Bioarray chip reaction apparatus and its manufacture

• US 20050158819A1
• Filed: 10/27/2004
• Published: 07/21/2005
• 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:
  US10/976,077
• Publication Number:
  US 20050158819A1
• Time in Patent Office: Days
• US Class Current: 435/68.100
• 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. A method of making probe chips comprising the steps of:

forming a plurality of probe arrays on a wafer;

separating said wafer into a plurality of chips, each of said chips comprising at least one probe array thereon; and

mating at least one of said chips to a package, said package comprising a reaction chamber, said reaction chamber comprising inlets for flowing fluid therein, said at least one probe array in fluid communication with said reaction chamber.

2-92. -92. (canceled)

93. A holder for an array unit having a planar substrate and an array of chemical moieties on a surface of the substrate, the holder comprising:

a body with a retaining mechanism which releasably retains an array unit in a seated position, such that an array unit can be repeatedly inserted into and removed from the seated position in which it is retained in the holder;

a machine readable holder identifier which includes data on a characteristic of the holder or seated array.

94. A holder according to claim 93 wherein the holder identifier includes data on a spatial characteristic of the holder or seated array.

95. A holder according to claim 94 wherein the holder identifier includes data on a a position or dimension of an array unit seated in the holder.

96. A holder according to claim 95 wherein the holder identifier includes data on the position or dimension of the substrate of an array unit seated in the holder unit.

97. A holder according to claim 95 wherein the position or dimension data includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.

98. A holder according to claim 95 wherein the position or dimension data includes data on the z position of the seated array unit.

99. A holder according to claim 95 wherein the position data includes data on the angular orientation of the seated array unit.

100. A holder according to claim 95 wherein the holder identifier comprises a bar code.

101. A holder according to claim 95 wherein the holder additionally comprises a magnetic or solid state memory attached to the body and the identifier is carried by the memory.

102. A holder according to claim 95 additionally comprising a seated array unit.

103. A holder according to claim 102 wherein the seated array unit additionally includes an array unit identifier.

104. A holder according to claim 103 wherein the array unit identifier is a machine readable identifier.

105. A holder according to claim 104 wherein the array unit identifier comprises a bar code or is carried in a memory attached to the remainder of the array unit.

106. A holder according to claim 95 which has a maximum length and width each no greater than 50 cm, and a thickness no greater than 10 cm.

113. A holder according to claim 104 wherein the holder identifier comprises a bar code or is carried in a memory attached to the remainder of the holder.

107. A method of reading an array of chemical moieties on a substrate of an array unit, the method comprising:

seating the array unit in a holder, which holder carries a holder identifier;

mounting the holder with seated array unit into an array reader;

reading the holder identifier and retrieving data on a position or dimension of the seated array unit based on the read holder identifier; and

reading the array.

108. A method according to claim 107 wherein the position or dimension data includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.

109. A method according to claim 107 wherein the position or dimension data includes data on the z position of the seated array unit.

110. A method according to claim 107 wherein the position data includes data on the angular orientation of the seated array unit.

111. A method according to claim 107 additionally comprising reading an array unit identifier carried by the array unit.

112. A holder according to claim 111 wherein the array unit identifier is machine read.

114. A method according to claim 107 wherein the reading of the array comprises scanning an interrogating light over the array.

115. A method according to claim 114 wherein the interrogating light is a spot scanned across the array in an x and y direction, where x and y are the directions along a length and width of the array.

116. A method according to claim 114 wherein a position or dimension of an area over which the interrogating light is scanned is based on data retrieved using the read holder identifier.

117. A method comprising forwarding data representing a result of a reading obtained by the method of claim 107.

118. A method according to claim 117 wherein the data is communicated to a remote location.

119. A method comprising receiving data representing a result of a reading obtained by the method of claim 107.

120. A method of reading an array of chemical moieties on a substrate of an array unit, the method comprising:

seating the array unit in a holder, which holder carries a holder identifier;

reading the holder identifier and retrieving a characteristic of the holder or seated array based on the read holder identifier; and

when the retrieved characteristic does not meet a predetermined condition, rejecting the seated array unit for reading or generating an operator alert.

121. A method according to claim 120 wherein the retrieved characteristic of the holder or seated array comprises a spatial characteristic.

122. An apparatus for reading an array of chemical moieties on a substrate of an array unit, the apparatus comprising:

a receptacle into which is mountable a holder carrying a seated array unit, which holder carries a holder identifier;

a reader system to read the holder identifier and data from different chemical moieties of the array; and

a processor which retrieves data on a characteristic of the holder or seated array based on the read holder identifier.

123. An apparatus according to claim 122 wherein the processor retrieves data on a spatial characteristic of the holder or seated array based on the holder identifier.

124. An apparatus according to claim 123 wherein the processor retrieves data on a spatial characteristic which comprises data on a position or dimension of an array unit seated in the holder.

125. An apparatus according to claim 124 wherein the reader system comprises a first identifier reader to read the holder identifier, and an array reader to read the data from different chemical moieties of the array.

126. An apparatus according to claim 124 wherein the processor retrieves data which includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.

127. An apparatus according to claim 124 wherein the reader system also reads an array unit identifier carried by a seated array unit in the mounted holder.

128. An apparatus according to claim 125 additionally comprising a second identifier reader to read an array unit identifier carried by a seated array unit in the mounted holder.

129. An apparatus according to claim 124 wherein the reader system comprises a light system which provides and scans an interrogating light over the array.

130. An apparatus according to claim 129 wherein the light system provides a light spot which is scanned in an x and y direction across the array of the seated array unit in the mounted holder, where x and y are the directions along a length and width of the array.

131. An apparatus according to claim 129 wherein the processor controls a position or dimension of an area over which the interrogating light is scanned based on data retrieved using the read holder identifier.

132. An apparatus according to claim 122 wherein the processor retrieves data on a spatial characteristic of the holder and compares this with a predetermined condition in a memory and when the retrieved spatial characteristic does not meet the retrieved condition generates a user alert or inhibits reading of data from different chemical moieties of the array.

133. An apparatus according to claim 127 wherein:

the reader system comprises a light system which provides and scans an interrogating light over the array;

the processor controls a position or dimension of an area over which the interrogating light is scanned based on data retrieved using the read holder identifier; and

a position or dimension of the area over which the interrogating light is scanned is also based on data retrieved using the read array unit identifier.

134. An apparatus according to claim 124 wherein the array reader comprises a detector having a focal plane, wherein the position of the focal plane is adjusted relative to an array based on the data retrieved using the read holder identifier.

135. A computer program product for use with an apparatus of claim 124, comprising a computer readable storage medium having a computer program stored thereon for reading the holder identifier and retrieving data on the position or dimension of the seated array unit based on the read holder identifier.

136. A computer program product according to claim 135 wherein the program additionally reads an array identifier carried by a seated array unit in the mounted holder and retrieves data on the position or dimension of the array also based on the read array identifier.

137. A computer program product according to claim 136 wherein the program additionally controls a position or dimension of an area on the array of the seated array unit in the mounted holder, over which an interrogating light is scanned.