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 . A fluid containment structure comprising a form-in-place gasket disposed on a substrate.  
     
     
         94 . The fluid containment structure of  claim 93 , wherein the form-in-place gasket is between about 10 micrometers and about 250 micrometers thick.  
     
     
         95 . The fluid containment structure of  claim 93 , wherein the form-in-place gasket is between about 250 micrometers and about 15 millimeters thick.  
     
     
         96 . The fluid containment structure of  claim 93 , wherein the form-in-place gasket is between about 100 micrometers and about 3 millimeters wide.  
     
     
         97 . The fluid containment structure of  claim 93 , wherein the form-in-place gasket is adapted to be placed against a cover to form a fluid-tight seal that may be broken and reformed by removing and replacing the cover.  
     
     
         98 . The fluid containment structure of  claim 93 , further comprising an analysis component in operable relation to the substrate.  
     
     
         99 . The fluid containment structure of  claim 93 , wherein the substrate defines a depression in the substrate, the depression defining a well.  
     
     
         100 . A method of forming a fluid containment structure comprising depositing a gasket material onto a substrate, curing the gasket material to provide a form-in-place gasket, wherein the form-in-place gasket defines an interior area of the substrate, and the interior area and the form-in-place gasket together define the fluid containment structure.  
     
     
         101 . The method of  claim 100 , wherein the gasket material is self-leveling.  
     
     
         102 . The method of  claim 100 , wherein the gasket material is non-slumping.  
     
     
         103 . The method of  claim 100 , wherein the form-in-place gasket is of uniform thickness.  
     
     
         104 . The method of  claim 100 , wherein the form-in-place gasket is between about 10 micrometers and about 250 micrometers thick.  
     
     
         105 . The method of  claim 100 , wherein the form-in-place gasket is between about 250 micrometers and about 1500 micrometers thick.  
     
     
         106 . The method of  claim 100 , wherein the form-in-place gasket between about 100 micrometers and about 1000 micrometers wide.  
     
     
         107 . The method of  claim 100 , wherein the form-in-place gasket is between about 100 micrometers and about 3000 micrometers wide.  
     
     
         108 . The method of  claim 100 , wherein the gasket material is a self-leveling material that has a viscosity of between about 15,000 to about 50,000 centipoise.  
     
     
         109 . The method of  claim 100 , wherein the form-in-place gasket is adapted to be placed against a cover to form a fluid-tight seal that may be broken and re-formed by removing and replacing the cover.  
     
     
         110 . The method of  claim 100 , wherein curing comprises a process selected from the group comprising contacting the gasket material with moisture in the air, heating the gasket material, shining light on the gasket material, and contacting the gasket material with a catalyst.  
     
     
         110 . The method of  claim 100 , wherein the substrate further comprises an analysis component.  
     
     
         111 . The assay chamber according to  claim 100 , wherein the substrate defines a depression in the substrate, the depression defining a well.  
     
     
         112 . An apparatus comprising a plurality of assay chambers, the apparatus comprising, in order, a substrate, a form-in-place gasket, and a cover, wherein the form-in-place gasket, the substrate, and the cover together substantially define a plurality of assay chambers.  
     
     
         113 . The apparatus of  claim 111 , wherein the assay chambers are spaced at uniform intervals.  
     
     
         114 . The apparatus of  claim 113;  wherein the uniform interval is selected from the group consisting of about 4.5 mm, about 9 mm, and about 2.25 mm.  
     
     
         115 . The apparatus of  claim 114 , wherein the assay chambers are adapted to being placed in fluid communication with an external fluid dispensing system that handles multiple fluids in parallel.  
     
     
         116 . The apparatus of  claim 112 , wherein the form-in-place gasket, the substrate, and the cover together further define a plurality of inlets and outlets, each assay chamber in fluid communication with an inlet and an outlet.  
     
     
         117 . The apparatus of  claim 116 , wherein the inlets are adapted to being fluidically coupled to an external fluid dispensing system that handles multiple fluids in parallel.  
     
     
         118 . The apparatus of  claim 112 , wherein the inlets are spaced at uniform intervals.  
     
     
         119 . The apparatus of  claim 113;  wherein the uniform interval is selected from the group consisting of about 4.5 mm, about 9 mm, and about 2-25 mm.  
     
     
         120 . The apparatus of  claim 112 , further comprising a plurality of assay components, each analysis component being in operable association with one or more of the assay chambers.  
     
     
         121 . The apparatus of  claim 120 , wherein the analysis components are arrays, and wherein each assay chamber is in operable association with one or more of the arrays.  
     
     
         122 . The apparatus of  claim 112 , wherein the form-in-place gasket is between about 10 micrometers and about 250 micrometers thick.  
     
     
         123 . The apparatus of  claim 112 , wherein the form-in-place gasket is between about 250 micrometers and about 1.5 millimeters thick.  
     
     
         124 . The apparatus of  claim 112 , wherein the form-in-place gasket is between about 100 micrometers and about 3 millimeters wide.  
     
     
         125 . The apparatus of  claim 112 , wherein a fluid tight seal formed by the form-in-place gasket, the substrate, and the cover may be broken and re-formed by removing and replacing the cover.  
     
     
         126 . A method of performing an array hybridization experiment comprising: Contacting a target solution with an array disposed in an assay chamber, wherein the assay chamber is substantially defined by a substrate, a cover, and a form-in-place gasket, the form-in-place gasket positioned between the substrate and the cover, wherein the contacting is done under conditions and for a period of time sufficient to allow specific binding interactions between the target solution and the array, and Interrogating the array.  
     
