CN105308459A - Method and apparatus for diagnosing a nasopharyngeal carcinoma - Google Patents

Method and apparatus for diagnosing a nasopharyngeal carcinoma Download PDF

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CN105308459A
CN105308459A CN201480016674.9A CN201480016674A CN105308459A CN 105308459 A CN105308459 A CN 105308459A CN 201480016674 A CN201480016674 A CN 201480016674A CN 105308459 A CN105308459 A CN 105308459A
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trace
antigen
antibody
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evaluation unit
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T·舍佩尔
W·枚尔
J·兰纳
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Euroimmun Medizinische Labordiagnostika AG
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Euroimmun Medizinische Labordiagnostika AG
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/01DNA viruses
    • G01N2333/03Herpetoviridae, e.g. pseudorabies virus
    • G01N2333/05Epstein-Barr virus
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2469/00Immunoassays for the detection of microorganisms
    • G01N2469/20Detection of antibodies in sample from host which are directed against antigens from microorganisms

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Abstract

The invention relates to a method and an apparatus for diagnosing a nasopharyngeal carcinoma in a patient, in which a substrate having at least two antigens immobilized thereon is incubated with a bodily fluid belonging to the patient. In this case, the antigens are selected in such a manner that the latter each bind, at least in certain regions, to an antibody which is in the patient's bodily fluid and is specific when an Epstein-Barr viral infection occurs, so as to form an antigen-antibody complex. The formation of the particular antigen-antibody complex should be made visible with the aid of at least one marker on the substrate, which marker appears after the substrate has been incubated with a positive patient sample. After incubation, the surface of the substrate, in particular a region in which at least one visible marker appears during the formation of an antigen-antibody complex, is recorded using an optical device and the recording is supplied to an evaluation unit. The evaluation unit generates a suggested diagnosis on the basis of at least one property of the recorded marker. The technical solution described is distinguished by the fact that a membrane-based substrate, in particular a blot strip or a blot piece, is used, a value for a colour contrast between the recorded marker in the form of a band and a surface of the substrate surrounding the marker is determined in each case, and the suggested diagnosis is generated on the basis of a mathematical calculation rule which includes the colour contrast.

Description

For the method and apparatus of diagnosis of nasopharyngeal carcinoma
The present invention relates to the method for diagnosis of nasopharyngeal carcinoma (NPC) and device, wherein the matrix with at least two kinds of antigens fixed thereon is carried out incubation together with the body fluid of patient.At this, so select antigen, thus make described antigen combine with that exist in the body fluid of described patient, special when ebv infection occurs antibody at least partly thus form antigen-antibody complex.The formation of antigen-antibody complex becomes visible by means of the trace mark in described matrix, and described trace mark optical device carries out record.Finally, this record is sent to evaluation unit, at least one characteristic based on recorded trace mark in described evaluation unit generates diagnostic recommendations.
Nasopharyngeal carcinoma (being often also abbreviated as " NPC ") is a kind of Cancerous disease of nasopharynx.Nasopharynx cancer belongs to this monoid of H/N tumors.The genetic characteristics of Epstein-Barr virus (EBV), various environmental factor, dietary and each patient is considered to the main cause of region nasopharyngeal carcinoma.This disease is worldwide scattered, but appears at the certain areas of southern china in large quantities.Except genetic factor, environmental impact, such as dietary, be also considered to cofactor.
Due to EBV infect and nasopharyngeal carcinoma occur between mutual relationship, often EBV test macro is used for diagnosing corresponding tumor disease.In this case, known different test macro is infected, wherein by antigen direct-detection or carry out diagnose infections by serological method for diagnosis EBV.Due to the high technology when implementing direct-detection and the cost of time, serology is selected method, because it also allows the various different phases distinguishing EBV infection.At this, very generally, corresponding Serologic detection is carried out by the detection of the specific antibody by means of immunofluorescence test, ELISA or western blotting method.Suitable test macro is such as provided as linear trace or using name of product Anti-EBV (DY2790-1501G or M) as western blot using name of product Anti-EBV-EA (EI2795-9601A, G or M) as microtitration ELISA, using name of product EBV-Profil2 (DN2790-1601-2G or M) by EUROIMMUNMedizinischeLabordiagnostikaAG company.
