EP0243370A1 - Determination of clinical parameters by enzyme immunoprocess - Google Patents
Determination of clinical parameters by enzyme immunoprocessInfo
- Publication number
- EP0243370A1 EP0243370A1 EP86901372A EP86901372A EP0243370A1 EP 0243370 A1 EP0243370 A1 EP 0243370A1 EP 86901372 A EP86901372 A EP 86901372A EP 86901372 A EP86901372 A EP 86901372A EP 0243370 A1 EP0243370 A1 EP 0243370A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- zone
- enzyme
- antibodies
- antigen
- labelled
- 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- Withdrawn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
- G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
- G01N33/537—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody
- G01N33/538—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody by sorbent column, particles or resin strip, i.e. sorbent materials
-
- 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
- G01N33/54386—Analytical elements
-
- 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
- G01N33/54386—Analytical elements
- G01N33/54387—Immunochromatographic test strips
- G01N33/54391—Immunochromatographic test strips based on vertical flow
-
- 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
- G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
Definitions
- This invention relates to a diagnostic method and to a device for the qualitative and/or quantitative deter ⁇ mination of clinical parameters by enzyme immunoprocess using the affinity chromatography.
- the invention is particularly useful for the ana ⁇ lysis of biological substances in biological liquids such as urines, plasma, blood, exudates, tissue extracts, etc.
- the immunoenzyme diagnostic techniques have been known for a long time. They are based on the reaction between an antibody and its antigen one of which is con ⁇ jugated to an enzyme capable of giving a detecting reac ⁇ tion (of chromogen or other nature) when contacted with a suitable substrate. Thereafter, the enzyme-labelled anti ⁇ gen antibody complex, will give rise, by contact with the detector substrate, to a reaction that can be utilized for the qualitative or quantitative determination of the anti ⁇ gen or the antibody of interest.
- the enzyme immunotechniques most currently used in diagnostic are all suffering from a number of deficiencies that are substantially imputable ' .to the complicated and delicate procedures involved, and the long incubation times with intervening repeated washing of the reactive system.
- ELISA Enzyme-linked immunosorbent assay, Immunochem. , 8, 871-874, 1971
- ELISA Enzyme-linked immunosorbent assay
- This invention overcomes the problems encountered in the prior art techniques by providing a method and a device which enable to carry out, even on a quantitative basis, the determination of clinical parameters of what- ever nature, without recourse having to be made to any particular manipulations.
- a biological liquid containing the clinical parameter(s) to be determined is made to pass in a upward or downward direction along a conveniently shaped support which comprises: (a) an initial or intermediate zone on which substances may be adsorbed which are able to prevent interferences with the assay; (b) a zone onto which one or more antigens or enzyme-la ⁇ belled antibodies raised against one or more epitopes (N.R. Jerne, Angew. Chem. Int. Ed.
- Engl., 24; 1985, 810- 816 specific for the clinical parameter to be determin ⁇ ed, have previously adsorbed in a reversible manner;
- a further zone adjacent the preceeding zone, on which the antibodies or antigens forming the clinical parameters to be determined, are by known techniques immobilized in a quantity equivalent to, or greater than, that of .the enzy ⁇ me-labelled antibodies or antigens.
- this zone it is also possible to use antibodies raised against one or more epitopes different from the epitope(s) recognized by the antibodies of zone (b) (sandwich-assay).
- zone (c) the chromogenic substrate(s), for the enzyme-labelled antibo ⁇ dies' of zone (b), should be bound to zone (c).
- the chromogenic substrate(s) could be adsor ⁇ bed in reversible manner on a zone laying below.
- this zone (c) may have an anti-antibody immo ⁇ bilized thereon which is specific for an antigen-antibody complex, in which case the zone (b) is in turn divided , into two portions, with a first portion having, for exam- pie, the enzyme-labelled antigen adsorbed thereon and a second portion carrying the corresponding antibody, or conversely.
