Electrochemically active agents for pH modulation in biological buffers

Patent metadata

Field	Value
Publication number	US-10011549-B2
Application number	US-201514792553-A
Country	US
Kind code	B2
Filing date	Jul 6, 2015
Priority date	Jul 6, 2015
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

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.

First claim

What is claimed is:

1. An apparatus comprising:
an electrochemically active composition that includes a quinone derivative; and
at least one electrode, 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;
the apparatus is configured to control the at least one electrode to modulate a pH of at least a portion of the composition to predefined levels by the manipulation of the at least one electrode electrochemically reacting the quinone derivative in a targeted manner to thereby produce H + ions or OH − ions;
the quinone derivative is defined by a chemical formula selected from the group consisting of:

for chemical formulas I to XII, each R group is independently selected from the group consisting of: H, C n H 2n+1 , Cl, F, I, Br, OM, NO 2 , OH, OC n H 2n , OC n H 2n OH, O(C n H 2n O) y OH, O(C n H 2n O) y OC n H 2n+1 , O(C n H 2n O) y COOH, O(C n H 2n O) y COOM, COOH, COOM, COOC n H 2n+1 , CONHC n H 2n+1 , CON(C n H 2n+1 ) 2 , SO 3 H, SO 3 M, NH 2 , NHC n H 2n+1 , N(C n H 2n+1 ) 2 , NHC n H 2n OH, NHC n H 2n NH 2 , N(C n H 2n OH) 2 , N(C n H 2n NH) 2 , NHCOC n H 2n+1 , NC n H 2n+1 COC n H 2n+1 , NC n H 2n+1 COC n H 2n OH, NC n H 2n+1 COC n H 2n NH 2 , NC n H 2n+1 COC n H 2n SH, SH, SC n H 2n , SC n H 2n OH, S(C n H 2n O) y OH, S(C n H 2n O) y OC n H 2n+1 , S(C n H 2n O) y COOH, S(C n H 2n O) y COOM, OC n H 2n SH, O(C n H 2n O) y SH, O(C n H 2n O) y SC n H 2n+1 , C n H 2n , C n H 2n OC n H 2n , C n H 2n SC n H 2n , C n H 2n NHC n H 2n , C n H 2n N(C n H 2n+1 )C n H 2n , C n H 2n+1 , C n H 2n+1 OH, C n H 2n+1 OC n H 2n , C n H 2n+1 OC n H 2n OH, C n H 2n+1 O(C n H 2n O) y COOH, C n H 2n+1 O(C n H 2n O) y COOM, C n H 2n+1 COOH, C n H 2n+1 COOM, C n H 2n+1 COOC n H 2n+1 , C n H 2n+1 CONHC n H 2n+1 , C n H 2n+1 CONH(C n H 2n+1 ) 2 , C n H 2n+1 SO 3 H, C n H 2n+1 SO 3 M, C n H 2n+1 NH 2 , C n H 2n+1 NHC n H 2n+1 , C n H 2n+1 N(C n H 2n+1 ) 2 , C n H 2n+1 NHC n H 2n OH, C n H 2n+1 NHC n H 2n NH 2 , C n H 2n+1 N(C n H 2n OH) 2 , C n H 2n+1 N(C n H 2n NH 2 ) 2 , C n H 2n+1 NHCOC n H 2n+1 , C n H 2n+1 NC n H 2n+1 COC n H 2n OH, C n H 2n+1 NC n H 2n+1 COC n H 2n NH 2 , C n H 2n+1 NC n H 2n+1 COC n H 2n SH, C n H 2n+1 SH, C n H 2n+1 SC n H 2n , C n H 2n+1 SC n H 2n OH, C n H 2n+1 S(C n H 2n+1 O) y OH, C n H 2n+1 S(C n H 2n O) y OC n H 2n+1 , C n H 2n+1 S(C n H 2n O) y COOH, C n H 2n+1 S(C n H 2n O) y COOM, sugars, peptides, and amino acids;
at least one of the R groups is not hydrogen;
M is any metal cation or NH 4 + ;
n is an integer from 1 to 10 9 ; and
y is an integer from 1 to 10 9 .

2. The apparatus of claim 1 , wherein all of the R groups of the quinone derivative are different from each other.

3. The apparatus of claim 1 , wherein two or more of the R groups of the quinone derivative are the same.

4. The apparatus of claim 1 , wherein the reactivity between the nucleophile and the quinone derivative is reduced compared to the reactivity between the nucleophile and the unsubstituted quinone from which the quinone derivative is derived due to:
(i) increased steric hindrance of a nucleophile binding site by one or more of the R groups;
(ii) elimination of the nucleophile binding site by covalent bonding between the nucleophile binding site and one of the R groups; or
(iii) both (i) and (ii).

5. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

6. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

7. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

8. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

9. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

10. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

wherein X is C or N.

11. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

12. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

13. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

14. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

15. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

16. The apparatus of claim 1 , wherein the quinone derivative has the chemical formula:

wherein X is C or N.

17. An apparatus comprising:
an electrochemically active composition that includes:
a quinone derivative, 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; and
an additive selected from the group consisting of: an aqueous buffer, an organic solvent, an electrolyte, a buffer salt, a bioreagent, a biomolecule, a surfactant, a preservative, a cryoprotectant, and a combination of two or more thereof; and

at least one electrode, which the apparatus is configured to control to modulate a pH of at least a portion of the composition to predefined levels by the control of the at least one electrode electrochemically reacting the quinone derivative in a targeted manner to thereby produce H + ions or OH − ions.

18. The apparatus of claim 17 , wherein the composition is an aqueous solution.

19. An apparatus comprising:
an electrochemically active composition that includes a quinone derivative; and
at least one electrode, wherein:
a reactivity between (a) a nucleophile selected from the group consisting of: amines, thiols, amino acids, peptides, proteins, and a combination of two or more thereof, and (b) the quinone derivative is reduced compared to a reactivity between the nucleophile and an unsubstituted quinone from which the quinone derivative is derived; and
the apparatus is configured to control the at least one electrode to modulate a pH of at least a portion of the composition to predefined levels by

Assignees

• Bosch Gmbh Robert

Inventors

• Johnson Christopher
• Kavusi Sam
• Fomina Nadezda
• Ahmad Habib
• Maruniak Autumn
• Lang Christoph
• Raghunathan Ashwin

Classifications

• C12Q1/004

  mediator-assisted · CPC title

• C07C43/225

  containing halogen · CPC title

• G01N27/327

  Biochemical electrodes {, e.g. electrical or mechanical details for in vitro measurements} · CPC title

• C07C43/2055

  containing more than one ether bond · CPC title

• G01N27/302 Primary

  pH sensitive, e.g. quinhydron, antimony or hydrogen electrodes (ion selective electrodes G01N27/333, glass electrodes G01N27/36) · CPC title