The metainfective antibody response of EBV has very different results due to the complicacy of virus and the changeability of various different infective stage.Therefore, primarily occur the antibody belonging to antibody isotype IgM after infection in short time, it no longer exists for EA (early antigen) and VCA (viral capsid antigen) and after acute infection is disappeared or only exists with low-down activity.On the contrary, anti-VCAIgG antibody that is simultaneously about or that formed with delaying a little retains throughout one's life.In addition known, on the one hand, the VCAIgG antibody of very high titre for nasopharyngeal carcinoma generation be distinctive, and on the other hand, the detection of anti-VCAIgA antibody is suitable as supportive testimony in NPC diagnosis.Similarly, the anti-EA antibody horizontal of rising is distinctive in the patient with nasopharyngeal carcinoma.
The outstanding part of the ELISA-test macro of frequent use is, the antigen used, particularly VCA and EA, as potpourri exist, and therefore only can diagnose in the inspection of Patient Sample A from one group of antibody at least one antibody there is situation.On the other hand, blotting system provides such advantage, on film, namely there is antigen alone apart from each other, to such an extent as to can evaluate all antigen bands apart from each other, and this finally allows the very detailed evaluation of band pattern to work out diagnosis.Known in this case, in order to the evaluation of the band pattern in blotting system situation, use optical device, particularly scanner or camera, and carry out the evaluation of recorded image by means of suitable laboratory software.
Corresponding system for the Assessment of the test macro based on film is such as carried out providing and selling with title EUROBlotCamera or EUROBlotScanner by EUROIMMUNMedizinischeLabordiagnostikaAG company.The image correspondingly recorded fully automatically can carry out by means of the suitable software carrying out providing with name of product EUROLINESCAN managing, registering and electronic archive.
Similarly, from DE10061352A1, know the device for evaluating trace bar and method.The outstanding part of described device is, the image through the trace bar of incubation carries out digitizing by means of scanner and is also therefore delivered to electronic evaluation unit.Finally, the evaluation of trace bar is by considering that the painted or intensity of trace is carried out on described trace bar.For this reason, preferably settle trace bar alone so on the scanner, thus likely catch the discontinuous of the trace of the background coloration compared to trace bar and stain.
In a word, therefore can determine to there is the different test macros for diagnosing EBV to infect.But neither one can make direct testimony, particularly diagnostic recommendations about the enquirement that there is nasopharyngeal carcinoma risk in which kind of degree in patients to doctor in known test macro.This be primarily due to: only have when accurately and reliably determining the existence of specific antibody in Patient Sample A, particularly their combination occurs, and when preferably also having antibody titer, diagnosis is accurately and reliably only possible.
Therefore, from the known apparatus and method for diagnosing EBV to infect, following task becomes basis of the present invention: a kind of test macro is described, can make the judgement about there is nasopharyngeal carcinoma in patients with it with high reliability.At this, test macro to be described should be structured in known method, and fairly simple and reliably implement.Meanwhile, it realizes the diagnosis of low cost as much as possible under should making it possible to have high measurement sensitivity and specific situation at the same time.
Task described above method according to claim 1 and device according to claim 8 have come.Favourable embodiment of the present invention is the theme of dependent claims, and in the following description by partly making an explanation in more detail with reference to accompanying drawing.
The present invention is based on the method for diagnosis of nasopharyngeal carcinoma in patients, wherein the matrix with at least two kinds of antigens fixed thereon is carried out incubation together with the body fluid of described patient.At this, so select antigen, thus make described antigen separately at least partly with exist in the body fluid of described patient and the antibody special when ebv infection occurs combine thus form antigen-antibody complex.The formation of respective antigen-antibody complex becomes visible by means of at least one trace mark in described matrix, and described matrix is manifesting after incubation by described trace mark together with positive patient sample.After having carried out incubation, with the surface of matrix described in optical device record, particularly wherein show the region of at least one visible trace mark when forming antigen-antibody complex, and described record is delivered to evaluation unit.Based at least one characteristic of recorded trace mark, generate diagnostic recommendations by described evaluation unit.According to the present invention, mould described method so further, thus use the matrix based on film, particularly trace bar or trace sheet, be determined at the recorded trace mark made with strips separately and be centered around the value of the color contrast between the stromal surface around described trace mark, and generate diagnostic recommendations based on the mathematical computations rule comprising color contrast.
