Analytical Biochemistry System with Robotically Carried Bioarray

• US 20070128084A1
• Filed: 02/01/2007
• Published: 06/07/2007
• Est. Priority Date: 01/16/1996
• Status: Active Grant

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Helphrey, David, Coassin, Peter, Mc Neal, Jack
• Granted Patent: US 8,273,304 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• 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 2219/00292 in the shape of pipette tips
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00513 Essentially linear supports
• CPC Class Codes: B01J 2219/00527 Sheets
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 3/0275 : Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/508 : rigid containers not provided for above
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 2035/00118 : for multiple tests
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/1055 : for immobilising reagents, e.g. dried reagents
• CPC Class Codes: G01N 2035/1062 : for testing the liquid while it is in the transfer device
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 35/00029 : provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: G01N 35/0099 : comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 : with sample on test slide
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

An analytical biochemistry system featuring a substrate with reactants immobilized thereon at fixed, known locations, a holder supporting the substrate and a manipulator for transporting the holder to a fixed sample and to an inspection station. The reactants are binding agents for a target biomolecule in a sample which forms a bound substance having a detectable characteristic. The holder may be a standard pipettor, optionally carried by a robot arm or hand as the manipulator to contact the sample for detection of the presence of target biomolecules within the sample. In one embodiment, the holder is a pipette tip within which the substrate is housed, or it may be a pipette adapter which bears the substrate and fits within the sample wells of a standard microtiter plate. After appropriate incubation, the substrate and holder may be moved from contact with the sample, and the substrate may be exposed to any necessary development steps before being moved by the manipulator to a location for probing, such as by a beam. Probing of the substrate is performed to identify binding or complexing of target biomolecules of the sample with the reactants immobilized on the substrate, and may be accomplished via fluorescence detection, light scattering, autoradiography, or some other detection method.

Claims

1-99. -99. (canceled)

100. A device comprising:

a) a substrate, with a top surface and a bottom surface, wherein the bottom surface of the substrate comprises at least one array, wherein the array comprises reactant binding agents for a plurality of target biomolecules in a sample to form a bound substance having a detectable characteristic for detection of biomolecules within the sample, wherein the substrate is disposed in a downward facing orientation such that the bottom surface of the substrate contacts the target biomolecules; and

b) a holder wherein the holder is attached to the top surface of the substrate, wherein the holder is sized to fit within a corresponding well of a microtiter plate.

101. A device according to claim 100 wherein the bottom surf ace of the holder is flat.

102. A device according to claim 100 wherein the holder comprises a narrow bore for minimizing sample volume and maximizing proximity of the sample and the substrate.

103. A device according to claim 100 wherein the holder comprises an evaporation barrier.

104. A device according to claim 100 wherein the bottom surface of the holder is sufficiently narrow in diameter to fit thin a sample well of a microtiter plate.

105. A device according to claim 100 wherein the holder is made from plastic.

106. A device according to claim 100 wherein the substrate is a bioarray.

107. A device for bearing a substrate having reactant binding agents for at least one target biomolecule in a sample to form a bound substance having a detectable characteristic for detection of target biomolecules within the sample, the device comprising:

a holder having a bracket with opposed prongs, the opposed prongs bearing the substrate with distinct reactants in a spaced-apart relations the substrate disposed in a downward-facing orientation, wherein the bracket of the pipette adapter is placed on the sample for contact of the sample with the substrate.

108. The device of claim 107 wherein the holder has a coupling means for coupling the holder to a robotic arm.

109. The device of claim 107 wherein the holder has a coupling means for coupling the holder to a hand-held pipette.

110. The device of claim 107 wherein the bracket of the holder is sufficiently narrow in diameter to fit within a sample well of a microtiter plate.

111. The device of claim 107 wherein the bracket prongs of the holder have knobs positioning the substrate a fixed distance from the sample.

112. The device of claim 107 wherein the holder has an evaporation barrier disposed about the holder.

113. A device bearing a substrate having an array of reactant binding agents for a plurality of target biomolecules in a sample to form a bound substance having a detectable characteristic for detection of biomolecules within the sample, the device comprising:

a holder having an end with a flat bottom surface, the flat bottom surface bearing the substrate having an array of reactants in a spaced-apart relations the substrate being disposed in a downward facing orientation, so that, the array of reactants on the substrate can be brought into contact with the sample at the flat bottom surface of the holder.

114. The device of claim 113 wherein the holder has a coupling means for coupling the holder to a robotic arm.

115. The device of claim 113 wherein the holder has a coupling means for coupling the holder to a hand-held pipettor.

116. The device of claim 113 wherein the end of the holder having the flat bottom surface is sufficiently narrow in diameter to fit within a sample well of a microtiter plate.

117. The device of claim 113 wherein the flat bottom surface of the holder has knobs positioning the substrate a fixed distance from the sample.

118. The device of claim 113 wherein the holder has an evaporation barrier disposed about the holder.