MICROPOROUS MATERIALS, METHODS OF MAKING, USING, AND ARTICLES THEREOF

• US 20090011403A1
• Filed: 05/17/2005
• Published: 01/08/2009
• Est. Priority Date: 05/26/2004
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Voelkerding, Karl V., Elgort, Marc G., Durtschi, Jacob, Smith, Roger E.
• Granted Patent: US 8,304,026 B2
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: B01D 67/0065 by anodic oxidation
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: B01D 67/00931 by introduction of specific groups after membrane formation, e.g. by grafting
• CPC Class Codes: B01D 69/12 Composite membranes; Ultra-thin membranes
• CPC Class Codes: B01D 71/0221 Group 4 or 5 metals
• CPC Class Codes: B01D 71/02231 Palladium
• CPC Class Codes: B01D 71/02232 Nickel
• CPC Class Codes: B01D 71/025 Aluminium oxide
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• 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 2300/0681 Filter
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 20/00 : Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/68 : involving nucleic acids
• CPC Class Codes: C12Q 1/6813 : Hybridisation assays
• CPC Class Codes: C12Q 1/6844 : Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/703 : Viruses associated with AIDS
• CPC Class Codes: C12Q 2565/137 : Chromatographic separation
• CPC Class Codes: G01N 21/4738 : Diffuse reflection precedence is given to G01N21/55 - G01N21/57 if specular component is taken into consideration, e.g. also for testing fluids, fibrous materials
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6456 : Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: Y10T 428/249978 : Voids specified as micro

Abstract

Described herein are methods for separating one or more analytes present in a fluid sample. The methods involve passing the fluid through or into a microporous material, wherein the analytes are localized near the surface of the microporous material. Additional processing steps such as hybridization and amplification can be performed once the analyte is localized. In one method, once the analyte is localized, the analyte can be detected, counted, and correlated in order to determine the concentration of the analyte in the sample. In another method, the localized analyte is destabilized to make the localized analyte more accessible for chemical manipulation. Modified microporous materials and composite materials are also disclosed that can be used in any of the methods and articles described herein. The composite is composed of a microporous material and a pigment, wherein the pigment is incorporated in the microporous material. The pigments alter the optical properties of the microporous material, which enhances the detection of analyte once it is localized. Methods for making pigmented composites are also disclosed. In a further aspect, various kits and articles such as filtration devices containing any of the microporous materials described herein are provided.

Claims

1. A method for producing a pigmented composite, comprising

(a) contacting a microporous material with a tin compound to produce a first composite, and

(b) contacting the first composite with a pigment comprising an elemental metal, a metal oxide, a metal alloy, a metal salt, or a combination thereof to produce the pigmented composite.

2. The method of claim 1, wherein the microporous material comprises a ceramic, a metal, carbon, or glass.

3. The method of claim 1, wherein the microporous material comprises a metal oxide.

4. The method of claim 3, wherein the metal oxide comprises aluminum oxide, zirconium oxide, titanium oxide, a zeolite, or a combination thereof.

5. The method of claim 1, wherein the microporous material comprises an inorganic electrochemically formed material or an etch material.

6. The method of claim 1, wherein the microporous material comprises aluminum oxide that is electrochemically formed or etched.

7. The method of claim 1, wherein the microporous material comprises micropores having a diameter of from about 0.02 microns to about 0.2 microns.

8. The method of claim 1, wherein the microporous material comprises aluminum or titanium that has been anodized.

9. The method of claim 1, wherein the tin compound comprises an organotin compound or a tin salt.

10. The method of claim 1, wherein the tin compound comprises a compound that produces Sn⁺² ions in solution.

11. The method of claim 1, wherein the tin compound comprises SnCl₂.

12. The method of claim 1, wherein the pigment comprises a metal salt.

13. The method of claim 12, wherein when the metal salt comprises a transition metal salt.

14. The method of claim 13, wherein the transition metal salt comprises a palladium compound, a nickel compound, silver compound, gold compound, or a combination thereof.

