Fluidics Devices

• US 20080200343A1
• Filed: 02/15/2008
• Published: 08/21/2008
• Est. Priority Date: 02/15/2007
• Status: Active Grant

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Incorporated
• Inventors: Robinson, Thomas P., Clemens, Charles E., Mucic, Robert, Olsen, Gary T., Montalvo, Rudolph A., Foster, Clark, Gust, Gary R.
• Granted Patent: US 7,863,035 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/024 Storing results with means integrated into the container
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/088 Channel loops
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0605 : check valves
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• 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: B01L 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 27/27 : Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter

Abstract

The invention relates to fluidics as used in medical and diagnostic equipment and relates further to means for purifying, abstracting, filtering, detecting and/or measuring analytes in liquid samples.

Claims

1. A fluidics device, comprising:

a membranous diaphragm having a first and second side, said first side for coupling to a pump, and said second side for fluidic coupling to a flow channel and a plurality of check valves, said check valves each comprising;

i) a sealing surface comprising a valve seat that allows for regulated flow of fluid through said flow channel; and

ii) a flexible sealing structure for contacting said valve seat and occluding fluid flow therethrough when in a first position, and for promoting fluid flow therethrough when in a second position;

wherein said diaphragm and said flexible sealing structure are integral to one or more layers of a multilayer assembly; and

wherein said plurality of check valves alternate opening and closing in coordinated reciprocal fashion according to alternating positive and negative forces exerted on said diaphragm.

3. The fluidics device of claim 1 or 2 that processes no more than 1.5 mL of fluid at a time.

4. The fluidics device of claim 3 that processes no more than 150 ul of fluid at a time.

5. The fluidics device of claim 1 or 2 formed at least in part from the stacking of multiple individual polymeric laminate sheets, optionally held together by pressure sensitive adhesive sheets.

6. The fluidics device of claim 5 wherein one or more of said channels are formed by grooves, cuts or recesses in one or more of said individual plastic laminate sheets.

7. The fluidics device of claim 6 wherein at least one of said grooves, cuts or recesses is produced by a die-stamp, laser, chemical etching, or molding.

8. The fluidics device of claim 1 or 2 further comprising at least one working electrode in said flow channel.

9. The fluidics device of claim 8 further comprising one or more auxiliary electrodes.

10. The fluidics device of claim 1 or 2 that is a diagnostics device.

11. The fluidics device of claim 1 or 2 further comprising connectors for interface with a detection device.

12. The fluidics device of claim 11 wherein said connectors are configured in a two-dimensional grid of contact points.

13. The fluidics device of claim 11 wherein said connectors are ZIF connectors.

14. The fluidics device of claim 11 wherein said connectors are side or edge connectors.

15. The fluidics device of claim 1 or 2 further comprising an EEPROM.

16. The fluidics device of claim 1 or 2 further comprising an internal unused space designed for integration of one or more future functionalities.

17. The fluidics device of claim 1 or 2 that comprises a transparent or translucent plastic that permits visualization of circulation and recirculation of said fluid sample within.

20. The fluidics device of claim 1 or 19 wherein at least one of said one or more valves is a passive valve.

21. The fluidics device of claim 1 or 2 wherein at least one of said one or more valves is a bridge valve.

22. The fluidics device of claim 1 or 2 further comprising a means for pumping said fluid sample through said channel.

23. The fluidics device of claim 22 wherein said means for pumping said fluid sample is a pneumatic pump.

24. The fluidics device of claim 23 comprising a plurality of bridge or check valves actuated by a pneumatic, electromagnetic, or hydraulic pump and a diaphragm.

25. The fluidics device of claim 24 wherein said pneumatic pump is electrically driven.

26. The fluidics device of claim 1 or 2 comprising one or more immobilized biological binding partners or ligands in said flow channel.

27. The fluidics device of claim 26 wherein said one or more biological binding partners or ligands is immobilized using a self assembling monolayer that is affixed to a surface, optionally an electrode.

28. The fluidics device of claim 26 wherein said one or more biological binding partners or ligands are polynucleotides.

29. The fluidics device of claim 26 wherein said one or more biological binding partners are proteins, peptides or a mixture of both.

30. The fluidics device of claim 26 wherein said one or more biological binding partners is an antibody.

31. The fluidics device of claim 26 comprising an array of electrodes bound to one or more biological binding partners or ligands.

32. The fluidics device of claim 31 further comprising edge connectors for coupling said electrodes to a detector.

33. The fluidics device of claim 31 further comprising ZIF connectors for coupling said electrodes to a detector.

34. The fluidics device of claim 1 or 2 further comprising a cap for sealing said device following the addition of a sample.

35. The fluidics device of claim 1 or 2 further comprising a filter, adsorbent and/or absorbent for reducing or eliminating solutes or analytes in said fluid sample.

36. The fluidics device of claim 1 or 2 further comprising a plurality of different aptamers, ligands or biological binding partners immobilized on an array.

37. The fluidics device of claim 36 wherein said array is located in an elongated channel, optionally a serpentine channel.

38. The fluidics device of claim 37 wherein said array comprises immobilized nucleic acids.

39. The fluidics device of claim 37 wherein said array comprises immobilized peptides or proteins.

40. The fluidics device of claim 37 wherein said array comprises immobilized aptamers.

41. The fluidics device of claim 37 wherein said array comprises immobilized small molecules.

42. The fluidics device of claim 1 or 2 further comprising a detector that detects binding events between binding partners or ligands and complementary binding partner thereto in a fluid sample.