- zone (d) A zone on which there is adsorbed a chromogenic sub- strate for the antigen- or antibody-conjugated enzyme present in zone (b) or one or more support capable of allowing the flow of biological liquids (sandwich-assay).
- the biological liquid flowing up or down through the support by gravity, capillarity, chromatography or diffusion, will be caused to contact the zone (b) the first: the antigene or antibody that may be present will react with the complementary, enzyme-labelled antibodies or antigens.
- the thus formed complex, or combined system will rise (or fall) chromatographically along the support to pass through the zone (c) where the excess enzyme-labelled antibody or antigene, if any, will be bound to the comple ⁇ mentary, immobilized antigene or antibody.
- the specific complex will be bound forming a "sandwich" arrangement.
- the enzyme-labelled antigen-aritibody complex at- tains the chromogenic substrate to give rise to color (positive test) which can be , used for both quantitative and qualitative determination, for example, in comparison with a colorimetric scale.
- the enzyme-labelled antigen or anti- body in one case will be entirely fixed on the zone (c) by immunochemical reaction, thereby preventing it from attaining the chromogen substrate; in the other case (sandwich-assay) the enzyme-labelled antibody will not be fixed on the zone (c), and the colour formed during the passage of antibody-conjugated enzyme will be washed from the zone (negative test) by the flow of biological liquid.
- the system is based on a competi ⁇ tion between the antigen or antibody present in the biolo- gical liquid and the immobilized antigen or antibody whi ⁇ ch, in case of a negative response, functions in the first case as a barrier for the enzyme-labelled antibody or antigen to prevent migration thereof to the chromogen substrate-containing zone; in the second case as an un- reactive material which will not be able to bound the enzyme-labelled antibodies.
- the support device according to the invention may take the form of a strip, band, film, tube, specimen, flask, pad, etc.
- the various constituents may be either adsorbed or immobilized directly " onto the material forming the device or an appropriate solid carrier located inside the device, or fixed on the surface thereof in the form of a gel, powder, granules, microspheres, spheres, etc.
- the materials of the device, and the solid supports or carriers, at the various reaction zones, may be the same or different.
- suitable materials and carriers are glass, silica derivatives, paper or cellulose derivative*, metals, polymers such as polyvinyl chloride, polystyrene, polybutadiene, nylon, polyacryla ides, metha- crylates etc., polysaccharides or polyols, starch, stab ⁇ - ⁇ lized human or animal red blood cells, organic substanc such as BaSO , TiO , kaolin, diatomaceous earth, etc.
- Th device is preferably of an opaque material except the re ding-zone which is transparent.
- the immobilizing bond of the antigen or antibo on said materials may be achieved through physical chemical process (ester or amide bonding, etc.) accordi to the teachings in U.S. Patent No. 4,003,988 and t following references: B.K. Van Wee en and A.H.W. Schuur Febs Letters - Vol. 15, No. 3 - June, 1971, pp. 232-5; Leinikki and Suvi Passila, J. Clin. Path., 1976, 29, p 1116-20; B.R. Brön, F.E. Ashton et B.B. Diena, T Journal of Medical Microbiology - Vol. 15, No. 1, 198 pp. 1-9; A. Voller 1., D.E.
- the adsorption bond of the not immobilized const tuents may, on the other hand, occur by known technique matter as it is well known from the affinity chromatogr phy art.
- Both the immobilized and the enzyme-labelled 1 ant bodies useful to the invention can be polyclonal or mon clonal in toto or in fragments thereof, as for exampl Fab' and F(ab')2 radiation, possibly in admixture with one anothe and they may be specific for one or more active sites the antigen.
- Enzyme-labelling of the antigens or antibodies c be effected by known techniques such as those disclosed the above-mentioned text "Enzyme Immunoassay", by usi any enzyme capable of developing a chromogen reaction wi respect to , a substrate, such for example as peroxidas alkaline phosphatase, ⁇ -galactosidase or the like.
