APPARATUS FOR AND METHOD OF AUTOMATED PROCESSING OF BIOLOGICAL SAMPLES

• US 20110287447A1
• Filed: 05/11/2010
• Published: 11/24/2011
• Est. Priority Date: 05/12/2009
• Status: Active Grant

• Current Assignee: Life Technologies AS (Perspecta, Inc.)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Trolson, Norman, Norderhaug, Lars, Rivrud, Tommy, Zgonc, Kornelija, Kahatt, Espir, Hogan, Jamie, Nokleby, Lars, Egeberg, Morten
• Granted Patent: US 9,011,772 B2
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/563 Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: B01L 9/543 for disposable pipette tips, e.g. racks or cassettes
• CPC Class Codes: G01N 2035/00227 Monitoring a process (online)
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/0436 with pre-packaged reagents, i.e. test-packs
• CPC Class Codes: G01N 2035/0498 Drawers used as storage or dispensing means for vessels or cuvettes
• CPC Class Codes: G01N 2035/103 using disposable tips
• CPC Class Codes: G01N 2035/1039 Micropipettes, e.g. microcapillary tubes
• 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
• CPC Class Codes: Y10T 436/11 Automated chemical analysis

Abstract

Provided herein is a bioprocessing device, bioprocessing card, and fluidics cartridge for performing automated bioprocessing of a sample. The bioprocessing card may include a plurality of pipette tips; and at least one pump in fluid communication with the plurality of pipette tips. In some embodiments, the pumps and the pipette tips are in fluid communication through a processing channel which may be a microscale channel. Also provided herein is an automated bioprocessing device comprising: at least one bioprocessing card; at least one fluidic cartridge; and an automated control system configured to control automated bioprocessing of a sample. Further provided herein are methods of use of the device, card, and cartridge.

Claims

1. A bioprocessing card comprising

a. a plurality of pipette tips;

and

b. at least one pump in fluid communication with the plurality of pipette tips.

3. The bioprocessing card of claim 1 wherein the processing channel is a mesoscale channel.

4. The bioprocessing card of claim 1 wherein the processing channel is a microscale channel.

5. The bioprocessing card of any of claims 1-4 comprising at least three pumps.

6. The bioprocessing card of any of claims 1-5 comprising a plurality of control fluid connectors.

7. The bioprocessing card of claim 6 wherein a control fluid connector is configured to be in communication with a pipette tip.

8. The bioprocessing card of claim 6 wherein a control fluid connector is configured to be in communication with the at least one pump.

9. The bioprocessing card of claim 1-8 wherein the plurality of control fluid connectors are configured to be in communication with an air supply source.

10. The bioprocessing card of any of claims 1-9 comprising a plurality of valves.

11. The bioprocessing card of claim 10 wherein a valve is in communication with a pipette tip.

12. The bioprocessing card of any of claims 1-11 further comprising a membrane.

13. The bioprocessing card of claim 12 wherein the membrane is a silicone membrane.

14. The bioprocessing card of any of claims 1-13 further comprising a sealing foil.

28. The device of any of claims 15-2 wherein the at least one cartridge well further comprises a solid support.

29. The device of claim 28 wherein the solid support is a magnetic particle.

30. The device of claim 29 wherein the magnetic particle is a magnetic bead.

31. The device of any of claims 15-30 wherein the bioprocessing card is the bioprocessing card of any of claims 1-14.

2. The bioprocessing card of claim 0 wherein the plurality of pipette tips and the at least one pump are in fluid communication through a processing channel.

15. An automated bioprocessing device comprising:

a. at least one bioprocessing card,

b. at least one fluidic cartridge; and

c. an automated control system configured to control automated bioprocessing of a sample.

16. The device of claim 15 comprising more than one bioprocessing card.

17. The device of claim 15 comprising more than one fluidics cartridge.

18. The device of any of claims 15-17 comprising a manifold in communication with the bioprocessing card.

19. The device of claim 18 wherein the manifold is configured to apply atmospheric pressure, vacuum, and/or pressure to the bioprocessing card.

20. The device of claim 18 wherein the manifold is external to the device.

21. The device of claim 18 wherein the manifold is internal to the device.

22. The device of any of claims 15-21 comprising a heating and/or cooling block.

23. The device of any of claims 15-22 further comprising a magnetic assembly.

24. The device of any of claims 15-23 further comprising a graphical user interface.

25. The device of any of claims 15-24 further comprising a control panel.

26. The device of any of claims 15-25 wherein the fluidics cartridge includes at least one cartridge well.

27. The device of any of claims 15-26 wherein the fluidics cartridge includes an opening configured to receive a container configured to contain and confine a liquid.

32. The device of any of claims 15-30 wherein the bioprocessing card comprises:

a. a plurality of pipette tips; and

b. at least one pump in fluid communication with the plurality of pipette tips.

