CN1115851A - A method of detecting the presence of anomalies in a preservative treated sample, prepared from fresh biological tissue or cells in natural or cultured form, by infrared spectroscopy - Google Patents
A method of detecting the presence of anomalies in a preservative treated sample, prepared from fresh biological tissue or cells in natural or cultured form, by infrared spectroscopy Download PDFInfo
- Publication number
- CN1115851A CN1115851A CN 95106615 CN95106615A CN1115851A CN 1115851 A CN1115851 A CN 1115851A CN 95106615 CN95106615 CN 95106615 CN 95106615 A CN95106615 A CN 95106615A CN 1115851 A CN1115851 A CN 1115851A
- Authority
- CN
- China
- Prior art keywords
- sample
- infrared
- cell
- antiseptic
- spectrum
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003755 preservative agent Substances 0.000 title claims abstract description 23
- 230000002335 preservative effect Effects 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims description 34
- 238000004566 IR spectroscopy Methods 0.000 title claims description 10
- 238000010521 absorption reaction Methods 0.000 claims abstract description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000000524 functional group Chemical group 0.000 claims abstract description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 238000005102 attenuated total reflection Methods 0.000 claims abstract description 4
- 238000002329 infrared spectrum Methods 0.000 claims description 85
- 230000002421 anti-septic effect Effects 0.000 claims description 51
- 238000001228 spectrum Methods 0.000 claims description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- 230000036541 health Effects 0.000 claims description 18
- 235000002639 sodium chloride Nutrition 0.000 claims description 14
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 238000010183 spectrum analysis Methods 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 11
- 239000012266 salt solution Substances 0.000 claims description 10
- 239000011780 sodium chloride Substances 0.000 claims description 10
- 230000005855 radiation Effects 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 6
- 238000009795 derivation Methods 0.000 claims description 5
- 229940064004 antiseptic throat preparations Drugs 0.000 claims description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 3
- 239000002953 phosphate buffered saline Substances 0.000 claims description 3
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000002504 physiological saline solution Substances 0.000 claims description 2
- 239000004317 sodium nitrate Substances 0.000 claims description 2
- 235000010344 sodium nitrate Nutrition 0.000 claims description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 229910017053 inorganic salt Inorganic materials 0.000 claims 1
- 230000008859 change Effects 0.000 abstract description 21
- 230000005540 biological transmission Effects 0.000 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 151
- 210000004027 cell Anatomy 0.000 description 93
- 210000001519 tissue Anatomy 0.000 description 59
- 230000003595 spectral effect Effects 0.000 description 13
- 210000004698 lymphocyte Anatomy 0.000 description 10
- 230000003211 malignant effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 7
- 229960002668 sodium chloride Drugs 0.000 description 7
- 206010058314 Dysplasia Diseases 0.000 description 6
- 208000031662 Noncommunicable disease Diseases 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 230000005856 abnormality Effects 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 230000002440 hepatic effect Effects 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 230000000505 pernicious effect Effects 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010033040 Histones Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 229910014033 C-OH Inorganic materials 0.000 description 2
- 206010007134 Candida infections Diseases 0.000 description 2
- 229910014570 C—OH Inorganic materials 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 206010019695 Hepatic neoplasm Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000002149 gonad Anatomy 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 238000007790 scraping Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010008354 Cervix neoplasm Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920003350 Spectratech® Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- FRYDSOYOHWGSMD-UHFFFAOYSA-N [C].O Chemical compound [C].O FRYDSOYOHWGSMD-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000985 reflectance spectrum Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- SBIBMFFZSBJNJF-UHFFFAOYSA-N selenium;zinc Chemical compound [Se]=[Zn] SBIBMFFZSBJNJF-UHFFFAOYSA-N 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability
Abstract
The presence of anomalies in biological tissue and cells in natural or cultured form (e.g. cancerous tissue or cells) is detected by directing a beam of infrared light at a preservative treated sample, prepared from fresh biological tissue or cells, in either the transmission mode or the Attenuated Total Reflectance (ATR) mode. The anomaly is then determined by whether changes in infrared absorption have occurred, due to the vibration of at least one functional group of molecules present in the sample, which are characteristic of the anomaly. The preservative may be an aqueous solution of formalin, an aqueous solution of ethyl alcohol, or an aqueous solution of inorganic salts. The preservative treatment prevents degradation of the sample at room temperature which has been found to change the infrared absorption characteristics which can lead to misinterpretations.
Description
The present invention relates to unusual infrared spectrum probe method in antiseptic self-sow or fresh biological tissue of ARTIFICIAL CULTURE or cell sample.
In order to check leukaemia, people such as E.Benedetti are at Leukemia Research, and PP.1001-1008 has proposed following scheme in (Vol.9, Nov.8,1985):
I) with chemical means other cell and component separating in lymphocyte (lymphocytes) and the blood are come;
Ii) isolated lymphocyte (lymphocytes) is carried out vacuum drying;
Iii) dried lymphocyte (lymphocytes) is mixed with powdery KBr as bonding agent;
Iv) lymphocyte (lymphocytes)/KBr is ground to form smalls;
V) this smalls is pressed into small pieces in sampling receptacle;
Vi) utilize infrared spectrometric analyzer to measure the infrared spectrum of this sample.
Although people's such as Benedetti scheme is that effectively it has destroyed eucaryotic cell structure fully, thereby lost the important information about tissue or cellular abnormality that can therefrom obtain.In addition, people such as Benedetti does not take to prevent the rotten measure of lymphocyte (lympho-cytes).These defectives have seriously limited the range of application of people's proposed schemes such as Benedetti.
