Electrochemical Glucose Research Articles

Electrical Tissue Adhesives for Strain‐Insensitive In‐situ Biosensing

In‐situ biosensing, a rapidly evolving field that focuses on the development of biosensors capable of on‐site detection of biomolecules directly from local tissue regions, holds the potential to revolutionize medicine through real‐time monitoring, personalized diagnosis, and targeted therapies. However, interfacing rigid, nonstretchable biosensors with soft, deformable tissues presents significant challenges due to their fundamentally contradictory properties. Herein, an electrical tissue adhesive featuring an entangled adhesive polymer network interpenetrated with a sacrificial dissipative polymer network is developed, which can rapidly and robustly adhere electrochemical biosensors with biological tissues, enabling strain‐insensitive physiological monitoring. The electrical tissue adhesive achieves a high fracture toughness of up to 3000 J m−2, a low Young's modulus of around 20 kPa, superior stretchability up to 15 times its initial length, and an overall biosensor‐tissue interfacial toughness of up to 500 J m−2. Using an electrochemical glucose sensor as one example, it is demonstrated that the electrical tissue adhesive can maintain resilient glucose sensing under various stress states and stretch levels. Additionally, the application of the electrical tissue adhesive for in‐situ monitoring of exercise and diet in subjects with various BMIs is demonstrated by measuring glucose concentration in sweat.

Metal‐Organic Frameworks (MOFs) for Glucose Sensing: Advancing Non‐Invasive Detection Strategies in Diabetes Management

Effective glucose monitoring is critical for managing diabetes and preventing its associated complications. While commercial glucose monitoring devices predominantly rely on blood samples, emerging research focuses on detecting glucose in alternative biofluids, harnessing advanced nanomaterials. Among these, Metal‐Organic Frameworks (MOFs), composed of metal ions and organic ligands, have garnered significant attention due to their unique properties, including tunable porosity, high surface area, and abundant active sites conducive to glucose interaction. MOFs present a versatile platform for glucose sensing, offering potential in both enzymatic and non‐enzymatic detection methods. This review delves into the recent advancements in MOFs‐based electrochemical glucose sensors, providing a comprehensive analysis of various MOFs and their composites as electrode materials. The discussion highlights the structural attributes, functionalization strategies, and electrochemical performance of MOFs in glucose sensing, emphasizing their role in the development of next‐generation, non‐invasive glucose monitoring technologies. The review provides a comprehensive overview on the application of MOFs and MOFs‐based composites in both enzymatic and non‐enzymatic electrochemical‐based glucose sensing and highlights the synthesis, mechanism, functionalization and development in the detection strategy of MOFs in glucose sensing.

Lithium Niobate Perovskite as the Support for Silver Nanoparticles for Non-Enzymatic Electrochemical Detection of Glucose

Lithium niobate perovskite and silver nanoparticle-based nanocomposites (LNB:AgNPs) were explored for developing an electrochemical glucose sensor. The perovskite to silver nanoparticle ratios investigated were 4:1, 1:1, 1:2, 2:1, and 1:4. Among these, the 4:1 ratio, with the lowest silver content, demonstrated the most stable performance during glucose quantification via amperometry. The sensor’s response was evaluated measuring the current at a fixed potential of 0.7 V following the injection of 1 mM glucose with each addition. The calibration curve obtained from the recorded data exhibited a linear response within the 1 to 15 mM glucose concentration range, achieving a sensitivity of 2 μA/mM, a high correlation coefficient (R2 = 0.997), and a limit of detection (LOD) of 0.5 µM. The LNB4:1AgNP composite allowed taking advantage of the unique properties of both components in a balanced manner, maximizing the sensor performance in practical applications.

