Synthesis of a Ni–TiO2 Nanocomposite as an Enzyme–Less, Amperometric Sensor for Glucose Sensing & Monitoring
Authors: de los Rios Juan Pablo , Galvan Vicente , de los Rios Juan 
Published: September 2023

In 1994, the Center for Disease Control declared that diabetes had reached epidemic proportions. Since then, however, little has been done to suppress the yearly increasing statistics. As of 2019, global diabetes prevalence reached 463 million people (9.3%) and it is expected that by 2045, an astounding 700 million people (10.9%) worldwide will be diagnosed with this condition. Studies throughout the 2020 coronavirus (COVID–19) pandemic demonstrated that older age and presence of diabetes mellitus, hypertension, and obesity significantly increased the risk for hospitalization and death in COVID–19 patients. Presently, a positive diabetes diagnosis undoubtedly diminishes an individual’s health, and quality and duration of life. Efforts should focus on both raising awareness at a global scale and developing preventive measures and effective treatments as part of fundamental care and health. Reliable sensors for monitoring glucose levels continue to be of major importance for diabetes control and treatment.

Enzymatic biosensors with incorporated transductors, specifically glucose oxidase biosensors, have been studied and developed extensively for this mission. Despite their low detection limit and high selectivity, enzymatic biosensors often require complex immobilization techniques of the enzyme onto a substrate electrode and suffer from leakage and poor stability. Additionally, glucose oxidase biosensors can only work properly under specific temperatures, pHs, and chemical environments. Nonenzymatic amperometric biosensors continue to be investigated as potential alternatives to enzymatic biosensors. Previous literature has focused on the development of nanostructured metals, metal alloys, and metal oxides as electrocatalytic materials for glucose oxidation. Many of these materials display faster response times, lower detection limits, and better stability compared to enzymatic biosensors. However, their selectivity towards other carbohydrates besides glucose are often discernable and they can suffer from poisoning by intermediates and other ions.

Previous studies have examined the synergistic effects of nickel and titanium for the oxidation of glucose, however, these investigations often employ complex morphologies that require elaborate synthetic methods. Herein we expanded on prior work by presenting a simple chemical reduction of Ni nanoparticles unto a TiO2 anatase substrate with Vulcan carbon for development of a nonenzymatic sensor for the glucose electrooxidation reaction. Multiple wt. % of Ni to TiO2 were targeted to optimize the most active ratio towards the oxidation reaction. The four binary catalysts were characterized by X–ray diffraction (XRD), inductively coupled plasma optical emission spectroscopy (ICP–OES), scanning electron microscopy (SEM), and energy dispersive X–ray spectroscopy (EDS). Given that Ni3+ has been reported as the electroactive species for glucose oxidation, the Ni–TiO2/XC72R catalysts were first examined for an activation treatment in 0.1 M NaOH at various potential windows. Cyclic voltammetry studies for the four nanocomposites demonstrated a progressive increase in anodic peak height attributed to the cumulative nucleation of NiOOH from Ni(OH)2. The 3:1 (or 60%) Ni to Ti nanocomposite yielded the highest current density after the activation treatment and after a 1 mM glucose aliquot addition, showed to be the most electrochemically active catalyst for glucose oxidation.

The 60% Ni–TiO2/XC72R catalyst was then used to construct an enzyme–less, chronoamperometric sensor for glucose detection in alkaline medium. Using 50 µM aliquots of glucose at a potential of +0.7 V (vs Hg/HgO), the sensor responded rapidly (< 3 s), provided a sensitivity of 3300 µA mM-1 cm-2 with a linear range up to 1 mM, detection limits of 144 nM (S/N = 3), and excellent selectivity and reproducibility. These aliquot additions of 50 µM effectively cover the mean salivary glucose level range in healthy and diabetic individuals according to a 2020 study by Gupta and Kaur. Therefore, the 60% Ni–TiO2/XC72R nanocomposite can be employed as a noninvasive sensor in which users are not required to pinch for glucose detection. The aliquot concentrations were then increased to 1 mM glucose to mimic physiological blood conditions and cover an extended range of 1–20 mM. The sensor also displayed excellent response time (< 1 s), showed a sensitivity of 273.7 µA mM-1 cm-2, detection limits of 3.13 µM (S/N = 3), and excellent selectivity and reproducibility. Finally, the catalyst exhibited an ideal anti–poison capability to free chloride ions and negligible signals to interfering species of 0.1 M ascorbic acid, uric acid, and lactic acid. These results demonstrated that the 60% Ni–TiO2/XC72R nanocomposite is an effective catalyst for glucose electrooxidation and a promising candidate for an enzyme–less sensor for glucose detection and monitoring