United States Patent (USP) 5,038 has also proposed to utilize infrared spectroscopy to check the method for biological tissue under nature and the ARTIFICIAL CULTURE state or cellular abnormality on No. 039 (on August 6th, 1991, inventor P.T.T.Wong etc.).In this method, utilize infrared beam that biological tissue or cell sample are shone.This tissue or cell in the raw also can be through ARTIFICIAL CULTURE, and they are diffused in the water or are cut into slices, but still keep its natural form.Under radiation situation, at least one band frequency scope, utilize spectral analysis determine whether owing to sample at least one molecule functional group's vibration produced ultrared absorption, and this absorbing phenomenon is certain off-note.
The method that people such as P.T.T.Wong proposes in 5,038, No. 039 patent, pernicious colon epithelial cell in checking human body, effective especially when colon tumor tissue and liver tumour are organized.
On Dec 1st, 1992, people such as P.T.T.Wong were 5,168, in No. 162 United States Patent (USP)s with people such as P.T.T.Wong 5,038, the method that proposes in No. 039 patent is promoted and is used to check that cast-off cells are unusual, and utilize pap staining smear (Papani-colaousmear) and the cervical cell that obtain whether pernicious especially effective in inspection this moment.
Although people such as P.T.T.Wong are 5,038,039 and 5,168, the detection method that is proposed in No. 162 patents has been proved to be effectively, and its used sample must be through freezing in case rotten.Have now found that at room temperature, even in a short period of time, spectral absorption also significant variation can take place.Although people such as P.T.T.Wong are 5,038, disclosed the lipides that in five hours or longer time internal thymus tissue, contain branched chain fatty acid in No. 039 patent and increased (see this patent the 8th be listed as the 21st to 32 capable), but this patent can not make the people who knows this technology believe, under the room temperature, even if in very short time, the spectral absorption meeting in tissue or the cell changes, and the amplitude that this spectral absorption changes is enough in some cases to the demonstration that makes mistake, and causes thinking by mistake existing unusually.More meaningfully, the present patent application people finds that unexpectedly the variation of these spectral absorption can provide the reading that is similar to such as cancerous tissue or cell indication.
Usually, when obtaining to be used for the surgery sample of tissue examination, this sample is carried out freezing anticorrosion in the process that is transported to the Pathology Lab that carries out tissue examination.After arriving this laboratory, utilize the freezing microtome section technology that this sample is cut into slices, thereby be provided for the tissue sample of tissue examination.
According to 5,038, No. 039 United States Patent (USP) carries out infrared spectrum when detecting, and sample thickness must be less than about 20 microns, and operation at room temperature after must thawing.
If make sample thaw and at room temperature place even the very short time, have now found that generations rotten, this rotten absorption that can change spectrum, and provide in fact non-existent unusual mistake in some cases and indicate.
W.J.Potts Jr. is at " chemical infrared spectroscopy " (first volume in 1963: technology, the 238th～242 page) on research chemical material (for example cross-linked polymer and resin) optical characteristics has been proposed, the method of its infrared intensity particularly, soon respective material is filled up the hole in the solid-state little crystal block of sodium chloride, shield this crystal block so that make light on its outer surface can only pass this little crystal block volume, and this crystal block is placed in the infrared beam focusing system.Infrared spectrum can be used to obtain from the reflection of this chemical material surface emissivity (rather than utilizing the transmission of passing this material), and such spectrum that produces is very weak so that have very little value usually.When this paper formulation, people have dreamed up and a kind ofly have been called as the total reflection of decay (often being abbreviated as ATR) technology, thereby have obtained the more gratifying reflectance spectrum of quality yet recently.
Although the method that W.J.Potts Jr. is introduced is effective to the organic polymer and the resin material that in fact can not destroy, but the sample (for example deriving from the sample of fresh biological tissue or cell) that can not make the people who knows this technology use sodium chloride to preserve at room temperature can going bad is used for surveying wherein unusual by Infrared spectroscopy.In addition, thus the moisture content in these samples can dissolve the sodium chloride crystal block makes its inefficacy.But W.J.Potts Jr. has pointed out just to have known as far back as 1963 that at least the transmission that is used to pass this sample from the reflection or the utilization of sample radiation obtains infrared spectrum really.
In " use infrared spectroscopy, principle, technology and problem analysis are found the solution " book (A.Lee Smith,, 84～86 pages in 1979), point out that the reflected radiation of ATR spectrum can provide the absorption that is very similar to transmitted spectrum on 86 pages.
Need a kind of like this detection method, it is existing unusual that this method utilizes Infrared spectroscopy to check in the biological tissue of nature or ARTIFICIAL CULTURE or the cell, wherein this tissue or cell rotten quilt is at room temperature postponed till certain degree, so that it can not hinder the detection of abnormality or give the result who makes mistake.
According to the present invention, it has proposed a kind of Infrared spectroscopy of utilizing and has surveyed unusual method in antiseptic nature or fresh biological tissue of ARTIFICIAL CULTURE or cell sample, and it contains following steps:
A) shine through antiseptic sample with infrared beam;
B) utilize spectral analysis, at least the infrared absorption of determining whether to have taken place obviously to be different from the sample in this processing the variation that wherein comes from preservative treatment and brought in a band frequency scope changes, and this absorption changes at least that vibration by the functional group of a molecule in the sample of this processing is produced and is certain unusual feature.
