A flexible glucose biosensor modified by reduced-swelling and conductive zwitterionic hydrogel enzyme membrane.

This paper reports a flexible glucose biosensor which is modified by a reduced-swelling and conductive zwitterionic hydrogel enzyme membrane that contains two forms of chemical cross-links. One chemical cross-linking is induced by thermal initiators and forms the basal network of the hydrogel. Another cross-linking is achieved by the coordination interactions between the multivalent metal ion Al3+ and anionic group -COO- of zwitterionic poly-carboxy betaine (pCBMA), which significantly increase the cross-linking density of the zwitterionic hydrogel, improving the reduced-swelling property and reducing the pore size. The better reduced-swelling property and reduced diameters of pores within the zwitterionic hydrogel make less glucose oxidase (GOx) leakage, thus significantly improving the enzyme membrane's service life. By introducing the Al3+ and Cl-, the conductivity of the zwitterionic hydrogel is enhanced approximately 10.4-fold. According to the enhanced conductivity, the reduced-swelling property, and the high GOx loading capacity of the zwitterionic hydrogel, the sensitivity of the biosensor with GOx/pCBMA-Al3+ is significantly improved by 5 times and has a long service life. Finally, the proposed GOx/pCBMA-Al3+ biosensor was applied in non-invasive blood glucose detection on the human body, verifying the capability in practice.

pH-responsive persistent luminescence nanoprobes biosensor for autofluorescence-free determination of glucose level in human samples and fingerprint encryption.

Glucose level is an important indicator of diabetes, and maintaining an appropriate physiological concentration of glucose is important for human health. However, traditional optical sensors are interfered by the interference of strong background autofluorescence and natural responsive luminescence, which severely limits their application in complex biological samples. Herein, as a novel glucose biosensing probe, green-emitting Zn2GeO4:Mn2+, Eu3+ (ZGME) persistent luminescence nanoparticles (PLNPs) with pH stimulus-responsive was prepared by a facile one-pot hydrothermal method. We also investigated the pH stimulus-responsive luminescence behaviour of ZGME over a range of pH values from 2.8 to 8.0. Taking advantage of the interesting property that ZGME photoluminescence intensity has a pH response, within an extraordinarily narrow pH range of 5.0-6.5 for highly selectivity and sensitive determination of glucose level in human samples by acid-responsive quenching and persistent luminescent performance. The detection results show high accuracy of the measured values of glucose in serum with a wide detection range (2.5 µg L-1-10 mg L-1) and low detection limit (0.5 µg L-1). Finally, the pH-responsive persistent luminescence also makes ZGME promising for high-level fingerprint information encryption. Hence, the established pH stimulation-responsive PLNPs-based biosensing probe offers excellent performance with high selective, accuracy and signal-to-noise ratio for detection of glucose level in human samples.

Multi-walled carbon nanotubes functionalized with a new Schiff base containing phenylboronic acid residues: application to the development of a bienzymatic glucose biosensor using a response surface methodology approach.

An innovative supramolecular architecture is reported for bienzymatic glucose biosensing based on the use of a nanohybrid made of multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with a Schiff base modified with two phenylboronic acid residues (SB-dBA) as platform for the site-specific immobilization of the glycoproteins glucose oxidase (GOx) and horseradish peroxidase (HRP). The analytical signal was obtained from amperometric experiments at - 0.050 V in the presence of 5.0 × 10-4 M hydroquinone as redox mediator. The concentration of GOx and HRP and the interaction time between the enzymes and the nanohybrid MWCNT-SB-dBA deposited at glassy carbon electrodes (GCEs) were optimized through a central composite design (CCD)/response surface methodology (RSM). The optimal concentrations of GOx and HRP were 3.0 mg mL-1 and 1.50 mg mL-1, respectively, while the optimum interaction time was 3.0 min. The bienzymatic biosensor presented a sensitivity of (24 ± 2) × 102 µA dL mg-1 ((44 ± 4) × 102 µA M-1), a linear range between 0.06 mg dL-1 and 21.6 mg dL-1 (3.1 µM-1.2 mM) (R2 = 0.9991), and detection and quantification limits of 0.02 mg dL-1 (1.0 µM) and 0.06 mg dL-1 (3.1 µM), respectively. The reproducibility for five sensors prepared with the same MWCNT-SB-dBA nanohybrid was 6.3%, while the reproducibility for sensors prepared with five different nanohybrids and five electrodes each was 7.9%. The GCE/MWCNT-SB-dBA/GOx-HRP was successfully used for the quantification of glucose in artificial human urine and commercial human serum samples.

