Functionalized platform for individual molecule or cell characterization

• US 20050287523A1
• Filed: 05/26/2005
• Published: 12/29/2005
• Est. Priority Date: 06/01/2004
• Status: Abandoned Application

• Current Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Hope-Weeks, Louisa J., Letant, Sonia E., Terminello, Louis J., van Buuren, Anthony W.
• Application Number:
  US11/140,391
• Publication Number:
  US 20050287523A1
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0896 Nanoscaled
• CPC Class Codes: B01L 3/50857 using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/03 Cuvette constructions

Abstract

A system for characterization of a single molecule or cell sample by directing a beam onto the sample to produce energy emanating from the sample. A periodic sample holder with through-pores containing the sample is positioned to receive the beam. At least one pore is provided in the sample holder for holding the sample. The energy emanating from the sample is detected by a detector. The sample holder can be used to study individual molecules, viruses, or cells by various techniques including x-ray diffraction, chemical analysis, optical or electron microscopy, or electrochemistry.

Claims

1. An apparatus for characterization of a sample, comprising:

a source for directing a beam onto the sample to produce energy emanating from the sample,

a sample holder,

at least one pore in said sample holder for holding the sample, and

a detector for detecting said energy emanating from the sample.

2. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a nano-size pore.

3. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a micro-size pore.

4. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a single molecule.

5. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a biological molecule.

6. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a non-biological sample.

7. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a small crystal.

8. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a protein.

9. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a virus.

10. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a pseudo-protein crystal.

11. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder holds the sample in a hydrated state.

12. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a cell.

13. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder is a pore that holds a spore.

14. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder for holding the sample is a through-pore that extends through said sample holder.

15. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder for holding the sample is a through-pore that extends through said sample holder and said through-pore is an aperture with localized oxide.

16. The apparatus for characterization of a sample of claim 1 wherein said at least one pore in said sample holder for holding the sample is a through-pore that extends through said sample holder and said through-pore is an aperture with localized TEOS oxide.

17. The apparatus for characterization of a sample of claim 1 wherein said beam is an x-ray beam.

18. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is a pulsed x-ray beam.

19. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is a neutron beam.

20. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is an electron beam.

21. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is a photon beam.

22. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is a photon beam for optical experiments.

23. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is an ion beam.

24. The apparatus for characterization of a sample of claim 1 wherein said diffractive beam is an ion beam for SIMS measurements.

25. The apparatus for characterization of a sample of claim 1 wherein said sample holder comprises a silicon platform.

26. The apparatus for characterization of a sample of claim 1 wherein said sample holder comprises a rigid silicon platform.

27. The apparatus for characterization of a sample of claim 1 including means for moving said sample holder.

28. The apparatus for characterization of a sample of claim 1 including a linking system connected to said at least one pore in said sample holder for anchoring the sample in said at least one pore.

29. The apparatus for characterization of a sample of claim 1 including a cross-linking system connected to said at least one pore in said sample holder for anchoring the sample in said at least one pore.

30. The apparatus for characterization of a sample of claim 1 including a cross-linking system connected to said at least one pore in said sample holder for anchoring larger proteins in said at least one pore.

31. The apparatus for characterization of a sample of claim 1 including a cross-linking system connected to said at least one pore in said sample holder for anchoring enzymes in said at least one pore.

32. The apparatus for characterization of a sample of claim 1 including a covalent anchor connected to said at least one pore in said sample holder.

41. The apparatus for characterization of a sample of claim 1 wherein said pore means for holding the sample is a through-pore that extends through said sample holder means.

42. The apparatus for characterization of a sample of claim 1 wherein said pore means for holding the sample is a through-pore that extends through said sample holder means and said through-pore is an aperture with localized oxide.

43. The apparatus for characterization of a sample of claim 1 wherein said pore means for holding the sample is a through-pore that extends through said sample holder means and said through-pore is an aperture with localized TEOS oxide.

33. An apparatus for characterization of a sample, comprising:

source means for directing a beam onto the sample to produce energy emanating from the sample,

sample holder means,

pore means in said sample holder means for holding the sample, and

detector means for detecting said energy emanating from the sample.

34. The apparatus for characterization of a sample of claim 33 wherein said source means is a source for producing an x-ray beam and said energy emanating from the sample is a diffraction pattern.

35. The apparatus for characterization of a sample of claim 33 wherein said source means is a source for producing a pulsed x-ray beam and said energy emanating from the sample is a diffraction pattern.

36. The apparatus for characterization of a sample of claim 33 wherein said source means is a source for producing a neutron beam.

37. The apparatus for characterization of a sample of claim 33 wherein said source means is a source for producing an electron beam.

38. The apparatus for characterization of a sample of claim 33 wherein said source means is a source for producing a photon beam.

