Bioarray chip reaction apparatus and its manufacture

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.

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 . (canceled)  
     
     
         93 . An array assay device, said device comprising: (a) a substrate receiving element for receiving a substrate having at least on array thereon, said substrate receiving element comprising a bottom surface; and (b) a compression element for urging said bottom surface in a direction towards a substrate when present in said substrate receiving element so as to hold said bottom surface in a fixed position relative to said substrate.  
     
     
         94 . The array assay device according to  claim 93 , wherein, when said bottom surface is held in said fixed position relative to a substrate when present in said device, said bottom surface ranges from about 0.1 mm to about 2 mm from said substrate.  
     
     
         95 . The array assay device according to  claim 93 , wherein said bottom surface further comprises a sealing element for producing a seal around at least one array positioned on a substrate when held in said fixed position.  
     
     
         96 . The array assay device according to  claim 95 , wherein said seal is substantially vapor and fluid tight.  
     
     
         97 . The array assay device according to  claim 95 , wherein said sealing element produces an assay volume of from about 10.mu.l to about 1000.mu.l.  
     
     
         98 . The array assay device according to  claim 95 , wherein said substrate comprises a plurality of arrays and said sealing element produces a plurality of individual seals around each array.  
     
     
         99 . The array assay device according to  claim 98 , wherein each of said individual seals is substantially vapor and fluid tight.  
     
     
         100 . The array assay device according to  claim 93 , wherein said sealing element is a gasket  
     
     
         101 . The array assay device according to  claim 93 , further comprising at least one access port.  
     
     
         102 . The array assay device according to  claim 101 , wherein said device comprises a plurality of access ports.  
     
     
         103 . The array assay device according to  claim 101 , wherein said device comprises at least a first fluid introduction port and a second venting port.  
     
     
         104 . The array assay device according to  claim 101 , wherein said at least one port is resealable.  
     
     
         105 . The array assay device according to  claim 93 , further comprising a removable array holder.  
     
     
         106 . The array assay device according to  claim 105 , wherein said array holder is configured to be used with an array scanner.  
     
     
         107 . A system for performing array assays, said system comprising: (a) an array assay device according to  claim 93;  and (b) a substrate having at least one array.  
     
     
         108 . A method for performing an array assay, said method comprising: (a) providing an array assay device comprising: (i) a bottom surface, (ii) a substrate receiving element for receiving a substrate having at least on array thereon, and (iii) a compression element for urging said bottom surface in a direction towards a substrate when present in said substrate receiving element so as to hold said bottom surface in a fixed position relative to said substrate; (b) positioning a substrate comprising at least one array in said substrate receiving element; (c) urging said bottom surface in a direction towards said positioned substrate using said compression element, whereby said bottom surface is fixed relative to said substrate present in said receiving element; and (e) contacting a sample to said at least one array.  
     
     
         109 . The method according to  claim 108 , further comprising producing a seal around said at least one array.  
     
     
         110 . The method according to  claim 109 , wherein said seal is substantially vapor and fluid tight.  
     
     
         111 . The method according to  claim 108 , wherein said device comprises at least one port and said sample is introduced through said port.  
     
     
         112 . The method according to  claim 108 , further comprising mixing said sample with said at least one array.  
     
     
         113 . The method according to  claim 112 , wherein said mixing is accomplished by an air bubble.  
     
     
         114 . The method according to  claim 108 , further comprising retaining said substrate in an array holder.  
     
     
         115 . A method comprising, following contacting said at least one array to a sample according to  claim 108 , reading said at least one array.  
     
     
         116 . The method according to  claim 115 , where in said at least one array is read while in the array holder of  claim 114 .  
     
     
         117 . A method comprising forwarding data representing a result of a reading obtained by the method of  claim 115  from a first location to a second location.  
     
     
         118 . The method according to  claim 117 , wherein said second location is remote from said first location.  
     
     
         119 . A method comprising receiving data representing a result of a reading obtained by the method of  claim 115 .  
     
     
         120 . A method for performing an array assay, said method comprising: (a) receiving a pre-packaged substrate having at least one array in the array assay device of  claim 93  from a remote site; (b) performing an array assay using said received array assay device; (c) removing said pre-packaged substrate from said array assay device; and (d) reading said at least one array to obtain a result.  
     
     
         121 . The method according to  claim 120 , wherein said pre-packaged substrate comprises a substrate retained in an array holder in said array assay device.  
     
     
         122 . A method for performing an array assay and reading a result of said array assay, said method comprising: (a) performing an array assay using the array assay device of  claim 93  comprising a substrate having at least on array retained in an array holder; (b) removing said retained substrate having at least one array from said array assay device; and (c) mounting said retained substrate having at least one array on an array scanner so that said retained substrate having at least one array may be read by said scanner while retained in said array holder.  
     
     
         123 . The method according to  claim 122 , further comprising reading said mounted at least one array.  
     
     
         124 . A kit for performing an assay, said kit comprising: (a) at least one array assay device according to  claim 93;  and (b) instructions for using said at least one array assay device in an array based assay.  
     
     
         125 . The kit according to  claim 124 , further comprising at least one array holder.  
     
     
         126 . The kit according to  claim 124 , further comprising at least one array.  
     
     
         127 . The kit according to  claim 124 , further comprising reagents for generating a labeled sample.  
     
     
         128 . The kit according to  claim 124 , wherein said kit further comprises a buffer.  
     
     
         129 . The kit according to  claim 124 , wherein said kit further comprises a wash medium.