Nanomaterial-assisted wearable glucose biosensors for noninvasive real-time monitoring:Pioneering point-of-care and beyond

This review explores glucose monitoring and management strategies,emphasizing the need for reliable and userfriendly wearable sensors that are the next generation of sensors for continuous glucose detection.In addition,examines key strategies for designing glucose sensors that are multi-functional,reliable,and cost-effective in a variety of contexts.The unique features of effective diabetes management technology are highlighted,with a focus on using nano/biosensor devices that can quickly and accurately detect glucose levels in the blood,improving patient treatment and control of potential diabetes-related infections.The potential of next-generation wearable and touch-sensitive nano biomedical sensor engineering designs for providing full control in assessing implantable,continuous glucose monitoring is also explored.The challenges of standardizing drug or insulin delivery doses,low-cost,real-time detection of increased blood sugar levels in diabetics,and early digital health awareness controls for the adverse effects of injectable medication are identified as unmet needs.Also,the market for biosensors is expected to expand significantly due to the rising need for portable diagnostic equipment and an ever-increasing diabetic population.The paper concludes by emphasizing the need for further research and development of glucose biosensors to meet the stringent requirements for sensitivity and specificity imposed by clinical diagnostics while being cost-effective,stable,and durable.

Hierarchically porous cellulose nanofibril aerogel decorated with polypyrrole and nickel-cobalt layered double hydroxide for high-performance nonenzymatic glucose sensors

With increasing emphasis on green chemistry,biomass-based materials have attracted increased attention regarding the development of highly efficient functional materials.Herein,a new pore-rich cellulose nanofibril aerogel is utilized as a substrate to integrate highly conductive polypyrrole and active nanoflower-like nickel-cobalt layered double hydroxide through in situ chemical polymerization and electrodeposition.This ternary composite can act as an effective self-supported electrode for the electrocatalytic oxidation of glucose.With the synergistic effect of three heterogeneous components,the electrode achieves outstanding glucose sensing performance,including a high sensitivity(851.4μA·mmol^(−1)·L·cm^(−2)),a short response time(2.2 s),a wide linear range(two stages:0.001−8.145 and 8.145−35.500 mmol·L^(−1)),strong immunity to interference,outstanding intraelectrode and interelectrode reproducibility,a favorable toxicity resistance(Cl^(‒)),and a good long-term stability(maintaining 86.0%of the original value after 30 d).These data are superior to those of some traditional glucose sensors using nonbiomass substrates.When determining the blood glucose level of a human serum,this electrode realizes a high recovery rate of 97.07%–98.89%,validating the potential for highperformance blood glucose sensing.

Reusable electrochemical non-enzymatic glucose sensors based on Au-inlaid nanocages

Mass detection of glucose,which is required in many applications,remains challenging.The commercial enzyme-based glucose test strips cannot be reused,and current non-enzymatic glucose sensors exhibit a narrow range of detection and slow glucose oxidation kinetics.Herein,controlled etching of Prussian blue analogue(PBA)nanocubes at the vertices is conducted and Au nanoparticles(Au NPs)are subsequently inlaid in the etched cavities by in-situ reduction of HAuCl4.The unique AuNP-PBA nanocomplexes exhibit low electrochemical potential for glucose oxidation,high electrocatalytic activity,and rapid redox electron transfer rate.Covalent immobilization of the Au-inlaid nanomaterials on a fine Au wire leads to a non-enzymatic glucose sensor with a particularly wide linear detection range(10μM to 16 mM),excellent anti-interference,and fast response.More importantly,the sensor is reusable,and its sensitivity is well maintained even after 150 times of detection.This new-concept material promises to enable high-throughput glucose detection at a low cost,which is essential in diabetic management and other healthcare applications.

Pd-based nanoporous metals for enzyme-free electrochemical glucose sensors

Nanoporous metals （NPMs） show potential applications as enzyme-free glucose sensors. There are few reports on nanoporous Pd in this area even though their cost is much lower than other NPMs. In this work, we report the formation of Pd-based NPM with improved catalytic activity towards the oxidation of glucose. By dealloying metallic glasses, Pd-based NPMs with hi-continuous networks were obtained. All the Pd-based NPMs show high electrochemical catalytic activity towards glucose oxidation. In this study, NPM with an open, three-dimensional, ligament-channel nanoporous structure resulted by dealloying metallic Pd3oCu4oNiloP2o, producing a pore size of 11 nm and a ligament size of 7 nm as the best configuration towards the direct oxidation reaction of glucose.

