Iknife

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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 Surgeries conducted.jpg
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

An onkoknife, iKnife, or intelligent scalpel is a surgical knife that tests tissue as it contacts it during an operation and immediately gives information as to whether that tissue contains cancer cells. [1] 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), [2] breast tumour from normal breast tissue (90.9% sensitivity, 98.8% specificity) [3] and recognises histological features of poor prognostic outcome in colorectal carcinoma. [4] Furthermore, the technology behind iKnife - rapid evaporative ionisation mass spectrometry (REIMS) - can identify Candida yeasts down to species level. [5]

Contents

Research and development

Zoltán Takáts, Ph.D., a 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 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 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. [6] 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 (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. [7] The first breakthrough came with desorption ionisation methods (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. [8] 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. [9]

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. [10]

Rapid evaporative ionization mass spectrometry

Lymph node excision Lymph node NPC.jpg
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 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 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. [11] It is estimated that the tissue identification accuracy during operation is higher than 92%. [12]

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. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Ion source</span> Device that creates charged atoms and molecules (ions)

An ion source is a device that creates atomic and molecular ions. Ion sources are used to form ions for mass spectrometers, optical emission spectrometers, particle accelerators, ion implanters and ion engines.

<span class="mw-page-title-main">Electrospray ionization</span> Technique used in mass spectroscopy

Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions using an electrospray in which a high voltage is applied to a liquid to create an aerosol. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized. ESI is different from other ionization processes since it may produce multiple-charged ions, effectively extending the mass range of the analyser to accommodate the kDa-MDa orders of magnitude observed in proteins and their associated polypeptide fragments.

<span class="mw-page-title-main">Lipidomics</span>

Lipidomics is the large-scale study of pathways and networks of cellular lipids in biological systems The word "lipidome" is used to describe the complete lipid profile within a cell, tissue, organism, or ecosystem and is a subset of the "metabolome" which also includes other major classes of biological molecules. Lipidomics is a relatively recent research field that has been driven by rapid advances in technologies such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, dual polarisation interferometry and computational methods, coupled with the recognition of the role of lipids in many metabolic diseases such as obesity, atherosclerosis, stroke, hypertension and diabetes. This rapidly expanding field complements the huge progress made in genomics and proteomics, all of which constitute the family of systems biology.

<span class="mw-page-title-main">Matrix-assisted laser desorption/ionization</span> Ionization technique

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 biomolecules and various organic molecules, which tend to be fragile and fragment when ionized by more conventional ionization methods. It is similar in character to electrospray ionization (ESI) in that both techniques are relatively soft ways of obtaining ions of large molecules in the gas phase, though MALDI typically produces far fewer multi-charged ions.

<span class="mw-page-title-main">Mohs surgery</span> Surgery used to treat skin cancers

Mohs surgery, developed in 1938 by a general surgeon, Frederic E. Mohs, is microscopically controlled surgery used to treat both common and rare types of skin cancer. During the surgery, after each removal of tissue and while the patient waits, the tissue is examined for cancer cells. That examination dictates the decision for additional tissue removal. Mohs surgery is the gold standard method for obtaining complete margin control during removal of a skin cancer using frozen section histology. CCPDMA or Mohs surgery allows for the removal of a skin cancer with very narrow surgical margin and a high cure rate.

<span class="mw-page-title-main">Field desorption</span>

Field desorption (FD) is a method of ion formation used in mass spectrometry (MS) in which a high-potential electric field is applied to an emitter with a sharp surface, such as a razor blade, or more commonly, a filament from which tiny "whiskers" have formed. This results in a high electric field which can result in ionization of gaseous molecules of the analyte. Mass spectra produced by FD have little or no fragmentation because FD is a soft ionization method. They are dominated by molecular radical cations M+. and less often, protonated molecules . The technique was first reported by Beckey in 1969. It is also the first ionization method to ionize nonvolatile and thermally labile compounds. One major difference of FD with other ionization methods is that it does not need a primary beam to bombard a sample.

Surface-enhanced laser desorption/ionization (SELDI) is a soft ionization method in mass spectrometry (MS) used for the analysis of protein mixtures. It is a variation of matrix-assisted laser desorption/ionization (MALDI). In MALDI, the sample is mixed with a matrix material and applied to a metal plate before irradiation by a laser, whereas in SELDI, proteins of interest in a sample become bound to a surface before MS analysis. The sample surface is a key component in the purification, desorption, and ionization of the sample. SELDI is typically used with time-of-flight (TOF) mass spectrometers and is used to detect proteins in tissue samples, blood, urine, or other clinical samples, however, SELDI technology can potentially be used in any application by simply modifying the sample surface.

<span class="mw-page-title-main">Thermospray</span>

Thermospray is a soft ionization source by which a solvent flow of liquid sample passes through a very thin heated column to become a spray of fine liquid droplets. As a form of atmospheric pressure ionization in mass spectrometry these droplets are then ionized via a low-current discharge electrode to create a solvent ion plasma. A repeller then directs these charged particles through the skimmer and acceleration region to introduce the aerosolized sample to a mass spectrometer. It is particularly useful in liquid chromatography-mass spectrometry (LC-MS).

