WO2003060517A2 - Composition adhesive diffusible pour dispositifs reactifs secs multicouche - Google Patents

Composition adhesive diffusible pour dispositifs reactifs secs multicouche Download PDF

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Publication number
WO2003060517A2
WO2003060517A2 PCT/IB2003/000055 IB0300055W WO03060517A2 WO 2003060517 A2 WO2003060517 A2 WO 2003060517A2 IB 0300055 W IB0300055 W IB 0300055W WO 03060517 A2 WO03060517 A2 WO 03060517A2
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WO
WIPO (PCT)
Prior art keywords
sample
layer
analyte
reagent
absorbent
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PCT/IB2003/000055
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English (en)
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WO2003060517A3 (fr
Inventor
Lloyd S. Schulman
Michael J. Pugia
Karlheinz Hildenbrand
Spencer H. Lin
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Bayer Healthcare Llc
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Application filed by Bayer Healthcare Llc filed Critical Bayer Healthcare Llc
Priority to AU2003201460A priority Critical patent/AU2003201460A1/en
Priority to US10/459,825 priority patent/US20030215358A1/en
Publication of WO2003060517A2 publication Critical patent/WO2003060517A2/fr
Publication of WO2003060517A3 publication Critical patent/WO2003060517A3/fr
Priority to US10/966,858 priority patent/US7713474B2/en

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    • 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
    • G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • 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
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/525—Multi-layer analytical elements

