Polymerized crystalline colloidal array sensors

• US 5,898,004 A
• Filed: 11/06/1996
• Issued: 04/27/1999
• Est. Priority Date: 11/06/1996
• Status: Expired due to Term

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Asher, Sanford A., Holtz, John H.
• Primary Examiner(s): McKane, Joseph K.
• Assistant Examiner(s): BAXAM, DEANNA L
• Application Number:
  US08/743,816
• Time in Patent Office: 902 Days
• Field of Search: 252/582, 252/588, 252/315.1, 252/583, 524/916, 524/458, 424/487, 356/334, 436/518, 436/517, 436/527, 436/532, 359/296, 359/886, 205/777.5, 205/781.5, 205/792
• US Class Current: 436/518
• CPC Class Codes: B01J 13/00 Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
• CPC Class Codes: G01J 3/18 using diffraction elements, e.g. grating gratings per se G02B
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7723 Swelling part, also for adsorption sensor, i.e. without chemical reaction
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 31/222 for investigating moisture content
• CPC Class Codes: G02B 26/002 the movement or the deformation controlling the frequency of light, e.g. by Doppler effect

Abstract

Novel sensor devices composed of a crystalline colloidal array (CCA) polymerized in a hydrogel are disclosed. The hydrogels are characterized as being capable of shrinking and swelling in response to specific stimuli applied thereto. As the hydrogels shrink or swell, the lattice structure of the CCA embedded therein changes, thereby changing the wavelength of light diffracted by the CCA. Thus by monitoring the change in diffracted wavelength, the concentration of a stimulus is determined. The gels can be modified to sense numerous different stimuli. The sensor devices are specific in that they are modified to react with only one species or family of species. These sensors have various applications in areas including, for example, environmental and chemical systems, chemomechanical systems, sensor devices and medical diagnostic tools. Various methods for making and using these devices are also disclosed.

Claims

1. A sensor device comprising:

a hydrogel that undergoes a volume change in response to a specific chemical stimulus; and

a light diffracting crystalline colloidal array of charged particles polymerized in said hydrogel;

said crystalline colloidal array having a lattice spacing that changes when said volume of said hydrogel changes, thereby causing the diffracted wavelength of the crystalline colloidal array to change.

2. The sensor device of claim 1, wherein said hydrogel is comprised of a first comonomer that is a gel monomer, a crosslinking agent and a second comonomer that is a molecular recognition monomer.

3. The sensor device of claim 2, wherein said device detects a particular chemical stimulus by using as the second comonomer a monomer capable of recognizing the chemical species to be detected.

4. The sensor device of claim 2, wherein said hydrogel is hydrophilic.

5. The sensor device of claim 2, wherein said gel monomer is ion-free.

6. The sensor device of claim 5, wherein said gel monomer is selected from the group consisting of acrylamide gels, purified agarose gels, N-vinylpyrolidone gels, and methacrylate gels.

7. The sensor device of claim 6, wherein said gel monomer is N-isopropylacrylamide.

8. The sensor device of claim 1, wherein said volume change is between about 0.1 and 50%.

9. The sensor device of claim 1, wherein said molecular recognition monomer is selected from the group consisting of crown ethers, cyclodextrans and caloxarenes.

10. The sensor device of claim 9, wherein said monomer capable of molecular recognition is 4-acrylamidobenzo 18-crown-6 ether.

11. The sensor device of claim 1, wherein said crosslinking agent is selected from the group consisting of N,N'"'"'-methylenebisacrylamide, methylenebismethacrylamide and ethyleneglycol-dimethacrylate.

12. The sensor device of claim 11, wherein said crosslinking agent is N,N'"'"'-methylenebisacrylamide.

13. The sensor device of claim 1, wherein said charged particles are selected from the group consisting of colloidal polystyrene, polymethylmethacrylate, silicon dioxide, aluminum oxide, polytetrafluoroethylene and poly N-isopropylacrylamide.

14. The sensor device of claim 1, wherein said chemical stimulus is selected from the group consisting of lead ions, potassium ions and sodium ions.

15. The sensor device of claim 2, wherein said hydrogel further comprises a third monomer.

16. The sensor device of claim 15, wherein said third monomer is an acrylamide or a substituted acrylamide.

17. The sensor device of claim 1, wherein said hydrogel is comprised of a crosslinking agent, a gel monomer, and a biomolecular recognition component.

18. The sensor device of claim 17, wherein said biomolecular recognition component is selected from the group consisting of enzymes, antigens, nucleic acids, nucleic acid sequences, amino acids, amino acid sequences, peptides and antibodies.

