Laminated microarray interface device

• US 20020192701A1
• Filed: 08/02/2002
• Published: 12/19/2002
• Est. Priority Date: 03/09/2001
• Status: Active Grant

• Current Assignee: Roche NimbleGen, Inc. (Roche Holding AG)
• Original Assignee: BioMicro Systems, Inc. (Danaher Corporation)
• Inventors: Adey, Nils B.
• Granted Patent: US 7,235,400 B2
• Time in Patent Office: Days
• US Class Current: 435/6.11
• CPC Class Codes: B01F 25/50 Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 31/86 with vibration of the receptacle or part of it
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/0883 : Serpentine channels
• CPC Class Codes: B01L 2300/0887 : Laminated structure
• CPC Class Codes: B01L 3/0293 : for liquids
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 9/52 : Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/00544 : using fluid flow
• CPC Class Codes: G01N 33/543 : with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 35/00 : Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: G01N 35/025 : having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates

Abstract

A device for forming a low volume reaction chamber on a substrate such as a microarray slide and its method of use is disclosed. The reaction chamber forming device has an adhesive laminate design that permits it to be manufactured as a disposable device. A preferred embodiment of the device includes pneumatically actuatable mixing bladders, which can be inflated or deflated to produce deflection of a wall of the reaction chamber in and out with respect to the reaction chamber to generate movement and mixing of fluid within the reaction chamber.

Claims

1. A reaction chamber forming interface device comprising:

a) a main structure comprising a plurality of substantially planar layers laminated together;

b) a gasket on a surface of said main structure, said gasket defining an open reaction chamber adapted to seal against a substrate to form a closed reaction chamber, said reaction chamber bounded by said substrate, a surface of said main structure, and said gasket;

c) at least one mixing bladder formed within said main structure adjacent said surface; and

d) at least one port providing communication between said mixing bladder and the exterior of said main structure and adapted to connect to an external pressure source to provide for the delivery of pressurized gas or liquid to said mixing bladder to produce inflation or deflation of said mixing bladder;

wherein inflation or deflation of said mixing bladder produces deflection of at least a portion of said surface.

2. The device of claim 1, wherein said pressure source delivers a pressurized gas or gaseous mixture to said mixing bladder.

3. The device of claim 1, wherein said pressure source delivers pressurized liquid to said mixing bladder.

4. The device of claim 1, adapted for use with a substrate that is a glass slide.

5. The device of claim 4, wherein said slide is a microarray slide.

6. The device of claim 4, wherein said slide is a histology slide.

7. The device of claim 4, wherein said slide is a cytology slide.

8. The device of claim 1, adapted for use with a substrate wherein the surface of the substrate against which said reaction chamber is formed is curved.

9. The device of claim 1, wherein said main structure further comprises a removal tab adapted to be grasped by a user to facilitate removal of said device from a substrate to which it is sealed.

10. The device of claim 1, further comprising a bar code or other identifying mark on said main structure.

11. The device of claim 1, wherein said device is constructed of materials of low thermal mass so said device can be brought to desired temperature quickly.

12. The device of claim 1, wherein said main structure is formed of multiple layers of polymeric sheet material laminated together.

13. The device of claim 12, wherein said polymeric sheet material is degassed by exposure to a vacuum for a period of time sufficient to prevent the release of significant amounts of gases during use of the device..

14. The device of claim 12, comprising at least one layer formed of copolyester plastic.

15. The device of claim 1, wherein said gasket is formed of an adhesive material.

16. The device of claim 1, wherein said gasket is formed of an adhesive sheet material.

17. The device of claim 1, wherein said gasket is formed of a plastically deformable material.

18. The device of claim 1, wherein said gasket is formed of a resilient material.

19. The device of claim 1, wherein said gasket comprises a material selected from the group consisting of acrylic, urethane, silicone, and rubber.

20. The device of claim 1, wherein said gasket is silk-screened onto said surface of said main structure.

21. The device of claim 1, wherein said gasket is printed onto said surface of said main structure.

22. The device of claim 1, wherein said at least one port exits said main structure on the side opposite said gasket.

23. The device of claim 9, wherein said at least one port exits said main structure on a surface of said removal tab and is connected to said mixing bladder by an channel formed in the interior of said main structure.

24. The device of claim 23, wherein pressure is applied to said removal tab with a clamp to connect said at least one port to at least one connector from said external pressure source.

