Method of binding a plurality of chemicals on a substrate by electrophoretic self-assembly

• US 6,107,038 A
• Filed: 08/14/1998
• Issued: 08/22/2000
• Est. Priority Date: 08/14/1998
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Hancock, William S., Hahnenberger, Karen, Choudhary, Gargi, Kuekes, Philip J., Lichtenwalter, Kay
• Primary Examiner(s): Horlick, Kenneth R.
• Application Number:
  US09/134,855
• Time in Patent Office: 739 Days
• Field of Search: 536/25.4, 530/412, 530/344, 204/450, 422/59, 422/68.1, 422/101, 435/288.6, 435/6, 436/94
• US Class Current: 435/6.12
• 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 2219/00585 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G11C 13/0014 comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 comprising bio-molecules
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

An electrophoretic technique is provided for moving a plurality of chemicals into distinct zones for immobilization on a solid surface. The technique includes introducing a first electrolyte and a second electrolyte into a channel, and interposing between the first and second electrolytes at least one solution containing a plurality of chemicals. Under a given electric field, the first electrolyte has anions with higher effective mobility than the chemicals and the second electrolyte has anions with lower effective mobility than the chemicals. When an electrical potential is applied across the length of the channel the plurality of chemicals in the solution are moved into spatial zones. The chemicals in the zones can then be bound to the interior surface of the channel. Chemicals so bound to the wall surface can be used to build very small structures such as arrays and electrical conducting structures.

Claims

1. A method for binding chemicals on a wall surface of a channel, comprising:

(a) introducing into the channel a first ionic species, a second ionic species and at least one solution having a plurality of chemicals, wherein under a given electric field the first ionic species has ions with higher effective mobility than the chemicals, and the second ionic species has ions with lower effective mobility than the chemicals;

(b) applying an electrical potential difference between the two ends of the channel to separate the plurality of chemicals in the solution into spatial zones; and

(c) binding a plurality of the chemicals to the wall surface after the zones have achieved a substantially steady state speed of migration in the channel.

2. A method according to claim 1 further comprising introducing a first electrolyte containing the first ionic species, and a second electrolyte containing the second ionic species into the channel, and interposing the at least one solution between said first and second electrolytes.

3. A method according to claim 1 further comprising binding a spacer on the wall surface of the channel prior to separating the chemicals in the solution in the channel, for binding the chemicals to the wall surface.

4. A method according to claim 1 wherein all the zones in the solution are connected in series and the series of zones is capped at one end by a zone of the ions of the first ionic species and at another end by a zone of the second ionic species and the chemicals are bound to the wall surface after the zones have achieved a steady state speed of migration in the channel.

5. A method according to claim 1 wherein each zone at steady state speed has substantially only one chemical species.

6. A method according to claim 5 wherein the chemicals include oligomers of monomers, said oligomers having selective affinity for partners.

7. A method according to claim 6 wherein the chemicals include oligonucleotides.

8. A method according to claim 7 wherein the oligonucleotides include charged bases.

9. A method according to claim 6 wherein the chemicals include polypeptides having selective affinity for partners.

10. A method according to claim 6 wherein the selective affinity comprises complementarity to other oligomers.

11. A method according to claim 5 wherein the chemicals include oligonucleotides, the oligonucleotides being selected from the group consisting of DNA, RNA, PNA, nucleosides linked by analogs of phosphodiester linkages, and a combination thereof.

12. A method according to claim 1 wherein a spatial zone of 10 microns or less in zone width is produced.

13. A method according to claim 3 wherein the at least some of the chemicals are stopped from further migration along the channel by rapid fixation on the channel surface.

14. A method according to claim 3 wherein the spacer is bound to the wall surface covalently.

15. A method according to claim 14 wherein the spacer is bound to the chemicals of the zones covalently and the binding is caused by photoreaction.

16. A method according to claim 14 wherein the spacer is bound to the chemicals of the zones covalently by means of a photoreactive azide group.

17. A method according to claim 14 wherein the wall surface has silanol group and the spacer is bound to the silanol group through reaction with a moiety selected from the group consisted of epoxy moiety, alkoxide moiety, and azide moiety.