19. The sensor device of claim 17, further comprising one or more linking molecules that link said biomolecular recognition component to said gel monomer.

20. The sensor device of claim 19, wherein said linking molecule is 5-(biotinamido)pentylamine.

21. The sensor device of claim 19, wherein said biomolecular recognition component has been reacted with a linking molecule that can be bound to a second linking molecule or to the gel.

22. The device of claim 21, wherein avidin is the linking molecule that can be bound to a second linking agent or to the gel.

74. The sensor device of claim 2, wherein said hydrogel is hydrophobic.

23. A method of making a sensor device comprising:

a) allowing charged colloidal particles to self-assemble into a crystalline colloidal array;

b) adding a first comonomer that is a gel monomer, a crosslinking agent, a second comonomer capable of molecular recognition and a polymerization initiator to a medium comprising said crystalline colloidal array; and

c) polymerizing the mixture of step b) to form a crystalline colloidal array embedded in a hydrogel, wherein said hydrogel undergoes a volume change in response to a chemical species.

24. The method of claim 23, including employing the device to detect a particular chemical stimulus by using as the second comonomer a monomer capable of recognizing the chemical stimulus to be detected.

25. The method of claim 24, including employing a UV photoinitiator and wherein said polymerization step is effected by exposing the mixture of step b) to UV light.

26. The method of claim 23, including employing a hydrogel that is hydrophilic.

27. The method of claim 23, including employing a gel monomer that is an ion-free gel.

28. The method of claim 27, including employing a gel monomer selected from the group consisting of acrylamide gels, purified agarose gels, N-vinylpyrolidone gels, and methacrylate gels.

29. The method of claim 28, including employing as said gel monomer N-isopropylacrylamide.

30. The method of claim 23, including employing a molecular recognition monomer selected from the group consisting of crown ethers, cyclodextrans, and caloxarenes.

31. The method of claim 30, including employing a 4-acrylamidobenzo 18-crown-6 ether.

32. The method of claim 23, including employing a crosslinking agent selected from the group consisting of N,N'"'"'-methylenebisacrylamide, methylenebismethacrylamide and ethyleneglycol-dimethacrylate.

33. The method of claim 32, including employing as said crosslinking agent N,N'"'"'-methylenebisacrylamide.

34. The method of claim 23, including employing charged particles selected from the group consisting of colloidal polystyrene, polymethylmethacrylate, silicon dioxide, aluminum oxide, polytetrafluoroethylene and poly(N-isopropylacrylamide) as said charged colloidal particles.

35. The method of claim 23, including employing in said hydrogel a third monomer.

36. The method of claim 35, including employing as said third monomer an acrylamide or a substituted acrylamide.

47. The method of claim 27, including employing charged particles selected from the group consisting of colloidal polystyrene, polymethylmethacrylate, silicon dioxide, aluminum oxide, polytetrafluoroethylene and poly N-isopropylacrylamide as said charged colloidal particles.

75. The method of claim 23, including employing a medium that is hydrophobic.

37. A method of making a sensor device comprising:

a) allowing charged colloidal particles to self assemble into a crystalline colloidal array;

b) adding a gel monomer, a crosslinking agent and a polymerization initiator to a medium comprising said crystalline colloidal array;

c) polymerizing the mixture of step b) to form a crystalline colloidal array embedded in a hydrogel; and

d) adding a biomolecular recognition component to the product of step c), wherein said hydrogel undergoes a volume change in response to a chemical species.

38. The method of claim 37, wherein said biomolecular recognition component is added to the product of step c) by use of one or more linking molecules.

39. The method of claim 38, wherein said biomolecular recognition component is reacted with a linking molecule that can be bound to either a second linking molecule or to the gel.

40. The method of claim 37, including the step of hydrolyzing the polymerized crystalline colloidal array of step c) before adding a biomolecular recognition component.

41. The method of claim 37, including employing a UV photoinitiator and wherein said polymerization step is effected by exposing the mixture of step b) to UV light.

42. The method of claim 37, including employing a gel monomer selected from the group consisting of acrylamide gels, purified agarose gels, N-vinylpyrolidone gels, and methacrylate gels.

43. The method of claim 42, including employing as said gel monomer N-isopropylacrylamide.

44. The method of claim 37, including employing a biomolecular recognition component selected from the group consisting of enzymes, antigens, nucleic acids, nucleic acid sequences, amino acids, amino acid sequences, peptides and antibodies.

45. The method of claim 37, including employing a crosslinking agent selected from the group consisting of N,N'"'"'-methylenebisacrylamide, methylenebismethacrylamide and ethyleneglycol-dimethacrylate.

