Method of producing insoluble carrier particles, insoluble carrier particles, measurement reagent, specimen analyzing tool, and immunoturbidimetric assay
The present invention provides a measurement reagent that is capable of suppressing nonspecific aggregation even when the amount of antibody to be carried is increased, and is capable of measuring in a wide measurement concentration range with high measurement sensitivity; an immunoturbidimetric assay using the same; and a method of producing thereof. A method of producing an insoluble carrier particle of the present invention is a method of producing an insoluble carrier particle carrying an antibody or an antigen on a particle surface thereof. The method includes a sensitization reaction processes in which the antibody or the antigen is brought into contact with the insoluble carrier particle in the presence of an amino acid with a charged polar side chain in a sensitization reaction solution. The insoluble carrier particles obtained by the producing method of the present invention show favorable dispersibility because nonspecific aggregation is suppressed. As can be seen from Examples 1-1 to 1-4 in FIG. 3 , when the insoluble carrier particles are applied to measurement by an immunoturbidimetric assay, a wide measurement concentration range and high measurement sensitivity can be achieved.
1. A method of producing an insoluble carrier particle carrying an antibody or an antigen on a particle surface thereof, comprising the following sensitization reaction process (A):
(A) bringing the antibody or the antigen into contact with the insoluble carrier particle in the presence of an amino acid with a charged polar side chain in a sensitization reaction solution, wherein a concentration of the amino acid with a charged polar side chain in the sensitization reaction solution is greater than 0.1 mol/L and is equal to or less than 1 mol/L.
2. The method of producing an insoluble carrier particle according to claim 1 , wherein the amino acid with a charged polar side chain is a basic amino acid or an acidic amino acid.
3. The method of producing an insoluble carrier particle according to claim 1 , wherein in the sensitization reaction process (A), the insoluble carrier particle is a latex particle.
4. The method of producing an insoluble carrier particle according to claim 3 , wherein in the sensitization reaction process (A), the latex particle is a latex particle for chemical bonding.
5. An insoluble carrier particle used in an immunoturbidimetric assay, wherein the insoluble carrier particle is produced by the method of producing an insoluble carrier particle according to claim 1 .
6. A measurement reagent used in an immunoturbidimetric assay, wherein the measurement reagent contains the insoluble carrier particle according to claim 5 .
7. The measurement reagent according to claim 6 , wherein
the measurement reagent contains an insoluble carrier particle group including a plurality of insoluble carrier particles,
the insoluble carrier particle group includes two types of insoluble carrier particle groups having different average particle sizes, and
at least one of the two types of insoluble carrier particle groups is an insoluble carrier particle group including a plurality of insoluble carrier particles according to claim 5 .
8. The measurement reagent according to claim 7 , wherein an insoluble carrier particle group having a larger average particle size out of the two types of insoluble carrier particle groups is an insoluble carrier particle group including a plurality of insoluble carrier particles according to claim 5 .
9. The measurement reagent according to claim 6 , wherein an average particle size of the insoluble carrier particle according to claim 5 is in a range of 0.03 to 2.0 μm.
10. The measurement reagent according to claim 6 , wherein an average particle size of the insoluble carrier particle according to claim 5 is in a range of 0.08 to 2.0 μm.
11. The measurement reagent according to claim 6 , wherein an average particle size of the insoluble carrier particle according to claim 5 is in a range of 0.12 to 0.5 μm.
12. A specimen analyzing tool, containing the measurement reagent according to claim 6 .
13. The specimen analyzing tool according to claim 12 , wherein the specimen analyzing tool is any one of a test piece, a cartridge, and a microchip.
14. An immunoturbidimetric assay, comprising:
an aggregation reaction process immunoreacting insoluble carrier particles carrying antibodies or antigens on particle surfaces thereof with measurement objects, which are antigens or an antibodies, to aggregate the insoluble carrier particles in an immunoreaction solution; and
a measurement process measuring change in turbidity of the immunoreaction solution due to the aggregation reaction, wherein the insoluble carrier particle according to claim 5 is used as the insoluble carrier particle.
15. The immunoturbidimetric assay according to claim 14 , wherein in the aggregation reaction process,
an insoluble carrier particle group including a plurality of insoluble carrier particles is used, and wherein
the insoluble carrier particle group includes two types of insoluble carrier particle groups having different average particle sizes, and
at least one of the two types of insoluble carrier particle groups is an insoluble carrier particle group including a plurality of insoluble carrier particles according to claim 5 .
16. The immunoturbidimetric assay according to claim 15 , wherein an insoluble carrier particle group having a larger average particle size out of the two types of insoluble carrier particle groups is an insoluble carrier particle group including a plurality of insoluble carrier particles according to claim 5 .
17. The immunoturbidimetric assay according to claim 14 , wherein an average particle size of the insoluble carrier particle according to claim 5 is in a range of 0.03 to 2.0 μm.
18. The immunoturbidimetric assay according to claim 14 , wherein an average particle size of the insoluble carrier particle according to claim 5 is in a range of 0.08 to 2.0 μm.
19. The immunoturbidimetric assay according to claim 14 , wherein an average particle size of the insoluble carrier particle according to claim 5 is in a range of 0.12 to 0.5 μm.