Definitions

  • Dry reagent analytical devices typically involve absorbent pads containing dispersed reagent systems which react with analytes (components to be detected) in fluid test samples applied to the device to provide a detectable response. Certain of these devices involve an enzymatic reaction with the analyte in the presence of a peroxidase and a hydroperoxide to cause a detectable color change in a redox dye and are normally based on the use of filter paper as the absorbent pad. Other such devices operate on the basis of immunoreactivity of a labeled antibody located in the reagent device which specifically binds with an analyte in the test sample to provide a detectable response in a specified region of the test device. Nitrocellulose is a preferred base material for this sort of device due to its flow through properties.
  • incompatible chemicals in dry reagent systems There are many examples of incompatible chemicals in dry reagent systems.
  • the base in white blood cell reagents causes premature hydrolysis of protease substrate.
  • Iron in occult blood reagents causes premature oxidation of redox dye indicators to their colored form, which is also the result of the presence of iodate in glucose reagents.
  • the copper can oxidize redox indicators such as tetramethylbenzidine to their colored form in the absence of creatinine.
  • Tests for occult blood in urine can be skewed by the presence of ascorbate in the urine test sample which acts as a reducing agent to cause false negative results and urine protein tests can be rendered inaccurate by the presence of buffers in the urine sample being tested.
  • Dry assay devices for determining white blood cells in urine can be influenced by interference due to proteins in the urine sample and whole blood assays, such as blood glucose and blood CKMB, suffer from interference caused by red blood cells.
  • the present invention provides a means for alleviating these problems by joining two layers of a dry reagent device, at least one of which layers contains a reagent for detection of an analyte, with a test fluid permeable layer comprising a blend of an aqueous based polymer dispersion and a water soluble polymer, which blend has been cast and dried to form an adhesive layer.
  • the top layer(s) must allow the test sample to pass to the lower layers while continuing to separate certain interfering chemicals and/or biochemicals.
  • metals such as copper or iron should be separated from redox indicators and bases from protease substrates.
  • Oxidants such as iodate and reactants such as ascorbate need to be separated from redox indicators such as tetramethylbenzidine.
  • the contact between the layers was either insufficient to allow the reactants to pass from one layer to the adjacent layer when that was desired, or the reactants migrated from one layer to another when that was not desired.
  • Nerbeck in U.S. 3,993,451 uses adhesives to secure reagent containing particles to a substrate layer.
  • the particles may be covered with a porous layer through which a component contained within a sample may pass to reach the reagent containing particles.
  • the adhesive is not used as a layer which separates reagent layers from detecting layers.
  • the solid particles form separate detecting units which do not rely on movement of the reaction product with an analyte into an adjacent layer for detection.
  • Japanese Patent 5-18959 discloses the use of a hydrophobic polymer which does not swell in water as an adhesive to secure reagent layers and Japanese patent 5-26875 discloses the use of a porous layer comprising a fluorine containing polymer as an adhesive to secure reagent layers.
  • the polymers used in these Japanese systems are hydrophobic and consequently, they hinder rapid movement of sample fluids through the layers. For rapid testing, the sample fluid should pass through the layers of the device within less than one second. A water soluble adhesive would permit rapid movement of the sample fluid, but would cause the layers to separate as the adhesive begins to dissolve.
  • the Greenquist '311 patent mentioned above also discloses a multilayer device for medical testing. Although the concept is valuable, in practice the multilayer device is not as satisfactory as would be desired. The layers must perform their intended function without interfering with the functioning of the adjacent layers. At the same time, the sample fluid must pass rapidly through the layers so that a result can be determined rapidly. Thus, the layers must act independently while not limiting the movement of the sample fluid. The present inventors have overcome these problems, in the multilayer device to be described below.
  • U.S. patent 4,824,640 a transparent layer is disclosed which is useful for containing analytical reagents which consists of a water soluble or water swellable component and an essentially insoluble film forming component.
  • analytical reagents which consists of a water soluble or water swellable component and an essentially insoluble film forming component.
  • a similar layer is employed in U.S. patent 6,187,268 Bl as an overcoat over a dry reagent layer.
