Detection Of Glucose In Serum Research Articles

The Mn-doped CeO2 nanoparticles with enhanced peroxidase-like activity for one-pot analysis of glucose at neutral pH based on bio-inorganic cascade reactions

Enzyme catalytic cascade reactions based on peroxidase nanozymes and natural enzymes have aroused extensive attention in analytical fields. However, a majority of peroxidase nanozymes perform well only in acidic environments, resulting in their optimal pH mismatch with a neutral pH of natural enzymes, further restricting their application in biochemical sensing. Herein, Mn-doped CeO2 (Mn/CeO2) performing enhanced peroxidase-like activity at neutral conditions was prepared via a facile and feasible strategy. An effective enzyme cascade catalysis system via integrating glucose oxidase (GOx) with Mn/CeO2 was developed for one-pot detection of glucose in serum at neutral conditions. Using one-pot multistep catalytic reactions, this work provided a detection platform that allows for faster detection and easier operations than traditional methods. Under optimized conditions, our assay performed a sensitive detection of glucose ranging from 2.0 μΜ to 300 μΜ and a low detection limit of 0.279 μΜ. Notably, favorable analytical outcomes for glucose detection in serum samples were obtained, exhibiting potential applications in clinical diagnosis.

Confinement-Induced Biocatalytic Activity Enhancement of Light- and Thermoresponsive Polymer@Enzyme@MOF Composites.

Metal-organic frameworks (MOFs) are favorable hosting materials for fixing enzymes to construct enzyme@MOF composites and to expand the applications of biocatalysts. However, the rigid structure of MOFs without tunable hollow voids and a confinement effect often limits their catalytic activities. Taking advantage of the smart soft polymers to overcome the limitation, herein, a protection protocol to encapsulate the enzyme in zeolitic imidazolate framework-8 (ZIF-8) was developed using a glutathione-sensitive liposome (L) as a soft template. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were first anchored on a light- and thermoresponsive porous poly(styrene-maleic anhydride-N,N-dimethylaminoethyl methacrylate-spiropyran) membrane (PSMDSP) to produce PSMDSP@GOx-HRP, which could provide a confinement effect by switching the UV irradiation or varying the temperature. Afterward, embedding PSMDSP@GOx-HRP in L and encapsulating PSMDSP@GOx-HRP@L into hollow ZIF-8 (HZIF-8) to form PSMDSP@GOx-HRP@HZIF-8 composites were performed, which proceeded during the crystallization of the framework following the removal of L by adding glutathione. Impressively, the biocatalytic activity of the composites was 4.45-fold higher than that of the free enzyme under UV irradiation at 47 °C, which could benefit from the confinement effect of PSMDSP and the conformational freedom of the enzyme in HZIF-8. The proposed composites contributed to the protection of the enzyme against harsh conditions and exhibited superior stability. Furthermore, a colorimetric assay based on the composites for the detection of serum glucose was established with a linearity range of 0.05-5.0 mM, and the calculated LOD value was 0.001 mM in a cascade reaction system. This work provides a universal design idea and a versatile technique to immobilize enzymes on soft polymer membranes that can be encapsulated in porous rigid MOF-hosts. It also holds potential for the development of smart polymer@enzyme@HMOFs biocatalysts with a tunable confinement effect and high catalytic performance.

Improvement of Hydrogen Peroxide and Glucose Detection in Serum using Persistent Luminescent Nanoparticles: Impact of Synthesis Parameters and Particle Size

