WO2000068683A1 - Procede et dispositif de determination du type et/ou de l'etat d'une maladie, et procede et appareil de criblage de medicaments - Google Patents
Procede et dispositif de determination du type et/ou de l'etat d'une maladie, et procede et appareil de criblage de medicaments Download PDFInfo
- Publication number
- WO2000068683A1 WO2000068683A1 PCT/JP2000/001552 JP0001552W WO0068683A1 WO 2000068683 A1 WO2000068683 A1 WO 2000068683A1 JP 0001552 W JP0001552 W JP 0001552W WO 0068683 A1 WO0068683 A1 WO 0068683A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- spectrum
- drug
- disease
- screening
- type
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 77
- 229940079593 drug Drugs 0.000 title claims abstract description 76
- 201000010099 disease Diseases 0.000 title claims abstract description 63
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 63
- 238000000034 method Methods 0.000 title claims abstract description 61
- 238000012216 screening Methods 0.000 title claims abstract description 34
- 238000000862 absorption spectrum Methods 0.000 claims abstract description 121
- 206010028980 Neoplasm Diseases 0.000 claims description 73
- 201000011510 cancer Diseases 0.000 claims description 73
- 238000001228 spectrum Methods 0.000 claims description 59
- 238000010183 spectrum analysis Methods 0.000 claims description 39
- 239000002246 antineoplastic agent Substances 0.000 claims description 23
- 241000700605 Viruses Species 0.000 claims description 20
- 241000894006 Bacteria Species 0.000 claims description 18
- 229940041181 antineoplastic drug Drugs 0.000 claims description 16
- 239000003242 anti bacterial agent Substances 0.000 claims description 10
- 239000003443 antiviral agent Substances 0.000 claims description 10
- 230000003115 biocidal effect Effects 0.000 claims description 8
- 238000007877 drug screening Methods 0.000 claims description 8
- 238000000295 emission spectrum Methods 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 description 131
- 238000010586 diagram Methods 0.000 description 40
- 238000005259 measurement Methods 0.000 description 35
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 21
- 238000010521 absorption reaction Methods 0.000 description 19
- 210000004748 cultured cell Anatomy 0.000 description 17
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 13
- 238000012545 processing Methods 0.000 description 13
- 241000588724 Escherichia coli Species 0.000 description 12
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 9
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 210000000170 cell membrane Anatomy 0.000 description 8
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 8
- 229960004316 cisplatin Drugs 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 230000002107 myocardial effect Effects 0.000 description 7
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- 108010029961 Filgrastim Proteins 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 229960004177 filgrastim Drugs 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 108010062867 Lenograstim Proteins 0.000 description 5
- 108010059993 Vancomycin Proteins 0.000 description 5
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 238000009509 drug development Methods 0.000 description 5
- 229960002618 lenograstim Drugs 0.000 description 5
- 210000004165 myocardium Anatomy 0.000 description 5
- 229960003165 vancomycin Drugs 0.000 description 5
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 5
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 5
- 229960004150 aciclovir Drugs 0.000 description 4
- BSJGASKRWFKGMV-UHFFFAOYSA-L ammonia dichloroplatinum(2+) Chemical compound N.N.Cl[Pt+2]Cl BSJGASKRWFKGMV-UHFFFAOYSA-L 0.000 description 4
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 description 3
- 229960003644 aztreonam Drugs 0.000 description 3
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 210000003699 striated muscle Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 206010003445 Ascites Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 238000010297 mechanical methods and process Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000005416 organic matter Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- MWWSFMDVAYGXBV-FGBSZODSSA-N (7s,9s)-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-FGBSZODSSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- 241000931526 Acer campestre Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010062129 Tongue neoplasm Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 229940073066 azactam Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000005274 electronic transitions Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229960003265 epirubicin hydrochloride Drugs 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 201000006134 tongue cancer Diseases 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229940107931 zovirax Drugs 0.000 description 1
Classifications
-
- 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
-
- 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
- G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
Definitions
- the present invention relates to a method and apparatus for determining the type and / or condition of a disease, and a method and apparatus for screening a drug.
- the present invention provides a method and apparatus for determining a disease type and z or a disease state capable of prompt and reliable diagnosis by specifying the specificity of a cell or the like from a physical aspect, and an efficient method for a target drug.
- the present invention relates to a method and an apparatus for cleaning a drug which can be selected.
- the present inventor has disclosed prior arts of Japanese Patent Application Laid-Open Nos. Hei 9-2858286, Hei 9-28552 96, Hei 9-286 739, and As disclosed in Japanese Patent Application Laid-Open No. Hei 9-128 6740, the “absolute specificity” of bioactivity (organic matter such as cells or an organic body that is an aggregate of such organic matter) is considered as a physical aspect. It proposes a method to elucidate from. This method uses a thermodynamic / statistical mechanical method that considers a single cell as a macroscopic system and points out the “absolute specificity” of bioactivity by focusing on the energy state of the system. is there.
- the biochemical mechanism of bioactivity is confined in a black box, and the atoms and molecules that constitute the components of cells and the like, including their quantum states, are identified by spectral analysis, and the bioactivity is identified.