  • the present invention involves a device suitable for the detection of an analyte in a fluid sample which comprises at least a first absorbent layer and a second absorbent layer. At least one of the layers contains a reagent system for the detection of the analyte.
  • the layers have dispersed between them an adhesive layer which is permeable to components of the fluid sample and which comprises a blend of an aqueous based polymer dispersion and a water soluble polymer which has been cast and dried to form the adhesive layer.
  • the fluid diffusable adhesive composition used in the present invention can be used to construct several types of multilayer devices, which at least have a diffusable adhesive composition between two absorbent layers.
  • This type of multilayered reagent can have open or sealed edges.
  • the adhesive layer holds discrete layers together and either of the discrete layers can be attached to a plastic support, such as a strip handle or a cassette, so that the person using the device can avoid direct contact with the sample fluid. Since the adhesive is permeable, it allows reagents and components of the fluid test sample to flow through the adhesive layer.
  • the multi-layer device can be made so that when a fluid sample is placed on the first absorbent layer, it is spread across the surface of the layer without interacting with the components of the sample.
  • the first absorbent layer may react with interfering components of the sample, permitting the component to be measured (the analyte) to pass through the adhesive layer to the second absorbent layer.
  • the first absorbent layer may react with the analyte, which is measured in place or the reaction product may pass through the adhesive layer to the second absorbent layer, where it is detected.
  • the second absorbent layer may absorb and retain a component of the fluid sample which has passed through the adhesive layer or it may contain a reagent which reacts with the analyte or the reaction product of the analyte received from the first absorbent layer.
  • the adhesive layer can be made so that it prevents the passage of components of the sample by physical separation. Thus, it may serve to concentrate the analyte by passing it while preventing other components from reaching the second absorbent layer.
  • the adhesive layer may contain additives which chemically bind certain of the sample components. In one embodiment, the adhesive layer passes certain components of the sample, leaving the more concentrated analyte on the first absorbent layer.
  • the water dispersible polymer may be either an anionic or cationic polyurethane dispersion, preferably an anionic polyurethane, in combination with a water soluble polymer, preferably a polyethylene oxide, a polyvinyl pyrrolidone, or a polyvinyl alcohol.
  • the permeable adhesive layer can contain exchange resins and ascorbate scavengers to remove buffering and ascorbate interference from the test sample.
  • the cation exchange resins may include those with oxidative anions such as bromate, iodate, periodate, and chromate or those containing polysulfonic acids, polycarboxylic acids, or polyphosphonic acids with transition metal oxidants such as iron, cobalt, or copper.
  • the permeable adhesive layer can also contain protein binding polymers to separate interfering proteins or antibodies from the sample as well as fillers such as TiO 2 or BaSO 4 to adjust the opacity or reflectance behavior of the reagent device.
  • Suitable protein binding polymers include, for example, positively charged polymers such as polyamines and polyamides and negatively charged polymers such as polysulfonic, polycarboxylic, and polyphosphonic acids. These polymers may be incorporated into the permeable layer by mixing into the adhesive formula and coating onto the reagent layers.
  • a multi-layer device for detecting an analyte (i.e. a substance to be detected) in a fluid sample includes a first absorbent layer for receiving a fluid sample, a second absorbent layer for receiving and absorbing a portion of the sample from the first absorbent layer, and a diffusable (permeable) adhesive layer disposed between the two absorbent layers, the adhesive layer not only binding the absorbent layers together but being capable of reacting with portions of the fluid sample to prevent their passage or to physically block passage of portions of the fluid sample. Additional absorbent layers and adhesive layers may be added as needed to carry out any particular analysis, as will be evident to those skilled in the art.
  • the first absorbent layer has several possible functions. It may merely absorb a fluid sample and spread it across the surface of the adhesive layer. Alternatively, it may react with interfering components of the sample, with the analyte passing through the adhesive layer to the second absorbent layer. In another alternative, the first absorbent layer may react with the analyte, which is then measured in place, or the reaction product is passed through the adhesive layer to the second absorbent layer for detection.