25. The device of claim 9, wherein said at least one port exits said main structure on an edge of said main structure and is connected to said mixing bladder by an channel formed in the interior of said main structure.

26. The device of claim 1, wherein said gasket comprises multiple openings adapted to form multiple reaction chambers when said device is attached to a substrate.

27. The device of claim 1, further comprising an inlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure.

28. The device of claim 27, wherein said gasket comprises a notch aligned with said inlet such that the region of said gasket adjacent said notch supports said main structure against collapse from the pressure of a pipetting device.

29. The device of claim 1, further comprising an outlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure.

30. The device of claim 29, wherein said gasket comprises a notch aligned with said outlet such that the region of said gasket adjacent said notch supports said main structure against collapse from the pressure of a pipetting device.

31. The device of claim 1, wherein said main structure comprises:

a) a main support layer;

b) an mixing bladder layer formed of an adhesive material and adhered to said main support layer, and having at least one opening formed therein to define said at least one mixing bladder; and

c) a diaphragm layer adhered to said mixing bladder layer, wherein said gasket is adhered to said diaphragm layer on the side opposite said mixing bladder layer.

32. The device of claim 31 wherein said diaphragm layer is made of a polyester film.

33. The device of claim 31 wherein said main structure further comprises a removal tab adapted to be grasped by a user to facilitate removal of said device from a substrate to which it is sealed, and wherein said at least one channel communicates with the exterior of said main structure through a port located on a face of said removal tab.

34. The device of claim 31, further comprising:

a) an inlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure.

35. The device of claim 31, further comprising

a) an outlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure.

36. The device of claim 1, wherein the opening of said at least one port is connected to said external pressure source by sealing a connector from said external pressure source to said at least one port.

37. The device of claim 36, wherein said sealing is provided by an adhesive between said connector and the opening of said at least one port.

38. The device of claim 36, wherein said sealing is provided by pressing said connector and the opening of said at least one port together with a resilient sealing member positioned therebetween.

39. The device of claim 36, wherein said connector is positioned with respect to said at least one port with an alignment means.

40. The device of claim 38, wherein said connector and said opening are pressed together by a clamp.

41. The device of claim 1, wherein said main structure comprises a plurality of alternating adhesive and non-adhesive layers.

42. The device of claim 41, wherein said at least one mixing bladder is defined by an opening in one said adhesive layer and bounded by two non-adhesive layers.

43. The device of claim 42, wherein said main structure further comprises at least one channel connecting said mixing bladder and said port, and wherein at least a portion of said at least one channel is defined by an opening in one said adhesive layer and bounded by two non-adhesive layers.

44. The device of claim 43, wherein said at least one channel and at least a portion of said at least one mixing bladder are defined by openings in the same adhesive layer.

45. The device of claim 43, wherein said at least one channel and at least a portion of said at least one mixing bladder are defined by openings in different adhesive layers.

47. The system of claim 46, further comprising:

a) at least one connector in communication with said pressure source and adapted to connect to said at least one port;

b) a base on which said substrate may be positioned;

c) an alignment means adapted to position said at least one connector in correct relationship to said at least one port to whereby said connector may be sealed to said port to provide communication between said pressure source and said mixing bladder.

48. The system of claim 46, further comprising a temperature control apparatus for maintaining said substrate, said reaction chamber forming device, and fluid within said reaction chamber at a desired temperature.

49. The system of claim 46, wherein said reaction chamber forming device further comprises an inlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure.

50. The system of claim 46, wherein said reaction chamber forming device further comprises an outlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure.

51. The system of claim 46, further comprising a waste collection cap comprising an outer casing containing an absorbent material and having at least one opening providing access to said absorbent material, wherein said waste collection cap is adapted to be placed over said outlet such that fluid exiting said outlet is wicked into said absorbent material via said at least one opening.

52. The system of claim 46, further comprising a port adapter having a flat surface adapted to fit against the top surface of said reaction chamber forming device over one of said inlet and said outlet, and a hole sized to receive and stabilize the tip of a device used to load fluids into said inlet or remove fluid from said outlet;

wherein in used said port adapter is secured to the top surface of said reaction chamber forming device with said hole positioned over one of said inlet and said outlet, to provide proper positioning of said tip with respect to said port.

