Minimally Invasive Glucose Monitoring Using a Highly Porous Gold Microneedles-Based Biosensor: Characterization and Application in Artificial Interstitial Fluid

Paolo Bollella,Sanjiv Sharma,Riccarda Antiochia,Federico Tasca,Anthony E G Cass

doi:10.3390/catal9070580

Abstract

In this paper, we present the first highly porous gold (h-PG) microneedles-based second-generation biosensor for minimally invasive monitoring of glucose in artificial interstitial fluid (ISF). A highly porous microneedles-based electrode was prepared by a simple electrochemical self-templating method that involves two steps, gold electrodeposition and hydrogen bubbling at the electrode, which were realized by applying a potential of −2 V versus a saturated calomel electrode (SCE). The highly porous gold surface of the microneedles was modified by immobilization of 6-(ferrocenyl)hexanethiol (FcSH) as a redox mediator and subsequently by immobilization of a flavin adenine dinucleotide glucose dehydrogenase (FAD-GDH) enzyme using a drop-casting method. The microneedles-based FcSH/FAD-GDH biosensor allows for the detection of glucose in artificial interstitial fluid with an extended linear range (0.1–10 mM), high sensitivity (50.86 µA cm−2 mM−1), stability (20% signal loss after 30 days), selectivity (only ascorbic acid showed a response about 10% of glucose signal), and a short response time (3 s). These properties were favourably compared to other microneedles-based glucose biosensors reported in the literature. Finally, the microneedle-arrays-based second-generation biosensor for glucose detection was tested in artificial interstitial fluid opportunely spiked with different concentrations of glucose (simulating healthy physiological conditions while fasting and after lunch) and by placing the electrode into a simulated chitosan/agarose hydrogel skin model embedded in the artificial ISF (continuous glucose monitoring). The obtained current signals had a lag-time of about 2 min compared to the experiments in solution, but they fit perfectly into the linearity range of the biosensor (0.1–10 mM). These promising results show that the proposed h-PG microneedles-based sensor could be used as a wearable, disposable, user-friendly, and automated diagnostic tool for diabetes patients.

Highlights

Optimal diabetes management requires accurate real-time monitoring of glucose
We described the fabrication and characterization of a novel glucose biosensor based on microneedles technology
The novelty of the work consists in the realization of a highly porous gold (h-PG) gold microneedles electrode and in the use of the mediator 6-(ferrocenyl)hexanethiol, realizing a second-generation biosensor with improved performance in terms of linear range, sensitivity, and selectivity

Summary

Introduction

Optimal diabetes management requires accurate real-time monitoring of glucose. People with diabetes have to test their blood sugar level several times every day to know how different foods, medications, and activities may affect it [1,2]. The normal blood glucose level (tested while fasting) for non-diabetics should be between 3.9 and 7.1 mmol/L (70–130 mg/dL). The common method for monitoring glucose concentrations involves sampling of a small amount of blood, usually from a fingertip, using a lancet that lightly pricks the skin, with discomfort for the patient, especially in children or elderly people. Several commercial glucose meters based on amperometric electrochemical technology have been realized to help patients manage blood glucose routine testing; they provide just a single glucose reading and require repeated finger pricks [3,4]

Methods

Discussion

Conclusion