Bioarray chip reaction apparatus and its manufacture

• US 20050003421A1
• Filed: 06/25/2004
• Published: 01/06/2005
• Est. Priority Date: 06/08/1994
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Winkler, James L., Goss, Virginia W., Besemer, Donald M.
• Application Number:
  US10/877,666
• Publication Number:
  US 20050003421A1
• Time in Patent Office: Days
• US Class Current: 506/7
• CPC Class Codes: B01F 33/252 using bubbles as loose mixing element
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/40 Mixers using gas or liquid agitation, e.g. with air supply tubes
• CPC Class Codes: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• 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 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00371 comprising electrodes
• 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 2219/00531 essentially square
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/00608 : 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 2219/00621 : 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 2219/00641 : the porous medium being continuous, e.g. porous oxide substrates
• 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 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B01L 2200/025 : Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 : for microfluidic devices
• CPC Class Codes: B01L 2200/0689 : Sealing
• CPC Class Codes: B01L 2200/12 : Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/147 : Employing temperature sensors
• 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 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0825 : Test strips
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/1805 : Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0439 : ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 : thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0611 : duck bill valves
• CPC Class Codes: B01L 2400/065 : sliding 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 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: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: H01L 21/67144 : Apparatus for mounting on conductive members, e.g. leadframes or conductors on insulating substrates
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.

Claims

1-92. -92. (Canceled).

93. A method of interrogating an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface, the method comprising:

(a) illuminating the features while the array is dry, with an interrogating light which is directed trough the substrate from the back surface and onto the chemical features on the front surface; and

(b) detecting light emitted from respective features in response to the interrogating light, which detected light has passed from the front surface, through the substrate and out the back surface;

wherein the light is emitted from locations of the features which are spaced from the front surface a distance of less than one-eighth of the wavelength of the illuminating light in a gas or a vacuum which is in contact with the dry array.

94. A method according to claim 93 wherein the light emitting locations of the chemical features are spaced from the front surface a distance of less than one-tenth of the wavelength of the illuminating light.

95. A method according to claim 93 wherein the light emitting locations of the chemical features are spaced from the front surface a distance of less than one-twentieth of the wavelength of the illuminating light.

96. A method according to claim 93 wherein the light emitting locations of the chemical features are spaced from the front surface a distance of less than one-fiftieth of the wavelength of the illuminating light.

97. A method according to claim 93 wherein the interrogating light is directed toward the back surface at an angle of between 0 and 45 degrees to a normal to the back surface.

98. A method according to claim 97 wherein the angle is less than 25 degrees.

99. A method according to claim 97 wherein the angle is less than 10 degrees.

100. A method according to claim 93 wherein the chemical features are polynucleotides.

101. A method according to claim 93 wherein the chemical features are amino acid polymers.

102. A method of interrogating an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface, the method comprising:

(a) illuminating the features while the array is dry, with an interrogating light which is directed through the substrate from the back surface and onto the chemical features on the front surface; and

(b) detecting light emitted from respective features in response to the interrogating light, which detected light has passed from the front surface, through the substrate and out the back surface;

wherein the light is emitted from locations of the features which are spaced from the front surface a distance of less than one-eighth of the wavelength of the emitted light in a gas or a vacuum which is in contact with the dry array.

103. A method according to claim 102 wherein the light is emitted from locations of the features which are spaced from the front surface a distance of less than one-tenth of the emitted light wavelength.

104. A method according to claim 102 wherein the light is emitted from locations of the features which are spaced from the front surface a distance of less than one fiftieth of the emitted light wavelength.

105. A method of interrogating an addressable array unit having a substrate with a back surface, and an array with a plurality of different chemical features on a front surface, the method comprising:

(a) illuminating the features while the array is dry, with an interrogating light which is directed through the substrate from the back surface and onto the chemical features on the front surface; and

(b) detecting light emitted from respective features in response to the interrogating light, which detected light has passed from the front surface, through the substrate and out the back surface;

wherein the light is emitted from locations of the features which are spaced from the front surface a distance such that the average detected signal from the dry array is at least 10% greater than would be detected under the same conditions except with the interrogating light and detected emitted light not passing through the substrate.

106. A method according to claim 105 wherein the average detected signal from the array is at least 40% greater.

107. A method according to claim 105 wherein the average detected signal from the array is at least 80% greater.

108. A package comprising:

an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface, the chemical features having a thickness of less than 100 nm; and

instructions to;

(i) interrogate the array with an interrogating light which is directed through the substrate from the back surface and onto the chemical features on the front surface; and

(ii) detect light emitted from respective features in response to the interrogating light, which detected light has passed from the front surface, through the substrate and out the back surface.

109. A package according to claim 108 wherein the features have a thickness of less than 50 nm.

110. A package according to claim 108 wherein the features have a thickness of less than 10 nm.

112. A method for use with an interrogating an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface, the method comprising:

(a) machine reading an identifier associated with the array unit;

(b) based on the read identifier, retrieving by a processor an instruction that the array should be interrogated and read through the substrate from the back surface.

113. A method according to claim 112 wherein the identifier is on the array substrate or a housing carrying the array substrate.

114. A method according to claim 112 wherein the instruction is retrieved from the read identifier.

115. A method according to claim 112 wherein the instruction is retrieved from a memory using data from the read identifier.