Analysis system

• US 8,835,184 B2
• Filed: 09/15/2008
• Issued: 09/16/2014
• Est. Priority Date: 09/14/2007
• Status: Active Grant

• Current Assignee: Biosenia Patents Limited
• Original Assignee: Biosenia Patents Limited
• Inventors: Redmond, Gareth, Kewell, Adrian, Kruger, Jan, Von Papen, Georg
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US12/678,016
• Publication Number:
  US 20110171754A1
• Time in Patent Office: 2,192 Days
• Field of Search: None
• US Class Current: 436/518
• 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 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/043 Hinged closures
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/5029 using swabs
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/054 Bubble trap; Debubbling
• CPC Class Codes: G01N 2021/058 Flat flow cell
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 33/54386 : Analytical elements

Abstract

An analysis system comprises a sampling cartridge (11) comprising a housing (21, 22) having an inlet (23) for receiving a fluid sample, a sensor (26, 45), and a guide (40, 42) extending between the inlet and the sensor for guiding sample into contact with the sensor. The system also has an optical detection reader (13) for optically inspecting the sensor. The cartridge housing has an inspection window (34) and the reader (13) comprises a socket to receive the cartridge (11), and an optical system (1183, 1186) for inspecting the sensor through the window. The cartridge comprises parallel microfluidic channel (42) for flow of sample from the inlet into contact with the sensor. The sensor comprises discrete sensor pads (45) in at least one channel, with an antibody, an antigen, or molecular imprinted polymer. The channels are of microfluidic size, having a cross-sectional area in the range of about 0.3 mm² to about 5 mm². At least one channel comprises a reagent pad (43) upstream of the sensor (45). The inlet of the cartridge comprises an extraction chamber (23) communicating with a draining chamber having a top reservoir (61) and a bottom reservoir (63), in turn communicating with a distribution chamber (40). Together, these chambers and the interfaces between them guide sample flow in a uniform manner between the channels and also remove impurity particles and bubbles.

Claims

1. A microfluidic structure comprising:

a fluidic channel, configured to guide a flow of a fluid comprising a target analyte along a length of the fluidic channel in a first direction, the fluidic channel having a width in a second direction perpendicular to the first direction and a depth in a third direction perpendicular to the first direction and the second direction, the fluidic channel comprising a non-porous material;

a reagent pad of porous material located within the fluidic channel and having a size in the second direction substantially similar to the width of the fluidic channel wherein the reagent pad has a size in the third direction that is substantially similar to the depth of the fluidic channel; and

a sensor pad of porous material located within the fluidic channel and downstream from the reagent pad and having a size in the second direction substantially similar to the width of the fluidic channel, the reagent pad and the sensor pad being separated by a free space diffusion zone having a length in the first direction between 0.5 and 5 mm,

wherein the sensor pad comprises immobilized target analyte-specific receptors that can bind the target analyte and/or a labelled product of a displacement, competition or sandwich affinity assay.

2. The microfluidic structure of claim 1, wherein the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or a labelled product of a displacement assay.

3. The microfluidic structure of claim 1, wherein the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or a labelled product of a competition assay.

4. The microfluidic structure of claim 3, wherein the reagent pad comprises releasable target analyte-linker-label conjugates and the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or the target analyte-linker-label conjugates.

5. The microfluidic structure of claim 1, wherein the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or a labelled product of a sandwich affinity assay.

6. The microfluidic structure of claim 1 further comprising a top layer that covers the fluidic channel.

7. The microfluidic structure of claim 6, wherein a portion of the top layer above the sensor pad comprises an optically clear inspection window allowing inspection of the sensor pad.

8. The microfluidic structure of claim 6, wherein there is a gap between the reagent pad or the sensor pad and the top layer.

9. The microfluidic structure of claim 8, wherein the gap is in the range of 0.05 to 0.5 mm.

10. The microfluidic structure of claim 6, wherein there is no gap between the reagent pad or the sensor pad and the top layer.

