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 . An apparatus for detecting an analyte in a test sample comprising:
 at least one probe array, wherein the at least one probe array comprises:
 a plurality of particles having biological polymers immobilized on the plurality of particles thereon; 
 a slide, wherein the plurality of particles are attached to a surface of the slide; and 
   a barcode for identifying the at least one probe array on the slide.   
     
     
         2 . The apparatus according to  claim 1 , wherein the different particles in the plurality of particles have different biological polymers immobilized thereon. 
     
     
         3 . The apparatus according to  claim 1 , wherein the plurality of particles are spheres. 
     
     
         4 . The apparatus according to  claim 1 , wherein the slide is silica. 
     
     
         5 . The apparatus according to  claim 1 , wherein the slide is glass. 
     
     
         6 . The apparatus according to  claim 1 , wherein the biological polymers are immobilized on the slide at a density exceeding 400 different biological polymers per cm 2 . 
     
     
         7 . The apparatus according to  claim 6 , wherein the biological polymers are immobilized on the slide at a density exceeding 100 different biological polymers per cm 2 . 
     
     
         8 . The apparatus according to  claim 1 , wherein the plurality of particles forms an ordered arrangement on the surface of the slide. 
     
     
         9 . The apparatus according to  claim 8 , wherein the ordered arrangement on the surface is circular. 
     
     
         10 . The apparatus according to  claim 8 , wherein the ordered arrangement on the surface is rectangular. 
     
     
         11 . The apparatus according to  claim 1 , wherein the at least one probe array is less than 9 probe arrays. 
     
     
         12 . The apparatus according to  claim 11 , wherein the at least one probe array is 1 probe array. 
     
     
         13 . A package for supporting a probe array, comprising:
 a plurality of particles having biological polymers immobilized on the plurality of particles thereon;   a slide, wherein the plurality of particles are attached to a surface of the slide; and   a top piece and a bottom piece, wherein the top bottom pieces house the first wafer, creating at least one cavity such that at least one probe array is in fluid communication with the reaction chamber.   
     
     
         14 . The package according to  claim 13 , further comprising a bar code associated with the at least one probe array. 
     
     
         15 . The package according to  claim 14 , further comprising at least one aligning pin and holes to assist in assembling the top piece and the bottom piece together. 
     
     
         16 . The package according to  claim 13 , further comprising screws to assemble the top piece, bottom piece and the at least one probe array together. 
     
     
         17 . The package according to  claim 13 , further comprising clamps to assemble the top piece, bottom piece and the at least one probe array together. 
     
     
         18 . The package according to  claim 13 , further comprising at least one inlet port to introduce a fluid into the cavity. 
     
     
         19 . The package according to  claim 18 , further comprising a septum to seal the at least one inlet ports. 
     
     
         20 . The package according to  claim 18 , further comprising at least one channel for fluid transfer between the at least one inlet port and the cavity. 
     
     
         21 . The package according to  claim 14 , further comprising at least one gasket to form a liquid tight seal around the cavity between the top piece and the at least one probe array. 
     
     
         22 . The package according to  claim 23 , wherein the gaskets are O-rings. 
     
     
         23 . The package according to  claim 14 , wherein the bottom piece comprises a depression to position the at least one probe array. 
     
     
         24 . A method of using a probe array, comprising:
 providing at least one probe array, wherein the at least one probe array comprises:
 a plurality of particles having biological polymers immobilized on the plurality of particles thereon and a slide, wherein the plurality of particles are attached to a surface of the slide; 
   providing a housing, wherein the housing comprises a cavity to accommodate a fluid to be in contact with the slide;   placing the slide into the housing;   sealably mounting the slide within the housing comprising a mounting surface and a fluid cavity, wherein the fluid cavity comprises at least one inlet port constructed to permit fluid flow into the cavity through the at least one inlet port, wherein the sealably mounting act provides the at least one probe array located inside the cavity;   introducing the fluid inside the cavity to hybridize the at least one probe array on the slide;   performing hybridization, wherein at least some of the polymers hybridizes to a target;   aligning the at least one probe array, wherein the at least one probe array comprises at least one alignment feature; and   detecting a signal from the at least one probe array using a scanner.   
     
     
         25 . The method according to  claim 24 , further comprising reading a bar code associated with the probe array, wherein the slide comprises a bar code. 
     
     
         26 . The method according to  claim 24 , wherein the inlet port comprises of a septum sealed port which uses one or more needles to permit fluid flow into the cavity. 
     
     
         27 . The method according to  claim 24 , further comprising a fluid mixing step, wherein the cavity is at least partially filled with the fluid during mixing. 
     
     
         28 . The method according to  claim 27  wherein the fluid mixing occurs using the motion of gas relative to fluid in the cavity. 
     
     
         29 . The method according to  claim 27  wherein said fluid mixing uses agitation. 
     
     
         30 . The method according to  claim 27  wherein said agitation uses vortexing. 
     
     
         31 . An apparatus for mixing a fluid, the apparatus comprising:
 a pump, wherein a first housing comprises the pump;   a probe array;   a substrate, wherein the substrate and the probe array create at least one cavity for a fluid;   at least one bubble disposed within said chamber, wherein the at least one bubble is moved by using the pump to move the bubble relative to the fluid to effect mixing the fluid.   
     
     
         32 . The apparatus as in  claim 31  wherein the at least one bubble is formed using a nitrogen gas. 
     
     
         33 . The apparatus as in  claim 31 , wherein, the pump transfers the fluid from a first container through the cavity and into a second container. 
     
     
         34 . The apparatus as in  claim 31 , wherein, the means for moving the fluid is through agitation. 
     
     
         35 . A fluidic station comprising:
 a base that is adapted to provide a framework for the fluidics station;   a mounting system coupled to the base, wherein the mounting system is movable between a loading position and a closed position, the mounting system comprising:
 a bottom piece adapted to receive a wafer, wherein a wafer comprises at least one probe array, wherein the bottom piece is adapted to receive a top piece positioned above the wafer forming at least one cavity for fluid to be in contact with the wafer and forming a package comprising at least an inlet port and an outlet port for fluid transfer and connecting with at least one cavity; 
   at least one needle coupled to the base frame, wherein the needle includes a distal end and side ports above the distal ends; and   at least one fluid source in communication with the at least one needle, wherein the wafer is insertable into the mounting system when in the loading position, and wherein the at least one needle is adapted to transfer liquid into the package through the liquid channels when in the closed position.