Device and Method for Preparing a Sample for an Analysis and Device and Method for Analyzing a Sample

• US 20090035746A1
• Filed: 06/21/2006
• Published: 02/05/2009
• Est. Priority Date: 06/27/2005
• Status: Abandoned Application

• Current Assignee: Siemens AG
• Original Assignee: Siemens AG
• Inventors: Zilch, Christian, Ehben, Thomas
• Application Number:
  US11/922,879
• Publication Number:
  US 20090035746A1
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C

Abstract

A device and method are disclosed for preparing a sample for an analysis and a device and method are disclosed for analyzing a sample. In at least one embodiment, a device is disclosed for preparing a sample for analysis including means for binding at lest one biological structure of the sample, means for releasing at least one biological molecule contained in the at least one structure, and means for binding the at least one released molecule. The means for binding the at least one structure and the means for binding the at least one molecule can move.

Claims

1. A device for preparing a sample for an analysis, comprising:

means for binding at least one biological structure of the sample;

means for releasing at least one biological molecule contained in the at least one biological structure;

means for binding the at least one released biological molecule; and

at least one magnetic field generator to move the means for binding the at least one biological structure and the means for binding the at least one biological molecule.

2. The device as claimed in claim 1, wherein the means for binding the structure are embodied as a first substrate, linkable to the structure to form a substrate-structure complex, and wherein the means for binding the molecule are embodied as a second substrate, linkable to the molecule to form a substrate-molecule complex.

3. The device as claimed in claim 2, wherein the first substrate has a protein-binding property.

4. The device as claimed in claim 3, wherein the protein-binding property is embodied as at least one antibody, wherein the at least one antibody is directed toward the structure.

5. The device as claimed in claim 2, wherein the second substrate has a nucleic-acid-binding property.

6. The device as claimed in claim 5, wherein the nucleic-acid-binding property is embodied as an oligonucleotide complementary to the molecule.

7. The device as claimed in claim 5, wherein the nucleic-acid-binding property is embodied as silane.

8. The device as claimed in claim 2, wherein the first and second substrates each comprise at least one magnetic bead.

9. The device as claimed in claim 1, wherein the means for binding the structure and the means for binding the molecule are embodied as a third substrate, linkable both to the structure to form a substrate-structure complex and to the molecule to form a substrate-molecule complex.

10. The device as claimed in claim 9, wherein the third substrate has a protein-binding property and a nucleic-acid-binding property.

11. The device as claimed in claim 10, wherein the protein-binding property is embodied as at least one antibody and the nucleic-acid-binding property is embodied as an oligonucleotide, wherein the at least one antibody is directed toward the structure and the oligonucleotide is complementary to the molecule.

12. The device as claimed in claim 10, wherein the protein-binding property is embodied as antibody and the nucleic-acid-binding property is embodied as silane, wherein the at least one antibody is directed toward the structure.

13. The device as claimed in claim 9, wherein the substrate comprises at least one magnetic bead.

14. The device as claimed in claim 1, comprising a number of process chambers which contain at least temporarily the means for binding the structure, the means for releasing the molecule and the means for binding the molecule.

15. The device as claimed in claim 14, wherein the process chambers are embodied as a preparation chamber for using the means for binding the structure, and the device further comprising,

a structure disruption chamber for using the means for releasing the molecule and the means for binding the molecule.

16. The device as claimed in claim 15, wherein the means for binding the structure are stored in the preparation chamber and the means for releasing the molecule and the means for binding the molecule are stored in the structure disruption chamber.

17. The device as claimed in claim 1, further comprising means for replicating the molecule.

18. The device as claimed in claim 17, wherein the replicating means are stored in the structure disruption chamber of the device.

19. The device as claimed in claim 17, wherein the replicating means are stored in a further process chamber of the device, said further process chamber being embodied as an amplification chamber.

20. The device as claimed in claim 19, wherein at least one process chamber embodied as washing chamber is arranged between the structure disruption chamber and the amplification chamber.

21. The device as claimed in claim 14, wherein the process chambers are connectable by lines at least at times.

22. The device as claimed in claim 21, wherein lines are embodied as microchannels.

23. The device as claimed in claim 22, wherein at least one valve is included to close off at least one of the microchannels.

24. The device as claimed in claim 22, wherein the microchannels are dimensioned such that both the substrate-structure complex and the substrate-molecule complex are transportable through them and wherein a disturbing exchange of other substances between the process chambers is prevented while the process steps are carried out.

25. The device as claimed in claim 14, further comprising a single-use unit and a controller, the process chambers being contained in the unit.

26. The device as claimed in claim 25, wherein the means for binding the structure are embodied as a first substrate, linkable to the structure to form a substrate-structure complex, and wherein the means for binding the molecule are embodied as a second substrate, linkable to the molecule to form a substrate-molecule complex and wherein at least one magnetic field generator and the substrate-molecule complex are present in the controller.

27. The device as claimed in claim 26, wherein the at least one magnetic field generator is arranged in the controller.

28. The device as claimed in claim 27, wherein the at least one magnetic field generator is movable relative to the unit.

29. The device as claimed in claim 27, wherein the unit is movable relative to the at least one magnetic field generator.

