IP Library › Granted Patent US 12,535,492
Granted Patent B2
US 12,535,492 · App. 18/394,339 · Granted Jan 27, 2026

Mass spectral tissue analysis

Inventors: Robert Graham Cooks (West Lafayette, IN); Livia Schiavinato Eberlin (Lafayette, IN); Christina Ramires Ferreira (West Lafayette, IN); Allison Lisa Dill (Indianapolis, IN); Demian R. Ifa (West Lafayette, IN)
Assignee: Purdue Research Foundation
G01N33/92H01J49/0036H01J49/165H01J49/0004H01J49/142
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Quick Facts
Patent No.
US 12,535,492
App. No.
18/394,339
Granted
Jan 27, 2026
Kind
B2
Abstract

The invention generally relates to mass spectral analysis. In certain embodiments, methods of the invention involve analyzing a lipid containing sample using a mass spectrometry technique, in which the technique utilizes a liquid phase that does not destroy native tissue morphology during analysis.

Claims (33)

1 . A method for assessing a tissue sample for presence of cancerous cells that are associated with brain, kidney, or prostate, the method comprising:

producing mass spectral data using a desorption electrospray ionization (DESI) technique that comprises directing a liquid phase that does not destroy native tissue morphology from a DESI probe onto the tissue sample to thereby desorb one or more compounds from the sample that are analyzed by a mass spectrometer;

receiving the mass spectral data of a tissue sample;

producing a mass spectral image of the tissue sample based on the mass spectral data;

receiving histochemical data of the tissue sample;

producing an optical image of the tissue sample from the histochemical data;

overlaying the mass spectral image of the tissue sample with the optical image of the tissue sample to produce an overlaid image; and

assessing the overlaid image for presence of cancerous cells that are associated with at least one type of cancer selected from the group consisting of brain, kidney, and prostate.

2 . The method according to claim 1 , wherein assessing comprises determining a distribution of the one or more compounds in the tissue sample based on an analysis of the overlaid image.

3 . The method according to claim 2 , further comprising grading the cancerous cells based on the distribution of the one or more compounds in the tissue sample.

4 . The method according to claim 3 , wherein the cancerous cells are indicative of brain cancer.

5 . The method of claim 1 , wherein the liquid phase is a solvent comprising dimethylformamide (DMF), acetonitrile (ACN), or tetrahydrofuran (THF).

6 . The method according to claim 5 , wherein the liquid phase comprises at least one other component.

7 . The method according to claim 6 , wherein the at least one other component is selected from the group consisting of ethanol (EtOH), water (H 2 O), acetonitrile (ACN), and a combination thereof.

8 . The method according to claim 1 , wherein the liquid phase is selected from the group consisting of: acetonitrile (ACN):ethanol (EtOH); methanol (MeOH):chloroform (CHCl 3 ); and acetonitrile (ACN):chloroform (CHCl 3 ).

9 . The method according to claim 1 , wherein the histochemistry data is produced by H&E staining.

10 . The method according to claim 1 , wherein the one or more compounds comprises one or more lipids.

11 . A method for assessing a tissue sample for presence of cancerous cells that are associated with brain, kidney, or prostate, the method comprising:

producing mass spectral data of a tissue sample comprising a cancerous section that is associated with brain, kidney, or prostate using a desorption electrospray ionization (DESI) technique that comprises directing a liquid phase that does not destroy native tissue morphology from a DESI probe onto the tissue sample to thereby desorb one or more compounds from the sample that are analyzed by a mass spectrometer;

receiving the mass spectral data of the tissue sample comprising the cancerous section that is associated with brain, kidney, or prostate;

producing a mass spectral image of the tissue sample comprising the cancerous section based on the mass spectral data;

receiving histochemical data of the tissue sample comprising the cancerous section;

producing an optical image of the tissue sample comprising the cancerous section from the histochemical data;

overlaying the mass spectral image of the tissue sample comprising the cancerous section with the optical image of the tissue sample comprising the cancerous section to produce an overlaid image;

identifying the cancerous section that is associated with brain, kidney, or prostate within the overlaid image; and

assessing the overlaid image to determine a grade of the cancerous section that is associated with brain, kidney, or prostate.

12 . The method according to claim 11 , wherein the mass spectral data is produced using a desorption electrospray ionization (DESI) technique operated in imaging mode.

13 . The method of claim 11 , wherein the liquid phase is a solvent comprising dimethylformamide (DMF), acetonitrile (ACN), or tetrahydrofuran (THF).

14 . The method according to claim 13 , wherein the liquid phase comprises at least one other component.

15 . The method according to claim 14 , wherein the at least one other component is selected from the group consisting of ethanol (EtOH), water (H 2 O), acetonitrile (ACN), and a combination thereof.

16 . The method according to claim 11 , wherein the liquid phase is selected from the group consisting of: acetonitrile (ACN):ethanol (EtOH); methanol (MeOH):chloroform (CHCl 3 ); and acetonitrile (ACN):chloroform (CHCl 3 ).

17 . The method according to claim 11 , wherein the histochemistry data is produced by H&E staining.

