Fluid processing device for oligonucleotide synthesis and analysis
View Patent ↗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 method comprising:
introducing a fluid including a first monomer into a first fluid distribution manifold of a fluid processing device;
opening, by a controller, a closed 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, wherein opening the closed surface tension control valve allows flow of the fluid to contact the at least one respective reaction site,
wherein the surface tension control valve is configured to be actuated by electromagnetic radiation directed at the surface tension control valve to change a contact angle of the fluid to a surface of the surface tension control valve,
wherein the at least one closed surface tension control valve is disposed between the first manifold and the at least one respective reaction site, and
wherein the open surface tension control valve is configured to allow the first monomer to move from the first manifold, through the open surface tension control valve, and into the at least one respective reaction site; and
forming an extended structure by the first monomer attaching to a first structure in the at least one respective reaction site.
2. The method of claim 1 , wherein in the extended structure, the first monomer is a first protected monomer, and 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 open surface tension control valve to form a closed surface tension control valve;
introducing a deprotecting agent into the first manifold then opening the closed surface tension control valve to form a reopened surface tension control valve;
moving the deprotecting agent from the first manifold, through the 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.
3. The method of claim 2 , 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.
4. The method of claim 1 , wherein the first structure is supported by a support and the method further comprises cleaving, with an introduced cleaving agent, the extended structure from the support to form a cleaved structure.
5. The method of claim 4 , 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.
6. The method of claim 1 , wherein the extended structure comprises a dimethyltrityl-protected phosphoramidite monomer.
7. The method of claim 1 , wherein the surface tension control valve is configured to open in response to electromagnetic radiation directed toward the surface tension control valve.
8. The method of claim 1 , wherein the surface tension control valve is configured to open in response to electromagnetic radiation emitted from an electromagnetic radiation source reflected toward the surface tension control valve.
9. The method of claim 8 , wherein the electromagnetic radiation is reflected by individually controlled-movement of a plurality of mirrors.
10. The method of claim 1 , wherein the 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.