- Control the vital activity of Specifically, for example, there is a method of detecting a spectrum peculiar to a cancer cell and planning and designing an anticancer drug or the like having a spectrum interacting with the spectrum.
- the method of the invention of the prior application described above has made it possible to quickly determine the type and condition of a disease and to select a drug by a very simple method called spectrum analysis.
- spectrum analysis a very simple method called spectrum analysis.
- the accuracy of the decision is not always sufficient, and there is still a great demand for a more efficient screening method.
- the present invention has been made by paying attention to the above points, and it is possible to quickly and reliably analyze the energy state of cells and drugs by performing a spectrum analysis and processing the results using a plurality of spectra as indices. It is an object of the present invention to provide a method and an apparatus for determining the type and condition of a disease or Z that can be determined, and a method and an apparatus for screening a drug capable of selecting a target drug more efficiently. Disclosure of the invention
- the method for determining a disease type and a Z or a disease state analyzes the absorption or release spectrum in a specific region of a cell obtained from a subject, and According to the result of the torque analysis, the type and / or condition of the disease is determined using the expression of the spectrum corresponding to at least two wave numbers in the specific area as an index.
- a spectrum analysis is performed on cells obtained from a subject.
- a simple method that can quickly determine the type of disease and Z or pathology, and performs spectrum analysis using the expression of the spectrum corresponding to at least two wave numbers within a specific wavelength range as an index By judging the results, it becomes possible to more reliably determine the type of disease and the like.
- the specific region may include an infrared region (preferably any one or all of 10.0 to 13157.9 cm- 1 ). Good to do.
- one of the wave numbers of the spectrum to be used as an index is set to 1261 cm- 1 (preferably 1261 4 cm— 1 ).
- Specific examples of the specific bacterium include drug-resistant bacteria.
- the apparatus for diagnosing the type of disease and Z or a disease state comprises: a spectrum analyzing means for analyzing absorption or emission spectrum in a specific region of a cell obtained from a subject; According to the result of the spectrum analysis obtained by the vector analysis means, the type of the disease and Z or the disease state are determined by using the expression of the spectrum corresponding to at least two wave numbers in the specific area as an index. And diagnostic means for diagnosing.
- the method of screening a drug according to the present invention comprises analyzing an absorption or release spectrum of a target drug in a specific region, and analyzing at least two of the absorption or release spectra in the specific region according to the result of the spectrum analysis.
- the target drug is screened using the expression of the spectrum corresponding to the wave number as an index.
- rapid screening can be performed by a simple method of performing a spectrum analysis of a target drug, and a screening corresponding to at least two wave numbers within a specific wavelength region can be performed.
- a screening corresponding to at least two wave numbers within a specific wavelength region can be performed.
- the specific region may be set so as to include an infrared region (preferably, any one or all of the range of 10.0 to 13157.9 cm- 1 ). It is also possible to screen an anticancer drug as a target drug.
- one of the wave numbers of the spectrum to be used as an index is 1261 cm- 1 or 1163 cm- 1 (preferably 1 2 61.4 cm- 1 or 1 1 63.1 cm- 1 ).
- the target drug can be an antibiotic, and specific examples of the antibiotic include those effective against drug-resistant bacteria.
- the target drug can be an antiviral agent.
- the screening device for a drug comprises: a spectrum analyzing means for analyzing an absorption or release spectrum of a target drug in a specific region; and a spectrum obtained by the spectrum analyzing means. Selecting means for screening the target drug based on the expression of a spectrum corresponding to at least two wave numbers in the specific area according to the result of the vector analysis. It is. BRIEF DESCRIPTION OF THE FIGURES
- FIG. 1 is a diagram showing a three-state maser model for explaining the basic matter of the present invention.
- FIG. 2 is a diagram showing the results of a spectrum analysis using cultured cells derived from rat ascites hepatoma as a sample.
- FIG. 3 is a diagram showing the results of spectrum analysis using cultured cells derived from mouse breast cancer as a sample.
- FIG. 4 is a diagram showing the results of a spectrum analysis using cultured cells derived from mouse malignant melanoma as a sample.
- FIG. 5 is a diagram showing the results of a spectrum analysis using cultured cells derived from human gastric cancer as a sample.
- FIG. 6 is a diagram showing the results of a spectrum analysis using cultured cells derived from human glioblastoma as a sample.
- FIG. 7 is a diagram showing the results of performing a vector analysis using cancer cells extracted from a breast cancer patient as a sample.
- FIG. 8 is a diagram in which peak wave numbers of infrared absorption spectra of various cancer cells are serialized.
- FIG. 9 is a diagram showing a state of a change in an energy state due to cell membrane destruction of a cancer cell.
- FIG. 10 is a diagram showing how the energy state changes due to the heating of the cancer cells.
- FIG. 11 is a diagram showing the results of a spectrum analysis performed using normal rat brain (white matter) cells as a sample.
- FIG. 12 is a diagram showing the results of a spectrum analysis using hepatocytes of a normal rat as a sample.
- FIG. 13 shows the results of a vector analysis using normal mouse mammary gland cells as a sample.
- FIG. 14 is a diagram showing the results of a spectrum analysis using normal human bone marrow cells as a sample.