Soft laser desorption (SLD) is laser desorption of large molecules that results in ionization without fragmentation. "Soft" in the context of ion formation means forming ions without breaking chemical bonds. "Hard" ionization is the formation of ions with the breaking of bonds and the formation of fragment ions.

<span class="mw-page-title-main">MALDI imaging</span>

MALDI mass spectrometry imaging (MALDI-MSI) is the use of matrix-assisted laser desorption ionization as a mass spectrometry imaging technique in which the sample, often a thin tissue section, is moved in two dimensions while the mass spectrum is recorded. Advantages, like measuring the distribution of a large amount of analytes at one time without destroying the sample, make it a useful method in tissue-based study.

<span class="mw-page-title-main">Desorption electrospray ionization</span>

Desorption electrospray ionization (DESI) is an ambient ionization technique that can be coupled to mass spectrometry (MS) for chemical analysis of samples at atmospheric conditions. Coupled ionization sources-MS systems are popular in chemical analysis because the individual capabilities of various sources combined with different MS systems allow for chemical determinations of samples. DESI employs a fast-moving charged solvent stream, at an angle relative to the sample surface, to extract analytes from the surfaces and propel the secondary ions toward the mass analyzer. This tandem technique can be used to analyze forensics analyses, pharmaceuticals, plant tissues, fruits, intact biological tissues, enzyme-substrate complexes, metabolites and polymers. Therefore, DESI-MS may be applied in a wide variety of sectors including food and drug administration, pharmaceuticals, environmental monitoring, and biotechnology.

<span class="mw-page-title-main">Laser spray ionization</span>

Laser spray ionization refers to one of several methods for creating ions using a laser interacting with a spray of neutral particles or ablating material to create a plume of charged particles. The ions thus formed can be separated by m/z with mass spectrometry. Laser spray is one of several ion sources that can be coupled with liquid chromatography-mass spectrometry for the detection of larger molecules.

<span class="mw-page-title-main">Matrix-assisted laser desorption electrospray ionization</span>

Matrix-assisted laser desorption electrospray ionization (MALDESI) was first introduced in 2006 as a novel ambient ionization technique which combines the benefits of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). An infrared (IR) or ultraviolet (UV) laser can be utilized in MALDESI to resonantly excite an endogenous or exogenous matrix. The term ‘matrix’ refers to any molecule that is present in large excess and absorbs the energy of the laser, thus facilitating desorption of analyte molecules. The original MALDESI design was implemented using common organic matrices, similar to those used in MALDI, along with a UV laser. The current MALDESI source employs endogenous water or a thin layer of exogenously deposited ice as the energy-absorbing matrix where O-H symmetric and asymmetric stretching bonds are resonantly excited by a mid-IR laser.

<span class="mw-page-title-main">Desorption atmospheric pressure photoionization</span>

Desorption atmospheric pressure photoionization (DAPPI) is an ambient ionization technique for mass spectrometry that uses hot solvent vapor for desorption in conjunction with photoionization. Ambient Ionization techniques allow for direct analysis of samples without pretreatment. The direct analysis technique, such as DAPPI, eliminates the extraction steps seen in most nontraditional samples. DAPPI can be used to analyze bulkier samples, such as, tablets, powders, resins, plants, and tissues. The first step of this technique utilizes a jet of hot solvent vapor. The hot jet thermally desorbs the sample from a surface. The vaporized sample is then ionized by the vacuum ultraviolet light and consequently sampled into a mass spectrometer. DAPPI can detect a range of both polar and non-polar compounds, but is most sensitive when analyzing neutral or non-polar compounds. This technique also offers a selective and soft ionization for highly conjugated compounds.

<span class="mw-page-title-main">Ambient ionization</span>

Ambient ionization is a form of ionization in which ions are formed in an ion source outside the mass spectrometer without sample preparation or separation. Ions can be formed by extraction into charged electrospray droplets, thermally desorbed and ionized by chemical ionization, or laser desorbed or ablated and post-ionized before they enter the mass spectrometer.

<span class="mw-page-title-main">Extractive electrospray ionization</span>

Extractive electrospray ionization (EESI) is a spray-type, ambient ionization source in mass spectrometry that uses two colliding aerosols, one of which is generated by electrospray. In standard EESI, syringe pumps provide the liquids for both an electrospray and a sample spray. In neutral desorption EESI (ND-EESI), the liquid for the sample aerosol is provided by a flow of nitrogen.

<span class="mw-page-title-main">Aerosol mass spectrometry</span> Application of mass spectrometry to aerosol particles

Aerosol mass spectrometry is the application of mass spectrometry to the analysis of the composition of aerosol particles. Aerosol particles are defined as solid and liquid particles suspended in a gas (air), with size range of 3 nm to 100 μm in diameter and are produced from natural and anthropogenic sources, through a variety of different processes that include wind-blown suspension and combustion of fossil fuels and biomass. Analysis of these particles is important owing to their major impacts on global climate change, visibility, regional air pollution and human health. Aerosols are very complex in structure, can contain thousands of different chemical compounds within a single particle, and need to be analysed for both size and chemical composition, in real-time or off-line applications.

