Sensor for monitoring an analyte

• US 20040072359A1
• Filed: 09/17/2003
• Published: 04/15/2004
• Est. Priority Date: 09/19/2002
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Southard, Glen E.
• Granted Patent: US 7,319,038 B2
• Time in Patent Office: Days
• US Class Current: 436/111
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 2600/00 Assays involving molecular imprinted polymers/polymers created around a molecular template
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: Y10T 436/17 Nitrogen containing
• CPC Class Codes: Y10T 436/173845 Amine and quaternary ammonium
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A food spoilage sensor comprising a macrocyclic transition metal complex of the general formula

wherein M is a transition metal ion; D₁, D₂, D₃ and D₄ can be the same or different and can be N or P; R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can be the same or different and form, taken together with the adjacent carbon atoms to which they are bonded and joined together, an aromatic or a cyclic group with at least one of the aromatic or cyclic groups possessing one or more polymerizable moieties is provided. The complex selectively binds biogenic amines, such as cadaverine, putrescine and histamine, which are released by food spoilage microorganisms. The sensor undergoes a detectable color change upon exposure to biogenic amine, thus indicating that food spoilage has probably occurred. In one embodiment, a polymer containing the macrocyclic transition metal complex is molecularly imprinted with the biogenic amine to impart selective binding affinity such that upon exposure to biogenic amine, a color change is detected.

Claims

1. A polymer comprising the reaction product of:

(a) a macrocyclic transition metal complex of the general formula;

wherein M is a transition metal ion;

D₁, D₂, D₃ and D₄ can be the same or different and can be N or P; and

each of R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸, taken together with the adjacent carbon atoms to which they are bonded, are joined together to form the same or different group selected from an aromatic or a cyclic group with at least one of the aromatic or cyclic groups possessing one or more polymerizable moieties;

(b) monomer; and

(c) optional crosslinking agent,

wherein said polymer undergoes a detectable color change upon exposure to a biogenic amine.

2. The polymer of claim 1 wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

3. The polymer of claim 1 wherein in the macrocyclic transition metal complex M is nickel(II) or palladium (II) and D₁, D₂, D₃, and D₄ are N.

4. The polymer of claim 2 wherein in the macrocyclic transition metal complex M is nickel(II) or palladium (II) and D₁, D₂, D₃, and D₄ are N.

5. The polymer of claim 1 wherein the biogenic amine is selected from the group consisting of cadaverine, putrescine and histamine.

6. The polymer of claim 1 wherein the a macrocyclic transition metal complex is of the formula:

32. A food container comprising the polymer of claim 1.

7. A molecularly imprinted polymer formed by the steps of:

(a) providing the reaction product of (i) a four-coordinate a macrocyclic transition metal complex of the general formula;

wherein M is a transition metal ion;

D₁, D₂, D₃ and D₄ can be the same or different and can be N or P; and

each of R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸, taken together with the adjacent carbon atoms to which they are bonded, are joined together to form the same or different group selected from an aromatic or a cyclic group with at least one of the aromatic or cyclic groups possessing one or more polymerizable moieties, and (ii) a target molecule comprising biogenic amine, said reaction product possessing a four or six-coordinate geometry;

(b) copolymerizing the reaction product of step (a) with monomer and crosslinking agent to form a polymer; and

(c) removing the target molecule from the polymer to provide a molecularly imprinted polymer which selectively binds to the target molecule and undergoes a detectable color change when the target molecule binds thereto.

8. The molecularly imprinted polymer of claim 7 wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

9. The molecularly imprinted polymer of claim 7 wherein in the macrocyclic transition metal complex M is nickel(II) or palladium (II) and D₁, D₂, D₃, and D₄ are N and wherein the reaction product formed in step (a) possesses a four coordinate geometry.

10. The molecularly imprinted polymer of claim 7 wherein in the macrocyclic transition metal complex M is iron (II) and D₁, D₂, D₃, and D₄ are N and wherein the reaction product formed in step (a) possesses a six coordinate geometry.

11. The molecularly imprinted polymer of claim 7 wherein the biogenic amine is selected from the group consisting of cadaverine, putrescine and histamine, we should claim Fe (II) too, since it would be the metal of choice for histamine.

