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{{Orphan|date=July 2014}}
{{Short description|A surgical tool that uses mass spectrometry to analyze tissue during surgery}}
Surgical Intelligent Knife (iKnife) {{lowercasetitle}}


[[File:Surgeries conducted.jpg|thumb|The iknife shortens the duration of a cancer surgery by eliminating long waits for results from the histological pathologist who now determines the boundary between cancerous and healthy tissue]]
==Iknife==
The '''iKnife''' is an innovative surgical tool that integrates [[mass spectrometry]] with an [[electrosurgical knife]] to provide real-time analysis of tissue during surgical procedures. This technology aids surgeons in distinguishing between cancerous and non-cancerous tissues, thereby improving the precision of surgical interventions.


'''Onkoknife''', '''iKnife''', or '''intelligent scalpel''' ([[English language|English]]: Jedi knife, onkoknife; [[Hungarian language|Hungarian]]: onkokés, intelligens sebészi kés) is a [[Surgical instrument|surgical]] knife, which tests tissue as it contacts it during an operation, and immediately gives information as to whether that tissue contains [[cancer]] cells.<ref name="Balog et al 2013">{{cite journal |doi=10.1126/scitranslmed.3005623 |pmid=23863833 |title=Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry |journal=Science Translational Medicine |volume=5 |issue=194 |pages=194ra93 |year=2013 |last1=Balog |first1=J |last2=Sasi-Szabo |first2=L |last3=Kinross |first3=J |last4=Lewis |first4=M. R |last5=Muirhead |first5=L. J |last6=Veselkov |first6=K |last7=Mirnezami |first7=R |last8=Dezso |first8=B |last9=Damjanovich |first9=L |last10=Darzi |first10=A |last11=Nicholson |first11=J. K |last12=Takats |first12=Z }}</ref> During a surgery this information is given continuously to the surgeon, significantly accelerating biological tissue analysis and enabling identification and removal of cancer cells. Electroknives have been in use since the 1920s and smart knife surgery is not limited only to cancer detection. In clinical studies the iKnife has shown impressive diagnostic accuracy - identifying benign gynaecological tissue from ovarian cancer (97.4% sensitivity, 100% specificity),<ref>{{Cite journal|last=Phelps|first=David L|last2=Balog|first2=Júlia|last3=Gildea|first3=Louise F|last4=Bodai|first4=Zsolt|last5=Savage|first5=Adele|last6=El-Bahrawy|first6=Mona A|last7=Speller|first7=Abigail VM|last8=Rosini|first8=Francesca|last9=Kudo|first9=Hiromi|date=May 2018|title=The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)|url=http://www.nature.com/articles/s41416-018-0048-3|journal=British Journal of Cancer|volume=118|issue=10|pages=1349–1358|doi=10.1038/s41416-018-0048-3|issn=0007-0920}}</ref> breast tumour from normal breast tissue (90.9% sensitivity, 98.8% specificity)<ref>{{Cite journal|last=St John|first=Edward R.|last2=Balog|first2=Julia|last3=McKenzie|first3=James S.|last4=Rossi|first4=Merja|last5=Covington|first5=April|last6=Muirhead|first6=Laura|last7=Bodai|first7=Zsolt|last8=Rosini|first8=Francesca|last9=Speller|first9=Abigail V. M.|date=December 2017|title=Rapid evaporative ionisation mass spectrometry of electrosurgical vapours for the identification of breast pathology: towards an intelligent knife for breast cancer surgery|url=http://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-017-0845-2|journal=Breast Cancer Research|volume=19|issue=1|doi=10.1186/s13058-017-0845-2|issn=1465-542X|pmc=5442854|pmid=28535818}}</ref> and recognises histological features of poor prognostic outcome in colorectal carcinoma.<ref>{{Cite journal|last=Alexander|first=James|last2=Gildea|first2=Louise|last3=Balog|first3=Julia|last4=Speller|first4=Abigail|last5=McKenzie|first5=James|last6=Muirhead|first6=Laura|last7=Scott|first7=Alasdair|last8=Kontovounisios|first8=Christos|last9=Rasheed|first9=Shanawaz|date=March 2017|title=A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife|url=http://link.springer.com/10.1007/s00464-016-5121-5|journal=Surgical Endoscopy|volume=31|issue=3|pages=1361–1370|doi=10.1007/s00464-016-5121-5|issn=0930-2794|pmc=5315709|pmid=27501728}}</ref> Furthermore, the technology behind iKnife - rapid evaporative ionisation mass spectrometry (REIMS) - can identify Candida yeasts down to species level.<ref>{{Cite journal|last=Cameron|first=Simon J. S.|last2=Bolt|first2=Frances|last3=Perdones-Montero|first3=Alvaro|last4=Rickards|first4=Tony|last5=Hardiman|first5=Kate|last6=Abdolrasouli|first6=Alireza|last7=Burke|first7=Adam|last8=Bodai|first8=Zsolt|last9=Karancsi|first9=Tamas|date=December 2016|title=Rapid Evaporative Ionisation Mass Spectrometry (REIMS) Provides Accurate Direct from Culture Species Identification within the Genus Candida|url=http://www.nature.com/articles/srep36788|journal=Scientific Reports|volume=6|issue=1|doi=10.1038/srep36788|issn=2045-2322|pmc=5107957|pmid=27841356}}</ref>
==Development==
The iKnife was developed by Dr. Zoltan Takats and his team at [[Imperial College London]]. The primary goal was to enhance the accuracy of surgical resections by providing immediate feedback on the nature of the tissue being cut. Traditional methods of tissue analysis, such as [[histopathology]], require time-consuming processes that are not feasible during surgery. The iKnife addresses this limitation by offering instantaneous results.