AbstractPersistent Luminescent Nanoparticles (PLNPs) emit prolonged light after excitation, allowing getting images with high signal‐to‐noise ratio, making them particularly beneficial for in vitro biodetection. In this study, we report the preparation of a library of gallium and zinc‐based Persistent Luminescent Nanoparticles doped with chromium (ZnGa2O4:Cr3+) through two distinct syntheses conducted at 120 °C for 12 hours or 24 hours, followed by a calcination at 500 °C or 750 °C. Using centrifugation, and starting from polydisperse samples, we demonstrated the ability to achieve different sizes in a monodisperse manner. Furthermore, our research revealed that ZnGa2O4:Cr3+ (ZGO) nanoparticles react differently with hydrogen peroxide (H2O2) based on their size, synthesis duration, and calcination temperature. We observed the most significant amplification of persistent luminescence for ZGO particles prepared at 120 °C for 12 hours and calcinated at 500 °C, with a size of approximately 100 nm, in the presence of 100 mM H2O2 (later named ZGO‐2). This study enabled the detection of H2O2 in serum without autofluorescence using the developed PLNPs, with a detection limit of up to 2.1 μM and a recovery rate of around 99 %. Additionally, we designed a glucose test for based on the responsiveness of ZGO PLNPs to H2O2. Using glucose oxidase, the glucose detection limit in serum was established around 0.13 μM, with a detection range between 0–5 μM. These findings could open new avenues to further control the size, synthesis, calcination temperature, and persistent luminescence of PLNPs, thus enhancing their utility in the development of new in vitro biosensors.

Bimetallic Cobalt Copper Organic Framework Integrating Multi-Wall Carbon Nanotubes and Gold Nanoparticles for Glucose Sensor

Bimetallic metal-organic framework (CuCo-BTC) was synthesized via a facile hydrothermal method and then CuCo-BTC/Au/multi-wall carbon nanotubes (MWCNTs) composite was prepared on copper foam (CuCo-BTC/Au/MWCNTs/CF) for glucose sensing. Due to the synergistic effect of bimetal active sites, the excellent conductivity and large surface area of MWCNTs, and the good catalytic activity of gold, CuCo-BTC/Au/MWCNTs/CF had increased active sites, enhanced charge transfer and improved electro-catalytic performance. As a result, under optimized conditions, the electrode exhibited a wide linear range of 0.01–5 mM, 5–9 mM, a sensitivity of 1.029 mA mM−1 cm−2, and a detection limit of 3.4 μM (S/N = 3) for glucose detection. Meanwhile, it demonstrated satisfactory selectivity, reproducibility and stability. Furthermore, the electrode was successfully applied for the detection of glucose in serum. This work validates the potential of the fabricated sensor for non-enzymatic blood glucose monitoring.

A PEDOT:PSS conductive hydrogel incorporated with Prussian blue nanoparticles for wearable and noninvasive monitoring of glucose

A PEDOT:PSS conductive hydrogel is incorporated with Prussian blue nanoparticles for the highly sensitive in vitro glucose detection and is applied as a skin patch on human subjects for the in vivo noninvasive monitoring of interstitial fluid (ISF) glucose via reverse iontophoresis technology. The biosensor achieves good correlation with the finger-stick blood glucose measurement. • The PEDOT:PSS/DF/PB hydrogel possessed an excellent operating stability. • The hydrogel-based sensor showed a competitive sensitivity of 340.1 μA·mM −1 ·cm −2 . • The wearable sensor noninvasively monitored the ISF glucose through RI-extraction. • The sensor showed good correlation with the results from commerical glucometer. Currently, there is no commercially-available noninvasive method for glucose monitoring in the interstitial fluid (ISF) mainly due to the measurement accuracy, sensitivity and/or the weak blood correlation. Here, we present an electrochemical biosensor based on PEDOT:PSS conductive hydrogel incorporated with Prussian blue nanoparticles (PBNPs) for the noninvasive and continuous monitoring of glucose on body. The hydrogel was prepared with the addition of dimethyl sulfoxide (DMSO) and Zonyl FS-300, which helped to improve the expanding of the polymer chains for the formation of better conductive and nanoporous networks. The hydrogel-based biosensor showed a low detection limit of 0.85 μM for glucose detection and high sensitivity up to 340.1 μA·mM −1 ·cm −2 , which was about 10-fold higher than the counterparts based on agarose and hydroxyethyl methacrylate (HEMA) hydrogels. Furthermore, it provided good accuracy with commercial glucometer for the glucose detection in serum. More importantly, incorporated with the reverse iontophoresis (RI), the hydrogel was applied as a skin patch on human subject for the in vivo noninvasive and continuous monitoring of ISF-borne glucose. The results showed good correlation with that measured by blood glucometer. We believe such glucose biosensor paves the way to clinically wearable noninvasive glucose monitoring in diabetics.