Utilize spectral analysis to determine and can comprise: with above-mentioned in a band frequency scope, utilize at least infrared beam shine the infrared spectrum that treated sample obtains and the spectrum parameter of deriving therefrom with by handling through same way as and the known similar infrared spectrum that obtains from similar sample fresh, normal and health tissues or cell and the spectrum parameter of therefrom derivation are compared.
By comparing, if testing sample and control between the sample no tangible infrared spectrum change or the spectrum parameter of deriving variation, then the work of obviously being determined by spectral analysis is finished, and does not exist unusually in its explanation test sample, and this sample is healthy and normal.
Yet,, obviously need do further comparison to determine being which type of unusual caused this variation actually if having obvious variation aspect the infrared spectrum or the spectrum parameter of being derived between testing sample and the control sample.
In addition, according to the present invention, utilize spectral analysis to determine also to comprise: with the above-mentioned spectrum parameter that in a band frequency scope, utilizes infrared beam to shine the resulting infrared spectrum of treated sample at least and derive therefrom with compare by handle and have the similar infrared spectrum that at least a similar sample of known exception characteristic obtains and the spectrum parameter of derivation thus through same way as.
Following content is included within the scope of the present invention, and promptly only certain treated sample is tested to detect at least a specific unusually, and does not carry out the tissue of this sample and treated normal health or the comparison test of cell.
Utilize spectral analysis to determine, can be by obtaining in above-mentioned at least one band frequency scope from the infrared radiation that passes this treated sample beam.
Utilize spectral analysis to determine, can in above-mentioned at least one band frequency scope, obtain by attenuated total reflection infrared radiation from this sample beam.
Through antiseptic sample can be to utilize any sample of handling in following one group of antiseptic, and these antiseptics comprise: formaldehyde, alcohol, salt solution and inorganic salts.
Formaldehyde can be formlinata aquae concentratac.
Alcohol can be methyl alcohol, ethanol or the potpourri of the two.
Salt solution can be common salt solution, phosphate buffer or certain physiology of balance salt solution, and this salt solution contains: lime chloride, magnesium chloride, potassium chloride, sodium acetate, sodium chloride and sodium citrate.
Inorganic salts can be sodium nitrate, sodium chloride or potassium bromide.
Above-mentioned at least one band frequency scope can be at least one frequency in following at least one frequency range, and these frequency ranges comprise: 500cm
-1To 900cm
-1, 900cm
-1To 1500cm
-1, 900cm
-1To 1800cm
-1And 2000cm
-1To 6000cm
-1
In present technique requires, the fresh biological tissue or the cell of nature or ARTIFICIAL CULTURE are meant, the tissue of up-to-date biological tissue that obtains or cell, ARTIFICIAL CULTURE or cell or the cell that comes off from fresh biological tissue, and these tissues or cell avoided room temperature environment to expose to the open air fully and cause rotten.
Surprisingly, can cause the subtle change of spectrum although found some antiseptics, but experiment showed, from the fresh biological tissue or the cell of state of nature or ARTIFICIAL CULTURE and obtain, detect through the Infrared spectroscopy of can utilizing unusually the antiseptic sample.In other words, have been found that these antiseptics can not shield the infrared absorption that causes owing to anomalies or give the indication that makes mistake.Its fundamental cause is the analysis mode difference to infrared spectrum.The spectrum parameter of particularly importantly, will be and deriving thus from the infrared spectrum of sample with compare from the infrared spectrum of similar sample (handle, be known as normal health or have known abnormal characteristic) and the spectrum parameter of derivation thus through the same manner.
Biological tissue or cell can obtain from various people or other mammiferous organ or tissue.
At least a variation of above-mentioned infrared absorption characteristic can be the variation of absorption intensity in the particular frequency range, the variation that produces the specific absorption frequency, or the particular functional group applied different pressures and the variation of the generation specific absorption frequency that causes.
As 1 day 5,168 Dec in 1992, No. 162 United States Patent (USP) was pointed, and the molecule functional group can be at least one in following molecule, carbohydrates, nucleic acid, histone or cell membrane lipid.
Equally, as 1 day 5,168 Dec in 1992, No. 162 United States Patent (USP) was pointed, and this functional group can be the C-OH base in di-phosphate ester (phosphodiester), histone and the carbohydrates in the nucleic acid, the CH in the lipid
2CH in base or protein, nucleic acid and the lipid
3Group.
Have, as 1 day 5,168 Dec in 1992, No. 162 United States Patent (USP) was pointed again, and this functional group can be CH from comprise carbohydrates
2CH in C-OH group, the lipid in phosphodiester group, histone and the carbohydrates in-OH group, the nucleic acid
2CH in group and protein, nucleic acid and the lipid
3At least one functional group that group is selected in interior functional group.
Yet, to some antiseptic because the existence of this antiseptic, spectrum can with 1 day 5,168 Dec in 1992, given slightly different on No. 162 United States Patent (USP)s.
Sample can be from a) fresh slicer, b) fresh puncture living tissue, c) new fresh cell of ARTIFICIAL CULTURE or d) prepare the cast-off cells, example wherein has:
I) pap staining smear (Papanicolaou Smears);
Ii) uterine neck sample;
Iii) interior uterine neck sample;
Iv) ectocervix sample;
V) vagina sample;
Vi) uterus sample;
Vii) bronchus sample.
