WO2008069720A1 - Devlce and method for cholesterol determination - Google Patents
Devlce and method for cholesterol determination Download PDFInfo
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- WO2008069720A1 WO2008069720A1 PCT/SE2007/001021 SE2007001021W WO2008069720A1 WO 2008069720 A1 WO2008069720 A1 WO 2008069720A1 SE 2007001021 W SE2007001021 W SE 2007001021W WO 2008069720 A1 WO2008069720 A1 WO 2008069720A1
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- cavity
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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
- G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150015—Source of blood
- A61B5/150022—Source of blood for capillary blood or interstitial fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150343—Collection vessels for collecting blood samples from the skin surface, e.g. test tubes, cuvettes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150755—Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N21/07—Centrifugal type cuvettes
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0605—Metering of fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0621—Control of the sequence of chambers filled or emptied
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N2021/0325—Cells for testing reactions, e.g. containing reagents
- G01N2021/0328—Arrangement of two or more cells having different functions for the measurement of reactions
Definitions
- the present invention relates to a device and a method for determining total cholesterol in blood.
- the invention concerns a sampling device and a method for spectrophotometric measurement of total cholesterol in blood.
- Cholesterol is a sterol lipid essential to the cells of the body and mainly produced by the liver. As cholesterol is hydrophobic it cannot be dissolved and transported in the bloodstream directly, but is transported as part of lipoproteins. Most of the blood cholesterol, about 80%, is present as part of LDL (low density lipoprotein) particles, but also other lipoproteins, such as HDL (high density lipoprotein), transport cholesterol. For clinical analytical purposes, both the levels of the LDL and HDL cholesterol are of marked interest, but also the total blood cholesterol concentration is very important.
- cholesterol dehydrogenase Another enzyme used in cholesterol determinations is cholesterol dehydrogenase the use of which is disclosed in an analytical element in the patent publication EP 0 244 825. According to this publication the sample has to be incubated at a specific temperature for a prescribed time.
- cholesterol dehydrogenase for determination of cholesterol is also disclosed in e.g. the US patents 4 892 816 and 4 181 575. Both patents concern the determination of total cholesterol by wet chemical methods including long incubation times and defined temperatures.
- a disposable device including a dry reagent of the type first disclosed in the US patent 4 088 448 was especially studied, as the use of this type of microcuvette offers several advantages.
- This microcuvette permits sampling of a liquid, mixing the sample with a suitable reagent, for instance for colour development, in the same vessel as the one used for the subsequent measurement.
- the sampling procedure is simplified, the number of utensils is reduced and in most cases, depending upon the type of analysis, the exactitude of the analysis is considerably improved by making the analysing procedure independent of the operating technique of the operator making the analysis.
- the procedure is also remarkably fast as it permits the liquid sample to be instantly mixed with the reagent and then permits measurement shortly afterwards, without time consuming intermediary steps.
- An objective of the invention concerns a sampling device and a method for simple quantitative determination of total cholesterol in blood.
- An other objective of the invention concerns a sampling device and a method for quantitative determination of total cholesterol in blood, which method can be performed at ambient temperature.
- An other objective of the invention is to provide a sampling device including a cholesterol reagent composition which can be stored for prolonged periods of time.
- Still an other objective of the invention is to provide a sampling device for quantitative rapid determination of total cholesterol in blood.
- the inventive sampling device is a sampling device for taking up a blood sample and for providing the blood sample for analysis of total cholesterol in said blood sample, said device comprising: a receiving cavity for receiving, through capillary action, the blood sample to be analysed, said receiving cavity having a predetermined small volume; and an analysis cavity, arranged in communication with the receiving cavity, said analysis cavity having a predetermined optical path length; said receiving cavity containing a dried buffer, and said analysis cavity containing a dried reagent.
- the inventive method is a method for quantitative determination of the total cholesterol concentration in a blood sample of serum/plasma by end point analysis comprising: a) contacting serum/plasma with a dried buffer, whereby the buffer is dissolved in the blood sample, buffering the same; b) contacting a small, defined volume of the buffered serum/plasma with a dried reagent, said reagent comprising cholesterol dehydrogenase; cholesterol esterase; one or more substances from the group consisting of diaphorase, phenazine methosulphate, phenazine ethosulphate, phenazine phenosulphate and Meldola blue; one or more substances from the group consisting of NAD, NADP, thio-NAD, thio-NADP, nicotinamide-purine dinucleotide, nicotinamide-methylpurine dinucleo-tide and nicotinamide-2- chloro-methylpurine dinucleo-tide; one or more sur
- Figure 1 is a schematic front view of one embodiment of the inventive sampling device.
