DISCOVERIES (ISSN 2359-7232), 2014, April-June

CITATION: 
Crutchfield CA, Clarke W. Present and Future Applications of High Resolution Mass Spectrometry in the Clinic. Discoveries 2014, Apr-Jun; 2(2): e17. DOI: 10.15190/d.2014.9

Submitted: June 4, 2014; Revised: June 28, 2014; Accepted: June 29, 2014; Published: June 30, 2014;

GO BACK to 2014, April-June issue 
GO BACK to DISCOVERIES

Present and Future Applications of High Resolution Mass Spectrometry in the Clinic

Christopher A. Crutchfield  (1), William Clarke (1,*)

(1) Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

*Correspondence to: William Clarke, PhD, MBA, DABCC , Johns Hopkins University School of Medicine, 1800 Orleans Street/Zayed Tower B-1020F, Baltimore, MD, USA; wclarke@jhmi

Abstract

High resolution mass spectrometers have directly enabled clinical applications of high clinical utility. These types of mass spectrometers are less known to the general public than their low resolution counterparts and are often ascribed to proteomics or biomarker discovery. This perception is rapidly changing as high resolution mass spectrometers see impact in the areas of clinical toxicology, forensic toxicology, microbiology, and molecular diagnostics as routine analyzers. Applications in these areas are made possible by the unique capacity of high resolution mass spectrometers, typically time-of flight or Orbitrap instruments, to characterize analytical species with sufficient mass resolution to better resolve molecular composition than lower resolution analyzers. This capacity confers a unique source of analytical specificity. In the future, this analytical specificity will likely be well applied to other clinical applications: mass spectrometry based tissue imaging, intraoperative determination of tumor boundaries, and evaluation of metabolic flux.

Access full text of the manuscript here: See full text (pdf)

References

1.   Wu AHB, French D. Implementation of liquid chromatography/mass spectrometry into the clinical laboratory. Clin Chim Acta. 2013 May;420:4–10. 

2.   Handelsman DJ, Wartofsky L. Requirement for Mass Spectrometry Sex Steroid Assays in the Journal of Clinical Endocrinology and Metabolism. J Clin Endocrinol Metab. 2013 Oct;98(10):3971–3. 

3.   Marshall AG, Hendrickson CL. High-Resolution Mass Spectrometers. Annu Rev Anal Chem. 2008;1(1):579–99. 

4.   Xian F, Hendrickson CL, Marshall AG. High Resolution Mass Spectrometry. Anal Chem. 2012 Jan 17;84(2):708–19. 

5.   Sleno L. The use of mass defect in modern mass spectrometry. J Mass Spectrom. 2012;47(2):226–36. 

6.   Mcnaught A, Wilkinson A. I{UPAC}. Compendium of Chemical Terminology, 2nd ed. (the “Gold Book”). WileyBlackwell; 2nd Revised edition; 

7.   De Hoffmann E. Tandem mass spectrometry: A primer. J Mass Spectrom. 1996 Feb 1;31(2):129–37. 

8.   Ekroos K, Chernushevich IV, Simons K, Shevchenko A. Quantitative Profiling of Phospholipids by Multiple Precursor Ion Scanning on a Hybrid Quadrupole Time-of-Flight Mass Spectrometer. Anal Chem. 2002 Mar 1;74(5):941–9. 

9.   Covey TR, Thomson BA, Schneider BB. Atmospheric pressure ion sources. Mass Spectrom Rev. 2009 Nov 1;28(6):870–97. 

10. Ho C, Lam C, Chan M, Cheung R, Law L, Lit L, et al. Electrospray Ionisation Mass Spectrometry: Principles and Clinical Applications. Clin Biochem Rev. 2003 Feb;24(1):3–12. 

11. Zenobi R, Knochenmuss R. Ion formation in MALDI mass spectrometry. Mass Spectrom Rev. 1998 Oct;17(5):337–66. 

12. Eichhorn P, Pérez S, Barceló D. Chapter 5 - Time-of-Flight Mass Spectrometry Versus Orbitrap-Based Mass Spectrometry for the Screening and Identification of Drugs and Metabolites: Is There a Winner? In: Amadeo R. Fernandez-Alba, editor. Comprehensive Analytical Chemistry. Elsevier; 2012 [cited 2014 Jan 31]. p. 217–72. Available from: http://www.sciencedirect.com/ science/article/pii/B9780444538109000092

13. Schneir AB, Cullen J, Ly BT. “Spice” girls: synthetic cannabinoid intoxication. J Emerg Med. 2011 Mar;40(3):296–9. 

14. Centers for Disease Control and Prevention (CDC). Emergency department visits after use of a drug sold as “bath salts”--Michigan, November 13, 2010-March 31, 2011. MMWR Morb Mortal Wkly Rep. 2011 May 20;60(19):624–7. 