  • the second absorbent layer also has several possible functions. It may absorb a portion of the sample passed through the adhesive layer, thereby concentrating the analyte in the first absorbent layer. Alternatively, it may receive a portion of the sample including the analyte and then react with the analyte to provide a product which is measured. In another alternative, the second absorbent layer may receive the reaction product produced in the first absorbent layer and concentrated by passage through the adhesive layer.
  • the adhesive layer is permeable. Thus, it is capable of making a physical separation of the fluid sample, either passing the analyte and preventing other components from passing through to the second absorbent layer or passing interfering components to concentrate the analyte.
  • the adhesive layer may react with certain components of the sample, thus trapping them in the adhesive layer. Or, it may contain additives capable of reacting with certain components and thereby blocking their passage through the adhesive layer.
  • the basic elements of the fluid permeable, adhesive membrane useful in the present invention involve an aqueous based polymer dispersion and a water soluble polymer.
  • the permeability of the membrane can be adjusted by varying the ratio of the polymer dispersion to the water soluble component. Typically, this ratio will range from 50 : 1 to 1 : 1 on a weight basis with a ratio of l0:l to 5:l excess of the film forming polymer dispersion being preferred.
  • An increase in the water dispersible polymer will increase the membrane's permeability, which is desirable when faster flow is desired.
  • increasing the concentration of the water soluble polymer will decrease the membrane's permeability in cases where greater contact, and accordingly more mixing of the reagents, is desired.
  • polyester-diols which generally have an average molecular weight of between 300 and 2000
  • diisocyanates the result is the formation of high molecular weight polyester urethanes.
  • Polyurethane dispersions have been commercially important since 1972.
  • Polyurethane ionomers are structurally suitable for the preparation of aqueous two phase systems. These polymers, which have hydrophilic ionic sites between predominantly hydrophobic chain segments are self dispersing and, under favorable conditions, form stable dispersions in water without the influence of shear forces and in the absence of dispersants.
  • anionic polyurethanes such as Bayhydrol DLN
  • diols bearing a carboxylic acid or a sulfonate group are introduced and the acid groups are subsequently neutralized, for example, with tertiary amines.
  • Sulfonate groups are usually built via a diaminoalkanesulfonate, since these compounds are soluble in water.
  • the resulting polyurethane resins have built ionic groups which provide mechanical and chemical stability as well as good film forming adhesion properties.
  • Cationic polyurethane dispersions such as Praestol E 150 from Stockhausen
  • Chemical Co. may also be used in forming the membrane.
  • One method of preparing cationic polyurethanes is by the reaction of a dibromide with a diamine. If one of these components contains a long chain polyester segment, an ionomer is obtained.
  • polyammonium polyurethanes can be prepared by first preparing a tertiary nitrogen containing polyurethane and then quaternizing the nitrogen atoms in a second step. Starting with polyether based NCO prepolymers, segmented quaternary polyurethanes are obtained.
  • polyurethane ionomers The most important property of polyurethane ionomers is their ability to form stable dispersions in water spontaneously under certain conditions to provide a binary colloidal system in which a discontinuous polyurethane phase is dispersed in a continuous aqueous phase.
  • the diameter of the dispersed polyurethane particles can be varied between about 10 and 5000 nm.
  • Polyurethane dispersions which are ionic with the ionic radicals being sulphonate, carboxylate or ammonium groups are particularly suitable.
  • other film forming polymer dispersions such as those formed by polyvinyl or polyacrylic compounds, e.g.
  • polyvinylacetates or polyacrylates By combining the polymer dispersion with a water soluble polymer there is formed a matrix which forms a swellable network like web. The tighter the web, the smaller the pores and the slower the flow of the test fluid through the matrix.
  • water soluble polymers the known polymers such as, for example, polyacrylamides, polyacrylic acids, cellulose ethers, polyethyleneimine, polyvinyl alcohol, copolymers of vinyl alcohol and vinyl acetate, gelatine, agarose, alginates and polyvinylpyrrolidone are suitable.
  • This second polymer component is sometimes referred to as the swelling component due to its swellability by absorbing water.
  • Polyethyleneoxides, polyvinylpyrrolidones and polyvinylalcohols are preferred. These polymers can vary widely in molecular weight so long as they are water soluble and miscible with the aqueous polymer dispersion.
  • Polyethylene oxides of a molecular weight from 300,000 to 900,000 g/mol and poly-vinylpyrrolidone having a molecular weight of from 30,000 to 60,000 g/mol are particularly suitable.
  • the molecular weight of the water soluble polymer is not critical so long as they are miscible with the polymer dispersion and allow the incorporation of assay specific reagents such as buffers, indicators, enzymes and antibodies.