18. A method according to claim 1 comprising separating the chemicals into at least 1,000 spatial zones of chemicals.

19. A method according to claim 1 comprising separating the chemicals into spatial zones of chemicals such that the majority of the zones each have a zone width of 10 microns or less.

20. A method of positioning a plurality of desired chemicals in ordered positions on a wall surface of a channel, comprising:

(a) binding the desired chemicals to affinity moieties to form targeting chemicals, each affinity moiety having affinity for its specific counterpart chemical;

(b) introducing into the channel a first ionic species, a second ionic species, and at least one solution having a plurality of the counterpart chemicals to the desired chemicals with affinity moieties, wherein under a given electric field the first ionic species has ions with higher effective mobility than the counterpart chemicals, and the second ionic species has ions with lower effective mobility than the counterpart chemicals;

(c) applying an electrical potential difference between the two ends of the channel to separate the plurality of counterpart chemicals in the solution into spatial zones;

(d) binding the counterpart chemicals to the wall surface; and

(e) binding the targeting chemicals to their corresponding counterpart chemicals.

21. A method according to claim 20 further comprising introducing a first electrolyte containing the first ionic species and a second electrolyte containing the second ionic species into the channel, and interposing the at least one solution between said first and second electrolytes.

22. A method according to claim 20 further comprising binding a spacer on the wall surface of the channel prior to separating the counterpart chemicals in the channel, for binding the counterpart chemicals to the wall surface after the zones have been established.

23. A method according to claim 22 wherein all the zones are connected in series and the series is capped at one end by a zone of the ions of the first ionic species and at another end by a zone of the ions of the second ionic species and the binding of the counterpart chemicals to the wall surface occurs after the zones have achieved a steady state speed of migration in the channel.

24. A method according to claim 20 further comprising hybridizing at least a portion of the counterpart chemicals with matching oligomers in the targeting chemicals.

25. A method according to claim 24 wherein the matching oligomers include oligonucleotides.

26. A method according to claim 20 wherein the counterpart chemicals include oligonucleotides, the oligonucleotides being selected from the group consisting of DNA, RNA, PNA, nucleosides linked by analogs of phosphodiester linkages, and a combination thereof.

27. A method according to claim 20 further comprising connecting two or more of the counterpart chemicals together via molecular structures, wherein at least one of the molecular structures has a portion complementary to a portion of at least one of the connected counterpart chemicals.

28. A method according to claim 27, wherein at least one molecular structure connected to one of the counterpart chemicals is capable of conducting electricity.

29. A method according to claim 27 wherein the molecular structure is less than 1 micron in its smallest dimension.

30. A device for anchoring a plurality of chemical structures, comprising:

a channel having an interior channel wall, the channel wall having a plurality of zones, each zone having a different species of binder chemical attached to the channel wall, wherein the binder chemical species are capable of binding a targeting chemical species and the zones are arranged in order of effective mobilities of the binder chemicals in a solution in a given electric field.

31. A device according to claim 30 wherein the species of binder molecules each have a portion complementing a corresponding portion in one of the targeting chemical species.

32. A device according to claim 30 wherein the majority of the zones each have a zone width of 10 microns or less.

33. A device according to claim 30 comprising more than 10,000 zones.

34. A device according to claim 30, wherein the targeting chemical species comprise oligonucleotides.

35. A device according to claim 34, wherein the oligonucleotides are selected from the group consisting of DNA, RNA, PNA nucleosides linked by analogs of phosphodiester linkages, and combinations thereof.

36. A device according to claim 30 further comprising secondary molecular structures immobilized on the binder chemical species via target chemical species that are bound to the binder chemical species, at least a portion of the secondary molecular structures being connected to other secondary molecular structures immobilized on the binder chemical species.

37. A device according to claim 36 wherein at least some of the secondary molecular structures can conduct electricity.

38. A device according to claim 37, wherein at least some of the secondary molecular structures are connected to enable electrical communication with electrical components.

39. A device according to claim 30 further comprising a plurality of channels each having binder chemical species.

40. An electrical device, comprising:

a substrate having a two-dimensional arrangement of a plurality of zones, wherein within in each zone the substrate is attached to a different molecular structure comprised of a binder species coupled to an electrically conductive component and further wherein the binder species is capable of coupling to a target species and the zones are arranged in order of effective mobilities of the target species in a solution in a given electric field.