Facile synthesis of CuO-Co_(3)O_(4)prickly-sphere-like composite for non-enzymatic glucose sensors

In the field of glucose sensors,the development of inexpensive and high-efficiency electrochemical glucose sensors is the current research hotspot.In this paper,CuO-Co_(3)O_(4)composite with a prickly-sphere-like morphology is prepared by the facile hydrothermal method for the non-enzymatic electrochemical glucose detection.X-ray diffraction,scanning electron microscopy,transmission electron microscopy,energy-dispersive X-ray spec-troscopy,and X-ray photoelectron spectroscopy are used to analyze the structure,composition,and morphology of the material.In addition,the electrochemical catalytic perfor-mance of CuO-Co_(3)O_(4)to glucose is obtained by cyclic voltammetry and chronoamperometry.The excellent elec-trochemical sensing performance may be attributed to the large number of catalytic sites in the prickly-sphere-like composite and the synergistic effect of Cu and Co.Under an applied voltage of 0.55 V,CuO-Co_(3)O_(4)composite shows sensitivity to glucose(1503.45μA·(mmol·L^(-1))^(-1)-cm^(-2)),a low detection limit(21.95μmol·L^(-1)),excellent selectivity,a high level of reproducibility,and good sta-bility.This indicates that the CuO-Co_(3)O_(4)composite has a broad prospect of non-enzymatic glucose sensing application.

A CuNi/C Nanosheet Array Based on a Metal–Organic Framework Derivate as a Supersensitive Non-Enzymatic Glucose Sensor

Bimetal catalysts are good alternatives for nonenzymatic glucose sensors owing to their low cost, high activity, good conductivity, and ease of fabrication. In the present study, a self-supported CuNi/C electrode prepared by electrodepositing Cu nanoparticles on a Ni-based metal–organic framework(MOF) derivate was used as a non-enzymatic glucose sensor. The porous construction and carbon scaffold inherited from the Ni-MOF guarantee good kinetics of the electrode process in electrochemical glucose detection. Furthermore, Cu nanoparticles disturb the array structure of MOF derived films and evidently enhance their electrochemical performances in glucose detection. Electrochemical measurements indicate that the CuNi/C electrode possesses a high sensitivity of17.12 mA mM^(-1) cm^(-2), a low detection limit of 66.67 nM,and a wider linearity range from 0.20 to 2.72 mM. Additionally, the electrode exhibits good reusability, reproducibility, and stability, thereby catering to the practical use of glucose sensors. Similar values of glucose concentrations in human blood serum samples are detected with our electrode and with the method involving glucose-6-phosphate dehydrogenase; the results further demonstrate the practical feasibility of our electrode.

Highly-dispersed iron element decorated nickel foam synthesized by an acid-free and one-pot method for enzyme-free glucose sensor

The highly-dispersed iron element decorated Ni foam was prepared by simple immersion in a ferric nitrate solution at room temperature without using acid etching, and characterized by X-ray powder diffraction(XRD), scanning electron microscopy(SEM), EDAX spectrum(EDAX mapping) and Raman spectroscopy. The EDAX spectrum illustrated that iron element was highly-dispersed over the entire surface of nickel foam, and the Raman spectroscopy revealed that both Ni-O and Fe-O bonds were formed on the surface of the as-prepared electrode. Moreover, the iron element decorated Ni foam electrode can be used as non-enzymatic glucose sensor and it exhibits not only an ultra-wide linear concentration range of 1-18 mmol/L with an outstanding sensitivity of 1.0388 m A·mmol/(L·cm2), but also an excellent ability of stability and selectivity. Therefore, this work presents a simple yet effective approach to successfully modify Ni foam as non-enzymatic glucose sensor.

Calibration of the Circuit Measurement for the Glucose Sensor

The extended gate field effect transistor (EGFET)has many advantages such as the fabrication is easy,low cost, easy to operate etc.The EGFET was applied to biosensor in recent years.In this study,the tin oxide (SnO_2)pH sensitive membrane was deposited on ITO glass,when the surface voltage which pH membrane changes,the gate voltage and current channel of MOSFET will change immediately to detect concentration of the glucose sensor.In this study we have devoted to research about the calibration of the circuit measurement for the glucose sensor,and study the calibration system of the drift and hysteresis.

"Dry" NiCo2O4 Nanorods for Electrochemical Non-enzymatic Glucose Sensing

A rod-like NiCo2O4 modified glassy carbon electrode was fabricated and used for non-enzymatic glucose sensing. The NiCo2O4 was prepared by a facile hydrothermal reaction and subsequently treated in a commercial microwave oven to eliminate the residual water introduced during the hydrothermal procedure. Structural analysis showed that there was no significant structural alteration before and after microwave treatment. The elimination of water residuals was confirmed by the stoichiometric ratio change by using element analysis. The microwave treated NiCo2O4 (M-NiCo2O4) showed excellent performance as a glucose sensor (sensitivity 431.29 μA·mmol/L-1·cm-2). The sensing performance decreases dramatically by soaking the M-NiCo2O4 in water. This result indicates that the introduction of residual water during hydrothermal process strongly affects the electrochemical performance and microwave pre-treatment is crucial for better sensory performance.

