Sample processing device and method

• US 20050019875A1
• Filed: 08/16/2004
• Published: 01/27/2005
• Est. Priority Date: 12/29/2000
• Status: Active Grant

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: CHEN Ching-Too
• Inventors: Chen, Shuqi
• Granted Patent: US 6,964,862 B2
• Time in Patent Office: Days
• US Class Current: 435/91.200
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0832 cylindrical, tube shaped
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1861 using radiation
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/5082 Test tubes per se
• 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 35/1002 Reagent dispensers
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A device for processing a biological sample includes a processing unit having at least one opening to receive a sample vessel and a plurality of processing stations positioned along the opening. The processing stations each have a compression member adapted to compress the sample vessel within the opening and thereby move a substance within the sample vessel among the processing stations. An energy transfer element can be coupled to one or more of the processing stations for transferring thermal energy to the content at a processing station.

Claims

1. A sample processing apparatus, comprising:

a processing unit having an opening to receive at least one sample vessel containing at least one sample, the processing unit having at least a first processing station and a second processing station positioned along the opening,

the first processing station including a first compression member adapted to compress the sample vessel within the opening and a first energy transfer element for transferring energy to or from the contents at the first processing station, and

the second processing station including a second compression member adapted to compress the sample vessel within the opening and a second energy transfer element for transferring energy to or from the contents at the second processing station, wherein compression of the sample vessel by of one of the compression members displaces a substance within the sample vessel between the processing stations.

2. The sample processing apparatus of claim 1, further comprising at least one sensor for detecting a signal from the content within the sample vessel.

3. The sample processing apparatus of claim 2, wherein the sensor comprises an optical sensor for measuring a light signal from the contents with the sample vessel.

4. The sample processing apparatus of claim 3, wherein the light signal comprises fluorescent light.

5. The sample processing apparatus of claim 3, wherein the light signal comprises chemiluminescence.

6. The sample processing apparatus of claim 2, wherein the sensor monitors the signal from the content within the sample vessel in real time.

7. The sample processing apparatus of claim 2, wherein the sensor comprises a spectrum sensor for measuring a spectrum signal from the content within the sample vessel.

8. The sample processing apparatus of claim 2, wherein the sensor comprises a charge coupled device for imaging the content within the sample vessel.

9. The sample processing apparatus of claim 1, further comprising a plurality of sensors for detecting multiple wavelength light signals from the content within the sample vessel.

10. The sample processing apparatus of claim 1, further comprising an energy source for applying energy to the sample within the sample vessel to generate a signal from the sample.

11. The sample processing apparatus of claim 10, wherein the energy source comprises a light source.

12. The sample processing apparatus of claim 10, wherein the energy source comprises an electronic source.

13. The sample processing apparatus of claim 1, further comprising at least one energy insulator positioned adjacent at least one processing station.

14. The sample processing apparatus of claim 1, further comprising at least one energy insulating compression member positioned adjacent at least one processing station for compressing the sample vessel to close at least a portion of the sample vessel.

15. The sample processing apparatus of claim 1, wherein at least one of the energy transfer elements comprises at least one of an electronic heat element, a microwave source, a light source, an ultrasonic source and a cooling element.

16. The sample processing apparatus of claim 1, further comprising a control system coupled to at least one energy transfer element to control the energy transferred to or from that energy transfer element.

17. The sample processing apparatus of claim 16, further comprising a temperature sensor coupled to the control system.

18. The sample processing apparatus of claim 1, wherein at least one processing station further comprises a heat sink.

19. The sample processing apparatus of claim 1, wherein at least one processing station includes a stationary member opposing the respective compression member across the opening, wherein the respective compression member compresses the sample vessel against the stationary member within the opening.

20. The sample processing apparatus of claim 1, further comprising a driver coupled to at least one compression member to selectively move that compression member and thereby compress the sample vessel within the opening.

21. The sample processing apparatus of claim 20, wherein the driver comprises a motor and is coupled to the at least one compression member by a cam.

22. The sample processing apparatus of claim 20, wherein the driver comprises an electromagnetic actuating mechanism.

23. The sample processing apparatus of claim 1, further comprising an electrophoresis system comprising a pair of electrodes adapted to have a predetermined voltage difference and an electrode actuator for inserting the electrodes into the sample vessel.

24. The sample processing apparatus of claim 1, further comprising a reagent injector cartridge actuator adapted to receive a reagent injector cartridge having at least one needle in fluid communication with a reagent reservoir, the reagent injector cartridge actuator operable to move the reagent injector cartridge to inject a quantity of reagent into the sample vessel.

25. The sample processing apparatus of claim 1, wherein at least one of the compression members is constructed from a rigid material.

26. The sample processing apparatus of claim 1, wherein at least one of the compression members comprises a block having a rectilinear, planar surface for engaging the sample vessel.

27. The sample processing apparatus of claim 1, wherein at least one of the compression members comprises a block having non-planar surface for engaging the sample vessel.