Cobalt‐Based Ferrite Modified Carbon Nanotubes Fibers for Flexible and Disposable Microelectrode Toward Electrochemical Glucose Sensing

ABSTRACTGlucose detection is critical in clinical health and the food industry, particularly in the diagnosis of blood sugar levels. Carbon‐based fiber materials have recently featured prominently as non‐enzymatic electrochemical glucose detectors. Herein, cobalt‐based ferrite (CoFe2O4) in the form of nanoparticles has been successfully fabricated over the carbon nanotubes (CNTs) fiber via a simple hydrothermal process. Fabricated microelectrode (CoFe2O4@CNTs) was investigated as an electrocatalyst toward the non‐enzymatic electrochemical glucose sensors. The structure and morphology of the modified fiber were studied by scanning electron microscopy including energy‐dispersive X‐ray spectroscopy. The electrochemical capability of the microelectrode was analyzed by using different electrochemical techniques including cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy (EIS). The proposed sensors exhibited a superb sensitivity of 0.21 µAcm−2 mM−1, a good linear range from 1 to 9 mM, and a lower detection limit of 1.7 mM. Further investigation via EIS indicated the low charge transfer resistance as compared to the bare CNTs‐based fiber. Outcomes revealed that the material can potentially prove promising for the disposable microelectrode toward electrochemical glucose sensing.

ZnFe(PBA)@Ti3C2Tx nanohybrid-based highly sensitive non-enzymatic electrochemical sensor for the detection of glucose in human sweat

The ZnFe prussian blue analogue [ZnFe(PBA)] was infused with Ti3C2Tx (MXene) denoted as ZnFe(PBA)@Ti3C2Tx and was prepared by an in-situ sonication method to use as a non-enzymatic screen printed electrode sensor. The advantage of non-enzymatic sensors is their excellent sensitivity, rapid detection, low cost and simple design. The synthesized ZnFe(PBA)@Ti3C2Tx was characterized for its physical and chemical characterization by XRD, Raman, XPS, EDAX, and FESEM analysis. It possessed multiple functionalized layers and a cubic structure in the nanohybrid. Further, the sensor was investigated by using electroanalytical studies such as cyclic voltammetry and chronoamperometry analysis. The enhanced surface area with a cubic structure of ZnFe(PBA) and the excellent electrical response of Ti3C2 nanosheet support the advancement of a non-enzymatic electrochemical glucose sensor with improved sensitivity of 973.42 µA mM−1 cm−2 with the limit of detection (LOD) of 3.036 µM (S/N = 3) and linear detection range (LDR) from 0.01 to 1 mM.

Oxophilic Sn to promote glucose oxidation to formic acid in Ni nanoparticles.

The electrochemical glucose oxidation reaction (GOR) presents an opportunity to produce hydrogen and high-value chemical products. Herein, we investigate the effect of Sn in Ni nanoparticles for the GOR to formic acid (FA). Electrochemical results show that the maximum activity is related to the amount of Ni, as Ni sites are responsible for catalyzing GOR via the NiOOH/Ni(OH)2 pair. However, the GOR kinetics increases with the amount of Sn, associated with an enhancement of the OH- supply to the catalyst surface for Ni(OH)2 reoxidation to NiOOH. NiSn nanoparticles supported on carbon nanotubes (NiSn/CNT) exhibit excellent current densities and direct GOR via C-C cleavage mechanism, obtaining FA with a Faradaic efficiency (FE) of 93% at 1.45 V vs. reversible hydrogen electrode. GOR selectivity is further studied by varying the applied potential, glucose concentration, reaction time, and temperature. FE toward FA production decreases due to formic overoxidation to carbonates at low glucose concentrations and high applied potentials, while acetic and lactic acids are obtained with high selectivity at high glucose concentrations and 55 °C. Density functional theory calculations show that the SnO2 facilitates the adsorption of glucose on the surface of Ni and promotes the formation of the catalytic active Ni3+ species.

A Versatile Method to Create Antibody/Split‐Enzyme Complexes and Its Application to a Rapid, Homogeneous, and Universal Electrochemical Immunosensing System

