Method for conducting receptor-ligand association reaction and reactor used therefor

• US 20030148403A1
• Filed: 01/27/2003
• Published: 08/07/2003
• Est. Priority Date: 02/01/2002
• Status: Abandoned Application

• Current Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Original Assignee: Fuji Photo Film Co Limited (Fujifilm Holdings Corporation)
• Inventors: Nakajima, Kenji
• Application Number:
  US10/351,391
• Publication Number:
  US 20030148403A1
• Time in Patent Office: Days
• US Class Current: 435/7.9
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00574 radioactive
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00578 electrophoric
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: C12Q 1/6832 : Enhancement of hybridisation reaction
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2527/101 : Temperature
• CPC Class Codes: C12Q 2565/137 : Chromatographic separation
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing

Abstract

A method for conducting a receptor-ligand association reaction includes the steps of holding a biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing receptors or ligands in a reaction vessel covered by a jacket whose temperature can be controlled, and forcibly feeding a reaction solution containing a ligand or receptor labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively associating the ligand or receptor contained in the reaction solution with the receptors or ligands contained in the plurality of absorptive regions of the biochemical analysis unit. According to this method, it is possible to efficiently associate a ligand or receptor with receptors or ligands fixed in the absorptive regions of the biochemical analysis unit and produce biochemical analysis data having an excellent quantitative characteristic with good repeatability.

Claims

1. A method for conducting a receptor-ligand association reaction comprising steps of holding a biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing receptors or ligands in a reaction vessel covered by a jacket whose temperature can be controlled, and forcibly feeding a reaction solution containing a ligand or receptor labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively associating the ligand or receptor contained in the reaction solution with the receptors or ligands contained in the plurality of absorptive regions of the biochemical analysis unit.

2. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which further comprises a step of recycling the reaction solution into the reaction vessel via a solution circulation passage provided with a filter so that the reaction solution is forcibly fed to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively associating the ligand or receptor contained in the reaction solution with the receptors or ligands contained in the plurality of absorptive regions of the biochemical analysis unit.

3. A method for conducting a receptor-ligand association reaction in accordance with claim 2 which further comprises a step of recycling the reaction solution into the reaction vessel via a static mixer provided in the solution circulation passage so that the reaction solution is forcibly fed to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively associating the ligand or receptor contained in the reaction solution with the receptors or ligands contained in the plurality of absorptive regions of the biochemical analysis unit.

4. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which further comprises a step of forcibly feeding the reaction solution so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit alternately in different directions, thereby selectively associating the ligand or receptor contained in the reaction solution with the receptors or ligands contained in the plurality of absorptive regions of the biochemical analysis unit.

5. A method for conducting a receptor-ligand association reaction in accordance with claim 4 which comprises a step of forcibly feeding the reaction solution so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit alternately in different directions and forcibly feeding the reaction solution into a pair of solution passages connected to the reaction vessel one on either side of the biochemical analysis unit held in the reaction vessel and each having a static mixer, thereby selectively associating the ligand or receptor contained in the reaction solution with the receptors or ligands contained in the plurality of absorptive regions of the biochemical analysis unit.

6. A method for conducting a receptor-ligand association reaction in accordance with claim 1 wherein the reaction solution contains a ligand or receptor labeled with a labeling substance selected from a group consisting of a radioactive labeling substance, a fluorescent substance and a labeling substance which generates chemiluminescence emission when it contacts a chemiluminescent substrate.

7. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, and forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with a labeling substance and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit.

8. A method for conducting a receptor-ligand association reaction in accordance with claim 2 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, and forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with a labeling substance and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit.

9. A method for conducting a receptor-ligand association reaction in accordance with claim 3 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, and forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with a labeling substance and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit.

10. A method for conducting a receptor-ligand association reaction in accordance with claim 4 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, and forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with a labeling substance and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit.

11. A method for conducting a receptor-ligand association reaction in accordance with claim 5 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, and forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with a labeling substance and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit.

12. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing an antigen or an antibody in the reaction vessel covered by the jacket whose temperature can be controlled, and forcibly feeding the reaction solution containing an antibody or an antigen labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody or the antigen labeled with a labeling substance and contained in the reaction solution with the antigen or the antibody contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

13. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with a labeling substance so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the labeling substance and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

14. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with an enzyme which generates chemiluminescence emission when it contacts a chemiluminescent substrate so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the enzyme and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

15. A method for conducting a receptor-ligand association reaction in accordance with claim 2 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with an enzyme which generates chemiluminescence emission when it contacts a chemiluminescent substrate so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the enzyme and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

16. A method for conducting a receptor-ligand association reaction in accordance with claim 3 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with an enzyme which generates chemiluminescence emission when it contacts a chemiluminescent substrate so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the enzyme and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

17. A method for conducting a receptor-ligand association reaction in accordance with claim 4 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with an enzyme which generates chemiluminescence emission when it contacts a chemiluminescent substrate so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the enzyme and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

18. A method for conducting a receptor-ligand association reaction in accordance with claim 5 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with an enzyme which generates chemiluminescence emission when it contacts a chemiluminescent substrate so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the enzyme and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

19. A method for conducting a receptor-ligand association reaction in accordance with claim 1 which comprises steps of holding the biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing specific binding substances whose structure or characteristics are known in the reaction vessel covered by the jacket whose temperature can be controlled, forcibly feeding the reaction solution containing a substance derived from a living organism and labeled with a hapten so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby selectively hybridizing the substance derived from a living organism, labeled with the hapten and contained in the reaction solution with the specific binding substances contained in the plurality of absorptive regions of the biochemical analysis unit, and forcibly feeding a reaction solution containing an antibody to the hapten labeled with an enzyme which generates a fluorescent substance when it contacts a fluorescent substrate so as to cut through the plurality of absorptive regions formed in the biochemical analysis unit, thereby binding the antibody labeled with the enzyme and contained in the reaction solution with the hapten contained in the plurality of absorptive regions of the biochemical analysis unit by an antigen-antibody reaction.