18 . The method according to claim 11 , wherein the one or more compounds comprises one or more lipids.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 22, 2024
From: COOKS, ROBERT GRAHAM; EBERLIN, LIVIA SCHIAVINATO; FERREIRA, CHRISTINA RAMIRES; DILL, ALLISON LISA; IFA, DEMIAN R.
To: PURDUE RESEARCH FOUNDATION
Reel/Frame 067181/0420 →
Continuity (6)
Continuation 17331264 · May 26, 2021
Continuation 15891793 · Feb 8, 2018
Continuation 14880623 · Oct 12, 2015
Continuation 13475305 · May 18, 2012
Provisional Application 61487363 · May 18, 2011
Related Publication 20240219410A1 · Jul 4, 2024
References Cited (264)
US 4224031A · Mee et al. · 1980 [cited by applicant]
US 4755670A · Syka et al. · 1988 [cited by applicant]
US 4757198A · Korte et al. · 1988 [cited by applicant]
US 4885076A · Smith et al. · 1989 [cited by applicant]
US 5152177A · Buck et al. · 1992 [cited by applicant]
US 5583281A · Yu · 1996 [cited by applicant]
US 5756994A · Bajic · 1998 [cited by applicant]
US 6297499B1 · Fenn · 2001 [cited by applicant]
US 6452168B1 · McLuckey et al. · 2002 [cited by applicant]
US 6627881B1 · Bertrand et al. · 2003 [cited by applicant]
US 6982416B2 · Villinger et al. · 2006 [cited by applicant]
US 7154088B1 · Blain et al. · 2006 [cited by applicant]
US 7335897B2 · Takats et al. · 2008 [cited by applicant]
US 7384793B2 · McCash et al. · 2008 [cited by applicant]
US 7564027B2 · Finch et al. · 2009 [cited by applicant]
US 7902499B2 · Hiraoka et al. · 2011 [cited by applicant]
US 7915579B2 · Chen et al. · 2011 [cited by applicant]
US 7930924B2 · Krogh et al. · 2011 [cited by applicant]
US 8030088B2 · McCash et al. · 2011 [cited by applicant]
US 8294892B2 · Sardashti et al. · 2012 [cited by applicant]
US 8330119B2 · Chen et al. · 2012 [cited by applicant]
US 9921233B2 · Cooks et al. · 2018 [cited by applicant]
US 11047869B2 · Cooks et al. · 2021 [cited by applicant]
US 20020045160A1 · Carrion · 2002 [cited by examiner]
US 20040011954A1 · Park · 2004 [cited by applicant]
US 20050117864A1 · Dziekan et al. · 2005 [cited by applicant]
US 20050247870A9 · Park · 2005 [cited by applicant]
US 20060192107A1 · DeVoe et al. · 2006 [cited by applicant]
US 20060200316A1 · Kanani et al. · 2006 [cited by applicant]
US 20060249668A1 · Goldberg et al. · 2006 [cited by applicant]
US 20060275909A1 · Spitzer et al. · 2006 [cited by applicant]
US 20070151232A1 · Dalla Betta et al. · 2007 [cited by applicant]
US 20070259445A1 · Cerda · 2007 [cited by applicant]
US 20080128608A1 · Northen et al. · 2008 [cited by applicant]
US 20080179511A1 · Chen et al. · 2008 [cited by applicant]
US 20080272294A1 · Kovtoun · 2008 [cited by applicant]
US 20090071834A1 · Hafeman et al. · 2009 [cited by applicant]
US 20090090856A1 · Grant et al. · 2009 [cited by applicant]
US 20090280300A1 · Craighead et al. · 2009 [cited by applicant]
US 20090306230A1 · Semikhodskii et al. · 2009 [cited by applicant]
US 20100019143A1 · Dobson et al. · 2010 [cited by applicant]
US 20110108724A1 · Ewing et al. · 2011 [cited by applicant]
US 20110108726A1 · Hiraoka et al. · 2011 [cited by applicant]
US 20110193027A1 · Mackenzie et al. · 2011 [cited by applicant]
US 20120119079A1 · Ouyang et al. · 2012 [cited by applicant]
US 20130023005A1 · Chen et al. · 2013 [cited by applicant]
US 20130112017A1 · Ouyang et al. · 2013 [cited by applicant]
US 20130112867A1 · Ouyang et al. · 2013 [cited by applicant]
US 20130273560A1 · Cooks et al. · 2013 [cited by applicant]
US 20130299694A1 · Sato et al. · 2013 [cited by applicant]
US 20150338413A1 · Agar · 2015 [cited by applicant]
WO 2004060278A2 · 2004 [cited by applicant]
WO 2009102766A1 · 2009 [cited by applicant]
WO 2010127059A1 · 2010 [cited by applicant]
Pope, 2012, Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy, J Neurooncol 107:197-205. [cited by applicant]
Rao, 2010, Development of a validated high-throughput LC-ESI-MS method for determination of sirolimus on dried blood spots, Biomed. Chromat., 24:1356-1364. [cited by applicant]
Regenthal, 1999, Drug Levels: Therapeutic and Toxic Serum/Plasma Concentrations of Common Druds, J. Clin. Monitor Comp., 15:529-544. [cited by applicant]
Regenthal, M. Krueger, C. Koeppel and R. Preiss, J. Clin. Monitor Comp., 1999, 15, 529-544. [cited by applicant]
Roach, 2010, Nanospray desporption electrospray ionization: an ambient method for liquid-extraction surface sampling in mass spectrometry, Analyst, 135:2233-2236. [cited by applicant]
Rohle, 2013, An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells, Science 340:626-630. [cited by applicant]
Ronn, 1995, High-Performance Liquid Chromatorgraphy Determination of Dapsone, Monoacetyldapsone, and Pyrimethamine in Filter Paper Blood Spots, Therap. Drug Monitor., 17:79-83. [cited by applicant]
Rosch, 2007, Anionic Lipids enriched at the ExPortal of [cited by applicant]
Saint-Marcoux, 2007, Current role of LC-MS in therapeutic drug monitoring, Anal. Bioanal. Chem., 388:1327-1349. [cited by applicant]
Santos, 2003, Detection of Group A Beta-Hemolytic Streptococcus Employing three Different Detection Methods: Culture, Rapid Antigen Detecting Test, and Molecular Assay, Brazilian Journal of Infectious Diseases, 7:297-30… [cited by applicant]