11. The microfluidic structure of claim 1 further comprising an absorption pad of fluid absorbing material located within the fluidic channel and downstream from the sensor pad.

12. The microfluidic structure of claim 11, wherein the sensor pad and the absorption pad are separated by a second diffusion zone.

13. The microfluidic structure of claim 1, wherein the pads are held in place via recesses which form part of the fluidic channel.

14. The microfluidic structure of claim 1, wherein the pads are held in place via a single or multiple discontinuous areas of adhesive coatings which form part of the fluidic channel.

15. The microfluidic structure of claim 1, wherein the pads are integrated into the fluidic channel as part of a supporting assembly of non-porous material.

16. The microfluidic structure of claim 15, wherein the pads are held in place via a single or multiple discontinuous areas of adhesive coatings which form part of the supporting assembly.

17. The microfluidic structure of claim 15, wherein the supporting assembly is held in place via a recess which forms part of the fluidic channel.

18. The microfluidic structure of claim 15, wherein the supporting assembly is held in place via a single or multiple discontinuous areas of adhesive coatings which form part of the fluidic channel.

19. The microfluidic structure of claim 15, wherein the supporting assembly is held in place via a single or multiple discontinuous areas of adhesive coatings on the underside of the supporting assembly.

20. The microfluidic structure of claim 1, wherein the fluidic channel has an opening at the downstream end of the channel to act as a vent to assist fluid flow in the first direction.

21. The microfluidic structure of claim 20, wherein the size of the opening of the vent is between about 0.1 and 5 mm.

22. The microfluidic structure of claim 1, wherein the length of the fluidic channel is between about 25 and 50 mm, the width of the fluidic channel is between about 1.3 and 5 mm and the depth of the fluidic channel is between about 0.25 and 1 mm.

23. The microfluidic structure of claim 1, wherein the cross-sectional area of the fluidic channel is between about 0.3 and 5 mm².

24. The microfluidic structure of claim 23, wherein the pads have widths of between about 1.3 and 5 mm and lengths of between about 2 and 25 mm.

25. The microfluidic structure of claim 1, wherein the labelled product of a displacement, competition or sandwich affinity assay includes a fluorescent label.

26. The microfluidic structure of claim 1, wherein the immobilized target analyte-specific receptors are antibodies that bind the target analyte and/or the labelled product of a displacement, competition or sandwich affinity assay.

27. The microfluidic structure of claim 1, wherein the immobilized target analyte-specific receptors are antigens that are bound by the target analyte and/or the labelled product of a displacement, competition or sandwich affinity assay.

28. The microfluidic structure of claim 1, wherein the immobilized target analyte-specific receptors are molecularly imprinted polymers that bind the target analyte and/or the labelled product of a displacement, competition or sandwich affinity assay.

29. A fluidic chip comprising a plurality of separate microfluidic structures as defined in claim 1.

30. The fluidic chip of claim 29, further comprising a single top layer that covers the fluidic channels of the plurality of microfluidic structures.

31. The fluidic chip of claim 29, wherein the plurality of separate microfluidic structures are spaced by between about 0.5 and 5 mm.

32. A sampling cartridge comprising an extraction chamber, a draining chamber, and the fluidic chip according to claim 29, wherein:

the extraction chamber is in fluid communication with the draining chamber via a draining duct, fluid travelling from the extraction chamber to the draining chamber in a first direction;

the draining chamber is configured to spread fluid from the extraction chamber in a second direction and in a third direction; and

each of the plurality of separate microfluidic structures comprising a fluidic channel in fluid communication with the draining chamber via a sample inlet port.

33. The sampling cartridge of claim 32, wherein:

the draining chamber includes;

i. a top reservoir and a bottom reservoir, fluid flowing from the top reservoir into the bottom reservoir in the first direction, the top and bottom reservoirs having widths in a second direction perpendicular to the first direction and depths in a third direction perpendicular to the first direction and the second direction;

ii. an interface between the top and bottom reservoirs in the form of an elongated slot extending in the second direction;

the fluidic chip includes a distribution chamber in communication with the bottom reservoir of the draining chamber, fluid travelling from the draining chamber to the distribution chamber in the first direction, the distribution chamber configured to spread fluid flow from the bottom reservoir in the second direction and in the third direction; and

the fluidic chip includes a plurality of separate microfluidic structures, each comprising a fluidic channel in fluid communication with the distribution chamber via a sample inlet port.

