Glucose Biosensor Applications Research Articles

The importance of factorial design on the optimization of biosensor performance: immobilization of glucose oxidase as a case study.

Conventionally, the optimization of glucose biosensors is achieved by varying the concentrations of the individual reagents used to immobilize the enzyme. In this work, the effect and interaction between glucose oxidase enzyme (GOx), ferrocene methanol (Fc), and multi-walled carbon nanotubes (MWCNTs) at different concentrations were investigated by a design of experiments (DoE). For this analysis, a factorial design with three factors and two levels each was used with the software RStudio for statistical analysis. The data were obtained by electrochemical experiments on the immobilization of GOx-Fc/MWCNT at different concentrations. The results showed that the factorial DoE method was confirmed by the non-normality of the residuals and the outliers of the experiment. When examining the effects of the variables, analyzing the half-normal distribution and the effects and contrasts for GOx-Fc/MWCNT, the factors that showed the greatest influence on the electrochemical response were GOx, MWCNT, Fc, and MWCNT:Fc, and there is a high correlation between the factors GOx, MWCNT, Fc, and MWCNT:Fc, as shown by the analysis of homoscedasticity and multicollinearity. With these statistical analyses and experimental designs, it was possible to find the optimal conditions for different factors: 10mMmL-1 GOx, 2mgmL-1 Fc, and 15mgmL-1 MWCNT show a greater amperometric response in the glucose oxidation. This work contributes to advancing enzyme immobilization strategies for glucose biosensor applications. Systematic investigation of DoE leads to optimized immobilization for GOx, enables better performance as a glucose biosensor, and allows the prediction of some outcomes.

Designing Nanocomposite-Based Electrochemical Biosensors for Diabetes Mellitus Detection: A Review.

This review will unveil the development of a new generation of electrochemical sensors utilizing a transition-metal-oxide-based nanocomposite with varying morphology. There has been considerable discussion on the role of transition metal oxide-based nanocomposite, including iron, nickel, copper, cobalt, zinc, platinum, manganese, conducting polymers, and their composites, in electrochemical and biosensing applications. Utilizing these materials to detect glucose and hydrogen peroxide selectively and sensitively with the correct chemical functionalization is possible. These transition metals and their oxide nanoparticles offer a potential method for electrode modification in sensors. Nanotechnology has made it feasible to develop nanostructured materials for glucose and H2O2 biosensor applications. Highly sensitive and selective biosensors with a low detection limit can detect biomolecules at nanomolar to picomolar (10-9 to 10-12 molar) concentrations to assess physiological and metabolic parameters. By mixing carbon-based materials (graphene oxide) with inorganic nanoparticles, nanocomposite biosensor devices with increased sensitivity can be made using semiconducting nanoparticles, quantum dots, organic polymers, and biomolecules.

Photonic Interpenetrating Polymer Network Fibers Comprising Intertwined Solid-State Cholesteric Liquid Crystal and Polyelectrolyte Networks for Sensor Applications.

Uniform-sized photonic interpenetrating polymer network (IPN) fibers comprising intertwined solid-state cholesteric liquid crystal (CLCsolid) and anionic poly(acrylic acid) (PAA) or cationic poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) networks (photonic IPNPAA or IPNPDMAEMA fibers) were developed for sensor applications. IPNPAA or IPNPDMAEMA fibers with a perfect photonic structure were fabricated inside Teflon tube templates without any treatments for realizing a planar orientation in those fibers. The dominant wavelength of the photonic color from a photograph taken with a cellular phone was used to measure the photonic color change. Photonic IPNPAA fibers treated with KOH (IPNKOH fibers) were used for sensing humidity and divalent metal ions. The linear ranges for relative humidity and Ca2+ detection were 21-92% and 0.5-3.5 mM, and their limits of detection (LODs) were 7.86% and 0.07 mM, respectively. The photonic IPNPAA (or IPNPDMAEMA) fiber immobilized with urease (IPNPAA-urease) (or glucose oxidase (IPNPDMAEMA-GOx)) was used for urea (or glucose) biosensor application. The photonic IPNPAA-urease (or IPNPDMAEMA-GOx) fiber was red-shifted in response to urea (or glucose) in the linear range of 10-60 mM (or 2-16 mM) with an LOD of 2.54 mM (or 0.76 mM). These photonic IPN fibers are promising because of their easy fabrication and miniaturization, battery-free device, cost-effectiveness, and visual detection without using sophisticated analytical instruments. The developed photonic IPN fibers provide new possibilities for the widespread use of photonic sensors in cutting-edge wearable technology and beyond.