Platinum nanozyme-hydrogel composite (PtNZHG)-impregnated cascade sensing system for one-step glucose detection in serum, urine, and saliva

Bovine serum albumin was used as a nucleation template and stabilizer to prepare platinum nanozymes with high and specific peroxidase-like activity. Together with glucose oxidase, the best-performing nanozyme was entrapped in the 3D porous matrix of a polyethylene glycol hydrogel to fabricate the platinum nanozyme-hydrogel composite (PtNZHG). PtNZHG affords an independent glucose sensing unit, where the catalytic cascade reaction occurs with minimized diffusion resistance of unstable intermediates. This sensing unit was embedded within the confined detection zone of a plastic chip with a 3D hydrophilic fluid path to produce an efficient platform for the stand-alone detection of glucose. The glucose-containing sample was introduced into the device by capillary force, and the colored product generated by the catalytic cascade reaction was concentrated at the detection zone to markedly amplify the colorimetric response and thus increase detection sensitivity (detection range = 0.01–10 mM, detection limit = 3.9 µM). One-step glucose detection could be completed within 15 min, and analysis could be performed using a smartphone camera. The feasibility and practicality of our sensing system were demonstrated by the high recoveries of 83–105% observed for serum, urine, and saliva samples, the high specificity toward glucose without significant interference (<1%) from other sugars, and excellent long-term stability and reproducibility after two-month storage. Thus, our results are expected to advance the monitoring of glucose in human fluids and promote the biosensing of other substrates.

Simultaneous Detection of Serum Glucose and Glycated Albumin on a Paper-Based Sensor for Acute Hyperglycemia and Diabetes Mellitus.

Diabetes mellitus is one of the most common chronic diseases worldwide. Generally, the levels of fasting or postprandial blood glucose and other biomarkers, such as glycated albumin, glycated hemoglobin, and 1,5-anhydroglucitol, are used to diagnose or monitor diabetes progression. In the present study, we developed a sensor to simultaneously detect the glucose levels and glycation ratios of human serum albumin using a lateral flow assay. Based on the specific enzymatic reactions and immunoassays, a spiked glucose solution, total human serum albumin, and glycated albumin were measured simultaneously. To test the performance of the developed sensor, clinical serum samples from healthy subjects and patients with diabetes were analyzed. The glucose level and glycation ratios of the clinical samples were determined with reasonable correlation. The R-squared values of glucose level and glycation ratio measurements were 0.932 and 0.930, respectively. The average detection recoveries of the sensor were 85.80% for glucose and 98.32% for the glycation ratio. The glucose level and glycation ratio in our results were crosschecked with reference diagnostic values of diabetes. Based on the outcomes of the present study, we propose that this novel platform can be utilized for the simultaneous detection of glucose and glycation ratios to diagnose and monitor diabetes mellitus.

Sulfur vacancy promoted peroxidase-like activity of magnetic greigite (Fe3S4) for colorimetric detection of serum glucose

Herein, sulfur vacancies in magnetic greigite (SVs-Fe3S4) nanosheets were synthesized by a one-step solvothermal method by adjusting the ethylene glycol: water ratio. Electron paramagnetic resonance spectroscopy (EPR) and X-ray photoelectron spectroscopy (XPS) revealed that SV-rich Fe3S4 and SV-poor Fe3S4 were acquired using 100% ethylene glycol and 100% water as solvent, respectively. A peroxidase-like activity assay demonstrated that maximum reaction rates for H2O2-mediated oxidation of 3,3′,5,5′-tetramethyl-benzidine (TMB) catalyzed by the SV-rich Fe3S4 was 2.3 times higher than SV-poor Fe3S4. Density functional theory (DFT) calculations and reactive oxygen species (ROS) detection confirmed that the enhanced peroxidase-like activity by SV-rich Fe3S4 was attributed to efficient adsorption of H2O2 and subsequent decomposition to hydroxyl radicals (•OH) on the SVs sites of Fe3S4. The SV-rich Fe3S4 nanozyme was employed to develop a simple, highly sensitive and selective assay for glucose detection with a linear range of 0.5–150 μM and a detection limit of 0.1 μM (S/N = 3). A smartphone application (App) was designed and applied to efficiently detect serum glucose with the integrated analytical system based on the SV-rich Fe3S4. These new findings highlight the important role of surface defects in nanozymes on generating peroxidase-like activity for glucose detection in point-of-care diagnosis.