Stretchable Nanofiber-Based Felt as a String Electrode for Potential Use in Wearable Glucose Biosensors.

Nanofiber technology is leading the revolution of wearable technology and provides a unique capability to fabricate smart textiles. With the novel fabrication technique of electrospinning, nanofibers can be fabricated and then manufactured into a durable conductive string for the application of smart textiles. This paper presents an electrospun nanofiber mesh-based (NF-Felt) string electrode with a conducting polymer coating for an electrochemical enzymatic glucose sensor. The surface area of a nanofiber matrix is a key physical property for enhanced glucose oxidase (GOx) enzyme binding for the development of an electrochemical biosensor. A morphological characterization of the NF-Felt string electrode was performed using scanning electron microscopy (SEM) and compared with a commercially available cotton-polyester (Cot-Pol) string coated with the same conducting polymer. The results from stress-strain testing demonstrated high stretchability of the NF-Felt string. Also, the electrochemical characterization results showed that the NF-Felt string electrode was able to detect a glucose concentration in the range between 0.0 mM and 30.0 mM with a sensitivity of 37.4 µA/mM·g and a detection limit of 3.31 mM. Overall, with better electrochemical performance and incredible flexibility, the NF-Felt-based string electrode is potentially more suitable for designing wearable biosensors for the detection of glucose in sweat.

A biosensor based on Fe3O4@MXene-Au nanocomposites with high peroxidase-like activity for colorimetric and smartphone-based detection of glucose.

A novel magnetic nanozyme Fe3O4@MXene-Au nanocomposite, which possessed higher peroxidase-like activity than that of Fe3O4 nanoparticles and Fe3O4@MXene nanocomposites, was developed. The outstanding magnetic properties of the nanozyme endowed it with the ability of simple and rapid separation, achieving great recyclability. Based on Fe3O4@MXene-Au nanocomposites and glucose oxidase (Glu Ox), a highly selective colorimetric biosensor for glucose detection was developed. Fe3O4@MXene-Au nanocomposites can catalyze H2O2 produced from glucose catalyzed by glucose oxidase to ·OH and oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB) with a significant absorbance at 652 nm. The linear range of glucose was 0-1.4 mM under optimal conditions, with a limit of detection (LOD) of 0.11 mM. Glucose in human whole blood was successfully detected with satisfactory recoveries. Furthermore, a facile agarose hydrogel detection platform was designed. With smartphone software, glucose detection can be realized by the agarose hydrogel platform, demonstrating the potential in on-site and visual detection of glucose.

Investigation of GOx Stability in a Chitosan Matrix: Applications for Enzymatic Electrodes.

In this study, we designed a new biosensing membrane for the development of an electrochemical glucose biosensor. To proceed, we used a chitosan-based hydrogel that entraps glucose oxidase enzyme (GOx), and we crosslinked the whole matrix using glutaraldehyde, which is known for its quick and reactive crosslinking behavior. Then, the stability of the designed biosensors was investigated over time, according to different storage conditions (in PBS solution at temperatures of 4 °C and 37 °C and in the presence or absence of glucose). In some specific conditions, we found that our biosensor is capable of maintaining its stability for more than six months of storage. We also included catalase to protect the biosensing membranes from the enzymatic reaction by-products (e.g., hydrogen peroxide). This design protects the biocatalytic activity of GOx and enhances the lifetime of the biosensor.

Nature-Inspired Biomolecular Corona Based on Poly(caffeic acid) as a Low Potential and Time-Stable Glucose Biosensor.