AbstractIn this study, a versatile method is developed to create an antibody/split‐enzyme complex for use in electrochemical immunosensors. SpyCatchers are genetically fused at each terminus of flavin adenine dinucleotide‐dependent glucose dehydrogenase (FAD‐GDH) and a protease recognition sequence is inserted into a loop region to prepare a soluble protein and the split GDH. SpyTag‐fused single‐chain variable fragments (scFvs) are employed, which leads to the simple preparation of antibody‐split enzyme complexes (split AECs). The addition of pentameric C‐reactive protein (CRP), as a representative multimeric protein, restored the GDH activity of the split AECs, as the two split AEC fragments formed active GDH when in close proximity. CRP in human serum is electrochemically detected within 5 min without any washing steps with a clinically relevant CRP detection range (0.03–1 mg dL−1). The detection system is expanded to detect hemoglobin, SARS‐CoV‐2 spike protein, and inactivated SARS‐CoV‐2 by exchanging the scFvs. These results show that the convenient preparation method of the split GDH and the split AEC by the insertion of the protease recognition sequence and the use of SpyCatcher/SpyTag can realize a rapid, homogeneous, and universal electrochemical detection system that can be integrated into a commercially available electrochemical glucose sensor.

Fabrication of a novel non-enzymatic glucose sensor based on ruthenium supported by a combination of PBA nanocubes and MOF nanosheets

The development of novel catalysts with high catalytic activity is of high importance of electrochemical non-enzymatic glucose sensing. Herein, a sensitive non-enzymatic electrochemical sensor (Ru@NiCo-MOF/NiFe-PBA) has been synthesized using a fast, simple and eco-friendly method. The high stability of PBA and the large specific surface area (two-dimensional nanosheet structure) of MOF support the excellent electrochemical performance, while the incorporation of the highly active metal Ru enhances the electrochemical activity even more. The results reveal that the sensitivities of the sensor are 1070.77 and 487.62 μA mM−1 cm−2, corresponding to linear ranges of 0.01–0.67 mM and 0.67–5.07 mM, respectively. Meanwhile, the sensor has a low detection limit (0.446 μM) and a short response time (2 s), making it a strong candidate for non-enzymatic glucose sensors. The successful detection of glucose in saliva further demonstrates its potential for practical applications. Therefore, Ru@NiCo-MOF/NiFe-PBA will make an impact in the field of glucose monitoring and detection.

Electrochemical non-enzymatic glucose biosensors based on Au-thiol-linked molecular architectures

In this work, an electrochemical non-enzymatic glucose sensor consisting of di-methanethiol-grafted poly (3,4-propylenedioxythiophene), gold nanoparticles (Au NPs), and reduced graphene oxide (rGO) was synthesized by a one-step method through Au-S chemisorption. The structure and morphology of the as-prepared poly (ProDOT-(MeSH)2)/Au/rGO composite were characterized by FT-IR, XRD, EDX, TEM, SEM, and XPS, and the electrochemical performance of the composite was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) on glassy carbon electrode (GCE). The results show that because of the hydrogen bond interaction between the thiol group on the polymer units and the functional groups on GO, poly (ProDOT-(MeSH)2)/Au/rGO was successfully prepared. In addition, due to the unique morphological structure of the composite and the ability to absorb glucose molecules through hydrogen bonds, the poly(ProDOT-(MeSH)2)/Au/rGO electrode possesses excellent selectivity and unique sensitivity (46.13 μA mM−1 cm−2) for sensing glucose in the linear range of 0.04–16.0 mM with a detection limit of (S/N = 3) 0.01. This paper demonstrates that the poly(ProDOT-(MeSH)2)/Au/rGO composite holds great promise for application as a new glucose sensor in life science.

Ag@Au core–shell nanoparticles modified glassy carbon electrode synthesized by simple displacement reaction for non-enzymatic electrochemical glucose sensing

In this study, a new strategy was presented to enhance glucose sensor performance by modifying a glassy carbon electrode (GCE) with Ag@Au alloy nanoparticles. The synthesis process was designed with a simple replacement reaction to grow the gold layer onto the silver nanparticles to form a core–shell nanostructure. The resulting nanocomposite modified electrode exhibited superior electrocatalytic activity and stability in glucose sensing. Electrochemical measurements were undertaken to assess the performance of the as-synthesized Ag@Au/GCE. The Ag@Au core–shell nanoparticles modified GCE exhibited outstanding catalytic activity towards glucose detection, resulting in a high current response and a robust linear relationship between concentrations (10 μM–10 mM); the detection limit was remarkably low, at 0.04 μM. This sensor demonstrated a wide linear range, low detection limit, and high levels of selectivity and stability, rendering it suitable for accurate glucose quantification in biological samples.

