Lithographic mask design and synthesis of diverse probes on a substrate

• US 20060094040A1
• Filed: 09/21/2005
• Published: 05/04/2006
• Est. Priority Date: 12/17/1996
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Hubbell, Earl A., Stryer, Lubert, Mittmann, Michael P.
• Application Number:
  US11/232,584
• Publication Number:
  US 20060094040A1
• Time in Patent Office: Days
• US Class Current: 435/6.11
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07K 1/045 using devices to improve synthesis, e.g. reactors, special vessels
• CPC Class Codes: C07K 1/047 Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/08 : Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G03F 7/00 : Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor using photoresist structures for special production processes, see the relevant places, e.g. B44C, H01L, e.g. H01L21/00, H05K
• CPC Class Codes: G03F 7/70466 : Multiple exposures, e.g. combination of fine and coarse exposures, double patterning or multiple exposures for printing a single feature stitching G03F7/70475

Abstract

Systems and methods of synthesizing probes on a substrate are provided. One or more shift reticles are utilized to uniformly add monomers to the substrate at specified locations. The shift reticles are shifted relative to the substrate between monomer addition steps. Additionally, characteristics of the desired probes may be specified at synthesis time.

Claims

1. A method of synthesizing rows of probes including an interrogation position on a substrate, comprising the steps of

coupling non-interrogation position monomers on the substrate in a first region having a first width, and

coupling rows of interrogation position monomers on the substrate in a second region having a second width, the second region being within the first region and the second width being less than the first width.

2. The method of claim 1, wherein each row of probes includes a different monomer at the interrogation position.

3. The method of claim 2, wherein the interrogation position monomers include A, C, G, and T(U).

4. The method of claim 1, the probes that are within the first region and not the second region do not include interrogation position monomers.

5. The method of claim 1, wherein coupling the non-interrogation position monomers on the substrate, comprises

coupling monomers on the substrate at locations specified by at least one shift reticle,

shifting the at least one shift reticle relative to the substrate, and

after shifting the at least one shift reticle, coupling monomers on the substrate at locations specified by the at least one shift reticle.

6. The method of claim 5, wherein the probes synthesized on the substrate include multiple monomers that were coupled to the substrate utilizing the at least one shift reticle.

7. The method of claim 1, wherein coupling the interrogation position monomers on the substrate, comprises

coupling monomers on the substrate at locations specified by an interrogation position reticle,

shifting the interrogation position relative to the substrate, and

after shifting the interrogation position reticle, coupling monomers on the substrate at locations specified by the interrogation position reticle.

8. The method of claim 7, wherein the interrogation position reticle is shifted in a direction perpendicular to a direction that the at least one shift reticle is shifted.

12. The substrate of claim 8, further comprising the step of shifting the shift reticle relative to the substrate in order to couple a second layer of different types of monomers on the substrate at the specified locations.

9. A substrate, comprising

multiple rows of probes including an interrogation position monomer coupled to the substrate, and

at least one row of probes that do not include an interrogation position monomer coupled to the substrate between two rows of probes the do include an interrogation position monomer.

10. The substrate of claim 9, wherein the multiple rows of probes including an interrogation position monomer include four rows of probes wherein each rows of probes includes a different monomer at the interrogation position.

11. The substrate of claim 10, wherein the interrogation position monomers include A, C, G, and T(U).

13. A method of synthesizing probes on a substrate, comprising

coupling monomers on the substrate at locations specified by a plurality of shift reticles, each shift reticle being for coupling a specific monomer on the substrate and including a monomer addition region for coupling an interrogation position monomer,

shifting the plurality of shift reticles relative to the substrate in a first direction, and

after shifting the plurality of shift reticles, coupling monomers on the substrate at locations specified by the plurality of shift reticles so that probes are synthesized on the substrate including different interrogation positions.

14. The method of claim 13, wherein each shift reticle includes rectangular monomer addition regions that are longer in a second direction that is perpendicular to the first direction.

15. The method of claim 14, wherein each shift reticle includes an interrogation position monomer addition region that are at a different location in the second direction.

16. The method of claim 13, wherein the plurality of shift reticles include at least one region in a same location that does not couple monomers on the substrate so that probes of varying lengths may be synthesized at the same time.