High-performance Glucose Biosensor Research Articles

The Implementation of a High Performance Glucose Biosensor Based on Differential EGFET and Chopper Amplifier

The Implementation of a High Performance Glucose Biosensor Based on Differential EGFET and Chopper Amplifier

Study of electrochemical biosensor for determination of glucose based on Prussian blue/gold nanoparticles-chitosan nanocomposite film sensing interface

A highly electroactive bilayer composite film sensing interface of Prussian blue (PB)/gold nanoparticles-chitosan (AuNPs-CS) was modified on Au electrode through electrochemical deposition and coating method followed by integrating glucose oxidase (GOx) into the interfacial matrix to fabricate a high-performance glucose biosensor. The excellent electrocatalytic ability of the PB/AuNPs-CS composite film sensing interface for H2O2 was evaluated, which has a broad linear response of 0.01–7.95 mM, with a low detection limit (LOD) 0.269 μM and a high sensitivity of 511.82 μA·mM−1·cm−2. The enhanced electrocatalytic activity of this sensing interface for H2O2 is attributed to the protection from the network CS film to PB and the synergistic effect of PB and AuNPs. Consequently, an electrochemical biosensing interface was constructed with GOx immobilized as a model enzyme. The PB/GOx-AuNPs-CS biosensing nanocomposite film was capable of a fast steady-state response time (within 2 s) and high sensitivity to glucose with a wide linear range of: 0.025–2.00 mM (R 2 = 0.99), with a sensitivity of 40.41 μA·mM−1·cm−2 and a LOD of 1.62 μM; and 2.00–6.50 mM (R 2 = 0.98), with a sensitivity of 8.90 μA·mM−1·cm−2 and a LOD of 7.16 μM. The biosensor has good anti-interference and selectivity, which provides a promising wide linear range platform for clinical blood glucose detection in the future.

Nano/micro-scaled materials based optical biosensing of glucose

Diabetes is a chronic metabolic disease that lasts a person's life and the estimation of blood glucose concentration is one of the main diagnostic criteria for this disease. The past decade has witnessed a huge demand for new biocompatibility and high-performance glucose biosensors. Non-enzymatic optical glucose sensing using nano/microscaled materials has surged significantly as it provides a direct visualized and cost-effective way to measure glucose concentrations. This review, in a non-exhaustive way, considers some of the recent most important achievements in the glucose-sensitive optical biosensors based upon nano/microscaled materials. Such materials are capable of mimicking the activities of the enzymes which oxidize glucose to release H2O2. The overall framework of the review can be divided into three parts. The first part describes the colorimetric glucose sensing using nano/microscaled materials as enzyme mimics for the oxidation of different chromogenic substrates. In the second part, some recent developments in chromogenic substrate-free fluorescence glucose sensing facilitated by nano/microscaled materials are elaborated. The third part reviews the glucose-sensing through Förster resonance energy transfer (FRET) based assays. Finally, some current challenges, gaps in fundamental understanding and future improvements in the field of optical glucose biosensors are discussed.

A glucose biosensor based on glucose oxidase fused to a carbohydrate binding module family 2 tag that specifically binds to the cellulose-modified electrode

