WO-2026094858-A1 - METHOD FOR STABILIZING MEASUREMENT SENSITIVITY OF LATEX AGGLUTINATION IMMUNOASSAY REAGENT, METHOD FOR STORING LATEX AGGLUTINATION IMMUNOASSAY REAGENT, METHOD FOR SUPPRESSING NATURAL SEDIMENTATION OF LATEX PARTICLES, LATEX AGGLUTINATION IMMUNOASSAY METHOD, AND LATEX AGGLUTINATION IMMUNOASSAY REAGENT

Abstract

Provided is a method for stabilizing the measurement sensitivity of a latex agglutination immunoassay reagent containing, in an aqueous medium, latex particles to which an antibody or an antibody fragment thereof is bonded. The method for stabilizing the measurement sensitivity of a latex agglutination immunoassay reagent is characterized in that in the aqueous medium, the latex particles to which the antibody or antibody fragment thereof is bonded coexist with at least one amino acid or salt thereof selected from the group consisting of glycine, glutamic acid, and salts of these at a concentration of 5.0% (w/v) or greater.

Inventors

• SUZUKI, TAKUMA
• UZAWA, Kazuki
• MIYOSHI, SHOGO
• IMAI, TAKESHI

Assignees

• キヤノンメディカルダイアグノスティックス株式会社

Dates

Publication Date

20260507

Application Date

20251027

Priority Date

20241028

Claims (20)

1. A method for stabilizing the measurement sensitivity of a latex agglutination immunoassay reagent containing latex particles to which an antibody or an antibody fragment is bound in an aqueous medium, A method for stabilizing the measurement sensitivity of a latex agglutination immunoassay reagent, characterized by coexisting latex particles to which the antibody or antibody fragments are bound with at least one amino acid selected from the group consisting of glycine, glutamic acid, and their salts, in an aqueous medium at a concentration of 5.0% (w/v) or higher.
2. The stabilization method according to claim 1, wherein the concentration of the amino acid or its salt in the aqueous medium is 5.0% (w/v) or more and 10% (w/v) or less.
3. The stabilization method according to claim 1, wherein the aqueous medium is Gutt's buffer solution.
4. The stabilization method according to any one of claims 1 to 3, wherein the antibody is an antibody that recognizes the N-terminal pro-brain natriuretic peptide.
5. A method for storing a latex agglutination immunoassay reagent containing latex particles to which an antibody or an antibody fragment is bound in an aqueous medium, A method for preserving a latex agglutination immunoassay reagent, characterized in that latex particles to which the antibody or antibody fragments are bound are present in the aqueous medium, along with at least one amino acid selected from the group consisting of glycine, glutamic acid, and their salts, or a salt thereof, at a concentration of 5.0% (w/v) or higher.
6. The preservation method according to claim 5, wherein the concentration of the amino acid or its salt in the aqueous medium is 5.0% (w/v) or more and 10% (w/v) or less.
7. The preservation method according to claim 5, wherein the aqueous medium is Gutt's buffer solution.
8. The storage method according to claim 5, wherein the storage of the reagent is performed within the measuring device.
9. The storage method according to claim 5, wherein the storage of the reagent is by refrigerating and leaving the reagent undisturbed.
10. The storage method according to claim 5, wherein the storage period of the reagent is within 14 days from the start of storage of the reagent.
11. The storage method according to any one of claims 5 to 10, wherein the antibody is an antibody that recognizes the N-terminal pro-brain natriuretic peptide.
12. A method for suppressing the spontaneous sedimentation of latex particles in a latex agglutination immunoassay reagent containing latex particles to which an antibody or an antibody fragment is bound in an aqueous medium, A method for suppressing the spontaneous sedimentation of latex particles, characterized by coexisting latex particles to which the antibody or antibody fragments are bound with at least one amino acid selected from the group consisting of glycine, glutamic acid, and their salts, in an aqueous medium at a concentration of 5.0% (w/v) or more.
13. The method according to claim 12, wherein the concentration of the amino acid or its salt in the aqueous medium is 5.0% (w/v) or more and 10% (w/v) or less.
14. The method according to claim 12, wherein the aqueous medium is Gutt's buffer solution.
15. The method according to claim 12, wherein the spontaneous sedimentation is spontaneous sedimentation that occurs by storing the reagent in the measuring device.
16. The method according to claim 12, wherein the spontaneous sedimentation is spontaneous sedimentation that occurs by leaving the reagent to stand under refrigeration.
17. The method according to claim 12, wherein the spontaneous sedimentation is spontaneous sedimentation that occurs by storing the reagent within 14 days from the start of storage.
18. The method according to any one of claims 12 to 17, wherein the antibody is an antibody that recognizes the N-terminal pro-brain natriuretic peptide.
19. A latex agglutination immunoassay method for a target component in a sample, comprising reacting a sample containing the target component with latex particles to which an antibody or antibody fragment that recognizes the target component is bound, in an aqueous medium containing at least one amino acid or salt thereof selected from the group consisting of glycine, glutamic acid, and salts thereof at a concentration of 5.0% (w/v) or higher.
20. (1) A step of mixing a sample containing the component to be measured with an aqueous medium; and (2) A step of reacting the sample with an antibody that recognizes the component to be measured in the sample, or latex particles to which such antibody fragments are bound, in the aqueous medium. A method for latex agglutination immunoassay of a target component in a sample, wherein at least step (2) is performed in an aqueous medium containing at least one amino acid or a salt thereof selected from the group consisting of glycine, glutamic acid and salts thereof at a concentration of 5.0% (w/v) or higher.

