Microarray washing apparatus and method

• US 20050268943A1
• Filed: 06/08/2004
• Published: 12/08/2005
• Est. Priority Date: 06/08/2004
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schleifer, Arthur
• Application Number:
  US10/864,229
• Publication Number:
  US 20050268943A1
• Time in Patent Office: Days
• US Class Current: 134/18
• CPC Class Codes: B01J 2219/00281 Individual reactor vessels
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01L 13/02 for receptacle or instruments
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

Apparatus for contacting an array substrate with a fluid and novel methods for washing an array substrate are disclosed. In an embodiment, the apparatus includes a housing defining a wash chamber, a fluid inlet in fluid communication with the wash chamber, a drain in fluid communication with the wash chamber, a gas inlet adapted to direct a stream of gas over a surface of the array substrate, and a program controller in operable relation to the wash chamber, the program controller operable to perform a washing protocol which includes automatically filling the wash chamber with said fluid. A method as described includes placing the array substrate in a wash chamber, triggering a first drain and fill step, automatically performing a second drain and fill step, and automatically performing a slow drain step.

Claims

1. An apparatus for contacting an array substrate with a fluid, the apparatus comprising

a housing defining a wash chamber,

a fluid inlet in fluid communication with the wash chamber,

a drain in fluid communication with the wash chamber,

a gas inlet adapted to direct a stream of gas over a surface of the array substrate, and

a program controller in operable relation to the wash chamber, the program controller operable to perform a washing protocol which includes automatically filling the wash chamber with said fluid.

2. The apparatus of claim 1, further comprising a drain control element in operable relation to the drain, the drain control element adapted to provide at least two different rates of fluid removal from the wash chamber.

3. The apparatus of claim 2, wherein the drain control element is in operable relation to the program controller.

4. The apparatus of claim 1, wherein the drain is adapted to provide at least two different rates of fluid removal from the wash chamber.

5. The apparatus of claim 4, wherein the drain comprises at least two fluid outlets of different size, wherein each fluid outlet is in operable relation to a drain control element.

6. The apparatus of claim 5, wherein the drain control element is in operable relation to the program controller.

7. The apparatus of claim 1, wherein a fluid inlet control element is in operable relation to the fluid inlet.

8. The apparatus of claim 7, wherein the fluid inlet control element is in operable relation to the program controller.

9. The apparatus of claim 7, wherein the fluid inlet control element is a manifold adapted to receive fluid from a plurality of fluid sources and direct fluid from at least one of the fluid sources to the fluid inlet, the manifold comprising a plurality of valves in operable relation to the program controller.

10. The apparatus of claim 1, comprising at least two fluid inlets in fluid communication with the chamber, each fluid inlet adapted to be in fluid communication with a fluid source.

11. The apparatus of claim 1, comprising at least three fluid inlets in fluid communication with the chamber, each fluid inlet adapted to be in fluid communication with a fluid source.

12. The apparatus of claim 1, wherein the fluid inlet is adapted to spray said fluid on one or more of the array substrate and an interior surface of the washing chamber, the fluid inlet adapted to be in fluidic communication with a fluid source.

13. The apparatus of claim 1, wherein a gas inlet control element is in operable relation to the gas inlet.

14. The apparatus of claim 1, wherein a temperature control element is in operable relation to the wash chamber and is adapted to control the temperature of said fluid.

15. The apparatus of claim 14, wherein the temperature control element comprises a temperature modulating means adapted to modulate the temperature of said fluid.

16. The apparatus of claim 14, wherein the temperature control element comprises a temperature modulating means adapted to modulate the temperature of the housing, thereby modulating the temperature of said fluid in the wash chamber.

17. The apparatus of claim 14, further comprising a fluid delivery conduit in fluid communication with the fluid inlet and a fluid reservoir in fluid communication with the fluid inlet, wherein the housing comprises a thermal insulator, and wherein the temperature control element comprises a temperature modulating means operably associated with one or more of the group consisting of the fluid delivery conduit and the fluid reservoir.

18. The apparatus of claim 15, wherein the temperature control element further comprises a temperature sensor and a feedback control loop in operable relation to the temperature modulating means.