When this sample when organizing, it may be a hepatic tissue, and off-note shows that just there is malignant change in this hepatic tissue.
When this sample comprised cell, this cell may be the ovarian epithelial cell of human body.
When this sample when organizing, this tissue may be the cervix neoplasms tissue, off-note shows that then there is malignant change in this tissue.
When this sample is cast-off cells, this sample can utilize various organs and tissue by scraping blade, wash away, flushing, secretion or exudate obtain.
No matter with the sample that any method obtained, it unusually all represents to exist such as premalignant lesion, virus, bacterium, fungi and other infectiousness or Non Communicable Diseases (NCD).
Description of drawings:
By giving an example, accompanying drawing has been described concrete scheme of the present invention.
Fig. 1 is used for detecting through the unusual equipment block diagram that exists of preservative treatment sample by Infrared spectroscopy, and this sample prepares from the fresh biological tissue of state of nature or ARTIFICIAL CULTURE.
Fig. 2 has provided 2800 to 3020cm
-1The infrared spectrum that obtains by fresh, normal, healthy hepatic tissue sample in the frequency range, this sample are without preservative treatment and preservation at room temperature, and the measurement of this infrared spectrum is to have passed through different time variations.
Fig. 3 has provided the similar infrared spectrum with Fig. 2, so difference wherein is at without antiseptic normal health tissue and malignant change tissue.
Fig. 4 has provided 900 to 1500cm
-1The infrared spectrum that air-dry sample by the fresh cervical cell that comes off in the frequency range obtains and this sample are at room temperature preserved measured infrared spectrum after three days, and wherein this cervical cell has been diagnosed out height dysplasia and without preservative treatment.
Fig. 5 has provided 900 to 1500cm
-1In the sample cell that the infrared spectrum that obtains by the wet sample through antiseptic fresh, normal, the healthy cervical cell that comes off in the frequency range and this wet sample are having single infrared window after air-dry under the room temperature measured infrared spectrum.
Fig. 6 has provided 900 to 1800cm
-1Measured infrared spectrum after the infrared spectrum that obtains by the air-dry sample through antiseptic fresh, normal, the healthy cervical cell that comes off in the frequency range and this sample are at room temperature preserved three months.
Fig. 7 has provided 900 to 1800cm
-1Measured infrared spectrum after at room temperature preserving three months by the infrared spectrum that obtains through the air-dry sample of the cervical cell that comes off antiseptic, fresh, that be diagnosed as low dysplasia (CIN1) and this sample in the frequency range.
Fig. 8 has provided 950 to 1500cm
-1Measured infrared spectrum after at room temperature preserving 15 hours by the infrared spectrum that obtains through antiseptic, fresh, normal, the healthy cervical cell sample that comes off and this sample in the frequency range.
Fig. 9 has provided 950 to 1500cm
-1Measured infrared spectrum after at room temperature preserving one and a half months by the infrared spectrum that obtains through the cervical cell sample that comes off antiseptic, fresh, that be diagnosed as mild dysplasia (CINII) and this sample in the frequency range.
Figure 10 has provided 950 to 1500cm
-1By two kinds of infrared spectrums that obtain through antiseptic uterine neck living tissue sample, all from the flesh tissue preparation, one of them is the normal health tissue to these two kinds of samples in the frequency range, and another is diagnosed in conventional organization mode and has malignant change.
Figure 11 has provided 950 to 1500cm
-1In the frequency range by two groups through antiseptic, from the infrared spectrum that the cervical cell specimen samples that comes off of new fresh cell obtains, wherein one group of sample is the normal health cell, and another group sample is diagnosed as inflammation.
Figure 12 has provided 900 to 1500cm
-1In the frequency range by two groups through infrared spectrum antiseptic, that obtain from the air-dry specimen samples of the cervical cell that comes off of new fresh cell, wherein one group of sample is the normal health cell, and another group sample is diagnosed as and is subjected to Oidiomycetes (Candida) and infects.
Figure 13 has provided 950 to 1500cm
-1In the frequency range by two groups through the antiseptic infrared spectrum that obtains from the fresh cervical cell specimen samples that comes off, wherein one group of sample is the normal health cell, and another group sample is diagnosed as and has CIN1 dysplasia and HPV virus (human paparoma virus).
Figure 14 has provided 950 to 1500cm
-1Measured ATR infrared spectrum after the ATR infrared spectrum that obtains by the air-dry sample through the pernicious gonad cell of antiseptic ARTIFICIAL CULTURE in the frequency range and this sample are at room temperature preserved 20 hours.
Refer now to Fig. 1, wherein provided infrared light supply 1, infrared beam focus lamp 2 and 3, sample cell and support 4, Michelson interferometer 5, infrared detector 6, computing machine 7 and numeric display unit 8.In following test, the support of this infrared light supply 1, infrared beam focus lamp 2 and 3, sample cell and support 4, Michelson interferometer 5 and infrared detector 6 are ingredients of Nicolet Magna IR 550 Fourier Tranform infrared interferometers, and they can obtain from thermoelectric instrument (Canada) company limited of Ontario, Canada Mississauga.Be used to measure the sample cell of transmitted infrared light spectrum and the sample cell of support 4 and have single infrared optics window, deposit sample on it, or have two infrared optics windows, between it, place sample.Be used to measure the sample cell of ATR infrared spectrum and the sample cell of support 4 is the contact Sampler that has the ZnSe crystal
TMATR annex (Spectrum Technologies PLC), it is obtained by Spectra-Tech, Inc. (US) 652 Glenbrook Road, P.O. Box 2190 Stamford, Connecticut of Stamford, the Connecticut State.
