Flow-thru chip cartridge, chip holder, system and method thereof

• US 20040137604A1
• Filed: 11/12/2003
• Published: 07/15/2004
• Est. Priority Date: 12/22/1999
• Status: Active Grant

• Current Assignee: Angle Europe Limited (ANGLE Plc)
• Original Assignee: MMV Financial Inc.
• Inventors: Mateer, David G, Goodman, Jack, Torres, Matthew, Yang, Hongjun, Smith, Ian Stuart Richard
• Granted Patent: US 7,326,561 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• 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 2400/06 Valves, specific forms thereof
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 7/00 Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• 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 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00

Abstract

A system for performing hybridization assays comprises a cartridge for housing a flow through device, where the cartridge includes a test fluid chamber for facilitating a substantially uniform flow of a test fluid mixture through the flow through device, and a fluidics station to deliver the test fluid mixture to the cartridge. The cartridge has a chip holder that holds the flow-through device, which has an array of microchannel passages. The chip holder has a support for placement of the flow though device, the test fluid chamber for directing a substantially uniform flow of a test fluid mixture through the array of microchannel passages of the flow through device, and a first port that receives the test fluid mixture. The cartridge has a sealing system for preventing the leakage of the test fluid around the flow through device. The test fluid chamber is defined in part by a spade-like surface having an inlet for the test fluid mixture.

Claims

1. A cartridge for housing a flow through device, comprising:

a flow through device having a first side, a second side, and an array of microchannel passages extending through the first and second sides; and

a chip holder for holding the flow through device, the chip holder comprising;

a body with a support that supports the flow though device;

a flow surface formed within the body, the flow surface facing the first side;

a test fluid chamber defined at least by the flow surface and the first side, and configured to produce a substantially uniform flow of a test fluid mixture through the microchannel passages; and

a first port communicating with the test fluid chamber for passing the test fluid mixture into the test fluid chamber.

2. The cartridge of claim 1, further including a base for supporting the chip holder.

3. The cartridge of claim 1, wherein the flow surface is angled.

4. The cartridge of claim 1, wherein the flow surface includes a trench that is sloped relative to the first side, from a first portion to a second portion of the flow surface, to provide a greater spacing at the first portion than at the second portion from the first side.

5. The cartridge of claim 4, wherein the first port is formed at the first portion and the trench has a slope of about 1°

to about 4°

relative to the first side.

6. The cartridge of claim 5, wherein the slope is about 2.55°

relative to the first side.

7. The cartridge of claim 1, wherein the body has a second port for draining the test fluid mixture that has passed through the flow through device.

8. The cartridge of claim 1, further including a first seal contacting the first side to prevent leakage of the test fluid in the test fluid chamber.

9. The cartridge of claim 8, wherein the first seal contacts a perimeter region of the flow through device on the first side to direct flow of the test fluid mixture though the flow through device and to prevent leakage of the test fluid mixture around the flow through device.

10. The cartridge of claim 1, further including first and second seals in contact with perimeter regions of the first and second sides of the flow through device to prevent leakage of the test fluid mixture.

11. The cartridge of claim 10, wherein the second seal has a channel to direct a flow of the test fluid mixture to the second port.

12. The cartridge of claim 10, wherein the first and second seals are made of Viton rubber.

13. The cartridge of claim 8, wherein the support comprises a first shelf disposed around the flow surface, and the seal is sandwiched between the first side and the first shelf.

14. The cartridge of claim 1, further including an observation window, which is supported on the body for viewing the second side of the flow through device.

15. The cartridge of claim 14, wherein the body has a second shelf disposed around the first shelf, the observation window being seated over the second shelf.

16. The cartridge of claim 1, further including a low scatter window disposed over the second side of the flow through device.

17. The cartridge of claim 2, further including a cover with an opening positioned over the second side for passage of an optical signal therethrough.

18. The cartridge of claim 17, wherein the base, the chip holder, and the cover are constructed from a metal coated with a low light scattering coating.

19. The cartridge of claim 17, wherein the base, the chip holder, and the cover are injection molded as one piece.

20. The cartridge of claim 17, wherein the base is coupled to the cover with a fastener.

21. The cartridge of claim 20, wherein the fastener comprises a plurality of shoulder screws and spring washers, the base having complementary threaded portions for receiving threaded portions of the shoulder screws.

22. The cartridge of claim 20, wherein the fastener comprises a latch.

23. The cartridge of claim 22, wherein the cover and the base are hinged opposite the latch.

24. The cartridge of claim 1, wherein the body has a recess formed on an opposite side of the flow surface, wherein the recess forms a thermal chamber for controlling the temperature of the test fluid in the test fluid chamber.

25. The cartridge of claim 2, wherein the base has a recess for receiving the chip holder and the body has a recess formed on an opposite side of the flow surface, the recesses forming a thermal chamber for controlling the temperature of the test fluid in the test fluid chamber.

26. The cartridge of claim 25, further including an insert positioned in the recesses and defines the thermal chamber, the insert isolating the thermal fluid within the thermal chamber to prevent the test fluid from contamination.

