Laminated microarray interface device

• US 7,235,400 B2
• Filed: 08/02/2002
• Issued: 06/26/2007
• Est. Priority Date: 03/09/2001
• Status: Expired due to Fees

• Current Assignee: Roche NimbleGen, Inc. (Roche Holding AG)
• Original Assignee: BioMicro Systems, Inc. (Danaher Corporation)
• Inventors: Adey, Nils B.
• Primary Examiner(s): Beisner; William H.
• Application Number:
  US10/211,503
• Publication Number:
  US 20020192701A1
• Time in Patent Office: 1,789 Days
• Field of Search: 435/287.2, 435/293.1
• US Class Current: 435/287.2
• 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 microfluidic interface device for adhering to a substrate to form a sealed reaction chamber, comprising:

a flexible main structure comprising a plurality of substantially planar flexible layers laminated together, wherein the layers comprise;

a support layer;

a diaphragm layer laminated directly or indirectly to the support layer; and

at least two mixing bladders disposed between the support layer and the diaphragm layer; and

an adhesive gasket laminated directly or indirectly to the diaphragm layer of said main structure, wherein said gasket defines the wall of a reaction chamber and is adapted to reversibly seal against a substrate to form a closed reaction chamber, said reaction chamber bounded by said substrate, the diaphragm layer, and said gasket;

wherein said flexible main structure is sufficiently flexible that the gasket is capable of being released from the substrate without breaking the substrate during disassembly; and

wherein each mixing bladder has at least one port providing communication between said mixing bladder and the exterior of said main structure and is adapted to connect to an external source of pressure or vacuum to produce alternate inflation or deflation of said mixing bladders and out of phase deflection of the diaphragm overlaying each opening of the mixing bladder layer, to thereby cause mixing of the fluid in the chamber.

2. 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.

3. The device of claim 2, wherein said at least one port exits in said main structure on a surface of said removal tab and is connected to said mixing bladder by channel formed in the interior of said main structure.

4. The device of claim 3, 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.

5. The device of claim 2, 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.

6. 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.

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

8. The device of claim 7, 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.

9. The device of claim 7, comprising at least one layer formed of copolyester plastic.

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

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

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

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

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

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

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

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

18. 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, wherein each of said reaction chambers includes two or more mixing bladders.

19. 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.

20. The device of claim 19, 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.

21. The system of claim 19, further comprising a sealing structure for sealing said inlet selected from the group consisting of adhesive tape and a plug.

22. 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.

23. The device of claim 22, 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.

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

a substantially planar flexible mixing bladder layer laminated between the support layer and the diaphragm layer and comprising at least two independent openings defining the wall of the mixing bladder.

25. The device of claim 1, wherein said diaphragm layer is made of a polyester film.

26. The device of claim 1, further comprising an adhesive between a connector and the opening of one or more port.

27. The device of claim 1, further comprising a resilient sealing member positioned between a connector and the opening of one or more port.

28. The device of claim 27, wherein said connector and said opening are pressed together by a clamp.

29. The device of claim 1, further comprising a connector positioned with respect to one or more port with an alignment means.

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

31. The device of claim 30, wherein at least one mixing bladder is defined by an opening in one said adhesive layer and bounded by two non-adhesive layers.

32. The device of claim 31, wherein said main structure further comprises at least one channel connecting said mixing bladders 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.

33. The device of claim 32, wherein said at least one channel and at least a portion of said mixing bladders are defined by openings in the same adhesive layer.

34. The device of claim 32, wherein said at least one channel and at least a portion of said mixing bladders are defined by openings in different adhesive layers.

35. The system of claim 1, 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.

36. The system of claim 1, 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.

37. The system of claim 1, further comprising an alignment jig having a slot to receive said substrate, wherein placement of said reaction chamber forming device produces correct positioning of said reaction chamber forming device with respect to said substrate.

38. The system of claim 1, 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.

39. The system of claim 1, 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.

40. The system of claim 1, 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.

41. The system of claim 1, further comprising a clamp adapted to clamp said reaction chamber forming device and said substrate together.

42. The system of claim 1, further comprising a disassembly jig having a slot adapted to receive said substrate and adapted to secure said substrate while said reaction chamber forming device is peeled off of said substrate.

43. A microfluidic interface device of claim 1, wherein the reaction chamber comprises:

a) a surface of the main structure having stronger adhesive properties to said adhesive gasket relative to said substrate, such that upon removal of said device from the substrate the adhesive gasket preferentially binds to the main structure and releases from the substrate; and

b) said adhesive gasket comprised of liquid impermeable adhesive material, such that upon removal of said device from the substrate the adhesive gasket preferentially binds to the main structure and releases from the substrate;

wherein said reaction 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.

44. The hybridization chamber forming device of claim 43, wherein said adhesive gasket has a thickness of about 25 μ

m.