Electrochemical Glucose Sensors: Classification, Catalyst Innovation, and Sampling Mode Evolution.

Glucose sensors are essential tools for monitoring blood glucose concentration in diabetic patients. In recent years, with the increasing number of individuals suffering from diabetes, blood glucose monitoring has become extremely necessary, which expedites the iteration and upgrade of glucose sensors greatly. Currently, two main types of glucose sensors are available for blood glucose testing: enzyme-based glucose sensor (EBGS) and enzyme-free glucose sensor (EFGS). For EBGS, several progresses have been made to comprehensively improve detection performance, ranging from enhancing enzyme activity, thermostability, and electron transfer properties, to introducing new materials with superior properties. For EFGS, more and more new metallic materials and their oxides are being applied to further optimize its blood glucose monitoring. Here the latest progress of electrochemical glucose sensors, their manufacturing methods, electrode materials, electrochemical parameters, and applications were summarized, the development glucose sensors with various noninvasive sampling modes were also compared.

Reusable gallium-based electrochemical sensor for efficient glucose detection

Among wearable sensing devices, electrochemical sensors are overwhelming in biochemical detection due to their simple design but high sensitivity. Most electrochemical sensors are disposable, which significantly impairs the service life. Here we present a reusable gallium (Ga)-based multi-layer electrochemical glucose biosensor to extend noninvasive monitoring of glucose in the interstitial fluid. This multilayer sensor includes Ga as a conductive interconnector, poly(3,4-ethylenedioxythiophene) as an electrode layer to prevent oxidation and metal leakage, a nano-Pt layer to enhance the electrochemical properties, and a nano-Prussian blue layer for reducing the hydrogen peroxide reduction potential. Most importantly, the biosensors can be renewed by automatically removing the modified nanocomposites via the electrolysis-induced bubbles and by electroplating without impairing the whole structure of the biosensor. The biosensor showed high sensitivity (24.6 μA mM-1 cm-2), wide linear range (0.01-26 mM), excellent stability (i.e., pH, long-term use) and superior selectivity, that is comparable to those of the current electrochemical tools for glucose detection. More importantly, incorporated with the reverse iontophoresis (RI), the Ga-based hybrid sensor was applied as a skin patch on mice for the in vivo noninvasive and continuous monitoring of ISF-borne glucose. The results showed a good correlation with that measured by blood glucometer. As a whole, this Ga-based electrochemical biosensor should endow new functions like biochemical analysis in biofluids for Ga-based soft bioelectronic sensing devices, in which almost are physical sensors. We believe that the reusability of electrochemically controllable processes may further inspire the development of more integrated and long-term stable gallium-based biosensing devices.

Study on the performance of MoS2/Au composites for non-enzymatic electrochemical glucose detection

Abstract Glucose concentration is considered an indicator for the diagnosis of diabetes, highlighting the importance of accurate glucose detection. Non-enzymatic electrochemical sensors have been extensively studied for glucose detection applications, with nanocomposites composed of molybdenum disulfide (MoS2) and gold nanoparticles (Au NPs) demonstrating high catalytic activity. In this study, a nanocomposite material composed of MoS2 and Au NPs (MoS2/Au) was synthesized and employed to construct a non-enzymatic electrochemical glucose biosensor. The detection limit of this sensor was explored, reaching as low as 1 mM. Additionally, compared to MoS2, the MoS2/Au nanocomposite exhibited a higher linear correlation coefficient and sensitivity, with a linear range of 1–25 mM and a sensitivity of 417.556 μA mM−1 cm−2. The sensor demonstrated excellent performance within the range of human blood glucose concentrations, showing potential for real-time monitoring and precise measurement of glucose levels. Furthermore, it exhibited good stability and reproducibility. These findings indicate the potential applications of MoS2/Au in biosensors and immunoassays.

