Innovations in Analytical Oncology - Status quo of Mass Spectrometry-Based Diagnostics for Malignant Tumor


  • Sen Takeda Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110, Shimo-Kateau, Chuo, Yamanashi, 409-3898, Japan
  • Kentaro Yoshimura Department of Anatomy and Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110, Shimo-Kateau, Chuo, Yamanashi, 409-3898, Japan
  • Kenzo Hiraoka Clean Energy Research Center, University of Yamanashi, 4-4-37, Takeda, Kofu, Yamanashi, 400-8510, Japan



Cancer, Diagnosis, Imaging, Electrospray, Ionization, Regression, Surgery


Recent innovations in mass spectrometry make it possible to diagnose malignant tumors through a rapid, non-destructive and less-expensive way. One of the important facets in this achievement lies in the development of several superior ionization techniques that are essentially derivatives of two authentic methods; matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI). In this review article, we introduce a novel cancer diagnostic system based on probe electrospray ionization (PESI) and logistic regression algorithm. This method uses a very fine needle with a tip diameter of several hundreds nm, which serves as a sampling as well as ionization device. Only a few picolitre (pL) of sample are sufficient to acquire mass spectra for making a diagnosis. Furthermore, as this method does not require any sample pre-treatments that often disorganize the original molecular composition of samples, it has a potential in delineating substances that have been missed by conventional analytical methods. By implementing this technology, we have successfully made in situ diagnosis of malignant tumors in human tissues and in living animals. On the other hand, there are two promising and competitive diagnostic methods; one is desorption ionization mass spectrometry (DESI-MS), and the other is rapid evaporation ionization mass spectrometry (REI-MS) coupled with electrical surgical knife. They are also promising technologies in the new era of analytical oncology. We compare these three methods briefly and attempt to give a new perspective in cancer diagnostics.


Klebs E. Die Einschmelzungs-Methode, ein Beitrag zur mikroskopischen Technik. Archiv für mikroskopische Anatomie 1869; 5: 164-66.

Waldeyer W. Untersuchungen über den Ursprung und den Verlauf des Achsencylinders bei Wirbelthieren und Wirbellosen. Henle und Pfeiffer’sche Zeitschrift für rationelle Medizin 1863; pp. 193-256.

Coons AH, Kaplan MH. Localization of antigen in tissue cells; improvements in a method for the detection of antigen by means of fluorescent antibody. J Exper Med 1950; 91(1): 1-13. Epub 1950/01/01.

Min HK, Lim S, Chung BC, Moon MH. Shotgun lipidomics for candidate biomarkers of urinary phospholipids in prostate cancer. Anal Bioanal Chem 2011; 399(2): 823-30. Epub 2010/10/19.

Shiea J, Cho YT, Lin YH, et al. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to rapidly screen for albuminuria. Rapid communications in mass spectrometry: RCM 2008; 22(23): 3754-60. Epub 2008/11/05.

Zaima N, Sasaki T, Tanaka H, et al. Imaging mass spectrometry-based histopathologic examination of atherosclerotic lesions. Atherosclerosis 2011; 217(2): 427-32. Epub 2011/04/26.

Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989; 246(4926): 64-71. Epub 1989/10/06.

Tsuyama N, Mizuno H, Masujima T. Mass spectrometry for cellular and tissue analyses in a very small region. Anal Sci Int J Jpn Soc Anal Chem 2011; 27(2): 163-70. Epub 2011/02/16.

Taylor GI. Disintegration of water drops in an electric field. ProcRoyal SocLondon A 1964; 280: 383-97.

Hiraoka K, Nishidate K, Mori K, Asakawa D, Suzuki S. Development of probe electrospray using a solid needle. Rapid communications in mass spectrometry: RCM 2007; 21(18): 3139-44. Epub 2007/08/22.

Yoshimura K, Chen LC, Asakawa D, Hiraoka K, Takeda S. Physical properties of the probe electrospray ionization (PESI) needle applied to the biological samples. Journal of mass spectrometry: JMS 2009; 44(6): 978-85. Epub 2009/03/24.

Okabe S, Hirokawa N. Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells. J Cell Biol 1988; 107(2): 651-64. Epub 1988/08/01.