Facile preparation of a hollow core-shell nanocomposite for the ultrasensitive sensing of glucose

A core-shell Cu(OH)2@Au@Co(OH)2 nanocomposite with hollow nano-flower morphology fabricated by a facile and non-surfactant template-engaged reaction was applied for highly sensitive detection of glucose. The prussian blue analogues (PBA) of core-shell nanocubes (CuFe@Au@CoFe) were synthesized as the template through the accurate control of the reaction rate. In this nanocubes, Au nanoparticles for accelerating electron transfer rate were reduced at the interface of CoFe (core) and CuFe (shell) to improve their conductivity. These nanocubes were then etched controllably to form three-dimensional hollow nanoflowers stacked by nanosheets. It provided abundant electrode-electrolyte channels and high surface areas for OH− and glucoses adsorption and the following reactions. Due to the sandwich structure and synergic effect of the nanomaterials, the as-prepared sensors exhibited an ultrahigh sensitivity of 3427 μA mM-1 cm-2 for glucose detection, as well as a wide linear range of 0.001–5.2 mM with a low detection limit of 0.5 μM. In addition, the Cu(OH)2@Au@Co(OH)2 nanocomposite showed long-term stability and good reproducibility for glucose detection in serum with comparable results as measured with commercial glucometer. We believe the nanocomposite provided a good candidate for glucometer in future clinical applications.

Plasmonic Detection of Glucose in Serum Based on Biocatalytic Shape-Altering of Gold Nanostars.

Nanoparticles have been used as signal transducers for optical readouts in biosensors. Optical approaches are cost-effective with easy readout formats for clinical diagnosis. We present a glucose biosensor based on the biocatalytic shape-altering of gold nanostars via silver deposition. Improved sensitivity was observed due to the nanostars clustering after being functionalised with glucose oxidase (GOx). The biosensor quantified glucose in the serum samples with a 1:1000 dilution factor, and colorimetrically distinguished between the concentrations. The assay demonstrated good specificity and sensitivity. The fabricated glucose biosensor is a rapid kinetic assay using a basic entry level laboratory spectrophotometric microplate reader. Such a biosensor could be very useful in resource-constrained regions without state-of-the-art laboratory equipment. Furthermore, naked eye detection of glucose makes this a suitable biosensor for technology transfer to other point-of-care devices.

Non-enzymatic detection of serum glucose using a fluorescent nanopolymer probe.

A fluorescent probe is described for the determination of serum glucose after hepatotoxin-induced liver injury. The probe is based on the use of a water-soluble polymer and has been prepared from a multi-functional azlactone polymer as the linker, amino boronic acid, and Alizarin Red as the signalling moiety. The excitation/emission peaks of the polymeric fluorescent probe are at 468/567nm. Fluorescence is reduced on addition of glucose. Intensity drops linearly in the 0.1mM to 14mM glucose concentration range. The probe was applied to non-enzymatic detection of glucose in rat serum after CCl4-induced liver damage. Graphical abstract A polymer based fluorescent probe has been constructed and applied for non-enzymatic monitoring of serum glucose following hepatotoxin induced liver injury.

Fluorometric determination of glucose based on a redox reaction between glucose and aminopropyltriethoxysilane and in-situ formation of blue-green emitting silicon nanodots.

A method is described for fluorometric detection of glucose. It is based on the finding that silicon nanodots (SNDs) are formed from glucose and aminopropyltriethoxysilane (APTES) under mild experimental conditions. The SNDs thus formed have an average diameter of ∼2nm, exhibit good water dispersibility, blue fluorescence (with excitation/emission maxima at 410/475nm), broad pH tolerance, and are photostable. The assay was applied to the quantification of glucose with high sensitivity, good specificity, and over a wide detection range (from 10μM to 0.9mM). It was applied to the determination of glucose in spiked serum samples and gave satisfactory results and recoveries. Graphical abstract Schematic presentation of serum glucose detection based on a redox reaction between glucose and aminopropyltriethoxysilane and in-situ formation of blue-green emitting silicon nanodots.

