Fluid processing device for oligonucleotide synthesis and analysis

Abstract

The present teachings provide a fluid processing device adapted to produce different oligomers in a plurality of respective reaction sites. The fluid processing device can comprise a first manifold for delivering reactants to the plurality of reaction sites, and a second manifold for removing waste from, and optionally delivering wash fluid to, the plurality of reaction sites. Surface tension control valves can be disposed in fluid communication with the first manifold and can selectively allow reactants and/or fluids into the reaction sites. A method of making oligonucleotides is also provided.

1 . A fluid processing device comprising: 
 a plurality of reaction sites;    a first fluid transport manifold in fluid communication with each of the plurality of the reaction sites;    a second fluid transport manifold in fluid communication with each of the plurality of sites; and    a plurality of surface tension control valves, at least one of the plurality of surface tension control valves disposed between the first manifold and at least one respective reaction site of the plurality of reaction sites, each surface tension control valve being in fluid communication with the first manifold and the at least one respective reaction site.    
     
     
         2 . The fluid processing device of  claim 1 , wherein the first manifold contains one or more nucleic acid base selected from adenine, cytosine, guanine, and thymine.  
     
     
         3 . The fluid device of  claim 1 , further comprising a dimethyltrityl-protected phosphoramidite nucleotide monomer disposed in the first manifold.  
     
     
         4 . The fluid processing device of  claim 1 , further comprising a planar substrate, wherein the first manifold, the second manifold, and the plurality of reaction sites are formed in the substrate.  
     
     
         5 . The fluid processing device of  claim 1 , wherein at least one of the plurality of surface tension control valves comprises a light-actuated valve.  
     
     
         6 . The fluid processing device of  claim 1 , wherein at least one of the plurality of surface tension control valves comprises an electrically-actuated valve.  
     
     
         7 . The fluid processing device of  claim 1 , wherein at least one of the plurality of surface tension control valves comprises a temperature-actuated valve.  
     
     
         8 . The fluid processing device of  claim 1 , further comprising a fluid communication directly between two adjacent reaction sites of the plurality of reaction sites.  
     
     
         9 . A system comprising the fluid processing device of  claim 1 , a plurality of respective different sources of nucleic acid bases, and a loading device for individually loading the different nucleic acid bases from the plurality of respective different sources into the first manifold.  
     
     
         10 . A system including the fluid processing device of  claim 1 , and a pressure differential source in fluid communication with one or more of the first manifold and the second manifold.  
     
     
         11 . A system comprising the fluid processing device of  claim 5 , and an electromagnetic radiation source adapted to emit electromagnetic radiation toward one or more of the plurality of surface tension control valves.  
     
     
         12 . The system of  claim 11 , wherein the electromagnetic radiation source includes a laser.  
     
     
         13 . The system of  claim 11 , further comprising a reflective device adapted to reflect electromagnetic radiation emitted from the electromagnetic radiation source toward one or more of the plurality of surface tension control valves.  
     
     
         14 . The system of  claim 13 , wherein the reflective device comprises a plurality of individually moveable mirrors.  
     
     
         15 . The system of  claim 11 , further comprising a control unit operatively connected to the electromagnetic radiation source and adapted to control the electromagnetic radiation source.  
     
     
         16 . The system of  claim 11 , further comprising at least one focusing lens disposed along an emission beam path between the electromagnetic radiation source and at least one of the plurality of surface tension control valves.  
     
     
         17 . The system of  claim 1 , wherein the fluid processing device comprises at least one fluid communication between at least two of the plurality of reaction sites, and the at least one fluid communication bypasses the first and second manifolds.  
     
     
         18 . A system comprising the fluid processing device of  claim 1 , and a thermal cycling block adapted to hold the fluid processing device such that at least one of the plurality of reaction sites is in heat-transfer communication with the thermal cycling block.  
     
     
         19 . A system comprising the fluid processing device of  claim 1 , and a rotatable platen comprising a top surface, and a holder adapted to hold the fluid processing device in or on the top surface.  
     
     
         20 . A system comprising the fluid processing device of  claim 1 , and a pump adapted to connect to the first manifold and force liquid into the first manifold.  
     
     
         21 . A system comprising the fluid processing device of  claim 6 , and an electricity source electrically connected to the electrically-actuated valve.  
     
     
         22 . The system of  claim 21 , further comprising a control unit operatively connected to the electricity source and adapted to control the electricity source.  
     
     
         23 . A system comprising the fluid processing device of  claim 7 , and a heater in heat-transfer communication with the temperature-actuated valve.  
     
     
         24 . The system of  claim 23 , further comprising a control unit operatively connected to the heater and adapted to control the heater.  
     
     
         25 . A method comprising: 
 introducing a first monomer into a first fluid distribution manifold of a fluid processing device;    opening at least one surface tension control valve in fluid communication with both the first fluid distribution manifold and at least one respective reaction site, to form an open surface tension control valve;    moving the first monomer from the first manifold, through the at least one open surface tension control valve, and into the at least one respective reaction site; and    attaching the first monomer to a first structure in the at least one respective reaction site to form an extended structure.    
     
     
         26 . The method of  claim 25 , wherein the first monomer is a first protected monomer, the extended structure is a protected extended structure, and the method further comprises: 
 washing the at least one respective reaction site subsequent to the attaching;    closing the at least one surface tension control valve;    introducing a deprotecting agent into the first manifold then opening the at least one surface tension control valve to form at least one reopened surface tension control valve;    moving the deprotecting agent from the first manifold, through the at least one reopened surface tension control valve, and into the at least one respective reaction site; and    deprotecting the protected extended structure to form a deprotected extended structure.    
     
     
         27 . The method of  claim 26 , further comprising: 
 introducing a wash reagent into a second manifold in fluid communication with the at least one respective reaction site;    moving the wash reagent from the second manifold into the at least one respective reaction site; and    removing the wash reagent from the at least one respective reaction site to form a washed and deprotected extended structure.    
     
     
         28 . The method of  claim 25 , wherein the first structure is supported by a support and the method further comprises cleaving the extended structure from the support to form a cleaved structure.  
     
     
         29 . The method of  claim 28 , further comprising moving the cleaved structure from the at least one respective reaction site into a second reaction site that is in fluid communication with the at least one respective reaction site.  
     
     
         30 . The method of  claim 25 , wherein the extended structure comprises a dimethyltrityl-protected phosphoramidite monomer.  
     
     
         31 . The method of  claim 25 , wherein opening the at least one surface tension control valve comprises directing electromagnetic radiation toward the at least one surface tension control valve.  
     
     
         32 . The method of  claim 25 , wherein opening at least one surface tension control valve comprises reflecting electromagnetic radiation emitted from an electromagnetic radiation source toward the at least one surface tension control valve.  
     
     
         33 . The method of  claim 32 , wherein the reflecting comprises individually controlling movement of a plurality of mirrors.  
     
     
         34 . The method of  claim 25 , wherein the at least one surface tension control valve comprises a plurality of surface tension control valves, and the at least one respective reaction site comprises a plurality of respective reaction sites.