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 holder for an array unit having a planar substrate and an array of chemical moieties on a surface of the substrate, the holder comprising: a body with a retaining mechanism which releasably retains an array unit in a seated position, such that an array unit can be repeatedly inserted into and removed from the seated position in which it is retained in the holder; a machine readable holder identifier which includes data on a characteristic of the holder or seated array.  
     
     
         94 . A holder according to  claim 93  wherein the holder identifier includes data on a spatial characteristic of the holder or seated array.  
     
     
         95 . A holder according to  claim 94  wherein the holder identifier includes data on a a position or dimension of an array unit seated in the holder.  
     
     
         96 . A holder according to  claim 95  wherein the holder identifier includes data on the position or dimension of the substrate of an array unit seated in the holder unit.  
     
     
         97 . A holder according to  claim 95  wherein the position or dimension data includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.  
     
     
         98 . A holder according to  claim 95  wherein the position or dimension data includes data on the z position of the seated array unit.  
     
     
         99 . A holder according to  claim 95  wherein the position data includes data on the angular orientation of the seated array unit.  
     
     
         100 . A holder according to  claim 95  wherein the holder identifier comprises a bar code.  
     
     
         101 . A holder according to  claim 95  wherein the holder additionally comprises a magnetic or solid state memory attached to the body and the identifier is carried by the memory.  
     
     
         102 . A holder according to  claim 95  additionally comprising a seated array unit.  
     
     
         103 . A holder according to  claim 102  wherein the seated array unit additionally includes an array unit identifier.  
     
     
         104 . A holder according to  claim 103  wherein the array unit identifier is a machine readable identifier.  
     
     
         105 . A holder according to  claim 104  wherein the array unit identifier comprises a bar code or is carried in a memory attached to the remainder of the array unit.  
     
     
         106 . A holder according to  claim 95  which has a maximum length and width each no greater than 50 cm, and a thickness no greater than 10 cm.  
     
     
         107 . A method of reading an array of chemical moieties on a substrate of an array unit, the method comprising: seating the array unit in a holder, which holder carries a holder identifier; mounting the holder with seated array unit into an array reader; reading the holder identifier and retrieving data on a position or dimension of the seated array unit based on the read holder identifier; and reading the array.  
     
     
         108 . A method according to  claim 107  wherein the position or dimension data includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.  
     
     
         109 . A method according to  claim 107  wherein the position or dimension data includes data on the z position of the seated array unit.  
     
     
         110 . A method according to  claim 107  wherein the position data includes data on the angular orientation of the seated array unit.  
     
     
         111 . A method according to  claim 107  additionally comprising reading an array unit identifier carried by the array unit.  
     
     
         112 . A holder according to  claim 111  wherein the array unit identifier is machine read.  
     
     
         113 . A holder according to  claim 104  wherein the holder identifier comprises a bar code or is carried in a memory attached to the remainder of the holder.  
     
     
         114 . A method according to  claim 107  wherein the reading of the array comprises scanning an interrogating light over the array.  
     
     
         115 . A method according to  claim 114  wherein the interrogating light is a spot scanned across the array in an x and y direction, where x and y are the directions along a length and width of the array.  
     
     
         116 . A method according to  claim 114  wherein a position or dimension of an area over which the interrogating light is scanned is based on data retrieved using the read holder identifier.  
     
     
         117 . A method comprising forwarding data representing a result of a reading obtained by the method of  claim 107 .  
     
     
         118 . A method according to  claim 117  wherein the data is communicated to a remote location.  
     
     
         119 . A method comprising receiving data representing a result of a reading obtained by the method of  claim 107 .  
     
     
         120 . A method of reading an array of chemical moieties on a substrate of an array unit, the method comprising: seating the array unit in a holder, which holder carries a holder identifier; reading the holder identifier and retrieving a characteristic of the holder or seated array based on the read holder identifier; and when the retrieved characteristic does not meet a predetermined condition, rejecting the seated array unit for reading or generating an operator alert.  
     
     
         121 . A method according to  claim 120  wherein the retrieved characteristic of the holder or seated array comprises a spatial characteristic.  
     
     
         122 . An apparatus for reading an array of chemical moieties on a substrate of an array unit, the apparatus comprising: a receptacle into which is mountable a holder carrying a seated array unit, which holder carries a holder identifier; a reader system to read the holder identifier and data from different chemical moieties of the array; and a processor which retrieves data on a characteristic of the holder or seated array based on the read holder identifier.  
     
     
         123 . An apparatus according to  claim 122  wherein the processor retrieves data on a spatial characteristic of the holder or seated array based on the holder identifier.  
     
     
         124 . An apparatus according to  claim 123  wherein the processor retrieves data on a spatial characteristic which comprises data on a position or dimension of an array unit seated in the holder.  
     
     
         125 . An apparatus according to  claim 124  wherein the reader system comprises a first identifier reader to read the holder identifier, and an array reader to read the data from different chemical moieties of the array.  
     
     
         126 . An apparatus according to  claim 124  wherein the processor retrieves data which includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.  
     
     
         127 . An apparatus according to  claim 124  wherein the reader system also reads an array unit identifier carried by a seated array unit in the mounted holder.  
     
     
         128 . An apparatus according to  claim 125  additionally comprising a second identifier reader to read an array unit identifier carried by a seated array unit in the mounted holder.  
     
     
         129 . An apparatus according to  claim 124  wherein the reader system comprises a light system which provides and scans an interrogating light over the array.  
     
     
         130 . An apparatus according to  claim 129  wherein the light system provides a light spot which is scanned in an x and y direction across the array of the seated array unit in the mounted holder, where x and y are the directions along a length and width of the array.  
     
     
         131 . An apparatus according to  claim 129  wherein the processor controls a position or dimension of an area over which the interrogating light is scanned based on data retrieved using the read holder identifier.  
     
     
         132 . An apparatus according to  claim 122  wherein the processor retrieves data on a spatial characteristic of the holder and compares this with a predetermined condition in a memory and when the retrieved spatial characteristic does not meet the retrieved condition generates a user alert or inhibits reading of data from different chemical moieties of the array.  
     
     
         133 . An apparatus according to  claim 127  wherein: the reader system comprises a light system which provides and scans an interrogating light over the array; the processor controls a position or dimension of an area over which the interrogating light is scanned based on data retrieved using the read holder identifier; and a position or dimension of the area over which the interrogating light is scanned is also based on data retrieved using the read array unit identifier.  
     
     
         134 . An apparatus according to  claim 124  wherein the array reader comprises a detector having a focal plane, wherein the position of the focal plane is adjusted relative to an array based on the data retrieved using the read holder identifier.  
     
     
         135 . A computer program product for use with an apparatus of  claim 124 , comprising a computer readable storage medium having a computer program stored thereon for reading the holder identifier and retrieving data on the position or dimension of the seated array unit based on the read holder identifier.  
     
     
         136 . A computer program product according to  claim 135  wherein the program additionally reads an array identifier carried by a seated array unit in the mounted holder and retrieves data on the position or dimension of the array also based on the read array identifier.  
     
     
         137 . A computer program product according to  claim 136  wherein the program additionally controls a position or dimension of an area on the array of the seated array unit in the mounted holder, over which an interrogating light is scanned.