Herein, we present a novel biosensor based on nature-inspired poly(caffeic acid) (PCA) grafted to magnetite (Fe3O4) nanoparticles with glucose oxidase (GOx) from Aspergillus niger via adsorption technique. The biomolecular corona was applied to the fabrication of a biosensor system with a screen-printed electrode (SPE). The obtained results indicated the operation of the system at a low potential (0.1 V). Then, amperometric measurements were performed to optimize conditions like various pH and temperatures. The SPE/Fe3O4@PCA-GOx biosensor presented a linear range from 0.05 mM to 25.0 mM, with a sensitivity of 1198.0 µA mM-1 cm-2 and a limit of detection of 5.23 µM, which was compared to other biosensors presented in the literature. The proposed system was selective towards various interferents (maltose, saccharose, fructose, L-cysteine, uric acid, dopamine and ascorbic acid) and shows high recovery in relation to tests on real samples, up to 10 months of work stability. Moreover, the Fe3O4@PCA-GOx biomolecular corona has been characterized using various techniques such as Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and Bradford assay.

Biosensors and biomarkers for determining gestational diabetes mellitus and jaundice in children.

Gestational diabetes and jaundice are the correlated diseases predominantly found in mother and newborn child. Jaundice is a neonatal complication with an increased risk when mother has gestational diabetes. Mothers with diabetes at an early stage of gestational age are at higher risk for hyperbilirubinemia (jaundice) and hypoglycemia. So, it is mandatory to monitor the condition of diabetes and jaundice during the pregnancy period for a healthy child and safest delivery. On the other hand, nanotechnology has displayed a rapid advancement that can be implemented to overcome these issues. The development of high-performance diagnosis using appropriate biomarkers provides their efficacy in the detection gestational diabetes and jaundice. This review covers the aspects from a fast-developing field to generate nanosensors in the nanosized dimensions for the applications to overcome these complications by coupling diagnostics with biomarkers. Further, the serum-based biomarkers have been discussed for these inborn complications and also the diagnosis with the current trend.

A molecularly imprinted electrochemical biosensor based on hierarchical Ti2Nb10O29 (TNO) for glucose detection.

A novel molecularly imprinted electrochemical biosensor for glucose detection is reported based on a hierarchical N-rich carbon conductive-coated TNO structure (TNO@NC). Firstly, TNO@NC was fabricated by a novel polypyrrole-chemical vapor deposition (PPy-CVD) method with minimal waste generation. Afterward, the electrode modification with TNO@NC was performed by dropping TNO@NC particles on glassy carbon electrode surfaces by infrared heat lamp. Finally, the glucose-imprinted electrochemical biosensor was developed in presence of 75.0 mM pyrrole and 25.0 mM glucose in a potential range from + 0.20 to + 1.20 V versus Ag/AgCl via cyclic voltammetry (CV). The physicochemical and electrochemical characterizations of the fabricated molecularly imprinted biosensor was conducted by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) method, X-ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy (EIS), and CV techniques. The findings demonstrated that selective, sensitive, and stable electrochemical signals were proportional to different glucose concentrations, and the sensitivity of molecularly imprinted electrochemical biosensor for glucose detection was estimated to be 18.93 µA µM-1 cm-2 (R2 = 0.99) at + 0.30 V with the limit of detection (LOD) of 1.0 × 10-6 M. Hence, it can be speculated that the fabricated glucose-imprinted biosensor may be used in a multitude of areas, including public health and food quality.

Reduced Graphene Oxide and Polyaniline Nanofibers Nanocomposite for the Development of an Amperometric Glucose Biosensor.

The control of glucose concentration is a crucial factor in clinical diagnosis and the food industry. Electrochemical biosensors based on reduced graphene oxide (rGO) and conducting polymers have a high potential for practical application. A novel thermal reduction protocol of graphene oxide (GO) in the presence of malonic acid was applied for the synthesis of rGO. The rGO was characterized by scanning electron microscopy, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, and Raman spectroscopy. rGO in combination with polyaniline (PANI), Nafion, and glucose oxidase (GOx) was used to develop an amperometric glucose biosensor. A graphite rod (GR) electrode premodified with a dispersion of PANI nanostructures and rGO, Nafion, and GOx was proposed as the working electrode of the biosensor. The optimal ratio of PANI and rGO in the dispersion used as a matrix for GOx immobilization was equal to 1:10. The developed glucose biosensor was characterized by a wide linear range (from 0.5 to 50 mM), low limit of detection (0.089 mM), good selectivity, reproducibility, and stability. Therefore, the developed biosensor is suitable for glucose determination in human serum. The PANI nanostructure and rGO dispersion is a promising material for the construction of electrochemical glucose biosensors.

