Methods for making a device for concurrently processing multiple biological chip assays

• US 20050282156A1
• Filed: 07/01/2005
• Published: 12/22/2005
• Est. Priority Date: 06/07/1995
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Fodor, Stephen P.A., Rava, Richard P., Trulson, Mark, Norviel, Vernon A.
• Application Number:
  US11/173,366
• Publication Number:
  US 20050282156A1
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00639 the compounds being trapped in or bound to a porous medium
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00662 Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00707 : separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01L 2300/041 : Connecting closures to device or container
• CPC Class Codes: B01L 2300/044 : pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/046 : Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 : Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2400/0683 : mechanically breaking a wall or membrane within a channel or chamber
• 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 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50853 : with covers or lids
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• 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 21/64 : Fluorescence; Phosphorescence
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates

Abstract

Methods for concurrently processing multiple biological chip assays by providing a biological chip plate comprising a plurality of test wells, each test well having a biological chip having a molecular probe array; introducing samples into the test wells, subjecting the biological chip plate to manipulation by a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes; and subjecting the biological chip plate to a biological chip plate reader that interrogates the probe arrays to detect any reactions between target molecules and probes.

Claims

1-31. -31. (canceled)

32. A chemical array apparatus comprising:

a breakaway seal applied to a surface of a planar substrate, the breakaway seal surrounding a microarray attached to the substrate surface, wherein a portion of the breakaway seal is removable to create a gap in the breakaway seal.

33. The chemical array apparatus of claim 32, wherein the breakaway seal comprises one or both of a physical seal and a chemical seal.

34. The chemical array apparatus of claim 32, wherein the breakaway seal provides fluid isolation to the microarray.

35. The chemical array apparatus of claim 34, wherein the breakaway seal retains a fluid with the microarray until the gap is created, the gap being created on the portion of the breakaway seal that provides a drainage path for the fluid to a perimeter edge of the planar substrate.

36. The chemical array apparatus of claim 34, wherein the fluidly isolated microarray is from a plurality of microarrays attached to the surface of the substrate, and wherein during an assay of the isolated microarray, the breakaway seal retains a fluid with the isolated microarray, such that a remainder of the plurality of microarrays is unaffected by the assay of the isolated microarray.

37. The chemical array apparatus of claim 32, wherein the microarray is from a plurality of microarrays attached to the surface of the substrate, and wherein the breakaway seal provides the plurality of microarrays fluid isolation from one another.

38. The chemical array apparatus of claim 32, wherein the breakaway seal comprises a plurality of sides, the microarray being surrounded by respective sides of the breakaway seal to provide fluid isolation, the respective sides that surround a microarray comprise one or both of a side shared by an adjacent microarray and a side unshared by an adjacent microarray.

39. The chemical array apparatus of claim 38, wherein the gap is created on a respective side surrounding the microarray that is unshared by an adjacent microarray.

40. The chemical array apparatus of claim 32, wherein the breakaway seal forms a channel or path located between adjacent microarrays on the substrate surface.

41. The chemical array apparatus of claim 32, wherein the microarray is from a plurality of microarrays, the plurality of microarrays being arranged in an array pattern that is spatially addressable, the microarray of the plurality comprising a plurality of a chemical or biochemical polymer attached to the substrate surface in a spatially addressable subarray pattern, the breakaway seal having a grid pattern that corresponds to the array pattern, the grid pattern comprising a plurality of zones, the microarray being surrounded by a respective zone of the breakaway seal.

42. The chemical array apparatus of claim 32, wherein the breakaway seal has physical sidewalls that extend a height from the substrate surface, the height being greater than a height that the microarray extends from the substrate surface, the sidewalls being capable of retaining a fluid with the microarray.

43. The chemical array apparatus of claim 32, wherein the breakaway seal is formed by changing a chemical characteristic of the substrate surface along sides surrounding the microarray, the changed characteristic of the substrate retaining a fluid with the microarray using one or both of a hydrophobic effect and a hydrophilic effect.

44. The chemical array apparatus of claim 32, further comprising:

a removable cover extending over and in contact with the breakaway seal to enclose or shield the microarray.

45. The chemical array apparatus of claim 44, wherein the microarray is from a plurality of microarrays attached to the substrate surface in an array pattern, the cover shielding the plurality of microarrays, the cover optionally being selectively removable in sections to uncover a respective microarray relative to a remainder of the plurality of microarrays, the cover being intact over the remainder of the microarrays when a section of the cover is selectively removed.

