Releasable polymer arrays

• US 20040248162A1
• Filed: 03/02/2004
• Published: 12/09/2004
• Est. Priority Date: 12/17/2002
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: McGall, Glenn H., Cuppoletti, Andrea
• Application Number:
  US10/791,005
• Publication Number:
  US 20040248162A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• 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 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• 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: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 21/04 : with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 7/06 : having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 : having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, 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 80/00 : Linkers or spacers specially adapted for combinatorial chemistry or libraries, e.g. traceless linkers or safety-catch linkers

Abstract

Methods are provided for fabricating an array of polymers wherein the polymers may be released from the surface of the array by activation of a cleavable moiety. Also provided are arrays of polymers having of polymers wherein the polymers can be released from the surface of the array by activation of a releasable group. Arrays of nucleic acids wherein a nucleic acid probe may be released from the array by activation of a releasable groups and methods for fabrication of such arrays are also disclosed.

Claims

2-1. The method of claim 3 wherein said photogroup is activated by light having a wavelength of 313 m and below.

3-2. The method of claim 3 wherein said photogroup is activated by light having a wavelength of about 313 nm and below, but not above 313 mm.

8. A method for releasing polymers from an array of polymers on a solid substrate, said method comprising the steps of:

providing a solid substrate;

attaching a plurality of linkers to said solid substrate, said solid substrate having a surface, each said linker comprising a cleavable moiety, wherein said cleavable moiety is activatable only at a distinct set of conditions and wherein activation of said cleavable moiety disrupts the linker to allow release of the polymer from the array, to provide a plurality of attached linkers and wherein each said linker has two terminal ends, the first end of which is attached to the substrate and the second end of which is away from the substrate and comprises a reactive group covered by a photoprotective removable group having a first activation energy wavelength;

selectively exposing said photoprotective removable group on said attached linkers to light to selectively remove said photoprotective groups and provide unprotected reactive groups in one or more predefined regions;

exposing under reactive conditions said one or more predefined regions with exposed reactive groups to a first monomer and attaching said first monomer to the exposed reactive groups, wherein sad first monomer comprises a reactive group protected by a photoprotective removable group having said first activation energy wavelength;

selectively exposing said photoprotective removable groups on said attached linkers or said attached first monomer to light to selectively remove said photoprotective groups and expose reactive groups in one or more predefined regions;

exposing under reactive conditions said one or more predefined regions with exposed reactive groups to a second monomer and attaching said second monomer to said exposed groups, wherein sad second monomer comprises a reactive group protected by a photoprotective removable group having a first activation energy wavelength;

repeating said steps of selectively exposing photoprotective removable groups and exposing reactive groups to further monomers each compising a reactive group protected by a photoprotective removable group until the desired array of polymers is complete and subjecting the array to the distinct set of conditions to release the array of polymers.

9. A method for releasing polymers from an array of polymers on a solid substrate according to claim 8 wherein said monomer is a nucleotide.

10. A method for releasing polymers from an array of polymers on a solid substrate according to claim 8 wherein said clevable moiety comprises a photogroup having a second wavelength of activation energy, wherein said first wavelength of activation energy is different than said second wavelength of activation energy and where said cleavable moiety comprising a photogroup is not released by exposure to said first wavelength of light.

11. A method for releasing polymers from an array of polymers on a solid substrate according to claim 10 wherein said photogroup is selected from the group consisting of

12. A method for releasing polymers from an array of polymers on a solid substrate according to claim 10 wherein said second energy of activation wavelength is about 313 nm and below.

13. A method for releasing polymers from an array of polymers on a solid substrate according to claim 8 wherein said monomer is an amino acid.

14. A method for releasing polymers from an array of polymers on a solid substrate according to claim 8 wherein said cleavable moiety comprises a compound selected from the group consisting of

15. A releasable polymer array comprising a substrate having a linker comprising a cleavable moiety which is labile under a set of conditions and attached to said linker is a polymer, wherein said polymer can be released by exposure of the array to the set of conditions.

16. A releasable polymer array according to claim 15 wherein said polymer is a nucleic acid.

17. A releasable polymer array according to claim 16 wherein said nucleic acid is an oligonucleotide.

18. A releasable polymer array according to claim 15 wherein said cleavable moiety comprises a photogroup.

19. A releasable polymer array according to claim 18 wherein said photogroup is selected from the group consisting of

20. A releasable polymer array according to claim 18 wherein said polymer is a peptide.

21. A releasable polymer arrays according to claim 18 wherein said cleavable moiety comprises a compound selected from the group consisting of

22. A polymer array having releasable polymers, said array comprising a substrate having attached thereto polymers, wherein one or more of said polymers comprises a cleavable moiety which is labile under a distinct set of conditions wherein said releasable group allows release of the polymer upon activation.

23. A nucleic acid array according to claim 22 wherein said cleavable moiety comprises a photogroup which may be activated by light having a wavelength of 313 nm and below.

24. A nucleic acid array according to claim 22 wherein said cleavable moiety is photogroup comprises a compound selected from the group consisting of

25. A nucleic acid array according to claim 22 wherein said cleavable moiety is a photogroup comprises a compound selected from the group consisting of

26. A polymer array having releasable polymers according to claim 22 wherein said polymers are nucleic acids.

27. A polymer array having releasable polymers according to claim 26 wherein said nucleic acids are oligonucleotides.

28. A polymer array having releasable polymers according to claim 22 wherein said polymers are selected from the group consisting of proteins and peptides.

29. A method for fabricating a polymer array having releasable polymers, said method comprising the steps of:

providing a substrate;

attaching a plurality of linkers to said substrate, said linkers comprising a cleavable moiety which is labile under a distinct set of conditions;

reversibly modifying said cleavable moiety with a protecting group to provide a reversibly modified cleavable moiety wherein said modified cleavable moiety is not labile under the distinct set of conditions;

attaching a first monomer to said linker;

attaching a second monomer to said linker or to the first monomer;

repeating said step of attaching said further monomer until the desired array of polymers is complete; and

demodifying said reversibly modified releasable group.

30. A method for fabricating a polymer array according to claim 29 wherein said cleavable moiety comprises a photogroup.

31. A method for fabricating a polymer array according to claim 30 wherein said protecting group is