Multiplexed active biologic array

• US 7,150,997 B2
• Filed: 03/15/2005
• Issued: 12/19/2006
• Est. Priority Date: 07/09/1996
• Status: Expired due to Fees

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Nanogen, Inc.
• Inventors: Kovacs, Gregory T. A.
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US11/081,123
• Publication Number:
  US 20050155863A1
• Time in Patent Office: 644 Days
• Field of Search: 422/68.1, 422 8201- 8203, 422/82.05, 204412-413, 436/73, 436/79, 436 86- 90, 436 93- 95, 436106-113, 436/164, 436127-132, 436149-151, 436/172, 436/501, 436/503, 436/508, 436512-513, 436/518, 436/527
• US Class Current: 436/149
• 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 2219/00527 Sheets
• 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 2219/00621 by physical means, e.g. trenches, raised areas
• 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 2219/00722 Nucleotides
• CPC Class Codes: G01N 27/27 Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/17 Nitrogen containing
• CPC Class Codes: Y10T 436/170769 N-Nitroso containing [e.g., nitrosamine, etc.]
• CPC Class Codes: Y10T 436/171538 : Urea or blood urea nitrogen
• CPC Class Codes: Y10T 436/173845 : Amine and quaternary ammonium
• CPC Class Codes: Y10T 436/20 : Oxygen containing
• CPC Class Codes: Y10T 436/200833 : Carbonyl, ether, aldehyde or ketone containing
• CPC Class Codes: Y10T 436/203332 : Hydroxyl containing

Abstract

A method of addressing and driving an electrode array includes the step of addressing one or more electrodes within the array using a plurality of row and column lines. In one aspect of the method, a value corresponding to a voltage is stored in a local memory associated with each electrode. The addressed electrodes are then driven at the voltages corresponding to the stored values. In another aspect of the method, a driving element associated with each addressed electrode is selectively coupled with a voltage line so as to charge the electrode with the voltage on the voltage line. The device and methods may be used in the synthesis of biopolymers such as oligonucleotides and peptides.

Claims

1. A method of addressing and driving a biologic electrode array comprising the steps of:

providing a chip having an array of electrodes formed on a thermally-isolated membrane having at least one controllable heating element, each electrode being associated with a local memory;

addressing one or more electrodes within the array using a plurality of row and column lines, wherein each addressable electrode is connectable to a single row line and a single column line;

storing a value in the local memory of each addressed electrode representative of a voltage that is to be applied to each addressed electrode; and

driving the addressed electrodes at the voltage corresponding to the stored values.

2. The method of claim 1 wherein the local memory stores a binary value representing a voltage to be applied to the addressed electrode.

3. The method of claim 1 wherein the addressing step is performed using a row decoder and a column decoder.

4. The method of claim 1 wherein the local memory is an EEPROM.

5. A method of addressing and driving a biologic electrode array comprising the steps of:

providing a chip having an array of electrodes formed on a thermally-isolated membrane having at least one controllable heating element, each electrode being associated with a driving element;

addressing one or more electrodes within the array using a plurality of row and column lines, wherein each addressable electrode is connectable to a single row line and a single column line;

selectively coupling the driving element of the one or more addressed electrodes with a voltage line so as to charge the addressed electrode with the voltage on the voltage line.

6. The method of claim 5 wherein the voltage applied to the voltage line is changed between different voltages.

7. A method of carrying out biological reactions on a biologic electrode array comprising the steps of:

providing a chip having an array of electrodes formed on a thermally-isolated membrane having at least one controllable heating element, each electrode being associated with a local memory;

providing a reaction medium including reactants within close proximity of the array of electrodes;

addressing one or more electrodes within the array using a plurality of row and column lines, wherein each addressable electrode is connectable to a single row line and a single column line;

storing a value in the local memory of each addressed electrode representative of a voltage that is to be applied to each addressed electrode;

driving the one or more addressed electrodes at the voltage corresponding to the stored values, whereby the electrical field created at the one or more electrodes is used to react the reactants contained in the reaction medium at a location adjacent to the electrode; and

cycling the temperature of at least one controllable heating element.

8. The method according to claim 7 wherein the reactants are nucleic acids.

9. The method according to claim 8 wherein the reaction synthesizes oligonucleotides.

10. The method according to claim 9 wherein an array of oligonucleotides is synthesized proximal to a surface of the chip containing the array of electrodes.

11. The method according to claim 7 wherein the reactants are amino acids.

12. The method according to claim 11 wherein the reaction synthesizes peptides.

13. The method according to claim 7 wherein the reaction comprises deprotecting a reactant disposed proximal to the charged electrode.

14. The method according to claim 7 wherein the one or more electrodes are positively charged so as to hydrolyze water.

15. A method of carrying out biological reactions on a biologic electrode array comprising the steps of:

providing a chip having an array of electrodes formed on a thermally-isolated membrane having at least one controllable heating element, each electrode being associated with a driving element;

providing a reaction medium including reactants within close proximity of the array of electrodes;

addressing one or more electrodes within the array using a plurality of row and column lines, wherein each addressable electrode is connectable to a single row line and a single column line;

selectively coupling the driving element of the one or more addressed electrodes with a voltage line so as to charge the addressed electrode with the voltage on the voltage line, whereby the electrical field created at the one or more electrodes is used to react the reactants contained in the reaction medium at a location adjacent to the electrode; and

cycling the temperature of at least one controllable heating element.

16. The method according to claim 15 wherein the reactants are nucleic acids.

17. The method according to claim 16 wherein the biological reaction synthesizes oligonucleotides.

18. The method according to claim 17 wherein an array of oligonucleotides is synthesized proximal to a surface of the chip containing the array of electrodes.

19. The method according to claim 15 wherein the reactants are amino acids.

20. The method according to claim 19 wherein the reaction synthesizes peptides.

21. The method according to claim 15 wherein the biological reaction comprises deprotecting a reactant disposed proximal to the charged electrode.

22. The method according to claim 15 wherein the one or more electrodes are positively charged so as to hydrolyze water.

23. An biologic electrode array comprising:

a semiconductor substrate having at least one controllable heating element;

a matrix of electrode sites disposed on the semiconductor substrate;

a local memory coupled to each electrode site;

row and column decoders for addressing the electrode sites using a plurality of row and column lines;

a data line for delivering to the local memory a value indicative of a characteristic of an electrical stimulus to be applied at the electrode site; and

a driving element located at each electrode site, the driving element delivering the electrical stimulus to each electrode site in response to the stored value in the local memory.

24. The device of claim 23 wherein the electrical stimulus is a voltage.

25. The device of claim 23 wherein the row and column decoders are disposed on the semiconductor substrate.

26. The device of claim 23 wherein at least a portion of the array is formed using CMOS fabrication techniques.

27. The device of claim 23 further comprising a permeation layer disposed over the matrix of electrode sites.

28. The device of claim 23 wherein the data line delivers a binary value to the local memory.