EP1152242B1 - Receptacle pour essais immunologiques - Google Patents

Receptacle pour essais immunologiques Download PDF

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Publication number
EP1152242B1
EP1152242B1 EP99951118A EP99951118A EP1152242B1 EP 1152242 B1 EP1152242 B1 EP 1152242B1 EP 99951118 A EP99951118 A EP 99951118A EP 99951118 A EP99951118 A EP 99951118A EP 1152242 B1 EP1152242 B1 EP 1152242B1
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EP
European Patent Office
Prior art keywords
container
molecules
immunoassay
adsorption
protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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EP99951118A
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German (de)
English (en)
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EP1152242A4 (fr
EP1152242A1 (fr
Inventor
Hayao Akita Sumitomo Bakelite Co. Ltd. TANAKA
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Sumitomo Bakelite Co Ltd
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Sumitomo Bakelite Co Ltd
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Application filed by Sumitomo Bakelite Co Ltd filed Critical Sumitomo Bakelite Co Ltd
Publication of EP1152242A1 publication Critical patent/EP1152242A1/fr
Publication of EP1152242A4 publication Critical patent/EP1152242A4/fr
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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
    • 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

Definitions

  • the present invention relates to a container used for storage, dilution, or reaction of a reagent and/or a test sample, in an immunoassay for detecting an antigen or an antibody through antigen-antibody reaction.
  • samples used for clinical diagnosis such as serum and urine
  • samples used for clinical diagnosis such as serum and urine
  • samples used for clinical diagnosis are collected from patients, placed in a container, and stored therein until the samples are subjected to assay
  • clinically important proteins contained in the samples such as albumin, transferrin, and immunoglobulin
  • Most containers used for clinical diagnosis including syringes and cups used in the step of collecting a sample, tubes used in the step of storing the sample, and centrifugation tubes and test tubes used in the step of purifying, concentrating, or diluting the sample, are formed from polypropylene or polystyrene, and such a container is not subjected to surface treatment. Therefore, when even a trace amount of proteins contained in the sample is adsorbed onto the container in each step, the concentration of the proteins is expected to vary greatly after all the steps have been performed, as compared with the concentration of the proteins at the time of collection of the sample.
  • the price of a reagent in immobilized form accounts for about 80% the cost of a clinical test kit sold by a clinical test drug manufacturer. Therefore, when reduction in the reagent due to adsorption onto a container is suppressed, production costs are greatly reduced.
  • a solid phase method (a type of immunoassay method) assay is carried out by utilizing proteins immobilized onto the surface of a container for an immunoassay. Therefore, a solid phase method employs a container subjected to "high adsorption treatment," in which, in order to increase the amount of a reagent which is to be immobilized onto the surface of the container, a hydrophilic-hydrophobic balance of the surface is regulated through introduction of a functional group such as a hydroxyl group, thereby increasing the saturation adsorption amount of the reagent.
  • high adsorption treatment in which, in order to increase the amount of a reagent which is to be immobilized onto the surface of the container, a hydrophilic-hydrophobic balance of the surface is regulated through introduction of a functional group such as a hydroxyl group, thereby increasing the saturation adsorption amount of the reagent.
  • a container used for such a method is provided without consideration of molecular adsorption; i.e., the container is formed from polystyrene or polypropylene in consideration of only shapability, transparency, and low-temperature resistance, and the container is not subjected to surface treatment for suppressing adsorption of molecules. From the viewpoint of characteristics of the container, no attempt has been made to solve problems such as loss of a reagent and reduction in sensitivity.
  • a blocking method is most widely carried out, in which a container is coated with a protein inactive to a sample which is to be assayed. Since the method basically utilizes non-specific adsorption of the protein onto the container, blocking effects may differ from container to container, and may depend on the state of the protein. In addition, since the inactive protein is non-specifically adsorbed onto the container, the protein is easily detached from the container into a solution, and thus the container cannot be used for storing the solution.
  • Japanese Patent Application Laid-Open ( kokai ) Nos. 6-174726 and 7-128336 disclose a technique in which such detachment of a protein is eliminated by chemically immobilizing the protein onto a container.
  • the structure of the protein may vary in accordance with drying temperature, storage temperature, and storage time, and thus the container is not widely used in practice.
  • the protein When the higher-order structure of a protein adsorbed onto a container varies, the protein induces secondary adsorption.
  • the protein When a protein which is inactive in a free state is adsorbed onto or chemically bound to a container, the protein cannot completely maintain its inactive state, due to alteration of the higher-order structure. Therefore, even when adsorption of another protein onto the container can be prevented, variance of the higher-order structure induces secondary adsorption between the proteins.
  • EP 0 137 292 A2 describes a container for immunobiological assays.
  • the container is prepared from a material containing hydrophilic functional groups and includes inter alia polyhydroxy ethyl methacrylate.
  • US-4,472,357 A reveals a container for storing or holding human blood wherein the blood contacting surface of the container is provided with a hydrophilic coating comprising a polymer made from 2-hydroxyethyl methacrylate.
  • JP 08033472 relates to a cell reserver wherein at least a part of the surface of the reserver is coated with a polymer mainly composed of an alkoxyalkyl acrylate.
  • the present inventors have performed extensive studies on characteristics of a container, and have found that when the saturation amount of molecules which are adsorbed onto the container, the molecules being used for an immunoassay, is controlled to a predetermined value or less, loss of a reagent or a sample is prevented during storage, dilution, and reaction, and the sample can be assayed at high sensitivity.
  • MPC 2-methacryloyloxyethylphosphocholine
  • BMA butylmethacrylate copolymer
  • Fig. 1 shows the concentration of proteins after bovine serum and albumin have been stored in the container for an immunoassay of the present invention at -80°C for 48 hours.
  • Fig. 2 shows reaction efficiency when an immunoassay is carried out in the container of the present invention.