- FIG. 15 is a diagram in which the peak wave numbers of the infrared absorption spectrum of normal cells are serialized.
- FIG. 16 is a diagram showing the results of a spectrum analysis using cisplatin as a sample.
- FIG. 17 is a diagram showing the results of spectrum analysis using carboplatin as a sample.
- FIG. 18 is a diagram showing the results of spectrum analysis using doxorubicin hydrochloride (adriacin) as a sample.
- FIG. 19 is a diagram showing a result of a spectrum analysis using dimustine hydrochloride (ACNU) as a sample.
- ACNU dimustine hydrochloride
- FIG. 20 is a diagram showing second derivative data of the infrared absorption spectrum of doxorubicin hydrochloride (adriacin).
- FIG. 21 is a diagram showing second derivative data of the infrared absorption spectrum of dimustine hydrochloride (ACNU).
- FIG. 22 is a diagram showing second derivative data of the infrared absorption spectrum of mouse myocardium.
- FIG. 23 is a diagram showing second derivative data of the infrared absorption spectrum of the striated muscle of the mouse.
- Figure 24 shows the second derivative data of the infrared absorption spectrum of mouse smooth muscle. is there.
- 2 5 2 6 is a diagram illustrating a scan Bae-vector analysis results when using Escherichia coli as a sample is a diagram showing the spectral analysis results when Azutoreonamu the (Azakutamu) and samples.
- FIG. 27 is a diagram showing the results of a spectrum analysis using transplatin as a sample.
- FIG. 28 is a diagram showing second derivative data of the infrared absorption spectrum of lenograstim (neutrogin).
- Fig. 29 is a diagram showing the second derivative data of the infrared absorption spectrum of filgrastim (Gran).
- FIG. 30 is a diagram showing second derivative data of an infrared absorption spectrum of human bone marrow fluid.
- FIG. 31 is a flowchart showing a method for determining the type of disease and the Z or disease state according to the embodiment of the present invention.
- FIG. 32 is a block diagram showing the configuration of a diagnosis device for the type of disease and Z or a disease state according to the embodiment of the present invention.
- FIG. 33 is a flowchart showing a method for screening a drug according to the embodiment of the present invention.
- FIG. 34 is a block diagram showing the configuration of the drug screening device according to the embodiment of the present invention.
- the present invention employs a thermodynamic-statistical-mechanical method in which one cell is regarded as a macroscopic system, and elucidates the absolute characteristics of cells etc. by focusing on the energy state of the system. Take a position to do. Therefore, in the present invention, cells are regarded as “thermodynamically unbalanced open systems”. For example, cancer cells, normal cells, etc., differ in the state of their systems (state of quantum intrinsic energy). It can be observed as
- the normal cell is in the state E n, and the normal cell that has successfully transited to the state E m (metastable state) through the state E h as a result of absorbing the appropriate energy E i is a cancer cell
- inductive transition of a cancer cell from the metastable state Em to or near the state En requires contact with the system and another system having an energy level that can resonate.
- Anticancer drugs share their energy level, which is the reason for their selective action on cancer cells.
- FT-IR Fastier-Transform Infrared spectroscopy
- the measurement error of wavenumber is 0 1 cm one 1 within the is FTIR.; Using (Shimadzu FTIR 8 1 0 0 and 8 3 0 0), the processing of the sample at room temperature and A measurement was made. In the measurement using FT-IR, care must be taken so that the cells of the sample are dispersed in the measurement area.
- FIG. 2 to FIG. 7 are diagrams showing an example of the results of performing a spectrum analysis on various cancer cells.
- A in each figure shows the infrared absorption spectrum measured by FT-IR as the wave number (cm- 1 ) on the horizontal axis
- B shows the data of (A). This is processed so that the wave number of the absorption peak becomes clear through second-order differentiation.
- Fig. 2 shows cultured cells from rat ascites hepatoma (AH7974)
- Fig. 3 shows cultured cells from mouse breast cancer (Ehr1ich)
- Fig. 4 shows cultured cells from mouse malignant melanoma.
- B16 shows cultured cells from human gastric cancer (HGC27)
- Fig. 6 shows cultured cells from human glioblastoma (U251)
- Fig. 7 shows cancer cells extracted from breast cancer patients Is the data for each sample.
- FIG. 8 is a diagram in which peak wave numbers of infrared absorption spectra of various cancer cells are serialized.
- FIG. 8 shows data obtained by adding 12 types of cancer cell samples in addition to the samples shown in FIGS. 2 to 7 above.
- cultured cells derived from human tongue cancer SCCKN
- cultured cells derived from human colon cancer C-11
- cultured cells derived from human gastric cancer 1KN45 MCH66, MCH271
- cultured cells derived from human breast cancer MDA4A4
- cultured cells derived from human colorectal cancer HT29
- cultured cells derived from human glioblastoma A—) ⁇ 72, U87MG, Becker, SF126, and Arcus
- various cancer cells have a wavenumber of 1 261.4 cm- 1 as a unique absorption vector common to all, and some but not all common It can be seen that there is a unique absorption spectrum common to all the cancer cells. That is, it is considered that the cancer cells have absorption spectra corresponding to at least two wave numbers in the infrared region.
