EP0708921A1 - Test device - Google Patents
Test deviceInfo
- Publication number
- EP0708921A1 EP0708921A1 EP94921016A EP94921016A EP0708921A1 EP 0708921 A1 EP0708921 A1 EP 0708921A1 EP 94921016 A EP94921016 A EP 94921016A EP 94921016 A EP94921016 A EP 94921016A EP 0708921 A1 EP0708921 A1 EP 0708921A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- binding molecule
- analyte
- specific binding
- antibody
- immobilised
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
Definitions
- the present invention relates to a device for detecting the presence of analyte in a sample of a body fluid, in particular a sample other than a serum sample.
- analytes are typically immunoglobulin molecules but may also be other proteins.
- Immunoglobulin molecules are known to occur in such non-serum body fluids as saliva and urine.
- the immunoglobulin molecules of classes IgA, IgG and IgM predominate in saliva.
- Saliva and urine are secreted body fluids and collection of samples is easily and simply carried out.
- tests and devices known for detecting analytes in samples of a particular body fluid include biochemical assays of the amount and/or presence of particular proteins or immunoglobulins; so called 'sandwich assays' for immunoglobulins and the use of electrophoresis to identify individual classes of immunoglobulins.
- Devices used to detect analytes such as immunoglobulins in saliva include various probes consisting of a stick with an absorbent or adsorbent pad of material at one end. Such probes are disclosed in EP-A-0418739, EP-A- 0442231 and US-A-5103838.
- the probes of the prior art additionally include detection systems capable of identifying antibodies in saliva.
- Detection systems used in the past on diagnostic probes of this type have employed enzyme-linked assays or particle-agglutination assays to produce visibly detectable results.
- Samples of urine and saliva which a clinician might wish to assay generally contain levels of antibody which may be 2 or 3 orders of magnitude lower than the levels of antibody found in serum or plasma samples.
- Antibody concentration in urine and saliva samples is influenced by several factors, and shows natural variability. The antibody concentration may be lowered when urinary output is increased through ingestion of large volumes of fluid prior to sampling, or when saliva production has been artificially increased through stimulation by citric, or other acids.
- the present invention seeks to solve this problem by providing a device with an inbuilt means for detecting false negative results arising from use of an invalid sample.
- a device for the detection of an analyte present in a body fluid of an animal species comprising a substrate and on the substrate in discrete locations :
- the advantage of this device is contained in the final step of binding the characteristic molecule to a second immobilised specific binding molecule. This step ensures that a sufficient quantity of characteristic molecule is present to give meaningful results and therefore that particular test can be readily verified.
- the overall concentration of characteristic molecule in a test sample is easily quantitated and if the level is sufficiently high then the risk of a false negative result is significantly reduced.
- GB-A-2204398 relates to an assay device which also contains a mobile labelled first specific binding molecule, a means for detecting analyte and an immobilised second specific binding molecule. However, it differs significantly from the device of the present invention because the first specific binding molecule is specific for the analyte rather than for a characteristic molecule of the species being tested as is the case with the present invention. This means that using the device of GB-A-2204398 it is not possible to determine whether the sample is viable and, thus, to eliminate false negatives.
- the term 'binary complex' is used to define the complex formed by the specific binding molecule bound to a particle on the substrate and a characteristic molecule which may include analyte molecules.
- the analyte may be an antibody.
- the term 'mobile' when used in connection with the first specific binding molecule, indicates that the first specific binding molecule is not immobilised on the substrate.
- characteristic molecule refers to a molecule which is typically found in the type of sample to be tested and which will therefore be present in detectable concentration if the sample is viable. For example, in saliva samples, it is usual to find detectable quantities of IgG, and IgG would therefore be a suitable characteristic molecule for saliva samples .
- the first specific binding molecule would, in that case, bind specifically to all antibodies of the IgG isotype.
- the device of the present invention is suitable for the detection of an analyte in any body fluid but it is especially useful for overcoming the problems of detecting analytes in saliva and urine samples where the concentrations of analytes tend to vary. It is also useful for other body fluids such as blood.