Yoshimura K, Chen LC, Yu Z, Hiraoka K, Takeda S. Real-time analysis of living animals by electrospray ionization mass spectrometry. Anal Biochem 2011; 417(2): 195-201. Epub 2011/07/12.

Chen LC, Yoshimura K, Yu Z, et al. Ambient imaging mass spectrometry by electrospray ionization using solid needle as sampling probe. Journal of mass spectrometry: JMS 2009; 44(10): 1469-77. Epub 2009/08/18.

(a) Tanabe K. Penalized Logistic Regression Machines: New methods for statistical prediction 1, (2001a), Cooperative Research Report 143, "Estimation and Smoothing methods in Nonparametric Statistical Models", Institute of Statistical Mathematics, 2001; pp. 163-194. (b) Tanabe K. Penalized logistic regression machines: New methods for statistical prediction 2, (2001b), Proceedings of 2001 Workshop on Information-Based Induction Science (IBIS2001), 2001; pp. 71-76. (c) Tanabe K. Penalized Logistic Regression Machines and Related Linear Numerical Algebra, (2003), KOKYUROKU No.1320, "The Numerical Solution of Differential Equations and Linear Computation", Institute for Mathematical Sciences, Kyoto University 2003; pp. 239-249. (d) Matsui T, Tanabe K, Eds. Speaker identification with dual penalized logistic regression machine. The Speaker and Language Recognition Workshop 2004.

Willems SM, van Remoortere A, van Zeijl R, Deelder AM, McDonnell LA, Hogendoorn PC. Imaging mass spectrometry of myxoid sarcomas identifies proteins and lipids specific to tumour type and grade, and reveals biochemical intratumour heterogeneity. J Pathol 2010; 222(4): 400-9. Epub 2010/09/15.

Hayasaka T, Goto-Inoue N, Sugiura Y, et al. Matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry reveals a layered distribution of phospholipid molecular species in the mouse retina. Rapid communications in mass spectrometry: RCM 2008; 22(21): 3415-26. Epub 2008/10/08.

Takats Z, Wiseman JM, Gologan B, Cooks RG. Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 2004; 306(5695): 471-3. Epub 2004/10/16.

Cooks RG, Ouyang Z, Takats Z, Wiseman JM. Detection Technologies. Ambient mass spectrometry. Science 2006; 311(5767): 1566-70. Epub 2006/03/18.

Chang DY, Lee CC, Shiea J. Detecting large biomolecules from high-salt solutions by fused-droplet electrospray ionization mass spectrometry. Anal Chem 2002; 74(11): 2465-9. Epub 2002/06/19.

Eberlin LS, Dill AL, Golby AJ, et al. Discrimination of human astrocytoma subtypes by lipid analysis using desorption electrospray ionization imaging mass spectrometry. Angew Chem Int Ed Engl 2010; 49(34): 5953-6. Epub 2010/07/06.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO Classification of Tumors of the Central Nervous System: WHO Press 2007.

Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cooks RG. Desorption electrospray ionization mass spectrometry for lipid characterization and biological tissue imaging. Biochim Biophys Acta 2011; 1811(11): 946-60. Epub 2011/06/08.

Balog J, Szaniszlo T, Schaefer KC, et al. Identification of biological tissues by rapid evaporative ionization mass spectrometry. Anal Chem 2010; 82(17): 7343-50. Epub 2010/08/05.

Schafer KC, Balog J, Szaniszlo T, et al. Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry. Anal Chem 2011; 83(20): 7729-35. Epub 2011/09/16.

Chen LC, Hashimoto Y, Furuya H, Takekawa K, Kubota T, Hiraoka K. Rapid detection of drugs in biofluids using atmospheric pressure chemi/chemical ionization mass spectrometry. Rapid communications in mass spectrometry: RCM 2009; 23(3): 333-9. Epub 2009/01/07.




How to Cite

Takeda, S., Kentaro Yoshimura, & Hiraoka, K. (2012). Innovations in Analytical Oncology - Status quo of Mass Spectrometry-Based Diagnostics for Malignant Tumor . Journal of Analytical Oncology, 1(1), 74–80.