- Suc enzymes may, for example, be conjugated by means of gluta- raldehyde, dimaleimide and the esters thereof according t the techniques disclosed in the word "Enzyme Immunoassay” , pp. 54 to 113, mentioned above.
- Both the antibodies and the antigens may be atta ched to a support without restriction as to the quantit which may, in any case, be varied from 1 to 10 mg/sq c according to the concerned type of analysis, with only th provision that the immobilized component and the enzyme labelled component should be present in at least stoichio metrically equivalent amounts.
- a quanti tative determination is possible by determining the leve of the developed color either in an arbitrary way or b means or a suit'able reflection reader.
- the initial or intermediate separatio zone may merely consist of a material capable of function ing as a chromatographic support onto which such substan ⁇ ces are enabled to be previously adsorbed as are effective to remove compounds interfering with the identification reaction.
- a material capable of function ing as a chromatographic support onto which such substan ⁇ ces are enabled to be previously adsorbed as are effective to remove compounds interfering with the identification reaction may be made of: - ion-exchange resins to sequester heavy metals; immobilized enzymes to degrade urea or other metabolites; antiprotein antibodies to remo ⁇ ve albumin; antibodies that are specific for molecules having similarity to the antigen to be determined, etc.
- the in ⁇ vention provides a means enabling to determine in a sim ⁇ ple, fast and accurate manner a great deal of different clinical parameters: for example, peptide hormones such as HCG, LH, steroid hormones such as progesterone, estrone - _ -* -»
- glucuronide pregnanediol glucuronide, or other 'parameters of broad clinical interest such as streptolysin, immune globulins, viruses such as herpes viruses, HTLV-3 virus etc.
- attached to the same support may be several enzyme-labelled antigens and/or antibodies along with the corresponding immobilized antibodies and/or antigens the ⁇ reby permitting a number of clinical parameters to be determined in a simultaneous manner due to the presence, at different zones, of a corresponding number of chromogen substrates that are preferably such as to produce diffe ⁇ rent colors by reaction with different enzyme-labelled complexes.
- the sym ⁇ bol ⁇ designates the antigen; the symbol ⁇ > Q indicates the immobilized antigen; the symbol indicates the enzyme-conjugated antigen while the sym ⁇ bols /—— - / _) , H, in a similar manner designate the antibody, the immobilized antibody and the enzyme-con ⁇ jugated antibody, respectively.
- the sym- , bol (—•indicates the chromogen substrate, N—Q the immobilized anti-antibody, and the arrow designates the direction of the incoming liquid.
- FIG. 1 diagrammatically shows an arrangement enabling, according to one embodiment of the invention, to determine an antigen and including a support (strip, tube or other means) with a first zone containing the enzyme-labelled antibody that is specific for the antigen to be determin ⁇ ed, a second zone adjacent the first one which contains the immobilized antigen and which is followed by a sepa ration zone and, finally, a zone carrying the chromoge substrate thereon.
- a support strip, tube or other means
- th tube ends may be closed by porous septa.
- - Figure 2 shows the case when an antibody is to be deter mined.
- the biological liquid is caused to percolate in a downwar direction as indicated by an arrow, to successively conta ct the enzyme-labelled antigene in a first place, then th immobilized antibody and, in a last place, the chromoge substrate which instead of being adsorbed onto the soli support, may be added to the solution going out of th bottom end of the device.
- FIG. 3 shows, for the case in Figure 1, the variou migration steps .under condition ' s of positivity (+) and-o negativity (-) of the test (presence or absence of th antigen concerned) .
- - Figure 4 shows another embodiment similar to that i Fig. 1 from which it differs in that the immobilized anti gen is preagglutinated with the enzyme-labelled antibody thus, any antigen present in the biological liquid wil compete with the immobilized antigen to release the la belled antibody thereby enabling this latter to migrate t the chromogen substrate.
