Detection Of Glucose In Saliva Research Articles

Highly sensitive SERS sensors for glucose detection based on enzyme@MOFs and ratiometric Raman

Diabetes is a common chronic metabolic disease. The frequent fluctuation of glucose is the main cause of most diabetes complications, which in turn causes harm to the health of patients. Surface-enhanced Raman scattering (SERS) spectroscopy has attracted much attention in the rapid detection of glucose due to its unique molecular fingerprinting ability, ultra-high sensitivity and fast response. However, due to the low affinity between glucose and SERS substrate, poor signal, susceptibility to complex environmental interference, and poor stability of SERS detection, it is still a challenge for SERS to accurately and sensitively determine glucose in complex environments. In this work, we encapsulated 4-mercaptobutyronitrile (4-MBN) as an internal standard (IS) in Au@Ag NRs inside and then Au@4-MBN@Ag NRs, Leucomalachite Green (LMG), glucose oxidase (GOx) and horseradish peroxidase (HPR) were encapsulated in ZIF-8 to prepare a tandem enzyme catalytic ratiometric SERS sensor Au@4-MBN@Ag@LMG@ZIF-8(GOx, HPR) for the detection of glucose in saliva. Because ZIF-8 enhanced the catalytic activity of the enzyme, the ability of glucose enrichment, and weakens the aggregation of Ag NRs. The internal standard signal molecule improves the accuracy and sensitivity of detection. The ratiometric Raman signal I412/I2233 of glucose has a good linear relationship with the concentration in the range of 0.1–100 μM, and the limit of detection (LOD) could be down to 0.03 μM. At the same time, it has excellent selectivity, repeatability and accuracy. The recovery rate of glucose in saliva is 96.50%–105.56 %, which proves the feasibility of the method. The Au@4-MBN@Ag@LMG@ZIF-8(GOx, HPR) sensor prepared in this study showed excellent SERS performance, which was able to detect glucose quickly, sensitively and accurately. This work provides a new strategy for the design of enzyme-catalyzed SERS sensors.

Zirconium copper oxide microflowers based non-enzymatic screen-printed electrochemical sensor for the detection of glucose in saliva, urine, and blood serum.

Zirconium copper oxide microflowers (Zr/CuO MF) based non-enzymatic sensor was developed for glucose detection in saliva, urine, and blood. An easy urea hydrolysis method was employed for the synthesis of the metal oxide and further calcined to improve the catalytic property. The flower-like morphology of the Zr/CuO was confirmed by SEM analysis and the presence of copper and zirconium was examined using energy dispersive X-ray analysis (EDAX). The Zr/CuO MF modified screen-printed electrodes exhibited excellent glucose sensing performance in 0.15M NaOH medium and could quantify glucose in the range from 10µM to 27mM. A high sensitivity of 1.815 ± 0.003mAmM-1cm-2 was obtained for lower glucose concentration from 15µM to 3mM and 1.250 ± 0.006mAmM-1cm-2 for higher concentration glucose from 3 to 27mM. The limit of detection of the fabricated sensor was found to be 0.8µM. The sensor displayed high selectivity and stability towards glucose in different body fluids like saliva, urine, and blood serum at a working potential of 0.6V (vs. Ag/AgCl). In saliva, urine, and serum samples, the sensor exhibited excellent recovery of 95-108, 92-108, and 93-101% in saliva, urine, and serum, respectively, with a relative standard deviation of less than 10%, demonstrating high accuracy and reliability of the sensor. The developed sensor is promising for developing an invasive and non-invasive point-of-care testing device for glucose detection.

Non-invasive, ultrasensitive detection of glucose in saliva using metal oxide transistors

Transistor-based biosensors represent an emerging technology for inexpensive point-of-care testing (POCT) applications. However, the limited sensitivity of the current transistor technologies hinders their practical deployment. In this study, we developed tri-channel In2O3/ZnO heterojunction thin-film transistors (TFTs) featuring the surface-immobilized enzyme glucose oxidase to detect glucose in various biofluids. This unusual channel design facilitates strong coupling between the electrons transported along the buried In2O3/ZnO heterointerface and the electrostatic perturbations caused by the interactions between glucose and surface-immobilized glucose oxidase. The enzyme selectively binds to glucose, causing a change in charge density on the channel surface. By exploring this effect, the solid-state biosensing TFT (BioTFT) can selectively detect glucose in artificial and real saliva over a wide range of concentrations from 500 nM to 20 mM with limits of detection of ∼365 pM (artificial saliva) and ∼416 nM (real saliva) in less than 60 s. The specificity of the sensor towards glucose has been demonstrated against various interfering species in artificial saliva, further highlighting its unique capabilities. Moreover, the BioTFTs exhibited good operating stability upon storage for up to two weeks, with relative standard deviation (RSD) values ranging from 2.36% to 6.39% for 500 nM glucose concentration. Our BioTFTs are easy to manufacture with reliable operation, making them ideal for non-invasive POCT applications.