15. Wu AH, Gerona R, Armenian P, French D, Petrie M, Lynch KL. Role of liquid chromatography–high-resolution mass spectrometry (LC-HR/MS) in clinical toxicology. Clin Toxicol. 2012 Sep;50(8):733–42. 

16. Kronstrand R, Brinkhagen L, Birath-Karlsson C, Roman M, Josefsson M. LC-QTOF-MS as a superior strategy to immunoassay for the comprehensive analysis of synthetic cannabinoids in urine. Anal Bioanal Chem. 2014 Jan 15; 

17. Anizan S, Concheiro M. Simultaneous quantification of 28 synthetic cathinones and metabolites in urine by liquid chromatography-high resolution mass spectrometry. Anal Bioanal Chem. 2013;405(29):9437–48. 

18. Rosano TG, Wood M, Ihenetu K, Swift TA. Drug Screening in Medical Examiner Casework by High-Resolution Mass Spectrometry (UPLC–MSE-TOF). J Anal Toxicol. 2013 Oct 1;37(8):580–93. 

19. Marzinke MA, Clarke W, Wang L, Cummings V, Liu T-Y, Piwowar-Manning E, et al. Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection. Clin Infect Dis. 2014 Jan 1;58(1):117–20. 

20. Clark AE, Kaleta EJ, Arora A, Wolk DM. Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. Clin Microbiol Rev. 2013 Jul;26(3):547–603. 

21. Tan KE, Ellis BC, Lee R, Stamper PD, Zhang SX, Carroll KC. Prospective evaluation of a matrix-assisted laser desorption ionization-time of flight mass spectrometry system in a hospital clinical microbiology laboratory for identification of bacteria and yeasts: a bench-by-bench study for assessing the impact on time to identification and cost-effectiveness. J Clin Microbiol. 2012 Oct;50(10):3301–8. 

22. Huang AM, Newton D, Kunapuli A, Gandhi TN, Washer LL, Isip J, et al. Impact of Rapid Organism Identification via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Combined With Antimicrobial Stewardship Team Intervention in Adult Patients With Bacteremia and Candidemia. Clin Infect Dis. 2013 Jul 29;cit498. 

23. Marko DC, Saffert RT, Cunningham SA, Hyman J, Walsh J, Arbefeville S, et al. Evaluation of the Bruker Biotyper and Vitek MS Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems for Identification of Nonfermenting Gram-Negative Bacilli Isolated from Cultures from Cystic Fibrosis Patients. J Clin Microbiol. 2012 Jun 1;50(6):2034–9. 

24. Dingle TC, Butler-Wu SM. MALDI-TOF Mass Spectrometry for Microorganism Identification. Clin Lab Med. 2013 Sep;33(3):589–609. 

25. Pusch W, Kostrzewa M. Application of MALDI-TOF Mass Spectrometry in Screening and Diagnostic Research. Curr Pharm Des. 2005 Aug 1;11(20):2577–91. 

26. Gao X, Tan B-H, Sugrue RJ, Tang K. MALDI mass spectrometry for nucleic acid analysis. Top Curr Chem. 2013;331:55–77. 

27. Gabriel S, Ziaugra L, Tabbaa D. SNP Genotyping Using the Sequenom MassARRAY iPLEX Platform. Current Protocols in Human Genetics. John Wiley & Sons, Inc.; 2001. Available from: http://onlinelibrary.wiley.com/doi/10.1002/0471142905.hg0212s60/abstract

28. Ecker DJ, Sampath R, Massire C, Blyn LB, Hall TA, Eshoo MW, et al. Ibis T5000: a universal biosensor approach for microbiology. Nat Rev Microbiol. 2008 Jul;6(7):553–8. 