15. The method of claim 1, wherein the tin compound is dissolved in an organic solvent to produce a tin solution.

16. The method of claim 15, wherein the tin solution further comprises water.

17. The method of claim 1, wherein the pigment is dissolved in an organic solvent to produce a pigment solution.

18. The method of claim 17, wherein the pigment solution further comprises water.

19. The method of claim 1, wherein in step (b), the first composite is contacted with a first pigment followed by contacting the first composite with a second pigment.

20. The method of claim 19, wherein the first pigment comprises a palladium compound and the second pigment comprises a nickel compound.

21. The method of claim 1, wherein the microporous material comprises aluminum oxide, the tin compound comprises a tin salt, and the pigment comprises a first pigment and second pigment, wherein the first composite is contacted with a first pigment comprising a palladium compound followed by contacting the first composite with a second pigment comprising a nickel compound.

22. The method of claim 1, wherein after step (b), heating the second composite.

23. The method of claim 1, further comprising after step (b), applying a suspension matrix to the pigmented composite, wherein the suspension matrix is localized near the surface of the pigmented composite.

24. The method of claim 23, wherein the suspension matrix comprises an oligonucleotide, a polysaccharide, a protein, an organic or inorganic polymer or macromolecule, or a combination thereof.

25. The method of claim 23, wherein when the suspension matrix comprises an oligonucleotide, wherein the oligonucleotide comprises a nucleic acid.

26. A pigmented composite produced by the method of claim 1.

28. An article comprising the pigmented composite of claim 26.

49. The method of claim 30, wherein the microporous material comprises the pigmented composite of claim 26.

27. A pigmented composite comprising a microporous material, a tin compound, and at least one pigment, wherein the tin compound and pigment are incorporated in the microporous material.

29. An article comprising the pigmented composite of claim 27.

50. The method of claim 30, wherein the microporous material comprises the pigmented composite of claim 27.

30. A method for detecting an analyte, comprising

(a) passing a fluid sample comprising the analyte through or into a microporous material, wherein the analyte is localized near the surface of the microporous material;

(b) destabilizing at least some of the localized analyte; and

(c) detecting the destabilized analyte.

31. The method of claim 30, wherein the destabilizing step comprises (1) contacting the localized analyte with a base;

(2) agitating the localized analyte;

(3) heating the localized analyte;

(4) contacting the localized analyte with one or more ionic species;

(5) contacting the localized analyte with one or more enzymes;

(6) applying an electrical charge or ionizing energy to the localized analyte;

(7) contacting the localized analyte with an organic solvent, or a combination of any of the steps above.

32. The method of claim 30, wherein the destabilizing step comprises contacting the localized analyte with a base.

33. The method of claim 32, wherein the base has a pH of greater than 9.

34. The method of claim 32, wherein the base has a pH of from 10 to 12.

35. The method of claim 32, wherein the base comprises an inorganic base or a buffer.

36. The method of claim 30, wherein the destabilizing step comprises agitating the localized analyte.

37. The method of claim 36, wherein the agitation step comprises sonication, vortex mixing, or pumping.

38. The method of claim 30, wherein the destabilizing step comprises heating the localized analyte above 25°

C. from 60°

C. to 100°

C.

39. The method of claim 30, wherein the delocalizing step comprises contacting the localized analyte with one or more ionic species.

40. The method of claim 39, wherein the ionic species comprises phosphate ions, borate ions, or a combination thereof.

41. The method of claim 30, wherein the destabilizing step comprises contacting the localized analyte with one or more enzymes.

42. The method of claim 41, wherein the enzyme comprises a restriction endonuclease, a nick enzyme, or a helicase.

43. The method of claim 30, wherein the microporous material comprises an inorganic electrochemically formed membrane or an etch membrane.

44. The method of claim 30, wherein the microporous material comprises micropores having a diameter of less than 0.2 microns.

45. The method of claim 30, wherein the microporous material comprises micropores having a diameter of from about 0.02 microns to about 0.2 microns.