When operation, biological tissue or cell sample are positioned in the transmission or ATR sample cell of sample cell and support 4, pass the sample in sample cell and the support 4 and be focused mirror 3 from the infrared beam of light source 1 (focusing on through focus lamp 2) to focus on detector 6 places by Michelson interferometer 5.Anyly all measured, and this calculates and provides reading through computing machine 7 and shows on numeric display unit 8 by Michelson interferometer 5 and detector 6 by the unusual infrared absorption that produces in the sample.The output data of this computing machine can be through programming be healthy or comprises unusually that and for example this anomalies may be optimum, heterophemia or pernicious so that numeric display unit 8 can directly be pointed out this sample.
In following checking test of the present invention, infrared spectrum is to utilize to obtain by living tissue sample, the scraping tissue sample that obtains cast-off cells and ARTIFICIAL CULTURE cell sample with reference to figure 1 described equipment.
In Fig. 2, provided 2800 to 3020cm
-1The infrared spectrum that the infrared spectrum that obtains by fresh, normal, healthy hepatic tissue sample in the frequency range and this sample at room temperature obtain through different time.In Fig. 2,1 representative is fresh, normal, the infrared spectrum of health tissues sample, 2 represent the infrared spectrum after this sample is at room temperature preserved a hour, 3 represent the infrared spectrum after this sample is at room temperature preserved two hours, 4 represent the infrared spectrum after this sample is at room temperature preserved three hours, and 5 represent the infrared spectrum after this sample is at room temperature preserved four hours.
Fig. 2 explanation, infrared spectrum absorb and the decline phenomenon occurs, the length of holding time at room temperature that its fall depends on this sample.
Fig. 3 has provided and similar infrared spectrum shown in Figure 2, it at the normal health hepatic tissue (with------expression) and from histology find to exist malignant change hepatic tissue (with---expression), both through evisceration after all not by the present invention carry out preservative treatment just horse back carry out the infrared absorption inspection.
Comparison diagram 2 will find that with Fig. 3 spectral absorption intensity is at 2960cm
-1About frequency range on a declining curve, and among Fig. 2 normal health to be organized in room temperature long more following standing time, the infrared spectrum that has malignant change tissue among Fig. 3 is with regard to more near infrared spectrum fresh among Fig. 2, normal, health tissues.In fact, the infrared spectrum of 5 representatives may be misinterpreted as among Fig. 3 with solid line among Fig. 2---the infrared spectrum of the pathological tissues of expression.
In addition, identical therewith, for rotten under the room temperature, undressed tissue or cell, also may produce the misunderstanding of other tissue abnormalities.
Fig. 4 has provided 900 to 1500cm
-1The infrared spectrum that air-dry sample by the fresh cervical cell that comes off in the frequency range obtains, wherein this cervical cell has been diagnosed out the height heterophemia and without preservative treatment.
In Fig. 4,---represent the infrared spectrum of the air-dry fresh cervical cell that comes off, and--on behalf of identical sample,----at room temperature preserve measured infrared spectrum after three days.Can find out significantly that from Fig. 4 after sample was at room temperature placed three days, huge variation had taken place for shape, frequency and the intensity of various absorption bandses in its overall optical spectral limit.
Fig. 5 has provided 900 to 1500cm
-1Infrared spectrum by obtaining in the frequency range through antiseptic fresh, normal, the healthy cervical cell sample that comes off.This preservative treatment process comprises: sample is immersed physiology of balance salt solution, remove redundant solution with hydro-extractor, this sample is positioned on the sample holder again.
In Fig. 5,---representative is through the infrared spectrum of antiseptic, fresh, normal, the healthy wet sample of cervical cell that comes off, and--on the infrared window of sample on being loaded on sample cell of----TYP air-dry after measured infrared spectrum.Can find out significantly from Fig. 5, for through antiseptic sample, its at room temperature the infrared spectrum of air-dry front and back do not change substantially.Making us interested especially is, through antiseptic wet similar to the infrared spectrum of corresponding undressed normal health cell with the infrared spectrum of exsiccata (referring to 1 day 5,168 Dec in 1992, No. 162 United States Patent (USP) the 4th row 45 to 57 row).
Fig. 6 has provided 900 to 1800cm
-1Measured infrared spectrum after the infrared spectrum that obtains by the air-dry sample through antiseptic fresh, normal, the healthy cervical cell that comes off in the frequency range and this sample are at room temperature preserved three months.This preservative treatment process comprises: it is 1% sodium-chloride water solution that this sample is immersed with the weight calculation, removes redundant solution with hydro-extractor, then this sample is positioned on the sample holder.Spectrum is measured after air-dry under the room temperature at sample again.Can find out significantly that from Fig. 6 the sample after the preservative treatment is trimestral preservation under room temperature, its spectral absorption does not change substantially.
Fig. 7 has provided 900 to 1800cm
-1Measured infrared spectrum after at room temperature preserving three months by the infrared spectrum that obtains through the cervical cell sample that comes off antiseptic, fresh, that be diagnosed as low heterophemia (CINI) and this sample in the frequency range.The antiseptic mode of cell is identical with the processing mode of cell among Fig. 6.Can find out significantly that from Fig. 7 for treated sample, its spectrum does not at room temperature change in the trimestral time substantially.
