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 . 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.  
     
     
         3 . The array assay device according to  claim 2 , 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.  
     
     
         4 . The array assay device according to  claim 2 , 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.  
     
     
         5 . The array assay device according to  claim 4 , wherein said seal is substantially vapor and fluid tight.  
     
     
         6 . The array assay device according to  claim 4 , wherein said sealing element produces an assay volume of from about 10 μl to about 1000 μl.  
     
     
         7 . The array assay device according to  claim 4 , wherein said substrate comprises a plurality of arrays and said sealing element produces a plurality of individual seals around each array.  
     
     
         8 . The array assay device according to  claim 7 , wherein each of said individual seals is substantially vapor and fluid tight.  
     
     
         9 . The array assay device according to  claim 2 , wherein said sealing element is a gasket.  
     
     
         10 . The array assay device according to  claim 2 , further comprising at least one access port.  
     
     
         11 . The array assay device according to  claim 10 , wherein said device comprises a plurality of access ports.  
     
     
         12 . The array assay device according to  claim 10 , wherein said device comprises at least a first fluid introduction port and a second venting port.  
     
     
         13 . The array assay device according to  claim 10 , wherein said at least one port is resealable.  
     
     
         14 . The array assay device according to  claim 2 , further comprising a removable array holder.  
     
     
         15 . The array assay device according to  claim 14 , wherein said array holder is configured to be used with an array scanner.  
     
     
         16 . A system for performing array assays, said system comprising: (a) an array assay device according to  claim 2;  and (b) a substrate having at least one array.  
     
     
         17 . 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.  
     
     
         18 . The method according to  claim 17 , further comprising producing a seal around said at least one array.  
     
     
         19 . The method according to  claim 18 , wherein said seal is substantially vapor and fluid tight.  
     
     
         20 . The method according to  claim 17 , wherein said device comprises at least one port and said sample is introduced through said port.  
     
     
         21 . The method according to  claim 17 , further comprising mixing said sample with said at least one array.  
     
     
         22 . The method according to  claim 21 , wherein said mixing is accomplished by an air bubble.  
     
     
         23 . The method according to  claim 17 , further comprising retaining said substrate in an array holder.  
     
     
         24 . A method comprising, following contacting said at least one array to a sample according to  claim 17 , reading said at least one array.  
     
     
         25 . The method according to  claim 24 , where in said at least one array is read while in the array holder of  claim 23 .  
     
     
         26 . A method comprising forwarding data representing a result of a reading obtained by the method of  claim 24  from a first location to a second location.  
     
     
         27 . The method according to  claim 26 , wherein said second location is remote from said first location.  
     
     
         28 . A method comprising receiving data representing a result of a reading obtained by the method of  claim 24 .  
     
     
         29 . 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 2  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.  
     
     
         30 . The method according to  claim 29 , wherein said pre-packaged substrate comprises a substrate retained in an array holder in said array assay device.  
     
     
         31 . 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 1  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.  
     
     
         32 . The method according to  claim 31 , further comprising reading said mounted at least one array.  
     
     
         33 . A kit for performing an assay, said kit comprising: (a) at least one array assay device according to  claim 2;  and (b) instructions for using said at least one array assay device in an array based assay.  
     
     
         34 . The kit according to  claim 33 , further comprising at least one array holder.  
     
     
         35 . The kit according to  claim 33 , further comprising at least one array.  
     
     
         36 . The kit according to  claim 33 , further comprising reagents for generating a labeled sample.  
     
     
         37 . The kit according to  claim 33 , wherein said kit further comprises a buffer.  
     
     
         38 . The kit according to  claim 33 , wherein said kit further comprises a wash medium.  
     
     
         39 . An apparatus for packaging a substrate, said apparatus comprising: 
 a substrate having a first surface and a second surface, said first surface comprising a probe array and said second surface being an outer periphery of said first surface;    a body having a mounting surface, an upper surface, and a cavity bounded by said mounting surface and said upper surface, said second surface being attached to said cavity and said first surface being within said cavity; and    a cover attached to said mounting surface for defining an upper boundary to said cavity;    wherein said cavity comprises a diffuser and a concentrator, said diffuser and said concentrator permitting laminar fluid flow through said cavity.    
     
     
         40 . The apparatus of  claim 39  wherein said probe array comprises an array of oligonucleotide probes.  
     
     
         41 . The apparatus of  claim 39  wherein said cover comprises a depression for receiving a temperature control element to maintain a reaction temperature in said cavity.  
     
     
         42 . The apparatus of  claim 39  wherein said cover comprises a first half mated to a second half.  
     
     
         43 . The apparatus of  claim 42  wherein said first half and said second half are injection molded plastic.  
     
     
         44 . The apparatus of  claim 42  wherein said first half comprises a first channel and a second channel, said first channel being in fluid communication with said diffuser and said second channel being in fluid communication with said concentrator.  
     
     
         45 . The apparatus of  claim 44  wherein said second half comprises a third channel and a fourth channel, said third channel being in fluid communication with said first channel, and said fourth channel being in fluid communication with said second channel.  
     
     
         46 . The apparatus of  claim 45  wherein said first channel and said second channel comprise reenterable seals for sealing fluid in said cavity.  
     
     
         47 . The apparatus of  claim 39  wherein said body further comprises an alignment structure, said alignment structure used for maintaining said body in a desired position when mounted on a detection system.  
     
     
         48 . The apparatus of  claim 47  wherein said alignment structure comprises a plurality of bores.  
     
     
         49 . The apparatus of  claim 48  wherein said alignment structure comprises a plurality of pins.