Development of mobile biosensor reader for wearable sweat glucose biosensor application

Sweat contains numerous biomarkers, including glucose, which can provide valuable insights into an individual’s metabolic state. Noninvasive glucose monitoring eliminates the need for frequent finger pricks or blood samples, offering greater convenience and reducing discomfort for individuals with diabetes. These biosensors are designed to detect and quantify glucose levels through various sensing mechanisms, such as enzymatic reactions or electrochemical measurements. The integration of biosensors into wearable devices, such as smartwatches, patches, or flexible electronics, allows for mobile glucose monitoring in sweat. Accurate glucose measurements require calibration and validation against reference measurements, such as blood glucose levels. Research focuses on developing calibration algorithms and improving the accuracy and reliability of mobile glucose biosensors in sweat.

Chitosan–Fe3O4 Nanoparticles Cryogel for Glucose Biosensor Development

Chitosan was widely used as a supporting material for enzyme immobilization. However, the non-conductive properties of chitosan could be a severe problem in the application of biosensors with electrochemical detection. This research aimed to modify the chitosan cryogel with Fe3O4 nanoparticles for glucose biosensor application. The glucose biosensor used glucose oxidase enzyme as biological sensing element which was immobilized on the working electrode of electrochemical detection. Chitosan-Fe3O4 composite cryogel was used as supporting material for glucose oxidase immobilization. The detection optimization was also performed by varying the operating conditions such as buffer pH and reaction temperature. The result showed the optimum conditions were the addition of Fe3O4 nanoparticles for 4% (w/v), phosphate buffer solution of 100 mM with pH of 7.0, and reaction temperature at 25°C. The glucose determination showed linearity for increasing oxidation peak and decreasing reduction peak with the glucose concentration, with regression equation of y = -6.804x – 104.32 and y = 4.5872x + 133.37 respectively. Furthermore, the limit of detection and limit of quantification for oxidation peaks were 0.38 mM and 1.25 mM respectively. The reduction peak showed a limit of detection of 0.32 mM and a limit of quantification of 1.07 mM.

Development and Practical Application of Glucose Biosensor Based on Dendritic Gold Nanostructures Modified by Conducting Polymers.

In this study, graphite rod (GR) electrodes were electrochemically modified by dendritic gold nanostructures (DGNs) followed by immobilization of glucose oxidase (GOx) in the presence of mediator phenazine methosulfate (PMS). Modified with polyaniline (PANI) or polypyrrole (Ppy), GOx/DGNs/GR electrodes were used in glucose biosensor design. Different electrochemical methods were applied for the registration of glucose concentration, and constant potential amperometry (CPA) was chosen as the best one. PANI and Ppy layers synthesized enzymatically on the GOx/DGNs/GR electrodes extended the linear glucose determination range, the width of which depended on the duration of PANI- and Ppy-layers formation. Enzymatically formed polypyrrole was determined as the most suitable polymer for the modification and formation of the glucose biosensor instead of polyaniline, because it was 1.35 times more sensitive and had a 2.57 times lower limit of detection (LOD). The developed glucose biosensor based on the Ppy/GOx/DGNs/GR electrode was characterized by appropriate sensitivity (59.4 μA mM−1 cm−2), low LOD (0.070 mmol L−1), wide linear glucose determination range (up to 19.9 mmol L−1), good repeatability (8.01%), and appropriate storage stability (33 days). The performance of the developed glucose biosensor was tested in biological samples and beverages.