Fig. 8 has provided 900 to 1500cm
-1Measured infrared spectrum after at room temperature preserving 15 hours by the infrared spectrum that obtains through antiseptic, fresh, normal, the healthy cervical cell sample that comes off and this sample in the frequency range.This preservative treatment process comprises: the sample immersion is calculated 1% formlinata aquae concentratac with weight, remove excessive solution with hydro-extractor, then this sample is put into sample cell.
In Fig. 8,---represent the infrared spectrum of fresh, normal, healthy cell to absorb, and------representative is at room temperature preserved this sample that measured infrared spectrum absorbs after 15 hours.As can be seen, the sample after the preservative treatment is after 15 hours, and its spectral absorption does not change substantially.Making us interested especially is, through the infrared spectrum of the preservative treatment sample infrared spectrum similar (referring to 1 day 5,168 Dec in 1992, No. 162 United States Patent (USP) the 4th row 45 to 57 row) to corresponding undressed, normal, healthy cell.
In Fig. 9,---representative absorbs through the infrared spectrum of the cervical cell sample that comes off antiseptic, fresh, that be diagnosed as mild dysplasia (CINII), and--measured infrared spectrum absorbed after on behalf of this sample,----at room temperature preserve one and a half months.This preservative treatment process comprises: fresh wet sample is placed on the surface of the crystallization potassium bromide window that is loaded on the sample holder.At this sample air-dry laggard capable spectral measurement under room temperature.Can find out significantly that from Fig. 9 after antiseptic sample was at room temperature placed one and a half months, its infrared spectrum did not change substantially.
Figure 10 has provided 950 to 1500cm
-1Frequency range is interior by two groups of infrared spectrums that obtain through antiseptic, fresh uterine neck living tissue sample, wherein------representative is treated, normal, the infrared spectrum of health tissues, and---representative is diagnosed as the infrared spectrum of the tissue with malignant change in conventional organization mode.The preservative treatment process of this sample comprises: sample is immersed phosphate-buffered saline, removes unnecessary salt solution, and the sample that should wet is then put sample holder into.
The most significant spectral absorption difference comprises the result of study that is listed in the malignant change organizational aspects down:
A) at 970cm
-1, 1025cm
-1, 1047cm
-1, 1080cm
-1, 1160cm
-1, 1240cm
-1, 1400cm
-1And 1460cm
-1Marked change will take place in absorption intensity near the wave band;
B) at 1080cm
-1And 1160cm
-1Obviously skew will take place in absorption spectrum near the wave band;
Figure 11 has provided 950 to 1500cm
-1In the frequency range by two groups through antiseptic, scrape the infrared spectrum that the cervical cell specimen samples that comes off obtains from fresh, wherein------represent the spectrum of normal health cell, and---represent the spectrum that is diagnosed as cell with inflammation.Processing mode to wet cell among the preservative treatment of this cell and Fig. 5 is identical.
The most significant spectral absorption difference comprises the result of study that is listed in the cell aspect with inflammation down:
A) at 970cm
-1, 1025cm
-1, 1047cm
-1, 1080cm
-1, 1160cm
-1, 1300cm
-1, 1400cm
-1And 1460cm
-1Marked change will take place in absorption intensity near the wave band;
B) at 1080cm
-1And 1240cm
-1Obviously skew will take place in absorption spectrum near the wave band;
Figure 12 has provided 900 to 1500cm
-1Frequency range is interior by two groups of infrared spectrums that obtain through antiseptic, the fresh air-dry specimen samples of the cervical cell that comes off, wherein--and----represents the spectrum of normal health cell, and---representative is subjected to the spectrum of the cell of monilial infection after diagnosing.The mode of describing among the preservative treatment mode of this cell and Fig. 6 is identical.
The most significant spectral absorption difference is included in 930cm
-1, 1160cm
-1And 1240cm
-1Be subjected to the variation of monilial infection cell absorption intensity near the wave band, and 1025cm
-1Near the broadening of strong absorption bands scope.
Figure 13 has provided 950 to 1500cm
-1Frequency range is interior by two groups of infrared spectrums that obtain through the antiseptic fresh cervical cell sample that comes off, wherein------represents the spectrum of normal health cell, and---representative has the variation of the cell absorption intensity of CINI dysplasia and HPV virus (human paparoma virus) after diagnosing.
In Figure 14,---represent 950 to 1500cm
-1The ATR infrared spectrum that obtains by air-dry sample in the frequency range through the pernicious gonad cell of antiseptic ARTIFICIAL CULTURE, and--on behalf of this air-dry sample,----preserve measured ATR infrared spectrum after 20 hours.The preservative treatment mode of this cell is identical with the method described in Fig. 5.Can find out significantly from Figure 14, for this through antiseptic sample, during at room temperature three days in, its spectral absorption does not change substantially, only minor alteration has taken place in the baseline of this absorption spectrum, and this does not influence and detects unusual existence.
Other utilizable antiseptic exemplifies as follows, it is the aqueous solution of ethanol, methyl alcohol, ether, ethylene glycol or their mixing, and, use other salt solution but not phosphate-buffered saline and balance physiological saline as antiseptic, and use other inorganic salts but not sodium chloride and potassium bromide as antiseptic, these are all within the scope that the present invention comprised.Antiseptic can be aqueous solution, or is solid-state or for gaseous formaldehyde.