Therefore, central scope of the present invention is, detect the contrast of the trace mark that at least two manifest in the matrix through incubation, that is the luminance difference between the trace mark manifested with strips and the stromal surface region being centered around around these bands, and so it is carried out quantitatively, thus can by carrying out suitable evaluation to make the testimony of the risk about individual patient with nasopharyngeal carcinoma for detected contrast value.In order to evaluate and generate diagnostic recommendations, be captured in the contrast value of the band that matrix manifests when Ag-Ab combines and occurs and by means of statistical calculations model, it evaluated.As statistical calculations model, preferably use Logic Regression Models, particularly binary logistic regression model or multinomial Logic Regression Models, wherein using for band alone record and put in described computation model as parameter with quantitative contrast value.Based on the result that described computation model provides by using contrast value, in evaluation unit, generate diagnostic recommendations, this diagnostic recommendations is finally for the doctor implementing to check provides the answer to following problems: whether the Patient Sample A checked allows to draw the conclusion that there is nasopharyngeal carcinoma in described patient.
In order to obtain the value through quantizing of the contrast about trace mark, preferably in the mode of carrying out resolving according to gray shade scale to check each recorded band, and corresponding value is specified for this contrast.According to a special embodiment, in this minimum contrast value for band, that is for the situation that band does not highlight in color for the stromal surface of surrounding, distribute 0 (zero) this value; With for maximal value, that is maximum-contrast, distribute 255 (255) this value.Therefore, the contrast of recorded trace mark is preferably demarcated within the value scope of 0≤L≤255.
For the evaluation carried out according to the present invention, preferably, it is suitable for having more than the trace bar of two kinds of antigens fixed thereon and/or trace sheet.Particularly advantageously, at least five kinds of antigens be fixed on Blotting matrix are used, preferably these antigens of VCAGP125, VCAP19, EBNA-1, P22 and EA-D.
In order to preferably realize test result accurately and reliably, the trace sheet equipment antigen so given trace bar and/or use separately, thus just belong to the antibody of at least two kinds of different antibodies classifications there is situation to check Patient Sample A.According to a very special scheme further of the present invention, by use suitable enzyme conjugate just belong to the antibody of antibody isotype IgA, IgG and IgM there is situation to check for described inspection and the Patient Sample A that arranges.
The method of carrying out according to the present invention mainly based on: by means of mathematics computing model, particularly binary logistic regression model, determines diagnostic recommendations.Such model forms a ratio from probability and inverse probability (it is determined by means of suitable e-function).According to a special scheme further of the present invention, the contrast value of band is used as the parameter of binary logistic regression model and forms the index of the e-function used at least in part alone.By means of the calculating so carried out, finally determine probability, can the situation that exists for nasopharyngeal carcinoma in checked patient reach a conclusion with it.At this, checked Patient Sample A being incorporated into is separately in two groups one group, i.e. positive patient sample sets or negative patient sample's group.In order to ensure the corresponding division of Patient Sample A, specify that suitable probable value is as ultimate value.
There is provided suitable band contrast value as parameter in order to the computation model that uses in evaluation unit can be given, arrange such optical coding unit, record the color contrast of band alone for its surrounding environment of the patient's bar through incubation or the trace sheet (EUROAssay) through incubation with it.Such record cell or be camera, or be scanner.When corresponding matrix being carried out together with positive patient sample incubation, there is the formation of so-called antigen-antibody complex, to such an extent as to form dark bands as trace mark.Depend on the antibody titer of Patient Sample A, band is stained with different intensity, to such an extent as to the contrast between band and the matrix areas being centered around around this band can correspondingly change.By means of described optical coding unit, record the band through the matrix of incubation and the aberration detected for surrounding environment or contrast.
In described evaluation unit, the image recorded is stained the next gray level image staining value with having 0 to 255 with regard to it and compares, and correspondingly classify by means of camera or scanner.Based on the intensity of colour of the band so detected or the contrast between band and the matrix areas being centered around around this band, finally realize the generation of diagnostic recommendations., detected contrast value is put in described mathematics computing model, particularly Logic Regression Models for this reason, and determine that described Patient Sample A is positive or negative sample based on detected result.