39. The apparatus for characterization of a sample of claim 33 wherein said source means is a source for producing an ion beam.

40. The apparatus for characterization of a sample of claim 33 including means for moving said sample holder means.

44. The apparatus for characterization of a sample of claim 33 including a linking system connected to said pore means in said sample holder means for anchoring the sample in said pore means.

45. The apparatus for characterization of a sample of claim 33 including a cross-linking system connected to said pore means in said sample holder means for anchoring the sample in said pore means.

46. The apparatus for characterization of a sample of claim 33 including a cross-linking system connected to said pore means in said sample holder means for anchoring larger proteins in said pore means.

47. The apparatus for characterization of a sample of claim 33 including a cross-linking system connected to said pore means in said sample holder means for anchoring enzymes in said pore means.

48. The apparatus for characterization of a sample of claim 33 including a covalent anchor connected to said pore means in said sample holder.

49. A method of characterization of a sample, comprising the steps of:

producing a beam,

providing a sample holder,

providing at least one through-pore in said sample holder that extends through said sample holder,

positioning the sample in said sample holder,

positioning said beam and said sample holder so that the sample receives said beam, and

detecting energy released from the sample.

50. The method for characterization of a sample of claim 49 wherein said step of providing at least one through-pore in said sample holder comprises providing a nano-size through-pore in said sample holder.

51. The method for characterization of a sample of claim 49 wherein said step of providing at least one through-pore in said sample holder comprises providing a micro-size through-pore in said sample holder.

52. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a single molecule in said through-pore in said sample holder.

53. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a biological molecule in said through-pore in said sample holder.

54. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a non-biological molecule in said through-pore in said sample holder.

55. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a small crystal in said through-pore in said sample holder.

56. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a protein in said through-pore in said sample holder.

57. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a virus in said through-pore in said sample holder.

58. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a pseudo-protein crystal in said through-pore in said sample holder.

59. The method for characterization of a sample of claim 49 wherein said step of positioning the sample in said sample holder comprises positioning a cell in said through-pore in said sample holder.

60. The method for characterization of a sample of claim 49 wherein said step of producing a beam comprises producing an x-ray beam.

61. The method for characterization of a sample of claim 49 wherein said step of producing a beam comprises producing a pulsed x-ray beam.

62. The method for characterization of a sample of claim 49 wherein said step of producing a beam comprises producing a neutron beam.

63. The method for characterization of a sample of claim 49 wherein said step of directing a beam onto the sample comprises directing an electron beam onto the sample.

64. The method for characterization of a sample of claim 49 wherein said step of directing a beam onto the sample comprises directing a proton beam onto the sample.

65. The method for characterization of a sample of claim 49 wherein said step of directing a beam onto the sample comprises directing an ion beam onto the sample.

66. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder comprises providing at least one pore in a silicon platform.

67. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder comprises providing at least one pore in a rigid silicon platform.

68. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder includes providing a linking system connected to said at least one pore in said sample holder for anchoring the sample in said at least one pore.

69. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder includes providing a cross-linking system connected to said at least one pore in said sample holder for anchoring the sample in said at least one pore.

70. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder includes providing a cross-linking system connected to said at least one pore in said sample holder for anchoring larger proteins in said at least one pore.

71. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder includes providing a cross-linking system connected to said at least one pore in said sample holder for anchoring enzymes in said at least one pore.

72. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder includes providing a covalent anchor connected to said at least one pore in said sample holder.

73. The method for characterization of a sample of claim 49 wherein said step of providing at least one pore in said sample holder includes providing at least one pore in said sample holder that holds the sample in a hydrated state.

74. A sample holder apparatus adapted for characterization of a sample using a beam, comprising:

a rigid platform having a first side and a second side, and

a through-pore in said rigid platform that extends through said rigid platform from first side to said second side, wherein said through-pore being is of size that holds a single molecule sample or a single cell sample, and wherein said through-pore has an entrance on said first side for receiving said single molecule sample or a single cell sample and the beam and an exit on said second side.

75. The sample holder apparatus of claim 74 wherein said through-pore is a nano-size through-pore.

76. The sample holder apparatus of claim 74 wherein said through-pore is a micro-size through-pore.

77. The sample holder apparatus of claim 74 wherein said through-pore is an aperture with localized oxide.

78. The sample holder apparatus of claim 74 wherein said through-pore is an aperture with localized TEOS oxide.

79. The sample holder apparatus of claim 74 including a linking system connected to said through-pore for anchoring the sample in said through-pore.

80. The sample holder apparatus of claim 74 including means for moving said rigid platform.

81. The sample holder apparatus of claim 74 wherein said rigid platform is a rigid silicon platform.

82. The sample holder apparatus of claim 74 wherein said rigid platform is a rigid glass platform.