Combinatorial Electrochemical Synthesis

• US 20020008038A1
• Filed: 12/22/2000
• Published: 01/24/2002
• Est. Priority Date: 06/24/1998
• Status: Abandoned Application

• Current Assignee: Therasense Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Therasense Incorporated (Abbott Laboratories Incorporated)
• Inventors: Heller, Adam, Caruana, Daren J.
• Application Number:
  US09/746,840
• Publication Number:
  US 20020008038A1
• Time in Patent Office: Days
• US Class Current: 205/261
• 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 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• 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 2219/00621 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 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/00752 Alloys
• CPC Class Codes: C07B 2200/01 Charge-transfer complexes
• 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: C40B 40/18 Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 60/14 for creating libraries
• 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

Abstract of Disclosure

An array of selectively addressible microelectrodes for combinatorial synthesis of complex polymers or alloys.

Claims

1. A device comprising:

a) a plurality of selectively adressable microelectrodes;

b) a conductive matrix disposed on each microelectrode, the matrix comprising carbon, hydrogen and functional reactive groups, wherein the functional reactive groups are activated or deactivated by applying a current or a potential to the conductive matrix; and

c) a source of current or potential arranged and configured to selectively provide a current or voltage to each microelectrode,

wherein each of the selectively addressable microelectrodes has a smallest lateral dimension, and wherein each microelectrode is separated from other microelectrodes of the device by a distance of at least ten times the smallest lateral dimension of the microelectrode.

17. A method for selective synthesis of an array of compounds, the method comprising steps of:

a) providing a device comprising;

(i) a plurality of selectively addressable microelectrodes;

(ii) a conductive matrix disposed on each microelectrode, the matrix comprising carbon, hydrogen and functional reactive groups, wherein the functional reactive groups are activated or deactivated by applying a current or a potential to the conductive matrix; and

(iii) a source of current or potential configured and arranged to selectively provide a current or voltage to each microelectrode,

wherein each of the selectively addressable microelectrodes has a smallest lateral dimension, and wherein each microelectrode is separated from other microelectrodes of the device by a distance of at least ten times the smallest lateral dimension of the microelectrode;

b) providing a first reactant; and

c) selectively applying to one or more microelectrodes a current or potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes to induce binding of the first reactant to the conductive matrix.

18. The method according to claim 44, further comprising repeating the step of selectively applying to one or more microelectrodes a potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes to induce binding of an additional reactant to form an array of compounds.

19. The method according to claim 44, further comprising selectively applying to one or more microelectrodes a potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes to induce binding of a second reactant to the first reactant.

20. The method according to claim 44, wherein the faradaic reaction causes a chemical change in one or more of the functional reactive groups, the reactant, or a chemical species, in the immediate vicinity of the microelectrode.

21. The method according to claim 47, wherein the chemical change is a change in ionic concentration or an oxidation or a reduction of the functional reactive groups, the reactant, or the chemical species.

22. The method according to claim 48 wherein the change in ionic concentration is a change in pH.

23. The method according to claim 48, further comprising providing an enzyme, wherein the chemical change is a change in ionic concentration, and wherein adjustment of the ionic concentration in the immediate vicinity of the microelectrode modulates activity of the enzyme in the immediate vicinity of the microelectrode.

24. The method according to claim 44 wherein the reactant comprises a nucleotide.

25. The method according to claim 44 wherein the reactant comprises an amino acid.

26. The method according to claim 44 wherein the reactant comprises an organic compound, an inorganic compound or a metal-organic ion.

27. The method according to claim 53 wherein the organic compound is ascorbic acid or benzoquinone.

28. The method according to claim 53 wherein the inorganic compound is iron, cobalt, ruthenium, osmium or copper.

2. The device according to claim 28, wherein the smallest lateral dimension is a diameter.

3. The device according to claim 28, wherein the smallest lateral dimension is measured from one edge of the microelectrode to an opposite edge of the microelectrode.

4. The device according to claim 28, wherein each microelectrode is separated from other microelectrodes of the device by a distance of at least twenty times the smallest lateral dimension of the electrode.

5. The device according to claim 28, wherein the smallest lateral dimension of one or more of the microelectrodes is less than 100 μ

m.

7. The device according to claim 28, wherein the smallest lateral dimension of one or more of the microelectrodes is 0.1 μ

m to 1 μ

m.

