Development of boronic acid grafted random copolymer sensing fluid for continuous glucose monitoring

Abstract

We have previously presented a microelectromechanical system (MEMS) based viscometric sensor for continuous glucose monitoring using protein Concanavalin A (Con A). To address its drawbacks, including immunotoxicity and instability issues, we have synthesized stable, biocompatible copolymers poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA) for viscosity based glucose sensing. We found that PAA-ran-PAAPBA showed very high binding specificity to glucose. Several key factors such as polymer compositions, polymer molecular weights and polymer concentrations have been investigated to optimize viscometric responses. This polymer is able to detect glucose under physiological pH conditions in a reversible manner. Therefore, it has the potential to enable a highly reliable, continuous monitoring of glucose in subcutaneous tissue using the MEMS device.

Figure 1

a) Schematic illustration of the MEMS viscometric device and its sensing mechanism design. b) Synthesis route of poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA).

Figure 2

a) Viscosity responses of 15 mM glucose PBS solution to polymer 1 (2.3% of PAAPBA, from 0 to 45 mg/mL). b) Viscosity profile of polymer 2 (2.9% of PAAPBA) solutions to glucose (from 0 to 500 mM). c) Viscosity responses of different polymers (2–5 with the percentage of the PAAPBA varied from 2.9%, 4.7%, 8.7% and 0%, respectively) to various glucose concentrations. For polymer 3, the viscosity was out of the detection limit when the glucose concentration is higher than 9 mM. d) Viscosity responses of polymer 3 (44.4 mg/mL, 4.7% of PAAPBA) solutions to monosaccharides: glucose, fructose, galactose and mannose; and disaccharides: cellobiose, lactose and sucrose.

Figure 3

Viscosity response of polymer 3 (31 mg/mL) to glucose. (high points) Treatment with 28 mM of glucose. (low points) Dialysis against buffer for 12 h except the first run which was in PBS.

Scheme 1

Interaction of boronic acid and D-glucose.