Three-dimensional array of supports for solid-phase parallel synthesis and method of use
View Patent ↗A three-dimensional (3D) array of solid-phase supports is adapted to provide parallel synthesis of a library of molecules with 3D diversity. Individual locations in the 3D array may be assigned to selected molecules in the library such that molecules may be synthesized at and retrieved from such locations. Also, the supports include aperture walls in stacked plates; the supports may be suspended within stacked plate apertures; the 3D array include discrete supports arranged in columns in one or more wells; the supports include tube inner walls or be suspended in tubes, the tubes being secured in stacked, two-dimensional (2D) frameworks; or the supports include beads contained in porous enclosures having non-porous side walls and being secured in stacked, 2D frameworks. A support transfer device enables transfer of solid-phase supports used in a 3D array. Such apparatus includes: a rack of rods sized to be inserted through supports and a mechanism to prevent supports from coming off the rack; tubes connected to a vacuum manifold to suction supports one Z plane at a time; or a transfer block having recesses to receive one or more support and at least one gate withholding supports from passing through the gate when in a closed position. A method of 3D synthesis includes: a) functionalizing solid-phase supports; b) placing supports in a 3D array; and c) performing parallel synthesis with 3D diversity. At least one unique R 1 group member may be assigned to each Z plane.
1. An apparatus for performing parallel synthesis of a library of molecules with three-dimensional (3D) diversity, comprising:
a well plate comprising a plurality of wells in a two-dimensional (2D) array, each of said plurality of wells having one end which is open and one end which is closed; and
a plurality of discrete solid phase supports disposed in each of said plurality of wells in a single stacked column arrangement, which arrangement forms a 3D array of solid phase supports for performing parallel synthesis of a library of molecules with 3D diversity, wherein said discrete supports are sized relative to said wells such that only a single stacked column arrangement of supports occupies each of said plurality of wells.
2. An apparatus for performing parallel synthesis of a library of molecules with 3D diversity, comprising:
a well plate comprising a plurality of parallel troughs in a two-dimensional (2D) array, each of said plurality of troughs having one end which is open and one end which is closed; and
a plurality of discrete solid phase supports disposed in each of said plurality of troughs, which plurality of supports form a plurality of single stacked column arrangements, which arrangements forms a 3D array of solid phase supports for performing parallel synthesis of a library of molecules with 3D diversity, wherein said discrete solid phase supports are sized relative to said troughs such that a plurality of single stacked column arrangements of supports occupies each trough.
3. The apparatus as in claims 1 or 2 , wherein the supports are functionalized.
4. The apparatus as in claims 1 or 2 , wherein the supports are fabricated using material selected from the group consisting of resin, glass, silica gel, alumina gel, cellulose, polyolefins, polypropylene, polyethylene, polytetrafluoroethylene, poly(cholortrifluoroethylene), polyamides, polyimides, poly(paraxylylenes), and phenol-formaldehyde polymers, that are functionalized and compatible for use in combinatorial chemistry.
5. The apparatus as in claims 1 or 2 , wherein individual locations in the 3D array are assigned to selected molecules in the library such that selected molecules are synthesized at and retrieved from their respective locations.
6. The apparatus as in claims 1 or 2 , wherein the supports are selected from the group consisting essentially of rods, disks, tubes, rings, sheets, and spheres.
7. The apparatus as in claims 1 or 2 , wherein the supports in said columns are coupled together.
8. The apparatus of claim 4 , wherein the supports are fabricated using a halogenated polyolefin.
9. The apparatus of claim 3 , wherein the supports comprise a functionalized graft co-polymer of polypropylene, polyethylene, polytetrafluoroethylene, poly(chlorotrifluoroethylene) or polyolefin.
10. The apparatus of claim 9 , wherein the supports comprise a functionalized graft co-polymer of a halogenated polyolefin.
11. The apparatus as in claims 1 or 2 , wherein the supports are rods.
12. The apparatus as in claims 1 or 2 , wherein the supports are disks.
13. The apparatus as in claims 1 or 2 , wherein the supports are tubes.
14. The apparatus as in claims 1 or 2 , wherein the supports are rings.
15. The apparatus as in claims 1 or 2 , wherein the supports are sheets.
16. The apparatus as in claims 1 or 2 , wherein the supports are spheres.
17. The apparatus as in claims 1 or 2 , wherein the supports are beads.
18. The apparatus of claims 1 or 2 , wherein said supports comprise a releaseable coupling for interconnection of one of said supports to another.
19. The apparatus of claim 18 , wherein said coupling mechanism comprises a plug on one of said supports and a complementary socket on an adjacent support.
20. The apparatus of claim 7 , wherein said supports are disposed in a stackable enclosure, said enclosure being porous to allow for passage of reagent from one support to another within said column.
21. The apparatus of claim 20 , wherein said stackable porous enclosure comprises a cup.
22. The apparatus of claim 20 , wherein said supports are beads contained in said stackable porous enclosures, which enclosures are stacked in a column.
23. The apparatus of claims 1 or 2 , wherein said supports are stacked tubes having axially aligned apertures with a rod passing through the apertures of the tubes of a stack.