Micro-circuit system with array of functionalized micro-electrodes

• US 6,203,758 B1
• Filed: 11/10/1997
• Issued: 03/20/2001
• Est. Priority Date: 11/10/1997
• Status: Expired due to Fees

• Current Assignee: Ben Gurion University of The Negev
• Original Assignee: Bio-Pixels, Ltd.
• Inventors: Marks, Robert, Lellouche, Jean-Paul
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): GABEL, GAILENE
• Application Number:
  US08/966,618
• Time in Patent Office: 1,226 Days
• Field of Search: 204/112, 204/22, 204/403, 204/418, 204/419, 204/434, 422/68.1, 422/101, 422/82.01, 422/82.02, 422/82.03, 250/461.1, 250/461.2, 250/687, 435/6, 435/16, 435/5, 435/7.1, 435/970, 435/973, 549/223, 427/2.11, 427/2.13, 427/455, 427/470, 436/518, 436/525, 205/687
• US Class Current: 422/68.1
• 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 2219/0059 Sequential 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 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• 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 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01J 2219/0074 Biological products
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• 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: C12Q 1/6825 : Nucleic acid detection involving sensors
• 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 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• 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
• CPC Class Codes: G01N 15/1456 : without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 2015/1488 : Methods for deciding
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: H01J 49/04 : Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
• CPC Class Codes: H01L 2924/00 : Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/0002 : Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00
• CPC Class Codes: Y10S 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte

Abstract

A micro-circuit for performing analyses of multimolecular interactions and for performing molecular syntheses, comprising: (a) a support; (b) at least one micro-electrode attached to the support, the micro-electrode being selectively electronically activated and the micro-electrode having a protective layer which is removable; (c) a binding entity for attachment to the at least one micro-electrode, the binding entity being capable of attachment to at least one micro-electrode when the protective layer has been removed; and (d) a power source being operatively connected to at least one micro-electrode for electronically activating at least one micro-electrode. The micro-circuit of the present invention also includes embodiments featuring a micro-circuit reader for detecting the interaction of the binding entity to a complementary probe, as well as methods for making and using the micro-circuit of the present invention.

Claims

1. A micro-circuit system comprising:

(a) a support;

(b) a power source;

(c) a plurality of micro-electrodes attached to said support, each of said plurality of micro-electrodes being separately selectively electronically activatable by said power source;

(d) a metallic protective layer attached to said at least one micro-electrode, said protective layer being removed upon electronic activation of each micro-electrode by said power source, such that said metallic protective layer is removed from at least one micro-electrode; and

(e) a binding entity for attachment to said at least one micro-electrode with said metallic protective layer removed, such that said binding entity only attaches to each electrode when said metallic protective layer has been removed.

2. The micro-circuit of claim 1, wherein said at least one micro-electrode comprises a material selected from the group consisting of gold, aluminum, silver, tin, copper, platinum, palladium, semiconductor materials and indium tin oxide.

3. The micro-circuit of claim 1, wherein said support comprises a material selected from the group consisting of silicon, silicon dioxide, plastic, ceramic and glass.

4. The micro-circuit of claim 1, wherein said power source is a direct current source.

5. The micro-circuit of claim 1, wherein said metallic protective layer is constructed from copper.

6. The micro-circuit of claim 5, wherein said copper is attached to said micro-electrode by a process selected from the group consisting of electrodeposition, electroless plating and vapor deposition.

7. The micro-circuit of claim 1, further comprising an orientation layer, said orientation layer being attached to said protective layer.

8. The micro-circuit of claim 7, wherein said orientation layer comprises molecules formed from a material selected from the group consisting of thiolipid and terminally silylated lipid, wherein a sulfur group of said thiolipid is attached to said protective layer or a silicon group of said terminally silyated lipid is attached to said protective layer.

9. The micro-circuit of claim 8, wherein a structure of said molecules comprises a hydrocarbon backbone substituted with at least one functional moiety selected from the group consisting of (1,3)-diyne, amide and urethane.

10. The micro-circuit of claim 9, wherein said functional moiety of said hydrocarbon backbone is capable of polymerization, such that a covalent bond is formed between at least two of said molecules.

11. The micro-circuit of claim 9, wherein said functional moiety of said hydrocarbon backbone is capable of forming a hydrogen bond, such that a non-covalent bond is formed between at least two of said molecules.

12. The micro-circuit of claim 8, wherein said molecules are polyoxymethylene substituted with a functional moiety selected from the group consisting of sulfur, disulfide, silicon, and silicon dioxide.

13. The micro-circuit of claim 1, further comprising a reservoir for holding liquid buffer such that said buffer is able to contact said at least one micro-electrode.

21. The system of claim 1, wherein said plurality of micro-electrodes includes at least a first micro-electrode and at least a second micro-electrode with said metallic protective layer being removed, said at least a first micro-electrode having a second binding entity attached thereto, and said at least a second micro-electrode having a second binding entity attached thereto, wherein said first binding entity is different from said second binding entity.

14. An system comprising:

(a) a micro-circuit comprising;

(i) a support;

(ii) a power source;

(iii) a plurality of micro-electrodes attached to said support, each of said plurality of micro-electrodes being separately selectively electronically activatable by said power source;

(iv) a metallic protective layer attached to said at least one micro-electrode, said protective layer being removed upon electronic activation of each micro-electrode by said power source, such that said metallic protective layer is removed from at least one micro-electrode; and

(v) a binding entity for attachment to said at least one micro-electrode with said metallic protective layer removed, such that said binding entity only binds to each electrode when said metallic protective layer has been removed; and

(b) a micro-circuit reader for reading said micro-circuit.

15. The system of claim 14, wherein said micro-circuit reader comprises a light source for producing light and a detector for detecting emitted light.

16. The system of claim 15, wherein said light source is selected from the group consisting of Xenon lamp, laser and monochromator.

17. The system of claim 15, wherein said detector is selected from the group consisting of photomultiplier tube, charge-coupled device camera and multianode photomultiplier tube.

18. The system of claim 15, wherein said micro-circuit reader further comprises a microlens, said microlens focusing said light produced by said light source substantially on said micro-electrode, and said microlens focusing said emitted light on said detector.

19. The system of claim 15, wherein said micro-circuit reader further comprises a beam splitter, said beam splitter permitting said light produced by said light source to reach said micro-electrode, and said beam splitter reflecting said emitted light at an angle such that said emitted light is detectable by said detector.

20. The system of claim 14, wherein said plurality of micro-electrodes includes at least a first micro-electrode and at least a second micro-electrode with said metallic protective layer being removed, said at least a first micro-electrode having a second binding entity attached thereto, and said at least a second micro-electrode having a second binding entity attached thereto, wherein said first binding entity is different from said second binding entity.