- the analyte to be tested by the device of the present invention may be an antibody to a bacterial, viral, fungal or protozoal pathogen for example Helicobacter pylori , the Human Immunodeficiency viruses (HIV 1 and 2) , a Salmonella spp . , a Streptococcus species, polio virus, hepatitis A, hepatitis B surface antigen or hepatitis B core antigen, Candida spp. , Aspergillus spp . , Entamoeba spp . or Giardia spp .
- the analyte may also be an antibody to a tissue or species-specific antibody associated with autoimmune diseases, or allergic conditions.
- the analyte may be an antigen, for example a pathogen protein or a hormone, blood group characterising protein or any other protein or glycoprotein which may require detection. Nucleic acids can also be detected using the device of the present invention.
- the analyte should also form a portion of the characteristic molecule, or be a subset of characteristic molecules, which bind to the first specific binding molecule to form binary complex.
- the characteristic molecule when the analyte is an antibody of a particular isotype, for example IgG, IgM, IgE or IgA, the characteristic molecule will be any antibody of that isotype and the first specific binding molecule will be selected so that it binds to all antibodies of that isotype.
- the first specific binding molecule may be a lectin which binds to all glycoproteins present in the sample and labels them and if the analyte is a nucleic acid, a suitable first specific binding molecule would be a labelled low specificity nucleic acid probe.
- the analyte is a subset of the characteristic molecule, a portion of the labelled binary complex will contain the analyte and this is a particularly advantageous feature of the invention as it eliminates the need for more than one detectable label.
- the device provided by this invention is designed for use in diagnosing medical conditions suffered by humans.
- the first specific binding molecule will often be an antibody which will preferably be of the IgG or IgM isotype. Other isotypes of antibody may be similarly so used if required.
- the first specific binding molecule may be of polyclonal or monoclonal origin, and may be either an intact molecule or a specific binding-site containing fragment derived by enzymatic or chemical cleavage, or obtained through the application of recombinant DNA technology or peptide synthesis.
- the first specific binding molecule may be labelled with any convenient label.
- the label may*, in particular, allow the specific binding molecule to be visualised, or otherwise detected, when immobilised.
- Particles constitute preferred labels for this purpose.
- Particles coupled to the first specific binding molecule on the test device may be of any known type, for example, latex, colloidal metal, liposomes or polystyrene. Chromophores, fluorophores, and/or other labels may alternatively or additionally be used.
- the means for detecting the analyte on the test device may suitably comprise one or more discrete areas comprising an immobilised binding molecule specific for the analyte. Because the analyte forms a part of or is a subset of the characteristic binding molecule, it will already be bound to the detectably labelled first specific binding molecule and will therefore be detectable once it has been immobilised in the detection zone.
- analyte detection areas On the device since this allows quantitation of the analyte.
- the analyte is present only in small amounts, it will interact with the immobilised binding molecule in the first detection area, but there will be no surplus analyte which can pass to the further detection areas. If more analyte is present, some surplus may pass to the next detection area and so on so that the amount of analyte present will be indicated by the number of detection areas in which it is detected.
- two or more immobilised binding molecules specific for different analytes may be deposited on discrete areas of the test device, permitting the simultaneous detection of the presence of two or more different analytes in the same sample.
- the immobilised binding molecule in the detection area will generally be an immobilised pathogen protein, carbohydrate or other fragment, or a human tissue-derived protein, carbohydrate or other fragment, or a non-human species-derived protein, carbohydrate or other fragment.
- the immobilised binding molecule may also be an anti- idiotypic antibody.
- the immobilised binding molecule may be a monoclonal or polyclonal antibody which binds specifically to the protein or some other binding molecule specific for the particular protien to be detected.
- a suitable immobilised binding molecule would be a high specificity nucleic acid probe.
- Binary complexes which contain a characteristic molecule other than the analyte will not be immobilised or otherwise removed at location (b) , where the analyte is detected and will pass to location (c) , which functions as a verification station.
- a second specific binding molecule immobilises the complexes, which are then detectable by means of the label.
