Methods and devices for carrying out chemical reactions

• US 6,251,595 B1
• Filed: 06/18/1998
• Issued: 06/26/2001
• Est. Priority Date: 06/18/1998
• Status: Expired due to Term

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Gordon, Gary B., Dellinger, Douglas J.
• Primary Examiner(s): Venkat, Jyothsna
• Assistant Examiner(s): BAKER, MAURIE GARCIA
• Application Number:
  US09/100,152
• Time in Patent Office: 1,104 Days
• Field of Search: 422/68.1, 422/50, 422/131, 422/186, 204/400, 435/6, 435/7.1, 435/91.1, 436/501, 436/518, 436/149, 436/525, 427/2.13
• US Class Current: 506/40
• 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 2219/00565 Electromagnetic means
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00653 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 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• 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: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G11C 13/0014 comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 : comprising bio-molecules

Abstract

Methods and devices are disclosed for carrying out multiple chemical reactions. A plurality of electrodes supported by a semiconductor substrate is brought into proximity with a reaction medium, which comprises reagents for carrying out the chemical reactions. An item of numerical data is sent to storage means in each of a plurality of cells within the semiconductor substrate by means of a data bus. The item of numerical data is representative of an electric signal. An address is sent to address decoders in communication with the storage means. As a result, the item of numerical data is stored in the storage means. Electric signals are selectively applied to each of the electrodes by means of a plurality of digital analog converters, each electrically coupled to a respective electrode. Each of the digital analog converters is associated with a respective cell. In this way, a chemical reaction takes place proximal to and in response to the field at the electrodes to which the electric signals are selectively applied. A particular feature of the present invention is that the medium may be non-aqueous.

Claims

1. A method for carrying out multiple chemical reactions, said method comprising:

(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium, said reaction medium comprising reagents for carrying out said chemical reactions,

(b) sending an item of numerical data to storage means in each of a plurality of cells within said semiconductor substrate by means of a data bus, said item of numerical data participating in the selection of a voltage to be applied to said electrodes, and

(c) sending an address to address decoders in communication with said storage means, whereby said item of numerical data is stored in said storage means and electric signals are selectively applied to each of said electrodes by means of a plurality of digital analog converters, each electrically coupled to a respective electrode and each being present on said semiconductor substrate and associated with a respective cell and whereby a chemical reaction takes place proximal to and in response to the field at said electrodes to which said electric signals are selectively applied.

2. The method of claim 1 wherein said item of numerical data is binary numerical data.

3. The method of claim 1 wherein said item of numerical data is one bit in length and wherein said digital analog converters are integral with said storage means.

4. The method of claim 1 wherein an insulative layer covers said plurality of electrodes.

5. The method of claim 4 wherein said insulative layer is removable from said semiconductor substrate.

6. The method of claim 1 wherein said reagents are responsive to electric fields.

7. The method of claim 1 wherein said reagents are reagents for carrying out synthesis of polynucleotides.

8. The method of claim 5 wherein said reagents are nucleoside phosphoramidites or nucleoside phosphonates.

9. The method of claim 1 wherein an array of oligonucleotides is synthesized on a surface of said semiconductor substrate.

10. The method of claim 9 wherein from about 10² to about 10⁸ different oligonucleotides are synthesized, each in an area of from about 2 micron by 2 micron to about 500 by 500 micron.

11. The method of claim 9 wherein said oligonucleotides are about 10 to 30 nucleotides in length.

12. The method of claim 1 wherein said chemical reaction comprises selectively generating a reactive species at said electrodes.