46. The method of claim 30, wherein the microporous material comprises aluminum or titanium that has been anodized.

47. The method of claim 30, wherein the microporous material comprises a metal oxide.

48. The method of claim 47, wherein the metal oxide comprises aluminum oxide, zirconium oxide, titanium oxide, zeolite, or a combination thereof.

51. The method of claim 30, wherein the microporous material comprises a composite comprising a microporous material and a pigment, wherein the pigment is incorporated in the microporous material.

52. The method of claim 51, wherein the pigment is covalently attached to the microporous material.

53. The method of claim 52, wherein the pigment is attached to the microporous material by a linker.

54. The method of claim 53, wherein the linker comprises an organosilyl group.

55. The method of claim 52, wherein the pigment is attached to the microporous material by a hydroxyl group, a carboxyl group, a sulfhydryl group, an amine group, or a combination thereof present on the surface of the microporous material.

56. The method of claim 52, wherein the pigment comprises an organic dye.

57. The method of claim 56, wherein the organic dye comprises an isothiocyanate, a triazine, or an ester.

58. The method of claim 51, wherein the microporous material comprises a ceramic, a metal, carbon, or glass.

59. The method of claim 51, wherein the microporous material comprises a metal oxide.

60. The method of claim 59, wherein the metal oxide comprises aluminum oxide, zirconium oxide, titanium oxide, a zeolite, or a combination thereof.

61. The method of claim 51, wherein the microporous material comprises an inorganic electrochemically formed material or an etch material.

62. The method of claim 51, wherein the microporous material comprises micropores having a diameter of from about 0.02 microns to about 0.2 microns.

63. The method of claim 51, wherein the microporous material comprises aluminum oxide and the pigment comprises an organic dye, wherein the organic dye is covalently attached to the microporous material by a linker comprising an organosilyl group.

64. The method of claim 51, wherein the pigment is deposited on the microporous material.

65. The method of claim 64, wherein the pigment comprises an elemental metal, a metal oxide, a metal alloy, or a combination thereof.

66. The method of claim 65, wherein when the pigment comprises an elemental metal, the elemental metal comprises a transition metal.

67. The method of claim 66, wherein the transition metal comprises palladium, nickel, silver, gold, or a combination thereof.

68. The method of claim 51, wherein the microporous material comprises aluminum oxide and the pigment comprises one or more elemental transition metals deposited on the microporous material.

69. The method of claim 68, wherein the elemental transition metal comprises palladium, nickel, or a combination thereof.

70. The method of claim 30, wherein the fluid sample comprises a biofluid, wherein the biofluid comprises whole blood, serum, plasma, cerebral spinal fluid, urine, saliva, semen, sputum, bronchalveolar lavage fluid, joint aspirate, or wound drainage.

71. The method of claim 30, wherein the fluid sample comprises a bacterium, a virus, a fungus, a spore, a cell culture, a fecal excrement, an animal tissue or cell, a vegetable tissue or cell, a lysed ingredient thereof, or a combination thereof.

72. The method of claim 30, wherein the fluid sample is prefiltered or treated to remove impurities prior to passing through the microporous material.

73. The method of claim 30, wherein the fluid sample further comprises a buffer, a salt, an enzyme, a surfactant, a chaotropic agent, or a combination thereof.

74. The method of claim 30, wherein the fluid sample further comprises NaCl.

75. The method of claim 30, wherein the analyte comprises a virus, a protein, a parasite, a fungus, an effector molecule, a ligand, a receptor, a signal-generating molecule, a structural molecule, an ion, an antigen, an antibody, a tissue, a cell, a component of a cell, a bacterium, a protein, or a combination thereof.

76. The method of claim 30, wherein the analyte comprises a nucleic acid.

77. The method of claim 76, wherein the nucleic acid comprises RNA or DNA having at least about 1,500 bases or base pairs.