28. The sample processing apparatus of claim 1, wherein at least one of the compression members comprises an inflatable membrane that can be inflated by a fluid to impart a compressive force on the sample vessel.

29. The sample processing apparatus of claim 1, wherein at least one of the compression members comprises a pneumatic actuator to impart a compressive force on the sample vessel.

30. The sample processing apparatus of claim 1, wherein the substance comprises the at least one sample.

31. The sample processing apparatus of claim 1, wherein the substance comprises a reagent.

32. The sample processing apparatus of claim 1, further comprising a sample vessel and wherein the sample vessel comprises at least one sample-containing portion for holding at least one sample, the sample-containing portion having a wall constructed of a flexible material permitting substantial flattening of a selected section of the sample-containing portion, and a handling portion coupled to the sample-containing portion, the handling portion having a generally rigid construction to facilitate handling of the sample vessel.

33. The sample processing apparatus of claim 32, wherein the sample-containing portion of the sample vessel comprises a tubule.

34. The sample processing apparatus of claim 32, wherein the sample vessel has a filter contained therein structured to separate selected components of a sample material from other components of the sample material.

35. The sample processing apparatus of claim 32, further comprising at least one pressure gate disposed within the sample-containing portion to divide the sample-containing portion into a plurality of segments.

36. The sample processing apparatus of claim 35, wherein at least one of the segments contains a reagent.

37. The sample processing apparatus of claim 36, wherein the reagent comprises at least one of an anticoagulant, a cell lyses reagent, a nucleotide, an enzyme, a DNA polymerase, a template DNA, an oligonucleotide, a primer, an antigen, an antibody, a dye, a marker, a molecular probe, a buffer, and a detection material.

38. The sample processing apparatus of claim 32, wherein the sample-containing portion contains multilayer membranes for analyzing the sample.

39. The sample processing apparatus of claim 32, wherein the sample-containing portion contains a micro-array bio-chip for analyzing the sample.

40. The sample processing apparatus of claim 32, wherein the sample-containing portion includes a self-sealing injection channel formed therein, the self sealing injection channel being normally substantially free of sample material and capable of fluid communication with the sample material in the sample-containing portion.

41. The sample processing apparatus of claim 32, wherein the thickness of the wall of the sample-containing portion is less than or equal to 0.3 mm.

42. A method of processing a sample, comprising:

adding a sample to a sample vessel;

introducing the sample vessel into a sample processing apparatus as set forth in claim 1;

compressing the sample vessel with one of the first and second compression members to move the contents within the sample vessel from the respective one of the processing stations to the other processing station; and

transferring energy to the sample at at least one of the processing stations.

43. The method of claim 42, further comprising analyzing the sample by detecting a signal from the sample, and analyzing the detected signal to determine a condition of the sample.

44. The method of claim 43, wherein analyzing further comprises applying an excitation energy to the sample.

45. The method of claim 42, further comprising conducting electrophoresis analysis of the sample by:

applying a selective voltage to the sample;

detecting light emitted from the sample; and

analyzing the detected light to determine a condition of the sample.

46. The method of claim 42, further comprising:

applying an excitation energy to a bio-array member contained within the sample vessel;

detecting light emitted from the bio-array member; and

analyzing the detected light to determine a condition of the sample.

47. The method of claim 42, further comprising adding a reagent to the sample in the sample vessel.

48. The method of claim 42, further comprising displacing the contents within the sample vessel.

49. The method of claim 42, further comprising agitating the contents within the sample vessel.

50. The method of claim 42, further comprising adjusting the volume of the contents within the sample vessel.

51. The method of claim 42, further comprising mixing the contents within the sample vessel.

52. The method of claim 42, further comprising incubating the contents within the sample vessel at a temperature.

53. The method of claim 42, further comprising separating content components within the sample vessel.

54. The method of claim 42, further comprising effecting a reaction within a segment of the sample vessel.

55. The method of claim 54, wherein the reaction comprises thermal cycling nucleic acid amplification.

57. The method of claim 54, wherein the reaction comprises isothermal nucleic acid amplification.

58. The method of claim 57, wherein the isothermal nucleic acid amplification reaction comprises at least one of strand displacement amplification (SDA), rolling circle amplification (RCA), and transcription-mediated amplification (TMA).

59. The method of claim 54, wherein the reaction comprises hybridization of a probe to a nucleic acid.

60. The method of claim 54, wherein the sample vessel contains magnetic beads and the reaction occurs at the magnetic bead surface.

56. The method of claim 162, wherein the thermal cycling nucleic acid amplification reaction comprises at least one of polymerase chain reaction (PCR) and ligase chain reaction (LCR).

61. A sample vessel for holding a sample, comprising:

a sample containing portion having at least one pressure gate disposed within the sample containing portion to divide the sample containing portion into a plurality of segments, at least one segment of the sample containing portion having a wall constructed of a flexible material permitting substantial flattening of the segment of the sample containing portion.