- the infrared absorption spectrum specific to cancer cells Is not limited to the above wave numbers.
- Figure 9 is a diagram showing how the energy state changes due to cell membrane destruction of cancer cells.
- A shows the second derivative data of the infrared absorption spectrum measured immediately after the destruction
- B c represents the second derivative de one another when the two minutes after the fracture has elapsed shows a
- C second derivative de one another when the 5 minutes after the fracture has elapsed
- FIG. 10 is a diagram showing a state of change in energy state due to heating of cancer cells
- (A) shows the second derivative data of the infrared absorption spectrum measured before heating
- (B) shows the second derivative data immediately after heating for 30 minutes
- (C) shows the second derivative data 30 minutes after heating.
- the energy state E m unique to the cancer cell becomes the other energy state E m * From the fact that the energy state E m is metastable.
- FIGS. 11 to 14 show examples of the results of spectrum analysis performed on various normal cells.
- A shows a measured infrared absorption space-vector with FT-IR
- B is the c specific is obtained by secondary differential processing data
- A is Fig. 11 shows normal rat brain (white matter) cells
- Fig. 12 shows normal rat hepatocytes
- Fig. 13 shows normal mouse mammary cells
- Fig. 14 shows normal human bone marrow cells. Is the data for each sample.
- FIG. 15 shows a diagram in which the peak wave numbers of the infrared absorption spectrum of some of the 30 types of normal cells for which the measurement was performed are arranged.
- infrared absorption spectrum was measured using FT-IR using various general anticancer agents as samples.
- the samples used were all pure drug saline solutions.
- FIGS. 16 to 19 show examples of the results of spectrum analysis performed on various anticancer agents.
- (A) shows the infrared absorption spectrum measured by FT-IR
- (B) shows the data of (A) subjected to the second-order differentiation.
- Fig. 16 shows cisplatin
- Fig. 17 shows carboplatin
- Fig. 18 shows doxorubicin hydrochloride [Drug name: adriacin (Kyowa Hakko)]
- Fig. 19 shows dimustine hydrochloride
- Each of the anticancer drugs shown in FIGS. 16 to 19 has an absorption spectrum with a wave number of 1 261.4 cm ⁇ 1 , which is exactly one of the absorption spectra unique to cancer cells. Yes. Also has an absorption scan Bae-vector to the wave number 1 1 63. 1 cm- 1 for Shisuburachin and doxorubicin hydrochloride, for AC NU is the wave number 1 203. 6 cm one 1 and 1 2 1 1. 3 cm- 1 Also have an absorption spectrum, which also closely matches the absorption spectrum unique to cancer cells.
- each of the anticancer drugs shown in FIGS. 16 to 19 is a strong killing anticancer drug that is the first choice in cancer chemotherapy.
- Fluorouracil, methotrexate, and bleomycin hydrochloride are relatively mild anticancer agents. Therefore, the absorption spectrum at a wavenumber of 1 26 1. 4 cm one 1 be shared with cancer cells, is considered to be a prerequisite for a powerful anti-cancer agent.
- the fact that there are many cancer cells in which an anticancer drug having an absorption spectrum of wave number 1 261.4 cm 1 is completely ineffective has a strong absorption spectrum of wave number 1 261.4 cm 1. It is also clear that the condition of a suitable anticancer drug cannot be sufficient. This suggests that the above-mentioned cancer cells are allowed to take a plurality of states other than the energy state corresponding to the absorption spectrum having a wave number of 1261.4 cm- 1 .
- epirubicin hydrochloride which is an anticancer drug that is unique to the heart muscle and eliminates the side effects of myocardial toxicity [drug name: pharmarubicin] (Faluminaria Kyowa Hakko)], or other anticancer drugs that are not originally considered to have myocardial toxicity, require the absence of an absorption spectrum at a wavelength of 127.17 cm- 1 : there.
- Infrared absorption spectra were measured using doxorubicin hydrochloride, epinorevicin hydrochloride, cisplatin, carboblatin, ACNU, mouse myocardium, striated muscle, and smooth muscle as samples.
- FIG. 20 to FIG. 24 are diagrams showing an example of the second derivative data of the infrared absorption spectrum measured for each of the above samples.
- Fig. 20 shows doxorubicin hydrochloride
- Fig. 21 shows epilubicin hydrochloride
- Fig. 22 shows mouse myocardium
- Fig. 23 shows mouse striated muscle
- Fig. 24 shows mouse smooth muscle. This is the second derivative data when
- FIG. 25 is a diagram showing a spectrum analysis result when E. coli was used as a sample
- FIG. 26 is a diagram showing a spectrum analysis result when aztreonam was used as a sample.
- A shows a measured infrared absorption spectrum in FT-IR
- B is obtained by second-order differential processing data
- an absorption peak at a wavenumber of 125.9.4 cm- 1 was identified as an infrared absorption spectrum common to E. coli and Aztreonam. Et al is, the wave number 1 2 5 9. 4 cm- 1 absorption spectrum is also present in the cisplatin is one of the anticancer agent mentioned above (Fig. 1 6) and Karupopurachin (FIG. 7). This suggests that cisplatin and carpoplatin may have the potential to damage E. coli.