== Research and development ==
==Technology==
'''Zoltán Takáts''', [[Ph.D.]], a [[Hungary|Hungarian]] research [[chemist]] associated with [[Semmelweis University]], in [[Budapest]], invented the ''intelligent surgical knife''. He currently is Professor of Analytical Chemistry at [[Imperial College London]] (UK). His ''iKnife'' has been tested in three hospitals from 2010 through 2012. Following laboratory analysis of tissue samples in 302 patients that were included in a data base, they included 1624 of cancer and 1309 of non-cancer samples.
The iKnife operates by utilizing the principles of [[mass spectrometry]]. When the electrosurgical knife cuts through tissue, it generates a smoke that contains ionized particles. These particles are then analyzed by a mass spectrometer, which identifies the chemical composition of the tissue. The data is compared against a database of known tissue types, allowing the surgeon to determine whether the tissue is malignant or benign.


The current pilot version for the iKnife cost the creating Hungarian scientist, MediMass Ltd. (''Old Buda'' based company) participating in the research, colleagues at Imperial College, and the Hungarian government approximately £200 thousand (68 million HUF). According to Takáts, the investments will have been worth it, however, as the device is on a likely path to marketing.
==Applications==
The iKnife has been primarily used in [[oncological surgery]], where precise removal of cancerous tissue is critical. It has shown promise in surgeries involving the [[breast]], [[stomach]], and [[colon]], among others. By providing real-time feedback, the iKnife helps reduce the likelihood of leaving behind cancerous tissue, which can lead to recurrence.


The instrument has been acquired by the Massachusetts [[Waters Corporation]] for development by ''MediMass Ltd.'', which identifies it as substantive innovative technology labelled, "Intelligent late" and "REIMS", according to their press release on 23 July 2014.<ref>{{cite web|url=http://www.parameter.sk/rovat/technika-tudomany/2014/07/23/amerikai-ceg-vasarolta-fel-magyar-intelligens-kes-technologiat|title=Amerikai cég vásárolta fel a magyar Intelligens Kés technológiát|first=|last=parameter.sk|publisher=}}</ref> The business transaction included all ''MediMass'' innovation, including patents, software, databases, and human resources related to the technology.
==Advantages==
* '''Real-time analysis''': The iKnife provides immediate feedback, allowing surgeons to make informed decisions during the procedure.
* '''Increased accuracy''': By distinguishing between different tissue types, the iKnife enhances the precision of surgical resections.
* '''Reduced need for repeat surgeries''': Accurate removal of cancerous tissue reduces the chances of recurrence, potentially decreasing the need for additional surgeries.