78. The method of claim 76, wherein the nucleic acid comprises a virion.

79. The method of claim 78, wherein the virion comprises an HIV virion.

80. The method of claim 76, wherein the nucleic acid is labeled with a detectable tracer, wherein the detectable tracer comprises a group comprising a fluorescent microbead, a quantum dot, a surface plasmon resonance particle, a fluorescence generating enzyme, a fluorescent dye, or a combination thereof.

81. The method of claim 76, wherein after step (a), the localized nucleic acid comprises a specifically localized target nucleic acid.

82. The method of claim 81, wherein the specifically localized target nucleic acid is labeled with a tracer comprising a fluorescent nucleic acid dye.

83. The method of claim 76, wherein after step (a) the localized nucleic acid comprises a non-specifically localized nucleic acid.

84. The method of claim 83, wherein the non-specifically localized nucleic acid comprises a target nucleic acid labeled with a specific binding probe comprising a fluorescent tracer.

85. The method of claim 83, wherein the non-specifically localized nucleic acid comprises a target nucleic acid hybridized with a specific binding probe to form a surface localized hybrid.

86. The method of claim 30, wherein at least some of the analyte is labeled either before or after step with a detectable tracer (a) to produce a labeled analyte.

87. The method of claim 30, wherein the detection step (b) is performed by optical detection.

88. The method of claim 86, wherein after step (b), (c) counting the labeled analyte on the microporous material, and (d) correlating the counted analyte with the known volume of the fluid sample to determine the analyte concentration in the fluid sample.

89. The method of claim 85, wherein the surface localized hybrid is labeled with fluorescent nucleic acid dye.

90. The method of claim 76, wherein the nucleic acid is labeled with a detectable tracer comprising two or more different detectable tracer molecules attached to the nucleic acid.

91. The method of claim 90, wherein the detectable tracer molecules comprise fluorescent tracer molecules.

92. The method of claim 91, wherein the labeled nucleic acid has a sufficient fluorescence to achieve a signal-to-noise ratio of greater than 3.

93. The method of claim 91, wherein the labeled nucleic acid has a sufficient fluorescence to achieve a signal-to-noise ratio from about 3 to about 10.

94. The method of claim 86, wherein the labeled analyte is counted by optical interrogation of a detection area sufficiently small so as to allow none or one labeled analyte to be detected within the detection area.

95. The method of claim 86, wherein the labeled analyte is optically detected with a scanning confocal epifluorometer.

96. The method of claim 86, wherein the labeled analyte is optically detected with a CCD array based fluorescent device.

97. The method of claim 30, wherein prior to step (a), adding a suspension matrix to the fluid sample, wherein the suspension matrix interacts with the analyte.

98. The method of claim 97, wherein the suspension matrix comprises an oligonucleotide, a polysaccharide, a protein, an organic or inorganic polymer or macromolecule, or a combination thereof.

99. The method of claim 97, wherein the suspension matrix comprises calf thymus nucleic acid or salmon sperm nucleic acid.

100. The method of claim 97, wherein the suspension matrix comprises polyethylene glycol or polyvinyl pyrrolidone.

101. The method of claim 97, wherein the localized analyte, the suspension matrix, or a combination is destabilized.

102. The method of claim 30, wherein prior to step (a), localizing a suspension matrix on the microporous material, wherein after step (a), some analyte is localized on the suspension matrix.

103. The method of claim 102, wherein the localized analyte, the suspension matrix, or a combination is destabilized.

104. A method for amplifying a nucleic acid, comprising

(a) passing a fluid sample comprising the nucleic acid through or into a microporous material, wherein the nucleic acid is localized near the surface of the microporous material;

(b) destabilizing at least some of the localized nucleic acid; and

(c) amplifying the destabilized nucleic acid.

105. A method for hybridizing a nucleic acid, comprising

(a) passing a fluid sample comprising the nucleic acid through or into a microporous material, wherein the nucleic acid is localized near the surface of the microporous material;

(b) destabilizing at least some of the localized nucleic acid; and

(c) hybridizing the destabilized nucleic acid.