27. The cartridge of claims 25, wherein the recess of the base is complementary to a low-end portion of the chip holder.

28. The cartridge of claim 26, further including means for distributing a thermal fluid into the thermal chamber.

29. The cartridge of any one of claim 1-28, wherein the flow through device is a FLOW-THRU-CHIP™

.

30. The cartridge of any one of claims 1-28, further including a fluid delivery mechanism for delivering the test fluid mixture through the first port.

50. A method of performing a biomolecular assay, comprising:

controlling a passage of buffer solution from a buffer reservoir into the chip cartridge of any of claims 1-28;

controlling the passage of a target or probe compound into the buffer solution to form the test fluid mixture; and

circulating the test fluid mixture to the cartridge in a closed loop.

51. An apparatus for performing biomolecular assays, comprising the cartridge of any one of claims 1-28.

52. A system for performing biomolecular assays, comprising the cartridge of any one of claims 1-28.

31. A chip holder for holding a flow through device having a first side, a second side, and an array of microchannel passages extending through the first and second sides, comprising:

a body with a support adapted to support the flow though device;

a flow surface formed within the body, the flow surface adapted to face the first side;

a test fluid chamber defined at least by the flow surface and the first side upon supporting the flow through device, and configured to produce a substantially uniform flow of a test fluid mixture through the microchannel passages; and

a first port communicating with the test fluid chamber for passing the test fluid mixture into the test fluid chamber.

32. The chip holder of claim 31, wherein the flow surface is angled.

33. The chip holder of claim 31, wherein the flow surface includes a trench that is sloped relative to the first side, from a first portion to a second portion of the flow surface, to provide a greater spacing at the first portion than at the second portion from the first side.

34. The chip holder of claim 33, wherein the first port is formed at the first portion and the trench has a slope of about 1°

to about 4°

relative to the first side.

35. The chip holder of claim 34, wherein the slope is about 2.55°

relative to the first side.

36. The chip holder of claim 31, wherein the body has a second port for draining the test fluid mixture that has passed through the flow through device.

37. The chip holder of claim 31, wherein the support comprises a first shelf disposed around the flow surface, the support being adapted to seat a seal, which is adapted to be sandwiched between the first side and the first shelf.

38. The chip holder of claim 37, wherein the body has a second shelf disposed around the first shelf, the second shelf being adapted to seat an observation window.

39. The chip holder of claim 31, wherein the body has a recess formed on an opposite side of the flow surface, wherein the recess forms a thermal chamber for controlling the temperature of the test fluid in the test fluid chamber.

40. A system for performing hybridization assays, comprising:

a cartridge for housing a flow through device, comprising;

a flow through device having a first side, a second side, and an array of microchannel passages extending through the first and second sides; and

a chip holder for holding the flow through device, the chip holder comprising;

a body with a support that supports the flow though device;

a flow surface formed within the body, the flow surface facing the first side;

a test fluid chamber defined at least by the flow surface and the first side, and configured to produce a substantially uniform flow of a test fluid mixture through the microchannel passages; and

a first port communicating with the test fluid chamber for passing the test fluid mixture into the test fluid chamber; and

a fluidics station for delivering the test fluid mixture to the cartridge.

41. The system of claim 40, further comprising a temperature controller for controlling the temperature of the test fluid in the test fluid chamber.

42. The system of claim 40, wherein the fluidics station comprises:

a pump for moving fluid through a fluid path;

a buffer selection valve for controlling a passage of buffer solutions from buffer reservoirs;

a sample injection valve for controlling the passage of a target or probe compound into the fluid path to form the test fluid mixture; and

a re-circulation control valve in the fluid path and communicating with the buffer selection valve for controlling fluid flow, wherein the re-circulation valve is switchable between an open circuit mode and a closed circuit mode,

wherein in the open circuit mode, the pump communicates with one or more of the buffer solutions to direct the buffer solutions through the sample injection valve and the cartridge, and

wherein in the closed circuit mode, the pump flows the test fluid flow through the sample injection valve and the cartridge in a closed loop.

43. The system of claim 40, further comprising:

a system controller for monitoring and controlling fluid delivery, timing, and temperature of the system.

44. The system of claim 40, wherein the flow surface is angled.

45. The system of claim 40, wherein the flow surface includes a trench that is sloped relative to the first side, from a first portion to a second portion of the flow surface, to provide a greater spacing at the first portion than at the second portion from the first side.

46. The system of claim 45, wherein the first port is formed at the first portion and the trench has a slope of about 1°

to about 4°

relative to the first side.

47. The system of claim 46, wherein the slope is about 2.55°

relative to the first side.

48. The system of claim 40, wherein the body has a second port for draining the test fluid mixture that has passed through the flow through device.

49. The system of claim 40, wherein the body has a recess formed on an opposite side of the flow surface, wherein the recess forms a thermal chamber for controlling the temperature of the test fluid in the test fluid chamber.