Apparatus and method for polymer synthesis using arrays

Abstract

A polymer synthesis apparatus ( 20 ) for building a polymer chain including a head assembly ( 21 ) having an array of nozzles ( 22 ) with each nozzle coupled to a reservoir ( 23 ) of liquid reagent ( 24 ), and a base assembly ( 25 ) having an array of reaction wells ( 26 ). A transport mechanism ( 27 ) aligns the reaction wells ( 26 ) and selected nozzles ( 22 ) for deposition of the liquid reagent ( 24 ) into selected reaction wells ( 26 ). A sliding seal ( 30 ) is positioned between the head assembly ( 21 ) and the base assembly ( 25 ) to form a common chamber ( 31 ) enclosing both the reaction well ( 26 ) and the nozzles ( 22 ) therein. A gas inlet ( 70 ) into the common chamber ( 31 ), upstream from the nozzles ( 22 ), and a gas outlet ( 71 ) out of the common chamber ( 31 ), downstream from the nozzles ( 22 ), sweeps the common chamber ( 31 ) of toxic fumes emitted by the reagents. Each reaction well ( 26 ) includes an orifice ( 74 ) extending into the well ( 26 ) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution ( 76 ) in the well ( 26 ) for polymer chain growth therein. A pressure regulating device ( 82 ) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well ( 26 ) and a second gas pressure exerted on an exit ( 80 ) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution ( 76 ) is expelled from the well ( 26 ) through the orifice ( 74 ). A method of synthesis of a polymer chain in a synthesis apparatus ( 20 ) is also included.

1 . A polymer synthesis apparatus for building a polymer chain by sequentially adding polymer units to a solid support in a liquid reagent comprising: 
 a base assembly including a reaction well, and having at least one orifice extending into said well;    at least one solid support disposed in said well for growing and immobilizing a polymer chain thereon;    reagent solution in said well in contact with said solid support and at least one polymer unit of said polymer chain affixed to said solid support;    retaining means positioned in said well, and formed and dimensioned to substantially prevent passage of said solid support through said orifice;    said orifice having an entrance into said well and an exit, and being of a size and dimension to form a capillary liquid seal to retain said reagent solution in said well to enable polymer chain growth therein when a pressure differential between a first gas pressure exerted on said reaction well and a second gas pressure exerted on said orifice exit is less than a predetermined amount; and    a pressure regulating device for controlling said pressure differential such that upon said pressure differential exceeding said predetermined amount, said reagent solution being expelled from said well through said orifice.    
   
   
       2 . The polymer synthesis apparatus as defined in  claim 1  wherein, 
 said retaining means comprises a filter member disposed in said well between said one orifice and said support structure.    
   
   
       3 . The polymer synthesis apparatus as defined in  claim 2  wherein, 
 said filter member is composed of a glass fiber frit.    
   
   
       4 . The polymer synthesis apparatus as defined in  claim 2  wherein, 
 said filter member and said orifice cooperate in a manner forming said capillary liquid seal.    
   
   
       5 . The polymer synthesis apparatus as defined in  claim 1  further including: 
 a top chamber mechanism cooperating with a top surface of said base assembly to form a top chamber enclosing said reaction well therein, said regulating device communicating with said top chamber to regulate said pressure differential.    
   
   
       6 . The polymer synthesis apparatus as defined in  claim 1  wherein, 
 said solid support is provided by controlled pore glass (CPG).    
   
   
       7 . The polymer synthesis apparatus as defined in  claim 1  wherein, 
 said polymer chain is an oligonucleotide.    
   
   
       8 . The polymer synthesis apparatus as defined in  claim 1  further including: 
 a bottom chamber mechanism cooperating with a bottom surface of said base assembly to form a bottom chamber enclosing said orifice therein, said regulating device communicating with said bottom chamber to regulate said pressure differential.    
   
   
       9 . A polymer synthesis apparatus for building a polymer chain by sequentially adding polymer units in a reagent solution, said apparatus comprising: 
 a head assembly having a plurality of nozzles mounted thereto in generally spaced-apart relation, each nozzle being coupled to a reservoir of liquid reagent for controlled delivery therethrough;    a base assembly having at least one reaction well;    a transport mechanism coupled to at least one of said head assembly and said base assembly to produce relative movement therebetween to position said reaction well and a selected one nozzle in alignment for deposition of a liquid reagent into said reaction well for synthesis of a polymer chain; and    a sliding seal positioned between said head assembly and said base assembly forms a common chamber enclosing both said reaction well and said nozzles therein.    
   
   
       10 . The polymer synthesis apparatus as defined in  claim 9  wherein, 
 each said nozzle terminates proximate a substantially planar bottom surface of said head assembly, and    said base assembly includes a substantially planar top surface in opposed relation to said head bottom surface.    
   
   
       11 . The polymer synthesis apparatus as defined in  claim 10  wherein, 
 said sliding seal is provided by a balloon seal having one end affixed to one of said head bottom surface and said base top surface, and an opposite end in sliding contact with the other of said base top surface and said head bottom surface.    
   
   
       12 . The polymer synthesis apparatus as defined in  claim 11  wherein, 
 said opposite end tapers radially inwardly toward an interior portion of said chamber in a manner such that upon increase in pressure in said chamber, the seal integrity between said opposite end and the other of said base top surface and said head bottom surface increases.    
   
   
       13 . The polymer synthesis apparatus as defined in  claim 11  wherein, 
 said seal opposite end includes a substantially    stick-free coating or layer in sliding contact with the other of said base top surface and said head bottom surface.    
   
   
       14 . The polymer synthesis apparatus as defined in  claim 11  wherein, 
 said coating or layer comprises TEFLON®.    
   
   
       15 . The polymer synthesis apparatus as defined in  claim 11  wherein, 
 the other of said base top surface and said head bottom surface in sliding contact with said seal opposite end includes a substantially stick-free coating or layer therebetween.    
   
   
       16 . The polymer synthesis apparatus as defined in  claim 15  wherein, 
 said coating or layer comprises TEFLON®.    
   
   
       17 . The polymer synthesis apparatus as defined in  claim 12  wherein, 
 said seal one end is mounted to said base bottom surface, and said seal opposite end is in sliding contact with said base top surface.    
   
   
       18 . The polymer synthesis apparatus as defined in  claim 9  wherein, 
 said transport mechanism includes a stepped motor operably coupled to one of the head assembly and the base assembly for incremental movement thereof.    
   
   
       19 . The polymer synthesis apparatus as defined in  claim 9  wherein, 
 said transport mechanism is operably coupled to said base assembly for movement thereof.    
   
   
       20 - 71 . (canceled)  
   
   
       72 . A method of synthesis for building a polymer chain by sequentially adding polymer units to at least one solid support for growing a polymer chain thereon in a liquid reagent, said method comprising the steps of: 
 depositing a liquid reagent in a reaction well in contact with at least one solid support and at least one polymer unit of said polymer chain affixed to said solid support to sequentially add a polymer unit to said polymer chain, said well having at least one drain orifice extending out of said well, and being of a size and dimension to form a capillary liquid seal to retain said reagent solution in said well to enable polymer chain growth on said solid support;    creating a gas pressure differential within said reaction well such that said pressure differential exerted on an exit of said drain orifice exceeds a predetermined amount necessary to overcome said capillary liquid seal and expel said reagent solution from said well through said drain orifice; and    controlling said pressure differential through a pressure regulating device for one of raising said pressure differential above said predetermined amount and lowering said pressure differential below said predetermined amount, wherein said pressure differential is created by forming a vacuum.