The method of immobilization of glucose oxidase (GOD) on electrodes is especially important for the fabrication and performance of glucose biosensors. In this study, a carbohydrate binding module family 2 (CBM2) was successfully fused to the C terminal of GOD with a natural linker (NL) in endo-β-xylanase by genetic recombination, and a fusion GOD (GOD-NL-CBM2) was obtained. The CBM2 was used as an affinity adsorption tag for immobilization of the GOD-NL-CBM2 on a cellulose modified electrode. The specific activity of GOD-NL-CBM2 was comparable to that of the wild type GOD. In addition, the CBM2 tag of fusion GOD almost maintained its highest binding capacity under optimal catalytic conditions (pH 5.0, 50 °C). The morphology and composition analysis of the cellulose film reacted with and without GOD or GOD-NL-CBM2 confirmed the immobilization of GOD-NL-CBM2. The electrochemical properties of the GOD-NL-CBM2/cellulose film bioelectrode, with a characteristic peak of H2O2 at +0.6 V in the presence of glucose, revealed the capability of the immobilized GOD-NL-CBM2 to efficiently catalyze glucose and produce H2O2. Additionally, the current signal response of the biosensor to glucose was linear in the concentration range from 1.25 to 40 mM (r2 ≥ 0.99). The sensitivity and detection limit of the GOD-NL-CBM2/cellulose film bioelectrode were 466.7 μA mol−1 L cm-2 and 0.475 mM (S/N = 3), respectively. Moreover, the glucose biosensor exhibited a rapid current change (< 5 s), high reproducibility (Relative standard deviation, RSD < 5%), substrate selectivity and stability, and retained about 80 % of the original current response after 2 months. The affinity adsorption-based immobilization strategy for GOD provides a promising approach to develop a high performance glucose biosensor.

Metal oxide-based composite for non-enzymatic glucose sensors

The increasing demand for monitoring the glucose concentration in the blood of diabetic patients has aroused the attention of researchers to prepare high-performance glucose biosensors. After decades of development, enzyme-based biosensors have gradually matured and commercialized, but they still suffer from insufficient stability due to the inherent defects of the enzyme. Non-enzymatic glucose sensor was proposed to address this issue. The introduction of nanotechnology has provided more possibilities for the preparation of highly efficient catalytic materials. Among the synthesized electrocatalysts, metal oxides are one of the most important components owing to their outstanding properties. Recent studies have integrated metal oxides with other materials to further improve sensor performance. This review focuses on the application of metal oxide-based hybrid structure in the glucose sensor, mainly including metal oxide/metal oxide, metal/metal oxide, and carbon material/metal oxide. The preparation method, electrochemical properties, and catalytic mechanism of the sensors are discussed in detail. Finally, we present some of the existing challenges and make personal predictions for the future development of non-enzymatic glucose sensors.

High-performance glucose biosensor based on green synthesized zinc oxide nanoparticle embedded nitrogen-doped carbon sheet

A new, highly selective, sensitive and stable enzymatic glucose sensor was fabricated on glassy carbon electrode (GCE) using zinc oxide (ZnO) nanoparticles embedded nitrogen-doped carbon sheets (ZnO@NDCS), glucose oxidase (GOx) (assigned as GCE/ZnO@NDCS/GOx). First, ZnO@NDCS were synthesized by a simple hydrothermal method. Zn powder, aqueous ammonia, and peach extract were served as the precursor for ZnO NPs, nitrogen and carbon, respectively. The fabricated GCE/ZnO@NDCS/GOx biosensor exhibited a high and reproducible sensitivity of 231.7 μA mM−1 cm−2. Also, showed a wide linear range from 0.2 to 12 mM with a correlation coefficient R2 = 0.998 and lowest detection limit (based on S/N ratio = 3) of 6.3 μM. The GCE/ZnO@NDCS/GOx biosensor is acceptably stable, selective, and it was successfully applied to the quantitative monitoring of glucose in human blood serum. The synthesized ZnO@NDCS nanocomposite may be found useful in other applications in the fields of solar cells and optoelectronic devices. These encouraging results suggest a simple and effective method obtain electrode material for the enzymatic glucose sensor.

ZnO nanorod-based FET biosensor for continuous glucose monitoring

Abstract This paper reports a high-performance glucose biosensor using ZnO nanorod-based field effect transistor (FET) to continuously monitor glucose concentration. Sensing area reduction of the sensor for minimally-invasive glucose monitoring with high sensitivity and good stability is demonstrated. The biosensor is fabricated via a hydrothermal growth of semiconducting ZnO nanorods between source and drain micro-electrodes incorporating with alternating current (AC) electric-field control. ZnO nanorod structured FET acts as a frequency mixer to transduce glucose concentration into a current change at certain difference frequency, which is measured by a lock-in amplifier. Due to the large surface-to-volume ratio of ZnO nanorods and the advanced frequency mixing detection scheme, good anti-jamming capability and long-term stability are realized. The glucose sensor achieves a high sensitivity of 1.6 mA/(μM-cm 2 ), a glucose concentration detection limit of 1 μM, and excellent long-term stability shown in 38-h continuous monitoring. In contrast to the state-of-the-art glucose sensors, the developed biosensor exhibits competitive advantages in sensitivity, long-term stability, tiny size and fabrication cost, which indicates its promising application potential in wearable continuous glucose monitoring for diabetics.