33. A method for processing a sample comprising:

a. providing an automated bioprocessing device comprising;

b. a bioprocessing card; and

c, a fluidics cartridge containing the sample;

d. selecting a protocol on an automated control system; and

e. running the protocol.

34. The method of claim 33 wherein the fluidics cartridge further comprises at least two cartridge wells.

35. The method of claim 34 wherein at least one magnetic particle is located in at least one of the cartridge wells.

36. The method of any of claims 33-35 wherein each cartridge well is configured to hold a fluid.

37. The method of any of claims 33-35 wherein the bioprocessing card comprises:

a. a plurality of pipette tips; and

b. at least one pump in fluid communication with the plurality of pipette tips.

38. The method of claim 33 wherein running the protocol includes:

a. aspirating a fluid from a first cartridge well located on the fluidics cartridge using a first pipette tip;

b. transporting the fluid through a processing channel to a second pipette tip; and

c. expelling the fluid through the second pipette tip into a second well located on the fluidics cartridge.

39. The method of claim 38 wherein the aspirating, transporting, and expelling is repeated.

40. The method of any of claims 33-39 wherein the processing channel is a mesoscale channel.

41. The method of any of claims 33-39 wherein the processing channel is a microscale channel.

42. The method of any of claims 33-41 wherein the fluid is selected from at least one of a buffer, reagent, wash, proteinase, antibody, sample, or eluate.

43. The method of any of claims 33-42 wherein the bioprocessing device further comprises a magnetic assembly.

44. The method of any of claims 33-43 wherein the method comprises

a. applying a magnetic field to at least a portion of the fluidics cartridge;

b. attracting at least one magnetic particle located in the fluid in a cartridge well;

c. removing the fluid from the cartridge well.

45. The method of claim 44 further comprising resuspending the magnetic particle in a fluid.

46. The method of any of claims 33-45 wherein the bioprocessing device further comprises a heating/cooling block.

47. The method of claim 46 further comprising heating and/or cooling at least a portion of the fluidics cartridge.

48. An automated method of bioprocessing comprising:

a. inserting at least one fluidics cartridge into a bioprocessing device, said fluidics cartridge comprising at least one cartridge well containing at least one fluid;

b. inserting at least one bioprocessing card into the bioprocessing device, said bioprocessing card comprising;

i. a plurality of pipette tips; and

ii. at least one pump in fluid communication with the plurality of pipette tips;

c. initiating a bioprocessing protocol on the bioprocessing device, the protocol comprising one or more of the following;

i. controlling pumps and valves on the bioprocessing card to transfer fluids, reagents and/or samples between one or more cartridge wells,

ii. controlling pumps and valves on the bioprocessing card to mix fluids, reagents and/or samples in a cartridge well; and

/or

iii. controlling pumps and valves on the bioprocessing card to remove fluids, reagents and/or samples from the at least one cartridge well.

49. A method of applying one or more fluids to a solid support comprising the steps of:

a. inserting at least one fluidics cartridge into a bioprocessing device, the fluidics cartridge comprising one or more cartridge wells containing a solid support therein;

b. inserting at least one bioprocessing card into the bioprocessing device, the bioprocessing card comprising;

i. a plurality of pipette tips;

ii. at least one pump in communication with the plurality of pipette tips; and

c. performing a pumping sequence on said Card, wherein said pumping sequence comprises entering one or more processing cycles wherein fluid is pumped between the one or more cartridge wells through the processing channel of the bioprocessing card.

50. A system for sample bioprocessing, comprising:

a. a fluidics cartridge that includes a first well and a second well, wherein the first well holds a fluid sample that includes one or more magnetic particles;

b. a bioprocessing card that includes a first pipette tip, a second pipette tip, and a pump that are in fluid communication along a processing channel and that is placed in proximity to the fluidics cartridge so that the first pipette tip is in fluid communication with the first well and the second pipette tip is in fluid communication with the second well;

c. a manifold that is in physical communication with the bioprocessing card;

d. a magnetic assembly that is placed in proximity to the fluidics cartridge;

e. a memory that includes instructions for a sample preparation protocol; and

f. a processor that is in electronic communication with the manifold, the magnetic assembly, and the memory, that reads the instructions from the memory, and that according to the instructions

i. activates the magnetic assembly to apply a magnetic field to the first well so that at least one magnetic particle of the one or more magnetic particles of the fluid sample is attracted and

ii. signals the manifold to apply pressure and/or vacuum to the bioprocessing card activating fluid valves of the first pipette tip, the second pipette tip, and the pump to move a portion of the fluid sample from the first well through the processing channel, to the second well producing a bioprocessed sample in the first well.

51. The system of claim 50, further comprising a heat/cooling block that is placed in proximity to the fluidics cartridge, that is in electronic communication with the processor, and that receives a signal from the processor to heat or cool of the fluidics cartridge according to the instructions.