- - Figure 5 shows a further variation of the method o determining antigens.
- the support comprise a first zone containing an enzyme-labelled antigen, second zone having a corresponding antibody adsorbed ont it, and then a zone containing an immobilized anti-antibo dy (for example, sepharose protein-A or anti-IgC bound t PVC) again followed by the chromogen substrate; in thi case too, it is only the competition with the free antige present in the biological liquid that causes the enzyme labelled antigen to attain the substrate, whereas th antibody-antigen complex is kept trapped on the anti-anti body.
- an immobilized anti-antibo dy for example, sepharose protein-A or anti-IgC bound t PVC
- FIGS. 6a and 6b show a different type of device, a seen in cross-sectional view and in plan view from th .above, respectively.
- the device comprises a support stri 2 provided with holes 1 for a liquid to pass therethroug and with an impervious transparent coating 3 which permit the chroroogen-containing layer 4 to be inspected visually
- reading may be effected either visually, fo qualitative determination, or by the aid of a reflectio reader, in the case of a quantitative determination.
- th sizes of the individual zones may vary in each particula case and are commonly in the range of the few mm to few c values.
- certain details have not been show which could make for a more practical use of the inventiv support, such for example as support handles, means fo taking off (by suction) of biological liquid, marking indicative of the side to which the biological liquid i to be admitted, colorimetric scales arranged to one sid of the zones containing the chromogen subs ate, etc..
- the devices according to the invention may also b symmetrical devices having the enzyme-labelled componen arranged at both ends thereof, these latter being followe by the above-described sequential zones, in order to pre ⁇ vent the liquid from being uncorrectly admitted.
- conveniently packaged compact units may be provided which possess the sterile, stable, condi- tioned characteristics as required, etc..
- the method and device according to the invention are versatile and prac ⁇ tical in use and can be used for a large range of clinical analysis without the need for particular equip- ments or operations being involved. They are moreover, and above all, capable of giving analysis results in a short period of time, usually of the order of the minutes.
- Anti-HCG (10 ml) from rabbit is precipitated 3 times with 18% anhydrous sodium sulfate and the product recovered from 10 ml distilled water following to each precipitation. Then, the product is dialyzed one night at +4°C against phosphate buffer at 7.2 pH, 10 mMols.
- the dialyzed solution is treated with 100 mg of peroxidase RZ 3.00 and 25 mcl of 25% glutaraldehyde for 48 hours at +4°C.
- the solution is eluted on Sephadex G150 balanced with sodium chloride, 50 mMols.
- the eluted anti- HCG - peroxidase complex may be stored at -20°C.
- c Preparation of the labelled, support-adsorbed antibody Glass, 50 g, is treated with anti-HGC peroxidase, 5 ml, 1:500 diluted in phosphate buffer, 10 mMols, pH 7.2, and the product dried overnight at 37°C.
- a glass column (3.5 mm inside diameter, 15 cm high) is filled from bottom to top with the following materials: adsorbed anti-HCG peroxidase, immobilized HCG, adsorbed chromogen prepared as above.
- the glass column is closed at both ends with cotton wool or suitable porous stoppers. f. Carrying out of the analysis
- the above-described column is contacted with urine to be analysed which will rise up the column by capillari ⁇ ty.
- HCG anti-HCG peroxidase contained in the first column portion; in proceeding on its rising path,it will no longer produce any agglutination reaction with the immobilized HCG conta- ined in the second column portion so that it continues its way up to the last column portion containing the chromogen substrate which will develop a blue color by reaction with the enzyme; in the case of sandwich-assay, the complex will be specifically bound to zone (c) by immunochemical reac- tion, and the blue colour will be developed by the reaction with the enzyme and the chromogen substrate, developing a blue colour which will be read in the zone (c).