High performance electrochemical glucose sensor based on three-dimensional MoS2/graphene aerogel

Two-dimensional (2D) nanosheets have been extensively explored as electrode materials for the development of high-performance electrochemical biosensors due to their unique structural characteristics. Nevertheless, 2D nanosheets suffer from sheet aggregation issues limiting the electrical conductivity of layered metal sulfides or hydroxides. Here, we report high-performance glucose biosensors based on a three-dimensional (3D) aerogel composed of interconnected 2D MoS2 and graphene sheet. 3D MoS2/graphene aerogel (MGA) provides a large surface area for the effective immobilization of enzymes, and continuous framework of electrically conductive graphene sheets. Flow-injection amperometric evaluation of the glucose biosensor using a 3D MGA electrode exhibits a rapid response (∼4s), a linear detection range from 2 to 20mM, a sensitivity of 3.36μA/mM, and a low limit of detection of 0.29mM. Moreover, the interference response from oxidizable species, such as ascorbic acid, uric acid and dopamine is negligible at an operating potential of −0.45V.

3D NiO hollow sphere/reduced graphene oxide composite for high-performance glucose biosensor

The 3D NiO hollow sphere/reduced graphene oxide (rGO) composite was synthesized according to the coordinating etching and precipitating process by using Cu2O nanosphere/graphene oxide (GO) composite as template. The morphology, structure, and composition of the materials were characterized by SEM, TEM, HRTEM, XPS, and Raman spectra, and the electrochemical properties were studied by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and amperometry. Moreover, the electrochemical activity of the composite materials with different morphologies were also investigated, which indicating a better combination of the NiO hollow sphere and the rGO. Used as glucose sensing material, the 3D NiO hollow sphere/rGO composite modified electrode exhibits high sensitivity of ~2.04 mA mM−1 cm−2, quick response time of less than 5 s, good stability, selectivity, and reproducibility. Its application for the detection of glucose in human blood serum sample shows acceptable recovery and R.S.D. values. The outstanding glucose sensing performance should be attributed to the unique 3D hierarchical porous superstructure of the composite, especially for its enhanced electron-transfer kinetic properties.

Ni(OH)2/NiO nanosheet with opulent active sites for high-performance glucose biosensor

A novel non-enzymatic glucose sensor has been successfully fabricated based on Ni(OH)2/NiO nanosheet with unique defect-rich structure synthesized via a high-power, microwave-assisted hydrothermal method. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy were applied to characterize the composition and morphology of the materials. High-resolution transmission electron microscopy and Raman spectroscopy results verified that the Ni(OH)2/NiO nanosheets had abundant surface defects and additional active edge sites. Moreover, the glucose electrocatalytic properties of the defect-rich Ni(OH)2/NiO nanosheet were investigated through electrochemical methods, indicating that the fabricated biosensor had a high sensitivity of 2931.4μAmM−1cm−2, a wide linear range from 0.09mM to 3.62mM, and a low detection limit of 5.0μM (S/N=3). The excellent glucose-sensing properties can be attributed to the synergic effect of Ni(OH)2 and NiO, as well as the unique defect-rich structure of the active materials that produces opulent exposed active sites for glucose oxidation. The successful application of defect engineering to glucose sensing will pave a new way for the development of more efficacious catalyst.

