Osmolarity-responsive hydrogel sensors and method of use

Patent metadata

Field	Value
Publication number	US-9976974-B2
Application number	US-201615006496-A
Country	US
Kind code	B2
Filing date	Jan 26, 2016
Priority date	Jan 27, 2015
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

Osmolarity-responsive hydrogel sensors, particularly biosensors, containing quaternary ammonium functionality, which are useful for, inter alia, continuous osmolarity monitoring with no pH interference, are disclosed. Methods of using the osmolarity-responsive hydrogels are also disclosed.

First claim

What is claimed is:

1. A sensor, comprising:
a hydrogel that is sensitive to changes in osmolarity and substantially insensitive to changes in pH, comprising:
a hydrated, crosslinked copolymer comprising residues of the formula:

wherein:
n is at least 1,000;
Y is —(C═O)—Z or
Y is

Z is —NR 1 R 2 or —OR 7 ;
each of R 1 and R 2 is independently H, (C 1 -C 6 )alkyl, benzyl, residue derived from —(C 1 -C 6 )alkylenyl-NH—C═O—CH═CH 2 or a quaternary ammonium-substituted linker group and counteranion; and
optionally, wherein at least a portion of said R 1 or said R 2 in said copolymer are said residues derived from —(C 1 -C 6 )alkylenyl-NH—C═O—CH═CH 2 ;
at least one of a portion of said R 1 , said R 2 , or said R 7 in said copolymer are said quaternary ammonium-substituted linker group and counteranion;
each R 3 is independently H or (C 1 -C 6 )alkyl;
each R 4 , R 5 , and R 6 is independently (C 1 -C 6 )alkyl;
each R 7 is independently (C 1 -C 6 )alkyl, benzyl, or said quaternary ammonium-substituted linker group and counteranion; and
each R 11 is independently H or (C 1 -C 4 )alkyl; and

a transducer associated with said hydrogel to convert a change in a physical quantity or a chemical quantity associated with said hydrogel to an electrical signal.

2. The sensor of claim 1 , wherein said copolymer further comprises:
at least one residue of:
hydroxy(C 1 -C 6 )alkyl(meth)acrylate;
(meth)acrylic acid;
alkyl ethers;
vinyl ether;
vinyl pyrrolidone;
styrene copolymerized with allyl alcohol;
4-vinylphenol;
vinyl acetate;
ethylene copolymerized with vinyl acetate;
a zwitterionic monomer; or
a fully-neutralized sodium acrylate monomer.

3. The sensor of claim 1 ,
wherein said —(C 1 -C 6 )alkylenyl-NH—C═O—CH═CH 2 is -methylenyl-NH—C═O—CH═CH 2 .

4. The sensor of claim 1 ,
wherein said quaternary ammonium-substituted linker group is a quaternary ammonium-substituted (C 1 -C 6 )alkyl.

5. The sensor of claim 4 ,
wherein said quaternary ammonium-substituted C 1 -C 6 alkyl is trimethyl ammonium n-propylenyl.

6. The sensor of claim 1 ,
wherein Y is —C 6 H 4 CH 2 N + (CH 3 ) 3 CI − .

7. The sensor of claim 1 ,
wherein said copolymer is formed from a reaction of an acrylamide, a quaternary ammonium-functionalized monomer, and optionally N,N-methylene-bisacrylamide;
wherein said quaternary ammonium-substituted linker group is 3-acrylaminopropyl)trimethylammonium chloride, quaternary ammonium-substituted (meth)acrylate, or (ar-vinylbenzyl)trimethyl ammonium chloride.

8. The sensor of claim 1 ,
wherein said copolymer comprises the reaction product of:
75 mole % to 95 mole % of acrylamide;
6 mole % to 15 mole % of 3-acrylaminopropyl)trimethylammonium chloride or (ar-vinylbenzyl)trimethyl ammonium chloride; and
0.5 mole % to 10 mole % of N,N-methylene-bisacrylamide.

9. The sensor of claim 1 ,
wherein said copolymer comprises the reaction product of:
78 mole % to 92 mole % of acrylamide;
7 mole % to 12 mole % of 3-acrylaminopropyl)trimethylammonium chloride or (ar-vinylbenzyl)trimethyl ammonium chloride; and
1 mole % to 5 mole % of N,N-methylene-bisacrylamide.

10. The sensor of claim 1 ,
wherein said copolymer comprises the reaction product of:
87 mole % to 89 mole % of acrylamide;
9 mole % to 11 mole % of 3-acrylaminopropyl)trimethylammonium chloride or (ar-vinylbenzyl)trimethyl ammonium chloride; and
2 mole % to 4 mole % of N,N-methylene-bisacrylamide.

11. The sensor of claim 1 ,
wherein said counteranion is an anion selected from the group consisting of a halide and methyl sulfate.

12. The sensor of claim 1 ,
wherein said counteranion is a fluoride ion, a chloride ion, or an iodide ion.

13. The sensor of claim 1 , further comprising:
a plurality of magnetic particles associated with said hydrogel.

14. The sensor of claim 1 ,
wherein said hydrogel is contained in a chamber of a fixed volume.

15. The sensor of claim 1 ,
wherein said transducer is a pressure transducer, a magnetic sensor, an optical sensor, an electrical sensor, or a viscoelastic sensor.

16. The sensor of claim 1 ,
wherein said sensor is a single-use sensor.

17. The sensor of claim 1 , further comprising:
a signal transmitter for transmitting said electrical signal to a controller.

18. The sensor of claim 17 ,
wherein said signal transmitter is reusable.

19. The sensor of claim 17 ,
wherein said signal transmitter is wireless.

20. A sensor system, comprising:
an array of sensors, the array of sensors comprising the sensor of claim 1 ; and
a signal transmitter for transmitting said electrical signal to a controller.

21. The sensor system of claim 20 ,
wherein said array of sensors is prepared by inkjet printing.

22. A method of measuring osmolarity of a fluid, comprising:
contacting the sensor of claim 1 with said fluid;
measuring a value of a physical change in said hydrogel; and
converting said value to an electrical signal;
wherein said physical change is a change in volume, a change in magnetic field, or a change in an optical property.

Assignees

• Univ Utah Res Found

Inventors

• Nguyen Tram
• Magda Jules John
• Cho Seung-Hei
• Tathireddy Prashant

Classifications

• G01N33/48785

  Electrical and electronic details of measuring devices for physical analysis of liquid biological material not specific to a particular test method, e.g. user interface or power supply · CPC title

• H01R13/533

  Bases, cases made for use in extreme conditions, e.g. high temperature, radiation, vibration, corrosive environment, pressure (H01R13/52 takes precedence) · CPC title

• G01N27/045 Primary

  Circuits (measuring resistance per se G01R27/00, e.g. G01R27/22) · CPC title

• G01N13/04

  Investigating osmotic effects · CPC title

• G01N33/48707 Primary

  by electrical means (G01N33/49, G01N33/493 take precedence) · CPC title