- FIGS. 27A and 27B show the results of spectrum analysis using transbratin as a sample, where FIG. 27A shows the measured infrared absorption spectrum and FIG. 27B shows the second derivative data. —It shows the data.
- transplatin has a common absorption spectrum of 125.9.4 cm- 1 with E. coli, but matches the absorption spectrum unique to cancer cells. It turns out that the spectrum does not exist. This suggests that even if transplatin is a coordination isomer of cisplatin, it does not have the ability to damage cancer cells, but may have the ability to damage Escherichia coli. Can be
- MRSA methicillin-resistant Staphylococcus aureus
- S.A. Staphylococcus aureus
- V.M. vancomycin
- Table 1 below shows the absorption peak wavenumbers of the infrared absorption spectrum measured for each sample.
- infrared absorption spectra were measured using lenograstim [drug name: Neutrogin (Chugai Pharmaceutical)], filgrastim [drug name: Gran (Sankyo)] and bone marrow fluid of normal human as a sample.
- lenograstim drug name: Neutrogin (Chugai Pharmaceutical)
- filgrastim drug name: Gran (Sankyo)
- bone marrow fluid of normal human as a sample.
- Lenograstim and filgrastim are both drugs used to increase leukocytes used in bone marrow transplantation.
- Nograstim is a drug extracted from the ovaries of Chinese hamsters
- filgrastim is a drug synthesized by Escherichia coli and has a different molecular structure from renodalastim.
- FIGS. 28 to 30 show the second derivative data of the infrared absorption spectrum measured for each of the above samples.
- FIG. 28 shows Lenograstim
- FIG. 29 shows Filgrastim
- FIG. Are data obtained when bone marrow fluid was used as each sample.
- a KOS virus which is a kind of herpes virus and has drug sensitivity
- Infrared absorption spectrum was measured using FT-IR with acyclovir [chemical name: Zovirax (Sumitomoichi Nippon Welcome Co., Ltd.)] known as an effective antiviral agent against the KOS virus.
- acyclovir chemical name: Zovirax (Sumitomoichi Nippon Welcome Co., Ltd.)
- fibroblasts VEO cells
- MRC5 cells lizard monkey kidney cells
- the infrared absorption spectrum was measured one day, three days, and five days later.
- the infrared absorption spectrum of acyclovir, an antiviral agent was also measured.
- Table 2 below shows the absorption peak wavenumbers of the infrared absorption spectrum measured for each sample.
- the absorption frequency of the anti-viral agent acyclovir between the newly absorbed absorption spectrum of each sample cell and the absorption spectrum of acyclovir 1105.1 cm- 1 and 1
- the agreement of the absorption spectrum can be confirmed for 1 22.5 cm- 1 .
- the idea of observing the absolute specificity of a cell as a difference in the energy state of the system can be judged to be valid even when applied to viruses and antiviral agents.
- the method and apparatus for determining the disease type and Z or the disease state capable of quickly and accurately determining the disease state, and the efficiency of the drug as described below It is possible to realize a method and an apparatus for screening a drug which enables a proper selection.
- FIG. 31 is a flowchart showing a method for determining the type of disease and Z or the disease state according to the present embodiment.
- step 101 in the method of the present embodiment, first, in step 101 (indicated by S 101 in the figure, the same applies hereinafter), live cells are collected from a subject, and the cells are collected. Used as a sample.
- the subject from which the cells are collected is not limited to humans, and is widely applied to animals and plants. This is clear from the experimental data described above.
- the collected cells may be cultured or the like.
- care must be taken that the cells used as the sample do not change the energy state of the system due to cell membrane destruction or heating. Specifically, it is desirable to handle sample cells at low temperatures.
- the living cells collected in step 101 are subjected to measurement of the absorption spectrum in the infrared region using, for example, FT-IR. Since this measurement is performed in a very short period of time, it is possible to observe the energy state of the cell as it is without killing the cell.
- step 103 the disease of the infrared absorption spectrum measured in step 102 is determined based on the expression of the spectrum corresponding to at least two wave numbers in the infrared region. The type and medical condition are determined.
- the infrared absorption spectrum peculiar to cancer cells is required to have a wavenumber of 12.61.4 cm- 1 as well as 11.63.1 cm ⁇ ⁇ 11.68.8 cm " 1 , 1 20 3.6 cm _ ⁇ 1 2 1 1.3 cm— 1 2 24.7 cm " 1 , 1 2 57.5 cm—
- 3 cm- 1 and 1 3 1 9 may be an indicator at least one wavenumber of such 3 cm- 1 (see Figure 8). If an absorption spectrum corresponding to these wave numbers is present in the measurement result, the subject is determined to be a cancer.
- the infection state of the subject is diagnosed based on whether or not an absorption spectrum corresponding to the infrared absorption spectrum is present in the measurement result.
- the infrared absorption spectra such as the above-mentioned wavenumbers of 110.15 cm- 1 and 112.25 cm- 1 are used as indices.
- the infection state of the subject is diagnosed based on whether or not an absorption spectrum corresponding to them is present in the measurement result.