For instance, can be according to the present invention detected tissue or cellular abnormality comprise premalignant lesion, virus, bacterium, fungi and other infection and Non Communicable Diseases (NCD), infrared absorption takes place owing to the vibration of at least one molecule functional group in the sample in this moment at least in this sample in a frequency range, and this absorption promptly is the feature of this tissue or cellular abnormality.This can determine by conventional test, and the molecule functional group who is detected can be from such as obtaining cell carbon hydrate, lipid, protein or the nucleic acid.
Typical case's Non Communicable Diseases (NCD) has cancer, diabetes, cirrhosis and arthritis.
Can detect existence unusual (for example malignant change) and the various tumor tissues that can test or the example of cell comprises according to the present invention: the cancer cell and the tumour cell of colorectum tumour (being used for checking colon cancer), liver tumour (being used to check liver cancer), cutaneum carcinoma, brain tumor, oophoroma, cancer of the stomach, cancer of the esophagus, the cancer of the uterus, cervical carcinoma and other blood.
Claims (13)
1. one kind is utilized Infrared spectroscopy to survey unusual method in antiseptic, nature or fresh biological tissue ARTIFICIAL CULTURE, that comprise cast-off cells or cell sample, and this method comprises:
A) shine through antiseptic sample with infrared beam;
B) utilize spectral analysis, at least the infrared absorption of determining whether to have taken place obviously to be different from the variation that wherein comes from preservative treatment and brought in a band frequency scope in this treated sample changes, and this absorption changes at least that vibration by a molecule functional group in this treated sample is produced and is certain unusual feature.
2. utilize spectral analysis to determine to comprise according to the process of claim 1 wherein: with above-mentioned in a band frequency scope, utilize at least infrared beam shine the infrared spectrum that treated sample obtains and the spectrum parameter of deriving therefrom with by handling through same way as and the known similar infrared spectrum that obtains from similar controlled sample fresh, normal and health tissues or cell and the spectrum parameter of therefrom derivation are compared.
3. above-mentionedly utilize spectral analysis to determine to comprise according to the process of claim 1 wherein: with the above-mentioned spectrum parameter that in a band frequency scope, utilizes infrared beam to shine the resulting infrared spectrum of treated sample at least and derive therefrom with compare by handle and have the similar infrared spectrum that at least a similar sample of known exception characteristic obtains and the spectrum parameter of derivation thus through same way as.
4. above-mentionedly utilize spectral analysis to determine in above-mentioned at least one band frequency scope according to the process of claim 1 wherein by obtaining from the infrared radiation that passes this treated sample beam.
5. above-mentionedly utilize spectral analysis to determine in above-mentioned at least one band frequency scope, to obtain according to the process of claim 1 wherein by attenuated total reflection infrared radiation from this sample beam.
6. be to utilize following one group of sample that at least one of the preservatives is handled according to the process of claim 1 wherein through antiseptic sample, these antiseptics comprise: formaldehyde, alcohol, salt solution and inorganic salts.
7. according to the method for claim 6, wherein formaldehyde is formlinata aquae concentratac.
8. according to the method for claim 6, wherein alcohol is the aqueous solution of ethanol water, methanol aqueous solution and ethanol and carbinol mixture.
9. according to the method for claim 6, wherein antiseptic is a salt solution, and this salt solution is selected from common salt solution, phosphate-buffered saline and balance physiological saline.
10. according to the method for claim 6, wherein antiseptic is a kind of material that is selected among sodium nitrate, sodium chloride and the potassium bromide.
11., wherein can be wet or dried state through antiseptic sample according to the method for claim 1 and 6.
12. according to the method for claim 1 and 6, wherein comprise humidogene fabric texture or cell through antiseptic sample, this tissue or cell are placed on the surface as the crystalline inorganic salt of solid-state antiseptic.