A nonenzymatic laser-induced flexible amperometric graphene electrode for glucose detection in saliva

Graphene is a suitable transducer for wearable sensors because of its high conductivity, large specific surface area, flexibility, and other unique considerable features. Using a simple, fast galvanic pulse electrodeposition approach, a unique nonenzymatic glucose amperometric electrode was successfully developed based on well-distributed fine Cu nanoparticles anchored on the surface of 3D structure laser-induced graphene. The fabricated electrode allows glucose detection with a sensitivity of 2665 µA/mM/cm2, a response time of less than 5 s, a linear range of 0.03–4.5 mM, and a LOD of 0.023 µM. It also detects glucose selectively in the presence of interfering species such as ascorbic acid and urea. These provide the designed electrode the advantages for glucose sensing in saliva with 97% accuracy and present it among the best saliva-range non-enzymatic glucose sensors reported to date for real-life diagnostic applications.

A microfluidic cloth-based photoelectrochemical analytical device for the detection of glucose in saliva

Photoelectrochemical (PEC) detection is a widely used detection method that uses light to stimulate and photocurrent signals to detect the target. Due to the disengagement of the excitation unit and the detection unit, the PEC background signal is reduced, and the detection sensitivity is improved. In this work, we report the first demonstration of PEC detection for microfluidic cloth-based analytical devices (μCADs). Using PEC μCADs integrated with cadmium sulfide quantum dots (CdS QDs) and multiwalled carbon nanotubes (MWCNTs), the nonenzymatic, sensitive and rapid measurement of glucose in saliva has been achieved. For the cloth-based device, the PEC reaction zone and cloth-based electrodes can be fabricated by inexpensive wax-based and carbon ink-based screen-printing, respectively. By the layer-by-layer method, the as-prepared poly (dimethyl diadly ammonium chloride-functionalized) MWCNTs (PDDA-MWCNTs) and CdS QDs are successively adsorbed onto the working electrode surface of the cloth-based device. In the presence of an excitation source and glucose, the CdS QDs generate a strong oxidizing electron hole that can then continuously oxidize glucose to produce an electrical signal for glucose detection. Under optimized conditions, a linear dependence is obtained between the PEC signal and glucose concentrations in the range of 0.05–1000 μM with a detection limit of 15.99 nM. In the detection range, the cloth-based device also shows acceptable selectivity, reproducibility, and long-term stability. Moreover, the method has been implemented for the detection of glucose in real saliva samples, suggesting good potential for biochemical applications.

Enzyme-Free Tandem Reaction Strategy for Surface-Enhanced Raman Scattering Detection of Glucose by Using the Composite of Au Nanoparticles and Porphyrin-Based Metal-Organic Framework.

In this work, an S hybrid nanosheet with multiple functions is synthesized by in situ modification of gold nanoparticles (AuNPs) onto two-dimensional (2D) metalloporphyrinic metal-organic framework (MOF) (Cu-tetra(4-carboxyphenyl)porphyrin chloride(Fe(III)), designated as AuNPs/Cu-TCPP(Fe). Cu-TCPP(Fe) nanosheets contribute peroxidase-like activity, and AuNPs have glucose oxidase (GOx) mimicking performance, which induce the cascade catalysis reactions to convert glucose into hydrogen peroxide (H2O2), and then, by using AuNP catalysis, H2O2 oxidizes the no Raman-active leucomalachite green (LMG) into the Raman-active malachite green (MG). Simultaneously, in the presence of AuNPs, sensitive and selective surface-enhanced Raman scattering (SERS) determination of glucose can be achieved. The bioenzyme-free SERS assay based on such AuNPs/Cu-TCPP(Fe) nanosheets is used for detection of glucose in saliva, showing good recovery from 96.9 to 100.8%. The work paves a new way to design a nanozyme-based SERS protocol for biomolecule analysis.

Characterization and Validation of a Platinum Paper‐based Potentiometric Sensor for Glucose Detection in Saliva

AbstractA paper‐based potentiometric sensor was constructed and characterized for the detection of glucose in saliva. Dilution of the samples was optimized to afford the optimum experimental conditions of measurements. The performance allows for detecting abnormal high glucose concentrations observed in diabetes patients. Repeatability data were presented and the performance of the sensor compared to literature examples showing suitable characteristics at a much lower cost. The validation in real saliva samples was performed against a commercial colorimetric kit showing that glucose could be effectively determined in the 4–10 mM range based on the comparison with a reference method.