One step synthesis of AuNPs@MoS2-QDs composite as a robust peroxidase- mimetic for instant unaided eye detection of glucose in serum, saliva and tear

A graphene analogous of transition metal dichalcogenides, mainly molybdenum disulfide (MoS2), have recently attracted wide attention due to its catalytic and electrical properties. Herein, we report a simple one step synthesis of gold nanoparticles (AuNPs) decorated over MoS2 quantum dots (AuNPs@MoS2-QDs) as a robust peroxidase- mimetic material. The AuNPs@MoS2-QDs composite catalyzes the peroxidase substrate of 3, 3′, 5,5′-tetramethylbenzidine (TMB) oxidation in the presence of H2O2 to produce a bluish-green colored product. The peroxidase mimetic behavior of AuNPs@MoS2-QDs composite complies with the steady state kinetics and is stable in harsh conditions such as high or low temperature and pH. The developed composite system has been used for sensitive and selective detection of glucose. The developed biosensor shows an excellent detection in dynamic ranges from 1 to 400 μM (R2∼0.996) with the detection limit of 0.068 μM in PBS buffer solution. Low Km value (0.06 mM) of AuNPs@MoS2-QDs has shown strong binding affinity towards substrates along with high values of Vmax (10.6 × 10−6 Ms−1) indicating greater catalytic reaction rate. Further the biosensor is developed as a portable test kit for detection of glucose in biological fluids like serum, tear and saliva utilizing agarose hydrogel as a visual detection platform. Our portable sensing kit shows an excellent response for detection of glucose in real samples compared to the conventional methods.

A Palladium‐Doped Graphitic Carbon Nitride Nanosheet with High Peroxidase‐Like Activity: Preparation, Characterization, and Application in Glucose Detection

AbstractHerein, a novel palladium‐doped graphitic carbon nitride nanosheet (g‐C3N4‐PdNPs) is reported. The prepared g‐C3N4‐PdNPs has a 6.7 and 14.0 times higher peroxidase‐like activity in comparison with pure Pd nanoparticles (PdNPs) and graphitic carbon nitride (g‐C3N4) nanosheets respectively, and can be stably stored for 3 months. The high peroxidase‐like activity make g‐C3N4‐PdNPs effectively catalyze H2O2‐mediation oxidization of 3,3,5,5′‐tetramethylbenzidine to generate a color change from colorless to blue under lower concentration level and shorter time. The g‐C3N4‐PdNPs can be used as peroxidase mimetic to develop sensitive and specific colorimetric method for the rapid detection of glucose in the serum, and to fabricate a simple and cheap portable test kit for instrument‐free visual detection of glucose in serum. The portable test kit possesses obvious advantages such as low‐cost, short detection time, tiny sample consumption, excellent specificity, and higher visual sensitivity. The visual detection limit of portable test kit is lower than the glucose concentration in the serum of a diabetic. Using portable test kit, the glucose in serum can be visually detected by bare eye observation within 30 min with only 30 µL serum consumption. The success of this study provided a potential approach for low‐cost and instrument‐free “see” diabetes in clinical early diagnosis.

Growth of CuO nanoneedles on graphene quantum dots as peroxidase mimics for sensitive colorimetric detection of hydrogen peroxide and glucose

Graphene quantum dots-copper oxide nanocomposites (GQDs/CuO) are facilely fabricated by the growth of CuO nanoneedles on graphene quantum dots under mild conditions. The as-prepared GQDs/CuO nanocomposites could be used as an effective peroxidase mimics to catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue-colored solution. Investigations on the mechanism indicate that the nature of peroxidase-like activity of GQDs/CuO nanocomposites originates from OH radical generation. The increase of absorbance at 652nm induced by the catalytic effect of GQDs/CuO nanocomposites offers accurate detection of H2O2 in the range of 0.5–10μM, along with a detection limit of 0.17μM. A colorimetric method for serum glucose detection is also proposed by combining the GQDs/CuO catalytic reaction and the enzymatic oxidation of glucose with glucose oxidase. This method is simple, sensitive and selective for glucose detection with a linear range from 2 to 100μM with a detection limit of 0.59μM.