13. according to the process of claim 1 wherein that this frequency range is at least one frequency range in the following frequency range, these frequency ranges comprise: 500cm
-1To 900cm
-1, 900cm
-1To 1500cm
-1, 900cm
-1To 1800cm
-1And 2000cm
-1To 6000cm
-1
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2126915 | 1994-06-28 | ||
| CA 2126915 CA2126915A1 (en) | 1994-06-28 | 1994-06-28 | Method of detecting the presence of anomalies in a preservative treated sample, prepared from fresh biological tissue or cells in natural or cultured form, by infrared spectroscopy |
| US40144295A | 1995-03-09 | 1995-03-09 | |
| US08/401442 | 1995-03-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1115851A true CN1115851A (en) | 1996-01-31 |
Family
ID=25677345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 95106615 Pending CN1115851A (en) | 1994-06-28 | 1995-06-28 | A method of detecting the presence of anomalies in a preservative treated sample, prepared from fresh biological tissue or cells in natural or cultured form, by infrared spectroscopy |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0767902A1 (en) |
| JP (1) | JPH10505412A (en) |
| CN (1) | CN1115851A (en) |
| AU (1) | AU2730095A (en) |
| WO (1) | WO1996000892A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457049C (en) * | 2003-09-30 | 2009-02-04 | 西泰克公司 | Automated cytological sample classification |
| CN106404842A (en) * | 2016-11-29 | 2017-02-15 | 国网浙江省电力公司电力科学研究院 | Metallographic structure assessment test method |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU734799B2 (en) * | 1996-02-26 | 2001-06-21 | Martin Leonard Ashdown | Spectroscopic determination of characteristics of biological material |
| AUPN825796A0 (en) | 1996-02-26 | 1996-03-14 | Ashdown, Martin | The application of infrared (ir) spectrometry to the investigations of components of blood and other body fluids |
| US5945674A (en) * | 1997-07-30 | 1999-08-31 | Vysis, Inc. | Method of identifying cellular types in a biological sample supported on an absorptive substrate by infrared spectroscopy |
| EP1178311A4 (en) * | 1999-05-10 | 2003-04-09 | Tomoya Sato | Method and apparatus for determining the type and/or condition of disease and method and apparatus for screening drug |
| US9606057B2 (en) | 2010-06-01 | 2017-03-28 | Todos Medical Ltd. | Biochemical analysis of PBMC |
| WO2012153326A1 (en) | 2011-05-11 | 2012-11-15 | Todos Medical Ltd. | Diagnosis of cancer |
| WO2014191980A1 (en) * | 2013-05-28 | 2014-12-04 | Todos Medical Ltd. | Differential diagnosis of benign tumors |
| GB2545877B (en) * | 2015-09-10 | 2021-09-15 | Sierra Medical Ltd | ATR-FTIR computational analysis of Barrett's esophagus and esophageal cancers |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5168162A (en) * | 1991-02-04 | 1992-12-01 | Cornell Research Foundation, Inc. | Method of detecting the presence of anomalies in exfoliated cells using infrared spectroscopy |
-
1995
- 1995-06-23 EP EP95922382A patent/EP0767902A1/en not_active Withdrawn
- 1995-06-23 AU AU27300/95A patent/AU2730095A/en not_active Abandoned
- 1995-06-23 WO PCT/CA1995/000370 patent/WO1996000892A1/en not_active Application Discontinuation
- 1995-06-23 JP JP8502672A patent/JPH10505412A/en active Pending
- 1995-06-28 CN CN 95106615 patent/CN1115851A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457049C (en) * | 2003-09-30 | 2009-02-04 | 西泰克公司 | Automated cytological sample classification |
| US7803624B2 (en) | 2003-09-30 | 2010-09-28 | Cytyc Corporation | Automated cytological sample classification |
| CN106404842A (en) * | 2016-11-29 | 2017-02-15 | 国网浙江省电力公司电力科学研究院 | Metallographic structure assessment test method |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1996000892A1 (en) | 1996-01-11 |
| AU2730095A (en) | 1996-01-25 |
| JPH10505412A (en) | 1998-05-26 |
| EP0767902A1 (en) | 1997-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2008831C (en) | Method of detecting the presence of anomalies in biological tissues and cells in natural and cultured form by infrared spectroscopy | |
| Schinker et al. | High-frequency densitometry-a new method for the rapid evaluation of wood density variations | |
| Ci et al. | Fourier transform infrared spectroscopic characterization of human breast tissue: implications for breast cancer diagnosis | |
| JP4156373B2 (en) | An assembly device for the measurement of the optical properties of multilayer structures. | |
| Pallua et al. | Fourier transform infrared imaging analysis in discrimination studies of squamous cell carcinoma | |
| CN1115851A (en) | A method of detecting the presence of anomalies in a preservative treated sample, prepared from fresh biological tissue or cells in natural or cultured form, by infrared spectroscopy | |
| das Chagas e Silva de Carvalho et al. | Diagnosis of inflammatory lesions by high-wavenumber FT-Raman spectroscopy | |
| Zhang et al. | Dielectric and double debye parameters of artificial normal skin and melanoma | |
| Sato et al. | Raman spectroscopy and its use for live cell and tissue analysis | |
| Ge et al. | The detection of structure in wood by X-ray CT imaging technique | |
| Gatter et al. | Is it necessary to embed bone marrow biopsies in plastic for haematological diagnosis? | |
| CN1067314A (en) | Detect in the cell be stripped from infrared spectrum and to have unusual method | |
| Brown et al. | Diffuse reflectance near infrared spectroscopy can distinguish normal from enzymatically digested cartilage | |
| Zhang et al. | Application of THz time-domain spectroscopy to diagnose gastric cancer tissues in surgical resected specimens | |
| CN1804593A (en) | Method for distinguishing epithelial carcinoma property by single cell Raman spectrum | |
| CN110108647A (en) | A kind of discrimination method and identification system of meat kind | |
| US6270986B1 (en) | Method of preserving biological tissue specimens and method of infrared spectroscopic analysis which avoids the effects of polymorphs | |
| Li et al. | Edge detection on terahertz pulse imaging of dehydrated cutaneous malignant melanoma embedded in paraffin | |
| CN109540833A (en) | A kind of tumor tissue in vitro identification method and its application based on terahertz time-domain spectrum | |
| CN109913215B (en) | Near ultraviolet carbon-based fluorescent probe and preparation method and application thereof | |
| Csoka et al. | Application of the Fourier analysis to determine the demarcation between juvenile and mature wood | |
| Sreeshyla et al. | Diagnostic aids in oral precancer and cancer | |
| Han et al. | Non-destructive Detection of Blackheart Potatoes Based on Energy Spectrum of VIS/NIR Transmittance | |
| CN105277506A (en) | Near-infrared diffuse reflection spectrum rapid recognition method for human body colorectal cancer tissue | |
| Czaja et al. | New method for the microscopic, nondestructive acquisition of ultraviolet resonance Raman spectra from plant cell walls |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |