WO1987007384A1 - Dispositif d'analyse immunologique enzymatique - Google Patents

Dispositif d'analyse immunologique enzymatique Download PDF

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Publication number
WO1987007384A1
WO1987007384A1 PCT/US1987/000198 US8700198W WO8707384A1 WO 1987007384 A1 WO1987007384 A1 WO 1987007384A1 US 8700198 W US8700198 W US 8700198W WO 8707384 A1 WO8707384 A1 WO 8707384A1
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WO
WIPO (PCT)
Prior art keywords
immunochemically
immunochemically reactive
vessel
antibody
aforesaid
Prior art date
Application number
PCT/US1987/000198
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English (en)
Inventor
Michael J. Walsh
Original Assignee
Quidel
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Filing date
Publication date
Application filed by Quidel filed Critical Quidel
Publication of WO1987007384A1 publication Critical patent/WO1987007384A1/fr

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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
    • 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

Definitions

  • This invention relates to immunology, and, more particularly to immunoassays generally and to enzyme immunoassays specifically.
  • the antibody or antigen to be determined was "sandwiched" by an immunochemical reaction between a solid surface treated with an immunological species reactive with the species to be determined and the same or a different reactive immunological species which has been coupled to an enzyme label.
  • the principles of these types of ELISAs are discussed by Belanger, L., Alternative Approaches in Enzyme Tmmunoassays, Scand. J. Immunol., Vol 8, Suppl. 7, 33-41, 1978 (Chapter 4 in
  • Filter paper, glass, various plastics (chemical polymers), and other solid support surfaces have been used for many years. Examples of such a system which used antibody (or antigen) coated polystyrene beads are described by Bohn. et al., in U. S. Patent No.
  • the invention is embodied in a kit for carrying out an enzyme immunoassay to determine the presence, absence or amount of an immunochemically bindable substance.
  • the kit includes, along with packaging, information, protective packing, etc., a soluble immunochemically binding substance which is reactive with the immunochemically bindable substance which is to be determined, said soluble immunochemically binding substance being conjugated to an enzyme or other label which is capable, upon reaction with a developer, of developing a distinctive color and which is in a form which will dissolve in a liquid sample suspected of containing the bindable substance to be determined.
  • the kit also includes a column comprising an elongate at least partially transparent tube having a proximal end adapted to receive liquid sample and a distal end adapted to discharge the liquid sample when it has passed through the tube, solid particle packing filling at least a portion of the tube intermediate the proximal and distal ends thereof, at least one mutually contiguous assay group of the solid packing particles having bound on the surface thereof an insoluble immunochemically binding substance which is reactive with the immunochemically bindable substance to be determined and which upon reaction with the bindable substance to the surface of the solid particles and a developing reagent which is reactive with the conjugated enzyme or other label to form upon reaction with said enzyme or other label a distinctive color.
  • the immunochemically bindable substance to be determined is frequently an antigen but may be an antibody or other immunological substance. If the substance to be determined is an antigen, then the soluble and insoluble immunochemically binding substances may be either antibodies or parts of antibodies to the antigen to be determined and immunochemically reactive species of any type e.g. virus or virus fragments, bacterial cell constituents, haptens on a carrier, etc. While reference is made here to antigens and antibodies, any suitable immunochemical couple may be used.
  • Polyclonal antibodies or parts thereof may be used in insoluble form and in soluble form, but it has been found to be advantageous in some instances that at least one of the soluble and insoluble immunochemically binding substances is a monoclonal antibody, and in some instances there are advantages in having both the soluble and insoluble immunochemically binding substances in the form of different monoclonal antibodies or parts thereof to the antigen to be determined.
  • any solid particulate matter may form the solid support in the column. It has been found convenient, however, to provide solid packing particles in the form of microbeads of, for example, polystyrene, nylon, agarose, cellulose or a combination of these. At least a portion of the beads, or other particles, such as cellulose or modified cellulose fibers, fritted glass, etc., have the insoluble immunochemically binding substance bound to the surface thereof.
  • a mutually contiguous reference group of the solid packing particles having bound to the surfaces thereof a biochemical substance which does not bind the bindable substance to be determined is very convenient and increases the confidence level in the assay. Such a control is not fundamental to the invention, however, and is merely a desired option.
  • the biochemical substance is preferably bound to the surface of the reference solid packing particles immunochemically equivalently to the binding of the insoluble immunochemically binding reagent to the assay packing particles.
  • An immunochemically equivalent binding means as the phrase is used here, that the reagents and the procedures for binding are the same or are sufficiently similar that the binding reagent system is immunochemically inert to or reacts with all significant components of the sample in substantially the same way and degree regardless of which immunochemical substance is bound.
  • the column comprises at least two assay groups of solid packing particles having bound to the respective surfaces thereof immunochemically different insoluble immunochemically binding substances for substantially simultaneously detecting, in the respective assay groups, at least two immunochemically different bindable substances in a single sample liquid.
  • the column comprises means of concentrating the particles having bound thereto immunochemically binding substances adjacent the interior surface of the tube to increase the visibility of such particles throughout the wall of the tube. This means is, in one form, a short cylinder closed at both ends with projections extending outwardly.
  • the cylinder resides in the center of the column, by reason of the spacers which keep the cylinder surface approximately equidistant from the column walls, and concentrates the immunochemically coated particles adjacent the column walls where they are more visible than would be the case if the concentrating means were not present.
  • the invention also encompasses a method for determining the presence, absence or amount of an immunochemically bindable substance in a liquid sample.
  • the method steps may include, in any of many desired sequences of steps, the step of incubating in the liquid sample suspected of containing the immunochemically bindable substance to be determined a conjugate comprising a soluble immunochemical binding substance for the bindable substance and a label which is capable of reacting with a developer to form a colored product, the binding substance being specifically immunochemically reactive with the bindable substance.
  • the product of the incubation if the bindable substance to be determined is present in the sample, is a conjugate of the binding substance, the bindable substance and the label.
  • the product of the preceding step is passed through a column comprising an elongate at least partially transparent tube having a proximal end adapted to discharge the liquid sample when it has passed through the tube, solid particle packing filling at least a portion of the tube intermediate the proximal and distal ends thereof, at least one mutually contiguous assay group of the solid packing particles having bound on the surface thereof an insoluble immunochemically binding substance which is reactive with the immunochemically bindable substance to be determined, and which upon reaction with the bindable substance, binds the bindable substance to the surface of the solid particles.
  • a principal reaction product, if the bindable substance is present in the sample, is a sandwich of insoluble binding substance on the particles, the bindable substance, the soluble binding substance and the label.
  • a developing solution is then passed through the column.
  • the developing reagent which is reactive with the label to form upon reaction with said label a distinctive color.
  • the result of this series of steps is a colored band or portion in the column the intensity of which is proportional to the amount of bindable substance in the sample.
  • the assay can, in many circumstances, be carried out as a one-step assay in which all of the reagent and the sample are simply introduced into the device of this invention substantially simultaneously.
  • the immunochemically bindable substance to be determined is an antigen
  • the soluble immunochemically binding substance is an antibody which is conjugated to an enzyme label
  • the insoluble immunochemically binding substance is an antibody.
  • At least one of the soluble and insoluble immunochemically binding substances may be a monoclonal antibody, or both the soluble and insoluble immunochemically binding substances may be, respectively, different monoclonal antibodies to the antigen to be determined.
  • Figure 1 is a side view of a device constructed and arranged in accordance with the principles of this invention.
  • Figure 2 is a cross section of the device as shown in Figure 1 taken on the diameter thereof.
  • Figure 3 is a cross-section of an alternative configuration for the device of this invention.
  • Figure 4 illustrates the inclusion of solutions in a kit assembled in accordance with this invention.
  • the concept of the present invention involves a rapid immunoassay based .on the flow-through, one- direction properties of a small chromatographic column.
  • Specific "sandwiching" antibodies are bound to a solid support of microbeads or microspheres, or other solid particles, as one-half of the antibody-antigen-antibody- enzyme complex.
  • a solution phase antibody-enzyme conjugate forms the other half of the complex and effectively sandwiches and is thereby immobilized by any antigen present in the sample. Excess Ab-enzyme conjugate is then rinsed away using a wash solution.
  • a developer or substrate solution is added, in this case utilizing a precipitating chromophore as a byproduct of the antibody-enzyme conjugate - substrate reaction.
  • the presence of the precipitated chromophore or color on the microbeads indicates the presence of the specific enzyme.
  • This immobilization of the antibody-enzyme conjugate, on the microbeads signals specific "sandwiching" of the antigen found in the patient's sample. Color formation on the beads therefore indicates the presence of the antigen in the patient sample, or a positive result.
  • a wash step rinses away any residual "non-sandwiched" antibody enzyme conjugate from the microbeads, and there is no substrate color formation on the microbeads.
  • a color-forming enzyme assay is described but only as an example. Fluorescent labels, etc., may be used. The result is a rapid, simple enzyme immunoassay system which requires very little manipulation and an easy-to-read end-point determination. Note here also the possible inclusion of a negative control region of microbeads or plastic filter as an additional advantage - ease of readability.
  • the Ab-enzyme conjugate is preincubated with the patient sample and, when antigen is present, one half of the "aandwich" occurs - the antibody-enzyme conjugate binds to the antigen in solution.
  • the system is tailored so that this reaction takes place very quickly, usually in less than five minutes.
  • This reaction fluid, sample and antibody-enzyme conjugate is then introduced onto the top of the enzyme immunoassay column and allowed to flow through the column by gravity force, though suction could be used.
  • Conjugate-bound antigen is recognized by the antibodies located on the microbeads and bound by them as the sample flows through the column.
  • the sample may be allowed to incubate in place for a. short time to assure an efficient reaction.
  • the presence of antigen in the sample allows for the immobilization of the antibody- enzyme conjugate on the surface of the microbead. Without antigen present, the antibody-enzyme conjugate flows through the column unaffected.
  • the column is then rinsed with a wash buffer to remove any remaining antibody-enzyme conjugate which might otherwise react with the substrate and produce a false positive result. After the wash, only that antibody-enzyme conjugate which is specifically sandwiched through the antigen-antibody solid surface remains. Due to the one-direction flow of this device, this wash step proves to be simple and very efficient in removing unbound antibody-enzyme conjugate.
  • the developer is then loaded onto the column and flows down through the column which includes the potential antigen sandwiching region. Should this substrate contact immobilized enzyme (from the antibody- enzyme conjugate), a reaction occurs which results in a precipitating chromophore and color formation on the beads.
  • color formation signals a positive result, and lack of color a negative result; other signals may also be used to detect a positive reaction.
  • the column is constructed in a transparent tube to aid visualization.
  • the column could consist of two zones - a test or indicator region, and a control region.
  • Antibody specific to the antigen being tested for is bound to the solid surface of the test or indicator region.
  • Nonspecific antibody or protein is bound to the solid surface of the control region.
  • the surfaces are stacked vertically in the enzyme immunoassay column to accommodate an easy visual reference of the test layer to the control layer.
  • this column concept can be used as a series of stackable units, each to determine a single analyte or its control. These units are stacked during assembly to form one column which would, as the sample percolated through, run several different assays. A mixture of conjugates could then be poured through, followed by the substrate solution.
  • the solid surfaces of both regions are microbeads composed of, but not limited to, polystyrene, nylon, agarose, cellulose, or a combination thereof.
  • Alternative solid surfaces include various inserts, filters, fritted surfaces, paper, etc.
  • the key property is a surface to which antibody can be bound, either covalently or otherwise, through any number of biochemical reactions and through which fluids can pass freely, subject to the physical constraints of the system.
  • Another property is the transparency of the column to allow for the visual end-point readability.
  • the column also allows for a one-direction flow of reaction fluid through and by a potential sandwich forming region, thereby enabling localization. immobilization, and concentration of enzyme-containing complexes, and subsequent intensification of specific color formation.
  • the design of this invention also includes the possibility of antibody detection.
  • a specific antigen or an antibody specific for an antibody may be bound to the solid surface and facilitate detection of another antibody.
  • Certain disease states are monitored by the immunological spikes or sudden titer increases in specific antibody types or class.
  • This assay design permits convective mixing of the sample and/or other test reagents as they percolate through the column matrix solid phase. This is an advantage over assay systems where no stirring or mixing occurs as the test runs. Mixing leads to greater sensitivity or a faster assay at an equivalent sensitivity. Plus, the mixing that is accomplished, as the sample flows, requires no hands-on time, unlike the vortexing needed in a coated tube assay, or the rocking required in a latex hemagglutination-type test.
  • a device may be constructed according to this invention using a clear or transparent walled vessel of some kind, such as the cylindrical vessel 10, with a fluid inlet 12, shown in Figure 1 in which there is disposed a band, or a plurality of bands, of small particles, e.g. microbeads, to which one or an immunochemical couple is bound, thus forming a solid phase having thereon one immunochemically active member of a couple, the other member of which couple would normally be the species to be determined.
  • a clear or transparent walled vessel of some kind such as the cylindrical vessel 10
  • a fluid inlet 12 shown in which there is disposed a band, or a plurality of bands, of small particles, e.g. microbeads, to which one or an immunochemical couple is bound, thus forming a solid phase having thereon one immunochemically active member of a couple, the other member of which couple would normally be the species to be determined.
  • This band of immunologically reactive surfaced particles is identified at 14, and may comprise, among the many possible configurations and c ompo s it i ons , g l a s s , p o l y s t y r e n e , polymethylmethacrylate, silica or other beads, of porous particles or fibers, which have bound on the surface antibodies, antigens, haptens, etc.
  • the band is shown as developed, e.g. blue compared with white or off-white before development.
  • the immunochemical band It is desirable to define the immunochemical band by a band of non-immunochemically active particles (or particles of different immunochemical activity) shown at 16 and 18. It is also desirable to provide an absorbent pad 20 which may also support the layers just mentioned.
  • the absorbent pad may be of cotton, paper or other absorbent material.
  • Figure 3 depicts an alternative embodiment wherein the container 110 with fluid inlet 112 contains a plurality of immunochemically active solid particle bands separated by non-immunochemically active bands.
  • band 114 is immunochemically active and is defined by bands 116 and 118 which are of different or no immunochemical activity.
  • Band 118 also defines the top of immunochemically active band 120.
  • Band 122 is immunochemically non-reactive and defines the bottom of band 120 and the top of immunochemically active band 124.
  • Band 126 is immunochemically non-reactive and defines the bottom of band 124 and the top of immunochemically active band 128 the bottom of which is defined by immunochemically nonreactive band 130.
  • An absorbent body 132 may be provided.
  • the invention may be embodied in a kit which includes one or more solutions, such as, for example a container 134 of antibody-enzyme conjugate, for example, or antigen-conjugate solution, etc. or even of wash solution 136 and container 138 of developer solution 138. Suitable boxes, supports, etc. may also be provided.
  • solutions such as, for example a container 134 of antibody-enzyme conjugate, for example, or antigen-conjugate solution, etc. or even of wash solution 136 and container 138 of developer solution 138.
  • Suitable boxes, supports, etc. may also be provided.
  • the design of this invention is such that there is a minimum of hands-on manipulation, a common source of error, and no external equipment is required. Its simplicity of operation and ease of readability are two of its greatest assets. Also, because the invention is self contained, it lends itself readily to automation and batching of samples.
  • the assay column may be envisioned as stackable units which may be interconnected so that sample flows from one to the next below, etc., eventually flowing into a reservoir. This permits testing for multiple analytes as well as multiple controls in a single specimen, with no significant increase in time or assay complexity. Furthermore, the column, when viewed from the side, appears to intensify the color, compared to known systems having a filter with color viewed from above. The concentration of bindable substance, sandwich and colored enzyme product into a very thin layer increases the sensitivity of the assay. Another advantage is ease of use.
  • the assay column may be freestanding. Samples are simply added and then allowed to flow through at a controlled rate, which can be optimized for each test. Again, while the sample flows, no hands-on time is required.
  • the column may be self-contained, with a sample and wash collecting reservoir, running the assay becomes simpler and neater, with no additional sample handling or complicated disposal of spent reagents or
  • Assay columns may have a device attached to the top, a reagent/ sample distribution chamber which would permit all the test samples, reagents, and wash solutions to be added initially to the chamber at one time. The reagents would then flow out of the chamber in the proper order to permit the test to run with no additional manipulation.
  • the device is at least partially transparent plastic or glass and is inert.
  • Any porous physically and chemically stable material with the ability to bind, covalently or noncovalently, a variety of substances, including proteins - antibodies, allergens, antigens, drugs and their metabolites, bacteria and digested protein from bacteria, polypeptides, steroids, hormones, enzymes, cofactors, vitamins may be used.
  • Low nonspecific binding of proteins, including labelled antibody, antigen, drugs, allergens is desired. Both a high surface area and a good flow-through rate are desirable and advantageous.
  • Polystyrene, nylon, agarose, cellulose, polyvinyl chloride, paper, glass fiber, scintered glass, or a combination of particles of any of the above substances may be used within the device.
  • a number of groups of particles containing bound substances e.g. different antigens, different drugs, or a mixture thereof, etc. to accomplish a number of analyte tests in one procedure is contemplated.
  • Liposomes containing chromophores, enzyme substrates, antibody-enzyme conjugates or any other potential reactant may be included.
  • Liquid Enzyme-Conjugates and Labelled Components include any items listed above, but not so limited, may contain any of a variety of enzymes used in EIA technology such as Alkaline Phosphatase, Horseradish Peroxidose, B-Galactosidase, but any color forming label may be used.
  • this invention would also work well with fluorescent conjugates, such as Fluorescein Isothiocyanate (FITC) , Rhodamine T, Rhodamine M, Rhodamine ITC, etc.
  • FITC Fluorescein Isothiocyanate
  • Rhodamine T Rhodamine T
  • Rhodamine M Rhodamine M
  • Rhodamine ITC etc.
  • histological stains could be used to localize the presence of certain enzymes, whether they be in the sample itself or part of a conjugate.
  • the properties should include - a visual end product, either by eye or with a fluorimeter a source of exciting light, as well as immobility, either through insoluble precipitation at the reaction site, or the property of being bound to the labelling molecule (protein, etc.) itself.
  • alkaline phosphatase enzyme conjugates some of the possibilities include 5-Bromo - 4-Chloro - 3-Indolyl Phosphate, 3- Indoxyl Phosphate, Napththol AS Phosphate, and Nitroblue Tetrazolium.
  • Peroxidase-enzyme conjugates some possibilities include 3-3 Diaminobenzidine
  • Wash solutions may be simple biological buffer systems, such as a phosphate buffered saline, for example, as required for the assay system and may include ionic or non-ionic detergents as necessary.
  • Detergents could include Polyoxy ethylene Sorbitan monolaurate (Tween-20), Nonidet P-40 (NP-40) and Triton X-100.
  • the process of this invention may be carried out in any of a great variety of types of apparatus or kits.
  • the kit shown in the drawing is merely exemplary of one form of a kit which may be used.
  • One important feature of this invention is that it is adaptable to a number of analytes which may be tested for simultaneously sensitive assays for a number of components. It is possible, for example, to provide an immunochemical assay column of the type described in this invention which can be used to detect the presence or absence of HCG antigen, strep-A, drugs of abuse, allergens, specific IgE antibodies, or any other combination of non-interfering immunochemical materials. In some instances, it may be desirable to test the same sample for two or more different antibodies or antigens. As pointed out above, the invention permits a very rapid immunochemical assay, which is more sensitive than many previous commercially available assays, which has a very high degree of reliability and repeatability, and which is inexpensive to manufacture and simple to use.
  • This invention is suitable for use in clinical laboratories, hospitals, and by individuals to aid in the diagnosis of disease or in the early detection of pregnancy, or in the detection of the presence of drugs of abuse, or other immunochemical materials.

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Abstract

Dispositif permettant de concentrer un produit en sandwich d'analyse immunologique enzymatique dans une bande très étroite (14) dans une colonne (10) pour le développement et la lecture visuelle. Le dispositif peut être réalisé en utilisant un récipient ou une colonne translucide ou transparent (10), comportant un orifice d'entrée de fluide, dans lequel est disposée une bande (14) ou une pluralité de bandes (14) de petites particules auxquelles est lié un couple immunochimique, l'autre organe du couple étant l'espèce à déterminer. La bande immunochimique (14) est définie par des bandes (16), (18), de particules immunochimiquement inactives. Un coussinet absorbant (23) peut soutenir les bandes.
PCT/US1987/000198 1986-05-30 1987-02-02 Dispositif d'analyse immunologique enzymatique WO1987007384A1 (fr)

Applications Claiming Priority (2)

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US86939486A 1986-05-30 1986-05-30
US869,394 1986-05-30

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WO1987007384A1 true WO1987007384A1 (fr) 1987-12-03

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Cited By (11)

* Cited by examiner, † Cited by third party
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WO1995019569A1 (fr) * 1994-01-13 1995-07-20 Abion Beteiligungs- Und Verwaltungsgesellschaft Mbh Colonnes de reaction destinees a des mesures multiples et simultanees et procede
WO1996042017A1 (fr) * 1995-06-08 1996-12-27 Tepnel Medical Limited Determinations immunologiques
DE19543240A1 (de) * 1995-11-20 1997-05-22 Abion Ohg Einwegauftragsvorrichtung sowie Kit
WO1997028448A1 (fr) * 1996-01-30 1997-08-07 Abion Beteiligungs- Und Verwaltungsgesellschaft Mbh Materiau support pouvant etre charge par un flux traversant pour dosages en phase solide
WO2002008457A2 (fr) * 2000-07-25 2002-01-31 Axaron Bioscience Ag Procede et dispositif d'analyse d'echantillons chimiques ou biologiques
EP1223429A1 (fr) * 2001-01-13 2002-07-17 Dentognostics GmbH Méthode pour la détection de micro-organismes vivants
WO2003098215A1 (fr) * 2002-05-16 2003-11-27 Medmira Inc. Dispositif de detection rapide d'anticorps de la vaccine, procede et kit d'essai y relatifs
WO2008145722A1 (fr) 2007-05-30 2008-12-04 Senova Gesellschaft für Biowissenschaft und Technik mbH Dispositif et procédé pour essais de liaison
CN102213717A (zh) * 2010-04-02 2011-10-12 王立莉 免疫纳米粒子层析测定方法及实施该方法的装置
EP2487490A1 (fr) 2011-02-11 2012-08-15 FZMB GmbH Forschungszentrum für Medizintechnik und Biotechnologie Test de liaison hétérogène doté d'une capacité d'évaluation optique améliorée ou phase solide poreuse pour tests de liaison dotés d'une capacité d'évaluation optique améliorée
CN112505026A (zh) * 2020-11-23 2021-03-16 深圳大学 一种大豆过敏原可视化凝胶检测装置和方法