Electrochemical glucose sensor based on a phenothiazine derivative mediator with nicotinamide adenine dinucleotide-dependent glucose dehydrogenase

The phenothiazine derivative (M2) was utilized as a redox mediator for the redox processes of the nicotinamide adenine dinucleotide (NAD+) cofactor. The composite solutions were prepared by mixing NAD+-dependent glucose dehydrogenase with NAD+, M2, poly-l-lysine, and glutaraldehyde. Glucose sensors were fabricated by casting various composite solutions onto the reduced graphene oxide-modified gold electrode and additional Nafion coating processes. The composition of electrode materials (ratio and amount of each component) and measurement conditions (applied potential, pH, and temperature) were optimized to obtain the highest sensitivity. The sensor showed a low reference effect, high selectivity toward interfering species, and long-term stability. The glucose sensor performed well when human serum was injected as the actual sample and compared with a standard solution. These findings promote the development of electrochemical sensors based on other NAD+-dependent enzymes.

Glucose Oxidase-Based Glucose Biosensing with a Simple Dual Ag/AgCl Probe Conductivity Readout.

We describe a conductometric assay of the enzymatic conversion of glucose to gluconic acid by dissolved glucose oxidase (GOx), using the generation of proton and gluconate from the reaction product dissociation for glucose detection. Simple basics of ionic conductivity, a silver/silver chloride wire pair, and a small applied potential translate glucose-dependent GOx activity into a scalable cell current. Enzyme immobilization and complex sensor design, involving extra nanomaterials or microfabrication of electrode structures, are entirely avoided, in contrast to all modern electrochemical glucose biosensors. Assay calibration showed a response linearity up to 500 μM, with a sensitivity of about 1.3 nA/μM. Selectivity tests excluded signals from sugars other than glucose, and glucose quantifications with recovery rates close to 100% were reached with a model sample and a beverage. Easy use of elementary physicochemical phenomena and a satisfactory performance are assets of the proposed non-amperometric glucose biosensing strategy. Assay integration into a planar dual electrode platform, with or without microfluidic application option, is feasible because of the simplicity of the sensor readout and suggests a route to affordable glucose analysis in beverage, food, and body fluid samples.

One‐Pot Carbothermal Reduction Preparation of Cu‐BTC@Cu/C Heterostructure for Enhanced Nonenzymatic Electrochemical Glucose Sensing

AbstractA heterostructure based on MOFs with a small lattice mismatch is ideal for improving glucose‘s electrochemical sensing performance. Herein, a novel one‐pot carbothermal reduction technique to prepare Cu‐BTC@Cu/C heterostructure with intimate interfacial contact and high yield was developed, by in situ integrating Cu‐BTC (Cu3(BTC)2 ⋅ 3H2O) and its derived Cu/C nanocomposites. Structure characterizations demonstrated that Cu‐BTC@Cu/C heterostructure shows a synergistic effect in the combination of these two components, with more electrochemical active sites and lower resistance. Compared with each individual component, Cu‐BTC@Cu/C heterostructure exhibits better glucose electrooxidation performance. Under optimal condition, an extremely sensitive nonenzymatic glucose sensor with a low detection limit of 6.78 μM, sensitivity of 911.03 μA mM−1 cm−2, linear range of 0.001–2.0 mM, and anti‐interference performance is presented. Meanwhile, the newly constructed sensor was effectively employed for detecting glucose in honey sample with perfect recoveries, showing its great potential toward glucose monitoring in real sample. In addition, it has been demonstrated Cu(II) can be induced into Cu(I) by glucose in solution, while Cu(I) could be electrochemically converted to Cu(II), therefore achieving a Cu(I)/Cu(II) redox cycle. It offers a promising strategy for synthesis of advanced electrocatalysts with high efficiency and promising applications in this paper.

Graphene/PEDOT/Ni-Based electrochemical Non-Enzymatic glucose sensor

Compared to enzymatic glucose sensors, non-enzymatic glucose sensors offer significant advantages in sensitivity, stability, and cost. In this study, a green and simple electrochemical method was employed to prepare an electrochemical non-enzymatic glucose sensor based on graphene/PEDOT/Ni materials. The modified electrode was characterized using scanning electron microscopy (SEM), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The electrochemical behavior of glucose on the modified electrode was investigated, and the results indicated that the sensor exhibited a good electrochemical response to glucose. Experimental conditions were optimized, and under the optimal conditions, the sensor showed a good linear relationship with glucose concentration in the range of 0.0001 to 7 mM, with a detection limit of 0.012 μM. The sensitivity was 1561 μA·mM−1·cm−2, demonstrating excellent reliability, stability, and accuracy.