Bimetallic Bi/Pt peroxidase mimic and its bioanalytical applications

In this work, bimetallic Bi/Pt nanoparticles in bovine serum albumin biomolecular scaffold (BSA-Bi/PtNPs) were synthesized through a facile and green method. As compared with BSA-PtNPs, the BSA-Bi/PtNPs possess enhanced peroxidase-like catalytic activity. Moreover, the BSA-Bi/PtNPs are stable in harsh conditions such as high temperature, extreme pH environments, and high ionic strength, as well as in common biological matrixes. These prominent advantages enable the BSA-Bi/PtNPs to be applied to a wide range of fields. Bioassays, such as serum glucose detection, extracellular hydrogen peroxide (H2O2) monitor, and cancer cells labeling, have been realized with satisfying results. The linear range of glucose determination was from 1 to 100 μM and the limit of detection (LOD) was 0.2 μM. The H2O2 released from each MCF-7 cell after stimulation was calculated to be 2.66 × 10−16 mol/s. By utilizing folic acid as a recognition element, tumor cell could be readily distinguished by BSA-Bi/PtNPs and the LOD for MCF-7 cell detection was 90 cells.

Chitosan–gold nanoparticles as peroxidase mimic and their application in glucose detection in serum

Chitosan–AuNPs possess peroxidase-like activity and can be used for the detection of glucose in serum.

A novel one-step colorimetric assay for highly sensitive detection of glucose in serum based on MnO2 nanosheets

A label-free and sensitive method for glucose detection is proposed based on the color change of MnO2 nanosheet colloidal suspension.

Nanocrystalline Cellulose-Assisted Generation of Silver Nanoparticles for Nonenzymatic Glucose Detection and Antibacterial Agent.

Nanocrystalline cellulose (NCC) is a kind of natural biopolymers with merits of large surface area, high specific strength and unique optical properties. This report shows that NCC can serve as the substrate, allowing glucose to reduce Tollen's reagent to produce silver nanoparticles (AgNPs) at room temperature. The generation of AgNPs is affected by the factors such as the concentrations of silver ions, NCC and glucose, as well as the different reaction temperatures. The AgNPs with NCC are applied for the development of a visual, quantitative, nonenzymatic and high-sensitive assay for glucose detection in serum. This assay is also used for monitoring the concentration change of glucose in medium during cell culture. For the antibacterial activity, the minimal inhibitory concentration (MIC) of the generated AgNPs with NCC is much lower than that of commercial AgNPs, attributed to the good dispersion of AgNPs with the presence of NCC. As NCC exhibits unique advantages including green, stable, inexpensive, and abundant, the NCC-based generation of AgNPs may find promising applications in clinical diagnosis, environmental monitoring, and the control of bacteria.

Fast and Effective Turn‐on Paper‐based Phosphorescence Biosensor for Detection of Glucose in Serum

AbstractIn this study, a turn‐on paper‐based optical analytical system with a rapid, sensitive and quantitative response for glucose was developed. The luminescence sensing material, crystalline iridium(III)‐Zn(II) coordination polymers, or Ir‐Zne, was grown electrochemically on stainless steel mesh and then deposited on filter paper. This sensing substrate was subsequently built up under glucose oxidase encapsulated in hydrogel and then immobilized on egg membrane with the layer‐by‐layer method. Once the glucose solution was dropped onto the paper, the oxygen content was depleted simultaneously with a concomitant increase in the phosphorescence of Ir‐Zne. The detection limit for glucose was 0.05 mM. The linear dynamic range for the determination of glucose was 0.05–8.0 mM with a correlation coefficient (R2) of 0.9956 (y=68.11 [glucose]−14.72). The response time was about 0.12 s, and the sample volume was less than 5 μL. The effects of mesh size, buffer concentration, pH, enzyme concentration, temperature, and interference, and the stability of the biosensor, have also been studied in detail. Finally, the biosensor was successfully applied to the determination of glucose in human serum.