- cancer cells can be analyzed by a simple method of performing energy spectrum analysis on living cells obtained from a subject. You can quickly determine the type and condition of the disease, such as whether it is present or infected with the MRSA or KOS virus. In addition, by using the absorption spectrum corresponding to a plurality of wave numbers in the infrared region as an index and determining the spectrum measurement result, it is possible to more reliably determine the type of disease and the like. become. Next, an embodiment of an apparatus for diagnosing the type and / or condition of a disease according to the present invention will be described.
- FIG. 32 is a block diagram showing the configuration of the diagnostic device according to the present embodiment.
- the present apparatus 1 includes a spectrum measuring device 10 as a vector analyzing means for analyzing an absorption or emission spectrum of cells obtained from a subject, and And a diagnostic processing unit 11 as a diagnostic means for diagnosing the type of the disease and the Z or the medical condition based on the measurement result of the spectrum measuring device 10.
- a spectrum measuring instrument 10 for example, FT-IR or the like for measuring an absorption spectrum in an infrared region is used.
- diagnosis processing section 11 data on an infrared absorption spectrum as an index of diagnosis of a disease type or the like is set in advance.
- a living cell collected from a subject is used as a sample, and a spectrum measuring device 10 measures an infrared absorption spectrum, and the measurement result is diagnosed. It is sent to the processing unit 11.
- the infrared absorption spectrum measured by the spectrum measuring device 10 is compared with at least two infrared spectrums in the infrared region. The expression of the spectrum corresponding to the wave number is specified. The type and condition of the disease are diagnosed as markers.
- the present invention is not limited to this, and the degree of progress of the disease can also be determined.
- the infrared absorption spectrum unique to cancer cells is considered to change due to the metastasis of the cancer, etc., so that the wave number of the spectrum as an index is made to correspond to the cancer site and the like.
- the degree of progression of the cancer can be determined. This can also be considered for bacterial and viral infections.
- FIG. 33 is a flowchart showing a drug development method according to the present embodiment.
- a new drug-a drug that is an existing drug that is expected to have a new effect (including side effects) (target drug) for example, FT—The absorption spectrum is measured in the infrared region using IR and the like.
- step 202 for the infrared absorption spectrum measured in step 201, the expression of the spectrum corresponding to at least two wave numbers in the infrared region is used as an index, and Screeding is performed.
- the target agent is an anticancer agent
- the screening is performed on condition that an absorption spectrum corresponding to at least one of them is present in the spectrum measurement result of the target drug.
- the absorption spectrum at a wavenumber of 127.0 cm- 1 is used as an index, and the absorption spectrum that matches that is measured for the target drug. Screening should be done on condition that it does not exist in the result.
- the target drug is an antibiotic effective for MRSA
- the above-mentioned wave numbers of 1076.2 cm—1195.58 cm— 1 , 1234.4 cm— 1 and 1
- an absorption spectrum corresponding to at least one of them exists in the spectrum measurement result of the target drug Screening should be carried out on condition that this is the case.
- screening may be performed using an infrared absorption spectrum having a wavenumber of 1259.4 cm- 1 as an index.
- the target agent is an effective antiviral agent K_ ⁇ _S virus wavenumber 1 1 0 5 described above.
- 5 cm- 1 like the infrared absorption scan of Screening may be performed using the vector as an index, provided that at least one absorption spectrum corresponding to the absorption spectrum is present in the spectrum measurement result of the target drug.
- the absorption spectrum used as an index for antibiotics effective for MRSA is not limited to the above.
- the above values are only confirmed by measurement using vancomycin as a sample, and it is highly possible that other absorption spectra unique to MRSA exist. If such other spectra can be identified, vancomycin can be expected to develop effective antibiotics. The same is true for antibiotics effective against Escherichia coli and antivirals effective against KOS virus. Also, here, the description has been made assuming that the FT-IR having a measurement accuracy of ⁇ 0.1 cm- 1 is used. However, even when the measurement accuracy is lower than this, screening of the drug is possible.
- ⁇ 1 cm- 1 may be specifically be obtained about the measurement accuracy, the wave number of the absorption spectrum of the indicator, a decimal digit of the above values be rounded off I do not care.
- an FT-IR with a measurement accuracy better than ⁇ 0.1 cm— 1 , in which case the absorption spectrum within the above range should be used. It can be used as an indicator.
- the target drug is effective against cancer cells, bacteria, and viruses can be determined by a simple method of performing spectrum analysis. Efficient screening is possible, and more efficient screening is performed by judging and processing the spectrum measurement results of the target drug using infrared absorption spectra corresponding to multiple wave numbers as indices. Can be implemented. Such a method is considered to be particularly effective for primary screening in drug development. Can be As a result, the time and cost required for drug development can be significantly reduced. In addition, the method is very effective in eliminating the side effects of existing drugs. In other words, there are some side effects of drugs that are essential to the original action and those that are not essential, and it was difficult to discover the difference using conventional drug development methods. For example, as in the case of myocardial toxicity described above, it is easy to determine whether the side effect is essential to the original effect by specifying an energy spectrum specific to the side effect This can greatly reduce the time and cost of developing drugs that eliminate side effects.