     
         127 . The method of  claim 126 , wherein the substrate and the cover are substantially planar.  
     
     
         128 . The method of  claim 126 , wherein the substrate defines a depression in the substrate, the depression defining a well.  
     
     
         129 . The method of  claim 126 , wherein the cover defines a depression in the cover, the depression defining a well.  
     
     
         130 . The method of  claim 126 , further comprising an array substrate disposed within the assay chamber the array substrate having a surface, wherein the array is disposed on the surface of the array substrate.  
     
     
         131 . The method of  claim 126 , wherein at least one of the substrate or the cover has an interior surface, wherein the molecular array is disposed on the interior surface.  
     
     
         132 . The method of  claim 126 , wherein the chamber further comprises an inlet port.  
     
     
         133 . The method of  claim 126 , wherein the chamber further comprises an outlet port.  
     
     
         134 . The method of  claim 126 , wherein the chamber has no port.  
     
     
         135 . The method of  claim 126 , wherein contacting comprises depositing the target solution into a well defined at least in part by one of the substrate or the cover and placing the other one of the substrate or cover over the well with the form-in-place gasket positioned between the substrate and the cover such that a fluid tight seal is formed by the form-in-place gasket positioned between the substrate and the cover.  
     
     
         136 . The method of  claim 126 , wherein contacting comprises introducing the target solution into the chamber via an inlet port in fluid communication with the chamber.  
     
     
         137 . The method of  claim 126 , wherein the assay chamber is adapted to opening at the form-in-place gasket to allow access to the array.  
     
     
         138 . The method of  claim 126 , wherein the assay chamber is adapted for interrogation of the array without displacing the cover from the substrate.  
     
     
         139 . The method of  claim 126 , wherein the form-in-place gasket has a thickness of between about 10 micrometers and about 1.5 millimeters.  
     
     
         140 . The method of  claim 126 , wherein the form-in-place gasket has a width of between about 100 micrometers and about 3 millimeters.  
     
     
         141 . The method of  claim 126 , further comprising, before interrogating the array, submerging the array chamber in a wash buffer and, while the array chamber is submerged, displacing the cover from the substrate to allow wash buffer to contact the array.  
     
     
         142 . A method of forming an assay chamber comprising depositing a gasket material onto a substrate, curing the gasket material to provide a form-in-place gasket, and positioning a cover adjacent the substrate to provide the assay chamber, the assay chamber having the form-in-place gasket disposed between the cover and the substrate.  
     
     
         143 . The method of  claim 142 , wherein the gasket material is self-leveling.  
     
     
         144 . The method of  claim 142 , wherein the gasket material is non-slumping.  
     
     
         145 . The method of  claim 142 , wherein the form-in-place gasket is of uniform thickness.  
     
     
         146 . The method of  claim 142 , wherein the form-in-place gasket is between about 10 micrometers and about 250 micrometers thick.  
     
     
         147 . The method of  claim 142 , wherein the form-in-place gasket is between about 250 micrometers and about 1500 micrometers thick.  
     
     
         148 . The method of  claim 142 , wherein the form-in-place gasket between about 100 micrometers and about 1000 micrometers wide.  
     
     
         149 . The method of  claim 142 , wherein the form-in-place gasket between about 100 micrometers and about 3000 micrometers wide.  
     
     
         150 . The method of  claim 142 , wherein curing is done before positioning.  
     
     
         151 . The method of  claim 142 , wherein the gasket material is contacted with the cover before curing.  
     
     
         152 . The method of  claim 142 , wherein the gasket material is a self-leveling silicone material that has a viscosity of between about 15,000 to about 50,000 centipoise.  
     
     
         153 . The method of  claim 142 , wherein the cover may be placed against the form-in-place gasket to form a fluid-tight seal that may be broken and reformed by removing and replacing the cover.  
     
     
         154 . The method of  claim 142 , wherein the form-in-place gasket forms a non-releasable seal between the cover and the substrate.  
     
     
         155 . The method of  claim 142 , wherein curing comprises contacting the gasket material with moisture in the air.  
     
     
         156 . The method of  claim 142 , wherein curing comprises heating the gasket material.  
     
     
         157 . The method of  claim 142 , wherein curing comprises shining light on the gasket material.  
     
     
         158 . The method of  claim 142 , wherein curing comprises contacting the gasket material with a catalyst.  
     
     
         159 . The method of  claim 142 , wherein one of the cover or substrate further comprises an analysis component.  
     
     
         160 . An assay chamber comprising a substrate, a cover, and a form-in-place gasket disposed between the substrate and the cover.  
     
     
         161 . The assay chamber according to  claim 160 , wherein the form-in-place gasket has a thickness of between about 10 micrometers and about 1.5 millimeters.  
     
     
         162 . The assay chamber according to  claim 160 , wherein the form-in-place gasket has a width of between about 100 micrometers and about 3 millimeters.  
     
     
         163 . The assay chamber according to  claim 160 , wherein the assay chamber further comprises an analysis component.  
     
     
         164 . The assay chamber according to  claim 160 , wherein the substrate defines a depression in the substrate, the depression defining a well.  
     
     
         165 . The assay chamber according to  claim 160 , wherein the cover defines a depression in the cover, the depression defining a well.