Described method and being especially for the outstanding part of this device used, the calibration of self recording apparatus only must be carried out before instrument starts running, and then need only carry out with the longer time interval.And it is optional in each calibration of measuring when starting.
Below, explain the present invention by reference to accompanying drawing in more detail according to embodiment, and do not limit total inventive concept.There is shown herein:
Fig. 1: through the EUROLine-EBV-Profil2 of the EUROIMMUNmedizinischeLabordiagnostikaAG company of incubation; And
Fig. 2: through the western blot-Anti-EBV of the EUROIMMUNmedizinischeLabordiagnostikaAG company of incubation.
The EUROLine-protos test suite PROTOS of EUROIMMUN company is particularly useful for the qualify in vitro mensuration of the people's antibody for five kinds of EBV-antigens VCAGP125, VCAP19, EBNA-1, P22 and EA-D (especially belonging to people's antibody of immunoglobulin class IgG) in serum or blood plasma so far depicted in figure 1.Except antigen VCAGP125 (it exists with the form of purifying in affinity chromatography natively), described antigen is all recombinant antigen.By using according to method of the present invention it is possible that also make quantitative testimony by means of above mentioned test, particularly about the probability that there is nasopharyngeal carcinoma in checked patient.
The test-strips being coated with described antigen is carried out incubation in first incubation step together with diluted patients serum.When positive, specific antibody combines with respective antigen.In second step, test-strips is carried out incubation, described enzyme conjugate catalysis color reaction subsequently together with enzyme conjugate (namely through anti-human igg, IgA or the IgM conjugate of enzyme labeling).Depend on used enzyme conjugate, the antibody belonging to immunoglobulin class IgG, IgM or IgA in Patient Sample A can be detected in like fashion.When there is the formation of antigen-antibody complex, the position that for this reason arrange of each band as trace mark in test-strips manifests.
If IgG antibody is not combined with EBNA-1, but IgG and IgM antibody are combined with VCA in this respect, and so this can be result from first or de novo EBV to infect.If IgG antibody is combined with EBNA-1 and VCA, but the combination of IgM antibody and VCA does not occur, so this can be result from the EBV that terminated to infect.In contrast, if although there occurs the combination of IgG antibody and p22 and VCA, but IgG antibody is not combined with EBNA-1, and so this can be result from the EBV terminated that lost EBNA-1 antibody to infect.
In order to carry out incubation, according to the number of the Patient Sample A of examine, respectively load the wide area damping fluid of the used time dilution in sight of 1.5ml to incubation groove.From pack, take out requisite number object test-strips with tweezers, and it is directly put into separately the incubation groove that is equipped with damping fluid.After this, carry out first time incubation, wherein by test-strips at room temperature incubation 15 minutes on wobbler.Subsequently, liquid is extracted out completely from groove.
Now, at each, the diluted Patient Sample A loading 1.5ml in the incubation groove of test-strips is housed, and on wobbler under room temperature (+18 DEG C to+25 DEG C) incubation 30 minutes.Subsequently, liquid is extracted out completely from each groove, and the wide area buffer solution three times (five minutes) of the used time dilution in sight of each 1.5ml on wobbler.Then, respectively the enzyme conjugate (in this case, anti-human igg or IgA through alkali phosphatase enzyme mark) of used time in sight of 1.5ml dilution is pipetted in incubation groove, and at room temperature incubation 30 minutes on wobbler.After this conjugate incubation, again liquid is extracted out completely from groove, and the wide area buffer solution three times (five minutes) of the used time dilution in sight of each 1.5ml on wobbler.For back to back substrate incubation, respectively the substrate solution of 1.5ml is pipetted in incubation groove, and at room temperature incubation ten minutes on wobbler.Subsequently, liquid is extracted out completely from each groove, and with distilled water or deionized water by each test-strips rinsing three times (one minute).