- Figure 1 also schematically illustrates one embodiment of a method of using said sampling device.
- Figure 2 is a graph disclosing the correlation between cholesterol determination according to an embodiment of the inventive method and a reference method.
- the invention relates in particular to total cholesterol determination in small volumes of blood.
- blood is intended to mean whole blood, plasma and/or serum.
- the blood which is introduced into the device is neither diluted nor pre-treated.
- small volumes means volumes between 0.1 and 0.001 ml, preferably between 0.03 and 0.001 ml.
- serum/plasma or "plasma/serum” is intended to encompass blood serum, blood plasma and any intermediate stages in between.
- a blood fraction as "serum" or "plasma” is that if a blood sample is analysed, without addition of anti-coagulants, within a few minutes after acquiring the blood from a patient, true serum will not have time to form, and the measurement is made on an intermediary stage between plasma and serum after removal of the blood cells. If the removal of cells and the measurement is made almost directly after acquiring the blood from a patient, the measurement will essentially be made on plasma. A blood component which is present in both plasma and serum will, due to the removal of the fibrinogen from serum, be present in a concentration of 3% less in plasma as compared with the concentration in serum.
- the term "cavity” is intended to be construed as a volume or chamber defined by wall surfaces.
- the cavities (volumes) of the device according to the present invention are not however completely defined, or enclosed, by these surfaces, but have inlets and/or outlets where the surfaces are not completely joined together.
- the cavities (volumes) are usually not evacuated, but may contain a gas (generally air), a dried reagent and/or buffer, a liquid (such as a blood sample when the device is in use), etc.
- the sampling device of the present invention is designed in such a way that it holds the dried buffer separate from the dried reagent, thus making it possible to keep the reagent at a pH irrespective of the buffer pH while the reagent is in dried form (e.g.
- the shelf life of the inventive device can be greatly improved. This is achieved by equipping the sampling device with a plurality of cavities.
- a serum/plasma sample is introduced into the sampling device, and in this case only the receiving and analysis cavities are needed.
- a sample of undiluted whole blood is introduced into the device.
- the device has to be designed so as to include additional cavities adapted for removal of the blood cells of the sample through centrifugation, as the cells, if present in the analysis cavity, will interfere with the cholesterol determination.
- a device which discloses the removal of blood cells by centrifugal action and which may be used is e.g. the device of the US patent 5 472 671 (which is hereby incorporated by reference).
- the receiving cavity has a predetermined volume, which allows it to receive a predetermined, invariable volume of blood (serum/plasma) which may then be transferred to the analysis cavity. This ensures that a specific and known volume is reacted with the dried reagent in the analysis cavity.
- the analysis cavity has a predetermined optical path length, which ensures that when a photometer is used over the analysis cavity for obtaining a measurement value, this value may be directly correlated to the cholesterol concentration of a blood sample therein.
- the inventive method may thus also include centrifugation of whole blood for removing blood cells and fibrinogen from the whole blood before the serum thus obtained is contacted with the dry reagent in the sampling device.
- the inventive method may include contacting unaltered whole blood with an anti-coagulating agent and subjecting the obtained mixture to centrifugation for removing blood cells before the plasma thus obtained is contacted with the dry reagent in the sampling device.
- a sampling device comprising four cavities may be employed: a first cavity 1 (an inlet cavity) in connection with the surroundings of the sampling device via an inlet, and optionally containing a dry additive such as a wetting agent and/or an anti-coagulating agent, for receiving a sample of blood, preferably whole blood, from outside of the device through capillary action; a second cavity 2 (a centrifugation reception cavity), preferably non-capillary, connected to the first cavity 1 and into which the sample may be transferred through centrifugal action; a third cavity 3 (the receiving cavity), preferably capillary and containing the dried buffer and optionally a wetting agent, in connection with the second cavity 2 and into which the serum/plasma fraction of the sample may be
- a preferred use of the four cavity device above is to introduce whole blood into the device directly from a pricked finger of a patient.
- the blood is first drawn, step 10, into the inlet cavity 1 through capillary action. This may be aided by a wetting agent in dry form deposited in the inlet cavity 1 at manufacture of the device, and by the device having a pointy design providing a point at the inlet of the inlet cavity 1 which may make contact with the blood of the pricked finger.
- the device may then be subjected to centrifugal action, step 11 , such that the blood is transferred from the inlet cavity 1 to the centrifugation reception cavity 2, and such that the blood cells of the blood are essentially separated, step 12, from the plasma.
- the blood plasma is, through capillary action, drawn, step 13, from the centrifugation reception cavity 2 into the receiving cavity 3, where dried buffer is quickly dissolved in a specific volume of the plasma defined by the volume of the receiving cavity 3.
