Electrochemical Glucose Sensor Research Articles

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

AbstractEffective 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.

Salivary glucose detection based on platinum metal hydrogel prepared mouthguard electrochemical sensor

A mouthguard electrochemical sensor for salivary glucose detection based on platinum metal hydrogel is proposed in this work. Conventional enzyme-based electrochemical glucose sensors are fraught with issues such as high cost, oxygen dependency, intricate immobilization procedures, and susceptibility to variations in temperature, pH, and so on. The detection of glucose in saliva, as a non-invasive sensing approach, presents a more convenient solution for diabetes monitoring. This study employs Pt metal hydrogel as the electrocatalytic material for glucose, with its microstructure characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. The sensor's electrochemical properties, sensing performance, anti-interference capability, and stability were assessed through methods including cyclic voltammetry (CV), chronoamperometry, and electrochemical impedance spectroscopy (EIS). Under neutral pH phosphate buffer (PB) solution in the laboratory setting, the sensor demonstrated an outstanding linear range (0–40 mM) and a low detection limit (0.119 mM). Implemented in a wearable mouthguard format, this electrochemical sensor enables the detection of glucose in physiological environments, specifically saliva, exhibiting favorable detection characteristics: a linear range of 0.58–3.08 mM and a detection limit of 0.082 mM. This innovation thus offers a practical and efficacious tool for the non-invasive monitoring of glucose levels relevant to diabetes management.

A Wearable Electrochemical Sensor Based on Single-Atom Pt Anchored on Activated NiCo-LDH/Ti3C2Tx for Real-Time Monitoring of Glucose.

Wearable, noninvasive sweat sensors enable real-time monitoring of metabolites in human health management. However, the commercial enzyme-based and currently nonenzymatic glucose sensor represents sluggish glucose oxidation kinetics and a narrow sensing range. Rational design of sensitive materials is significant yet faces a huge challenge. Herein, we construct a single-atom Pt supported on NiCo-LDH/Ti3C2Tx heterostructures (Pt1-NiCo-LDH/Ti3C2Tx) as the nonenzymatic electrochemical glucose sensor sensitive materials for selective detection of glucose level in human sweat. The obtained Pt1-NiCo-LDH/Ti3C2Tx with improved structural stability and enhanced charge transfer efficiency shows a low oxidation peak potential of 0.49 V, high sensitivity of 506.6 μA mM-1 cm-2, a low detection limit of 0.035 μM, and long-term stability toward the glucose detection. The wearable sensor, coupled with a wireless transmission module and a signal processing chip, is used for real-time perspiration glucose monitoring during outdoor exercise. The result is comparable to that of high-performance liquid chromatography (HPLC). This research provides a new paradigm for designing a wearable nonenzymatic electrochemical glucose sensor, enabling noninvasive real-time monitoring of glucose concentrations in human sweat.

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.

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 fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). 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.

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.

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.

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.

Self-powered microfluidic-based sensor for noninvasive sweat analysis

This study introduces a novel self-powered, microfluidic sweat sensing system. The device features a flexible thermoelectric system that enables efficient on-demand sweat extraction and data transmission. Both the thermoelectric generator (TEG) and the microfluidic system are thoroughly evaluated through numerical simulations and experimental testing. The device integrates electrochemical sensors for glucose, pH, and ion detection, along with solid-liquid triboelectric nanosensors to measure sweat rate. It demonstrates high selectivity for target analytes. Sweat, extracted via iontophoresis with carbagel, interacts with electrodes coated with ion-selective membranes (ISM) and glucose oxidase, producing an open-circuit potential. This selective detection of analytes results in distinct output differences. Additionally, the device delivers stable results within 20 minutes, reducing analysis time while maintaining a strong correlation with blood biomarker concentrations. This partially flexible, noninvasive system has potential applications in monitoring electrolyte loss and glucose imbalances through sweat.

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.

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 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.

Growth of WO3 nanostructure deposited on TiO2 nanotube arrays for electrochemical enzyme-free glucose sensor

In this study, a novel WO3-TiO2 hybrid nanostructure-based electrochemical non-enzymatic glucose biosensor has been developed. The anodization method was utilized to successfully produce TiO2 nanotubes on Ti6Al4V alloy functioning as substrates and WO3 nanomaterial decorate on the surface of TiO2 nanotubes (TNTs) deposited through electrochemical technique. The incorporation of WO3 on TNTs has resulted in a high electroactive surface and more degradation resistance in comparison to pure TNTs, resulting in enhanced electron transfer rate and electrode stability. High-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FE-SEM), and X-ray diffraction were used to investigate the crystalline structure and morphology of the WO3-TiO2 nanostructure. The electrochemical properties of the hybrid electrodes were investigated employing amperometry, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The hybrid electrode had a promising sensitivity (1228.12 μA/mM/cm2), low detection limit (0.19 mM), wide linear range (1.0–6.5 mM), and short response time (2-s). The sensors also demonstrated superior levels of reproducibility, repeatability, and stability.