34. The sampling cartridge of claim 33, wherein the depth of the bottom reservoir of the draining chamber in the third direction is between about 0.25 and 2 mm.

35. The sampling cartridge of claim 33, wherein the depth of the bottom reservoir of the draining chamber in the third direction is substantially the same as a dimension of the distribution chamber of the fluidic chip.

36. The sampling cartridge of claim 33, wherein the width of the bottom reservoir of the draining chamber in the second direction is substantially the same as a dimension of the distribution chamber of the fluidic chip.

37. The sampling cartridge of claim 32 wherein the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or a labelled product of a displacement assay.

38. The sampling cartridge of claim 32, wherein the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or a labelled product of a competition assay.

39. The sampling cartridge of claim 38, wherein the reagent pad comprises releasable target analyte-linker-label conjugates and the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or the target analyte-linker-label conjugates.

40. The sampling cartridge of claim 32, wherein the immobilized target analyte-specific receptors of the sensor pad can bind the target analyte and/or a labelled product of a sandwich affinity assay.

41. The sampling cartridge of claim 32, wherein the draining chamber is configured to separate one or more bubbles from the fluid flowing through the draining chamber.

42. The sampling cartridge of claim 32, wherein the interface between the top and bottom reservoirs is configured to filter impurity particles from the fluid flowing through the draining chamber.

43. The sampling cartridge of claim 32, wherein the reagent pad and the sensor pad within each microfluidic structure are separated by a free space diffusion zone having a length in the first direction between 0.5 and 5 mm.

44. The sampling cartridge of claim 32, wherein each microfluidic structure comprises a fluidic channel having a width between about 1.3 and 5 mm and a depth between about 0.25 and 1 mm and a cross-sectional area of the fluidic channel is between about 0.3 and 5 mm².

45. The sampling cartridge of claim 32, further comprising an inspection window for inspecting the sensor pad in each microfluidic structure.

46. The sampling cartridge of claim 32, wherein the fluidic chip further comprises a single top layer that covers the fluidic channels of the plurality of separate microfluidic structures.

47. The sampling cartridge of claim 46, wherein there is no possibility of fluid cross-over between the plurality of separate microfluidic structures.

48. The sampling cartridge of claim 46, wherein the plurality of separate microfluidic structures are spaced by between about 0.5 and 5 mm.

49. The sampling cartridge of claim 32, wherein the fluidic chip is arranged in the sampling cartridge such that fluid flows along the fluidic channels of the microfluidic structures in the first direction.

50. The sampling cartridge of claim 32, wherein the fluidic chip is arranged in the sampling cartridge such that fluid flows along the fluidic channels of the microfluidic structures in the third direction.

51. The sampling cartridge of claim 32,

wherein the sampling cartridge comprises a swab pressing means.

52. The sampling cartridge of claim 51, wherein the pressing means comprises a hinged handle, wherein closure of the handle causes an inserted swab to be pressed and a fluid to flow from the swab into the extraction chamber.

53. The sampling cartridge of claim 32, wherein the sampling cartridge comprises a membrane over the extraction chamber to allow injection of a fluid by a syringe.

54. An analysis system comprising:

the sampling cartridge as defined in claim 32; and

an optical detection reader comprising a socket to receive at least part of the sampling cartridge, and an optical system for inspecting the sensor pad in each microfluidic structure through the inspection window of the sampling cartridge.

55. The analysis system of claim 54, wherein the sampling cartridge includes guiding rails that facilitate its insertion into the optical detection reader.

56. A method comprising flowing a fluid through the sampling cartridge of claim 49 wherein the first direction is in an upright direction.