analyzed by a mass spectrometer. DESI-MS and other solvent-based ambient ionization MS methods has been widely employed for the analysis of small molecules, primarily metabolites and lipids, directly from biological tissue specimens to determine their molecular composition and leverage the mass spectral data acquired for diagnostic purposes. These methods have been deployed for the discrimination of normal and cancerous regions of tissue samples for many solid tumor indications, including breast, brain, prostate, ovarian, and colorectal, among others.
48:
contains cancerous cells using machine learning algorithms and statistical models. In early-stage clinical research, the MasSpec Pen system was able to distinguish various cancer tissues, including thyroid, breast, lung, and ovarian tumor tissues, from their normal counterparts with an overall accuracy of 96.3%. A follow-up study in illustrating the use of the device for detection of serous ovarian carcinoma in ex vivo tissue biopsies allowed for the discrimination of normal and cancerous ovarian samples with a clinical sensitivity and specificity of 94.0% and 94.4%, respectively.
126:
the normal and cancer samples. The model was able to distinguish between the normal and cancerous ovarian samples with 98.3%, 100.0%, and 92.3% overall accuracy on a training, validation, and test set of samples. Further, the report evaluated the ability of the MasSpec Pen system to distinguish ovarian cancer from fallopian tube and peritoneum tissue, two of the most common sites for ovarian cancer metastasis. Accuracies of 87.9% and 92.6% were achieved for the discrimination of cancer from fallopian tube and peritoneum tissues, respectively.
100:
can be manipulated by hand to direct the analysis. To use the system, the tip of the 'pen' is placed in contact with the surface to be sampled and the user triggers the initiation of a sampling procedure by pressing an integrated foot pedal. This signals a syringe pump to deliver a small aliquot of solvent through a polymer tube to a reservoir at the tip of the 'pen' that remains in contact with the sample. Analytes are then extracted from the sample into the solvent droplet by a
83:, in which ions are generated directly from a sample without need for extensive sample preparation or chromatographic separations. The MasSpec Pen can further be categorized as a solid-liquid extraction based ambient ionization method, described as methods that utilize a solvent system to gently extract molecules from a sample surface that are subsequently analyzed by a mass spectrometer.
63:, first reported the invention of the MasSpec Pen in 2017. Within her laboratory, the device has been used to analyze human tissue biopsies, including normal and cancerous breast, lung, ovarian, and thyroid samples. The MasSpec Pen is currently being evaluated for use on freshly excised tissue biopsies and for intraoperative use during oncology surgeries.
20:
99:
The MasSpec Pen, initially described in 2017, is a solvent-based ambient ionization technique but differs from its predecessors due to the handheld nature of the device, allowing analysis of samples distant from the mass spectrometer in a geometry independent manner. The MasSpec Pen used a probe that
267:
Zhang, Jialing; Sans, Marta; DeHoog, Rachel J.; Garza, Kyana Y.; King, Mary E.; Feider, Clara L.; Bensussan, Alena; Keating, Michael F.; Lin, John Q.; Povilaitis, Sydney; Katta, Nitesh; Milner, Thomas E.; Yu, Wendong; Nagi, Chandandeep; Dhingra, Sadhna; Pirko, Christopher; Brahmbhatt, Kirtan A.; Van
137:
tissue samples to discriminate between healthy pancreas and pancreatic tumor tissue. The device was also used to detect cancerous margins near adjacent structures of the pancreas such as the bile duct. The system was used in 18 pancreatic cancer surgeries and the data collected allowed the detection
125:
Performance of the MasSpec Pen for ovarian cancer diagnosis was further evaluated in a report published in 2019. The authors analyzed 160 human ovarian tissue samples, including 78 normal ovary and 82 serous carcinomas, with the MasSpec Pen and developed classification models to discriminate between
117:
The MasSpec Pen was designed to assist in the detection of positive surgical margins during solid tumor debulking procedures to assist in the complete excision of cancer surgeries. The device was initially used to analyze 253 human tissue biopsies, including normal and cancerous breast, lung, ovary,
47:
tissue sample analysis. The system collects biological molecules from a tissue sample surface via a solid-liquid extraction mechanism and transports the molecules to a mass spectrometer for analysis. The composition of the extracted molecules can then be used to predict if the tissue sample analyzed
1342:
King, Mary E.; Zhang, Jialing; Lin, John Q.; Garza, Kyana Y.; DeHoog, Rachel J.; Feider, Clara L.; Bensussan, Alena; Sans, Marta; Krieger, Anna; Badal, Sunil; Keating, Michael F.; Woody, Spencer; Dhingra, Sadhna J.; Yu, Wendong; Pirko, Christopher; Brahmbhatt, Kirtan A.; Van Buren, George; Fisher,
104:
mechanism. After a 3 second extraction period, the droplet is aspirated into the mass spectrometer using the vacuum from the mass spectrometer as the vacuum source. Once inside the mass spectrometer, the analytes within the solvent droplet are de-solvated and ionized via an
268:
Buren, George; Carter, Stacey; Fisher, William E.; Thompson, Alastair; Grogan, Raymon H.; Suliburk, James; Eberlin, Livia S. (December 16, 2020). "Direct
Molecular Analysis of In Vivo and Freshly Excised Tissues in Human Surgeries with the MasSpec Pen Technology".
