Analytical biochemistry system with robotically carried bioarray

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.

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 . (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.  
     
     
         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.  
     
     
         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.  
     
     
         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.  
     
     
         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.  
     
     
         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.