Laser-induced graphene (LIG)-based Au@CuO/V₂CT_x MXene non-enzymatic electrochemical sensors for the urine glucose test

Highlights

• Laser-induced graphene (LIG) electrodes were fabricated as one-off urine glucose test sensor strips.

• Au@CuO nanocatalyst was synthesized to mimic the glucose oxidase and develop the urine glucose test sensor.

• The effect of V₂CT_x MXene on the LIG-based non-enzymatic urine glucose test sensor was explored.

• The developed sensor was demonstrated to achieve an ultrahigh sensitivity of 1.124 × 10⁶ μA mM⁻¹ cm⁻².

Abstract

Glucose monitoring is of great significance for the health management of diabetic patients. Herein, non-enzymatic glucose sensors were developed by modifying Au@CuO or Au@CuO/V₂CT_x MXene nanocomposites (NCs) on the surface of disposable laser-induced graphene (LIG) electrode. The structures and morphologies were confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and elemental analysis. The electrochemical performances of NCs were investigated by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and chronoamperometry (CA). The results demonstrated that both Au@CuO/LIG and Au@CuO/V₂CT_x MXene/LIG have excellent electrocatalytic activity for glucose oxidation in an alkaline medium. However, it was found that Au@CuO/V₂CT_x MXene/LIG was easily oxidized. Hence, the combination of Au@CuO/LIG was preferred for glucose test. Under optimized conditions, the electrochemical sensor achieved a detection range of 0.005 to 5.0 mM with a sensitivity of 1.124 × 10⁶ μA mM⁻¹ cm⁻². The response time was 1.5 s and the limit of detection (LOD) was as low as 1.8 μM. The sensor has good selectivity and stability (84.12 % activity retained after 6 weeks). Its affordable price, disposable usage and portable essence are suitable for clinical application. Our study presented a novel strategy to the field of non-enzymatic glucose sensing.

Introduction

Diabetes is a metabolic disease attracting worldwide attention. It seriously affects the physical and mental health and quality of life of patients and their families. Studies by 2021 showed that diabetes has caused 6.7 million deaths and also brought a heavy burden to the healthcare system. What's more, if diabetes is not well controlled, serious complications such as cardiovascular, ophthalmic and nephritic diseases will push the patients to the abyss of death [1], [2], [3], [4], [5], [6]. In addition, diabetes is a risk factor for COVID-19, which is sweeping the world [7], [8].

For the moment, the blood glucose test is the gold standard for diagnosing diabetes [9]. It requires samples to be obtained through needles, which is invasive and may lead to wound infection [10]. This is unfriendly to patients with needle phobia [11]. Studies have pointed out that psychological factors such as fear and resistance will cause fluctuations in blood glucose levels [12], which reduces the reliability of test results [13], [14]. It has been suggested that elevated blood glucose reflects a moment in time and may be difficult to capture in the early phase of the impaired regulation of blood glucose. On the contrary, urine glucose can accumulate over time and the increase in blood glucose can be easily captured in urine [15]. It should be noted that studies have shown a correlation between urine glucose levels and blood glucose/diabetes [16], [17], [18]. Therefore, urine glucose is more likely to timely reflect the occurrence of blood glucose disorders in prediabetes. More importantly, urine sample can be obtained in non-invasive and they are easy to be operated.

Enzymatic sensors such as glucose oxidase (GOx) sensors [19], [20], [21], [22] are commonly used for glucose detection. However, natural enzymes have inherent disadvantages, such as sensitive to the external environment, easy to deactivate, difficult to preserve, and expensive [23], [24]. When Fe₃O₄ nanomaterial with peroxidase-like activity was discovered [25], the field of “nanozyme” attracted the attention all over the world. Nanozyme is a kind of nanomaterials with enzymatic activity [26], [27]. They not only have the catalytic activity of natural enzyme, but also overcomes the disadvantage of being susceptible to external conditions. They are stable in performance, low cost and easy to prepare [28], [29], [30], [31].

Non-enzymatic glucose electrochemical sensor is based on glucose in a specific condition by nanozyme oxidation to generate electrical signals. Many nanozymes with glucose oxidase-like activity have been reported, each with its own advantages. For example, nickel (Ni) nanomaterials, cobalt (Co) nanomaterials, copper (Cu) nanomaterials and Ni/Co/Cu-based metal–organic frameworks (MOF) [32], [33], [34], [35] have low cost, high stability and high chemical activity. Au nanomaterials have good biocompatibility, good electrocatalytic activity for glucose oxidation, provide large surface area with rich catalytic sites and they are easy to be prepared [36], [37]. As the p-type semiconductor, CuO has established its important material-role because of its remarkable catalytic activity, good stability and affordable price [38]. Individual nanomaterials have their own characteristics, and it is possible to combine the materials to achieve superimposed and superior properties [39]. Such as Cu-Pd [40], Cu-Ag [41], Pt-Ni [33], Pt₃Ru₁ [42] and Ni-Co [43], [44], [45]. In this study, we proposed Au nanoparticles (NPs) with good electrical conductivity as the core and semiconductor CuO NPs as the porous shell to prepare Au@CuO nanocore-shell structure. This metal–semiconductor nanocomposites (NCs) not only combines the advantages of different components, but also generates new synergistic properties caused by the interaction between metal and semiconductor components.

Laser-induced graphene (LIG) electrodes can be mass-produced with just a computer and a computer-controlled laser engraving machine [46]. LIG with high surface area and abundant folds are inexpensive and disposable, which has a great potential for practical application [47], [48], [49], [50], [51]. Two-dimensional (2D) transition metal carbides and nitrides (MXene) is a type of 2D graphene analogue, obtained by adding hydrofluoric acid (HF) [52] or LiF + HCl [53] etched the precursor MAX. Due to its outstanding properties such as large specific surface area, high electrical conductivity, good biocompatibility, excellent hydrophilicity and environmental friendliness, MXene is widely used in the fields of sensing, energy storage and environmental restoration [53], [54], [55]. Both LIG and MXene have large π-conjugated systems, and they can be firmly combined by π-π stacking interaction. This combination is suitable for using as a catalytic substrate to fix more catalysts. In this study, V₂CT_x MXene was proposed to combine with Au@CuO to increase the specific surface area and electron transfer capability of the material [56].

To the best of our knowledge, the combination of Au@CuO/LIG and Au@CuO/V₂CT_x MXene/LIG have not been reported for non-enzymatic electrochemical sensors for urine glucose test (Scheme 1). This will provide new strategies to the field of non-enzymatic glucose sensing and offers new possibilities for the diagnosis and monitoring of diabetes.