A Noninvasive Sweat Glucose Biosensor Based on Glucose Oxidase/Multiwalled Carbon Nanotubes/Ferrocene-Polyaniline Film/Cu Electrodes

Abstract

Diabetes remains a great threat to human beings’ health and its world prevalence is projected to reach 9.9% by 2045. At present, the detection methods used are often invasive, cumbersome and time-consuming, thus increasing the burden on patients. In this paper, we propose a novel noninvasive and low-cost biosensor capable of detecting glucose in human sweat using enzyme-based electrodes for point-of-care uses. Specifically, an electrochemical method is applied for detection and the electrodes are covered with multilayered films including ferrocene-polyaniline (F-P), multi-walled carbon nanotubes (MWCNTs) and glucose oxidase (GOx) on Cu substrates (GOx/MWCNTs/F-P/Cu). The coated layers enhance the immobilization of GOx, increase the conductivity of the anode and improve the electrochemical properties of the electrode. Compared with the Cu electrode and the F-P/Cu electrode, a maximum peak current is obtained when the MWCNTs/F-P/Cu electrode is applied. We also study its current response by cyclic voltammetry (CV) at different concentrations (0–2.0 mM) of glucose solution. The best current response is obtained at 0.25 V using chronoamperometry. The effective working lifetime of an electrode is up to 8 days. Finally, to demonstrate the capability of the electrode, a portable, miniaturized and integrated detection device based on the GOx/MWCNTs/F-P/Cu electrode is developed. The results exhibit a short response time of 5 s and a correlation coefficient R2 of 0.9847 between the response current of sweat with blood glucose concentration. The LOD is of 0.081 mM and the reproducibility achieved in terms of RSD is 3.55%. The sweat glucose sensor is noninvasive and point-of-care, which shows great development potential in the health examination and monitoring field.

Review of Noninvasive Continuous Glucose Monitoring in Diabetics

“…Sweat contains a variety of blood-related substances that can reveal the human metabolic status. Among them, glucose concentration in sweat is considered to be a significant indicator of blood glucose concentration . Based on the transport of glucose in the systemic circulation and sweat, La Count and colleagues established a computational model that related sweat to blood glucose levels, and this algorithm accurately predicted blood glucose levels from that in sweat.…”

“…A variety of sweat sensors based on nanocomposite materials have been developed at present, most of which were based on electrochemical methods, such as ion electrophoresis (Figure 1v) 51,52 and glucose sensing electrodes. 20,53,54 The forearm, front chest, or back were typically selected for CGM, while attaching the sensor electrode to the smartwatch was considered to be a convenient and feasible solution. 55,56 Smart intimate textiles 57 and tattoos 52,58 had also been proposed for glucose monitoring.…”

“…According to microcurrent meter data, the sensor could detect samples with concentrations ranging from 0 to 14 mM, enabling instant, accurate, and noninvasive glucose monitoring. 20 Using NEXAR as a biosensor for the first time, Noura and colleagues constructed a highly selective electrochemical device with a detection range of 0−2 mM, a sensitivity of 16.8 μA/(mM• cm 2 ), and a specific response to glucose occurring within seconds (Figure 6ii). 61 Lin and colleagues constructed a sweat glucose sensor based on a PB−PEDOT NC electrode with a linear range of 6.25 μM to 0.8 mM and a detection limit of 4 μM.…”

“…Among them, glucose concentration in sweat is considered to be a significant indicator of blood glucose concentration. 20 Based on the transport of glucose in the systemic circulation and sweat, La Count and colleagues established a computational model 50 that related sweat to blood glucose levels, and this algorithm accurately predicted blood glucose levels from that in sweat. A variety of sweat sensors based on nanocomposite materials have been developed at present, most of which were based on electrochemical methods, such as ion electrophoresis (Figure 1v) 51,52 and glucose sensing electrodes.…”

“…It is essential to continuously monitor and regulate blood glucose. Noninvasive techniques include optical methods based on near-infrared (NIR) and Raman spectroscopy, , and nonoptical methods based on electrochemical sensors. , The key to noninvasive glucose monitoring is to explore biomaterials, such as saliva, sweat, and interstitial fluid (ISF), which glucose levels are closely related to blood. , In comparison to blood, these monitoring samples are easier to collect and will not hurt patients during the procedure and can be obtained whenever needed for a long time, ensuring the continuity of blood glucose monitoring. Using noninvasive devices to gather bodily fluids not only allows for painless monitoring and simple operation but also improves patient satisfaction and compliance, which is of great significance for CGM.…”