Enhanced Electrochemical Characteristics of the Glucose Oxidase Bioelectrode Constructed by Carboxyl-Functionalized Mesoporous Carbon.

This research revealed the effect of carboxyl-functionalization on the mesoporous carbon (MC)-fixed glucose oxidase (GOx) for promoting the properties of bioelectrodes. It showed that the oxidation time, temperature and concentration, can significantly affect MC carboxylation. The condition of 2 M ammonium persulfate, 50 °C and 24 h was applied in the study for the successful addition of carboxyl groups to MC, analyzed by FTIR. The nitrogen adsorption isotherms, and X-ray diffraction analysis showed that the carboxylation process slightly changed the physical properties of MC and that the specific surface area and pore size were all well-maintained in MC-COOH. Electrochemical characteristics analysis showed that Nafion/GOx/MC-COOH presented better electrocatalytic activity with greater peak current intensity (1.13-fold of oxidation peak current and 4.98-fold of reduction peak current) compared to Nafion/GOx/MC. Anodic charge-transfer coefficients (α) of GOx/MC-COOH increased to 0.77, implying the favored anodic reaction. Furthermore, the GOx immobilization and enzyme activity in MC-COOH increased 140.72% and 252.74%, leading to the enhanced electroactive GOx surface coverage of Nafion/GOx/MC-COOH electrode (22.92% higher, 1.29 × 10-8 mol cm-2) than the control electrode. Results showed that carboxyl functionalization could increase the amount and activity of immobilized GOx, thereby improving the electrode properties.

3D Hydrogen Titanate Nanotubes on Ti Foil: A Carrier for Enzymatic Glucose Biosensor.

Glucose oxidase (GOx) based biosensors are commercialized and marketed for the high selectivity of GOx. Incorporation nanomaterials with GOx can increase the sensitivity performance. In this work, an enzyme glucose biosensor based on nanotubes was fabricated. By using Ti foil as a carrier, hydrogen titanate nanotubes (HTNTs), which present fine 3D structure with vast pores, were fabricated in-situ by the hydrothermal treatment. The multilayer nanotubes are open-ended with a diameter of 10 nm. Then glucose oxidase (GOx) was loaded on the nanotubes by cross-linking to form an electrode of the amperometric glucose biosensor (GOx/HTNTs/Ti electrode). The fabricated GOx/HTNTs/Ti electrode had a linear response to 1-10 mM glucose, and the response time was 1.5 s. The sensitivity of the biosensor was 1.541 µA·mM-1·cm-2, and the detection limit (S/N = 3) was 59 µM. Obtained results indicate that the in-situ fabrication and unique 3D structure of GOx/HTNTs/Ti electrode are beneficial for its sensitivity.

Non-Invasive Blood Glucose Monitoring Technology: A Review.

In recent years, with the rise of global diabetes, a growing number of subjects are suffering from pain and infections caused by the invasive nature of mainstream commercial glucose meters. Non-invasive blood glucose monitoring technology has become an international research topic and a new method which could bring relief to a vast number of patients. This paper reviews the research progress and major challenges of non-invasive blood glucose detection technology in recent years, and divides it into three categories: optics, microwave and electrochemistry, based on the detection principle. The technology covers medical, materials, optics, electromagnetic wave, chemistry, biology, computational science and other related fields. The advantages and limitations of non-invasive and invasive technologies as well as electrochemistry and optics in non-invasives are compared horizontally in this paper. In addition, the current research achievements and limitations of non-invasive electrochemical glucose sensing systems in continuous monitoring, point-of-care and clinical settings are highlighted, so as to discuss the development tendency in future research. With the rapid development of wearable technology and transdermal biosensors, non-invasive blood glucose monitoring will become more efficient, affordable, robust, and more competitive on the market.