In order to evaluate, according to evaluation of programme, test-strips be opened, carry out air oxygen detrition, and record the band pattern of test-strips by means of scanner or camera.Recorded image is Electronically delivered to evaluation unit.In described evaluation unit, detect the contrast of band for the test-strips surface in the surrounding environment be close at it alone.The contrast of the band recorded or intensity of colour to be detected by means of gray scale by evaluation unit and correspondingly classify.For this reason, arrange the greyscales of 0 to 255, thus distribute a corresponding contrast value to each band.In like fashion, in test evaluation, first there is intensity of colour quantitative about band alone.
The contrast value of the various different band obtained in like fashion is put in Logic Regression Models as parameter, and finally determines probable value by means of described model.If this probable value is positioned on predetermined ultimate value, so checked Patient Sample A is classified as positive and generate corresponding diagnostic recommendations.Anticipate to there is nasopharyngeal carcinoma in this case in the patient that this sample derives from.In contrast, if define the probable value be positioned under predetermined ultimate value, so can think there is not corresponding tumour in checked patient.
In principle, it is contemplated that use dualistic logistic regression model or multinomial Logic Regression Models, and the contrast value of recorded band is alone put in corresponding model as parameter.Depend on the computation model used separately, use the contrast value of the different numbers of various different antigen bands.In addition, consider and whether the antibody belonging to antibody isotype IgG, IgM or IgA can be detected in patients serum, or the contrast value of inciting somebody to action band (such as, IgG-p22 and IgA-EBNA) is alone put in regression model as parameter in an appropriate manner.In a situation in which the method according to the present invention is applied, particularly advantageous computation model is that the variable had according to Wald " comprises " the dualistic logistic regression model of (all parameters) and " eliminating " (backward) and has the multinomial Logic Regression Models of variable " main effect " (all parameters and step by step adjustment backward).In order to determine the probability occurred about nasopharyngeal carcinoma, at least two (usually more multiple) contrast values of the various different band recorded are put in corresponding regression model as parameter.At this, each recorded band (therefore it have the aberration for surrounding environment) represents being formed of the compound be made up of antigen and the antibody that comprises in patients serum.In order to generate diagnostic recommendations as far as possible accurately, the situation that exists similarly just belonging to the antibody of different antibodies classification (i.e. classification IgA, IgG and IgM) carrys out test patient sample.
By means of the Logic Regression Models be stored in evaluation unit (probability of occurrence and inverse probability being placed in ratio by it), checked Patient Sample A is divided into two groups, i.e. positive group and negative sample group.Finally, based on this division, described evaluation unit generates diagnostic recommendations, and this diagnostic recommendations provides the answer to following problems: the risk that whether there is existing nasopharyngeal carcinoma in the patient that its serum checks.By considering color contrast or the intensity of colour of band alone, the evaluation of the band pattern that the test-strips through incubation presents provides relatively simple possibility there is diagnosing very accurately of situation by using known statistical method itself to work out about nasopharyngeal carcinoma.
Fig. 2 shows western blot test-strips, and it is mainly arranged for measuring from the qualify in vitro of the people's antibody for EBV-antigen (especially belonging to people's antibody of immunoglobulin class IgG) of serum or blood plasma so far.By using according to method of the present invention it is possible that also make quantitative testimony by means of above mentioned test, particularly about the probability that there is nasopharyngeal carcinoma in checked patient.
Described trace bar is coated with the Antigen extraction thing of the Epstein-Barr virus through electrophoretic separation.As be relevant to Fig. 1 explain, first trace bar is carried out incubation together with diluted Patient Sample A.When positive, specific antibody combines with corresponding antigen.In order to show these antibody, in second step, itself and correspondingly required enzyme conjugate (that is, anti-human igg, IgA or IgM conjugate through enzyme labeling) are carried out incubation, described enzyme conjugate catalysis color reaction subsequently together.
Depicted in figure 2 the incubation of western blot bar to close, sample incubation, washing, conjugate incubation, washing, substrate incubation and stop these steps to carry out.Again, when trace bar is carried out incubation by each leisure together with Patient Sample A positive at least in part, the evaluation of the band pattern of formation is automatically carried out by means of optical coding unit (particularly scanner or camera) and evaluation unit.