Hierarchically mesostructured porous TiO2 hollow nanofibers for high performance glucose biosensing

Effective immobilization of enzymes on an electrode surface is of great importance for biosensor development, but it still remains challenging because enzymes tend to denaturation and/or form close-packed structures. In this work, a free-standing TiO2 hollow nanofibers (HNF-TiO2) was successfully prepared by a simple and scalable electrospun nanofiber film template-assisted sol-gel method, and was further explored for glucose oxidase (GOD) immobilization and biosensing. This porous and nanotubular HNF-TiO2 provides a well-defined hierarchical nanostructure for GOD loading, and the fine TiO2 nanocrystals facilitate direct electron transfer from GOD to the electrode, also the strong interaction between GOD and HNF-TiO2 greatly enhances the stability of the biosensor. The as-prepared glucose biosensors show good sensing performances both in O2-free and O2-containing conditions with good sensitivity, satisfactory selectivity, long-term stability and sound reliability. The novel textile formation, porous and hierarchically mesostructured nature of HNF-TiO2 with excellent analytical performances make it a superior platform for the construction of high-performance glucose biosensors.

High-performance glucose biosensor based on chitosan-glucose oxidase immobilized polypyrrole/Nafion/functionalized multi-walled carbon nanotubes bio-nanohybrid film

A highly electroactive bio-nanohybrid film of polypyrrole (PPy)-Nafion (Nf)-functionalized multi-walled carbon nanotubes (fMWCNTs) nanocomposite was prepared on the glassy carbon electrode (GCE) by a facile one-step electrochemical polymerization technique followed by chitosan-glucose oxidase (CH-GOx) immobilization on its surface to achieve a high-performance glucose biosensor. The as-fabricated nanohybrid composite provides high surface area for GOx immobilization and thus enhances the enzyme-loading efficiency. The structural characterization revealed that the PPy-Nf-fMWCNTs nanocomposite films were uniformly formed on GCE and after GOx immobilization, the surface porosities of the film were decreased due to enzyme encapsulation inside the bio-nanohybrid composite materials. The electrochemical behavior of the fabricated biosensor was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and amperometry measurements. The results indicated an excellent catalytic property of bio-nanohybrid film for glucose detection with improved sensitivity of 2860.3μAmM−1cm−2, the linear range up to 4.7mM (R2=0.9992), and a low detection limit of 5μM under a signal/noise (S/N) ratio of 3. Furthermore, the resulting biosensor presented reliable selectivity, better long-term stability, good repeatability, reproducibility, and acceptable measurement of glucose concentration in real serum samples. Thus, this fabricated biosensor provides an efficient and highly sensitive platform for glucose sensing and can open up new avenues for clinical applications.

Direct electrochemistry of glucose oxidase immobilized on Au nanoparticles-functionalized 3D hierarchically ZnO nanostructures and its application to bioelectrochemical glucose sensor

Three-dimensional (3D) hierarchically ZnO nanoarchitecture with controlled morphology and dimensions was synthesized by trisodium citrate-assisted solution phase method and functionalized by Au nanoparticles (AuNPs) via in situ reduction of HAuCl4. The as-prepared AuNPs-functionalized 3D hierarchically ZnO nanostructure (Au–ZnO nanocomposite) were used as a novel immobilization matrix for glucose oxidase (GOD) and exhibited excellent direct electron transfer properties for GOD. The AuNPs-functionalized 3D hierarchically ZnO nanostructure (Au–ZnO nanocomposite) favored the immobilization of the glucose oxidase (GOD) and the penetration of water-soluble glucose molecules, which helped efficiently catalyze the oxidation of glucose and facile direct electron transfer for GOD. The as-fabricated glucose biosensor exhibited satisfactory analytical performance with a low detection limit (0.02mM) and an acceptable linear range from 1 to 20mM. These results indicated that AuNPs-functionalized 3D hierarchically ZnO nanomaterial is a promising candidate material for high-performance glucose biosensors.