289:
Zhang J, Sans M, DeHoog RJ, Garza KY, King ME, Feider CL, et al. (December 16, 2020). "Direct
Molecular Analysis of In Vivo and Freshly Excised Tissues in Human Surgeries with the MasSpec Pen Technology".
1130:
Gerbig S, Golf O, Balog J, Denes J, Baranyai Z, Zarand A, et al. (June 2012). "Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging".
91:
methods are often utilized to generate statistical models from the mass spectral data acquired from direct analysis of tissue samples to distinguish between healthy and diseased tissues.
826:
Pirro V, Jarmusch AK, Ferreira CR, Cooks RG (2017). "Ambient
Lipidomic Analysis of Brain Tissue Using Desorption Electrospray Ionization (DESI) Mass Spectrometry". In Wood P (ed.).
910:"Differentiation of prostate cancer from normal tissue in radical prostatectomy specimens by desorption electrospray ionization and touch spray ionization mass spectrometry"
553:
215:
Keating MF, Zhang J, Feider CL, Retailleau S, Reid R, Antaris A, et al. (September 2020). "Integrating the MasSpec Pen to the da Vinci
Surgical System for
616:
Li N, Nie H, Jiang L, Ruan G, Du F, Liu H (August 2020). "Recent advances of ambient ionization mass spectrometry imaging in clinical research".
312:
129:
The MasSpec Pen has also been implemented for the detection of pancreatic cancer during excision procedures. The MasSpec Pen was used on both
843:
529:
395:
1026:"Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer Aggressiveness by Ambient Ionization Mass Spectrometry Imaging"
84:
109:
mechanism. The ionized molecules are then analyzed by the mass spectrometer analyzer and the mass spectrum resulting is generated.
967:"Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids"
1175:"Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies"
60:
166:"Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system"
106:
661:"Multicenter Study Using Desorption-Electrospray-Ionization-Mass-Spectrometry Imaging for Breast-Cancer Diagnosis"
1408:
465:"Desorption electrospray ionization mass spectrometry for lipid characterization and biological tissue imaging"
1345:"Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology"
710:"Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis"
333:
Cooks RG, Ouyang Z, Takats Z, Wiseman JM (March 2006). "Detection
Technologies. Ambient mass spectrometry".
1232:
Eberlin LS, Margulis K, Planell-Mendez I, Zare RN, Tibshirani R, Longacre TA, et al. (August 2016).
66:
The MasSpec Pen has been licensed to Genio
Technologies, Inc., a subsidiary of MS Pen Technologies, Inc.
1075:"Epithelial ovarian carcinoma diagnosis by desorption electrospray ionization mass spectrometry imaging"
88:
708:
Calligaris D, Caragacianu D, Liu X, Norton I, Thompson CJ, Richardson AL, et al. (October 2014).
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291:
269:
1285:"Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging"
1283:
Eberlin LS, Tibshirani RJ, Zhang J, Longacre TA, Berry GJ, Bingham DB, et al. (February 2014).
313:"i2E Management Co., Inc. leads $ 1.25 million investment in Tulsa-based MS Pen Technologies, Inc"
1234:"Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging"
1155:
659:
Porcari AM, Zhang J, Garza KY, Rodrigues-Peres RM, Lin JQ, Young JH, et al. (October 2018).
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Dória ML, McKenzie JS, Mroz A, Phelps DL, Speller A, Rosini F, et al. (December 2016).
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769:"Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors"
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Kerian KS, Jarmusch AK, Pirro V, Koch MO, Masterson TA, Cheng L, Cooks RG (February 2015).
965:
Banerjee S, Zare RN, Tibshirani RJ, Kunder CA, Nolley R, Fan R, et al. (March 2017).
569:"Ambient Ionization Mass Spectrometry for Cancer Diagnosis and Surgical Margin Evaluation"
859:
Agar NY, Golby AJ, Ligon KL, Norton I, Mohan V, Wiseman JM, et al. (February 2011).
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Eberlin LS, Norton I, Orringer D, Dunn IF, Liu X, Ide JL, et al. (January 2013).