Poly-L-lysine-modified with ferrocene to obtain a redox polymer for mediated glucose biosensor application

Ferrocene-based polymers as redox mediators are considered versatile and important in the study of glucose biosensors. Poly-L-lysine (PLL), as a cationic polymer, possesses good properties including biocompatibility, biodegradation and water solubility. In this work, PLL was modified with ferrocene carboxylate in a very simple way by activating the carboxyl group of Fc, which reacted with the amino groups of the polymer. The resulting product was analysed by FTIR. Performance as a redox mediator (Fc-PLL) with the enzyme glucose oxidase was tested by cyclic voltammetry and showed an increase in the oxidation current in the presence of glucose in PBS pH 7.4. Additionally, performance as a biosensor was evaluated by amperometry and gave a linear range of 0–10 mM, a limit of detection of 23 μM, a sensitivity of 6.55 μA/cm2 mM and high selectivity. To evaluate the charged regions of Fc-PLL/GOx on the electrode surface, analysis by scanning electrochemical microscopy showed remarkable activity. The Fc-PLL redox polymer as a glucose biosensor has been well accepted as this kind of material, and the results showed remarkable activity as an electron transfer mediator between the redox polymer and the GOx enzyme.

Glucose Biosensor Based on Dendritic Gold Nanostructures Electrodeposited on Graphite Electrode by Different Electrochemical Methods

In this research, we have demonstrated a one-step electrochemical deposition of dendritic gold nanostructures (DGNs) on a graphite rod (GR) electrode without any template, seeds, surfactants, or stabilizers. Three electrochemical methods, namely, constant potential amperometry (CPA), pulse amperometry, and differential pulse voltammetry, were used for DGN synthesis on GR electrode and further application in enzymatic glucose biosensors. Formed gold nanostructures, including DGNs, were characterized by a field emission scanning electron microscopy. The optimal concentration of HAuCl4 (6.0 mmol L−1), duration of DGNs synthesis (400 s), electrodeposition potential (−0.4 V), and the best electrochemical method (CPA) were determined experimentally. Then the enzyme, glucose oxidase, was adsorbed on the surface of DGNs and covalently cross-linked with glutaraldehyde vapor. The enzymatic glucose biosensor based on DGNs electrodeposited at optimal conditions and modified with glucose oxidase showed a quick response (less than 3 s), a high saturation current (291 μA), appropriate linear range (up to 9.97 mmol L−1 of glucose, R2 = 0.9994), good repeatability (RSD 2.4, 2.2 and 1.5% for 2, 30, 97 mmol L−1 of glucose), low limit of detection (0.059 mmol L−1, S/N = 3) and good stability. Additionally, this biosensor could be successfully applied for glucose determination in real samples with good accuracy. These results proved the principle of enzymatic glucose biosensor development based on DGNs as the basis for further investigations.

One-pot scalable synthesis of rGO/AuNPs nanocomposite and its application in enzymatic glucose biosensor

A nanocomposite, rGO/AuNPs, was synthesized simultaneously using one-pot approach with gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) within gelatin which used as a reducing and stabilizing agent. Then, the fabricated nanocomposites were characterized by UV-Vis, transmission electron microscope (TEM) and field emission scanning electron microscope (FE-SEM). The optimal nanocomposite was determined using electrochemical approaches. After facile and eco-friendly synthesis of rGO/AuNPs nanocomposites, it was used to fabricate the bioanode of enzymatic glucose biosensors. After drop-casting the nanocomposites on a screen-printed electrode (SPE), the glucose oxidase (GOx) was immobilized on the pre-treated SPE through a protein cross-linking approach using glutaraldehyde (GA) as a crosslinking reagent and 2,5-dihydroxybenzaldehyde (DHB) as a mediator to improve the electrochemical performance. Then, electrochemical performance of enzyme immobilized nanocomposites was studied using the potentiostat. The results demonstrate that the enzymatic biosensor made of rGO/AuNPs nanocomposites showed enhanced the sensitivity of selectivity for detection of glucose.