- the second specific binding molecule may specifically bind any part of the complex. It is preferred for the second specific binding molecule to bind the characteristic molecule; so, for example, if the characteristic molecule is a human antibody isotype, the second specific binding molecule may again be anti-human antibody such as anti-human IgG.
- Other suitable binding molecules are as discussed above in relation to the first specific binding molecule and will again be chosen depending on the analyte and the characteristic molecule.
- the device may further comprise a sample receiving portion of adsorbent material continuous with or separate from the substrate. This flexibility of construction permits maximum utility of operation depending on how the sample is to be applied.
- the substrate material of the test device may be composed of paper or membrane.
- the substrate material may also optionally be a carbohydrate and may preferably be a nitrocellulose material.
- the device be constructed so that body fluid (or components of it) can flow to locations
- sample is wicked along the membrane or paper substrate by capillary action. No additional solvent is required although particular sample diluents may increase the speed at which a result is obtained, or enhance the signal obtained with a positive test result.
- a method for the detection of analytes present in the body fluid of an animal comprising:
- the detectable products in steps (iii) and (iv) are preferably visibly detectable, as they are when the label referred to in step (ii) is a particle.
- FIGURE 1 shows a perspective view of a device in accordance with the invention.
- a sampling device 10 comprises a substrate 12 formed from an adsorbent material, typically nitrocellulose paper, and, attached to the substrate, a sample receiving portion 14. On the substrate is positioned a first area 16 in which is contained an anti-human IgG antibody coupled to a particle.
- the particles may be of any known type, for example latex, colloidal metal, liposomes or polystyrene.
- Sample detection areas 18, 20 contain antibodies specific for the analyte immobilised on the nitrocellulose substrate 12.
- a particularly preferred analyte which this device may be used to detect is antibody to H. pylori and, therefore, in that case, the detection areas 18, 20 would contain an immobilised antigen specific for H. pylori antibody.
- the final area on the device is the verification area 22 which contains immobilised anti-human IgG. This may be the same as the anti-human IgG which is bound to the particles but this is not necessarily so.
- a sample is placed on the sample receiving portion 14 and, because of the adsorbent nature of the substrate 12, the sample wicks along the substrate until it reaches the first area 16.
- any human IgG present in the sample binds to the anti-IgG coupled to the particles to form a binary complex.
- the binary complex continues to wick along the substrate 12 until it encounters the first sample detection area 18.
- binary complex containing analyte binds to the immobilised antibody to form a discrete visible clustering on the sample detection area 18.
- Unbound binary complex continues to pass along the substrate until it reaches the second sample detection area 20 where any remaining analyte-containing binary complex will be immobilised to form a second discrete visible clustering.
- the device of the present invention is simple to use and provides a quick and easy method of verifying that the sample is a viable one.
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Glass Compositions (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Undergarments, Swaddling Clothes, Handkerchiefs Or Underwear Materials (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB939314584A GB9314584D0 (en) | 1993-07-14 | 1993-07-14 | Test device |
GB9314584 | 1993-07-14 | ||
PCT/GB1994/001522 WO1995002822A1 (en) | 1993-07-14 | 1994-07-14 | Test device |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0708921A1 true EP0708921A1 (en) | 1996-05-01 |
Family
ID=10738825