Description

Method for stabilizing the measurement sensitivity of latex agglutination immunoassay reagents, method for storing latex agglutination immunoassay reagents, method for suppressing spontaneous sedimentation of latex particles, latex agglutination immunoassay method, and latex agglutination immunoassay reagents. This invention relates to a method for stabilizing the measurement sensitivity of a latex agglutination immunoassay reagent, a method for storing a latex agglutination immunoassay reagent, a method for suppressing the spontaneous sedimentation of latex particles, a latex agglutination immunoassay method, and a latex agglutination immunoassay reagent. This application claims priority based on Japanese Patent Application No. 2024-189133, filed in Japan on October 28, 2024, and the contents of that application are incorporated herein by reference. Latex agglutination immunoassay is widely used in clinical testing as a method for measuring target components in a sample. This method involves using latex particles to which antibodies that specifically recognize the target component are bound. The degree of agglutination (turbidity) of the latex particles, resulting from the binding of the antigen (the target component) to the antibody-bound latex particles, is detected by optical means. The latex agglutination immunoassay reagents used in this method can be installed in automated analyzers commonly used in hospital and testing laboratory laboratories, enabling simple and rapid measurement using latex agglutination immunoassay. While latex agglutination immunoassay reagents, used in measurement methods utilizing latex agglutination immunoassay, are sold by many manufacturers, it is known that these reagents spontaneously agglutinate during storage, even in the absence of the target component (antigen). This agglutination of particles can prevent accurate measurement of agglutination resulting from the antigen-antibody reaction caused by the binding of the antigen to the antibody-bound latex particles, leading to unstable measurement sensitivity. As a method to suppress the destabilization of sensitivity due to such spontaneous aggregation, a method is known in which latex particles immobilized with proteins such as antibodies are dissolved in a 3 to 18 mM buffer selected from a buffer of phosphoric acid, 2-amino-2-hydroxymethyl-1,3-propanediol, and Goode's (Patent Document 1). Furthermore, Patent Document 1 also discloses that when a higher concentration buffer is used, spontaneous aggregation of particles cannot be suppressed and sensitivity may become even more unstable. The embodiments for carrying out the present invention will be described in detail below. The embodiments described below are merely examples of typical embodiments of the present invention, and this should not be interpreted as narrowing the scope of the invention. Note that numerical ranges indicated using "~" represent the range that includes the numbers before and after "~" as the minimum and maximum values, respectively. Furthermore, if multiple substances corresponding to each component are present in the solution, unless otherwise specified, the amount of each component in the solution refers to the total amount of those substances present during the reaction or in the reagent. In this embodiment, "% (w/v)" means the percentage of mass (g) based on volume (100 mL). In this embodiment, when we express that the antibody and the antigen to be measured "bind," "react," or that the antibody "recognizes" the antigen, we include the meanings commonly used in the field of this invention, and all are used synonymously. Methods for confirming the "binding" of the antibody and antigen include methods utilizing principles well known to those skilled in the art, such as antigen-immobilized ELISA, competitive ELISA, sandwich ELISA, surface plasmon resonance spectroscopy, immunochromatography, and quartz crystal microbalance spectroscopy. Furthermore, in this embodiment, "spontaneous sedimentation" of latex particles bound to antibodies or antibody fragments means that when a container containing latex particles bound to antibodies or antibody fragments is left standing, the latex particles naturally settle to the bottom of the container. Confirmation of "spontaneous sedimentation" of latex particles bound to antibodies or antibody fragments can be performed using methods such as the measurement sensitivity ratio before and after storage of the latex agglutination immunoassay reagent, or a decrease in the concentration ratio of latex particles bound to antibodies or antibody fragments. [Aqueous medium] Examples of aqueous media in this embodiment include deionized water, distilled water, and buffer solutions, with buffer solutions being preferred. Examples of buffering agents used in preparing the buffer solution include acetic acid buffers and Good's buffers, with Good's buffer solution being preferred. One type of buffering agent may be used alo