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WO1989001161A1 - Dosage turbimetrique - Google Patents

Dosage turbimetrique Download PDF

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Publication number
WO1989001161A1
WO1989001161A1 PCT/GB1988/000614 GB8800614W WO8901161A1 WO 1989001161 A1 WO1989001161 A1 WO 1989001161A1 GB 8800614 W GB8800614 W GB 8800614W WO 8901161 A1 WO8901161 A1 WO 8901161A1
Authority
WO
WIPO (PCT)
Prior art keywords
particles
analyte
sample
carry
mixture
Prior art date
Application number
PCT/GB1988/000614
Other languages
English (en)
Inventor
Jacques Janssens
Original Assignee
International Institute Of Cellular & Molecular Pa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by International Institute Of Cellular & Molecular Pa filed Critical International Institute Of Cellular & Molecular Pa
Publication of WO1989001161A1 publication Critical patent/WO1989001161A1/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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G01N33/54333—Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
    • 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
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00534—Mixing by a special element, e.g. stirrer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation

Definitions

  • This invention is concerned with agglutination assays.
  • Such assays are widely used to detect, or determine the concentration of, an analyte in a biological fluid.
  • At least one of the assay reagents is used in a form attached to fine solid particles suspended in the liquid assay medium, which particles are caused to agglutinate to an extent dependent upon the concentration of the analyte in the sample.
  • the extent of this agglutination can be measured by two main techniques.
  • One involves use of a particle counting device such as that sold by us under the Trade Mark IMPACT, which is adapted to count only particles in a specific size range. This technique has the advantage of high sensitivity and accuracy, and is being commercially used on an increasing scale.
  • the other main technique for determining the extent of agglutination is a turbidimetric technique which involves measuring the optical density of the assay mixture.
  • This technique has the advantages of being cheap and quick, and can be performed on the reaction mixture in the assay vessel. Its major disadvantage is lack of sensitivity. It will be appreciated that both the monomeric latex particles and the agglutinated particles increase the optical density of the reaction mixture, albeit to somewhat different extents.
  • Measuring optical density in order to determine agglutination involves measuring this difference which is generally rather slight. That is why the standard method is not very sensitive.
  • the present invention arises from the idea that, if the agglutinated particles could be removed from the reaction mixture, the optical density of the remaining reaction mixture would provide a much more sensitive and accurate measure of the amount of analyte in the sample.
  • the invention uses magnetically attractable particles to achieve this effect.
  • the invention provides a method of performing a turbidimetric assay for an analyte in a sample, which analyte is a member of an immuno-reaction system, by the use of: first magnetically attractable particles which carry a first species reactive with a member of the immuno-reaction system, but which are not agglutinatable by the analyte, and second particles which carry a second species reactive with a member of the immuno-reaction system, which method comprises the steps of incubating a mixture of the sample with the first particles, and with the second particles, together with any other required members of the immuno-reaction system, whereby agglutination takes place, to an extent related to the concentration of the analyte in the sample, resulting in the formation of an agglutinated product containing the first particles, applying a magnetic field to the mixture to bring down the first particles, and measuring the optical density of the mixture.
  • analyte is not critical to the invention. It may be an antigen or an antibody. O it may be a hapten. Different conditions may need to be used, as described below, depending on whether the analyte is mono-epitopic or poly-epitopic.
  • the nature of the sample is similarly not critical, but is frequently a body fluid such as plasma or serum.
  • the nature of the particles is not critical, and commercially available materials may be used. It is necessary that the first particles be magnetically attractable and the second be not magnetically attractable.
  • the particles may be of glass or ceramic or metal oxide, or an organic polymer e.g. polystyrene, in which case a suspension of the particles is generally known as a latex.
  • the second J particles need to be capable of changing the optical density of a fluid medium in which they are present at a concentration of, say, 1/500, for which purpose latex particles are suitable.
  • the species carried by these particles may be attached by chemical or physical 0 means well known in the art.
  • the first and second particles carry first and second species which are different from one another, but are both reactive with a member of the immuno- reaction system.
  • the analyte is an antigen or a ⁇ hapten
  • the first and second species may be selected from the analyte, an antibody to the analyte, and a second antibody to the said antibody.
  • the method involves incubating a mixture of the sample with the first particles, and with the second particles, 0 together with any other required members of the immuno- reaction system. Depending on circumstances, it may be necessary to incubate the sample with the first and second particles in sequence, in either order, or with both sets of particles together. 5 There follow descriptions of six different methods of performing the mixing and incubating steps of the invention.