Schwamborn, 2007, Identifying prostate carcinoma by MALDI-Imaging, International Journal of Molecular Medicine, 20 (2): 155-159. [cited by applicant]
Schwamborn, 2010, MALDI Imaging Mass Spectrometry—Painting Molecular Pictures, Mol. Oncol., 4(6):529-538. [cited by applicant]
Seeley, 2008, Imaging mass spectrometry: Towards clinical diagnostics, Proteomics Clin. Appl., 2:1435-1443. [cited by applicant]
Shiea, 2005, Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids, J. Rapid Communications in Mass Spectrometry, 19:3701-3704. [cited by applicant]
Shulman, 2012, Clinical Practice Guideline for the Diagnosis and Managment of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America, Clinical Infectious Diseases, 55:e86-e102. [cited by applicant]
Signoretti, 2000, Is a Prostate Basal Cell Marker and is Required for Prostate Development, American Journal of Pathology, 157(6):1769-1775. [cited by applicant]
Sokol, 2011, Miniature mass spectrometer equipped with electrospray and desorption electrospray ionization for direct analysis of organics from solids and solutions, Int. J. Mass Spectrom., In Press, Corrected Proof. [cited by applicant]
Soparawalla, 2011, In situ analysis of agrochemical residues on fruit using ambient ionization on a handheld mass spectrometer, Analyst, 136:4392-4396. [cited by applicant]
Spooner, 2009, Dried Blood Spots as a Sample Collection Technique for the Determination of Pharmacokinetics in Clinical Studies: Considerations for the Validation of a Quantitative Bioanalytical Method, Anal. Chem, 81:1… [cited by applicant]
Supporting Information for Eberlin, 2010, Cholesterol Sulfate Imaging in Human Prostate Cancer Tissue by Desorption Electrospray Ionization Mass Spectrometry, Anal. Chem. 82(9):3430-3434, 11 pages. [cited by applicant]
Suyagh, 2010, Development and validation of a dried blood spot-LC-APCI-MS assay for estimation of canrenone in paediatric samples, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 878:769-776. [cited by applicant]
Tachi, 2011, A clinical trial for therapeutic drug monitoring using microchip-based fluorescence polarization immunoassay, Anal. Bioanal. Chem., 401:2301-2305. [cited by applicant]
Takats, 2005, Ambient mass spectrometry using desorption electrospray ionization (DESI): instrumentation, mechanisms and applications in forensics, chemistry, and biology, J. Mass Spectrom, 40:1261-1275. [cited by applicant]
Takats,2004, Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization, Science, 306:471-473. [cited by applicant]
Tanaka, 1988, Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom., 2:151-153. [cited by applicant]
Tawa, 1989, Determination of the Aminoglycoside Antibiotics Sisomicin and Netilmicin in Dried Blood Spots on Filter Discs, by High-Performance Liquid Chromatography with Pre-col. Derivatization and Fluorimetric Detectio… [cited by applicant]
Taylor, 2011, The current role of liquid chromatography-tandem mass spectrometry in therapeutic drug monitoring of immunosuppressant and antiretrovial drugs, Clin. Biochem., 44:14-20. [cited by applicant]
Tian, 2008, Does Electrospray Ionization Produce Gas-Phase or Liquid-Phase Structures? 2008, J. Am. Chem. Soc., 130:10842-1084. [cited by applicant]
Turcan, 2012, IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype, Nature 483:479-483. [cited by applicant]
Valadon, 1972, Chromatography of Carotenoids Using Papers Filled with Silica Gel and with Alumina, Phytochemistry, 11:413-414. [cited by applicant]
Van Berkel, 2008, Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry, J Mass Spectrom, 43:1161-1180. [cited by applicant]
Van Berkel, 2008, Liquid microjunction surface sampling probe electrospray mass spectrometry for detection of durgs and metabolites in thin tissue sections, Journal of Mass Spectrometry, 43:500-508. [cited by applicant]
Van Hove, 2010, A concise review of mass spectrometry imaging, J. Chromatogr. 1217(25):3946-3954. [cited by applicant]
Venter, 2010 Surface Sampling by Spray-Desorption Followed by Collection for Chemical Analysis, Anal. Chem., 82:1674-1679. [cited by applicant]
Venter, 2013, Mechanizms of Real-Time, Proximal Sample Processing during Ambient Ionizatioin Mass Spectrometry, Analy. Chem, 86:233-249. [cited by applicant]
Wang, 2010, Paper Spray for Direct Analysis of Complex Mixtures Using Mass Spectrometry, 2010, Angew. Chem. Int. Ed., 49:877-880. [cited by applicant]
Wang, 2011, Direct Analysis of Biological Tissue by Paper Spray Mass Spectrometry, Anal. Chem., 83:1197-1201. [cited by applicant]
Wang, 2013, Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation, Science 340:622-625. [cited by applicant]
Watrous, 2011, The evolving field of imaging mass spectrometry and its impact on future biological research, Journal of Mass Spectrometry, 46(2):209-222. [cited by applicant]
Weller, 2011, Isocitrate Dehydrogenase Mutations: A Challenge to Traditional Views on the Genesis and Malignant Progression of Gliomas, Glia 59:1200-1204. [cited by applicant]
Wertz, 1986, Lipid of epidermis and Keratinized and Non-Keratinized Oral Epithelia, Comp. Biochem. Physiol. 83B(3):529-531. [cited by applicant]
Wiley, 2010, Screening of agrochemicals in foodstuffs using low-temperature plasma (LTP) ambient ionization mass spectrometry, Analyst, 135:971-979. [cited by applicant]