46. A system for processing a microarray of a chemical array comprising:

a chemical array that comprises a microarray attached to a surface of a planar substrate;

a breakaway seal provided on the planar substrate to surround the microarray, wherein a portion of the breakaway seal is removable to create a gap in the breakaway seal; and

a removable cover extending over and in contact with the breakaway seal to shield the microarray.

47. The system of claim 46, wherein the microarray is from a plurality of microarrays attached to the substrate surface in a spatially addressable array pattern, the breakaway seal comprising sidewalls in a grid pattern that form zones, the grid pattern corresponding to the array pattern.

48. The system of claim 46, wherein the breakaway seal is dimensioned to reduce contact between the cover and the microarray.

49. The system of claim 46, wherein the removable cover is taut over the breakaway seal to reduce contact between the cover and the microarray.

50. The system of claim 46, wherein the cover is removable by peeling the cover away from the breakaway seal.

51. The system of claim 47, wherein the cover is selective removably from the breakaway seal, such that when a section of the cover is selectively removed to expose a respective microarray, a remainder of the cover that shields a remainder of the plurality of microarrays remains intact and unaffected by the selective removal of the section.

52. The system of claim 51, wherein the selectively removable cover comprises a scored pattern corresponding to the grid pattern of the breakaway seal, such that the section of the cover is selectively removable by separating the section along respective scoring of the scored pattern.

53. The system of claim 52, wherein the section of the cover is further selectively removable by peeling the section away from the breakaway seal.

54. The system of claim 47, wherein the cover comprises a film layer and a grid frame layer, the grid frame layer having a plurality of grid frame units arranged in a frame grid pattern, the frame grid pattern corresponding to the grid pattern of the breakaway seal, the grid frame layer being adjacent and securely attached to the breakaway seal, the film layer overlying the grid frame layer, the film layer being readily separable from the grid frame layer relative to the secure attachment of the grid frame layer to the breakaway seal.

55. The system of claim 54, wherein the film layer comprises scoring in a scored pattern, the scored pattern corresponding to the grid frame pattern, the film layer being selectively separable from the grid frame layer in sections along the scoring, such that when a section of the film layer is removed, the section is peeled from a respective grid frame unit and separated from a remainder of the film layer along a portion of the scoring, the removed section exposing a underlying microarray that is otherwise surrounded by sidewalls of a respective zone of the breakaway seal and the respective grid frame unit, and the remainder of the film layer being unaffected by the removal of the film layer section.

56. The system of claim 47, wherein a zone of the grid pattern surrounds and provides fluid isolation to a respective microarray from other microarrays of the plurality, the removable cover being selectively removable from the zone to provide fluid access to the respective microarray that is otherwise surrounded by respective sidewalls of the breakaway seal, and wherein an unremoved portion of the cover remains intact and provides the other microarrays protection from physical damage and fluid contamination.

57. The system of claim 56, wherein during an assay of the respective microarray, a respective section of the cover is selectively removed from the zone to expose the respective microarray, a fluid deposited on the exposed respective microarray being retained by the respective sidewalls of the zone.

58. The system of claim 57, wherein during the assay of the isolated microarray, the removed cover section is applied over the deposited fluid retained by the respective sidewalls to help shield the fluid during the assay.

59. The system of claim 58, wherein further during the assay, localized pressure is deliberately applied to a sidewall of the respective sidewalls of the zone to create the gap in the breakaway seal, the deposited fluid being released through the created gap.

60. The system of claim 46, wherein the portion of the breakaway seal is removed by deliberately applying localized pressure to a sidewall of the breakaway seal, such that the portion breaks away to create the gap in the sidewall.

61. The system of claim 46, further comprising a fixture having a planar inclined surface and a shelf, the inclined surface and the shelf supporting the chemical array during an assay of the microarray.

62. The system of claim 47, wherein the removable cover is adhered to the breakaway seal using one or more of an adhesive at between the cover and an edge surface of a sidewall of the breakaway seal, an electrostatic attraction between the breakaway seal and the cover along the edge surface of a sidewall, and an adhesive strip in an adhesive grid pattern similar to the breakaway seal grid pattern between the cover and the edge surface of the sidewalls.

63. The system of claim 47, wherein the microarray comprises a plurality of a chemical or biochemical polymer attached to the substrate surface in a spatially addressable subarray pattern.

64. A method of processing a microarray of a chemical array of microarrays comprising:

applying a breakaway seal to a surface of a planar substrate to ultimately surround a microarray on the planar substrate;

processing the microarray with a fluid that is deposited on the microarray, the breakaway seal retaining the fluid with the microarray; and

breaking away a portion of the breakaway seal that retains the fluid with the microarray, the broken away portion creating a gap in the breakaway seal, the gap providing an exit for the release of the fluid from the microarray.

