Miniaturized genetic analysis systems and methods

• US 20050202504A1
• Filed: 05/06/2005
• Published: 09/15/2005
• Est. Priority Date: 06/29/1995
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Fodor, Stephen P.A., Lipshutz, Robert J., Rava, Richard P., Anderson, Rolfe C.
• Application Number:
  US11/124,575
• Publication Number:
  US 20050202504A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 2101/44 Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 31/86 with vibration of the receptacle or part of it
• CPC Class Codes: B01F 33/25 Mixers with loose mixing elements, e.g. loose balls in a receptacle
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/403 for mixing liquids B01F33/402, B01F33/405, B01F33/406 take precedence
• CPC Class Codes: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01F 33/451 wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/086 : using baffles or other fixed flow obstructions
• 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 3/502723 : characterised by venting arrangements
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• 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 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• 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 7/525 : with physical movement of samples between temperature zones

Abstract

The present invention provides a miniaturized integrated nucleic acid diagnostic device and system.

Claims

1-65. -65. (canceled)

66. An integrated microfluidic array device comprising:

a microfluidic component having a microfluidic feature for carrying a fluid of interest; and

an array component comprising a flexible array substrate supporting an addressable collection of probes, said array component in operable association with said microfluidic feature of the microfluidic component for analyzing said fluid of interest.

67. The integrated microfluidic array device of claim 66 wherein said flexible array substrate comprises a flexible base supporting, in order, a reflective layer, a transparent layer, and the addressable collection of probes.

68. The integrated microfluidic array device of claim 67 wherein said flexible array substrate further comprises a flexible support supporting the flexible base.

69. The integrated microfluidic array device of claim 66 wherein the microfluidic component includes an identifier.

70. The integrated microfluidic array device of claim 66 wherein the integrated microfluidic array device is flexible.

71. The integrated microfluidic array device of claim 66 wherein the integrated microfluidic array device is rigid.

72. The integrated microfluidic array device of claim 66, wherein said microfluidic component further comprises a reservoir for holding one of a washing buffer, a sample fluid, or a reagent solution, the reservoir in fluid communication with the microfluidic feature.

73. The integrated microfluidic array device of claim 66, wherein said microfluidic component further comprises a valve for controlling fluid flow, the valve in operable relation to the microfluidic feature.

74. The integrated microfluidic array device of claim 66 wherein said flexible array substrate comprises a polymer material selected from the group consisting of polyacrylamide, polyetheretherketone, polyacrylate, polymethacrylate, polyesters, polyolefins, polyethylene, polytetrafluoro-ethylene, polypropylene, poly(4-methylbutene), polystyrene, poly(ethylene terephthalate), nitrocellulose, cellulose acetate, poly(vinyl chloride), polyamides, nylon, poly(vinyl butyrate), cross-linked dextran, and agarose.

75. The integrated microfluidic array device of claim 66 wherein said microfluidic component and said array component are modular.

76. The integrated microfluidic array device of claim 66 wherein said microfluidic feature is a microfluidic sipper structure.

77. The integrated microfluidic array device of claim 66, wherein said microfluidic feature is adapted to perform at least one of a reaction, concentration, or separation process.

78. The integrated microfluidic device of claim 66 wherein the microfluidic component includes a chamber in fluid communication with the microfluidic feature, the flexible array substrate disposed within the chamber.

79. The integrated microfluidic array device of claim 66 further comprising a chamber defined in part by the flexible array substrate, the chamber in fluid communication with the microfluidic feature.

80. The integrated microfluidic array device of claim 66 wherein the array component comprises a plurality of addressable collections of probes, each addressable collection of probes associated with its own separate chamber defined in part by the array substrate.

81. The integrated microfluidic array device of claim 66 wherein more than one array component is joined to the microfluidic component.

82. The integrated microfluidic array device of claim 66 wherein more than one microfluidic component is joined to the array component.

83. The integrated microfluidic array device of claim 66, the array component further comprising an interface surface and the microfluidic component further comprising a mating surface, wherein the interface surface and the mating surface are adapted to fit together to form a fluid tight seal when the array component is in operable association with the microfluidic component.

84. The integrated microfluidic device of claim 83 wherein the array component is bonded to the microfluidic component using an adhesive.

85. The integrated microfluidic device of claim 83 wherein the array component is joined to the microfluidic component using ultrasonic welding.

86. The integrated microfluidic array device of claim 66, wherein said microfluidic component is adapted for interfacing to a standard multi-well plate.

87. The integrated microfluidic array device of claim 66 further comprising fiducial marks supported on the flexible array substrate.

88. The integrated microfluidic array device of claim 66 wherein the flexible array substrate has a thickness of less than about 800 microns.

89. A method of producing an integrated microfluidic array device comprising:

a) forming a plurality of arrays by fabricating a plurality of addressable collections of probes on a flexible array substrate;

b) forming a microfluidic component having a microfluidic feature; and

c) placing at least one of said arrays in fluid communication with said microfluidic feature of said microfluidic component.

90. The method of claim 89, further comprising, before step c), cutting the flexible array substrate to provide said at least one of said arrays for step c).

91. A method of performing a hybridization assay on a sample comprising:

a) obtaining an integrated microfluidic array device comprising a microfluidic component having a microfluidic feature, the microfluidic array device further comprising an array comprising a flexible array substrate supporting an addressable collection of probes in fluid communication with said microfluidic feature;

b) introducing said sample to the integrated microfluidic array device; and

c) contacting the addressable collection of probes with the sample for a time and under conditions sufficient to allow the sample to react with the probes, thereby performing the hybridization assay.

92. The method of claim 91, further comprising interrogating the array.

93. The method of claim 91, further comprising removing the array from the integrated microfluidic device prior to interrogating.

94. The method of claim 91, wherein the microfluidic array device further comprises a cover covering the array, the method further comprising removing the cover prior to interrogating the array.

95. The method of claim 91 further comprising mixing said sample during said reaction.

96. The method of claim 91 further comprising washing said array.

97. The method of claim 91 further comprising reading an identifier on the microfluidic device.