  • the adsorption amount of molecules is about 1-10 pmol/cm 2 or more; i.e., about 20-50% of molecules (e.g., proteins) used for an immunoassay are adsorbed onto the container, although the adsorption amount varies in accordance with the concentration of a solution containing such molecules and the contact area between the molecules and the container.
  • the adsorbed molecules (20-50% of all the molecules) are essential for reaction in the solution, reaction efficiency; i.e., assay sensitivity, is reduced by 20-50%. Meanwhile, when the adsorbed substance is such that it undergoes molecular structural changes due to adsorption to thereby cause unwanted reaction, considerable noise would result.
  • the container desirably meets the following conditions: the saturation adsorption amount of the molecules used in the immunoassay is 1 ⁇ 10 -1 pmol/cm 2 or less under the specific conditions in terms of concentration of the solution, temperature, and pH of the solvent-under which the reaction and assay are carried out.
  • the effect of the invention can be attained if the saturation adsorption amount of the molecules which participate in and/or affect the assay, among all molecules contained in the diluted serum, is always 1 ⁇ 10 -1 pmol/cm 2 or less at the diluted concentration of serum and under the specific conditions-in terms of concentration of the solution, temperature, and pH of the solvent-under which the reaction and assay are carried out.
  • the effect of the invention can be attained if the saturation adsorption amount of the molecules that undergo storage and dilution is always 1 ⁇ 10 -1 pmol/cm 2 or less under the specific conditions-in terms of concentration of the solution, temperature, and pH of the solvent-under which the reagent is removed from the storage container or dilution is carried out.
  • the reagent is stored in the container at a temperature as low as -80°C.
  • the saturation adsorption amount of molecules is 1 ⁇ 10 -1 pmol/cm 2 or less under the specific conditions-in terms of concentration, temperature, and pH-under which the reagent is removed from the container.
  • the saturation adsorption amount of the molecules is more preferably 1 ⁇ 10 -2 pmol/cm 2 or less, much more preferably 1 ⁇ 10 -3 pmol/cm 2 or less.
  • proteins e.g., enzymes, physiologically active proteins, and antibodies
  • nucleic acids e.g., glucose, and glutathione
  • physiologically active substances e.g., glucose, and others.
  • proteins e.g., enzymes, physiologically active proteins, and antibodies
  • nucleic acids e.g., amino acids, amino acids, and amino acids.
  • physiologically active substances e.g., amino acids, amino acids, and antibodies
  • nucleic acids e.g., amino acids, amino acids, and physiologically active substances.
  • physiologically active substances e.g., amino acids, amino acids, amino acids, and others.
  • physiologically active substances e.g., amino acids, amino acids, and others.
  • the saturation adsorption amount of the molecules can be measured by means of colloidal gold labeling immunoassay.
  • the present invention exerts excellent effects in addition to the aforementioned characteristic feature.
  • a protein is adsorbed onto a container, the structure of the protein is varied. Therefore, when an immunoassay is carried out, although a target protein is contained in a sample to be assayed, the protein may fail to be detected by an antibody, due to variation in the structure of the protein.
  • serum whose structure has been altered due to adsorption is assayed, even though serum must be assayed in the same state in which the serum is present in an organism.
  • the container of the present invention since a protein is not adsorbed onto the container, the structure of the protein is not altered, and thus when a clinical test is carried out by use of the container, serum can be assayed in a state similar to that in which serum is present in an organism. Therefore, the container of the present invention is very advantageously used as a container for an immunoassay.
  • the saturation adsorption amount of molecules In a container for an immunoassay, the saturation adsorption amount of molecules must be decreased at a portion with which a reagent or a sample is brought into contact; specifically, an inner surface of the container. Therefore, the molecular saturation adsorption amount at an inner surface of the container should be at least 1 ⁇ 10 -1 pmol/cm 2 or less.
  • the contact angle between the surface and water is preferably 30° or less (highly hydrophilic), more preferably 15° or less, much more preferably 1° or less (ultra-hydrophilic).
  • the contact angle between the surface of the resultant container and water becomes 1° or less (i.e., the container is ultra-hydrophilic), and the saturation adsorption amount of proteins becomes 1 ⁇ 10 -3 pmol/cm 2 or less, which is particularly preferable.
  • the product form of the container of the present invention is not particularly limited, and the container may assume conventionally used product forms, including a sample tube, a centrifugation tube, a multi-well plate, and a cuvette. However, in order to carry out storage, dilution, reaction, and assay of a sample in one container, the container preferably assumes a form of multi-well plate.
  • MPC-BMA butyl methacrylate copolymer
  • a commercially available polystyrene-made tube (Eiken tube for RIA No. 3, 70-12458) was used in "as is” form as a comparative tube.
  • Phosphate buffer (pH 7.4) solutions of biotin hydrazide (product of Dojindo) were prepared in advance (concentration of biotin hydrazide: 0.125 ⁇ g/mL, 0.250 ⁇ g/mL, and 0.500 ⁇ g/mL).
  • concentration of biotin hydrazide 0.125 ⁇ g/mL, 0.250 ⁇ g/mL, and 0.500 ⁇ g/mL.
  • biotin hydrazide was immobilized onto ELISA balls through covalent bonding via glutaraldehyde, to thereby prepare ELISA balls having three different immobilization densities of biotin hydrazide.
  • Each of the above-prepared ELISA balls was placed into the tubes of Reference Example 1, Example 1, and Comparative Example 1 (three tubes for each Example), a phosphate buffer (pH 7.4) solution of peroxydase-labeled avidin (product of Cappel) (concentration of avidin: 1 ⁇ g/mL) was injected into each tube (500 mL per tube), and reaction was carried out at room temperature for 30 minutes.
  • a phosphate buffer (pH 7.4) solution of peroxydase-labeled avidin product of Cappel
  • concentration of avidin 1 ⁇ g/mL
  • solutions of an enzyme-labeled anti-bovine-albumin antibody (product of Cosmo Bio) were prepared (concentration of the antibody: 0.1 ng/mL, 1 ng/mL, 10 ng/mL, and 100 ng/mL); each solution was injected into 24 wells of each plate; the plates were stored at -80°C for 48 hours; and after storage was completed, the concentration of the protein in each solution was measured by use of a substrate solution.
  • the adsorption amount of molecules or serum used for the assay is 1 ⁇ 10 -1 pmol/cm 2 or less, and thus loss of a reagent, which is caused by adsorption, is prevented during storage or dilution of the reagent. Therefore, when the container is used for a liquid-phase reaction, an assay can be carried out at high sensitivity and high accuracy, since there is prevented decrease in reaction efficiency, which is caused by adsorption of molecules to be assayed, or impediment of reaction due to adsorption of unwanted molecules.
  • the test can be carried out under conditions similar to those inside the body of an organism, since variation of the structure of serum components, which is caused by adsorption, does not occur in the container.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)