  • the finished film should be swellable so as to be permeable to the test fluid.
  • the polymers are dispersed/dissolved in a solvent (preferably aqueous) preparatory to its application to the surface of the dry reagent device by use of a dispenser as in the following examples.
  • aqueous polymer dispersions are mixed with an aqueous solution of the second polymer such as, for example, polyvinyl acetate dispersions with cellulose ethers, polyurethane dispersions with polyvinyl alcohol, polyurethane dispersions with gelatine or polyurethane dispersions with polyvinylpyrrolidone.
  • a surfactant is added to the formulation to enhance its spreadability and a thickener such as silica gel is added to thicken the formulation to a consistency which facilitates it being spread across the surface of the reagent device.
  • the formulation is then applied to the surface of the dry reagent device, such as by a Myer rod applicator or a wiped film spreader, and dried to remove solvent.
  • Typical dry thicknesses of the permeable membrane range from 1 to 100 mils (0.0254 to 2.54 mm).
  • Ascorbate interference with urine occult blood tests can be alleviated by incorporating ascorbate scavengers, such as a metal capable of oxidizing ascorbate bound to a polymer, into the membrane formulation.
  • ascorbate scavengers such as a metal capable of oxidizing ascorbate bound to a polymer
  • Polymer bound metal ascorbate scavengers are described in U.S. Patent 5,079,140.
  • Other oxidizing agents such as iodate and persulfate can be immobilized within the porous membrane to serve as ascorbate scavengers.
  • the diffusible adhesive of the present invention can be used advantageously in conjunction with immunoformats to provide sensitive assays for various analytes.
  • a transparent membrane according to the present invention can be prepared with an immobilized anti-binding label antibody contained therein.
  • this antibody will be immobilized within the membrane by attaching it to a larger entity such as a latex particle which is incorporated into the polymer blend which forms the membrane before it is cast onto the reagent device.
  • a larger entity such as a latex particle which is incorporated into the polymer blend which forms the membrane before it is cast onto the reagent device.
  • anti-FITC can be interspersed in the permeable membrane to capture FITC labeled anti- analyte antibody.
  • anti-analyte antibody labeled with a peroxidase is incorporated into the membrane, so that as test fluid flowing through the membrane analyte contained therein will bind with bound anti-analyte antibody and peroxidase labeled anti-analyte antibody to form a sandwich attached to the membrane thereby preventing the peroxidase from reaching the reagent layer, which contains a peroxide and a redox dye, and providing a colored response.
  • the response produced by the interaction of the analyte, peroxidase, peroxide and redox dye is inversely proportional to the concentration of the analyte in the fluid test sample.
  • reagents for reaction with an analyte in the first absorbent layer which receives the fluid sample may include enzymes such as oxidases, reductases, and proteases commonly used in clinical assays; affinity binders such as antibodies, nucleic acids, antigens, and proteins such as are used in both binding assays and reactions in which the analyte is converted to a detachable chemical.
  • reagents for reaction with an interfering component of the fluid sample may include enzymes to metabolize the interferent, reactants to convert interferent to non- reactive form, and binding agents to trap the interferent.
  • • reagents for reaction with an analyte in the second absorbent layer may include indicators producing signals in response to the analyte and enzymes or reactants for signal amplification.
  • reagents for reaction with an analyte in the second absorbent layer which analyte had been reacted in the first absorbent layer and passed through the adhesive layer include enzymes used in clinical assays and affinity binders used in binding assays and reactions in which a moiety of the analyte is detached.
  • additives to the adhesive layer capable of reacting with components of said sample include affinity binders or enzymes for removing interferents or generating signals.
  • a layer of filter paper is treated with a reagent solution for the analyte which is to be detected.
  • the treated filter paper is then coated with an adhesive layer of the invention and a second layer of untreated filter paper is added, which can serve to concentrate the reagent which has reacted with the analyte and then migrates through the adhesive layer into the untreated filter paper.
  • an adhesive layer includes a material which prevents migration of interfering compounds through the adliesive layer into the reagent layer.
  • a third example includes a top layer with a reagent for the analyte. The product of the reaction of the analyte and reagent passes through the adhesive layer and is detected in the bottom layer.