29. Tang Y-W, Lowery KS, Valsamakis A, Schaefer VC, Chappell JD, White-Abell J, et al. Clinical accuracy of a PLEX-ID flu device for simultaneous detection and identification of influenza viruses A and B. J Clin Microbiol. 2013 Jan;51(1):40–5. 

30. Sinotte M, Diorio C, Berube S, Pollak M, Brisson J. Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr. 2009 Feb 1;89(2):634–40. 

31. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, et al. Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity. Diabetes. 2011 May 1;60(5):1528–34. 

32. Holzinger ER, Grady B, Ritchie MD, Ribaudo HJ, Acosta EP, Morse GD, et al. Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6 variants. Pharmacogenet Genomics. 2012 Dec;22(12):858–67. 

33. Caprioli RM, Farmer TB, Gile J. Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS. Anal Chem. 1997 Dec 1;69(23):4751–60. 

34. Ellis SR, Bruinen AL, Heeren RMA. A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry. Anal Bioanal Chem. 2014 Feb 1;406(5):1275–89. 

35. McDonnell LA, Heeren RMA. Imaging mass spectrometry. Mass Spectrom Rev. 2007 Aug;26(4):606–43. 

36. Caprioli RM. Imaging mass spectrometry: Molecular microscopy for enabling a new age of discovery. Proteomics. 2014 Apr 1;14(7-8):807–9. 

37. Wu C, Dill AL, Eberlin LS, Cooks RG, Ifa DR. Mass spectrometry imaging under ambient conditions. Mass Spectrom Rev. 2013 May 1;32(3):218–43. 

38. Rauser S, Marquardt C, Balluff B, Deininger S-O, Albers C, Belau E, et al. Classification of HER2 Receptor Status in Breast Cancer Tissues by MALDI Imaging Mass Spectrometry. J Proteome Res. 2010 Apr 5;9(4):1854–63. 

39. Li H, Hummon AB. Imaging Mass Spectrometry of Three-Dimensional Cell Culture Systems. Anal Chem. 2011 Nov 15;83(22):8794–801. 

40. Balog J, Sasi-Szabó L, Kinross J, Lewis MR, Muirhead LJ, Veselkov K, et al. Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry. Sci Transl Med. 2013 Jul 17;5(194):194ra93–194ra93. 

41. Jackson SN, Ugarov M, Egan T, Post JD, Langlais D, Schultz JA, et al. MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrom. 2007 Aug;42(8):1093–8. 

42. Deng Y, Wu JT, Lloyd TL, Chi CL, Olah TV, Unger SE. High-speed gradient parallel liquid chromatography/tandem mass spectrometry with fully automated sample preparation for bioanalysis: 30 seconds per sample from plasma. Rapid Commun Mass Spectrom. 2002;16(11):1116–23. 

43. Wiechert W. C-13 metabolic flux analysis. Metab Eng. 2001 Jul;3(3):195–206. 

44. Munger J, Bennett BD, Parikh A, Feng X-J, McArdle J, Rabitz HA, et al. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat Biotechnol. 2008 Oct;26(10):1179–86. 

45. Hiller K, Metallo CM. Profiling metabolic networks to study cancer metabolism. Curr Opin Biotechnol. 2013 Feb;24(1):60–8. 

46. Fan TWM, Lane AN, Higashi RM. The promise of metabolomics in cancer molecular therapeutics. Curr Opin Mol Ther. 2004 Dec;6(6):584–92. 

47. Wise DR, Thompson CB. Glutamine Addiction: A New Therapeutic Target in Cancer. Trends Biochem Sci. 2010 Aug;35(8):427–33. 

48. Kullolli M, Knouf E, Arampatzidou M, Tewari M, Pitteri SJ. Intact MicroRNA Analysis Using High Resolution Mass Spectrometry. J Am Soc Mass Spectrom. 2014 Jan 1;25(1):80–7. 

49. Creemers EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012 Feb 3;110(3):483–95. 

50. Kelly RT, Tolmachev AV, Page JS, Tang K, Smith RD. The ion funnel: Theory, implementations, and applications. Mass Spectrom Rev. 2010 Mar 1;29(2):294–312. 

GO BACK to the 2014, April-June issue 
GO BACK to DISCOVERIES 
MEET OUR EDITORIAL BOARD 
SUBMIT A MANUSCRIPT

 Email us at info@discoveriesjournals.org if you have any questions.