What is the “intelligent knife” also called “iKnife” or REIMS?

It is a new mass spectrometry based technique that could be used routinely for cancer diagnostics and surgery in the future!


It is a cancer knife that identifies tumor cells!


The news section of the Journal of Science at page 221 in the July 19, 2013 issue reviewed a paper that was published in “Science Translational Medicine” in the following week that describes the “iKnife”, an invention of Zoltan Takats, a Hungarian chemist at the Imperial College London.

REIMS 1These graphics illustrate how the technique works. For more detail please review the literature found at the end of the blog.


Since my time in college I am fascinated by the technique called mass spectrometry. During my early studies in chemistry, biochemistry and cell biology I quickly became convinced that mass spectrometry is one of the most powerful techniques a scientist can have in his hands to tackle important biochemical, biological and biomedical questions. Unfortunately, at that time, to use the technique successfully we had to write our own program for the data interpretation. This we did by using Fortran, a general-purpose, programming language that is especially suited to numeric computation and scientific computing. However, all this has dramatically changed over the years. As you probably all know the mass spectrometry field has grown immensely in the last 25 years. To find out about the improvement made and how mass spectrometry has changed the way scientist work these days all one has to do is to go to the web site of the “American Society for Mass Spectrometry (ASMS)”. You can learn how these and other mass spectrometry techniques work from information available at that site.

Several novel ionization methods for the in-situ, and in-vivo mass spectrometric analysis of biological tissues have been developed in recent years. One of these is a technique called “Rapid Evaporative Ionization Mass Spectrometry (REIMS)”. The name implicates the underlying mechanism of ionization used. The ionization method used here is analogous to sonic spray or thermospray (off-filament) ionization and readily produces gaseous ions from tissues. The method produces small droplets and simultaneously generates ions that belong predominantly to various lipid constituents, especially to phospholipids. Furthermore, since these ionization methods cannot apply any static direct current (DC) potential onto the sample they yield positive and negative ions in a parallel fashion. 

REIMS is a newly emerging technique that allows near–real-time characterization of human tissue on the spot (in vivo). The technique analyzes the aerosol (“smoke”) that is released during an electrosurgical dissection, for example during a surgical procedure that aims to completely remove a tumor or cancerous growth. The coupling of the REIMS technology with electro-surgery for the diagnostics of tissue samples is known as the intelligent knife (iKnife).

Schaeffer et al. in a recent paper demonstrated that laser desorption ionization/mass spectrometric allow to investigate bulk and even vital tissues in situ and in real time originating from histological samples. The scientists report that a surgical laser can be used without the need for further nonsurgical instrumentation at the surgical site. The researcher argue that the technique is perfectly compatible with the current surgical environment. Their hope is that this technique will find its introduction into surgery rooms in the future and that it may become a part of routine surgeries.

However, laser surgery is currently not part of the most abundant surgical techniques. The researchers suggest that the recent introduction of hollow fiber light guides for carbon dioxide (CO2) lasers together with mass spectrometric tissue identification has the potential to use the technique in cancer surgery.


Graphical illustrations that show how the technique works.



J. Balog, L. Sasi-Szabó, J. Kinross, M. R. Lewis, L. J. Muirhead, K. Veselkov, R. Mirnezami, B. Dezső, L. Damjanovich, A. Darzi, J. K. Nicholson, Z. Takáts, Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry. Sci. Transl. Med. 5, 194ra93 (2013).

Denes J; Robinette S; Hester A; Szabo E; Szatmari I; Szonyi L; Kreuder J; Rauterberg E; et al. (1 Sep 2012). APPLICATION OF HIGH RESOLUTION MASS SPECTROMETRY IN NEWBORN SCREENING. JOURNAL OF INHERITED METABOLIC DISEASE. 35:S6-S6. Author weblink.

Gerbig S; Golf O; Balog J; Denes J; Baranyai Z; Zarand A; Raso E; Timar J; et al. (Jun 2012). Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging. Anal Bioanal Chem. 403:2315-2325. Author weblink DOI.

