Devices and methods for the synthesis of nucleic acids

Abstract

Cylindrical devices (frits) are prepared by embedding aminoalkyl- or mercaptoalkyl-modified Controlled Pore Glass (CPG) in high-density polyethylene. Methods and devices pertaining to their use in the synthesis of nucleic acids are described. A reusable synthesis column or a reusable 96-chamber synthesis plate have been designed to hold one to 96 of the said frits that are inserted reproducibly into the synthesis chambers with a frit insertor. A short gas surpressure is required to drive entry of chemical reagents into the said frit. Reagents are retained into the frit until a second, longer surpressure is applied to drain the said reagents.

1 . A single synthesis column produced by a process comprising:
 providing a cylinder having an open top and an open bottom end, embedding within the cylinder a cylindrical polyalkylene embedded silane-modified-CPG device, made by a process including: a) mixing an aqueous-free polyalkylene with a silane-modified CPG; b) filling a cylindrical well of an aluminum plate with said mixture; c) heating said plate at 180° C. to 220° C. for a predetermined schedule; and d) upon cooling, releasing from said plate said embedded device.   
   
   
       2 . The column according to  claim 1 , in which the said polyalkylene is selected from the group consisting of ultrahigh molecular weight polyethylene, high density polyethylene, low density polyethylene, polypropylene, and mixtures thereof. 
   
   
       3 . The column according to  claim 1 , in which the quantity of the said polyalkylene is preferably from 50 to 70% by weight, based on the total weight of the resin mixture. 
   
   
       4 . The column according to  claim 1 , in which silane-modified-CPG are controlled porous glass beads which have been modified with aminoalkyltrialkoxysilane, [alkylamino]alkyl(trialkoxy)silane or mercaptoalkyl(trialkoxy)silane and mixtures thereof. 
   
   
       5 . The column according to  claim 1 , wherein alkyl is selected from the group consisting of methyl, ethyl and propyl and wherein alkoxy is selected from the group consisting of methoxy, ethoxy and propoxy. 
   
   
       6 . The column according to  claim 1 , wherein the said embedded devices contain less than ten micromoles of reactive amino or mercapto moieties.