Wiseman, 2005, Mass Spectrometric Profiling of Intact Biological Tissue by Using Desorption Electrospray Ionization, Angew. Chem. Int. Ed., 44:7094-7097. [cited by applicant]
Wiseman, 2006, Tissue Imaging at Atmospheric Pressure using Desorption Electrospary Ionization (DESI) Mass Spectrometry, Angewandte Chemie-International Edition, 45(43):7188-7192. [cited by applicant]
Wiseman, 2007, Development of desorption electrospray ionization (DESI) mass spectrometry and its application to direct biological tissue analysis and meolecular imaging (UMI No. 320004) [Dctoral dissertation, Purdue Un… [cited by applicant]
Wiseman, 2008, Ambient molecular imaging by desorption electrospray ionization mass spectrometry, Nature Protocols, 3(3):517-524. [cited by applicant]
Wiseman, 2008, Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues, PNAS, 105:18120-18125. [cited by applicant]
Wu, 2009, Rapid, Direct Analysis of Cholesterol by Charge Labeling in Reactive Desorption Electrospray Ionization, Anal Chem. 81(18):7618-7624. [cited by applicant]
Xu, 2011, Oncometabolite 2-Hydroxyglutarate is a Competitive Inhibitor of alpha- Ketoglutarate-Dependent Dioxygenases, Cancer Cell, 19:17-30. [cited by applicant]
Yamashita, 1984, Electrospray Ion Source, Another Variation on the Free-Jet Theme, J. Phys. Chem. 88:4451-4459. [cited by applicant]
Abe, 2008, Inkjet-Printed Microfluidic Multianalyte Chemical Sensing Paper, Anal.Chem., 80:6928-6934. [cited by applicant]
Agar, 2011, Development of stereotactic mass spectrometry for brain tumor surgery, Neurosurgery, 68:280-289. [cited by applicant]
Alberici, 2010, Ambient mass spectrometry: briniging MS into the “real world”, Analytical and Bioanalytical Chemistry, 398(1):265-294. [cited by applicant]
Amary, 2011, IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours, J. Pathol., 224:334-343. [cited by applicant]
Andronesi, 2012, Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy, Sci Transl Med 4, 116ra114, 16 pages. [cited by applicant]
Aston Labs report, Histologically compatible tissue imaging, published May 6, 2009. [cited by applicant]
Badu-Tawiah, 2010, Enchanced lon Signals in Desorption Electrospray Ionization Using Surfactant Spray Solutions, J. Am. Soc. Mass Spectrom, 21:1423-1431. [cited by applicant]
Badu-Tawiah, 2013, Chemical Aspects fo the Extractive Methods of Ambient ionization Mass Spectrometry, Annu. Rev. Phys. Chem., 64:481-505. [cited by applicant]
Barfield, 2008, Application of dried blood spots combined with HPLC-MS/MS for the quantification of acetaminophen in toxicokinetic studies, J. Chromatogr. B 870:32-37. [cited by applicant]
Baumann, 2010, Determination of nicotine and cotinine in human serum by means of LC/MS, J. Chromatogr., B878:107-111. [cited by applicant]
Benowitz, 2003, Nicotine metabolite ratio as a predictor of cigarette consumption, Nicotine & Tobacco Research, 5:621-624. [cited by applicant]
Benowitz, 2009, Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeutics, Annu. Rev. Pharmacol. Toxicol., 49:57-71. [cited by applicant]
Benowitz, 2010, Nicotine Addiction, N. Engl. J. Med., 362:2295-2303. [cited by applicant]
Bergeron, 2000, Rapid Detection of Group B Streptococci in Pregnant Womoen at Delivery, N. Engl J Med, 343:175-179. [cited by applicant]
Bisno, 2001, Acute Pharyngitis, N. Engl. J. Med. 344:205-211. [cited by applicant]
Borger, 2012, Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping, Oncologist 17, 72-79. [cited by applicant]
Breadmore, 2004, Determination of ribavirin in human serum and plasma by capillary electrophoresis, Electrophoresis, 25:1615-1622. [cited by applicant]
Bruzewicz, 2008, Low-Cost Printing of Poly(dimethylsiloxane) Barriers to Define Microchannels in Paper, Anal. Chem., 80:3387-3392. [cited by applicant]
Campbell, 2013, Rapid Antigen Tests, Advanced Techniques in Diagnostic Microbiology, Springer, pp. 31-51. [cited by applicant]
Camurdan, 2008, Diagnostic value of rapid antigen detection test for streptococcal pharyngitis in a pediatric population, International J. Pediatric Otorhinolaryngology, 72:1203-1206. [cited by applicant]
Capper 2010, Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors, Brain Pathol 20, 245-254. [cited by applicant]
Carroll, 1975, Atmospheric Pressure Ionization Mass Spectrometry: Corona Discharge Ion Source for Use in Liquid Chromatograph-Mass Spectrometer-Computer Analytical System, Anal. Chem. 47:2369-2373. [cited by applicant]
Centers for Disease Control and Prevention. Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses-United States, 2000-2004. Morbidity and Mortality Weekly Report; 2008; 57(45):1226-8. [cited by applicant]
Centers for Disease Control and Prevention. Vital Signs: Current Cigarette Smoking Among Adults Aged 18 Years—United States, 2005-2010. Morbidity and Mortality Weekly Report 2011; 60(33):1207-12. [cited by applicant]
Chaurand, 2004, Assessing Protein Patterns in Disease Using Imaging Mass Spectrometry , J. Proteome Res., 3:245-252. [cited by applicant]
Chaurand, 2004, Integrating Histology and Imaging Masss Spectrometry, Analytical Chemistry, 76(4):1145-1155. [cited by applicant]
Checa, 2009, Determination of HIV drugs in biological matrices: A review, J.; Anal. Chim. Acta, 647:1-13. [cited by applicant]
