Methods of forming and using a solid-phase support
Disclosed herein are methods of method of making a substrate for performing a chemical synthesis reaction.
1. A method of making a substrate for performing a chemical synthesis reaction, the method comprising the steps of:
providing a dispensing plate comprising a plurality of recesses, wherein the plurality of recesses have one or more particles disposed therein;
aligning a plurality of reaction vessels with the plurality of recesses, such that each reaction vessel is aligned with a different recess, wherein the plurality of reaction vessels comprises a multiwell substrate comprising a plurality of wells;
dispensing particles from the recesses to the plurality of reaction vessels aligned with the plurality of recesses, the particles being functionalized for covalent attachment of a building block of a synthetic reaction;
permanently embedding the particles in the plurality of reaction vessels; and
adding the building block to the particles in a reaction vessel of the plurality of reaction vessels.
2. The method of claim 1 , wherein the providing step includes brushing the particles into the plurality of recesses of the dispenser plate.
3. The method of claim 1 , wherein the dispensing step further comprises contacting the dispensing plate and the multiwell substrate.
4. The method of claim 3 , wherein the dispensing step further comprises pivoting the dispensing plate into engagement with the multiwell substrate.
5. The method of claim 1 , wherein the embedding step comprises heating the plurality of reaction vessels.
6. The method of claim 5 , wherein the embedding step comprises providing a pressure to bias the plurality of reaction vessels against a heating element.
7. The method of claim 5 , wherein the embedding step comprises providing a pressure to the plurality of reaction vessels biasing the particles against the bottom of the reaction vessels.
8. The method of claim 1 , wherein one or more of the particles remain nonbonded to each reaction vessel.
9. The method of claim 8 further comprising the step of removing the one or more nonbonded particles from each reaction vessel.
10. The method of claim 1 , wherein the plurality of reaction vessels is constructed from a bottomless-well plate and a rigid sheet.
11. The method of claim 10 further comprising providing a layer of hot-melt adhesive to the rigid sheet to form a laminate sheet, applying the laminate sheet to a bottom surface of the bottomless-well plate thereby forming the plurality of reaction vessels.
12. The method of claim 1 , wherein the particles comprise microbeads.
13. The method of claim 1 , wherein the particles comprise controlled pore glass.
14. The method of claim 13 , wherein the particles comprise 1400 Angstrom controlled pore glass.
15. The method of claim 1 , wherein the particles are selected from the group consisting of glass, plastic, polystyrene, resin, gel, agarose and sepharose.
16. The method of claim 1 , wherein less than one-half of the particles is embedded into the reaction vessels.
17. The method of claim 1 , wherein less than 25% of the particles is embedded in the reaction vessels.
18. The method of claim 1 , wherein a majority of the surface of the particles is exposed.
19. The method of claim 1 , wherein the plurality of reaction vessels is plastic.