<span class="mw-page-title-main">Desorption/ionization on silicon</span> Soft laser desorption method

Desorption/ionization on silicon (DIOS) is a soft laser desorption method used to generate gas-phase ions for mass spectrometry analysis. DIOS is considered the first surface-based surface-assisted laser desorption/ionization (SALDI-MS) approach. Prior approaches were accomplished using nanoparticles in a matrix of glycerol, while DIOS is a matrix-free technique in which a sample is deposited on a nanostructured surface and the sample desorbed directly from the nanostructured surface through the adsorption of laser light energy. DIOS has been used to analyze organic molecules, metabolites, biomolecules and peptides, and, ultimately, to image tissues and cells.

<span class="mw-page-title-main">MasSpec Pen</span>

The MasSpec Pen, or the precìso MasSpec Pen System, is a mass spectrometry (MS) based cancer detection and diagnosis system that can be used for ex vivo and in vivo tissue sample analysis. The system collects biological molecules from a tissue sample surface via a solid-liquid extraction mechanism and transports the molecules to a mass spectrometer for analysis. The composition of the extracted molecules can then be used to predict if the tissue sample analyzed contains cancerous cells using machine learning algorithms and statistical models. In early-stage clinical research, the MasSpec Pen system was able to distinguish various cancer tissues, including thyroid, breast, lung, and ovarian tumor tissues, from their normal counterparts with an overall accuracy of 96.3%. A follow-up study in illustrating the use of the device for detection of serous ovarian carcinoma in ex vivo tissue biopsies allowed for the discrimination of normal and cancerous ovarian samples with a clinical sensitivity and specificity of 94.0% and 94.4%, respectively.

References

  1. 1 2 Balog, J; Sasi-Szabo, L; Kinross, J; Lewis, M. R; Muirhead, L. J; Veselkov, K; Mirnezami, R; Dezso, B; Damjanovich, L; Darzi, A; Nicholson, J. K; Takats, Z (2013). "Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry". Science Translational Medicine. 5 (194): 194ra93. doi:10.1126/scitranslmed.3005623. PMID   23863833. S2CID   206681695.
  2. ↑ Phelps, David L; Balog, Júlia; Gildea, Louise F; Bodai, Zsolt; Savage, Adele; El-Bahrawy, Mona A; Speller, Abigail VM; Rosini, Francesca; Kudo, Hiromi (May 2018). "The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)". British Journal of Cancer. 118 (10): 1349–1358. doi:10.1038/s41416-018-0048-3. ISSN   0007-0920. PMC   5959892 . PMID   29670294.
  3. ↑ St John, Edward R.; Balog, Julia; McKenzie, James S.; Rossi, Merja; Covington, April; Muirhead, Laura; Bodai, Zsolt; Rosini, Francesca; Speller, Abigail V. M. (December 2017). "Rapid evaporative ionisation mass spectrometry of electrosurgical vapours for the identification of breast pathology: towards an intelligent knife for breast cancer surgery". Breast Cancer Research. 19 (1): 59. doi:10.1186/s13058-017-0845-2. ISSN   1465-542X. PMC   5442854 . PMID   28535818.
  4. ↑ Alexander, James; Gildea, Louise; Balog, Julia; Speller, Abigail; McKenzie, James; Muirhead, Laura; Scott, Alasdair; Kontovounisios, Christos; Rasheed, Shanawaz (March 2017). "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". Surgical Endoscopy. 31 (3): 1361–1370. doi:10.1007/s00464-016-5121-5. ISSN   0930-2794. PMC   5315709 . PMID   27501728.
  5. ↑ Cameron, Simon J. S.; Bolt, Frances; Perdones-Montero, Alvaro; Rickards, Tony; Hardiman, Kate; Abdolrasouli, Alireza; Burke, Adam; Bodai, Zsolt; Karancsi, Tamas (December 2016). "Rapid Evaporative Ionisation Mass Spectrometry (REIMS) Provides Accurate Direct from Culture Species Identification within the Genus Candida". Scientific Reports. 6 (1): 36788. Bibcode:2016NatSR...636788C. doi:10.1038/srep36788. ISSN   2045-2322. PMC   5107957 . PMID   27841356.
  6. ↑ parameter.sk. "Amerikai cég vásárolta fel a magyar Intelligens Kés technológiát".
  7. ↑ 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
  8. ↑ van Hove et al., 2010.[ full citation needed ]
  9. ↑ Römpp, Andreas; Guenther, Sabine; Takats, Zoltan; Spengler, Bernhard (2011). "Mass spectrometry imaging with high resolution in mass and space (HR2 MSI) for reliable investigation of drug compound distributions on the cellular level". Analytical and Bioanalytical Chemistry. 401 (1): 65–73. doi:10.1007/s00216-011-4990-7. PMID   21516518. S2CID   206906670.
  10. ↑ Takats et al., 2004[ full citation needed ]
  11. ↑ Heath, Nick, The Intelligent knife that helps surgeons sniff out cancer , European Technology, November 26, 2014, distributed in TechRepublic Daily Digest, TechRepublic.com, November 27, 2014
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