Sample processing device and method

• US 6,780,617 B2
• Filed: 02/13/2001
• Issued: 08/24/2004
• Est. Priority Date: 12/29/2000
• Status: Expired due to Term

• Current Assignee: Roche Molecular Systems Inc (Roche Holding AG)
• Original Assignee: CHEN Ching-Too
• Inventors: Chen, Shuqi
• Primary Examiner(s): Redding, David A.
• Application Number:
  US09/782,732
• Publication Number:
  US 20020086417A1
• Time in Patent Office: 1,288 Days
• Field of Search: 435/91.2, 435/286.5, 435/287.2, 435/287.3, 435/288.7, 204/450-467, 204/604, 935/85, 935/88, 422/99, 422/101
• US Class Current: 435/91.2
• 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 the sample 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 sample at a processing station. The device can be used for PCR processing of nucleic acid samples. A sample vessel of the present invention can be a tubule flow-chamber having a plurality of segments separated by pressure gates. The sample vessel minimizes sample handling by providing a closed tubule in which distinct processing steps can be carried out in each of the segments of the tubule.

Claims

1. A thermal cycler comprising

a processing unit having an opening to receive a sample vessel containing a sample, the processing unit having a first processing station, a second processing station, and a third processing station positional 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 the sample at the first processing station,

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 the sample at the second processing station, and

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

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

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

4. The thermal cycler of claim 3, wherein the light signal comprises fluorescent light.

5. The thermal cycler of claim 2, wherein the sensor monitors the signal from the content within the sample vessel in real time.

11. The thermal cycler of claim 1, further comprising at least one energy insulator positioned adjacent at least one processing station.

12. The thermal cycler of claim 1, wherein at least one of the 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.

13. The thermal cycler 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.

14. The thermal cycler of claim 13, further comprising a temperature sensor coupled to the control system.

15. The thermal cycler of claim 1, wherein at least one processing station further comprises a heat sink.

16. The thermal cycler 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.

17. The thermal cycler 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.

18. The thermal cycler of claim 17, wherein the driver is a motor and is coupled to the at least one compression member by a cam.

19. The thermal cycler of claim 17, wherein the driver is an electromagnetic actuating mechanism.

20. The thermal cycler of claim 1, further comprising an energy source for applying energy to at the sample within the sample vessel to generate a signal from the sample.

21. The thermal cycler 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.

22. The thermal cycler 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.

23. The thermal cycler of claim 1, wherein compression of the sample vessel by one of the compression members displaces a reagent within the sample vessel between the processing stations.

24. A method of thermal cycling, comprising:

adding a sample to a sample vessel;

introducing the sample vessel into a thermal cycler as set forth in claim 1;

compressing the sample vessel with the first compression member to move the sample within the sample vessel from the first processing station to the second processing station;

transferring energy to the sample at the second processing station;

compressing the sample vessel with the second compression member; and

transferring energy to the sample at the first processing station.

25. The method of claim 24, further comprising adding a reagent to the sample in the sample vessel.

26. The method of claim 24, further comprising heating the sample in the first processing unit to a first temperature.

27. The method of claim 26, further comprising heating the sample in the second processing unit to a second temperature.

28. The method of claim 27, wherein the first temperature is effective to denature nucleic acid in the sample and the second temperature is one at which nucleic acid annealing and nucleic acid synthesis can occur.

29. The method of claim 24, further comprising analyzing the sample by detecting a signal from the sample, and analyzing the detected signal to determine a condition of the sample.

30. The method of claim 29, wherein analyzing further comprises applying an excitation energy to the sample.

31. The method of claim 24, 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.

32. The method of claim 24, 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.

33. The method of claim 24, further comprising agitating the sample within the sample vessel.

34. A method of thermal cycling, comprising:

adding a sample to a sample vessel;

introducing the sample vessel into a thermal cycler as set forth in claim 1;

compressing the sample vessel with the first compression member;

transferring energy to the sample with the second energy transfer element;

compressing the sample vessel with the second compression member;

transferring energy to the sample with the third energy transfer element;

compressing the sample vessel with the third compression member; and

transferring energy to the sample with the first energy transfer element.

35. The method of claim 34, further comprising agitating the sample within the sample vessel.

36. The method of claim 34, further comprising heating the sample in the first processing unit to a first temperature.

37. The method of claim 36, further comprising heating the sample in the second processing unit to a second temperature.

38. The method of claim 37, further comprising heating the sample in the third processing unit to a third temperature.

39. The method of claim 38, wherein the first temperature is effective to denature nucleic acid in the sample, the second temperature is one at which nucleic acid annealing can occur, and the third temperature is one at which nucleic acid synthesis can occur.

6. A thermal cycler comprising

a processing unit having an opening to receive a sample vessel containing a sample, the processing unit having 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 the sample 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 the sample at the second processing station, wherein compression of the sample vessel by of one of the compression members displaces the sample within the sample vessel between the processing stations.

7. The thermal cycler of claim 6, further comprising ax least one sensor for detecting a signal from the content within the sample vessel.

8. The thermal cycler of claim 7, wherein the sensor comprises an optical sensor for measuring light signal from the contents with the sample vessel.

9. The thermal cycler of claim 8, wherein the light signal comprises fluorescent light.

10. The thermal cycler of claim 7, wherein the sensor monitors the signal from the content within the sample vessel in real time.

40. A method of thermal cycling, comprising:

adding a sample to a sample vessel;

introducing the sample vessel into a thermal cycler as set forth in claim 6;

compressing the sample vessel with the first compression member to move the sample within the sample vessel from the first processing station to the second processing station;

transferring energy to the sample at the second processing station;

compressing the sample vessel with the second compression member; and

transferring energy to the sample at the first processing station.

41. The method of claim 40, further comprising adding a reagent to the sample in the sample vessel.

42. The method of claim 41, further comprising heating the sample in the first processing unit to a first temperature.

43. The method of claim 42, further comprising heating the sample in the second processing unit to a second temperature.

44. The method of claim 43, wherein the first temperature is effective to denature nucleic acid in the sample and the second temperature is one at which nucleic acid annealing and nucleic acid synthesis can occur.

45. The method of claim 40, further comprising analyzing the sample by detecting a signal from the sample, and analyzing the detected signal to determine a condition of the sample.

46. The method of claim 45, wherein analyzing further comprises applying an excitation energy to the sample.

47. The method of claim 40, 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.

48. The method of claim 40, 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.

49. The method of claim 40, further comprising agitating the sample within the sample vessel.