- the anti- HCG peroxidase in the first column portion in going up in a free manner, will attain the column zone containing the immobilized HCG to be bound thereto by immunochemi- cal reaction thereby being prevented from reaching the chromogen substrate. Thus, no color is developed; in the case of sandwich-assay, the anti-HCG peroxidase will not be bound in zone (c) and washed from the zone, in this way there will not be developed of colour.
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- 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)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Procédé et dispositif de détermination de paramètres cliniques dans des liquides biologiques par un procédé immunoenzymatique consistant à mettre séquentiellement en contact des liquides biologiques avec: a) des antigènes ou des anticorps marqués par une enzyme lesquels sont absorbés sur un support solide de manière réversible; b) des anticorps, des antigènes, des anti-anticorps ou des complexes antigènes-anticorps qui sont immobilisés sur un support solide en une quantité stoechiométriquement équivalente aux antigènes ou anticorps marqués par une enzyme; c) un ou plusieurs substrats chromogènes capables de produire une réaction évidente avec les enzymes conjuguées aux anticorps ou aux antigènes.A method and device for determining clinical parameters in body fluids by an enzyme immunoassay comprising sequentially contacting body fluids with: a) enzyme-labeled antigens or antibodies which are reversibly absorbed onto a solid support; b) antibodies, antigens, anti-antibodies or antigen-antibody complexes which are immobilized on a solid support in an amount stoichiometrically equivalent to the antigens or antibodies labeled with an enzyme; c) one or more chromogenic substrates capable of producing an obvious reaction with enzymes conjugated to antibodies or antigens.
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT19443/85A IT1200382B (en) | 1985-02-08 | 1985-02-08 | DETECTION AND / OR DOSAGE SYSTEM OF CLINICAL PARAMETERS BY IMMUNO ENZYMATIC ROUTE |
IT1944385 | 1985-02-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0243370A1 true EP0243370A1 (en) | 1987-11-04 |
Family
ID=11158028
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP86901372A Withdrawn EP0243370A1 (en) | 1985-02-08 | 1986-02-02 | Determination of clinical parameters by enzyme immunoprocess |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP0243370A1 (en) |
JP (1) | JPS62501989A (en) |
AU (1) | AU5511886A (en) |
DD (1) | DD245727A5 (en) |
ES (5) | ES8802256A1 (en) |
FI (1) | FI85194C (en) |
HU (1) | HUT56632A (en) |
IT (1) | IT1200382B (en) |
MW (1) | MW5287A1 (en) |
OA (1) | OA08640A (en) |
RO (1) | RO100056A2 (en) |
WO (1) | WO1986004683A1 (en) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4806311A (en) * | 1985-08-28 | 1989-02-21 | Miles Inc. | Multizone analytical element having labeled reagent concentration zone |
US4959305A (en) * | 1986-06-18 | 1990-09-25 | Miles Inc. | Reversible immobilization of assay reagents in a multizone test device |
CA1289872C (en) * | 1986-06-18 | 1991-10-01 | David L. Woodrum | Reversible immobilization of assay reagents in a multizone test device |