NiCo layered double hydroxide nanosheet arrays constructed via in-situ plasma etching as non-enzymatic electrochemical sensor for glucose in food

The design and construction of an efficient non-enzymatic glucose electrochemical sensor is of great significance for food quality assessment. Here, we have developed a method to fabricate highly efficient catalytic electrodes for glucose sensing in alkaline. This method utilizes microplasma assistance during the in-situ etching of NiCo layered double hydroxide nanosheet arrays on nickel foam (NiCo-LDH/NF). The NiCo-LDH nanosheets possessed uniform dispersion without agglomeration, high electrochemically active surface area, and excellent electron transfer efficiency (the electron transfer coefficient (α) up to 0.91, the catalytic rate constant (k) was 2.44 × 106 cm3 mol−1 s−1). The NiCo-LDH/NF-based non-enzymatic glucose sensor exhibits the broad linear range (0.4–150 μM), high sensitivity (98000 μA mM−1 cm−2), and the low detection limits (48.76 nM) with satisfactory reproducibility and selectivity. This work developed a simple and rapid in-situ approach for constructing non-enzymatic electrochemical sensors with high sensitivity.

A minimally invasive sensing system based on hydrogel microneedle patches and Au/Cu2O nanospheres modified screen-printed carbon electrode for glucose monitoring in interstitial skin fluid

Glucose monitoring in interstitial skin fluid (ISF) has become a novel approach for diabetes management. In this paper, a minimally invasive sensing system consisted of methacrylated hyaluronic acid (MeHA) based microneedle patches and Au/Cu2O nanospheres modified screen-printed carbon electrode (SPCE) was designed for glucose monitoring in the ISF of living mice. The highly swellable and biocompatible MeHA microneedle patches can effectively extract ISF from the skin, barely cause pain to the living mice. The glucose level in the extracted ISF was detected via an enzyme-free electrochemical sensor using the Au/Cu2O nanospheres as the electrocatalyst. The doping of Au into Cu2O resulted in a highly conductive and active electrocatalyst for glucose oxidation, which improved the sensing performance of glucose sensor. A wide linear range (0.02 – 6 mM), low detection limit (0.018 mM), and high sensitivity (110.38 μA mM−1 cm−2) were obtained under the optimized condition. The obtained results exhibited a comparable trend to those obtained from commercial glucometers. We have combined successfully MeHA patches for ISF extraction with enzyme-free electrochemical glucose sensor. Therefore, this novel sensing system holds great potential for diabetes management in a minimally invasive manner.

One-step green synthesis of flower-like non-precious metal (Cu, Ni, Fe or Zn) doped ZIF-67 and its application as non-enzymatic electrochemical glucose sensors

Co ions and imidazolate ligands can be self-assembled into a novel metal-organic frameworks (MOFs) with zeolite-like topological structures, which is named as ZIF-67. Flower-like ZIF-67 can be precisely prepared by one-step green synthesis method under specific experimental conditions, and has excellent enzyme-like electrocatalytic activity toward glucose. Non-precious metal (Cu, Ni, Fe or Zn) can be doped into flower-like ZIF-67 while maintaining zeolite-like topological structures, which may also be an important way to enhance the electrocatalytic performances of ZIF-67. In this study, flower-like non-precious metal (Cu, Ni, Fe or Zn) doped ZIF-67 was contrastively researched by physical characterizations and electrochemical techniques, and was employed as electrocatalysts for non-enzymatic electrochemical glucose sensors. Flower-like non-precious metal (Cu, Ni, Fe or Zn) doped ZIF-67 all exhibits perfect electrocatalytic activities toward glucose, among them the performance of Fe(5 %)-ZIF-67 is the most outstanding.

Directionally Exfoliated Ni/Co Hydroxide-Organic Framework Nanosheets for Enhanced Wearable Glucose Sensing.

We report two-dimensional (2D) Ni/Co-based metal hydroxide-organic framework nanosheets (Ni/Co-MHOF NSs) for the construction of an efficient electrochemical nonenzymatic glucose sensor. The nanosheet architecture maximizes the exposure of coordinatively unsaturated metal sites, which enables a largely improved electrocatalytic performance toward the glucose oxidation reaction. The as-designed nonenzymatic sensor exhibits a high sensitivity of 235.71 μA·mM-1·cm-2 and a wide linear range of 1-3000 μM. The sensor presents excellent selectivity against several potential interferences and a short response time of 3.0 s. Of interest, a high-performance flexible sensor is developed by depositing the Ni/Co-MHOF NSs on screen-printed electrodes, which reveal decent bending stability. The designed glucose sensor patch can attach to the human body and realize noninvasive glucose monitoring in human sweat. This work may shed light on the application of novel MHOFs in the field of wearable electrochemical sensing.