Again, according to the present invention, in described evaluation unit, detect color contrast or the intensity of colour of band alone, the luminance difference that is between band and background, wherein in described evaluation unit, carry out the calibration based on gray scale with the value of 0 to 255.The contrast value of band be alone considered as and be stored in the parameter among the binary logistic regression model in evaluation unit, wherein said contrast value forms the index of e-function at least in part.Therefore, based on the color contrast of detected band alone, determine probable value by means of regression model, described probable value is considered in the formulation of diagnostic recommendations.In order to generate diagnostic recommendations, based on comparing between determined probable value and prespecified ultimate value, Patient Sample A will be divided into two groups alone, namely there is the group of positive patient sample and there is the group of negative patient sample.Predicated in positive patient its Patient Sample A, can be thought to there is nasopharyngeal carcinoma in described patient with high probability.

Claims (11)

1. for the method for diagnosis of nasopharyngeal carcinoma in patients, in the process the matrix with at least two kinds of antigens fixed thereon is carried out incubation together with the body fluid of described patient, wherein so select antigen, thus make described antigen separately at least partly with to exist in the body fluid of described patient, the antibody special when ebv infection occurs combines thus forms antigen-antibody complex, the formation of antigen-antibody complex becomes visible by means of at least one trace mark in described matrix separately in the process, and be delivered to evaluation unit with optical device record at least two trace mark in the process, at least one characteristic based on recorded trace mark in described evaluation unit generates diagnostic recommendations,
It is characterized in that, use the matrix based on film, particularly trace bar or trace sheet, the value of the color contrast of trace mark for the background be centered around around described trace mark that respective mensuration is made with strips, and generate diagnostic recommendations based on mathematics computing model, in described mathematics computing model, utilize the color contrast detected as parameter at least in part.
2. method according to claim 1, is characterized in that, uses and has at least two kinds, has trace bar or the trace sheet of at least five kinds of antigens fixed thereon especially.
3. according to the method for claim 1 or 2, it is characterized in that, use VCAgp125, VCAp19, EBNA-1, p22 and/or EA-D as antigen.
4. according to the method for one of claims 1 to 3, it is characterized in that, there is situation to check this Patient Sample A in what just belong to the antibody of at least two kinds of different antibodies classifications.
5. according to the method for one of Claims 1-4, it is characterized in that, there is situation to check this Patient Sample A in what just belong to the antibody of antibody isotype IgG, IgM and IgA.
6. according to the method for one of claim 1 to 5, it is characterized in that, use Logic Regression Models as mathematics computing model.
7. according to the method for one of claim 1 to 6, it is characterized in that, use binary logistic regression model as mathematics computing model.
8. according to the method for one of claim 1 to 7, it is characterized in that, in described mathematics computing model, use at least one contrast value of the trace mark made using strips as parameter.
9. for the device of diagnosis of nasopharyngeal carcinoma in patients, described device has matrix, described matrix is fixed with at least two kinds of antigens, wherein so make described antigen, thus make described antigen at least partly with exist in the body fluid of described patient and the antibody special when ebv infection occurs combine thus form antigen-antibody complex, and in described matrix formed antigen-antibody complex trace mark can see; And there is optical device, the record of at least one trace mark can be produced by described optical device and can evaluation unit be delivered to, diagnostic recommendations can be generated based at least one characteristic of recorded trace mark in described evaluation unit,
It is characterized in that, described matrix is made for based on film, particularly as trace bar or as trace sheet, the value of the color contrast of trace mark for the background be centered around around described trace mark made with strips can be measured in described evaluation unit, and so make described evaluation unit, thus make it possible to by means of mathematics computing model by considering that the color contrast detected generates diagnostic recommendations.
10. device according to claim 9, is characterized in that, described trace bar or trace sheet are fixed the antigen that at least two kinds are selected from VCAgp125, VCAp19, EBNA-1 and EA-D.
11. devices according to claim 9 or 10, is characterized in that, described optical device is made for scanner and/or camera.
CN201480016674.9A 2013-02-01 2014-01-28 Method and apparatus for diagnosing a nasopharyngeal carcinoma Pending CN105308459A (en)

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DE201310001699 DE102013001699A1 (en) 2013-02-01 2013-02-01 Method and device for diagnosing a nasopharyngeal carcinoma
PCT/EP2014/051584 WO2014118151A1 (en) 2013-02-01 2014-01-28 Method and apparatus for diagnosing a nasopharyngeal carcinoma

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