Optical and microstructural characteristics of CuO thin films by sol gel process and introducing in non-enzymatic glucose biosensor applications

In this work, we reported the synthesis of copper oxide (CuO) thin films by sol-gel process assisted by spin coating technique at room temperature. Chemical characterization of CuO precursor solution was determined by Fourier Transformed Infrared Spectroscopy (FTIR) and thermal stability by Thermogravimetric/ Differential Scanning Calorimetry Analysis (TGA/DSC). The influence of variation parameters for the thin films were studied: speed deposition, number of layers and annealing effect on the deposited films. The optical properties of CuO thin films were analyzed using a spectrophotometer (UV–vis-NIR) in a range of 300−1100 nm. The calculated band gap for CuO this films was between 3.35 eV–3.89 eV for as deposited thin films and 2.4 eV–3.6 eV for annealed films. Homogeneous deposited films with monoclinic structure were determined using scanning electron microscopy (SEM) and X-Ray Diffraction respectively. The compositions and homogeneous elemental distributions were analyzed by energy dispersive spectroscopy (EDAX). From the profilometer measurement, the thicknesses of the CuO thin films prepared were found to be ∼1/2−1 μm, depending of speed deposition. Finally, CuO solution precursor and thin films were implemented in a glucose test which showed the formation of gluconic acid by FTIR, indicating the glucose oxidation due to CuO interaction.

Aligned Carbon Nanotube Films for Immobilization of Glucose Oxidase and its Application in Glucose Biosensor

Glucose oxidase (GOx) was immobilized between aligned carbon nanotube films (ACNTFs) using a cross-stacking method without any purification and functionalization processes. Direct electron transfer of GOx was achieved on the ACNTFs with reversible redox peaks observed at the formal potential of –0.448 V. When applied to the determination of glucose by cyclic voltammetry, the prepared enzymatic electrode exhibited a linear range from 1 to 5 mM under mediator-free physiological conditions, which makes it a promising candidate for the development of third-generation glucose biosensors.

A Novel Amperometric Glucose Biosensor Based on Fe3O4‐Chitosan‐β‐Cyclodextrin/MWCNTs Nanobiocomposite

AbstractA novel enzymatic biosensing platform toward glucose is achieved with nanocomposite of magnetic nanoparticles (Fe3O4−CS−CD) and multi‐walled carbon nanotubes (MWCNTs). The synergistic effect of chitosan, β‐cyclodextrin and MWCNTs can facilitate electron transfer between enzyme and electrode based on the promoting results of the cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The new biosensors exhibited direct electron transfer (DET) from enzyme to electrode after glucose oxidase (GOx) was immobilized on the modified electrode with the nanocomposite. Consequently, the enzymatic glucose biosensor displayed a considerably wide linear range (40 μM to 1.04 mM) with a high sensitivity of 23.59 μA mM−1cm−2, low detection limit of 19.30 μM, good selectivity, reproducibility and repeatability for detecting glucose. In addition, the current response still retained at 93.4 % after 25 days. Furthermore, the practical application of glucose biosensor was test in human serum samples with satisfactory accuracy, demonstrating promising and practical potential in biomedical diagnostics.

Enzymatically functionalized polyaniline thin films produced with one-step electrochemical immobilization and its application in glucose and urea potentiometric biosensors.