30. The device as claimed in claim 27, wherein the at least one magnetic field generator is embodied as permanent magnet.

31. The device as claimed in claim 27, wherein the at least one magnetic field generator is embodied as electromagnet.

32. A device for analyzing a sample, comprising:

a device for preparing a sample as claimed in claim 1; and

means for detecting the at least one molecule.

33. The device as claimed in claim 32, wherein the means for detecting the molecule is arranged at least partly in the amplification chamber.

34. The device as claimed in claim 32, wherein the means for detecting the molecule is arranged at least partly in a process chamber of the device, said process chamber being embodied as detection chamber.

35. The device as claimed in claim 32, wherein the means for detecting the molecule comprise further means for binding the molecule.

36. The device as claimed in claim 35, wherein the further means for binding the molecule are arranged on a detection unit and the detection unit is arranged at least partly in the detection chamber.

37. The device as claimed in claim 35, wherein the further means for binding the molecule is embodied as at least one catcher probe.

38. The device as claimed in claim 37, wherein the substrate-molecule complex is immobilizeable by the catcher probe.

39. The device as claimed in claim 36, wherein the detection unit comprises a magnetoresistive sensor.

40. The device as claimed in claim 36, wherein the detection unit comprises an optical sensor.

41. The device as claimed in claim 36, wherein the detection unit comprises a gravimetric sensor.

42. A method for preparing a sample using a device including means for binding at least one biological structure of the sample, means for releasing at least one biological molecule contained in the at least one biological structure, means for binding the at least one released biological molecule, and at least one magnetic field generator to move the means for binding the at least one biological structure and the means for binding the at least one biological molecule, the method comprising:

binding the at least one biological structure of the sample with the means for binding the structure;

moving the bound at least one biological structure with the at least one magnetic field generator;

releasing the at least one biological molecule contained in the bound at least one biological structure; and

binding the released at least one biological molecule with the means for binding the molecule.

43. The method as claimed in claim 42, wherein the means for binding the structure are embodied as a first substrate, by which the structure is bound to form a substrate-structure complex, and the means for binding the molecule are embodied as a second substrate, by which the molecule is bound to form a substrate-molecule complex.

44. The method as claimed in claim 42, wherein the means for binding the structure and the means for binding the molecule are embodied as a third substrate, by which the structure is bound to form a substrate-structure complex and by which the molecule is bound to form a substrate-molecule complex.

45. The method as claimed in claim 43, wherein, after the binding of the structure to the substrate, the resulting substrate-structure complex is separated from the sample.

46. The method as claimed in claim 45, wherein the separation is effected by moving the substrate-structure complex into the structure disruption chamber.

47. The method as claimed in claim 46, wherein the substrate comprises at least one magnetic bead and a magnetic field is used for moving the substrate-structure complex.

48. The method as claimed in claim 47, wherein the magnetic field is generated by the at least one electromagnet of the device.

49. The method as claimed in claim 47, wherein the magnetic field is generated by the permanent magnet of the device.

50. The method as claimed in claim 49, wherein the permanent magnet is moved for moving the substrate-structure complex.

51. The method as claimed in claim 47, wherein the single-use unit of the device is moved relative to the permanent magnet.

52. The method as claimed in claim 42, wherein, after the molecules have been released, the means for binding the structure is removed from the substrate.

53. The method as claimed in claim 52, wherein the protein-binding property of the substrate is removed by use of a protease enzyme.

54. The method as claimed in claim 52, wherein the released molecules are comminuted.

55. The method as claimed in claim 54, wherein each of the molecules is a nucleic acid and the nucleic acid is comminuted by a nuclease.

56. The method as claimed in claim 54, wherein the substrate-molecule complex is moved to and fro during comminution.

57. The method as claimed in claim 42, wherein the released molecules are denatured.

58. The method as claimed in claim 57, wherein the molecules are denatured by an increase in temperature.

59. The method as claimed in claim 57, wherein the molecules are denatured chemically.

60. The method as claimed in claim 42, wherein only a prokaryotic nucleic acid is bound to the substrate-molecule complex by the substrate.

61. The method as claimed in claim 42, wherein the substrate-molecule complex is moved into the amplification chamber of the device and an amplification of the molecule is carried out.

62. The method as claimed in claim 61, wherein the amplification is performed by means of a PCR, wherein the PCR comprises at least one thermal cycle.

63. The method as claimed in claim 61, wherein the nucleic acid is an RNA and is reverse transcribed into cDNA prior to the amplification.

64. A method for analyzing a sample, comprising:

preparing the sample by a method as claimed in claims 42; and

detecting the molecule.

65. The method as claimed in claim 64, wherein the molecule is detected by detecting a binding of the molecule to the catcher probe.

66. The method as claimed in claim 64, wherein the substrate-molecule complex is moved to the catcher probe.

67. The method as claimed in claim 64, wherein the immobilized magnetic beads are detected for detecting the hybridization.

68. A method for preparing a sample, comprising:

binding the at least one biological structure of a sample;

using at least one magnetic field generator to move the at least one bound biological structure;

releasing the at least one biological molecule contained in the bound structure; and

binding the released at least one biological molecule.