  • a diffusible adhesive was prepared as follows: (1) 75 g of a 50 mM monobasic phosphate buffer (Fisher, pH 7.0) and 0.5 g of a Pluronic P75 surfactant (BASF) were added to a 250 mL steel beaker. Then while stirring slowly 0.3 g of octanol followed by 5.0 g of Aerosil 200 silica gel (DeGussa AG) were added to the beaker. The stirring rate was increased to about 2000 rpm for several minutes to achieve complete dispersion of the contents of the beaker.
  • BASF Pluronic P75 surfactant
  • DIDNTB 5'.5'-Dinitro-3'.3'- Diiodo-3.4,5.6-Tetrabromophenosulfonephthalein
  • Filter paper (Whatman GF/30cm) was treated with the two solutions in sequence to saturate the paper, after which the treated filter paper was dried for 15 minutes at 90°C to produce the top layer reagent.
  • the adhesive coating solution was cast on the albumin reagent layer to a wet thickness of about 250 ⁇ m, after which the adhesive coated albumin reagent on the filter paper was dried at about 90°C for about 5 minutes.
  • a complete format was assembled in which a layer of glass filter paper (Whatman GF/30cm) was placed on the opposite side of the adhesive layer from the albumin reagent layer. That is, a test device contained three layers, i.e. an albumin reagent layer, a diffusible adhesive layer, and a layer of glass filter paper. This test device was compared with an albumin reagent layer made as described above, but which was not coated with the diffusible adhesive layer.
  • the albumin reagent layer In the first test, a sample containing 500 mg/L of albumin was applied to the albumin reagent layer without an adliesive coating and the result was compared with another 500 mg/L sample placed on the glass filter paper of the composite device. In the later case the albumin would have to pass through the filter paper and the adhesive layer to reach the reagent layer where it would be detected. In the comparative sample, the reagent layer would give an immediate response. The amount of albumin present was determined by reflectance measurement using a CLINITEK 200 instrument. When no sample had been added to the albumin reagent layer, the reflectance was 93.6% at a wave length of 610 nm at 1 minute from beginning of the analysis.
  • the reflectance was found to be 12.8%.
  • the reflectance was found to be 13.0 % when the sample was applied to the glass filter paper and reached the reagent layer by passing through the paper and the adhesive. It can be concluded that the filter paper and the adhesive had substantially no effect on the composition of the sample, which passed through them and reached the reagent layer.
  • a binding reagent layer is added to the diffusible adhesive layer to remove either a competing or interferring component, thus permitting the analyte to reach the detecting reagent layer.
  • a protein blocked diffusible adhesive composition was made in a similar manner to the adhesive composition described in Example I, as follows:
  • step (3) For each gram of the coating solution completed in step (2), 100 ⁇ L of a casein blocking solution was added. The mixture was vortexed in order to produce a homogenous coating solution. The adhesive coating solution was cast onto a peroxidase reagent layer.
  • the peroxidase reagent layer was prepared by: (a) preparing a 10 mg/mL solution of 3, 3', 5 5'tetraethylbenzidine,
  • step (d) dipping the dried paper of step (c) in a solution of 1400 U/mL of stock glucose oxidase
  • step (e) drying the impregnated paper of step (d) for 20 minutes at 40 °C.
  • the adhesive - peroxidase reagent layer combination was pressed onto a binding reagent layer, the binding reagent was prepared by:
  • Aerosil 200 (silica)
  • the sample contained both BSA-FITC (bovine serum albumin - anti- fluorescein isothiocyanate) and HRP-FITC (horseradish peroxidase- anti-fluorescein isothiocyanate), the later competing with the BSA-FITC.
  • BSA-FITC bovine serum albumin - anti- fluorescein isothiocyanate
  • HRP-FITC horse serum albumin - anti- fluorescein isothiocyanate
  • HRP-FITC was present, the reflectance was found to be 62.6 %, while when BSA-FITC was present the relectance was 45.7 %, indicating that HRP-FITC is capable of passing through the membrane when an excess of FITC is achieved
  • This example illustrates the use of a multi-layer device similar to that of Example II for measuring digoxin.
  • the reagent containing a substrate capable of detecting peroxidase and the protein binding layer were prepared as described in Example II. Then, those layers were placed on either side of a diffusible adhesive layer previously described to produce a three-layer device. The combined layers were cut into strips, each strip being covered with a polystyrene strip having square openings which served as sample wells.
  • Test samples were prepared containing 0, 25, 50, and lOO ⁇ g/mL of digoxin and 50 ml of a 50 mg/ml solution digoxin-BSA-HRP (digoxin-bovine serum albumin- horseradish peroxidase), and 50 mg of a 100 ⁇ g/ml solution of anti-digoxin labeled FITC. 45 ⁇ L of each sample mixture was added to a sample well on a strip to bring the sample into contact with the protein binding layer. The sample passed through the top layer and the adhesive layer into the reagent layer where a color response was developed.
  • digoxin-BSA-HRP digoxin-bovine serum albumin- horseradish peroxidase

