Iknife
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An onkoknife, iKnife, or intelligent scalpel is a
surgical Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery ...
knife that tests tissue as it contacts it during an operation and immediately gives information as to whether that tissue contains
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
cells. 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 - distinguishing benign ovarian tissue from cancerous tissue (97.4% sensitivity, 100% specificity), breast tumour from normal breast tissue (90.9% sensitivity, 98.8% specificity) and recognises histological features of poor prognostic outcome in colorectal carcinoma. Furthermore, the technology behind iKnife - rapid evaporative ionisation mass spectrometry (REIMS) - can identify Candida yeasts down to species level.


Research and development

Zoltán Takáts, Ph.D., a Hungarian research
chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a graduated scientist trained in the study of chemistry, or an officially enrolled student in the field. Chemists study the composition of ...
associated with
Semmelweis University Semmelweis University (Hungarian language, Hungarian: ''Semmelweis Egyetem'', ) is a research-led medical school in Budapest, Hungary, founded in 1769. With six faculties and a doctoral school it covers all aspects of medical and health sciences. ...
, in
Budapest Budapest is the Capital city, capital and List of cities and towns of Hungary, most populous city of Hungary. It is the List of cities in the European Union by population within city limits, tenth-largest city in the European Union by popul ...
, invented the ''intelligent surgical knife''. He currently is Professor of Analytical Chemistry at
Imperial College London Imperial College London, also known as Imperial, is a Public university, public research university in London, England. Its history began with Prince Albert of Saxe-Coburg and Gotha, Prince Albert, husband of Queen Victoria, who envisioned a Al ...
(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 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. The instrument has been acquired by the Massachusetts
Waters Corporation Waters Corporation is an American publicly traded analytical laboratory instrument and software company headquartered in Milford, Massachusetts. The company employs more than 7,800 people, with manufacturing facilities located in Milford, Taunto ...
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. The business transaction included all ''MediMass'' innovation, including patents, software, databases, and human resources related to the technology.


Principle of operation


History of direct examination of biological tissue by mass spectrometry (MS)

Direct examination of biological tissue by
mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
(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. The first breakthrough came with desorption ionisation methods ( secondary ionization mass spectrometry - SIMS,
matrix-assisted laser desorption ionization In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy-absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of ...
- MALDI) a release said. Using these methods, after appropriate sample preparation, chemical biological tissue imaging analysis may be achieved. 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. 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.


Rapid evaporative ionization mass spectrometry

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 data is at the
histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
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 Diathermy is electrically induced heat or the use of high-frequency electromagnetic currents as a form of physical therapy and in surgical procedures. The earliest observations on the reactions of the human organism to high-frequency electromagn ...
knife, a surgical
laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word ''laser'' originated as an acronym for light amplification by stimulated emission of radi ...
, or an
ultrasonic Ultrasound is sound with frequencies greater than 20 kilohertz. This frequency is the approximate upper audible limit of human hearing in healthy young adults. The physical principles of acoustic waves apply to any frequency range, includi ...
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 Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...
are important, which easily are detectable by
mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
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. It is estimated that the tissue identification accuracy during operation is higher than 92%. 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.


See also

*
Instruments used in general surgery There are many different Surgery, surgical specialties, some of which require specific kinds of Surgical instrument, surgical instruments to perform. General surgery is a specialty focused on the abdomen; the Thyroid, thyroid gland; Disease, dis ...


References


External links

* Cancer Research UK: An intelligent knife can tell ovarian cancer and healthy tissue apart. Could it make surgery smarte
"Intelligent knife" tells surgeon if tissue is cancerous by Sam Wong


* 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 TechRepublic Daily Digest, TechRepublic.com, November 27, 2014 * * https://web.archive.org/web/20140322224442/http://www.doublexscience.org/iknife-excises-uncertainty-in-tumor-resection/ {{MedInst Surgical instruments Mass spectrometry