- the device is again subjected to centrifugation, step 14, whereby the buffered plasma is transferred to the analysis cavity 4 where the dried reagent for the cholesterol determination is dissolved in the buffered plasma.
- the total cholesterol of the plasma is determined through absorption photometry.
- the sampling device may be disposable, i.e. it is arranged to be used only once.
- the sampling device provides a kit, which can be stably stored for a long time before use, for performing a determination of total cholesterol, since the sampling device is able to receive a liquid sample and holds all reagents needed in order to present the sample to cholesterol measurement. This is particularly enabled if the sampling device is adapted for use only once and may be formed without consideration of possibilities to clean the sampling device and re-apply a reagent.
- Identical units of the inventive sampling device may be mass produced with a very low tolerance for deviations, whereby measurements made using one specific unit may be directly compared with measurements made using other units of the same inventive sampling device.
- the sampling device may be moulded in a plastic material and thereby be manufactured at a low cost. Thus, it may still be cost-effective to use a disposable sampling device. Further, by forming the sampling device from a rigid plastic material, the devise may not be deformed during handling and use of the device, thus ensuring invariable volumes and shapes of the device cavities after manufacture, consequently also ensuring an invariable optical path length. According to one embodiment of the inventive method the following reaction steps are performed with the indicated reagent ingredients:
- the ingredients of the dried reagent are not restricted to those exemplified in the above reaction scheme, but are discussed in some detail below.
- the cholesterol esterase may be obtained from different species having different molar weights, pH optima etc.
- the coenzyme may be NAD, preferably ⁇ -NAD, NADP, thio-NAD, thio- NADP, nicotinamide-purine dinucleotide, nicotinamide-methylpurine dinucleotide and nicotinamide-2-chloro-methylpurine dinucleotide.
- cholesterol dehydrogenase can be obtained from different species having different molar weights, pH optima etc.
- Examples of publications concerning cholesterol dehydrogenase are the Japanese Patents Laid-open Nos. 89,183/1983 and 89,200/1983, wherein the preparation of cholesterol dehydrogenase is disclosed.
- cholesterol dehydrogenase only encompasses NAD- or NAD-analog-dependent enzymes.
- Diaphorase can also be obtained from different species and is commercially available. Diaphorase can however be replaced by known substances, such as phenazine methosulphate, phenazine ethosulphate, phenazine phenosulphate, Meldola blue etc. There are also other known NAD-analogs, such as the best known NADP, which can be reduced by the cholesterol dehydrogenase reaction and transfer the reduction to a dye or colour system.
- MTT (3-(4,5-dimethylthiazole-2-1 )-2,5-diphenyl-2H-tetrazolium bromide) is an example of a redox indicator dye, which yields a good result when used in the inventive method, although many other tetrazolium compounds can be used.
- colour- changing substances which are capable of changing colour when affected by NADH and diaphorase.
- Tetrazolium compounds are advantageous in that the formazan dye is formed irreversibly under normal reaction conditions.
- MTT is used as redox indicator dye and the absorbance is measured in the range 630-680nm, most specifically 640nm with a measurement for background correction in the range 700- 900nm or more specifically at 700 nm or 840nm.
- the wavelength for the absorbance measurement depends on the redox dye used.
- the wave length may vary between 500 and 750 nm.
- the reagent can contain non-ionic surfactants such as polyoxyethylenes and/or alkyl glucosides and/or thio-glucosides and/or copolymer and/or anionic surfactants such as bile acids or enzyme such as phospholipas as agents for lysing the lipoprotein.
- non-ionic surfactants such as polyoxyethylenes and/or alkyl glucosides and/or thio-glucosides and/or copolymer
- anionic surfactants such as bile acids or enzyme such as phospholipas as agents for lysing the lipoprotein.
- surfactants may be used for wetting the dry reagent matrix.
- the surfactant(s) should exhibit the following characteristics:
- the contents of the different components in the dried reagent composition are not critical, but calculated on a sample of 1 ml undiluted whole blood may preferably be in the following ranges:
- the above substances are mixed in order to form a suspension, which may be freeze-dried in the analysis cavity of the inventive sample device.
- the invention is illustrated by the following non-limiting example.
- a reagent solution including 1 % triton X-100 in water was prepared.
- MTT (3-(4,5-dimethylthiazole-2-1)-2,5-diphenyl-2H-tetrazolium bromide) was added to the solution and mixed until the MTT was dissolved.
- a Tris buffer solution having a pH of 9.0 was in a similar way filled into the receiving cavity 3 of the inventive disposable sampling devices.