43. The fluidics device of claim 42 wherein said detector is a calorimetric detector.

44. The fluidics device of claim 42 wherein said detector detects electronic properties of said binding events.

45. The fluidics device of claim 1 or 2 that is a micofluidics device.

46. The fluidics device of claim 1 or 2 that is a filtration device.

47. The fluidics device of claim 1 or 2 that is a purification or abstraction device.

49. The fluidics device of claim 1 or 2 that is designed to receive said fluid sample from a pipette tip.

50. The fluidics device of claim 49 that is designed to receive said fluid sample from a micropipette tip.

51. A rack for carrying a plurality of fluidics devices according to claim 42, wherein said rack is designed to position said devices relative to one another having a pitch of about 9 mm between successive sample reservoirs of said devices.

52. A detection device adapted to receive the fluidics device of claim 42.

55. The fluidics device of claim 1 wherein said diaphragm and flexible sealing structures are integral to and formed within the same laminate layer of said multilayer assembly.

56. The fluidics device of claim 1 or 2 wherein said channel comprises a cross-sectional dimension comprising a greater width than height.

57. The fluidics device of claim 1 or 2 wherein said channel has a cross-sectional dimension ranging from about 0.030″

to about 0.060″

in width and from about 0.006″

to about 0.014″

in height.

58. The fluidics device of claim 1 or 2 constructed from alternating laminate and adhesive layers having individual thicknesses in the range of from about 0.0005″

to about 0.030″

.

59. The fluidics device of claim 58 wherein said individual laminate layers are thicker than said individual adhesive layers.

60. The fluidics device of claim 59 wherein said individual laminate layers are from about 0.0005″

to about 0.010″

thick and said individual adhesive layers are from about 0.001″

to about 0.003″

thick.

61. The fluidics device of claim 1 or 2 wherein said device has a sample capacity of from about 50 ul to about 200 ul.

62. The fluidics device of claim 1 wherein one or more of said valve seats protrude from a planar structure to promote sealing upon engagement with a corresponding sealing structure.

63. The fluidics device of claim 62 wherein the magnitude of said protuberances relative to the base surface is independently selected from about 0.001″

to about 0.005″

.

64. The fluidics device of claim 62 wherein one of more of said valve seats are part of a hollow boss having a plurality of ports adjacent and fluidly coupled to one another in a nonlinear configuration, optionally a “

u-structure”

, and routing fluid from one fluidics plane in said device to one or more other fluidics planes in said device.

65. A fluidics device according to claim 1 or 2 further comprising internal space sufficient for one or more additional functionalities.

66. The fluidics device of claim 1 or 2 wherein said internal space is hollow, optionally comprising supporting structures, optionally ribs.

67. The fluidics device of claim 1 or 2 wherein said device is a diaphragm-mediated two-stroke circulation and recirculation device mediated by passive valving.

68. The fluidics device of claim 67 wherein said passive valving includes bridge valves.

69. A diagnostics kit comprising the device of fluidics device of claim 1 or 2.

70. The diagnostics kit of claim 68 wherein said device has a single cartridge capacity of no more than about 200 uL, wherein said array is contained in a flow channel having a length of from about 100 mm to about 200 mm, a cross-sectional dimension ranging from about 0.75 mm to about 2.0 mm in width and about 0.125 mm to about 0.40 mm in height, and wherein said device has an operational flow rate of from about 10 uL/sec to about 40 uL/sec.

71. The fluidics device of any one of the preceding claims, wherein said fluidics device in practice has a flow-rate of about 10-40 uL/sec.

72. The fluidics device of claim 70, wherein said flow-rate is continuous.

73. The fluidics device of claim 70, wherein said flow-rate is pulsed.

74. A method of determining analyte binding, comprising:

providing a fluidics device according to any of the preceding claims and having one or more analyte-specific binding ligands immobilized on an array thereon or in;

adding to said device a liquid sample suspected of containing one or more of said analytes;

circulating and recirculating said sample across said array; and

detecting binding of said analytes to said ligands.

75. The fluidics device of claim 1 or 2 wherein said device has a single cartridge capacity of no more than about 200 uL, wherein said array is contained in a flow channel having a length of from about 100 mm to about 200 mm, a cross-sectional dimension ranging from about 0.75 mm to about 2.0 mm in width and about 0.125 mm to about 0.40 mm in height, and wherein said device has an operational flow rate of from about 10 uL/sec to about 40 uL/sec.

2. A fluidics device comprising:

a body, said body comprising;

a channel within for transporting a fluid sample, said channel comprising a situs where an operation is performed on one or more components in said fluid sample;

an inlet port for receiving said fluid sample, said inlet port in fluid communication with said channel and also in communication with an enclosed gaseous environment; and

an outlet port in fluid communication with said inlet port such that upon operation of said device said fluid sample is recirculated through said channel to release gaseous bubbles into said enclosed gaseous environment while simultaneously allowing for facilitated diffusion and performance of said operation on said one or more components in said fluid sample.

18. The fluidics device of claim 2 further comprising one or more valves in fluid communication with said channel for regulating the flow of said fluid sample therethrough.

19. The fluidics device of claim 18 wherein at least one of said one or more valves is a check valve.

48. The fluidics device of claim 2 that receives said fluid sample through said inlet port in an upright position of from 15°

-90°

relative to horizontal, that processes said fluid sample in a 15°

-90°

position relative to horizontal, and wherein said receiving upright position and said processing upright position are not necessarily the same.

53. A valve comprising a flexible plastic laminate, said laminate comprising a plurality of substantially parallel slits anchored at each end and having a displaceable region therebetween that allows liquid to flow there under or over according to the direction of displacement of said displaceable region.

54. A fluidics device comprising one or more valves according to claim 53.