A high-performance glucose biosensor using covalently immobilised glucose oxidase on a poly(2,6-diaminopyridine)/carbon nanotube electrode

A highly-sensitive glucose biosensor amenable to ultra-miniaturisation was fabricated by immobilisation of glucose oxidase (GOx), onto a poly(2,6-diaminopyridine)/multi-walled carbon nanotube/glassy carbon electrode (poly(2,6-DP)/MWNT/GCE). Cyclic voltammetry was used for both the electrochemical synthesis of poly-(2,6-DP) on the surface of a MWNT-modified GC electrode, and characterisation of the polymers deposited on the GC electrode. The synergistic effect of the high active surface area of both the conducting polymer, i.e., poly-(2,6-DP) and MWNT gave rise to a remarkable improvement in the electrocatalytic properties of the biosensor. The transfer coefficient (α), heterogeneous electron transfer rate constant and Michaelis–Menten constant were calculated to be 0.6, 4s−1 and 0.20mM at pH 7.4, respectively. The GOx/poly(2,6-DP)/MWNT/GC bioelectrode exhibited two linear responses to glucose in the concentration ranging from 0.42μM to 8.0mM with a correlation coefficient of 0.95, sensitivity of 52.0μAmM−1cm−2, repeatability of 1.6% and long-term stability, which could make it a promising bioelectrode for precise detection of glucose in the biological samples.

Direct electrochemistry of glucose oxidase on sulfonated graphene/gold nanoparticle hybrid and its application to glucose biosensing

Sulfonated graphene nanosheet/gold nanoparticle (SGN/Au) hybrid was synthesized by electrostatic self-assembly of anionic SGN and positively charged gold nanoparticles. Due to the well-dispersivity of SGN in aqueous solution and its adequate negative charge, Au nanoparticles were assembled uniformly on graphene surface with high distribution. With the advantages of both graphene and Au nanoparticles, SGN/Au hybrid showed enhanced electrocatalytic activity towards O2 reduction. Furthermore, it provided a conductive and favorable microenvironment for the glucose oxidase (GOD) immobilization and thus promoted its direct electron transfer at the glassy carbon electrode. Based on the consumption of O2 caused by glucose at the interface of GOD electrode modified with SGN/Au hybrid, the modified electrode displayed satisfactory analytical performance, including high sensitivity (14.55 μA mM−1 cm−2), low detection limit (0.2 mM), an acceptable linear range from 2 to 16 mM, and also the prevention from the interference of some species. These results indicated that the prepared SGN/Au hybrid is a promising candidate material for high-performance glucose biosensor.

Reduced graphene oxide/PAMAM–silver nanoparticles nanocomposite modified electrode for direct electrochemistry of glucose oxidase and glucose sensing

Reduced graphene oxide/PAMAM–silver nanoparticles nanocomposite (RGO–PAMAM–Ag) was synthesized by self-assembly of carboxyl-terminated PAMAM dendrimer (PAMAM-G3.5) on graphene oxide (GO) as growing template, and in-situ reduction of both AgNO3 and GO under microwave irradiation. The RGO–PAMAM–Ag nanocomposite was used as a novel immobilization matrix for glucose oxidase (GOD) and exhibited excellent direct electron transfer properties for GOD with the rate constant (Ks) of 8.59s−1. The fabricated glucose biosensor based on GOD electrode modified with RGO–PAMAM–Ag nanocomposite displayed satisfactory analytical performance including high sensitivity (75.72μAmM−1cm−2), low detection limit (4.5μM), an acceptable linear range from 0.032mM to 1.89mM, and also preventing the interference of some interfering species usually coexisting with glucose in human blood at the work potential of −0.25V. These results indicated that RGO–PAMAM–Ag nanocomposite is a promising candidate material for high-performance glucose biosensors.

