Biomolecular attachment sites on microelectronic arrays and methods thereof

• US 8,288,155 B2
• Filed: 07/13/2007
• Issued: 10/16/2012
• Est. Priority Date: 09/30/1999
• Status: Expired due to Term

• Current Assignee: Ador Diagnostics S.R.L.
• Original Assignee: Gamida for Life B.V.
• Inventors: Havens, John R., Onofrey, Thomas J., Greef, Charles H., Kevorkian, Gregory J., Krotz, Jain, Lykstad, Kristie L., Raymond, Daniel E., Reese, Howard R., Rooney, Regina, Scott, John J.
• Primary Examiner(s): Yu, Melanie J
• Application Number:
  US11/777,919
• Publication Number:
  US 20090069198A1
• Time in Patent Office: 1,922 Days
• Field of Search: 435/287.2, 435/283.1, 435/7.1, 436/518, 436/807
• US Class Current: 435/287.2
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00635 by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00639 the compounds being trapped in or bound to a porous medium
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• 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 2219/0072 Organic compounds
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07C 319/02 of thiols
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• 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 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• 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: G01N 33/54353 : with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/545 : Synthetic resin

Abstract

Methods of addressing a biomolecule to a selectively addressable electrode are described. A permeation layer overlying a plurality of selectively addressable electrodes is provided. The permeation layer includes a reactive group that is adapted to bond to a biomolecule and that requires activation through a chemical transformation before bonding to the biomolecule. At least one selectively addressable electrode is biased such that a pH change occurs in an overlying solution of the at least one selectively addressable electrode. The reactive group in a portion of the permeation layer above the at least one selectively addressable electrode is then chemically transformed to an activated reactive group as a result of the pH change. A biomolecule is then bound to the permeation layer overlying the at least one selectively addressable electrode through the activated reactive group.

Claims

1. A method of addressing a biomolecule to a selectively addressable electrode, comprising the steps of:

providing a permeation layer overlying a plurality of selectively addressable electrodes, the permeation layer comprising a reactive group adapted to bond to a biomolecule, wherein the reactive group requires activation through a chemical transformation before bonding to the biomolecule;

biasing at least one selectively addressable electrode such that a pH change occurs in an overlying solution of the at least one selectively addressable electrode, wherein the reactive group in a portion of the permeation layer above the at least one selectively addressable electrode is chemically transformed to an activated reactive group as a result of the pH change; and

binding a biomolecule to the permeation layer overlying the at least one selectively addressable electrode through the activated reactive group.

2. The method of claim 1, wherein the reactive group is an acid labile group.

3. The method of claim 2, wherein the acid labile group is selected from the group consisting of imines, TBOC, FMOC, trityl, trifluoroacetamide, and esters.

4. The method of claim 2, wherein the reactive group is a thiol ester.

5. The method of claim 2, wherein the reactive group is a ketal.

6. The method of claim 1, wherein the biomolecule is covalently attached to the reactive group.

7. The method of claim 1, wherein the biomolecule is a nucleic acid.

8. The method of claim 1, wherein the biomolecule is selected from the group consisting of proteins, peptides, enzymes, and antibodies.