== Principle of operation ==
==Limitations==
While the iKnife offers significant advantages, it also has limitations. The technology requires a comprehensive database of tissue types for accurate analysis, and its effectiveness can be limited by the complexity of certain tissues. Additionally, the cost and availability of the technology may restrict its widespread adoption.


=== History of direct examination of biological tissue by mass spectrometry (MS) ===
==Future Directions==
Research is ongoing to expand the database of tissue types and improve the accuracy of the iKnife. There is also interest in applying the technology to other fields of surgery beyond oncology. As the technology evolves, it is expected to become a standard tool in surgical practice, enhancing the outcomes of various procedures.


Direct examination of biological tissue by [[mass spectrometry]] (MS) began in the 1970s, but at that time the next advance in technical conditions did not exist. The method did not provide any useful information on the chemical composition of the samples tested.<ref>INTELLIGENS SEBÉSZETI ESZKÖZ SZÖVETEK MŰTÉT KÖZBENI AZONOSÍTÁSA TÖMEGSPEKTROMETRIÁS MÓDSZERREL Szaniszló Tamás Dénes Júlia PhD-hallgató PhD, tudományos munkatárs Takáts Zoltán PhD, igazgató z.takats@imperial.ac.uk Semmelweis Egyetem CellScreen Alkalmazott KutatóközpontMagyar Tudomány • 2012/6</ref> The first breakthrough came with desorption ionisation methods ([[Secondary ion mass spectrometry|secondary ionization mass spectrometry]] - SIMS, [[matrix-assisted laser desorption ionization]] - MALDI) a release said. Using these methods, after appropriate sample preparation, chemical biological tissue imaging analysis may be achieved.<ref>van Hove et al., 2010.{{full citation needed|date=September 2018}}</ref> From the end of the 1990s, it became apparent that mass spectrometry data in imaging studies showed a high degree of tissue specificity, that tissue histology could determine mass spectral information, and vice versa.<ref name="Rompp2011">{{cite journal |doi=10.1007/s00216-011-4990-7 |pmid=21516518 |title=Mass spectrometry imaging with high resolution in mass and space (HR2 MSI) for reliable investigation of drug compound distributions on the cellular level |journal=Analytical and Bioanalytical Chemistry |volume=401 |issue=1 |pages=65–73 |year=2011 |last1=Römpp |first1=Andreas |last2=Guenther |first2=Sabine |last3=Takats |first3=Zoltan |last4=Spengler |first4=Bernhard }}</ref>
==Related pages==
 
* [[Mass spectrometry]]
In the case of the detected protein and peptide components, tissue-specific expression of the proteins is known commonly. Precise immunohistochemical methods are based on this phenomenon. The mass spectrometer detection, mainly from cell membranes and similar tissue, specifically, of complex lipids from similar tissue, however, yields surprising results. Since the distribution of proteins are in good agreement with the distribution patterns obtained by immunohistochemical methods, the distribution of the lipid components of the direct ionization mass spectrometric, previously were relative methods leading to the appearance of a new era in the study of biological specimens. The desorption electrospray ionization (DESI) was the first-MS technique, which allowed non-invasive testing of any objects (or organisms) without sample preparation, regardless of their shape or mechanical properties.<ref>Takats et al., 2004{{full citation needed|date=September 2018}}</ref>
* [[Electrosurgery]]
 
* [[Oncological surgery]]
=== Rapid evaporative ionization mass spectrometry ===
* [[Histopathology]]
[[File:Lymph node NPC.jpg|thumb|220PX|Lymph node excision]]
During the summer of 2009, '''rapid evaporative ionization mass spectrometry''' ('''REIMS''') was described. This is the second generation method. Primarily, lipid components of tissues provide the information, but different metabolite molecules and certain proteins also allow detection. The most important advantage of the specificity of mass [[Spectrometry, mass, electrospray ionization|spectrometry]] data is at the [[histological]] level, providing the opportunity to identify biological tissue based on chemical composition. The REIMS method is unique, in that, while the above-described mass spectrometry techniques specific to the particular method developed ion sources should be used, but it is difficult in the case of ion source devices used in surgical practice. With the operation of a variety of tissue-cutting tools, such as a [[diathermy]] knife, a surgical [[laser]], or an [[ultrasound|ultrasonic]] tissue atomizer, an aerosol is formed having a composition characteristic of the tissue cut, which also contains ionized cell constructs.
 