  • the analyte is an antigen, a poly-epitopic material, of which thyroid stimulating hormone (TSH) ° may be taken as an example.
  • the first species on the first magnetically attractable particles is a monoclonal antibody to the antigen.
  • the second species on the second particles is a polyclonal antibody to the antigen.
  • the method involves 5 incubating a mixture of the sample with the first particles in excess, whereby the analyte becomes bound to the antibody on the first particles. Because this is a monoclonal antibody, agglutination does not take place at this stage. Then the second particles are added, also in excess, and the system further incubated. Agglutination takes place at this stage, to an extent proportional to the amount of antigen in the sample. Because of the order of addition of the particles, all agglutinated particles contain at least one of the first magnetically attractable particles.
  • the analyte is an antigen.
  • the first magnetically attractable particles carry a monoclonal antibody to the antigen.
  • the second particles carry, not a polyclonal antibody, but another monoclonal antibody, different from that carried by the first particles, to the antigen.
  • the sample is mixed with the first and second particles, both in excess, and incubated. Agglutination takes place to an extent proportional to the amount of antigen in the sample. Because both sets of particles carry monoclonal antibodies to the antigen, all agglutinated particles comprise both first and second particles, and therefore contain at least one of the first magnetically attractable particles.
  • the analyte is an antigen and the first magnetically attractable latex carries a monoclonal antibody to the antigen.
  • the second particles may carry either a polyclonal " antibody to the antigen (as in A), or a different monoclonal antibody to the antigen (as in B).
  • the sample is incubated with an excess of the first particles, as a result of which the antigen becomes bound to the particles.
  • the mixture is spun- down, the supernatant discarded and the precipitate re- suspended in a smaller volume of liquid.
  • the second particles are then added and the mixture incubated, as a result of which agglutination takes place as before.
  • This variant involves reducing the volume of the reaction mixture between the first and second incubations, and is particularly attractive when the sample contains only a low concentration of analyte. It overcomes the problem that agglutination reactions 0 are difficult to perfro in very dilute solutions.
  • the analyte here is a hapten, a mono-epitopic species capable of raising antibodies only when bound to another material such as bovine serum albumin (BSA), for example a thyroid hormone such as T3 or T4.
  • BSA bovine serum albumin
  • the 5 first magnetically attractable particles carry the hapten on their surface.
  • the second particles carry antibodies to the hapten on their surface.
  • the method involves incubating a mixture of a sample containing the hapten with the first and second 0 particles. The first and second particles bind together to form agglutinated particles, and this binding is inhibited by the hapten which occupies binding sites on the antibody on the second particles. The extent of agglutination is therefore inversely 5 proportional to the analyte concentration in the sample.
  • E This is a variant on D.
  • the analyte is a hapten and the first magnetically attractable particles carry the hapten on their surface as before.
  • a first ° antibody to the hapten is used in solution.
  • the second particles carry on their surface second antibodies (or F(ab) 2 fragments thereof) to the first antibody.
  • the method involves incubating a mixture of a sample containing the analyte with the first antibody in solution and with the first and second particles.
  • the F(c) portion of the first antibody becomes bound to the second particles.
  • the hapten in the sample and the hapten bound to the first particles compete for binding with the F(ab) 2 sites of the first antibody. Agglutination involving both sets of particles takes place to an extent inversely proportional to the concentration of the analyte in the sample.
  • the analyte is a hapten.
  • a first antibody 0 to the hapten is used in solution.
  • the second particles carry the hapten on their surface.
  • the first magnetically attractable particles carry a monoclonal second antibody to the first antibody.
  • Also included in the system is a latex, the particles ⁇ of which carry a different monoclonal second antibody to the first antibody.
  • the method involves incubating a mixture of the sample with all the named reagents.
  • the hapten in the sample and the hapten on the second particles 0 compete for binding with first antibody.
  • First antibody bound to the free hapten from the sample is available for binding by the second antibody.
  • First antibody bound to hapten on the second particles is, by reason of steric inhibition, not able to take part in 5 agglutination reactions involving the first particles.
  • the two monoclonal second antibodies both bind to the first antibody, unless steric inhibition prevents this, resulting in agglutination.
  • the extent of agglutination is directly proportional to the ° concentration of hapten in the sample.
  • the result of all these methods is a reaction mixture containing agglutinated particles and unagglutinated particles in relative proportions which are related in some way to the analyte concentrations 5 in the sample.