Glucose and urea enzymatic biosensors were fabricated. One-step electrochemical immobilization process was used to produce thin polyaniline films with entrapped enzymes. Chronopotentiometric analysis, scanning electron microscopy, electrochemical impedance spectroscopy and optical reflectance spectroscopy were used to determine the structure-property relationship of the functionalized polymeric thin films. The device has a recognition stage connected to a potentiometric field-effect-transistor stage and is based on the measurement of microenvironment pH variation or locally produced ions. Optimization of biosensor fabrication and effective measurement conditions were performed. The optimized films presented sensitivity, linearity and detection range to glucose of 14.6 ± 0.4mV/decade, 99.8% and from 10-4M to 10-1mol/L. Two different biosensors were produced based on the enzymatic reaction of urea with selectivity to ammonium or hydroxyl ions. For ammonium ion selective film, the sensor's parameters were 14.7 ± 0.9mV/decade, 98.2% and from 10-5 to 10-1mol/L. For the hydroxyl ion selective film, the same parameters were 7.4 ± 0.5mV/decade, 98.1% and from 10-5 to 10-1mol/L. The change in the oxidation state of the polymeric matrix explains: i) the large loss of functionality of glucose biosensor in time, ii) the conservation of functionality to the hydroxyl ions for urea biosensor and iii) the selectivity variation of the ammonium ion selective urea biosensor. The results indicate that the polymeric matrix has indeed changeable selectivity, what can be applied in different situations for biosensors production.

Electrochemical fabrication of Ni nanoparticles-decorated electrochemically reduced graphene oxide composite electrode for non-enzymatic glucose detection

Nickel nanoparticles (NiNPs)-decorated electrochemically reduced graphene oxide (ERGO) nanocomposite (NiNPs/ERGO) was fabricated on an indium-tin-oxide electrode using a facile one-pot electrochemical approach for highly sensitive detection of glucose. The composition, crystallinity, and morphology of the nanocomposite were characterized by X-ray photoelectron spectroscopy, X-ray diffraction, field-emission scanning electron microscopy, and transmission electron microscopy. The as-prepared NiNPs/ERGO electrodes were also used for the amperometric determination of glucose in alkaline media, exhibiting non-enzymatic glucose biosensor behavior [linear range of 0.5–244 µM, detection limit of 40 nM signal-to-noise ratio=3]. The NiNPs/ERGO nanocomposites for glucose biosensor applications exhibited high electrocatalytic performance compared to bare NiNPs and bare ERGO structures. Furthermore, the fabricated non-enzymatic glucose sensors possessed excellent selectivity in the presence of ascorbic acid due to the synergistic effect of NiNPs and ERGO. These results indicate that the NiNPs/ERGO nanocomposite is a potential sensor for the voltammetric and amperometric detection of glucose.

The Novel biocatalytic cascade ZIF-8 capsule/Polysulfone Stereostructure and its Application in Amperometric Glucose Biosensors

The Novel biocatalytic cascade ZIF-8 capsule/Polysulfone Stereostructure and its Application in Amperometric Glucose Biosensors

Novel Glucose Oxidase Interlocked Prussian Blue/Polysulfone Stereo-Structure and its Application in Amperometric Glucose Biosensor

Novel Glucose Oxidase Interlocked Prussian Blue/Polysulfone Stereo-Structure and its Application in Amperometric Glucose Biosensor

Peroxidase-Like Activity of Smart Nanomaterials and Their Advanced Application in Colorimetric Glucose Biosensors.

Diabetes is a dominating health issue with 425 million people suffering from the disease worldwide and 4 million deaths each year. To avoid further complications, the diabetic patient blood glucose level should be strictly monitored despite there being no cure for diabetes. Colorimetric biosensing has attracted significant attention because of its low cost, simplicity, and practicality. Recently, some nanomaterials have been found that possess unexpected peroxidase-like activity, and great advances have been made in fabricating colorimetric glucose biosensors based on the peroxidase-like activity of these nanomaterials using glucose oxidase. Compared with natural horseradish peroxidase, the nanomaterials exhibit flexibility in structure design and composition, and have easy separation and storage, high stability, simple preparation, and tunable catalytic activity. To highlight the significant progress in the field of nanomaterial-based peroxidase-like activity, this work discusses the various smart nanomaterials that mimic horseradish peroxidase and its mechanism and development history, and the applications in colorimetric glucose biosensors. Different approaches for tunable peroxidase-like activity of nanomaterials are summarized, such as size, morphology, and shape; surface modification and coating; and metal doping and alloy. Finally, the conclusion and challenges facing peroxidase-like activity of nanomaterials and future directions are discussed.