Chen, 2009, What can we learn from Ambient Ionization Techniques?, J Am Soc Mass Spectrom, 20:1947-1963. [cited by applicant]
Cheung, 2008, Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation, Transplant Int., 21:140-145. [cited by applicant]
Chi, 2012, Prospective, high-throughput molecular profiling of human gliomas, J Neurooncol, 110:89-98. [cited by applicant]
Choi, 2012, 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH- mutated patients with gliomas, Nat Med 18:624-629. [cited by applicant]
Chughtai, 2010, Mass Spectrometric Imaging for Biomedical Tissue Analysis, Chem. Rev., 110:3237-3277. [cited by applicant]
Clerc, 2010, Routine use of point-of-care test: usefulness and application in clinical microbiology, et al., Clinical Microbiology and Infection, 16:1054-1061. [cited by applicant]
Cody, 2005, Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Condition, Anal. Chem. 77:2297-2302. [cited by applicant]
Cooks, 2011, New ionization methods and miniature mass spectrometers for biomedicine: DESI imaging for cancer diagnostics and paper spray ionization for therapeutic drug monitoring, Faraday Discuss. 149:247-267. [cited by applicant]
Coombes, 1984, A phenytoin assay using dried blood spot samples suitable for domiciliary therapeutic drug monitoring, Ann. Clin. Biochem., 21:519-522. [cited by applicant]
Cornett, 2006, A novel history-directed strategy for MALDI-MS tissue profiling that improves throughput ad cellular specificity in human breast cancer, Mol Cell Proteomics, 5(10):1975-1983. [cited by applicant]
Crecelius, 2005, Three-Dimensional Visualization of Protein Expression in Mouse Brain Structures Using Imaging Mass Spectrometry, Journal of the American Society for Mass Spectrometry, 16(7):1093-1099. [cited by applicant]
Dang, 2009, Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nature 462:739-744. [cited by applicant]
Dempsey, 2004, Nicotine metabolite ratio as and index of cytochrome P450 2A6 metabolic activity, Clin. Pharmacol. Ther., 76:64-72. [cited by applicant]
Dessi, 1994, Cholesterol Content in Tumor Tissues Is Inversely Associated with High-Density Lipoprotein Cholesterol in Serum in Patients with Gastrointestinal Cancer, Cancer, 73(2):253-258. [cited by applicant]
Dettmer, 2007, Mass Spectrometry-Based Metabolomics, Mass Spectrom. Rev., 2007, 26(1):51-78. [cited by applicant]
Dias-Santagata, 2010, Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine, EMBO Mol Med 2:146-158. [cited by applicant]
Dias-Santagata, 2011, Braf V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications, PLOS One, 6(3): e17948. [cited by applicant]
Didonato, 2003, Fixation Methods for the Study of Lipid Droplets by Immunofluorescence Microscopy, Journal of Histochemistry & Cytochemistry, 51(6):773-780. [cited by applicant]
Dill, 2009, Lipid profiles of canine invasive transitional cell carcinoma of the urinary bladder and adjacent normal tissue by desorption electrospray ionization imaging mass spectrometry, Anal Chem, 81:8758-8764. [cited by applicant]
Dill, 2010, Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry, Analytical and Bioanalytical Chemistry 398:2969-2978. [cited by applicant]
Dill, 2011, Multivariate Statistical Identification of Human Bladder Carcinomas Using Ambient Ionization Imaging Mass Spectrometry, A European Journal 17:2897-2902. [cited by applicant]
Dill, 2011, Perspectives in imaging using mass spectrometry, Chemical Communications, 47(10):2741-2746. [cited by applicant]
Eberlin, 2010, Cholesterol Sulfate Imaging in Human Prostate Cancer Tissue by Desorption Electrospray Ionization Mass Spectrometry, Analytical Chemistry 82:3430-3434. [cited by applicant]
Eberlin, 2010, Discrimination of human astrocytoma subtypes by lipid analysis using desorption electrospray ionization imaging mass spectrometry, Angew Chem Int Ed Engl 49:5953-5956. [cited by applicant]
Eberlin, 2010, Three-Dimensional Vizualization of Mouse Brain by Lipid Analysis Using Ambient Ionization Mass Spectrometry, Angew. Chem. Int. Ed., 49:873-876. [cited by applicant]
Eberlin, 2011, Nondestructive, Histologically Compatible Tissue Imaging by Desorption Electrospray Ionization Mass Spectrometry, ChemBioChem 12:2129-2132. [cited by applicant]
Eberlin, 2012, Classifying human brain tumors by lipid imaging with mass spectrometry, Cancer Res 72:645-654. [cited by applicant]
Eberlin, 2013, Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors, PNAS, 110(5):1611-1616. [cited by applicant]
Elhawary, 2011, Intraoperative real-time querying of white matter tracts during frameless stereotactic neuronavigation, Neurosurgery 68, 506-516; Discussion 516. [cited by applicant]
Elkhaled, 2012, Magnetic Resonance of 2-Hydroxyglutarate in IDH1-Mutated Low-Grade Gliomas, Science Translational Medicine, 4:116ra115. [cited by applicant]
Ellis, 2010, Imaging of Human Lens Lipids by Desorption Electrospray Ionization Mass Spectrometry, J. Am. Soc. Mass Spectrom. 21:2095-2104. [cited by applicant]
Espy, 2012, Rapid analysis of whole blood by paper spray mass spectrometry for point-of-care therapeutic drug monitoring, The Analyst, 137:2344-2349. [cited by applicant]