19. The apparatus of claim 1, further comprising a high liquid level sensor in operable relation to the wash chamber adapted to detect when the chamber is full or substantially full.

20. The apparatus of claim 1, further comprising a low liquid level sensor in operable relation to the wash chamber adapted to detect when the chamber is empty or nearly empty.

21. The apparatus of claim 1, wherein the wash chamber is sized to receive a hybridization chamber, the wash chamber having wash volume that is at least 25 times the retained volume of the hybridization chamber.

22. The apparatus of claim 1, wherein the wash chamber is shaped to slope down to the drain.

23. The apparatus of claim 1, wherein the drain comprises a grate for supporting said array substrate.

24. The apparatus of claim 23, wherein the drain comprises multiple fluid outlets disposed along the grate.

25. The apparatus of claim 1, further comprising a sensor adapted to indicate the presence of said array substrate in the wash chamber.

26. A method of washing an array substrate, the method comprising

placing the array substrate in a wash chamber,

triggering a first drain and fill step,

automatically performing a second drain and fill step, and

automatically performing a slow drain step.

27. The method of claim 26, further comprising, prior to triggering a first drain and fill step,

filling wash chamber with a first wash solution.

28. The method of claim 26, wherein placing the array substrate comprises placing a hybridization chamber in the wash chamber, and then disassembling the hybridization chamber while the hybridization chamber is submerged in a first wash solution in the wash chamber.

29. The method of claim 28, wherein the hybridization chamber has a retained fluid in contact with the array substrate, and disassembling the hybridization chamber results in diluting the retained fluid into the first wash solution by a factor of at least 25.

30. The method of claim 29, wherein disassembling the hybridization chamber in diluting the retained fluid into the first wash solution by a factor of at least 100.

31. The method of claim 26, wherein the array substrate comprises plurality of microarrays.

32. The method of claim 26, wherein triggering comprises providing a triggering signal to a program controller in operable relation to the wash chamber, wherein the program controller executes an automatic washing protocol comprising a sequence of operations including the first drain and fill step, the second drain and fill step, and the slow drain step.

33. The method of claim 31, wherein the program controller is programmed to perform a predetermined washing protocol.

34. The method of claim 31, wherein the program controller is responsive to user input to select parameters of operation.

35. The method of claim 27, wherein the first drain and fill step comprises

draining the first wash solution from the wash chamber, and

automatically filling the wash chamber with a second wash solution;

wherein the first drain and fill step takes less than about 10 seconds to complete.

36. The method of claim 35, wherein the first drain and fill step takes less than about 6 seconds to complete.

37. The method of claim 35, wherein the first drain and fill step takes less than about 4 seconds to complete.

38. The method of claim 35, wherein draining the first wash solution continues briefly after filling the wash chamber with the second wash solution starts.

39. The method of claim 35, wherein the second wash solution is the same as the first wash solution.

40. The method of claim 26, further comprising, after the first drain and fill step, incubating the array substrate under controlled conditions.

41. The method of claim 40, wherein the controlled conditions comprise stringent wash conditions.

42. The method of claim 26, wherein the second drain and fill step comprises

draining a second wash solution from the wash chamber, and

automatically filling the wash chamber with a third wash solution;

wherein the second drain and fill step takes less than about 10 seconds to complete.

43. The method of claim 42, wherein the second drain and fill step takes less than about 6 seconds to complete.

44. The method of claim 42, wherein the second drain and fill step takes less than about 4 seconds to complete.

45. The method of claim 42, wherein draining the second wash solution continues briefly after filling the wash chamber with the third wash solution starts.

46. The method of claim 26, further comprising one or more additional wash steps prior to automatically performing the slow drain step.

47. The method of claim 26, wherein the slow drain step comprises draining the wash chamber, the slow drain step taking at least about 3 seconds and at most about 120 seconds.

48. The method of claim 47, wherein the slow drain step further comprises directing a stream of gas across the surface of the array substrate as the wash chamber is being drained.

49. The method of claim 48, wherein the slow drain step takes at least about 4 seconds and at most about 100 seconds.

50. The method of claim 48, wherein the slow drain step takes at least about 5 seconds and at most about 75 seconds.