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP94921016A Withdrawn EP0708921A1 (en) | 1993-07-14 | 1994-07-14 | Test device |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0708921A1 (fi) |
JP (1) | JPH09500962A (fi) |
AU (1) | AU683072B2 (fi) |
CA (1) | CA2167061A1 (fi) |
FI (1) | FI960147A0 (fi) |
GB (1) | GB9314584D0 (fi) |
NO (1) | NO960149D0 (fi) |
NZ (1) | NZ268623A (fi) |
SG (1) | SG42864A1 (fi) |
WO (1) | WO1995002822A1 (fi) |
ZA (1) | ZA945159B (fi) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6686170B1 (en) | 1994-08-17 | 2004-02-03 | Abbott Laboratories | Assay devices with mobile control reagents |
DE19647545A1 (de) * | 1996-11-16 | 1998-05-20 | M & M Dental Medizin Gmbh | Verwendung zum Bestimmen des Kariesrisikos und dazu besonders geeignete Testeinrichtung |
AU757629B2 (en) | 1998-04-14 | 2003-02-27 | Otsuka Pharmaceutical Co., Ltd. | Methods for assaying antibody and device for assaying antibody |
JP4627607B2 (ja) * | 2001-05-14 | 2011-02-09 | 三菱化学メディエンス株式会社 | 複数項目及び総含有量の同時分析可能なイムノクロマトグラフ法及びイムノクロマトグラフ用ストリップ |
US7114403B2 (en) | 2003-05-30 | 2006-10-03 | Oakville Hong Kong Co., Ltd | Fluid collection and application device and methods of use of same |
DE602004031253D1 (de) | 2003-11-14 | 2011-03-10 | Alere Switzerland Gmbh | Flüssigprobenanalysevorrichtung mit verschliessbarem probenaufbewahrungsreservoir |
AU2006319681B2 (en) | 2005-11-30 | 2012-12-13 | Abbott Rapid Diagnostics International Unlimited Company | Devices and Methods for Detecting Analytes in Fluid Samples |
CA2658795A1 (en) | 2006-07-26 | 2008-02-07 | Abon Biopharm (Hangzhou) Co., Ltd. | A test device for detecting an analyte in a liquid sample |
CN104714008B (zh) * | 2015-02-04 | 2016-08-17 | 上海交通大学 | 一种免疫层析试纸条及其制作方法与检测方法 |
DE102020107918B4 (de) * | 2020-03-23 | 2021-11-18 | Digital Diagnostics AG | Detektion von viren |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW203120B (fi) * | 1985-10-04 | 1993-04-01 | Abbott Lab | |
EP0560410B1 (en) * | 1987-04-27 | 2002-10-02 | Inverness Medical Switzerland GmbH | A test device for performing specific binding assays |
IE904365A1 (en) * | 1990-02-13 | 1991-08-14 | Epitope | Stick probe device for detection of antibodies |
-
1993
- 1993-07-14 GB GB939314584A patent/GB9314584D0/en active Pending
-
1994
- 1994-07-14 JP JP7504413A patent/JPH09500962A/ja active Pending
- 1994-07-14 EP EP94921016A patent/EP0708921A1/en not_active Withdrawn
- 1994-07-14 CA CA002167061A patent/CA2167061A1/en not_active Abandoned
- 1994-07-14 AU AU71901/94A patent/AU683072B2/en not_active Ceased
- 1994-07-14 ZA ZA945159A patent/ZA945159B/xx unknown
- 1994-07-14 NZ NZ268623A patent/NZ268623A/en unknown
- 1994-07-14 WO PCT/GB1994/001522 patent/WO1995002822A1/en not_active Application Discontinuation
- 1994-07-14 SG SG1996000278A patent/SG42864A1/en unknown
-
1996
- 1996-01-12 FI FI960147A patent/FI960147A0/fi unknown
- 1996-01-12 NO NO960149A patent/NO960149D0/no unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9502822A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPH09500962A (ja) | 1997-01-28 |
SG42864A1 (en) | 1997-10-17 |
CA2167061A1 (en) | 1995-01-26 |
NZ268623A (en) | 1997-10-24 |
GB9314584D0 (en) | 1993-08-25 |
WO1995002822A1 (en) | 1995-01-26 |
ZA945159B (en) | 1996-01-15 |
FI960147A (fi) | 1996-01-12 |
NO960149L (no) | 1996-01-12 |
AU683072B2 (en) | 1997-10-30 |
NO960149D0 (no) | 1996-01-12 |
AU7190194A (en) | 1995-02-13 |
FI960147A0 (fi) | 1996-01-12 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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17P | Request for examination filed |
Effective date: 19951221 |
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AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
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17Q | First examination report despatched |
Effective date: 19970206 |
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RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: CORTECS (UK) LIMITED |
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RAP3 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: CORTECS (UK) LIMITED |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 19981204 |
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