Evans, 2003, Pharmacogenomics-Drug Disposition, Drug Target, and Side Effects, N. Engl. J. Med., 348:538-549. [cited by applicant]
Evans, 2004, Moving towards individualized medicine with pharmacogenomics, Nature, 429:464-468. [cited by applicant]
Fenn, 1989, Electrospray Ionization for Mass Spectrometry of Large Biomolecules, Science, 246:64-71. [cited by applicant]
Ferguson, 2011, Direct Ionization of Large Proteins and Protein Complexes by Desorption Electrospray Ionization—Mass Spectrometry, Anal. Chem. 2011, 83:6468-6473. [cited by applicant]
Fiore, 1992, Trends in Cigarette Smoking in the United States, Med. Clin. N. Am., 76:289-303. [cited by applicant]
Flanagan, 1994, Simple and Rapid HPLC of Quinince, Hydroxychloroquine, Chloroquine, and Desethychloroquine in Serum, Whole Blood, and Filter Paper-Adsorbed Dry Blood, Anal. Toxicol., 18:255-260. [cited by applicant]
Fox, 2006 Performance of Rapid Streptococcal Antigen Testing Varies by Personnel, J. Clin. Microbiol., 44:3918-3922. [cited by applicant]
Fujimoto, 1989, Fluorescence Polarization Immunoassay of Gentamicin or Netilmicin in Blood Spotted on Filter paper, Clin. Chem. 35(5):867-869. [cited by applicant]
Gao, 2008, Breaking the pumping speed barrier in mass spectrometry: discontinuous atmospheric pressure interface, Anal. Chem, 80:4026-4032. [cited by applicant]
Gao, 2008, Design and Characterization of a Multisource Hand-Held Tandem Mass Spectrometer, Anal Chem, 80:7198-7205. [cited by applicant]
Gaskell, 1997, Electrospray: Principles and Practice. J. Mass. Spect., 32:677-688. [cited by applicant]
Gerber, 2004, Rapid Diagnosis of Pharyngitis Caused by Group A Streptococci, Clinical microbiology reviews, 17:571-580. [cited by applicant]
Gerlowski, 1983, Physiologically based pharmacokinetic modeling: principles and applications, J. Pharm. Sci., 72:1103-1127. [cited by applicant]
Gieseker, 2001, Evaluating the American Academy of Pediatrics Diagnostic Standard for [cited by applicant]
Gonzalez-Serrano, 2013, Desorption Electrospray Ionization Mass Spectrometry Reveals Lipid Metabolism of Individual Oocytes and Embryos, Plos One, 8(9):e74981. [cited by applicant]
Green, 2010, The effect of electrospray solvent composition on desorption electrospray ionisation (DESI) efficiency and spatial resolution, Analyst, 135, 731-737. [cited by applicant]
Guo, 2012, The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas, Acta Neurochir (Wien) 154:1361-1370; Discussion 1370. [cited by applicant]
Harris, 2011, Ambient sampling/ionization mass spectrometry: applications and current trends, Analytical Chemistry 83:4508-4538. [cited by applicant]
Hartmann, 2009, Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas, Acta Neuropathol 118:469-474. [cited by applicant]
Havlicek, 2012, Current Trends in Microbial Diagnostics Based on Mass Spectrometry, Anal. Chem., 85:790-797. [cited by applicant]
Heine, 2008, Quantification of protease inhibitors and non-nucleoside reverse transcritpase inhibitors in dried blood spots by liquid chromatography-triple quadrupole mass spectrometry, J. Chromatogr. B, 867:205-212. [cited by applicant]
Henningfield, Nicotine Medications for Smoking Cessation, 1995, N. Engl. J. Med., 333:1196-1203. [cited by applicant]
Hiraoka, 2007, Development of probe electrospray using a solid needle, Rapid Commun. Mass Spectrometry, 21:3139-3144. [cited by applicant]
Holford, 1981, Understanding the Dosse-Effect Relationship: Clinical Application of Pharmacokinetic- Pharmacodynamic Models, Clin Pharmacokinet, 6:429-453. [cited by applicant]
Hou, 2011, Sampling Wand for an lon Trap Mass Spectrometer, Anal. Chem., 83:1857-1861. [cited by applicant]
Hsu, 2000, Characterization of phosphatidylinositol , phosphatidylinositol-4-phosphate, and phosphatidylinositol-4, 5-bisphosphate by electrospray ionization tandem mass spectrometry: a mechanix study, Journal of the Am… [cited by applicant]
Huang, 2010, Ambient Ionization Mass Spectrometry, Annual Review of Analytical Chemistry, 3:43-65. [cited by applicant]
Hukkanen, 2005, Metabolism and Disposition of Kinetics of Nicotine, Pharmacol. Rev., 57:79-115. [cited by applicant]
Iavarone, 2000, Effects of Solvent on the Maximum Charge State and Charge State Distribution of Protein lons Produced by Electrospray Ionization, J. Am. Soc. Mass Spectrom., 11:976-985. [cited by applicant]
Iavarone, 2004, Buffer Loading for Counteracting Metal Salt-Induced Signal Suppression in Electrospray Ionization, Anal. Chem., 76(14):3944-3950. [cited by applicant]
Ifa, 2007, Latent Fingerprint Chemical Imaging by Mass Spectrometry, Int. J. Mass Spectrom. 259(8):805. [cited by applicant]
Ifa, 2010, Desorption electrospray ionization and other ambient ionization methods: current progress and preview, Analyst, 135:669-681. [cited by applicant]
International Preliminary Report of Patentability for PCT/US2010/032881 from International Bureau, mailed Nov. 10, 2011, 10 pages. [cited by applicant]
International Preliminary Report on Patentability for PCT/US2009/045649 mailed Dec. 9, 2010, 7 pages. [cited by applicant]
International Preliminary Report on Patentability for PCT/US2012/040521, mailed on Dec. 19, 2013, 6 pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2010/032881, International Searching Authority, mailed Aug. 4, 2010, 10 pages. [cited by applicant]