13. The method of claim 1 wherein said chemical reaction comprises deprotecting a molecule at said electrode.

14. The method of claim 1 wherein said medium is a non-aqueous medium.

15. The method of claim 1 wherein said item of numerical data is representative of an electric signal.

16. A method for carrying out multiple chemical reactions, said method comprising:

(a) bringing a device into proximity with a reaction medium, said reaction medium comprising reagents for carrying out said chemical reactions, said device comprising (i) a semiconductor substrate, (ii) a plurality of electrodes supported by said semiconductor substrate, (iii) a plurality of cells within said semiconductor substrate, (iv) a plurality of digital analog converters, each electrically coupled to a respective electrode and each being present on said semiconductor substrate and associated with a respective cell, (v) address decoders in communication with each of said cells, (vi) a data bus for delivering binary numerical data to each of said cells, (vii) address buses for delivering addresses to said address decoders, and (viii) storage means in each of said cells for storing said numerical data, said storage means being in communication with said digital analog converter in said cell,

(b) sending binary numerical data to said storage means of each of said cells by means of said data bus, said binary numerical data being representative of an electric signal, and

(c) sending addresses to said address decoders whereby said binary numerical data is stored in said storage means and electric signals are selectively applied to each of said electrodes by means of said digital analog converters and a chemical reaction takes place proximal to and in response to the field at said electrodes.

17. The method of claim 16 wherein said reagents are reagents for carrying out synthesis of oligonucleotides.

18. A device comprising:

(a) a semiconductor substrate,

(b) at least one surface for carrying out chemical reactions,

(c) a plurality of electrodes supported by said semiconductor substrate,

(d) a plurality of cells within said semiconductor substrate,

(e) a plurality of digital analog converters, each electrically coupled to a respective electrode and each being present on said semiconductor substrate and associated with a respective cell,

(f) address decoders in communication with each of said cells,

(g) a data bus for delivering an item of numerical data to each of said cells,

(h) address buses for delivering addresses to said address decoders, and

(i) storage means in each of said cells for storing said item of numerical data, said storage means being in communication with said digital analog converter in said cell.

19. The device of claim 18 wherein said data bus is for delivering binary numerical data.

20. The device of claim 18 further comprising an insulative layer covering said device at least at said plurality of electrodes.

21. The device of claim 18 wherein said insulative layer is removable.

22. The device of claim 18 comprising from about 10² to about 10⁸ different cells, each in an area of from about 2 micron by 2 micron to about 500 by 500 micron.

23. The device of claim 18 further comprising means to electrically test the device before use.

24. A chip for electronically addressing a matrix of sites, each site to which may be directed a chemical reaction;

said chip comprising;

(a) a semiconductor substrate;

(b) a matrix of electronic circuit cells fabricated within said semiconductor substrate,

(c) address decoders for activating a cell in response to an address applied to said chip;

(d) a data bus for delivering binary numerical data to said cells;

(e) storage means in each of said cells for storing binary numerical data from the data bus when activated by addresses decoded by said address decoders,

(f) digital to-analog conversion means in each cell for converting binary numerical data into an electrical signal;

(g) an electrode plate connected to each of said digital-to-analog conversion means, wherein electrical signals representative of said binary numerical data are selectively applied to each of said electrode plates for the purpose of inducing, when the device is placed proximal to a chemical medium, selective chemical activity according to the binary numerical data provided.

25. A method for carrying out multiple chemical reactions, said method comprising:

(a) bringing a plurality of electrodes supported by a semiconductor substrate into proximity with a reaction medium, said reaction medium comprising reagents for carrying out said chemical reactions,

(b) sending an item of numerical data to storage means in each of a plurality of cells within said semiconductor substrate by means of a data bus, said item of numerical data being representative of an electric signal, and

(c) sending an address to address decoders in communication with said storage means, whereby said item of numerical data is stored in said storage means and electric signals are selectively applied to each of said electrodes by means of a plurality of digital analog converters, each electrically coupled to a respective electrode and each being present on said semiconductor substrate and associated with a respective cell, and whereby a chemical moiety proximal to said electrode is selectively activated for reaction with a reagent in said reaction medium, said selective activation being in response to the field at said electrodes to which said electric signals are selectively applied.

26. The method of claim 25 wherein said chemical moiety is a reagent for oligonucleotide synthesis.