ES2004066A6 (en) * | 1987-01-21 | 1988-12-01 | Euro Fassel Aktiebolag | A kit for qualitative and quantitative analysis of antigens, antibodies and/or microorganisms or other cells |
AU592174B2 (en) * | 1987-02-17 | 1990-01-04 | Genesis Labs, Inc. | Immunoassay test strip |
AU586552B2 (en) * | 1987-02-25 | 1989-07-13 | Genesis Labs, Inc. | Dry test strip for devices using oxygen demanding detection system |
EP0291194B8 (en) * | 1987-04-27 | 2003-10-22 | Inverness Medical Switzerland GmbH | Immunoassays and devices therefor |
US5641639A (en) * | 1987-04-29 | 1997-06-24 | Celltech Therapeutics Limited | Binding assay device |
WO1988008536A1 (en) * | 1987-04-29 | 1988-11-03 | Boots-Celltech Diagnostics Limited | Binding assay device |
IT1223295B (en) * | 1987-08-14 | 1990-09-19 | Boehringer Biochemia Srl | IMMUNODIAGNOSTIC DEVICE AND METHOD |
FR2621393B1 (en) * | 1987-10-05 | 1991-12-13 | Toledano Jacques | DEVICE FOR IMMUNOENZYMATIC DETECTION OF SUBSTANCES FROM A DROP OF BLOOD OR LIQUID FROM ANY BIOLOGICAL MEDIUM |
US5039607A (en) * | 1988-05-17 | 1991-08-13 | Syntex (U.S.A.) Inc. | Method for immunochromatographic analysis |
US5334513A (en) * | 1988-05-17 | 1994-08-02 | Syntex (U.S.A.) Inc. | Method for immunochromatographic analysis |
US5338513A (en) * | 1988-07-30 | 1994-08-16 | Boehringer Mannheim Gmbh | Test carrier for the analytical determination of a component of a liquid sample |
FR2634891B1 (en) * | 1988-08-01 | 1994-05-06 | Biotrol Laboratoires | METHOD AND DEVICE FOR THE QUALITATIVE AND / OR QUANTITATIVE DETERMINATION OF A LIGAND IN A FLUID |
US5079174A (en) * | 1988-12-08 | 1992-01-07 | Boehringer Mannheim Corporation | Apparatus for sequential determination of an analyte in a fluid sample |
DE3842702A1 (en) * | 1988-12-19 | 1990-06-21 | Boehringer Mannheim Gmbh | TEST CARRIER FOR ANALYTICAL EXAMINATION OF A SAMPLING LIQUID WITH THE AID OF A SPECIFIC BINDING REACTION OF TWO BIOAFFIN BINDING PARTNERS AND A CORRESPONDING TEST PROCEDURE |
GB8903627D0 (en) * | 1989-02-17 | 1989-04-05 | Unilever Plc | Assays |
EP0588958A1 (en) * | 1991-06-13 | 1994-03-30 | Pacific Biotech Inc. | Assay for the detection of specific ligands |
DE4121493A1 (en) * | 1991-06-28 | 1993-01-07 | Draegerwerk Ag | ANALYSIS DEVICE FOR THE QUANTITATIVE, IMMUNOLOGICAL DETERMINATION OF POLLUTANTS |
FI92882C (en) * | 1992-12-29 | 1995-01-10 | Medix Biochemica Ab Oy | Disposable test strip and process for its manufacture |
FR2725023B1 (en) * | 1994-09-28 | 1997-01-31 | Gks Technologies | DIRECT DIAGNOSIS OF HAPTENES |
JP3010699U (en) * | 1994-10-29 | 1995-05-02 | 株式会社ニッポンジーン | Chromatographic inspection device capable of direct urine collection |
FR2917171A1 (en) * | 2007-06-07 | 2008-12-12 | Biosynex Sarl | Detection of molecule of interest e.g. peptide in liquid sample by contacting the sample with first antibody, contacting the antibody with marked conjugate, contacting the first antibody with second antibody, and analysis of test zone |
CN102095860B (en) * | 2011-01-25 | 2013-12-18 | 厦门大学附属中山医院 | Syphilis specific IgG antibody western blot kit and preparation method thereof |
