System for photolithographic synthesis of polymer arrays
View Patent ↗The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.
1. A system for synthesizing an array of polymers, the system comprising:
a flow cell, wherein the flow cell comprises a flow cell body and a substrate, wherein the flow cell body and the substrate are configured to form a flow cell cavity, wherein the substrate includes an array synthesis surface within the flow cell cavity, and wherein the flow cell cavity includes an anti-reflective coating;
one or more fluidic ports configured to flow one or more fluids through the flow cell cavity; and
a light source configured to illuminate the array synthesis surface.
2. The system of claim 1 , wherein the flow cell cavity includes a back surface, wherein the back surface is located opposite the array synthesis surface, and wherein the back surface possesses the anti-reflective coating.
3. The system of claim 1 , wherein the array synthesis surface and the light source are configured such that illumination passes through the substrate before reaching the array synthesis surface.
4. The system of claim 1 , wherein the anti-reflective coating is configured to reduce reflection of one or more wavelengths within the flow cell cavity.
5. The system of claim 2 , wherein the anti-reflective coating is configured to reduce reflection of one or more wavelengths off of the back surface.
6. The system of claim 5 , wherein the one or more wavelengths include a wavelength above 340 nm.
7. The system of claim 6 , wherein the one or more wavelengths include a wavelength of 365 nm.
8. The system of claim 1 , wherein the substrate is a slide.
9. The system of claim 1 , wherein the substrate comprises a material selected from the group consisting of glass, quartz and silicon.
10. The system of claim 1 , additionally comprising:
a fluid delivery system, wherein the fluid delivery system is configured to be in fluid communication with the flow cell cavity through the one or more fluidic ports.
11. The system of claim 10 , wherein the fluid delivery system comprises a plurality of reagent reservoirs, and wherein the plurality of reagent reservoirs include reagent reservoirs containing solutions with monomers for the array of polymers.
12. The system of claim 11 , wherein the plurality of reagent reservoirs additionally includes a reagent reservoir which contains an index matching fluid, wherein the index matching fluid possesses an index matching fluid refractive index, wherein the substrate possesses a substrate refractive index, and wherein the index matching fluid refractive index is substantially equivalent to the substrate refractive index.
13. The system of claim 12 , wherein the index matching fluid refractive index is within about 10% of the substrate refractive index.
14. The system of claim 12 , wherein the system is configured to add the index matching fluid to the flow cell cavity before illumination of the array synthesis surface with the light source.
15. The system of claim 11 , wherein the monomers are amino acids or nucleoside phosphoramidites.
16. The system of claim 11 , wherein the monomers include a photolabile protecting group.
17. The system of claim 16 , wherein the light source is configured to provide one or more wavelengths capable of effecting removal of the photolabile protecting groups from the monomers.