  • the next step is to apply a magnetic field to the mixture to remove the magnetically attractable first particlesfrom suspension. Since all the agglutinated particles contain at least one of the first particles, the effect of this step is to remove from suspension all the agglutinated particles, together with any unagglutinated first particles, ⁇ nagglutinated second particles remain in suspension; the concentration of these is related in some way to the analyte concentration in the sample.
  • the optical density of the mixture is then measured and the measurement used to detect the presence of, or determine the concentration of, the analyte in the sample. Equipment for measuring optical density is commercially available and can be used in conventional manner.
  • the assay may be performed in a cuvette with parallel optical glass side walls through which the optical density measurement is made in a horizontal direction.
  • a magnet can be placed below the bottom of the cuvette in order to draw down the first particles;or a magnetic stirrer might be introduced into the bottom of the cuvette for the same purpose.
  • the assay may be performed in cups of a microtitre plate.
  • the optical density measurement would normally be made vertically by an instrument adapted to traverse from cup to cup of the plate.
  • the magnetic field needs to be applied between the cups so as to pull the magnetically attractable first particles to one side of each cup.
  • Figure 1 is a perspective diagramatic view of two-part equipment for effecting magnetic separation
  • Figures 2 and 3 are diagramatic sectional side elevations of the same equipment at different stages in the method.
  • a microtitre plate (10) including cups (12), each of which contains a reaction mixture (1*0 at the conclusion of the incubating step of the invention. Also shown is an adaptor (16) in the form of a plate with holes (18) to receive the cups of the microtitre plate and permanent magnets (20) positioned between the holes. As shown in figure 2, the microtitre plate (10) is initially separate from the adaptor (16), and the agglutinated and unagglutinated particles are present in uniform suspension in the reaction mixture (HO. In the next step as shown in figure 3, the microtitre plate has been lowered onto the adaptor and the two secured together with a clip (22).
  • the magnet has acted on the first particles i n tne reaction mixture, and has drawn them, as shown at (24), to the side wall of each cup.
  • the second particles remain in uniform suspension.
  • the optical density of the reaction mixture in one cup is being measured in the direction shown by the arrow (26).
  • a system where the optical density of the mixture is measured only after the magnetically attractable particles have been completely brought down may be regarded as an equilibrium one. It may alternatively be possible to perform the optical density measurement kinetically, by observing the rate or extent of the change of optical density of the mixture when the magnetic field is applied to it.
  • Example 1 is included by way of comparison.
  • Example 1 is included by way of comparison.
  • the samples were again of serum containing various known concentrations of TSH.
  • the first magnetically attractable latex particles carried a monoclonal antibody to the TSH.
  • the second latex particles carried a polycolonal antibody to TSH.
  • 0.05ml of sample were digested with 0.1ml pepsin in 0.1ml water for U minutes. Then 1ml glycine buffered saline (GBS)/BSA 1% was added, together with 0.05ml of tris buffer and 0.03ml of a 0.1% suspension of the first latex. The mixture was incubated to cause TSH from the sample to bind .to antibody on the magnetic latex. To 0.08ml of the resulting mixture was added 0.03ml of a 0.065% suspension of the second latex in buffer. This mixture was incubated for one hour, resulting in agglutination of particles to an extent proportional to the TSH concentration in the sample.
  • GBS glycine buffered saline
  • This experiment also demonstrates that an assay for TSH can be performed without the need for initial pepsin digestion of the sample.
  • FIG. 4 is a graph of optical density, expressed in arbitary figures, against TSH concentration in the sample, measured as ng/ml.
  • the graph includes three dose-response curves which were obtained as follows:
  • Curve A was obtained by a method as described in comparative Example 1 above and without use of a magnetic separation technique. The curve is substantially horizontal for much of its length, indicating that the assay is insensitive.
  • Curve B was obtained by an experiment according to Example 2 above. Note that the dose-response curve has a useful slope at TSH concentrations from 0 up to 100 ng/ml.
  • Curve C was obtained by an assay similar to that used for Curve B, but the measurements were made using an IMPACT particle counter. Below 5 ng/ml TSH the slope is rather small; from 5 to 100 ng/ml the sensitivity is comparable to that achieved by Curve B.
  • the method of this invention involving an agglutination assay and measurement of optical density, has the following advantages: a) It eliminates the step of sample transfer from one tube to another. Sample transfer involves expense and time, and can damage agglutinated particles which are not robust. Also sample transfer always raises carry ⁇ over problems from one tube to the next. b) It is very quick. Measurements can be made rapidly and vertically by moving the instrument head from one microtitre well to the next. c) It is at least as sensitive as a particle counting assay. d) It is enormously faster than immuno assays which depend on radioactive or fluorescent or luminous labels. e) It is more sensitive than RIA and comparable in this respect to fluorometric or luminescent immuno assays,