EP4062066A1 (en) | 2019-11-22 | 2022-09-28 | Nano Scale Machining GmbH | Fluid machine, in particular hydraulic machine |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2644249A1 (en) * | 1976-09-30 | 1978-04-06 | Abbott Lab | Reactive, stable metal and organic cpd. compsns. - comprising metal surface coated with polymer and coupled to enzymes, protein(s) etc. |
US4320111A (en) * | 1977-06-14 | 1982-03-16 | American Home Products Corporation | Immunologic compositions methods of preparation and use |
US4189304A (en) * | 1978-10-27 | 1980-02-19 | Miles Laboratories, Inc. | Device and method for detecting myoglobin |
US4331650A (en) * | 1980-07-18 | 1982-05-25 | Science Research Center, Inc. | Identification of reagins in the blood serum of allergen sensitized vertebrates |
JPS5818167A (en) * | 1981-07-24 | 1983-02-02 | Fuji Photo Film Co Ltd | Analyzing film and analysis using said film |
US4446232A (en) * | 1981-10-13 | 1984-05-01 | Liotta Lance A | Enzyme immunoassay with two-zoned device having bound antigens |
US4447546A (en) * | 1982-08-23 | 1984-05-08 | Myron J. Block | Fluorescent immunoassay employing optical fiber in capillary tube |
EP0149168B1 (en) * | 1983-12-19 | 1991-04-24 | Daiichi Pure Chemicals Co. Ltd. | Immunoassay |
-
1985
- 1985-02-08 IT IT19443/85A patent/IT1200382B/en active
-
1986
- 1986-02-02 WO PCT/EP1986/000055 patent/WO1986004683A1/en active IP Right Grant
- 1986-02-02 JP JP61501288A patent/JPS62501989A/en active Pending
- 1986-02-02 HU HU862003A patent/HUT56632A/en unknown
- 1986-02-02 AU AU55118/86A patent/AU5511886A/en not_active Abandoned
- 1986-02-02 EP EP86901372A patent/EP0243370A1/en not_active Withdrawn
- 1986-02-05 DD DD86286799A patent/DD245727A5/en not_active IP Right Cessation
- 1986-02-07 ES ES551760A patent/ES8802256A1/en not_active Expired
-
1987
- 1987-07-17 MW MW52/87A patent/MW5287A1/en unknown
- 1987-07-22 OA OA59169A patent/OA08640A/en unknown
- 1987-08-05 FI FI873398A patent/FI85194C/en not_active IP Right Cessation
- 1987-08-13 ES ES557662A patent/ES8900067A1/en not_active Expired
-
1988
- 1988-01-11 RO RO131733A patent/RO100056A2/en unknown
- 1988-01-15 ES ES557803A patent/ES8802259A1/en not_active Expired
- 1988-01-15 ES ES557802A patent/ES8802258A1/en not_active Expired
- 1988-02-01 ES ES557818A patent/ES8802260A1/en not_active Expired
Non-Patent Citations (1)
Title |
---|
See references of WO8604683A1 * |
Also Published As
Publication number | Publication date |
---|---|
AU5511886A (en) | 1986-08-26 |
WO1986004683A1 (en) | 1986-08-14 |
HUT56632A (en) | 1991-09-30 |
ES557802A0 (en) | 1988-04-16 |
ES8802260A1 (en) | 1988-04-16 |
FI873398A (en) | 1987-08-05 |
FI85194B (en) | 1991-11-29 |
OA08640A (en) | 1988-11-30 |
ES551760A0 (en) | 1988-04-16 |
ES8900067A1 (en) | 1988-11-16 |
ES8802256A1 (en) | 1988-04-16 |
FI85194C (en) | 1992-03-10 |
ES8802259A1 (en) | 1988-04-16 |
JPS62501989A (en) | 1987-08-06 |
ES8802258A1 (en) | 1988-04-16 |
ES557803A0 (en) | 1988-04-16 |
ES557818A0 (en) | 1988-04-16 |
DD245727A5 (en) | 1987-05-13 |
RO100056B1 (en) | 1990-10-30 |
FI873398A0 (en) | 1987-08-05 |
MW5287A1 (en) | 1988-11-09 |
ES557662A0 (en) | 1988-11-16 |
IT8519443A0 (en) | 1985-02-08 |
IT1200382B (en) | 1989-01-18 |
RO100056A2 (en) | 1991-03-23 |
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Inventor name: MANZATI, CLAUDIO Inventor name: IACCHERI, ENNIO Inventor name: PIRO, PAOLA |