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Sans M, Gharpure K, Tibshirani R, Zhang J, Liang L, Liu J, et al. (June 2017).
362:
164:
Zhang J, Rector J, Lin JQ, Young JH, Sans M, Katta N, et al. (September 2017).
512:
Cabral EC, Ifa DR (2015). "DESI Imaging of Small
Molecules in Biological Tissues".
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1041:
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431:
232:
182:
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DeHoog RJ, Zhang J, Alore E, Lin JQ, Yu W, Woody S, et al. (October 2019).
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382:. New Developments in Mass Spectrometry. Cambridge: Royal Society of Chemistry.
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Proceedings of the
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Proceedings of the
National Academy of Sciences of the United States of America
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Proceedings of the
National Academy of Sciences of the United States of America
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Proceedings of the National Academy of Sciences of the United States of America
714:
Proceedings of the National Academy of Sciences of the United States of America
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516:. Methods in Molecular Biology. Vol. 1203. Clifton, N.J. pp. 63–77.
416:"Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques"
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Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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933:
861:"Development of stereotactic mass spectrometry for brain tumor surgery"
19:
1098:
39:(MS) based cancer detection and diagnosis system that can be used for
1349:
Proceedings of the National Academy of Sciences of the United States
463:
Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cooks RG (November 2011).
18:
1343:
William E.; Suliburk, James; Eberlin, Livia S. (13 July 2021).
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analysis of tumor tissues using an anesthetized murine model.
219:
Tissue Analysis during a Robotic Assisted Porcine Surgery".
75:
Ambient ionization mass spectrometry for disease diagnosis
79:
The MasSpec Pen technology is based on the principles of
59:, Ph.D., an Assistant Professor of Chemistry at the
8:
514:Mass Spectrometry Imaging of Small Molecules
552:: CS1 maint: location missing publisher (
16:System to collect samples for cancer tests
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138:of cancerous tissue with high accuracy.
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1132:Analytical and Bioanalytical Chemistry
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113:Cancer diagnosis with the MasSpec Pen
7:
379:Ambient Ionization Mass Spectrometry
328:
326:
567:Ifa DR, Eberlin LS (January 2016).
85:Desorption electrospray ionization
14:
89:Multivariate statistical analysis
311:Seagraves S (23 January 2020).
376:Domin M, Cody R, eds. (2014).
170:Science Translational Medicine
95:MasSpec Pen analysis mechanism
1:
1042:10.1158/0008-5472.CAN-16-3044
871:(2): 280–89, discussion 290.
618:Journal of Separation Science
414:, Lanekoff I (January 2016).
297:10.1101/2020.12.14.20248101v1
275:10.1101/2020.12.14.20248101v1
61:University of Texas at Austin
52:Development and current usage
1251:10.1371/journal.pmed.1002108
877:10.1227/neu.0b013e3181ff9cbb
836:10.1007/978-1-4939-6946-3_14
677:10.1021/acs.analchem.8b01961
585:10.1373/clinchem.2014.237172
481:10.1016/j.bbalip.2011.05.006
432:10.1021/acs.analchem.5b04188
233:10.1021/acs.analchem.0c02037
183:10.1126/scitranslmed.aan3968
522:10.1007/978-1-4939-1357-2_7
1425:
33:precìso MasSpec Pen System
1144:10.1007/s00216-012-5841-x
1370:10.1073/pnas.2104411118
1310:10.1073/pnas.1400274111
1200:10.1073/pnas.1911333116
992:10.1073/pnas.1700677114
794:10.1073/pnas.1215687110
735:10.1073/pnas.1408129111
347:10.1126/science.1119426
102:solid-liquid extraction
630:10.1002/jssc.202000273
70:Principle of operation
24:
388:10.1039/9781782628026
22:
665:Analytical Chemistry
420:Analytical Chemistry
221:Analytical Chemistry
1361:2021PNAS..11804411K
1355:(28): e2104411118.
1301:2014PNAS..111.2436E
1191:2019PNAS..11621401D
1185:(43): 21401–21408.
1091:2016NatSR...639219D
983:2017PNAS..114.3334B
926:2015Ana...140.1090K
785:2013PNAS..110.1611E
726:2014PNAS..11115184C
671:(19): 11324–11332.
227:(17): 11535–11542.
1079:Scientific Reports
934:10.1039/C4AN02039A
573:Clinical Chemistry
81:ambient ionization
25:
1099:10.1038/srep39219
1036:(11): 2903–2913.
977:(13): 3334–3339.
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624:(15): 3146–3163.
531:978-1-4939-1356-5
397:978-1-84973-926-9
341:(5767): 1566–70.
176:(406): eaan3968.
37:mass spectrometry
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1409:Cancer screening
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1030:Cancer Research
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865:Neurosurgery
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