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
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Abstract

Procédé permettant le dosage turbimétrique d'un analyte constituant un élément d'un système d'immuno-réaction, mettant en oeuvre l'utilisation de premières particules magnétiquement attirables et portant une première espèce réagissant avec un élément du système d'immuno-réaction, mais non agglutinable par l'analyte, ainsi que de secondes particules portant une seconde espèce réagissant avec un élément du système d'immuno-réaction. On fait incuber l'échantillon avec les premières et les secondes particules, de manière à former un produit agglutiné contenant les premières particules, dans une mesure relative à la concentration d'analyte. On fait descendre les particules agglutinées au moyen d'un champ magnétique et l'on observe la densité optique du liquide superlatent. Lorsque l'analyte est un antigène ou un haptène, les premières particules portent de préférence un anticorps monoclonal, et les secondes particules peuvent porter un anticorps monoclonal ou polyclonal différent.
PCT/GB1988/000614 1987-07-28 1988-07-28 Dosage turbimetrique WO1989001161A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8717862A GB8717862D0 (en) 1987-07-28 1987-07-28 Turbidimetric assay
GB8717862 1987-07-28

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WO1989001161A1 true WO1989001161A1 (fr) 1989-02-09

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WO (1) WO1989001161A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0328071A3 (fr) * 1988-02-12 1991-05-08 The University Of Connecticut Méthode d'utilisation de particules magnétiques pour l'isolation, le captage et l'essai de ligats diagnostiques
WO1992005443A1 (fr) * 1990-09-15 1992-04-02 Medical Research Council Separation de reactif
EP0410893A3 (en) * 1989-07-28 1992-05-06 Mitsubishi Kasei Corporation Determination and detection of antibody and its immunoglobulin class
WO1992017781A1 (fr) * 1991-04-04 1992-10-15 International Murex Technologies Corporation Dosage par agglutination
EP0479448A3 (en) * 1990-10-02 1992-12-23 Beckman Instruments, Inc. Magnetic separation device
EP0421478A3 (en) * 1989-10-06 1993-04-28 Mitsubishi Kasei Corporation Method for immunochemical determination of hapten
US5374531A (en) * 1993-03-22 1994-12-20 Zynaxis, Inc. Immunoassay for determination of cells
US5583054A (en) * 1989-07-28 1996-12-10 Mitsubishi Kasei Corporation Determination and detection of antibody and its immunoglobulin class
DE19823719A1 (de) * 1998-05-27 1999-12-16 Max Planck Gesellschaft Verfahren und Vorrichtung zum Prozessieren von Kleinstsubstanzmengen
FR2797690A1 (fr) * 1999-08-20 2001-02-23 Bio Merieux Procede de detection d'un analyte et necessaire pour la mise en oeuvre de ce procede
DE10050029A1 (de) * 2000-10-06 2002-05-02 Stiftung Caesar Chemischer Sensor mit magnetischen Partikeln
CN104374924A (zh) * 2014-12-15 2015-02-25 山东博科生物产业有限公司 一种α1-抗胰蛋白酶免疫比浊法检测试剂盒
CN105527449A (zh) * 2015-12-24 2016-04-27 山东博科生物产业有限公司 一种载脂蛋白a1免疫比浊法检测试剂盒

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US4115535A (en) * 1977-06-22 1978-09-19 General Electric Company Diagnostic method employing a mixture of normally separable protein-coated particles
GB1590525A (en) * 1976-12-10 1981-06-03 Technicon Instr Biological analysis
US4279617A (en) * 1979-02-26 1981-07-21 Technicon Instruments Corporation Iummunoassay involving agglutination
DE3323137A1 (de) * 1982-06-28 1984-01-05 Abbott Laboratories, 60064 Chicago, Ill. Verfahren zum nachweis von mehrwertigen, spezifischen, bindenden substanzen in biologischen fluessigkeiten
JPS61128168A (ja) * 1984-11-27 1986-06-16 Mitsubishi Chem Ind Ltd 免疫分析方法
WO1986004684A1 (fr) * 1985-02-06 1986-08-14 Labsystems Oy Procede de depistage d'anticorps ou d'antigenes
EP0194156A1 (fr) * 1985-03-08 1986-09-10 Sanko Junyaku Co., Ltd. Procédé de détermination de la quantité d'un anticorps immunologique dans du sérum
EP0201755A1 (fr) * 1985-05-14 1986-11-20 Fisher Scientific Company Essai immunologique effectué dans un champ centrifuge au moyen de particules complémentaires à poids spécifiques différents