- FIG. 34 is a block diagram showing a configuration of a drug screening device according to the present embodiment.
- the present apparatus 2 includes a spectrum measuring device 20 as a spectrum analyzing means for analyzing an absorption or release spectrum of a target drug, and the spectrum measuring device. And a selection processing unit 21 as a selection means for screening a target drug based on the 20 measurement results.
- a spectrum measuring device 20 for example, FT-IR or the like for measuring an absorption spectrum in an infrared region is used.
- the selection processing unit 21 data on an infrared absorption spectrum as an index of drug selection is set in advance.
- the spectrum measuring device 20 measures the infrared absorption spectrum of the target drug, and sends the measurement result to the selection processing section 21.
- the selection processing unit 21 in the same manner as in the above-described step 202, at least two infrared absorption spectra measured by the spectrum measuring device 20 in the infrared region are used.
- the target drug is selected using the expression of the spectrum corresponding to the wave number as an index.
- the specific region in which the energy spectrum is analyzed is described as the infrared region, but the present invention is not limited to this.
- Cells Since the energy state of the system is expected to be in the region from ultraviolet to microphone mouth wave as electronic transition and molecular vibration and rotational energy, it is sufficiently possible to apply the present invention to such a region. It is believed that there is.
- the present invention has great industrial applicability as a measurement / test method for quickly and surely determining the type and condition of a disease and various devices for performing such a measurement / test. Further, the present invention has great industrial applicability as a method for quickly and surely screening various drugs and various devices for performing such screening.
Landscapes
- Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00908072A EP1178311A4 (en) | 1999-05-10 | 2000-03-14 | METHOD AND DEVICE FOR DETERMINING THE TYPE AND / OR STATE OF A SICKNESS, AND METHOD AND DEVICE FOR SCREENING MEDICINAL PRODUCTS. |
US09/986,613 US6743637B2 (en) | 1999-05-10 | 2001-11-09 | Disease type and/or condition determination method and apparatus and drug screening method and apparatus |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP11/128543 | 1999-05-10 | ||
JP12854399 | 1999-05-10 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/986,613 Continuation US6743637B2 (en) | 1999-05-10 | 2001-11-09 | Disease type and/or condition determination method and apparatus and drug screening method and apparatus |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000068683A1 true WO2000068683A1 (fr) | 2000-11-16 |
Family
ID=14987369
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2000/001552 WO2000068683A1 (fr) | 1999-05-10 | 2000-03-14 | Procede et dispositif de determination du type et/ou de l'etat d'une maladie, et procede et appareil de criblage de medicaments |
Country Status (3)
Country | Link |
---|---|
US (1) | US6743637B2 (ja) |
EP (1) | EP1178311A4 (ja) |
WO (1) | WO2000068683A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005017501A1 (en) * | 2003-08-14 | 2005-02-24 | National Research Council Of Cananda | Method of diagnosing colorectal adenomas and cancer using infrared spectroscopy |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09285296A (ja) * | 1996-04-23 | 1997-11-04 | Tomoya Satou | バイオアクティビティの形質変換状態の判定方法 |
JPH09286740A (ja) * | 1996-04-23 | 1997-11-04 | Tomoya Satou | バイオアクティビティの形質変換に影響を及ぼす物質の同定方法 |
JPH11502935A (ja) * | 1995-11-13 | 1999-03-09 | バイオ−ラッド ラボラトリーズ,インコーポレイティド | フーリエ変換赤外分光法を用いて細胞の異常を検出するための方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR117F (ja) * | 1961-11-14 | |||
US5124932A (en) * | 1988-03-10 | 1992-06-23 | Indiana University Foundation | Method for analyzing asymmetric clusters in spectral analysis |
CA2008831C (en) * | 1990-01-29 | 1996-03-26 | Patrick T.T. Wong | Method of detecting the presence of anomalies in biological tissues and cells in natural and cultured form by infrared spectroscopy |
US5197470A (en) * | 1990-07-16 | 1993-03-30 | Eastman Kodak Company | Near infrared diagnostic method and instrument |
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 |
US5596992A (en) * | 1993-06-30 | 1997-01-28 | Sandia Corporation | Multivariate classification of infrared spectra of cell and tissue samples |
AU2730095A (en) * | 1994-06-28 | 1996-01-25 | Patrick T.T. Wong | Infrared spectroscopy of a sample treated with preservative |
US5539207A (en) * | 1994-07-19 | 1996-07-23 | National Research Council Of Canada | Method of identifying tissue |
US5504332A (en) * | 1994-08-26 | 1996-04-02 | Merck & Co., Inc. | Method and system for determining the homogeneity of tablets |
US5733739A (en) * | 1995-06-07 | 1998-03-31 | Inphocyte, Inc. | System and method for diagnosis of disease by infrared analysis of human tissues and cells |
US6146897A (en) * | 1995-11-13 | 2000-11-14 | Bio-Rad Laboratories | Method for the detection of cellular abnormalities using Fourier transform infrared spectroscopy |