46. The method of claim 45, including employing as said crosslinking agent N,N'"'"'-methylenebisacrylamide.

48. The method of claim 38, including employing as said linking molecule 5-(biotinamido)pentylamine.

49. The method of claim 39, including employing avidin as the linking molecule that can be bound to a second linking agent or to the gel.

50. A sensor device comprising:

a first network comprising a crystalline colloidal array of charged particles polymerized in a hydrogel matrix; and

a second network interpenetrating with said first network comprising a polymer to which is attached a molecular recognition monomer, wherein said sensor device undergoes a volume change in response to a specific chemical species, said crystalline colloidal array having a lattice spacing that changes when said volume of said hydrogel changes, thereby causing the diffracted wavelength of the crystalline colloidal array to change.

51. The sensor device of claim 50, wherein said device detects a particular chemical species by using a second polymer in said second polymer network capable of recognizing the chemical species to be detected.

52. The sensor device of claim 50, wherein said charged particles are selected from the group consisting of colloidal polystyrene, polymethylmethacrylate, silicon dioxide, aluminum oxide, polytetrafluoroethylene and poly N-isopropylacrylamide.

53. The sensor device of claim 50, wherein said hydrogel is hydrophilic.

54. The sensor device of claim 50, wherein said hydrogel is comprised of a gel monomer which is ion-free.

55. The sensor device of claim 54, wherein said gel monomer is selected from the group consisting of acrylamide gels, purified agarose gels, N-vinylpyrolidone gels, and methacrylate gels.

56. The sensor device of claim 55, wherein said gel monomer is N-isopropylacrylamide.

57. The sensor device of claim 50, wherein said volume changes between 0.1 and 50%.

58. The sensor device of claim 50, wherein said molecular recognition monomer is selected from the group consisting of crown ethers, cyclodextrans and caloxarenes.

59. The sensor device of claim 58, wherein said monomer capable of molecular recognition is 4-acrylamidobenzo 18-crown-6 ether.

76. The sensor device of claim 50, wherein said hydrogel is hydrophobic.

60. A method of making a sensor device comprising:

a) allowing charged particles to self assemble into a crystalline colloidal array;

b) adding a first comonomer that is a gel monomer, a crosslinking agent and a polymerization initiator to said crystalline colloidal array;

c) polymerizing said mixture of step b) to form a hydrogel, such that a first network comprising a crystalline colloidal array polymerized in said hydrogel is formed;

d) diffusing a second comonomer having a molecular recognition monomer into said first network; and

e) polymerizing the product of step d) to create a second network which is interpenetrating with said first network, wherein said sensor device undergoes a volume change in response to a specific chemical stimulus.

61. The sensor device of claim 60, wherein said device is modified to detect different chemical stimuli by using as the second comonomer a monomer capable of recognizing the chemical stimuli to be detected.

62. The sensor device of claim 60, wherein said hydrogel is hydrophilic.

63. The sensor device of claim 60, wherein said gel monomer is ion-free.

64. The sensor device of claim 63, wherein said gel monomer is selected from the group consisting of acrylamide gels, purified agarose gels, N-vinylpyrolidone gels, and methacrylate gels.

65. The sensor device of claim 64, wherein said gel monomer is N-isopropylacrylamide.

66. The sensor device of claim 60, wherein said molecular recognition monomer is capable of binding to a selected analyte.

67. The sensor device of claim 66, wherein said molecular recognition monomer is selected from the group consisting of crown ethers, cyclodextrans and caloxarenes.

68. The sensor device of claim 67, wherein said monomer capable of molecular recognition is 4-acrylamidobenzo 18-crown-6 ether.

69. The sensor device of claim 60, wherein said crosslinking agent is selected from the group consisting of N,N'"'"'-methylenebisacrylamide, methylenebismethacrylamide and ethyleneglycol-dimethacrylate.

70. The sensor device of claim 68, wherein said crosslinking agent is N,N'"'"'-methylenebisacrylamide.

71. The sensor device of claim 60, wherein said charged particles are selected from the group consisting of colloidal polystyrene, polymethylmethacrylate, silicon dioxide, aluminum oxide, polytetrafluoroethylene and poly N-isopropylacrylamide.

72. The sensor device of claim 60, wherein said hydrogel is hydrophobic.

73. A sensor device for measuring analyte concentration in the tear fluid comprising:

a hydrogel that undergoes a volume change in response to a specific chemical stimulus;

a light diffracting crystalline colloidal array of charged particles polymerized in said hydrogel, said crystalline colloidal array having a lattice spacing that changes when said volume of said hydrogel changes, thereby causing the diffracted wavelength of the crystalline colloidal array to change; and

wherein said sensor device is placed on the eye.