A nanohybrid-based smartphone-compatible high performance electrochemical glucose sensor

A cost-effective and low-potential smartphone-compatible electrochemical sensor was constructed using a nanohybrid for the sensing of glucose in human and animal serum. The nanohybrid composed of gold nanoparticle (GNP) decorated cobalt hexacyanoferrate (CHCF) modified ZIF-67 (cobalt metal organic framework, CMOF) was synthesized and characterized by FTIR, XRD, and SEM with EDX analysis. The electrochemical characteristics of the nanohybrid were investigated by depositing the nanohybrid over a conventional glassy carbon electrode (GCE) and performing cyclic voltammetry, which revealed a stable redox peak with a formal potential of +0.23 V, corresponding to Co2+/3+ redox couple in GNP–CHCF–CMOF. Thus, developed sensor was utilized for the electrochemical glucose detection, which showed exceptional electrocatalytic activity over a linear detection range from 8.33 to 3793 μM with a low detection limit of 0.96 μM at a low potential of +0.35 V. Furthermore, the GNP–CHCF–CMOF/GCE sensor was employed for the detection of glucose spiked in human and rabbit serum samples, which showed excellent recoveries. A portable measurement device was fabricated which showed the real-time monitoring of glucose in a smartphone. This novel approach paves the way for the design and fabrication of cost-effective, low-potential sensors, which would reduce overall costs and enhance the performance of sensing devices.

A Biocompatible, Highly Sensitive, and Non-Enzymatic Glucose Electrochemical Sensor Based on a Copper-Cysteamine (Cu-Cy)/Chitosan-Modified Electrode.

A biocompatible, highly sensitive, and enzyme-free glucose electrochemical sensor was developed based on a copper-cysteamine (Cu-Cy)-modified electrode. The catalytically active biocompatible material Cu-Cy was immobilized on the electrode surface by the natural polymer chitosan (CTS). The electrochemical characterization and glucose response of the Cu-Cy/CTS/glassy carbon electrode (GCE) were investigated by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and constant potential amperometry. The significant electrocatalytic activity of Cu-Cy to the oxidation of glucose in an alkaline environment was revealed. Several crucial parameters, including the number of scanning cycles for electrode activation, applied potential, and the contents of Cu-Cy and chitosan, were investigated to understand their impact on the sensor's response. The proposed sensing platform exhibited linear ranges of 2.7 μM to 1.3 mM and 1.3 mM to 7.7 mM for glucose detection, coupled with high sensitivity (588.28 and 124.42 μA·mM-1·cm-2), and commendable selectivity and stability. Moreover, a Cu-Cy/CTS-modified screen-printed electrode (SPE) was further developed for portable direct detection of glucose in real samples.

Highly stable and selective determination of glucose by a modified glassy carbon electrode based on micro-rods [Ni(HL)NCS] complex as a novel modifier

Non-enzymatic glucose sensors have acquired a lot of attention, where the modifier materials perform as an electrocatalyst instead of an enzyme on the surface of electrodes. More active sites, increased synergistic reactions, and expanded contacts between the electrolyte and the catalyst are essential to enhance catalytic performances. Numerous efforts have been made to fabricate novel non-enzymatic glucose sensors with electrode modification strategies. Herein, a non-enzymatic electrochemical glucose sensor was constructed by a modified glassy carbon electrode (GCE) based on micro-rods [Ni(HL)NCS] complex (MR-NiC/GCE) as a novel modifier for the glucose detection. In alkali media, the non-enzymatic glucose sensor showed a linear dynamic range (LDR) of 100-1100 µM with an excellent limit of detection (LOD) of 15.8 μM (S/N= 3). The proposed sensor demonstrated remarkable stability (after recording 50 continuous cycles), good reproducibility, and significant anti-interference performance toward fructose (Fru), ascorbic acid (AA), dopamine (DA), citric acid (CA), uric acid (UA) and sucrose. According to this study, complexes can be an excellent suggestion to fabricate non-enzymatic glucose sensors.