Oligonucleotide synthesizer

Abstract

A process for making an oligonucleotide, the process including reacting a oligonucleotide precursor with a solid phase support within a reaction vessel, the reaction vessel being coupled to an actuator and having a resting position and inverting the reaction vessel via the actuator such that the reaction vessel is inverted relative to the resting position, wherein the inversion of the reaction vessel results in stirring of the solid phase support within the reaction vessel.

1 - 20 . (canceled) 
     
     
         21 . A method for creating an oligonucleotide, the method comprising:
 reacting an oligonucleotide precursor with a solid phase support within a reaction vessel; and   stirring the solid phase support within the reaction vessel using an overhead stirring assembly,   wherein the overhead stirring assembly is coupled to the reaction vessel and includes a stirring motor coupled to a stirring shaft, the stirring shaft inserted into the reaction vessel and configured to be actuated by the stirring motor to stir the solid phase support within the reaction vessel.   
     
     
         22 . The method of  claim 21 , further comprising one or more of: activation of one or more agents and/or reagents, coupling via delivery of an amidite to the reaction vessel, capping via one or more reagents, oxidation, detritylation, cleavage, and deprotection. 
     
     
         23 . The method of  claim 21 , wherein the solid phase support comprises a plurality of discrete resin pieces. 
     
     
         24 . The method of  claim 23 , wherein the plurality of discrete resin pieces comprises a plurality of resin beads. 
     
     
         25 . The method of  claim 21 , wherein the reaction vessel includes a stir blade, a stir bar, or both, the stir blade and the stir bar configured to agitate the solid phase support. 
     
     
         26 . The method of  claim 21 , further comprising:
 generating, within the reaction vessel, a plurality of bubbles configured to move relative to the solid phase support and agitate the solid phase support.   
     
     
         27 . The method of  claim 23 , wherein the plurality of discrete resin pieces comprise a low cross link resin, wherein the low cross link resin has a higher substitution between 0.3 to 0.8 mmol/g and the low cross link resin is configured for high swelling in acetonitrile. 
     
     
         28 . The method of  claim 27 , wherein the low cross link resin has a pore size between about 300 Å to 1000 Å. 
     
     
         29 . The method of  claim 21 , wherein the reaction vessel includes a top end and a bottom end, one or more of the top end and the bottom end having one or more openings sized and shaped to receive the stir shaft. 
     
     
         30 . The method of  claim 21 , wherein the reaction vessel includes a top end and a bottom end coupled together via a side wall, the top end and the bottom end being substantially perpendicular to a central axis of the stirring shaft. 
     
     
         31 . The method of  claim 21 , wherein the overhead stirring assembly includes a pump coupled to the reaction vessel via one or more fluid circulation features. 
     
     
         32 . The method of  claim 21 , wherein the stirring shaft extends from the stirring motor into one or more openings of the reaction vessel such that the stirring shaft is substantially parallel with a central axis of the reaction vessel. 
     
     
         33 . The method of  claim 21 , wherein the overhead stirring assembly includes one or more agitators configured to agitate the solid phase support within the reaction vessel, the one or more agitators coupled to the stirring shaft and disposed within an interior of the reaction vessel. 
     
     
         34 . The method of  claim 33 , wherein the one or more agitators have a maximum diameter less than a maximum diameter of the reaction vessel. 
     
     
         35 . The method of  claim 33 , wherein stirring motor, the stirring shaft, one or more seals, and the one or more agitators are coupled in series. 
     
     
         36 . The method of  claim 33 , wherein an agitator of the one or more agitators include a plurality of blades disposed at angle to a central axis of the agitator. 
     
     
         37 . The method of  claim 21 , wherein the overhead stirring assembly includes one or more seals configured to couple the stirring shaft to the reaction vessel. 
     
     
         38 . The method of  claim 21 , wherein the reaction vessel is comprised of a transparent material. 
     
     
         39 . The method of  claim 21 , wherein the reaction vessel is substantially cylindrical. 
     
     
         40 . A oligonucleotide synthesizer comprising:
 an overhead stirring motor coupled to a stirring shaft, the stirring motor configured to rotate the stirring shaft;   a substantially cylindrical reaction vessel coupled to the stirring shaft via one or more seals, wherein the stirring shaft extends into an opening of the reaction vessel when the stirring shaft is coupled to the reaction vessel such that the stirring shaft is substantially parallel to a central axis of the reaction vessel;   one or more agitators coupled to the stirring shaft such that the one or more agitators are disposed within the reaction vessel; and   a pump coupled to the reaction vessel via a fluid circulation feature,   
       wherein an oligonucleotide precursor is disposed within the reaction vessel and the oligonucleotide is reacted with a solid phase support, the stirring motor configured to stir the solid phase support within the reaction vessel.