[Paper Review] Non-Enzymatic Graphene-Based Biosensors for Continuous Glucose Monitoring

Mohamed Serry, Mahmoud A.S. Sakr|arXiv (Cornell University)|Sep 4, 2015

Electrochemical sensors and biosensors46 references3 citations

TL;DR

This paper presents a mediator-free, non-enzymatic graphene-Schottky junction biosensor for continuous glucose monitoring, leveraging interfacial band interactions to enable sensitive, stable, and interference-resistant glucose detection. It achieves a linear response from 0 to 15 mmol/L with a 0.5 mmol/L detection limit, offering a robust alternative to enzyme-based systems plagued by drift and instability.

ABSTRACT

A novel mediator-free, non-enzymatic electrochemical sensor, based on a graphene-Schottky junction, was fabricated for glucose detection. The sensor offers a promising alternative to the conventional enzyme-catalyzed electrochemical continuous glucose monitoring systems (CGM), as it overcomes many of the drawbacks attributed to the enzymatic nature; namely, irreversibility, drift, and interference with body fluids, which affect their accuracy, reliability and longevity. Enhanced performance of the sensors is demonstrated through the band interaction at the graphene-Schottky junction, which yields stronger forward/reverse currents in response to 50 μL glucose drop. Under optimized conditions, the linear response of the sensor to glucose concentration was valid in the range from 0 to 15 mmol/L with a detection limit of 0.5 mmol/L. The results indicated that the proposed sensor provided a highly sensitive, more facile method with good reproducibility for continuous glucose detection.

Motivation & Objective

• To develop a stable, enzyme-free glucose sensor for continuous monitoring that overcomes limitations of conventional enzymatic systems.
• To eliminate reliance on glucose oxidase by using a graphene-Schottky junction for direct electron transfer.
• To improve sensor longevity, accuracy, and resistance to interference from biological fluids.
• To achieve high sensitivity and reproducibility in physiological glucose concentration ranges.
• To demonstrate a mediator-free electrochemical detection mechanism based on interfacial band interactions.

Proposed method

• Fabrication of a graphene-Schottky junction using a graphene layer deposited on a semiconductor substrate to form a heterojunction.
• Utilization of interfacial band alignment at the graphene-semiconductor junction to modulate charge transfer in response to glucose.
• Employment of cyclic voltammetry and chronoamperometry to measure forward and reverse current responses to glucose exposure.
• Application of a 50 µL glucose drop to assess real-time electrochemical response under optimized conditions.
• Use of linear sweep voltammetry to evaluate sensor response across varying glucose concentrations (0–15 mmol/L).
• Evaluation of detection limit and reproducibility through repeated measurements under controlled conditions.

Experimental results

Research questions

• RQ1 Can a non-enzymatic graphene-Schottky junction sensor achieve reliable and sensitive glucose detection without mediators or enzymes?
• RQ2 How does the interfacial band interaction at the graphene-semiconductor junction enhance electron transfer for glucose sensing?
• RQ3 What is the linear dynamic range and limit of detection for this sensor in physiological conditions?
• RQ4 How does the sensor performance compare to conventional enzyme-based continuous glucose monitors in terms of stability and interference resistance?
• RQ5 To what extent does the sensor maintain reproducibility across repeated measurements?

Key findings

• The sensor exhibited a linear response to glucose concentration over the range of 0 to 15 mmol/L, demonstrating suitability for clinical monitoring.
• A detection limit of 0.5 mmol/L was achieved, indicating high sensitivity for physiological glucose levels.
• The graphene-Schottky junction generated stronger forward and reverse currents upon glucose exposure, confirming effective charge transfer modulation.
• The sensor showed good reproducibility, indicating consistent performance across repeated measurements.
• The mediator-free design eliminated the need for enzymes, reducing issues related to denaturation, drift, and interference from biological fluids.
• The band interaction at the heterojunction interface was critical for enhancing sensitivity and enabling direct electrochemical detection.