Analytical biochemistry system with robotically carried bioarray

• US 20050271552A1
• Filed: 05/05/2005
• Published: 12/08/2005
• Est. Priority Date: 01/16/1996
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Mc Neal, Jack D., Coassin, Peter J., Helphrey, David E.
• Application Number:
  US11/123,344
• Publication Number:
  US 20050271552A1
• 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.

Claims

1. A system for detecting the presence of a target biomolecule within a sample comprising:

a support surface treated with distinct reactants immobilized thereon in a spaced-apart relation, forming a substrate having a plurality of spaced-apart active sites,

at least one of the reactants being reactive with a target biomolecule to form a bound complex having a detectable characteristic,

holder means for supporting the substrate,

an inspection station having means for probing the spaced-apart active sites of the substrate for said detectable characteristic of the sample, and

manipulator means for bringing the holder means into contact with the sample and into said inspection station.

2-76. -76. (canceled)

77. A method of reading an array of moieties on at least a portion of a surface of a transparent slide which is opposite a first portion on an opposite surface, which array has been previously exposed to a sample, the method comprising:

(a) exposing the array to a sample by placing the slide in a vapor tight barrier;

(b) transferring the slide to an open environment for washing and drying of the array;

(c) mounting the slide on a slide holder and retaining the slide thereon in an enclosed and protected environment without the array contacting the holder; and

(d) inserting the holder into an array reader and reading the array.

83. A method according to claim 77, wherein the holder has front and rear clamp sets which can be moved apart to receive the slide therebetween, and wherein the slide is retained in the enclosed and protected environment by the clamp sets being urged against portions of the front and rear surfaces, respectively.

85. A method according to claim 77, wherein the holder has:

a body having side portions and a channel intermediate the side portions and extending in a direction between ends of the body; and

front and rear clamp member sets with members disposed about the channel, one set of which is fixed to the body side portions while the other set is movable to an open position away from the fixed set; and

, wherein the slide is retained in the enclosed and protected environment by being urged against the fixed clamp member set.

78. A method of reading an array of moieties on at least a portion of a rear surface of a transparent slide which is opposite a first portion on the front surface, which array has been previously exposed to a sample, the method comprising:

(a) exposing the array to a sample by placing the slide in a vapor tight barrier;

(b) transferring the slide to an open environment for washing and drying of the array;

(c) mounting the slide on a slide holder and retaining the slide thereon in an enclosed and protected environment in which the previously exposed array faces, and is spaced apart from, a backer member of the holder without the array contacting the holder; and

(b) inserting the holder into an array reader and reading the array.

79. A method according to claim 78, wherein the moieties are polynucleotides of different sequences.

80. A method according to claim 79, wherein the moieties are DNA of different sequences.

81. A method according to claim 78, wherein the array is read through the front side of the slide.

82. A method according to claim 81, wherein the array reading comprises directing a light beam through the slide from the front side and onto the array, and detecting a resulting signal from the array which has passed through the slide and out the slide front side.

84. A method according to claim 78, wherein the holder has front and rear clamp sets which can be moved apart to receive the slide therebetween, and wherein the slide is retained in the enclosed and protected environment by the clamp sets being urged against portions of the front and rear surfaces, respectively.

86. A method according to claim 78, wherein the holder has:

a body having side portions and a channel intermediate the side portions and extending in a direction between ends of the body, the backer member, comprising a bottom surface of the channel; and

front and rear clamp member sets with members disposed about the channel, one set of which is fixed to the body side portions while the other set is movable to an open position away from the fixed set; and

wherein the slide is retained in the enclosed and protected environment by being urged against the fixed clamp member set.

87. A method according to claim 86, wherein the clamp sets are resiliently urged toward one another, and wherein the movable set is moved to the open position prior to mounting the slide on the holder.

88. A method according to claim 87, additionally comprising a control member set positioned on the holder outside the channel and wherein the control member set is moved to move the movable clamp set to the open position.

89. A method according to claim 88, wherein the front clamp member set is fixed to the body side portions and the rear clamp member set is movable.

90. A method according to claim 89, wherein the control member set is moved rearward to move the clamp member set to the open position.

91. A method according to claim 78, wherein the holder additionally has a body having a channel with a closed end, wherein the backer member comprises a bottom surface of the channel;

and wherein the mounting of the slide on the holder comprises sliding the slide in an endways direction of the channel and into the enclosed and protected environment in which a leading end of the slide abuts the closed end of the channel.

92. A method according to claim 87, wherein members of each of the front and rear clamp member sets are disposed on opposite sides of the channel, and wherein the mounting of the slide on the holder comprises, when the clamp member sets are in the open position, sliding the slide in an endways direction of the channel between the clamp member sets and into the enclosed and protected environment.

93. A method according to claim 92, wherein the holder additionally has two spaced apart guides extending from the body adjacent respective sides of the channel, and wherein the slide is slid into the enclosed and protected environment along the guides and in which enclosed and protected environment a trailing end of the slide is positioned between the guides.

94. A method according to claim 93, wherein during the mounting of the slide portions of the slide front and rear surfaces are gripped and the gripped portions used to then slide the slide into the enclosed and protected environment, which gripped portions are positioned between the guides when the slide is in the enclosed and protected environment.

95. A method according to claim 94, additionally comprising removing the slide from the enclosed and protected environment, the removing comprising gripping portions of the slide front and rear surfaces which are between the guides and using the gripped portions to slide the slide in an endways direction opposite to that during the slide mounting.