Substrate preparation process
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 method for synthesizing arrays of oligonucleotide probes on a surface of a substrate, which comprises:
providing a reaction chamber comprising a door hingedly connected the reaction chamber;
placing the substrate into the reaction chamber, wherein the reaction chamber further comprises a plurality of automatic alignment pins which contact the substrate during the placing of the substrate into the reaction chamber, thereby aligning the substrate in a desired orientation with respect to the reaction chamber;
closing the door of the reaction chamber such that the reaction chamber encloses the substrate; and
exposing the surface of the substrate to a solution comprising a monomer such that at least one monomer binds to the surface of the substrate.
2. The method according to claim 1 , wherein the reaction chamber further comprises at least one fluid inlet and at least one fluid outlet thereby fluidly connecting the solution with the surface of the substrate.
3. The method according to claim 2 , wherein at least one fluid outlet is connected to a waste vessel for the fluid.
4. The method according to claim 1 , wherein the reaction chamber further comprises a gasket surrounding the substrate.
5. The method according to claim 1 , wherein the aligned substrate is held in place by a vacuum chuck.
6. The method according to claim 1 , which further comprises contacting the surface with a wash solution and washing the surface.
7. The method according to claim 6 , wherein the wash solution is a buffer.
8. The method according to claim 1 , which further comprises exposing the substrate to a sample; and
scanning the substrate.
9. The method according to claim 1 , further comprising photolysing the substrate after monomer addition.
10. The method according to claim 1 , wherein the reaction chamber further comprises a temperature control element.
11. The method according to claim 10 , further comprising controlling the temperature within the reaction chamber by adjusting the temperature control element.
12. The method according to claim 1 , further comprising deprotecting the monomer which is last added by exposing the substrate to an anhydrous organic amine.
13. The method according to claim 12 , which further comprises:
opening the door;
removing the substrate;
separating the substrate into segments; and
inserting or attaching the segments into a cartridge comprising a reaction chamber which provides fluid communication of an inlet and outlet port with the substrate.