Among them, in terms of using the REIMS method, the intact membrane-forming [[phospholipids]] are important, which easily are detectable by [[mass spectrometry]] on the one hand, and on the other hand, contain the combination of the characteristics of the particular tissue type. Mass spectrometric analysis is just one implementation of an effective extraction system development that was needed to cut the surgical site at the time of running the generated aerosol mass spectrometer. For this purpose, a so-called Venturi-tube serves, as well as the above-mentioned surgical hand pieces, being modified to smoke the aerosols through them. Analysis of the flue gas in the mass spectrometer is realized instantaneously, within a few tenths of a second, resulting in a tissue-specific phospholipid mass spectra being obtained, allowing a response by the surgeon in less than two seconds. The analysis of the collected spectra is made of special-evaluation software, which was developed for this purpose. The software continuously compares the incoming data during surgery, validates mass spectra stored in a database, assigns the appropriate class, and the result is displayed visually to the surgeon. It also may provide information to the surgeon via an audio signal.<ref>Heath, Nick, ''[http://www.techrepublic.com/blog/european-technology/the-intelligent-knife-that-helps-surgeons-sniff-out-cancer/?tag=nl.e101&s_cid=e101&ttag=e101&ftag=TRE684d531 The Intelligent knife that helps surgeons sniff out cancer]'', European Technology, November 26, 2014, distributed in TechRebuplic Daily Digest, TechRepublic.com, November 27, 2014</ref> It is estimated that the tissue identification accuracy during operation is higher than 92%.<ref>{{cite journal |doi=10.1021/ac5046752 |pmid=25671656 |title=Rapid Evaporative Ionization Mass Spectrometry Imaging Platform for Direct Mapping from Bulk Tissue and Bacterial Growth Media |journal=Analytical Chemistry |volume=87 |issue=5 |pages=2527–2534 |year=2015 |last1=Golf |first1=Ottmar |last2=Strittmatter |first2=Nicole |last3=Karancsi |first3=Tamas |last4=Pringle |first4=Steven D |last5=Speller |first5=Abigail V. M |last6=Mroz |first6=Anna |last7=Kinross |first7=James M |last8=Abbassi-Ghadi |first8=Nima |last9=Jones |first9=Emrys A |last10=Takats |first10=Zoltan |hdl=10044/1/45378 }}</ref>
 
Therefore, the method is suitable for use in a surgical environment for carrying out measurements, as well as for being a part of a complex tissue identification system used during surgical tumor removal, and it can assist the surgeon in the operating surgical site with accurate histological mapping. The rapid evaporative ionization mass spectrometry (REIMS) is a novel technique that allows electrosurgery cuts with near real-time characterization of human tissue in vivo analysis through analysis of the vapors released during the process of tissue and aerosols. The REIMS technology and electro-surgical procedure adds tissue diagnosis to the intelligent knife iKnife operating principle.<ref name="Balog et al 2013"/>
 
==See also==
* [[Instruments used in general surgery]]
 