Reusable, Non-Invasive, and Ultrafast Radio Frequency Biosensor Based on Optimized Integrated Passive Device Fabrication Process for Quantitative Detection of Glucose Levels.

The increase in the number of people suffering diabetes has been the driving force behind the development of glucose sensors to overcome the current testing shortcomings. In this work, a reusable, non-invasive and ultrafast radio frequency biosensor based on optimized integrated passive device fabrication process for quantitative detection of glucose level was developed. With the aid of the novel biosensor design with hammer-shaped capacitors for carrying out detection, both the resonance frequency and magnitude of reflection coefficient can be applied to map the different glucose levels. Meanwhile, the corresponding fabrication process was developed, providing an approach for achieving quantitative detection and a structure without metal-insulator-metal type capacitor that realizes low cost and high reliability. To enhance the sensitivity of biosensor, a 3-min dry etching treatment based on chlorine/argon-based plasma was implemented for realizing hydrophilicity of capacitor surface to ensure that the biosensor can be touched rapidly with glucose. Based on above implementation, a non-invasive biosensor having an ultrafast response time of superior to 0.85 s, ultralow LOD of 8.01 mg/dL and excellent reusability verified through five sets of measurements are realized. The proposed approaches are not limited the development of a stable and accurate platform for the detection of glucose levels but also presents a scheme toward the detection of glucose levels in human serum.

A novel electrochemical glucose biosensor based on a poly (L-aspartic acid)-modified carbon-paste electrode.

A new amperometric biosensor was fabricated by means of electropolymerization of L-aspartic acid on a carbon-paste electrode (CPE) for the bioelectrochemical determination of glucose. The electropolymerization process was conducted via cyclic voltammetry (CV). The modified CPE with poly (L-aspartic acid) (PAA) provided free carboxyl groups so as to immobilize the glucose oxidase (GOx), and further, enhanced the electrocatalytic activity of the hydrogen peroxide (H2O2). The biosensor displayed both good stability and good bioactivity. The sensitivity of the prepared biosensor was 5.3 µA cm-2 mM-1. Its linear range extended from 0.05 mM to 1.0 mM, with the low limit of detection (LOD) being 69.2 µM. The Michaelis-Menten constant was found to be 1.17 mM. Furthermore, the biosensor showed good anti-interference ability in relation to dopamine, uric acid, and ascorbic acid. Taken together, these results demonstrate that PAA/CPE is a promising material for the fabrication of glucose biosensor.

Fabrication of a low background signal glucose biosensor with 3D network materials as the electrocatalyst.

Glucose oxidase (GOx) based biosensor is an effective method to determine glucose level. However, the biosensors embedded with high electroactive species suffered from high background signal levels, which leading to relative low sensitivity for glucose sensing. In this work, a novel 3D network materials based glucose biosensor with low background signal was constructed, which demonstrated high sensitivity and selectivity towards glucose assay. Here, the combination of ionic liquid modified graphene sheets (GS-IL) and Au nanorods (Au NRs) acted as high electroactive catalyst, and thiol-containing silica sol-gel served as a nonconductive matrix to self-assembly of GS-IL and Au NRs to form the three-dimensional (3D) network materials. Meanwhile, the doping amount of the sol-gel had significant influences on electrochemical performance of the 3D network materials based biosensor. As a result, optimized 3.75% doping 3D network materials were selected to construct the glucose biosensor, which exhibited low background signal and high sensitivity. This biosensor was successfully applied in monitoring the glucose levels of serum and brain microdialysate samples.

Application of central composite design for the optimization of electrode surface composition for glucose biosensor fabrication.