International Search Report and Written Opinion mailed on Aug. 27, 2014, for International Patent Application No. PCT/US14/34767, filed Apr. 21, 2014, 20 pages. [cited by applicant]
International Search Report issued in International Application No. PCT/US2012/040521, mailed Oct. 29, 2012, 4 pages. [cited by applicant]
International Written Opinion issued in International Application No. PCT/US2012/040521, mailed on Oct. 29, 2012, 5 pages. [cited by applicant]
Jackson, 2007, Salt Tolerance of Desorption Electrospray Ionization (DESI), J. Am. Society for Mass Spectrometry, 18:2218-2225. [cited by applicant]
Jacob, 1999, Minor Tobacco Alkaloids as Biomarkers for Tobacco Use: Comparison of Users of Cigarettes, Smokeless Tobacco, Cigars, and Pipes, Am. J. Public Health, 89:731-736. [cited by applicant]
Jacob, 2002, Cancer Epidemiology, Biomarkers & Prevention, Cancer Epidemiol. Biomark. Prev., 11:1668-1673. [cited by applicant]
Jacob, 2011, Determination of the nicotine metabolites cotinine and trans-3′-hydroxycotinine in biologic fluids of smokers and non-smokers using Iquid chromatography-tandem mass spectrometry: Biomarkers for tobacco smok… [cited by applicant]
Jarvis, 1987, Comparison of Tests Used to Distinguish Smokers from Nonsmokers, Am. J. Public Health, 77:1435-1438. [cited by applicant]
Jolesz, 2011, Intraoperative imaging in neurosurgery: Where will the future take us? Acta Neurochir Suppl 109:21-25. [cited by applicant]
Kalinina, 2012, Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma, J Mol Med (Berl) 90:1161-1171. [cited by applicant]
Kebarle, 1993, From Ions in Solution to lons in the Gas Phase, Anal. Chem., 65(22):A972-A986. [cited by applicant]
Kim, 2006, A validated method for the determination of nicotine, cotinine, trans-3′-hydroxycotinine, and norcotinine in human plasma using solid-phase extraction and liquid chromatography-atmospheric pressure chemical i… [cited by applicant]
Koal, 2005, Quantificationof antiretroviral drugs in dried blood spot samples by means of liquid chromatography/tandem mass spectrometry, Rapid Commun. Mass Spectrom., 19: 2995-3001. [cited by applicant]
Kogelschatz, 2003, Dielectric-Barrier Discharges: Their History, Discharge Physics, and Industrial Applications, Plasma Chemistry and Plasma Processing, 23:1-46. [cited by applicant]
Koivunen, 2012, Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation, Nature 483:484-488. [cited by applicant]
Kondrat, 1978, Multiple Reaction Monitoring in Mass Spectrometry Mass Spectrometry for Direct Analysis of Complex-Mixtures. Analytical Chemistry, 50(14):2017-2021. [cited by applicant]
Korecka, 2009, Review of the newest HPLC methods with mass spectrometry detection for determination of immunosuppressive drugs in clinical practice, Ann. Transplant., 14:61-72. [cited by applicant]
Lai, 2011, Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin, J Clin Oncol 29, 4482-4490. [cited by applicant]
Laiko, 2000, Atmospheric Pressure Matrix-Assisted Laser Desoprtion/Ionization Mass Spectrometry, Analytical Chemistry, 72:652-657. [cited by applicant]
Lawson, 2009, From laboratory to bedside and back again: the use of dried blood spot analysis in paediatric care, J. Pharm. Pharmacol., Suppl 1: A33-A138. [cited by applicant]
Lazovic, 2012, Detection of 2-hydroxyglutaric acid in vivo by proton magnetic resonance spectroscopy in U87 glioma cells overexpressing isocitrate dehydrogenase-1 mutation, Neuro Oncol 14:1465-1472. [cited by applicant]
Lee, 1992. Thermally Assisted Electrospray Interface for Liquid Chromatography/Mass Spectrometry, Rapid Commun. Mass Spectrom., 6:727-733. [cited by applicant]
Lejeune, 2007, Simultaneous determination of monodesethylchloroquine, chloroquine, cycloguanil and proguanil on dried blood spots by reverse-phase liquid chromatography, J. Pharm. Biomed. Anal., 43:1106-1115. [cited by applicant]
Li, 1986, Fluorescence Polarization Immunoassay for Theophylline Modified for Use with Dried Blook Spots on Filter Paper, Clin. Chem., 32:552-555. [cited by applicant]
Li, 2008, Paper-Based Microfluidic Devices by Plasma Treatment, Anal. Chem, 80:9131-9134. [cited by applicant]
Li, 2009, Online Coupling of Electrochemical Reactions with Liquid Sample Desorption Electrospray Ionization-Mass Spectrometry, Anal. Chem., 81:9716-9722. [cited by applicant]
Li, 2011, Strategies in quantitative LC-MS/MS analysis of unstable small molecules in biological matrices, Biomed. Chromat., 25:258-277. [cited by applicant]
Linehan, 2010, The genetic basis of kidney cancer: a metabolic disease, Nat Rev Urol 7:277-285. [cited by applicant]
Liu, 2010, Development, Characterization, and Application of Paper Spray Ionization, Anal. Chem., 82:2463-2471. [cited by applicant]
Liu, 2011, Biological Tissue Diagnostics Using Needle Biopsy and Spray Ionization Mass Spectrometry, Analytical Chemistry, 83:9221-9225. [cited by applicant]
Liu, 2012, Signal and charge enhancement for protein analysis by liquid chromatography-mass spectrometry with desorption electrospray ionization, International J Mass Spectrometry 325-327:161-166. [cited by applicant]
Liu, 2013, Recent advances of electrochemical mass spectrometry, Analyst, 138:5519-5539. [cited by applicant]
