Electrochemically active agents for pH modulation in biological buffers

• US 10,041,905 B2
• Filed: 04/03/2017
• Issued: 08/07/2018
• Est. Priority Date: 07/06/2015
• Status: Active Grant

• Current Assignee: Robert Bosch GmbH
• Original Assignee: Robert Bosch GmbH
• Inventors: Johnson, Christopher, Kavusi, Sam, Fomina, Nadezda, Ahmad, Habib, Maruniak, Autumn, Lang, Christoph, Raghunathan, Ashwin
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US15/477,780
• Publication Number:
  US 20170205372A1
• Time in Patent Office: 491 Days
• CPC Class Codes: C07C 37/00 Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 37/07 with simultaneous reduction of C=O group in that ring
• CPC Class Codes: C07C 39/10 Polyhydroxy benzenes; Alkylated derivatives thereof C07C39/08 takes precedence
• CPC Class Codes: C07C 39/11 Alkylated hydroxy benzenes containing also acyclically bound hydroxy groups, e.g. saligenol
• CPC Class Codes: C07C 41/01 Preparation of ethers
• CPC Class Codes: C07C 41/24 by elimination of halogens, e.g. elimination of HCl
• CPC Class Codes: C07C 41/30 by increasing the number of carbon atoms, e.g. by oligomerisation
• CPC Class Codes: C07C 43/1783 with hydroxy or -O-metal groups bound to the aromatic rings
• CPC Class Codes: C07C 43/2055 containing more than one ether bond
• CPC Class Codes: C07C 43/225 containing halogen
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07C 45/42 by hydrolysis
• CPC Class Codes: C07C 46/06 of at least one hydroxy group on a six-membered aromatic ring
• CPC Class Codes: C07C 49/82 containing hydroxy groups
• CPC Class Codes: C07C 49/84 containing ether groups, groups, groups, or groups
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: G01N 27/302 pH sensitive, e.g. quinhydron, antimony or hydrogen electrodes ion selective electrodes G01N27/333, glass electrodes G01N27/36
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3275 Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: G01N 27/4163 : checking the operation of, or calibrating, the measuring apparatus G01N27/3274, G01N27/4175 and G01N33/0006 take precedence
• CPC Class Codes: G01N 27/4167 : pH electrodes therefor G01N27/302, G01N27/36
• CPC Class Codes: G01N 33/5438 : Electrodes

Abstract

Device and methods for use in a biosensor comprising a multisite array of test sites, the device and methods being useful for modulating the binding interactions between a (biomolecular) probe or detection agent and an analyte of interest by modulating the pH or ionic gradient near the electrodes in such biosensor. An electrochemically active agent that is suitable for use in biological buffers for changing the pH of the biological buffers. Method for changing the pH of biological buffers using the electrochemically active agents. The methods of modulating the binding interactions provided in a biosensor, analytic methods for more accurately controlling and measuring the pH or ionic gradient near the electrodes in such biosensor, and analytic methods for more accurately measuring an analyte of interest in a biological sample.

Claims

1. A method comprising:

a. providing a biosensor comprising a support in an solution, wherein

i. the support comprises (I) one or more electrodes and (II) a biomolecule interface layer having one or more immobilized probes thereon; and

ii. the solution comprises a quinone derivative;

b. adding a biomolecule analyte to the solution;

c. electrochemically reacting the quinone derivative using the one or more electrodes to produce at least one of an amount of H+ ions and an amount of OH−

ions, wherein at least one of;

the pH of the solution close to the one or more electrodes is controlled by the amount of H+ ions; and

the amount of OH−

ions produced; and

d. collecting signals from the biosensor,

wherein a reactivity between a nucleophile and the quinone derivative is reduced compared to a reactivity between the nucleophile and an unsubstituted quinone from which the quinone derivative is derived.

2. The method of claim 1, wherein:

the quinone derivative is defined by a chemical formula selected from the group consisting of;

3. The method of claim 1, wherein the solution contains one or more nucleophiles.

4. The method of claim 3, wherein the one or more nucleophiles are selected from the group consisting of:

amines, thiols, amino acids, peptides, proteins, and combinations thereof.

5. The method of claim 1, wherein the solution contains a reduced quinone derivative and electrochemically reacting the quinone derivative results in an electrochemical oxidation reaction of the reduced quinone derivative to make the pH of the solution more acidic.

6. The method of claim 5, wherein the concentration (C) of the reduced quinone derivative is 0 M<

C<

1 M.

7. The method of claim 1, wherein the solution contains an oxidized quinone derivative and electrochemically reacting the quinone derivative results in an electrochemical reduction reaction of the oxidized quinone derivative to make the pH of the solution more basic.

8. The method of claim 7, wherein the concentration (C) of the oxidized quinone derivative is 0 M<

C<

1 M.

9. The method of claim 1, wherein the solution contains one or more buffer components provided in a concentration (C) that is 0 M<

C<

1 M.

10. The method of claim 9, wherein the one or more buffer components are selected from the group consisting of:

organic solvents, electrolytes, bioreagents, biomolecules, surfactants, and combinations thereof.

11. The method of claim 1, further comprising measuring the pH of the solution and optionally continuously measuring the pH.

12. The method of claim 1, wherein the quinone derivative is electrochemically reacted by providing an amount of electric current.

13. The method of claim 12, wherein the pH is measured before providing the amount of electric current.

14. The method of claim 13, wherein the amount of electric current is selected based on the measured pH.