The use of a central composite design (CCD) for the optimization of electrode surface composition and its application to develop an amperometric glucose biosensor as a model system are described. A five-level three-factorial CCD was applied to determine the optimum electrode surface composition for three critical variables: amounts of carboxylated multiwall carbon nanotubes (c-MWCNT), titanium dioxide nanoparticles (TiO2NP), and glucose oxidase (GOx). The statistical significance of the model and factors were evaluated using the variance analysis (ANOVA) at 95% of confidence level. The optimized electrode surface composition was used for the fabrication of the glucose biosensor. The resulting biosensor showed linear response to glucose from 2.0 × 10-5 to 1.9 × 10-3 M with a detection limit of 2.1 × 10-6 M and sensitivity of 168.5 µA mM-1 cm-2 under optimal experimental conditions. Analytical performance parameters of the biosensor were also compared with those obtained with the glucose biosensors fabricated using the electrode compositions optimized by conventional one factor-at-a-time method and 22 CCD (for c-MWCNT and TiO2NP amounts). The optimization of the critical variables, achieved by CDD, leads us to fabricate the glucose biosensor in the best electrode surface composition which was promoted by the improved analytical performance. The proposed biosensor was applied to the analysis of glucose in serum samples and the obtained results were well correlated with the results of reference method. Graphical abstract ᅟ.

Ultrathin NiCo2O4 nanowalls supported on a 3D nanoporous gold coated needle for non-enzymatic amperometric sensing of glucose.

A disposable needle-type of hybrid electrode was prepared from a core of stainless steel needle whose surface was modified with a 3D nanoporous gold/NiCo2O4 nanowall hybrid structure for electrochemical non-enzymatic glucose detection. This hybrid electrode, best operated at 0.45 V (vs. SCE) in solutions of pH 13 has a linear response in the 0.01 to 21 mM glucose concentration range, a response time of <1 s, and a 1 µM detection limit (at an S/N ratio of 3). The remarkable enhancement compared to the solid gold/NiCo2O4 and stainless steel/NiCo2O4 hybrid electrodes in electrochemical performance is assumed to originate from the good electrical conductivity and large surface area of the hybrid electrode, which enhance the transport of mass and charge during electrochemical reactions. This biosensor was also applied to real sample analysis with little interferences. The electrode is disposable and considered to be a promising tool for non-enzymatic sensing of glucose in a variety of practical situations. Graphical abstract Ultrathin NiCo2O4 nanowalls supported on nanoporous gold that is coated on a stainless steel needle was fabricated for sensitive non-enzymatic amperometric sensing of glucose.

Electrochemical nonenzymatic sensing of glucose using advanced nanomaterials.

An overview (with 376 refs.) is given here on the current state of methods for electrochemical sensing of glucose based on the use of advanced nanomaterials. An introduction into the field covers aspects of enzyme based sensing versus nonenzymatic sensing using nanomaterials. The next chapter cover the most commonly used nanomaterials for use in such sensors, with sections on uses of noble metals, transition metals, metal oxides, metal hydroxides, and metal sulfides, on bimetallic nanoparticles and alloys, and on other composites. A further section treats electrodes based on the use of carbon nanomaterials (with subsections on carbon nanotubes, on graphene, graphene oxide and carbon dots, and on other carbonaceous nanomaterials. The mechanisms for electro-catalysis are also discussed, and several Tables are given where the performance of sensors is being compared. Finally, the review addresses merits and limitations (such as the frequent need for working in strongly etching alkaline solutions and the need for diluting samples because sensors often have analytical ranges that are far below the glucose levels found in blood). We also address market/technology gaps in comparison to commercially available enzymatic sensors. Graphical Abstract Schematic representation of electrochemical nonenzymatic glucose sensing on the nanomaterials modified electrodes. At an applied potential, the nanomaterial-modified electrodes exhibit excellent electrocatalytic activity for direct oxidation of glucose oxidation.

Current and Emerging Technology for Continuous Glucose Monitoring.

Diabetes has become a leading cause of death worldwide. Although there is no cure for diabetes, blood glucose monitoring combined with appropriate medication can enhance treatment efficiency, alleviate the symptoms, as well as diminish the complications. For point-of-care purposes, continuous glucose monitoring (CGM) devices are considered to be the best candidates for diabetes therapy. This review focuses on current growth areas of CGM technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors. The superiority of CGM systems is introduced firstly, and then the strategies for fabrication of minimally-invasive and non-invasive CGM biosensors are discussed, respectively. Finally, we briefly outline the current status and future perspective for CGM systems.