Enzyme bioconjugated PAMAM dendrimers for estimation of glucose in saliva

This research work intended to prepare and characterize novel dendrimer-based biosensors with an improved response for the detection of glucose in saliva. The nanoparticles of Fe3O4, a core material, encapsulated in PAMAM dendrimers to immobilize glucose oxidase in the presence of cross-linking agent, glutaraldehyde. Fe3O4 nanoparticles were synthesized by oxidative reaction of ferrous chloride and potassium hydroxide. A solvent-free or green chemistry concept was used to prepare PAMAM dendrimers (G4) using Michael addition and amidation reactions where ethylene diamine and methyl methacrylate were used as reactants. The particle size of Fe3O4 nanoparticles and dendrimers were in the range of 20–30 nm and 30–40 nm, respectively. Glucose was detected by photofluorometer using Tris(1, 10-phenanthroline) ruthenium (II) chloride hydrate [TPR(II)CH] as an indicator. The biosensor showed a response in 4–6 min both in the presence and absence of artificial saliva. The behavior of biosensor showed an increase in fluorescence intensity for the concentrations of glucose (5, 10, 15, and 20 ppm). Fourier-transform infrared spectroscopy and differential scanning calorimetry studies confirmed the synthesis of Fe3O4 nanoparticle and acted as a core of PAMAM dendrimers. This potential approach is a simple, cost-effective, and reproducible for noninvasive glucose detection in saliva.

Rational Design of Stimuli-Responsive Polymers Modified Nanopores for Selective and Sensitive Determination of Salivary Glucose.

The great pain and stress from finger-prick glucose measurements have resulted in great motivation to find noninvasive glucose monitoring technologies where salivary glucose measurement is desirable. However, the relative low concentration of glucose and coexisting chemicals in saliva challenges the sensitive and selective salivary glucose detection. In this article, we have rationally designed and constructed a salivary glucose sensor by modifying the inner wall of the Au-decorated glass nanopore with stimuli-responsive copolymer poly(3-(acryloylthioureido) phenylboronic acid-co-N-isopropylacrylamide) (denoted as PATPBA-co-PNIPAAm) via Au-S interaction. Notably, upon recognition of glucose, the copolymer could undergo a wettability switch and pKa shifts in the boronic acid functional groups, which significantly regulated the ion transport through nanopores, thus showing improved sensitivity with the detection limit of 1 nM. Moreover, benefiting from the multivalent boronic acid-glucose interaction and the cooperation of thiourea units, the copolymer exhibited good selectivity for glucose detection against the coexisting saccharides and other biological molecules in saliva. The nanopores with well-demonstrated analytical performance were finally applied for monitoring glucose in saliva. Together, this work unveiled a new platform for glucose detection in saliva, and promised to provide a new strategy for detecting other biomolecules in accessible biofluid involved in physiological and pathological events.

Naked-Eye Detection of Glucose in Saliva with Bienzymatic Paper-Based Sensor.

The high incidence of Diabetes Mellitus in low-income regions has promoted the development of low-cost alternatives to replace blood-based procedures. In this work, we present a bienzymatic paper-based sensor suitable for the naked-eye detection of glucose in saliva samples. The sensor was obtained by a stamping procedure and modified with chitosan to improve the colorimetric readout. The bienzymatic reaction of GOx-HRP coupled with 2,4,6-tribromo-3-hydroxy benzoic acid was applied for the detection of glucose within a range from 0 to 180 mgdL−1 in buffer and artificial saliva solutions. The visual readout was perceived by the naked eye and registered with an office scanner to evaluate the analytical performance. The results showed a limit of detection of 0.37 mgdL−1 (S/N = 3) with an R.S.D. of 1.69% and a linear range from 1 to 22.5 mgdL−1 with an R2 of 0.99235. The analysis of human saliva samples was performed without pre-processing, achieving recoveries from 92 to 114%. The naked-eye detection was evaluated under two different light settings, showing average recoveries of 108.58 and 90.65% for standard and low illumination. The proposed device showed potential for easy-to-use, sensitive, low-cost, fast, and device-free detection of salivary glucose suitable for untrained personnel operation and limited facilities.

Graphene based sensors in the detection of glucose in saliva – a promising emerging modality to diagnose diabetes mellitus

No more needles – a new modality to detect saliva glucose with graphene and its derivatives is on the horizon.

Printable organic thin film transistors for glucose detection incorporating inkjet-printing of the enzyme recognition element

The effect of device architecture upon the response of printable enzymatic glucose sensors based on poly(3-hexythiophene) (P3HT) organic thin film transistors is presented. The change in drain current is used as the basis for glucose detection and we show that significant improvements in drain current response time can be achieved by modifying the design of the sensor structure. In particular, we show that eliminating the dielectric layer and reducing the thickness of the active layer reduce the device response time considerably. The results are in good agreement with a diffusion based model of device operation, where an initial rapid dedoping process is followed by a slower doping of the P3HT layer from protons that are enzymatically generated by glucose oxidase (GOX) at the Nafion gate electrode. The fitted diffusion data are consistent with a P3HT doping region that is close to the source-drain electrodes rather than located at the P3HT:[Nafion:GOX] interface. Finally, we demonstrate that further improvements in sensor structure and morphology can be achieved by inkjet-printing the GOX layer, offering a pathway to low-cost printed biosensors for the detection of glucose in saliva.