Spatial Architecture of Modified Carbon Nanotubes/Electrochemically Reduced Graphene Oxide Nanomaterial for Fast Electron Transfer. Application in Glucose Biosensor

AbstractElectron transfer (ET) reactions in bioelectrocatalysis of enzymes at electrode surfaces require not only the efficient immobilization, but also highly conductive nanostructured platform, which allows for retaining its bioactivity and structural conformation. The novel architecture of spatially separated electrochemically reduced graphene oxide (ERGO) by multi‐walled carbon nanotubes functionalized with 4‐(pyrrole‐1‐yl) benzoic acid (MWCNT/PyBA) with the accurate porous structure could be an alternative for earlier approaches to the construction of bioelectrocatalytic systems with rapid diffusion of reagents from the solution to the enzyme molecule. The formation of ERGO/MWCNT/PyBA system was confirmed by electrochemical, spectroscopic and microscopic methods. The cyclic voltammetry experiments revealed that the presence of ERGO in the conductive material affects the electronic communication between the enzyme molecule and modified electrode surface greatly improving its ET properties resulting in a double increase of the heterogeneous ET rate constant value (ks=6.5 s−1). The fabricated glucose oxidase based biosensor sensitively detects glucose, therefore, ERGO/MWCNT/PyBA architecture could provide a novel and efficient platform for immobilization of redox enzymes.

Electropolymerization of aniline and (N-phenyl-o-phenylenediamine) for glucose biosensor application

Fabrication of conductive polyaniline nanofibers (PAnNFs) and poly(aniline-co-N-phenyl-o-phenylenediamine) nanoflakes [P(An-co-PoPD)] can promote a high surface area which influences rapid ion exchange and hence improved sensitivity in biosensor applications. Here, fabrication of two conductive films of PAnNFs from aniline monomer and a mixture of aniline/N-phenyl-o-phenylenediamine (oPD) monomers through cyclic voltammetry (potentiodynamic electropolymerization) technique was performed. The electrochemical features of aniline monomer generate polyaniline nanofibers compared to aniline with addition of oPD monomer that generate nano-flakes. Electro-fabricated electrodes were characterized by SEM, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A molecular recognition layer of glucose oxidase within chitosan (GOx:CHI) was applied to the electrode-supported polymer and produced chronoamperometry dose–responses to different glucose molar concentrations with sensitivities that were larger for P(An-co-PoPD) compared to PAnNFs electrode.

Bifunctional (Zn,Fe)3O4 nanoparticles: Tuning their efficiency for potential application in reagentless glucose biosensors and magnetic hyperthermia

In a new approach based on a two-step procedure, co-precipitation method followed by hydrothermal treatment in a microwave field, Zn-substituted Fe3O4 nanoparticles (ZnxFe3-xO4) were synthesized. Results of XRD, FT–IR and TEM analysis clearly demonstrate that nanoparticles were single phase, crystallizing in the spinel structure type (S.G. Fd3¯m) with crystallite size in the range of 2–20 nm, which strongly depends on Zn concentration. The produced nanoparticles were used for fabrication of modified carbon paste electrodes as a novel system for electrochemical non-enzymatic glucose detection. It was found that the increase of zinc concentration up to the value of x = 0.56 (Zn0.56Fe2.44O4) of as-prepared nanoparticles was followed with an increase of a performance of the modified carbon paste electrode toward glucose detection. Linear working range from 0.1 to 2 mM was obtained with detection limit of 0.03 mM, and with fast response time (<3 s). Proposed sensor was successfully applied for the determination of glucose level in real samples with satisfactory recovery. The synthesized zinc-ferrite samples were also tested as potential heating agents in magnetic hyperthermia. The heating ability (SAR value) increases with x value, reaching maximum for x = 0.37. This is correlated with changes of particle size and magnetic characteristics which strongly depend on Zn concentration.