20. A method for conducting a receptor-ligand association reaction in accordance with claim 1 wherein the biochemical analysis unit includes a substrate formed with a plurality of through-holes spaced apart from each other and the plurality of absorptive regions are formed by charging an absorptive material in the plurality of through-holes formed in the substrate and causing the absorptive material charged in the plurality of through-holes to contain receptors or ligands.

21. A method for conducting a receptor-ligand association reaction in accordance with claim 20 wherein the plurality of absorptive regions are formed by pressing an absorptive membrane containing an absorptive material into the plurality of through-holes formed in the substrate and causing the absorptive material pressed into the plurality of through-holes to contain receptors or ligands.

22. A method for conducting a receptor-ligand association reaction in accordance with claim 1 wherein the biochemical analysis unit is formed with 10 or more absorptive regions.

23. A method for conducting a receptor-ligand association reaction in accordance with claim 1 wherein each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 5 mm².

24. A method for conducting a receptor-ligand association reaction in accordance with claim 1 wherein the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 50 or more per cm².

25. A method for conducting a receptor-ligand association reaction in accordance with claims 20 wherein the substrate of the biochemical analysis unit has a property of attenuating radiation energy.

26. A method for conducting a receptor-ligand association reaction in accordance with claim 25 wherein the substrate of the biochemical analysis unit has a property of reducing the energy of radiation to ⅕

or less when the radiation travels in the substrate by a distance equal to that between neighboring absorptive regions.

27. A method for conducting a receptor-ligand association reaction in accordance with claim 20 wherein the substrate of the biochemical analysis unit has a property of attenuating light energy.

28. A method for conducting a receptor-ligand association reaction in accordance with claim 27 wherein the substrate of the biochemical analysis unit has a property of reducing the energy of light to ⅕

or less when the light travels in the substrate by a distance equal to that between neighboring absorptive regions.

29. A reactor for conducting a receptor-ligand association reaction comprising a reaction vessel covered by a jacket whose temperature can be controlled and provided with a biochemical analysis unit holding section for holding a biochemical analysis unit formed with a plurality of absorptive regions spaced apart from each other and containing receptors or ligands, and a reaction solution force-feeding means for forcibly feeding a reaction solution containing a ligand or receptor labeled with a labeling substance so as to cut through the plurality of absorptive regions of the biochemical analysis unit held by the biochemical analysis unit holding section.

30. A reactor for conducting a receptor-ligand association reaction in accordance with claim 29 which further comprises a solution circulation passage connected to the reaction vessel for recycling the reaction solution into the reaction vessel and a filter provided in the solution circulation passage.

31. A reactor for conducting a receptor-ligand association reaction in accordance with claim 29 which further comprises a static mixer provided in the solution circulation passage.

32. A reactor for conducting a receptor-ligand association reaction in accordance with claim 30 which further comprises a static mixer provided in the solution circulation passage.

33. A reactor for conducting a receptor-ligand association reaction in accordance with claim 29 wherein the reaction solution force-feeding means is constituted as a pump.

34. A reactor for conducting a receptor-ligand association reaction in accordance with claim 29 wherein the reaction solution force-feeding means is constituted so as to forcibly feed the reaction solution to cut through the plurality of absorptive regions formed in the biochemical analysis unit alternately in different directions.

35. A reactor for conducting a receptor-ligand association reaction in accordance with claim 30 wherein the reaction solution force-feeding means is constituted so as to forcibly feed the reaction solution to cut through the plurality of absorptive regions formed in the biochemical analysis unit alternately in different directions.

36. A reactor for conducting a receptor-ligand association reaction in accordance with claim 31 wherein the reaction solution force-feeding means is constituted so as to forcibly feed the reaction solution to cut through the plurality of absorptive regions formed in the biochemical analysis unit alternately in different directions.

37. A reactor for conducting a receptor-ligand association reaction in accordance with claim 32 wherein the reaction solution force-feeding means is constituted so as to forcibly feed the reaction solution to cut through the plurality of absorptive regions formed in the biochemical analysis unit alternately in different directions.

38. A reactor for conducting a receptor-ligand association reaction in accordance with claim 34 wherein a pair of solution passages are further connected to the reaction vessel one on either side of the biochemical analysis unit held in the reaction vessel and a static mixer is provided in each of the solution passages.

39. A reactor for conducting a receptor-ligand association reaction in accordance with claim 35 wherein a pair of solution passages are further connected to the reaction vessel one on either side of the biochemical analysis unit held in the reaction vessel and a static mixer is provided in each of the solution passages.

40. A reactor for conducting a receptor-ligand association reaction in accordance with claim 36 wherein a pair of solution passages are further connected to the reaction vessel one on either side of the biochemical analysis unit held in the reaction vessel and a static mixer is provided in each of the solution passages.

41. A reactor for conducting a receptor-ligand association reaction in accordance with claim 37 wherein a pair of solution passages are further connected to the reaction vessel one on either side of the biochemical analysis unit held in the reaction vessel and a static mixer is provided in each of the solution passages.

42. A reactor for conducting a receptor-ligand association reaction in accordance with claim 29 wherein the reaction solution force-feeding means is constituted as a syringe provided with a piston.