==References==
{{Reflist}}
 
==External links==
* Cancer Research UK: An intelligent knife can tell ovarian cancer and healthy tissue apart. Could it make surgery smarter?[https://scienceblog.cancerresearchuk.org/2018/08/17/an-intelligent-knife-can-tell-ovarian-cancer-and-healthy-tissue-apart-could-it-make-surgery-smarter/]
*[http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_17-7-2013-17-17-32 "Intelligent knife" tells surgeon if tissue is cancerous by Sam Wong]
* [http://www.livescience.com/40341-iknife-sniffs-out-cancer-cells.html Surgical Knife May Sniff Out Cancer By Tanya Lewis, Staff Writer | October 10, 2013]
* Heath, Nick, ''[http://www.techrepublic.com/blog/european-technology/the-intelligent-knife-that-helps-surgeons-sniff-out-cancer/?tag=nl.e101&s_cid=e101&ttag=e101&ftag=TRE684d531 The Intelligent knife that helps surgeons sniff out cancer]'', European Technology, November 26, 2014, distributed in TechRebuplic Daily Digest, TechRepublic.com, November 27, 2014
* http://www.healthline.com/health-news/tech-intelligent-knife-detects-cancer-cells-in-seconds-071813
* {{cite journal |doi=10.1136/bmj.e4505 |pmid=22791786 |pmc=3395735 |title=Reoperation rates after breast conserving surgery for breast cancer among women in England: Retrospective study of hospital episode statistics |journal=BMJ |volume=345 |pages=e4505 |year=2012 |last1=Jeevan |first1=R |last2=Cromwell |first2=D. A |last3=Trivella |first3=M |last4=Lawrence |first4=G |last5=Kearins |first5=O |last6=Pereira |first6=J |last7=Sheppard |first7=C |last8=Caddy |first8=C. M |last9=Van Der Meulen |first9=J. H. P }}
* http://www.doublexscience.org/iknife-excises-uncertainty-in-tumor-resection/
 
{{Surgical instruments}}
{{MedInst}}


[[Category:Surgical instruments]]
[[Category:Surgical instruments]]
[[Category:Medical lists]]
[[Category:Medical technology]]
[[Category:Mass spectrometry]]

Latest revision as of 19:22, 22 March 2025

A surgical tool that uses mass spectrometry to analyze tissue during surgery


Iknife[edit]

The iKnife is an innovative surgical tool that integrates mass spectrometry with an electrosurgical knife to provide real-time analysis of tissue during surgical procedures. This technology aids surgeons in distinguishing between cancerous and non-cancerous tissues, thereby improving the precision of surgical interventions.

Development[edit]

The iKnife was developed by Dr. Zoltan Takats and his team at Imperial College London. The primary goal was to enhance the accuracy of surgical resections by providing immediate feedback on the nature of the tissue being cut. Traditional methods of tissue analysis, such as histopathology, require time-consuming processes that are not feasible during surgery. The iKnife addresses this limitation by offering instantaneous results.

Technology[edit]

The iKnife operates by utilizing the principles of mass spectrometry. When the electrosurgical knife cuts through tissue, it generates a smoke that contains ionized particles. These particles are then analyzed by a mass spectrometer, which identifies the chemical composition of the tissue. The data is compared against a database of known tissue types, allowing the surgeon to determine whether the tissue is malignant or benign.

Applications[edit]

The iKnife has been primarily used in oncological surgery, where precise removal of cancerous tissue is critical. It has shown promise in surgeries involving the breast, stomach, and colon, among others. By providing real-time feedback, the iKnife helps reduce the likelihood of leaving behind cancerous tissue, which can lead to recurrence.

Advantages[edit]

  • Real-time analysis: The iKnife provides immediate feedback, allowing surgeons to make informed decisions during the procedure.
  • Increased accuracy: By distinguishing between different tissue types, the iKnife enhances the precision of surgical resections.
  • Reduced need for repeat surgeries: Accurate removal of cancerous tissue reduces the chances of recurrence, potentially decreasing the need for additional surgeries.

Limitations[edit]

While the iKnife offers significant advantages, it also has limitations. The technology requires a comprehensive database of tissue types for accurate analysis, and its effectiveness can be limited by the complexity of certain tissues. Additionally, the cost and availability of the technology may restrict its widespread adoption.

Future Directions[edit]

Research is ongoing to expand the database of tissue types and improve the accuracy of the iKnife. There is also interest in applying the technology to other fields of surgery beyond oncology. As the technology evolves, it is expected to become a standard tool in surgical practice, enhancing the outcomes of various procedures.

Related pages[edit]