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US4459358A (en) * 1982-12-29 1984-07-10 Polaroid Corporation Multilayer element for analysis
JPS6017358A (ja) * 1983-03-08 1985-01-29 Konishiroku Photo Ind Co Ltd 分析容器
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US3888629A (en) * 1971-09-08 1975-06-10 Kenneth Dawson Bagshawe Performance of chemical or biological reactions within an absorbent matrix pad
US3951748A (en) * 1974-11-11 1976-04-20 Medical Products, Inc. Sensitized matrix for detection of disease
US4180383A (en) * 1975-04-07 1979-12-25 Becton, Dickinson And Company Chamber holder for immobilized immunoadsorbent
US4256693A (en) * 1978-06-06 1981-03-17 Fuji Photo Film Co., Ltd. Multilayered integral chemical analysis element for the blood
US4246339A (en) * 1978-11-01 1981-01-20 Millipore Corporation Test device
US4366241B1 (fr) * 1980-08-07 1988-10-18
US4366241A (en) * 1980-08-07 1982-12-28 Syva Company Concentrating zone method in heterogeneous immunoassays
WO1982002211A1 (fr) * 1980-12-22 1982-07-08 Chandler Howard Milne Dispositif et procede de detection d'antigenes et d'anticorps
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WO1995019569A1 (fr) * 1994-01-13 1995-07-20 Abion Beteiligungs- Und Verwaltungsgesellschaft Mbh Colonnes de reaction destinees a des mesures multiples et simultanees et procede
WO1996042017A1 (fr) * 1995-06-08 1996-12-27 Tepnel Medical Limited Determinations immunologiques
DE19543240A1 (de) * 1995-11-20 1997-05-22 Abion Ohg Einwegauftragsvorrichtung sowie Kit
WO1997028448A1 (fr) * 1996-01-30 1997-08-07 Abion Beteiligungs- Und Verwaltungsgesellschaft Mbh Materiau support pouvant etre charge par un flux traversant pour dosages en phase solide
WO2002008457A3 (fr) * 2000-07-25 2002-11-21 Basf Lynx Bioscience Ag Procede et dispositif d'analyse d'echantillons chimiques ou biologiques
WO2002008457A2 (fr) * 2000-07-25 2002-01-31 Axaron Bioscience Ag Procede et dispositif d'analyse d'echantillons chimiques ou biologiques
US7455967B2 (en) 2000-07-25 2008-11-25 Axaron Bioscience Ag Device for analyzing chemical or biological samples
WO2002055733A2 (fr) * 2001-01-13 2002-07-18 Dentognostics Gmbh Procede pour deceler des micro-organismes vivants
WO2002055733A3 (fr) * 2001-01-13 2002-09-12 Dentognostics Gmbh Procede pour deceler des micro-organismes vivants
EP1223429A1 (fr) * 2001-01-13 2002-07-17 Dentognostics GmbH Méthode pour la détection de micro-organismes vivants
WO2003098215A1 (fr) * 2002-05-16 2003-11-27 Medmira Inc. Dispositif de detection rapide d'anticorps de la vaccine, procede et kit d'essai y relatifs
WO2008145722A1 (fr) 2007-05-30 2008-12-04 Senova Gesellschaft für Biowissenschaft und Technik mbH Dispositif et procédé pour essais de liaison
CN102213717A (zh) * 2010-04-02 2011-10-12 王立莉 免疫纳米粒子层析测定方法及实施该方法的装置
EP2487490A1 (fr) 2011-02-11 2012-08-15 FZMB GmbH Forschungszentrum für Medizintechnik und Biotechnologie Test de liaison hétérogène doté d'une capacité d'évaluation optique améliorée ou phase solide poreuse pour tests de liaison dotés d'une capacité d'évaluation optique améliorée
CN112505026A (zh) * 2020-11-23 2021-03-16 深圳大学 一种大豆过敏原可视化凝胶检测装置和方法

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