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
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Abstract

L'invention concerne un dispositif multicouche permettant de détecter un analyte dans un échantillon liquide, qui comprend au moins deux couches et une couche diffusible liquide. Au moins une des couches contient un système réactif pour détecter l'analyte.
PCT/IB2003/000055 2002-01-15 2003-01-13 Composition adhesive diffusible pour dispositifs reactifs secs multicouche WO2003060517A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2003201460A AU2003201460A1 (en) 2002-01-15 2003-01-13 Diffusable adhesive composition for multi-layered dry reagent devices
US10/459,825 US20030215358A1 (en) 2002-01-15 2003-06-12 Liquid permeable composition in dry reagent devices
US10/966,858 US7713474B2 (en) 2002-01-15 2004-10-14 Liquid permeable composition in dry reagent devices

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US34825302P 2002-01-15 2002-01-15
US60/348,253 2002-01-15

Related Child Applications (2)

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US10/459,825 Continuation-In-Part US20030215358A1 (en) 2002-01-15 2003-06-12 Liquid permeable composition in dry reagent devices
US10/966,858 Continuation-In-Part US7713474B2 (en) 2002-01-15 2004-10-14 Liquid permeable composition in dry reagent devices

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WO2003060517A3 WO2003060517A3 (fr) 2003-12-24

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004111638A1 (fr) 2003-06-12 2004-12-23 Bayer Healthcare Llc Composition permeable aux liquides dans des dispositifs a reactif sec
US7713474B2 (en) 2002-01-15 2010-05-11 Siemens Healthcare Diagnostics Inc. Liquid permeable composition in dry reagent devices
US7964372B2 (en) 2004-12-13 2011-06-21 Bayer Healthcare Llc Size self-limiting compositions and test devices for measuring analytes in biological fluids
CN114923965A (zh) * 2022-03-18 2022-08-19 杭州微策生物技术股份有限公司 一种一体式多指标传感器及其制作方法

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GB2085159A (en) * 1980-08-22 1982-04-21 Fuji Photo Film Co Ltd Multilayer element for use in quantitative chemical analysis
US4356149A (en) * 1979-07-02 1982-10-26 Fuji Photo Film Co., Ltd. Multi-layer chemical analytical materials
EP0162302A1 (fr) * 1984-04-19 1985-11-27 Fuji Photo Film Co., Ltd. Elément intégral d'analyse à plusieurs couches
US5171688A (en) * 1988-08-30 1992-12-15 Cholestech Corporation Self-corrected assay device
US5393493A (en) * 1989-02-09 1995-02-28 Fuji Photo Film Co., Ltd. Analytical element for whole blood

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Publication number Priority date Publication date Assignee Title
US3992158A (en) * 1973-08-16 1976-11-16 Eastman Kodak Company Integral analytical element
US4356149A (en) * 1979-07-02 1982-10-26 Fuji Photo Film Co., Ltd. Multi-layer chemical analytical materials
GB2085159A (en) * 1980-08-22 1982-04-21 Fuji Photo Film Co Ltd Multilayer element for use in quantitative chemical analysis
EP0162302A1 (fr) * 1984-04-19 1985-11-27 Fuji Photo Film Co., Ltd. Elément intégral d'analyse à plusieurs couches
US5171688A (en) * 1988-08-30 1992-12-15 Cholestech Corporation Self-corrected assay device
US5393493A (en) * 1989-02-09 1995-02-28 Fuji Photo Film Co., Ltd. Analytical element for whole blood

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7713474B2 (en) 2002-01-15 2010-05-11 Siemens Healthcare Diagnostics Inc. Liquid permeable composition in dry reagent devices
WO2004111638A1 (fr) 2003-06-12 2004-12-23 Bayer Healthcare Llc Composition permeable aux liquides dans des dispositifs a reactif sec
EP1636582A1 (fr) * 2003-06-12 2006-03-22 Bayer HealthCare LLC Composition permeable aux liquides dans des dispositifs a reactif sec
JP2007500363A (ja) * 2003-06-12 2007-01-11 バイエル・ヘルスケア・エルエルシー 乾燥試薬装置における液体透過性組成物
EP1636582A4 (fr) * 2003-06-12 2008-04-30 Siemens Healthcare Diagnostics Composition permeable aux liquides dans des dispositifs a reactif sec
US7964372B2 (en) 2004-12-13 2011-06-21 Bayer Healthcare Llc Size self-limiting compositions and test devices for measuring analytes in biological fluids
US9982289B2 (en) 2004-12-13 2018-05-29 Ascensia Diabetes Care Holdings Ag Size self-limiting compositions and test devices for measuring analytes in biological fluids
CN114923965A (zh) * 2022-03-18 2022-08-19 杭州微策生物技术股份有限公司 一种一体式多指标传感器及其制作方法

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