53. The system of claim 46, further comprising an alignment jig having a slot comprising first and second grooves adapted to receive said substrate, an overhang positioned over an end of said substrate when said substrate is fully inserted in said slot, and an opening providing access to a surface of said substrate;

wherein said opening is sized to permit said substrate to be placed within said opening with an end of said reaction chamber forming device aligned against said overhang, and wherein said placement of said reaction chamber forming device produces correct positioning of said reaction chamber forming device with respect to said substrate.

54. The system of claim 46, further comprising a brayer adapted to slide across the surface of said reaction chamber forming device, thereby pressing said reaction chamber forming device against said substrate to form an improved seal between said reaction chamber forming device and said substrate.

55. The system of claim 46, further comprising a roller adapted to roll across the surface of said reaction chamber forming device, thereby pressing said reaction chamber forming device against said substrate to form an improved seal between said reaction chamber forming device and said substrate.

56. The system of claim 46, further comprising a press adapted to apply pressure to the surface of said reaction chamber forming device, thereby pressing said reaction chamber forming device against said substrate to form an improved seal between said reaction chamber forming device and said substrate.

57. The system of claim 46, further comprising a clamp adapted to clamp said reaction chamber forming device and said substrate together.

58. The system of claim 46, further comprising a disassembly jig having a slot comprising first and second grooves adapted to receive said substrate and adapted to secure said substrate while said reaction chamber forming device is peeled off of said substrate.

59. The system of claim 46, further comprising a sealing structure for sealing said inlet selected from the group consisting of adhesive tape and a plug.

60. A method of performing a binding reaction with the device of claim 27, comprising the steps of:

a) sealing the reaction chamber forming device of claim 27 to the substrate to form a closed reaction chamber;

b) injecting fluid through the inlet into said closed reaction chamber; and

c) alternately inflating and deflating said at least one mixing bladder to generate movement of said fluid within said closed reaction chamber.

61. The method of claim 60, comprising the further step of bringing said substrate and said fluid within said closed reaction chamber to a desired temperature.

62. The method of claim 60, wherein said device further comprises an outlet passing through said main structure and providing fluid communication between said reaction chamber and the exterior of said main structure, said method comprising the further step of causing fluid to exit said closed reaction chamber via said outlet.

63. The method of claim 62, comprising the further step of collecting fluid exiting said closed reaction chamber via said outlet.

64. The method of claim 63, wherein said fluid is collected in a pipette tip.

65. The method of claim 63, wherein said fluid is collected in a waste collection cap.

66. The method of claim 60, wherein said binding reaction comprises a hybridization reaction.

67. The method of claim 60, wherein the fluid to be injected into the closed reaction chamber is preheated.

68. The method of claim 60, wherein said reaction chamber forming device and said substrate are preheated prior to the injection of fluid through the inlet into said closed reaction chamber.

70. The hybridization chamber forming device of claim 69, wherein said adhesive gasket has a thickness of about 25 μ

m.

46. A system for performing a reaction on the surface of a reactant-bearing substrate, comprising:

a) a reaction chamber forming device comprising;

i) a main structure comprising a plurality of substantially planar layers laminated together;

ii) a gasket on a surface of said main structure, said gasket defining an open reaction chamber adapted to seal against the substrate to form a closed reaction chamber, said reaction chamber bounded by said substrate, a surface of said main structure, and said gasket;

iii) at least one mixing bladder formed within said main structure adjacent said surface;

iv) at least one port providing communication between said mixing bladder and the exterior of said main structure and adapted to connect to a pressure source to provide for the delivery of pressurized gas or liquid to said mixing bladder to produce inflation or deflation of said mixing bladder,

wherein inflation or deflation of said mixing bladder produces deflection of at least a portion of said surface; and

b) a pressure source adapted to connect to said at least one port to deliver pressurized gas or liquid to said mixing bladder to generated mixing of fluid within said reaction chamber.

69. A hybridization chamber forming device comprising:

a) a lower surface formed of prime coated 3M Scotchpar™

P581291 polyester film; and

b) an adhesive gasket formed of 3M 501 FL acrylic transfer adhesive, said adhesive gasket comprising an opening defining the border of a hybridization chamber;

wherein said hybridization chamber forming device is adapted to adhere to a substrate to form a hybridization chamber bounded by said substrate, said lower surface, and said opening in said adhesive gasket.