Long, 1983, Limit of Detection, A Closer Look at the IUPAC Definition, Anal Chem., 55:712A-724A. [cited by applicant]
Losman, 2013, (R)-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible, Science 339:1621-1624. [cited by applicant]
Lozano, 2005, lonic Liquid lon Sources: Characterization of Externally Wetted Emitters, Journal of Colloid and Interface Science 282:415-421. [cited by applicant]
Lu, 1998, Drug-Metabolism Research Challenges in the New Millennium, Individual Variability in Drug Therapy and Drug Safety, Drug Metab. Dispos., 26:1217-1222. [cited by applicant]
Lu, 2012, IDH mutation impairs histone demethylation and results in a block to cell differentiation, Nature 483, 474-478. [cited by applicant]
Lui, 2013, Measuring Protein-Ligand Interactions Using Liquid Sample Desorption Electrospray Ionization Mass Spectrometry, Anal. Chem. 85:11966-11972. [cited by applicant]
Mandal, 2012, Solid probe assisted nanoelectrospray ionization mass spectrometry for biological tissue Diagnostics, Analyst, 137:4658-4661. [cited by applicant]
Manicke, 2009, Imaging of Lipids in Atheroma by Desorption Electrospray Ionization Mass Spectrometry, Analytical Chemistry 81(21):8702-8707. [cited by applicant]
Manicke, 2011, Assessment of paper spray ionization for quantitation of pharmaceuticlas in blood spots, Int. J. Mass Spectrom., 300:123-129. [cited by applicant]
Manicke, 2011, Quantitative Analysis of Therapeutic Drugs in Dried Blook Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring, J. Am. Soc. Mass. Spectrom., 22:1501-1507. [cited by applicant]
Mardis, 2009, Recurring mutations found by sequencing an acute myeloid leukemia genome, N Engl J Med 361:1058-1066. [cited by applicant]
Marinetti, 1976, In Lipid Chromatographic Analysis, Wuthier, R. E., Ed., Marcel Dekker: New York, 1976; vol. 1, pp. 59-109. [cited by applicant]
Martinez, 2007, Patterned Paper as a Platform for Inexpensive, Low-Volume Portable Bioassays, Angew. Chem. Int. Ed., 46:1318-1320. [cited by applicant]
Martinez, 2008, FLASH: A rapid method for prototyping paper-based microfluidic devices, Lab Chip 2008, 8:2146-2150. [cited by applicant]
Martinez, 2008, Three-dimensional microfluidid devices fabricated in layered paper and tape, PNAS, 105:19606-19611. [cited by applicant]
Masterson, 2011, Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospary Ionization Imaging Mass Spectrometry, J Am Soc Mass Spectrom, 22:1326-1333. [cited by applicant]
Miao, 2009, Direct Analysis of Liquid Samples by Desorption Electrospray Ionization-Mass Spectrometry (DESI-MS), J Am Soc Mass Spectrom, 20:10-19. [cited by applicant]
Monge, 2013, Mass spectrometry: recent advances in direct open air surface sampling/ionization, Chemical Reviews, 113:2269-2308. [cited by applicant]
Nemes, 2012, Ambient mass spectrometry for in vivo local analysis and in situ molecular tissue imaging, Trends in Analytical Chemistry 34:22-34. [cited by applicant]
Ntale, 2007, A field-adapted HPLC method for determination of amodiaquine and its metabolite in whole blood dried on filter paper, J. Chromatogr. B, 859:137-140. [cited by applicant]
Oppenheimer, 2010, A Molecular Analysis of Tumor Margins by MALDI Mass Spectrometry in Renal Carcinoma, Journal of Proteome Research, 9(5):2182-2190. [cited by applicant]
Otsuka, 2012, Scanning probe electrospray ionization for ambient mass spectrometry, Rapid Commun Mass Spectrom, 26(23):2725-32. [cited by applicant]
Parsons, 2008, An integrated genomic analysis of human glioblastoma multiforme, Science 321:1807-1812. [cited by applicant]
Yan, 2009, IDH1 and IDH2 mutations in gliomas, N Engl J Med, 360:765-773. [cited by applicant]
Yang, 2007, An ImmunoChip prototype for simultaneous detection of antiepileptic drugs using an enhanced one-step homogeneous immunoassay, Anal. Biochem., 365:222-229. [cited by applicant]
Yoshimura, 2011, Real-time analysis of living animals by electrospray ionization mass spectrometry, Anal. Biochem., 417:195-201. [cited by applicant]
Yu, 2013, Direct Electrospray Ionization Mass Spectrometric Profiling of Real-World Samples via a Solid Sampling Probe, J. Am. Mass Spectrom, 24:1612-1615. [cited by applicant]
Zettersten, 1998, Recessive x-linked ichthyosis: role of cholesterol-sulfate accumulation in the barrier abnormality, J. Invest. Dermatol., 111(5):784-790. [cited by applicant]
Zhang, 2012, Electrochemistry-Assisted Top-Down Characterization of Disulfide-Containing Proteins, Anal Chem., 84(8): 1-7. [cited by applicant]
Zhang, 2012, Mass Spectrometric Analysis of Thiol Proteins/Peptides Following Selenamide Derivatization and Electrolytic Reduction of Disulfide Bonds, Ohio University, 240 pages. [cited by applicant]
Zhang, 2012, Silica Coated Paper Substrate for Paper-Spray Analysis of Therapeutic Drugs in Dried Blood Spots, Anal. Chem., 84:931-938. [cited by applicant]
Zhang, 2014, Paper Spray Ionization of Noncovalent Protein Complexes, Anal. Chem. A-E. [cited by applicant]
Zheng, 2005, A Microfluidic Approach for Screening Submicroliter vols. against Multiple Reagents by Using Preformed Arrays of Nanoliter Plugs in a Three-Phase Liquid/Liquid/Gas Flow, Angew. Chem. Int. Ed., 44(17):2520-2… [cited by applicant]