12. The molecularly imprinted polymer of claim 7 wherein the a macrocyclic transition metal complex is of the formula:

33. A food container comprising the polymer of claim 7.

13. A process for preparing a polymer comprising:

copolymerizing a macrocyclic transition metal complex of the general formula;

wherein M is a transition metal ion;

D₁, D₂, D₃ and D₄ can be the same or different and can be N or P; and

each of R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸, taken together with the adjacent carbon atoms to which they are bonded, are joined together to form the same or different group selected from an aromatic or a cyclic group with at least one of the aromatic or cyclic groups possessing one or more polymerizable moieties, monomer and optional crosslinking agent, wherein said polymer undergoes a detectable color change upon exposure II to a biogenic amine.

14. The process of claim 13 wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

15. The process of claim 13 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N..

16. The process of claim 14 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

17. The process of claim 13 wherein the biogenic amine is selected from the group consisting of cadaverine, putrescine and histamine.

18. The process of claim 13 wherein the a macrocyclic transition metal complex is of the formula:

19. A process for preparing a molecularly imprinted polymer which comprises:

(a) providing the reaction product of (i) a four-coordinate a macrocyclic transition metal complex of the general formula;

wherein M is a transition metal ion;

D₁, D₂, D₃ and D₄ can be the same or different and can be N or P; and

each of R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸, taken together with the adjacent carbon atoms to which they are bonded, are joined together to form the same or different group selected from an aromatic or a cyclic group with at least one of the aromatic or cyclic groups possessing one or more polymerizable moieties, and (ii) a target molecule comprising biogenic amine, said reaction product possessing a six-coordinate geometry;

(b) copolymerizing the reaction product of step (A) with monomer and crosslinking agent to form a polymer; and

(c) removing the target molecule from the polymer to provide a molecularly imprinted polymer which selectively binds to the target molecule and undergoes a detectable color change when the target molecule binds thereto.

20. The process of claim 19 wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

21. The process of claim 19 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

22. The process of claim 20 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

23. The process of claim 19 wherein the biogenic amine is selected from the group consisting of cadaverine, putrescine and histamine.

24. The process of claim 19 wherein the a macrocyclic transition metal complex is of the formula:

25. A sensor for detecting the presence of biogenic amine in, on or in association with a fluid which comprises a polymer and a support structure having a surface, the polymer being attached to the support structure as a coating thereon,

wherein the polymer is formed by the steps of:

copolymerizing a macrocyclic transition metal complex of the general formula;

26. The sensor of claim 25 wherein the structure comprises a plastic sheet, film or tray which is utilized in the packaging of food products.

27. The sensor of claim 25 wherein the structure is an optical fiber.

28. The sensor of claim 25 wherein the biogenic amine is selected from the group consisting of cadaverine, putrescine and histamine.

29. The sensor of claim 25 wherein the macrocyclic transition metal complex is first reacted with a target molecule comprising a biogenic diamine prior to copolymerizing the complex, monomer and crosslinking agent, and thereafter the target molecule is removed from the polymer to provide a molecularly imprinted polymer which selectively binds to the target molecule and undergoes a detectable color change when the target molecule binds thereto.

30. The sensor of claim 25 wherein the color change is visible.

31. The sensor of claim 25 wherein the color change is from yellow to crimson when the transition metal ion is nickel (II) or iron (II) and is from green to purple when the transition metal ion is palladium (II).

42. The method of claim 3425 wherein the color change is from yellow to crimson when the transition metal ion is nickel (II) or iron (II) and is from green to purple when the transition metal ion is palladium (II).

34. A method for detecting a biogenic amine, comprising:

providing a polymer comprising the reaction product of a macrocyclic transition metal complex of the general formula;

wherein M is a transition metal ion;

D₁, D₂, D₃ and D₄ can be the same or different and can be N or P; and

each of R¹ and R², R³ and R⁴, R⁵ and R , and R⁷ and R⁸, taken together with the adjacent carbon atoms to which they are bonded, are joined together to form the same or different group selected from an aromatic or a cyclic group with at least one of the aromatic or cyclic groups possessing one or more polymerizable moieties, monomer and crosslinking agent,

exposing the polymer to a food product or body fluid; and

,

detecting any change in color by the polymer, said detected change being indicative of the presence of biogenic amine in, on or in association with the food product or body fluid.