Patent Citations (8)

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Publication number Priority date Publication date Assignee Title
GB1590525A (en) * 1976-12-10 1981-06-03 Technicon Instr Biological analysis
US4115535A (en) * 1977-06-22 1978-09-19 General Electric Company Diagnostic method employing a mixture of normally separable protein-coated particles
US4279617A (en) * 1979-02-26 1981-07-21 Technicon Instruments Corporation Iummunoassay involving agglutination
DE3323137A1 (de) * 1982-06-28 1984-01-05 Abbott Laboratories, 60064 Chicago, Ill. Verfahren zum nachweis von mehrwertigen, spezifischen, bindenden substanzen in biologischen fluessigkeiten
JPS61128168A (ja) * 1984-11-27 1986-06-16 Mitsubishi Chem Ind Ltd 免疫分析方法
WO1986004684A1 (fr) * 1985-02-06 1986-08-14 Labsystems Oy Procede de depistage d'anticorps ou d'antigenes
EP0194156A1 (fr) * 1985-03-08 1986-09-10 Sanko Junyaku Co., Ltd. Procédé de détermination de la quantité d'un anticorps immunologique dans du sérum
EP0201755A1 (fr) * 1985-05-14 1986-11-20 Fisher Scientific Company Essai immunologique effectué dans un champ centrifuge au moyen de particules complémentaires à poids spécifiques différents

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PATENT ABSTRACTS OF JAPAN, Vol. 10, No. 322, P-511; & JP,A,61 128 168, (16-06-1986). *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5158871A (en) * 1988-02-12 1992-10-27 University Of Connecticut Method of using magnetic particles for isolating, collecting and assaying diagnostic ligates
EP0328071A3 (fr) * 1988-02-12 1991-05-08 The University Of Connecticut Méthode d'utilisation de particules magnétiques pour l'isolation, le captage et l'essai de ligats diagnostiques
US5583054A (en) * 1989-07-28 1996-12-10 Mitsubishi Kasei Corporation Determination and detection of antibody and its immunoglobulin class
EP0410893A3 (en) * 1989-07-28 1992-05-06 Mitsubishi Kasei Corporation Determination and detection of antibody and its immunoglobulin class
EP0421478A3 (en) * 1989-10-06 1993-04-28 Mitsubishi Kasei Corporation Method for immunochemical determination of hapten
WO1992005443A1 (fr) * 1990-09-15 1992-04-02 Medical Research Council Separation de reactif
EP0479448A3 (en) * 1990-10-02 1992-12-23 Beckman Instruments, Inc. Magnetic separation device
WO1992017781A1 (fr) * 1991-04-04 1992-10-15 International Murex Technologies Corporation Dosage par agglutination
US5374531A (en) * 1993-03-22 1994-12-20 Zynaxis, Inc. Immunoassay for determination of cells
DE19823719A1 (de) * 1998-05-27 1999-12-16 Max Planck Gesellschaft Verfahren und Vorrichtung zum Prozessieren von Kleinstsubstanzmengen
US7105357B1 (en) 1998-05-27 2006-09-12 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E. V. Method and device for processing extremely small substance quantities
DE19823719B4 (de) * 1998-05-27 2011-12-15 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Verfahren zum Aufkonzentrieren von Substanzen
FR2797690A1 (fr) * 1999-08-20 2001-02-23 Bio Merieux Procede de detection d'un analyte et necessaire pour la mise en oeuvre de ce procede
WO2001014880A1 (fr) * 1999-08-20 2001-03-01 Bio Merieux Detection d'un analyte en utilisant deux types de particules
DE10050029A1 (de) * 2000-10-06 2002-05-02 Stiftung Caesar Chemischer Sensor mit magnetischen Partikeln
DE10050029B4 (de) * 2000-10-06 2004-09-23 Stiftung Caesar Chemischer Sensor mit magnetischen Partikeln
CN104374924A (zh) * 2014-12-15 2015-02-25 山东博科生物产业有限公司 一种α1-抗胰蛋白酶免疫比浊法检测试剂盒
CN105527449A (zh) * 2015-12-24 2016-04-27 山东博科生物产业有限公司 一种载脂蛋白a1免疫比浊法检测试剂盒

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