- sampling devices including the reagent and buffer were frozen at - 45 0 C and freeze-dried in order to obtain sampling devices including a dried reagent and a dried buffer in respective cavities.
- One obtained sampling device was used as follows:
- a defined serum/plasma sample volume is drawn into the receiving cavity 3 by capillary action.
- the dried buffer dissolves in the serum/plasma.
- the sampling device is then subjected to centrifugation such that the buffered serum/plasma is forced into the analysis cavity 4 containing the dried reagent.
- the dried reagent composition dissolves in the serum/plasma, whereby the pH changes to 8.5, and the serum/plasma cholesterol is reacted with cholesterol esterase and cholesterol dehydrogenase as defined in the above chemical reactions.
- the chemical reactions lead to a dye concentration change.
- transmission spectrometry measurements at 640 nm and compensation for background at 840 nm the concentration of cholesterol in the serum/plasma sample can be quantitatively determined.
- the whole process, from drawing in the sample to the measurement typically takes less than 5 minutes to perform, usually about 2 minutes.
- Figure 2 discloses the relationship between the cholesterol determination according to the present invention and a reference method for end-point determination, and as can be seen the agreement is good.
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007800445677A CN101583723B (en) | 2006-12-06 | 2007-11-21 | Devlce and method for cholesterol determination |
DE112007002921T DE112007002921T5 (en) | 2006-12-06 | 2007-11-21 | Apparatus and method for cholesterol determination |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0602607A SE532009C2 (en) | 2006-12-06 | 2006-12-06 | Cholesterol Detection Device and Method |
SE0602607-4 | 2006-12-06 | ||
US11/717,684 US20080138793A1 (en) | 2006-12-06 | 2007-03-14 | Method for cholesterol determination |
US11/717,684 | 2007-03-14 |
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WO2008069720A1 true WO2008069720A1 (en) | 2008-06-12 |
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PCT/SE2007/001021 WO2008069720A1 (en) | 2006-12-06 | 2007-11-21 | Devlce and method for cholesterol determination |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9851301B2 (en) | 2013-10-01 | 2017-12-26 | Roche Diagnostics Operations, Inc. | Method and device for recognizing a mixed or unmixed state of a sample |
WO2023118081A1 (en) * | 2021-12-23 | 2023-06-29 | Hemocue Ab | Cuvette for body fluid analysis |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4088448A (en) * | 1975-09-29 | 1978-05-09 | Lilja Jan Evert | Apparatus for sampling, mixing the sample with a reagent and making particularly optical analyses |
US4161425A (en) * | 1976-07-01 | 1979-07-17 | Beckman Instruments, Inc. | Enzymatic reagent system for total cholesterol assay using oxygen-rate method |
EP0244825A1 (en) * | 1986-05-09 | 1987-11-11 | Fuji Photo Film Co., Ltd. | Dry-type analytical element for cholesterol |
WO1990013016A1 (en) * | 1989-04-26 | 1990-11-01 | Migrata Uk Ltd | Cuvette |
WO2003023051A2 (en) * | 2001-09-11 | 2003-03-20 | Merck Patent Gmbh | Lateral flow test format for enzyme assays |
-
2007
- 2007-11-21 WO PCT/SE2007/001021 patent/WO2008069720A1/en active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4088448A (en) * | 1975-09-29 | 1978-05-09 | Lilja Jan Evert | Apparatus for sampling, mixing the sample with a reagent and making particularly optical analyses |
US4161425A (en) * | 1976-07-01 | 1979-07-17 | Beckman Instruments, Inc. | Enzymatic reagent system for total cholesterol assay using oxygen-rate method |
EP0244825A1 (en) * | 1986-05-09 | 1987-11-11 | Fuji Photo Film Co., Ltd. | Dry-type analytical element for cholesterol |
WO1990013016A1 (en) * | 1989-04-26 | 1990-11-01 | Migrata Uk Ltd | Cuvette |
WO2003023051A2 (en) * | 2001-09-11 | 2003-03-20 | Merck Patent Gmbh | Lateral flow test format for enzyme assays |
Non-Patent Citations (1)
Title |
---|
RAMSAY J.R. ET AL.: "The use of a layering technique for enhancing stability of lyophilized reagents", ANALYTICAL BIOCHEMISTRY, vol. 202, 1992, pages 331 - 336, XP000272982 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9851301B2 (en) | 2013-10-01 | 2017-12-26 | Roche Diagnostics Operations, Inc. | Method and device for recognizing a mixed or unmixed state of a sample |
WO2023118081A1 (en) * | 2021-12-23 | 2023-06-29 | Hemocue Ab | Cuvette for body fluid analysis |
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