Sabine Guenther, Karl-Christian Schäfer, Júlia Balog, Júlia Dénes, Tamás Majoros, Katalin Albrecht, Miklós Tóth, Bernhard Spengler, Zoltán Takáts; Electrospray Post-Ionization Mass Spectrometry of Electrosurgical Aerosols. Journal of The American Society for Mass Spectrometry November 2011, Volume 22, Issue 11, pp 2082-2089.

Ruth Hüttenhain, Martin Soste, Nathalie Selevsek, Hannes Röst, Atul Sethi, Christine Carapito, Terry Farrah, Eric W. Deutsch, Ulrike Kusebauch, Robert L. Moritz, Emma Niméus-Malmström, Oliver Rinner, and Ruedi Aebersold; Proteomics Reproducible Quantification of Cancer-Associated Proteins in Body Fluids Using Targeted Proteomics. Sci Transl Med 11 July 2012 4:142ra94.

Blandine Laferrère, David Reilly, Sara Arias, Nicholas Swerdlow, Prakash Gorroochurn, Baani Bawa, Mousumi Bose, Julio Teixeira, Robert D. Stevens, Brett R. Wenner, James R. Bain, Michael J. Muehlbauer, Andrea Haqq, Lillian Lien, Svati H. Shah, Laura P. Svetkey, and Christopher B. Newgard; Metabolism Differential Metabolic Impact of Gastric Bypass Surgery Versus Dietary Intervention in Obese Diabetic Subjects Despite Identical Weight Loss. Sci Transl Med 27 April 2011 3:80re2

Gregory D. Lewis, Laurie Farrell, Malissa J. Wood, Maryann Martinovic, Zoltan Arany, Glenn C. Rowe, Amanda Souza, Susan Cheng, Elizabeth L. McCabe, Elaine Yang, Xu Shi, Rahul Deo, Frederick P. Roth, Aarti Asnani, Eugene P. Rhee, David M. Systrom, Marc J. Semigran, Ramachandran S. Vasan, Steven A. Carr, Thomas J. Wang, Marc S. Sabatine, Clary B. Clish, and Robert E. Gerszten; Exercise and Metabolism Metabolic Signatures of Exercise in Human Plasma. Sci Transl Med 26 May 2010 2:33ra37

Muirhead LJ; Kinross J; FitzMaurice TS; Takats Z; Darzi A; Nicholson JK. (1 Aug 2012). Surgical systems biology and personalized longitudinal phenotyping in critical care. PERSONALIZED MEDICINE. 9:593-608. Author weblink DOI.

Schäfer KC, Dénes J, Albrecht K, Szaniszló T, Balog J, Skoumal R, Katona M, Tóth M, Balogh L, Takáts Z.; In vivo, in situ tissue analysis using rapid evaporative ionization mass spectrometry. Angew Chem Int Ed Engl. 2009;48(44):8240-2. doi: 10.1002/anie.200902546.

Strittmatter N; Düring RA; Takáts Z. (7 Sep 2012). Analysis of wastewater samples by direct combination of thin-film microextraction and desorption electrospray ionization mass spectrometry. Analyst. 137:4037-4044. Author weblink DOI.

Nicole Strittmatter,a   Emrys A. Jones,a   Kirill A. Veselkov,a   Monica Rebec,b   Jacob G. Bundya and   Zoltan Takats; Analysis of intact bacteria using rapid evaporative ionisation mass spectrometry. Chem. Commun., 2013,49, 6188-6190. DOI: 10.1039/C3CC42015A.

Takats Z; Denes J; Kinross J. (Feb 2012). Identifying the margin: a new method to distinguish between cancerous and noncancerous tissue during surgery. Future Oncol. 8:113-116. Author weblink DOI.

Chin-Lee Wu, Kate W. Jordan, Eva M. Ratai, Jinhua Sheng, Christen B. Adkins, Elita M. DeFeo, Bruce G. Jenkins, Leslie Ying, W. Scott McDougal, and Leo L. Cheng; Cancer Metabolomic Imaging for Human Prostate Cancer Detection. Sci Transl Med 27 January 2010 2:16ra8

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Categories: Cancer, Cancer Surgery, iKnife, Mass spectrometry

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5 replies

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