52. The system of claim 50 or 51, further comprising a card actuator to move the bioprocessing card with respect to the fluidics cartridge so that the depths of the first pipette tip and the second pipette tip in the first well and the second well can be varied, wherein the card actuator is in electronic communication with the processor and receives a signal from the processor to move the bioprocessing card according to the instructions.

53. The system of claim 52, further comprising a cartridge actuator to move the fluidics cartridge with respect to the bioprocessing card so that the first pipette tip can be moved from the first well to the second, wherein the cartridge actuator is in electronic communication with the processor and receives a signal from the processor to move the fluidics cartridge according to the instructions.

54. The system of claim 53, where the processor uses the card actuator and the cartridge actuator in concert to move fluid from the first well to the second well using the first pipette tip.

55. The system of any one of claim 50 to 54, further comprising an input/output device from which the processor can also read the instructions, wherein the input/output device is in electronic communication with the processor.

58. The system of any one of claim 50 to 57, further comprising a user interface device from which the processor receives a protocol selection from a user, wherein the input/output device is in electronic communication with the processor.

59. The system of claim 58, wherein the processor receives a protocol parameter from the user interface device that indicates a parameter selected by the user.

60. The system of claim 58 or 59, wherein the processor sends a system status to the user interface device.

61. The system of any one of claim 50 to 60, wherein the instructions comprise a scripting language format.

62. The system of claim 61, wherein the scripting language format comprises a bioprocessing sequence.

63. The system of claim 62, wherein the bioprocessing sequence comprises a step.

64. The system of claim 63, wherein the processor translates the step into a processing device signal.

65. The system of any one of claim 50 to 64, wherein the manifold applies pressure and/or vacuum to the bioprocessing card by activating one or more manifold valves of a plurality of manifold valves on the manifold.

66. The system of claim 65, wherein the manifold activates the one or more manifold values using a matrix of address lines to allow more than one bioprocessing card to perform the sample preparation protocol at substantially the same time.

67. The system of claim 66, wherein each manifold valve of the plurality of manifold valves can be addressed using two address lines of the matrix of address lines.

56. The system of C, wherein the bioprocessing card comprises a check valve.

57. The system of claim 56, wherein

a. the processor signals the manifold to apply pressure and/or vacuum to the bioprocessing card to close the check value and open all other card valves,

b. the processor signals the manifold to increase the pressure of the bioprocessing card to a system pressure,

c. the processor signals the manifold to open the check value, and

d. if the processor receives a system pressure from the manifold at the check value, then the processor determines that the bioprocessing card is present.

68. A method for sample bioprocessing, comprising:

a. reading instructions for a sample preparation protocol from a memory using a processor;

b. activating a magnetic assembly to apply a magnetic field to a first well of a fluidics cartridge so that at least one magnetic particle of one or more magnetic particles of a fluid sample is attracted using the processor, wherein the fluidics cartridge includes the first well and a second well, wherein the first well holds the fluid sample that includes the one or more magnetic particles, and wherein the magnetic assembly is in proximity to the fluidics cartridge; and

c. signaling a manifold to apply pressure and/or vacuum to a bioprocessing card activating fluid valves of a first pipette tip, a second pipette tip, and a pump to move a portion of the fluid sample from the first well through a processing channel, to the second well producing a bioprocessed sample in the first well using the processor, wherein the bioprocessing card includes the first pipette tip, the second pipette tip, and the pump that are in fluid communication along a processing channel, wherein the bioprocessing card is in proximity to the fluidics cartridge so that the first pipette tip is in fluid communication with the first well and the second pipette tip is in fluid communication with the second well, and wherein the manifold is in physical communication with the bioprocessing card.

69. A computer program product, comprising a tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for sample bioprocessing, comprising:

a. providing a system, wherein the system comprises distinct software modules, and wherein the distinct software modules comprise a protocol translation module, a magnetic assembly module, and a liquid transfer module;

b. reading instructions for a sample preparation protocol using the protocol translation module;

c. activating a magnetic assembly to apply a magnetic field to a first well of a fluidics cartridge so that at least one magnetic particle of one or more magnetic particles of a fluid sample is attracted using the magnetic assembly module, wherein the fluidics cartridge includes the first well and a second well, wherein the first well holds the fluid sample that includes the one or more magnetic particles, and wherein the magnetic assembly is in proximity to the fluidics cartridge; and

d. signaling a manifold to apply pressure and/or vacuum to a bioprocessing card activating fluid valves of a first pipette tip, a second pipette tip, and a pump to move a portion of the fluid sample from the first well through a processing channel, to the second well producing a bioprocessed sample in the first well using the liquid transfer module, wherein the bioprocessing card includes the first pipette tip, the second pipette tip, and the pump that are in fluid communication along a processing channel, wherein the bioprocessing card is in proximity to the fluidics cartridge so that the first pipette tip is in fluid communication with the first well and the second pipette tip is in fluid communication with the second well, and wherein the manifold is in physical communication with the bioprocessing card.