9. The device according to claim 28, wherein the conductive matrix comprises a redox polymer.

12. The device according to claim 28 wherein the conductive matrix comprises a polycation.

13. The device according to claim 28 wherein the conductive matrix has a thickness of 3 nm to 20 μ

m.

14. The device according to claim 28, wherein the functional reactive groups are independently selected from amines, aldehydes, carboxylic acids, or active esters.

15. The device according to claim 28 further comprising one or more reference electrodes.

16. The device according to claim 28 further comprising one or more counter-electrodes.

29. The method according to claim 44 wherein the method comprises:

a) providing a device comprising;

(i) a plurality of selectively addressable microelectrodes;

(ii) a redox polymer comprising poly(4-vinyl pyridine), osmium and amine reactive groups; and

(iii) a source of current or potential configured and arranged to selectively apply a current or voltage to each microelectrode;

b) providing a first nucleotide; and

c) selectively applying to one or more microelectrodes a current or potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes to induce binding of the first nucleotide to the redox polymer.

30. The method according to claim 56 further comprising:

d) providing a second nucleotide; and

e) selectively applying to one or more microelectrodes a current or potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes to induce binding of the second nucleotide to the redox polymer or to one or more of the first nucleotides.

31. The method according to claim 56 wherein the step of selectively applying to one or more microelectrodes a current or potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes induces binding of the first nucleotide to one or more of the amine reactive groups.

32. A method for selective synthesis of an array of compounds, the method comprising steps of:

a) providing a device comprising;

(i) a plurality of selectively addressable microelectrodes;

(ii) a conductive matrix disposed on each microelectrode, the matrix comprising carbon, hydrogen and functional reactive groups, wherein the functional reactive groups are activated or deactivated by applying a current or a potential to the conductive matrix; and

(iii) a source of current or potential providing a selective current or voltage to each microelectrode,

wherein each of the selectively addressable microelectrodes has a smallest lateral dimension, and wherein each microelectrode is separated from other microelectrodes of the device by a distance of at least ten times the smallest lateral dimension of the microelectrode; and

b) selectively applying to one or more microelectrodes a current or potential sufficient to cause a faradaic reaction in the immediate vicinity of the microelectrode to induce deposit of a metal onto the microelectrode.

6. The device according to claim 32, wherein the smallest lateral dimension of each of the microelectrodes of the device is the same.

33. The method according to claim 59 further comprising repeating the step of selectively applying to one or more microelectrodes a potential sufficient to cause a faradaic reaction in the immediate vicinity of the microelectrode to induce deposit of a second metal onto the microelectrode to synthesize a non-stoichiometric inorganic compound or metal alloy on the microelectrode.

34. The method according to claim 59 further comprising the step of inducing etching or dissolution of a portion of one or more metals deposited onto the microelectrode.

8. The device according to claim 34, wherein the smallest lateral dimension of each of the microelectrodes is the same.

35. The method according to claim 61 further comprising reacting by heating, oxidation, sulfidation, or consolidation to form an alloy or non-stoichiometric inorganic compound.

36. A method for selective synthesis of an array of compounds, the method comprising steps of:

a) providing a device comprising;

(i) a plurality of selectively addressable microelectrodes;

(ii) a conductive matrix disposed on each microelectrode, the matrix comprising carbon, hydrogen and functional reactive groups; and

(iii) a source of current or potential configured and arranged to selectively provide a current or voltage to each microelectrode,

wherein each of the selectively addressable microelectrodes has a smallest lateral dimension, and wherein each microelectrode is separated from other microelectrodes of the device by a distance of at least ten times the smallest lateral dimension of the microelectrode;

b) providing a first reactant;

c) providing an enzyme; and

d) selectively applying to one or more microelectrodes a current or potential sufficient to cause a faradaic reaction in the immediate vicinity of the one or more microelectrodes to change ionic concentration in the immediate vicinity of the one or more microelectrodes,

wherein change of the ionic concentration in the immediate vicinity of the one or more microelectrodes modulates activity of the enzyme, and

wherein the enzyme catalyzes reaction of the first reactant with the functional reactive groups.

10. The device according to claim 36, wherein the redox polymer comprises a transition metal, and wherein the transition metal is osmium, ruthenium, iron, copper or cobalt.

11. The device according to claim 36 wherein the redox polymer comprises a hydrogel.