Hydrothermal synthesis of CuO micro-/nanostructures and their applications in the oxidative degradation of methylene blue and non-enzymatic sensing of glucose/H2O2

In this paper, we report on the amino acids-/citric acid-/tartaric acid-assisted morphologically controlled hydrothermal synthesis of micro-/nanostructured crystalline copper oxides (CuO). These oxides were characterized by means of X-ray diffraction, nitrogen sorption, scanning electron microscopy, Fourier transform infrared, and UV–visible spectroscopy. The surface area of metal oxides depends on the amino acid used in the synthesis. The formation mechanisms were proposed based on the experimental results, which show that amino acid/citric acid/tartaric acid and hydrothermal time play an important role in tuning the morphology and structure of CuO. The catalytic activity of as-synthesized CuO was demonstrated by catalytic oxidation of methylene blue in the presence of hydrogen peroxide (H2O2). CuO synthesized using tyrosine was found to be the best catalyst compared to a variety of CuO synthesized in this study. CuO (synthesized in this study)-modified electrodes were used for the construction of non-enzymatic sensors, which displayed excellent electrocatalytic response for the detection of H2O2 and glucose compared to conventional CuO. The high electrocatalytic response observed for the CuO synthesized using tyrosine can be correlated with the large surface area, which enhances the accessibility of H2O2/glucose molecule to the active site that results in high observed current. The methodology adopted in the present study provides a new platform for the fabrication of CuO-based high-performance glucose and other biosensors.

Synthesis of mesostructured polyaniline using mixed surfactants, anionic sodium dodecylsulfate and non-ionic polymers and their applications in H2O2 and glucose sensing

Mesostructured polyaniline was prepared by the self-assembly of a mixture of an anionic surfactant, sodium dodecylsulfate and a non-ionic polymeric surfactant (polyethylene glycol, and block-co-polymers such as Pluronic P123 and Brij-35). Materials were characterized by a complementary combination of X-ray diffraction, Scanning electron microscopy, Fourier-transform infrared spectrometer and UV-visible spectrophotometer. Mesostructured polyaniline was used for construction of biosensor, which displayed excellent electrocatalytic response for the detection of H2O2 and glucose compared to conventional polyaniline. The electrocatalytic response observed in the case of mesostructured polyaniline can be correlated with the large surface area and nanopores which enhances the accessibility of H2O2/glucose molecule to the active site that result in high observed current. The methodology adopted in the present study provides a new platform for the fabrication of polyaniline based high-performance glucose and other biosensors.

Immobilization of glucose oxidase on rod-like and vesicle-like mesoporous silica for enhancing current responses of glucose biosensors

The use of rod-like and vesicle-like mesoporous SiO 2 particles for fabricating high performance glucose biosensors is reported. The distinctively high surface areas of mesoporous structures of SiO 2 rendered the adsorption of glucose oxidase (GOx) feasible. Both morphologies of SiO 2 enhanced the sensitivities of glucose biosensors, but by a factor of 36 for vesicle-like SiO 2 and 18 for rod-like SiO 2, respectively. The greater enhancement of vesicle-like SiO 2 can be accounted for by its higher specific surface area (509 m 2 g −1) and larger total pore volume (1.49 cm 3 g −1). Interestingly, the current responses of GOx immobilized in interior channels of the mesoporous SiO 2 were enhanced much more than those of simple mixtures of GOx and the mesoporous SiO 2. This suggests that the enhancement of current responses arise not only from the high surface area of SiO 2 for high enzyme loading, but also from the improved enzyme activity upon its adsorption on mesoporous SiO 2. Also compared were the performances of glucose biosensors with GOx immobilized on mesoporous SiO 2 by physical adsorption and by covalent binding to 3-aminopropyltrimethoxysilane (APTMS) modified SiO 2 using glutaraldehyde as the cross-linker. The covalent binding approach resulted in higher enzyme loading but lower current sensitivity than with the physical adsorption.

Designing a highly active soluble PQQ–glucose dehydrogenase for efficient glucose biosensors and biofuel cells

We report for the first time a soluble PQQ–glucose dehydrogenase that is twice more active than the wild type for glucose oxidation and was obtained by combining site directed mutagenesis, modelling and steady-state kinetics. The observed enhancement is attributed to a better interaction between the cofactor and the enzyme leading to a better electron transfer. Electrochemical experiments also demonstrate the superiority of the new mutant for glucose oxidation and make it a promising enzyme for the development of high-performance glucose biosensors and biofuel cells.