35. The method of claim 34 wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

36. The method of claim 34 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

37. The method of claim 35 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

38. The method of claim 34 wherein the biogenic amine is selected from the group consisting of cadaverine, putrescine and histamine.

39. The method of claim 34 wherein the a macrocyclic transition metal complex is of the formula:

40. The method of claim 34 wherein the macrocyclic transition metal complex is first reacted with a target molecule comprising biogenic diamine prior to copolymerizing the complex, monomer and crosslinking agent, and thereafter the target molecule is removed from the polymer to provide a molecularly imprinted polymer which selectively binds to the target molecule and undergoes a detectable color change when the target molecule binds thereto.

41. The method of claim 34 wherein the color change is visible.

43. A device for detecting a biogenic amine in a fluid comprising:

(a) a compartment having an inlet traversed by the fluid;

(b) a filtration unit mounted in the compartment downstream from the inlet and configured to filter out impurities in the fluid from the biogenic amine; and

,

(c) a biogenic amine-detecting material located in the compartment downstream from the filter to indicate the presence of the biogenic amine wherein said biogenic amine-detecting material undergoes a detectable color change upon exposure to a biogenic amine..

44. The device of claim 43 wherein the filtration unit possesses a pore size to filter impurities greater than one micron.

45. The device of claim 43 wherein the biogenic amine-detecting material comprises a macrocyclic transition metal complex of the general formula:

46. The device of claim 43 wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

47. The device of claim 43 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

48. The device of claim 46 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

49. The device of claim 43 wherein the biogenic amine to be detected is selected from the group consisting of cadaverine, putrescine and histamine.

50. The device of claim 43 wherein the macrocyclic transition metal complex is of the formula:

51. The device of claim 45 wherein the biogenic amine-detecting material further comprises an inert oxide selected from the group consisting of silica gel, titanium dioxide, titania oxide, cellulose and alumina.

52. The device of claim 43 which is a pipette or a syringe.

53. The device of claim 51 which is a pipette or a syringe.

54. The device of claim 43 wherein the fluid is associated with a food product.

55. The device of claim 43 wherein the fluid is a body fluid.

56. A test kit for determining the presence or absence of a biogenic amine in a representative sample of fluid, the kit comprising one or more of the devices of claim 43.

57. A test kit for determining the presence or absence of a biogenic amine in a representative sample of fluid, the kit comprising one or more of the devices of claim 45.

58. A test kit for determining the presence or absence of a biogenic amine in a representative sample of fluid, the kit comprising one or more of the devices of claim 50.

59. A test kit for determining the presence or absence of a biogenic amine in a representative sample of fluid, the kit comprising one or more of the devices of claim 51.

60. A method for detecting the presence of biogenic amine in a fluid, comprising:

exposing a fluid to a macrocyclic transition metal complex of the general formula;

61. The method of claim 60, wherein the aromatic groups to which R¹ and R², R³ and R⁴, R⁵ and R⁶, and R⁷ and R ⁸ can form when taken together with the adjacent carbon atoms to which they are bonded and joined together are selected from the group consisting of benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, and thiophene rings.

62. The method of claim 60 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

63. The method of claim 61 wherein in the macrocyclic transition metal complex M is nickel(II), palladium (II) or iron (II) and D₁, D₂, D₃, and D₄ are N.

64. The method of claim 60 wherein the biogenic amine to be detected is selected from the group consisting of cadaverine, putrescine and histamine.

65. The method of claim 60 wherein the macrocyclic transition metal complex is of the formula:

66. The method of claim 60 wherein the macrocyclic transition metal complex further comprises conjugate bases of a fluorescent agent compound.

67. The method of claim 66 wherein the fluorescent agent compound is a fluorophore.

68. The method of claim 67 wherein the fluorophore is selected from the group consisting of 9-anthracenecarboxylic acid, 1-naphthoic acid and carboxylic acid containing fluorosceins

69. The method of claim 60 wherein the fluid is associated with meat or fish.

70. The method of claim 60 wherein the fluid is a body fluid