Claims (4)

  1. Récipient pour dosage immunologique dans lequel la quantité d'absorption à saturation de molécules mesurée par le dosage immunologique par marquage à l'or colloïdal utilisée pour le dosage est de 1x10-1 pmol/cm2 ou moins, dans lequel au moins une surface interne du récipient est formée à partir de ou revêtue avec un copolymère 2-méthacryloyloxyéthylphosphocholine (MPC)/méthacrylate de butyle (BMA) (rapport de la MPC au BMA = 3/7), dans lequel l'angle de contact entre la surface interne du récipient et l'eau est de 30° ou moins.
  2. Récipient pour dosage immunologique selon la revendication 1, dans lequel l'angle de contact entre la surface interne du récipient et l'eau est de 15° ou moins.
  3. Récipient pour dosage immunologique selon la revendication 2, dans lequel l'angle de contact entre la surface interne du récipient et l'eau est de 1° ou moins.
  4. Récipient pour dosage immunologique selon l'une quelconque des revendications 1 à 3, dans lequel la quantité d'adsorption à saturation de molécules utilisée pour le dosage est de 1x10-3 pmol/cm2 ou moins.
EP99951118A 1998-12-24 1999-10-28 Receptacle pour essais immunologiques Expired - Lifetime EP1152242B1 (fr)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
JP36740498 1998-12-24
JP36740498 1998-12-24
JP5625399 1999-03-03
JP5625399 1999-03-03
JP21209699 1999-07-27
JP21209699 1999-07-27
PCT/JP1999/005979 WO2000039582A1 (fr) 1998-12-24 1999-10-28 Receptacle pour essais immunologiques