65. The method of claim 64, further comprising attaching a plurality of microarrays to the substrate surface in an array pattern either before or after the breakaway seal is applied, the microarray being from the plurality, the array pattern being spatially addressable, the microarray comprising a plurality of a chemical or biochemical polymer arranged in a subarray pattern that is spatially addressable.

66. The method of claim 64, wherein breaking away a portion of the breakaway seal comprises tilting and orienting the planar substrate in a direction such that the retained fluid will drain through the gap and off the planar substrate.

67. The method of claim 64, wherein the gap is created in the portion of the breakaway seal facing a perimeter edge of the planar substrate, such that the fluid is released in a direction of the facing perimeter edge off the planar substrate.

68. The method of claim 64, wherein breaking away a portion of the seal comprises:

holding the planar substrate at an incline angle, the incline angle being such that the fluid is prevented from exceeding the breakaway seal until the gap is created;

orienting the planar substrate such that a perimeter edge of the planar substrate is at a lowest position when inclined, the lowest position of the substrate perimeter edge being relative to other perimeter edges of the planar substrate; and

applying localized pressure to a sidewall of the portion of the breakaway seal surrounding the microarray, the gap being created in the sidewall, the fluid exiting through the gap off the planar substrate in the direction of the lowest substrate perimeter edge.

69. The method of claim 68, wherein the incline angle assists the fluid to flow through the gap when created.

70. The method of claim 64, further comprising:

covering the microarray with a removable cover, the cover being in contact with the breakaway seal, the cover shielding the microarray; and

removing the cover before processing the microarray, the removed cover providing fluid access to the microarray.

71. The method of claim 70, wherein the microarray is from a plurality of microarrays attached to the substrate surface in an array pattern, the cover being selectively removable from the breakaway seal, such that during removing, a section of the removable cover over the microarray is selectively removed before processing, a remainder of the removable cover being intact over the other microarrays, wherein selectively removing the section of the cover provides fluid access to the uncovered microarray while shielding the other microarrays from the fluid.

72. The method of claim 70, further comprising applying the removed cover on the fluid to help shield the fluid during processing.

73. The method of claim 64, further comprising one or more of:

rinsing the microarray with a wash solution that drains through the created gap;

scanning the microarray using scanning equipment to determine results of the processing;

storing the planar substrate until another microarray on the substrate having an intact breakaway seal is to be processed; and

processing another microarray on the substrate surrounded by an intact portion of the breakaway seal with another fluid when the processing of the microarray having the created gap in the breakaway seal is complete.

74. A removable cover for a chemical array apparatus comprising a sheet of material that overlies a microarray of the chemical array apparatus, the sheet being removable to provide fluid access to the microarray.

75. The removable cover of claim 74, wherein when the sheet is removed, the microarray is exposed, the removed sheet being reapplied on a fluid deposited on the exposed microarray during an assay, the reapplied sheet helping to shield the fluid during the assay of the microarray.

76. The removable cover of claim 74, wherein the chemical array apparatus comprises an array pattern of microarrays, the sheet overlying the microarrays of the array pattern, the sheet being independently removable from over a respective microarray of the array pattern, such that other microarrays of the chemical array apparatus remain covered.

77. The removable cover of claim 74, wherein the sheet of material is taut over the microarray to reduce contact between the sheet and the microarray.

78. The removable cover of claim 74, wherein the sheet is removable by peeling the sheet away from the chemical array apparatus.

79. The removable cover of claim 76, wherein the sheet is independently removably from the chemical array apparatus in sections, the independently removable sheet comprises a scored pattern corresponding to the array pattern of microarrays, such that a section of the sheet is selectively removed by separating the section along respective scoring of the scored pattern.

80. The removable cover of claim 76, wherein the sheet of material comprises a film layer and a grid frame layer, the grid frame layer having a plurality of grid frame units arranged in a frame grid pattern, the frame grid pattern corresponding to the array pattern of the microarrays, the grid frame layer being adjacent and securely attached to the chemical array apparatus, the film layer overlying the grid frame layer, the film layer being readily separable from the grid frame layer relative to the secure attachment of the grid frame layer to the chemical array apparatus.

81. The removable cover of claim 80, wherein the film layer comprises scoring in a scored pattern, the scored pattern corresponding to the grid frame pattern, the film layer being selectively separable from the grid frame layer in sections along the scoring, such that when a section of the film layer is selectively removed, the section is peeled from a respective grid frame unit and separated from a remainder of the film layer along a portion of the scoring, a remainder of the film layer being unaffected by the removal of the film layer section.