JPH09285286A (ja) | 1996-04-23 | 1997-11-04 | Tomoya Satou | バイオアクティビティの生命活性の制御方法 |
JPH09286739A (ja) | 1996-04-23 | 1997-11-04 | Tomoya Satou | バイオアクティビティの生命活性を制御する物質の計画設計方法 |
US5891619A (en) * | 1997-01-14 | 1999-04-06 | Inphocyte, Inc. | System and method for mapping the distribution of normal and abnormal cells in sections of tissue |
US6274871B1 (en) * | 1998-10-22 | 2001-08-14 | Vysis, Inc. | Method and system for performing infrared study on a biological sample |
WO2000037917A2 (en) * | 1998-12-23 | 2000-06-29 | Medispectra, Inc. | Systems and methods for optical examination of samples |
-
2000
- 2000-03-14 WO PCT/JP2000/001552 patent/WO2000068683A1/ja active Application Filing
- 2000-03-14 EP EP00908072A patent/EP1178311A4/en not_active Ceased
-
2001
- 2001-11-09 US US09/986,613 patent/US6743637B2/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11502935A (ja) * | 1995-11-13 | 1999-03-09 | バイオ−ラッド ラボラトリーズ,インコーポレイティド | フーリエ変換赤外分光法を用いて細胞の異常を検出するための方法 |
JPH09285296A (ja) * | 1996-04-23 | 1997-11-04 | Tomoya Satou | バイオアクティビティの形質変換状態の判定方法 |
JPH09286740A (ja) * | 1996-04-23 | 1997-11-04 | Tomoya Satou | バイオアクティビティの形質変換に影響を及ぼす物質の同定方法 |
Non-Patent Citations (1)
Title |
---|
See also references of EP1178311A4 * |
Also Published As
Publication number | Publication date |
---|---|
EP1178311A1 (en) | 2002-02-06 |
EP1178311A4 (en) | 2003-04-09 |
US6743637B2 (en) | 2004-06-01 |
US20020064882A1 (en) | 2002-05-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kochan et al. | In vivo atomic force microscopy–infrared spectroscopy of bacteria | |
Qian et al. | New method of lung cancer detection by saliva test using surface‐enhanced Raman spectroscopy | |
Guo et al. | Comparability of Raman spectroscopic configurations: a large scale cross-laboratory study | |
Notingher et al. | Spectroscopic study of human lung epithelial cells (A549) in culture: living cells versus dead cells | |
Zarnowiec et al. | Fourier transform infrared spectroscopy (FTIR) as a tool for the identification and differentiation of pathogenic bacteria | |
Bangalore et al. | Genetic algorithm-based method for selecting wavelengths and model size for use with partial least-squares regression: application to near-infrared spectroscopy | |
Sahu et al. | Spectroscopic techniques in medicine: The future of diagnostics | |
JP6912477B2 (ja) | 微生物の化学物質への暴露に対する反応の決定方法 | |
Xu et al. | High-speed diagnosis of bacterial pathogens at the single cell level by Raman microspectroscopy with machine learning filters and Denoising autoencoders | |
Arboleda et al. | Raman spectroscopy as a discovery tool in carbohydrate chemistry | |
Kalmodia et al. | Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy: An analytical technique to understand therapeutic responses at the molecular level | |
Deb et al. | Rapid detection of bacteria using gold nanoparticles in SERS with three different capping agents: Thioglucose, polyvinylpyrrolidone, and citrate | |
Mushtaq et al. | Surface-enhanced Raman spectroscopy (SERS) for monitoring colistin-resistant and susceptible E. coli strains | |
Wang et al. | Quantifying amyloid fibrils in protein mixtures via infrared attenuated-total-reflection spectroscopy | |
Liu et al. | Vibrational spectroscopy for decoding cancer microbiota interactions: current evidence and future perspective | |
Yap et al. | Detection of prostate cancer via IR spectroscopic analysis of urinary extracellular vesicles: a pilot study | |
Zendehdel et al. | Patterns prediction of chemotherapy sensitivity in cancer cell lines using FTIR spectrum, neural network and principal components analysis | |
Pinto et al. | Data-driven soft independent modeling of class analogy in paper spray ionization mass spectrometry-based metabolomics for rapid detection of prostate cancer | |
Li et al. | Label‐Free Detection of Glycan–Protein Interactions for Array Development by Surface‐Enhanced Raman Spectroscopy (SERS) | |
Pistiki et al. | Comparison of different label-free Raman spectroscopy approaches for the discrimination of clinical MRSA and MSSA isolates | |
Tahira et al. | Surface-enhanced Raman spectroscopy analysis of serum samples of typhoid patients of different stages | |
Gomez-Gonzalez et al. | Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept | |
Abu-Aqil et al. | Fast identification and susceptibility determination of E. coli isolated directly from patients' urine using infrared-spectroscopy and machine learning | |
Lin et al. | Postmortem Diagnosis of Fatal Hypothermia by Fourier Transform Infrared Spectroscopic Analysis of Edema Fluid in Formalin‐Fixed, Paraffin‐Embedded Lung Tissues | |
WO2000068683A1 (fr) | Procede et dispositif de determination du type et/ou de l'etat d'une maladie, et procede et appareil de criblage de medicaments |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA CN JP KR US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 616417 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000908072 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09986613 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 2000908072 Country of ref document: EP |