Publications (3)

Publication Number Publication Date
EP1152242A1 EP1152242A1 (fr) 2001-11-07
EP1152242A4 EP1152242A4 (fr) 2002-03-06
EP1152242B1 true EP1152242B1 (fr) 2005-12-28

Family

ID=27295858

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99951118A Expired - Lifetime EP1152242B1 (fr) 1998-12-24 1999-10-28 Receptacle pour essais immunologiques

Country Status (7)

Country Link
EP (1) EP1152242B1 (fr)
JP (1) JP3681983B2 (fr)
AT (1) ATE314147T1 (fr)
AU (1) AU6366799A (fr)
CA (1) CA2356857A1 (fr)
DE (1) DE69929248T2 (fr)
WO (1) WO2000039582A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8163560B2 (en) 2003-12-04 2012-04-24 Roche Diagnostics Operations, Inc. Coated test elements

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101068802B1 (ko) * 2003-06-25 2011-10-04 니치유 가부시키가이샤 배양체 형성용 용기 및 배양체의 형성 방법
US20110177955A1 (en) * 2004-10-12 2011-07-21 Luis Alberto Burzio Multiplexed protein adsorption assay
JP2009050201A (ja) * 2007-08-27 2009-03-12 Dainippon Printing Co Ltd 初期胚等用培養器具
US11421102B2 (en) * 2015-11-24 2022-08-23 Jsr Corporation Method for manufacturing porous particles, porous particles, carrier, column, and method for separating target substance
EP3467059B1 (fr) * 2016-05-24 2022-02-23 Japanese Foundation For Cancer Research Procédé de récupération de vésicules extracellulaires et récipient destiné à des vésicules extracellulaires
JP6911852B2 (ja) 2016-06-15 2021-07-28 日産化学株式会社 凍結保存用容器
EP3882627B1 (fr) * 2018-11-14 2024-07-10 Nissan Chemical Corporation Récipient et procédé de stockage, de prétraitement et d'analyse de matériel biologique

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BE789839A (fr) * 1971-10-08 1973-02-01 Ceskoslovenska Akademie Ved Procede pour le traitement superficiel d'articles
US4472357A (en) * 1981-11-18 1984-09-18 Medical Laboratory Automation, Inc. Blood bank cuvette cassette and label therefor
FI833207A0 (fi) * 1983-09-08 1983-09-08 Farmos Oy Reaktionskaerl foer immunologiska bestaemningar
JPS6091983A (ja) * 1983-10-25 1985-05-23 Susumu Kogyo Kk タンパク質固定用膜担体およびその製造方法
JPH0419561A (ja) * 1990-05-14 1992-01-23 Nippon Shokubai Co Ltd 免疫アッセイ用ブロッキング剤
JPH0833472A (ja) * 1994-07-25 1996-02-06 Terumo Corp 細胞リザーバー
JP3884510B2 (ja) * 1996-10-14 2007-02-21 日本油脂株式会社 固定化免疫学的活性物質の保存時安定化方法

Non-Patent Citations (1)

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Title
INTERNET CITATION, Retrieved from the Internet <URL:http://www.nof.co.jp/depart/lipidure-en/> [retrieved on 20041112] *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8163560B2 (en) 2003-12-04 2012-04-24 Roche Diagnostics Operations, Inc. Coated test elements

Also Published As

Publication number Publication date
EP1152242A4 (fr) 2002-03-06
EP1152242A1 (fr) 2001-11-07
JP3681983B2 (ja) 2005-08-10
AU6366799A (en) 2000-07-31
ATE314147T1 (de) 2006-01-15
CA2356857A1 (fr) 2000-07-06
DE69929248T2 (de) 2006-08-17
WO2000039582A1 (fr) 2000-07-06
DE69929248D1 (de) 2006-02-02

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