Advances on ultra-sensitive electrospun nanostructured electrochemical and colori metric sensors for diabetes mellitus detection

Recent developments in the biochemical and medicinal industries have been heavily focused on producing affordable glucose biosensors due to the condi nuous annual increase of diabetic patients worldwide.The devel-opment of a fast,accurate,and reliable glucose sensor will increase confidence in controlling di abetes mellitus and its assoclated health complications among the diabetic community.Electraspinning is a versatile method that can produce complex nanofbrous assemblies with attractiwe and functional characteristics from varlous polymers.Electrospun nanofibers demonstrated high efficiency in the immobilization of biological molecules,which can improve the sensing performance further.Integr ation of polymer electrospun nanofibers with metal nanoparticles,metal oxde or transition metal in producing nanobiocomposites is also a highly popul ar approach in the past few years.This report presents the current progress and research trends of the technique,focusing on varous ma-terials and fabrication strategies used to produce biosensing interfaces.This helps readers decide the suitable approach in designing highly sensitive,selective,fast,and inexpensive glucose sensors.

Current development in wearable glucose meters

Diabetes is one of the most disturbing chronic diseases in the world. The improvement of treatment efficiency brought by self-monitoring of blood glucose can relieve symptoms and reduce complications,which is considered as the gold standard of diabetes diagnosis and nursing. Compared to the traditional finger pricking measurement with painful and discontinuous processes, continuous blood glucose monitoring(CGM) presents superior advantages in wearable and continuous assessment of blood glucose levels. However, widely used implantable CGM systems at present require implantation operation and are highly invasive, so it is hard to be accepted by users. Except for the blood, available fluids in humans,such as interstitial fluid(ISF), sweat, tears and saliva, also contain glucose associated with blood sugar and can be extracted more easily. Therefore, these more accessible fluids are expected to realize minimized traumatic blood glucose monitoring. This review introduces the latest development of wearable minimally-/non-invasive CGM device, focusing on the types of blood substitute biological fluid and suitable monitoring approaches. We also analysis the merits and drawbacks of each method, and discuss the properties such as sensitivity, stability and convenience of each meter. Beyond highlighting recent key work in this field, we discuss the future development trend of wearable minimally-/non-invasive glucose meters.

Sandwich structure confined gold as highly sensitive and stable electrochemical non-enzymatic glucose sensor with low oxidation potential

The preparation of highly sensitive and stable non-enzymatic glucose sensors is critical to the prevention and treatment of diabetes.Fe_(3)O_(4)@Au@Co Fe-LDH is prepared through a spontaneous galvanic displacement reaction.A series of structural characterizations testify the successful formation of Fe_(3)O_(4)@Au@Co FeLDH electrocatalyst,with the Au intercalating between Fe_(3)O_(4)and LDH to form the sandwich structure.Cyclic voltammetry tests indicate that Au is responsible for the electrocatalytic oxidation of glucose.The characterizations of the electrochemical sensor for glucose detection indicate that Fe_(3)O_(4)@Au@Co FeLDH possesses high sensitivity of 6342μA m M^(-1)cm^(-2),with an extremely low oxidation potential of 0.82 V vs.RHE.Even with the high glucose concentration of 15 m M,the sensitivity remains at 4359μA m M^(-1)cm^(-2).Due to the broad linear detection range(0.0375 to 15.64 m M)and the low limit of detection(12.7μM),Fe_(3)O_(4)@Au@Co Fe-LDH is applicable towards practical application.Thanks to the sandwich structure,which confines the Au in between Fe_(3)O_(4)and Co Fe-LDH,the Fe_(3)O_(4)@Au@Co Fe-LDH glucose sensor shows high long-term stability and satisfactory selectivity.The successful synthesis of the sandwichstructured Fe_(3)O_(4)@Au@Co Fe-LDH provides a new conception for the design of highly sensitive and stable non-enzymatic glucose electrodes.

Glucose-sensitivity of core-shell microspheres and their crystalline colloidal arrays

Thermoresponsive core-shell microspheres are prepared and functionalized with 3-aminophenylboronic acid to make them responsive to glucose.The volume phase transition of the resulting particles is shifted to a lower temperature and a clear swelling is caused by the presence of glucose.The particles after the functionalization preserved their capability to form crystalline colloidal arrays.The changes of their properties may be used in the design of glucose sensors.

Integration of all-printed zinc ion microbattery and glucose sensor toward onsite quick detections

Rational design of microsystems and efficient integration of various functional modules that can directly realize the aimed functions are very attractive for portable and onsite practical applications,which is also significant in developing miniaturized and intelligent electronics and equipment.Unlike the conventional electrochemical glucose sensors that always need auxiliary complex systems for power supply,signal processing,and feedbacks,we design an all-printed glucose sensor integrated with a zinc ion microbattery(ZIMB)as a micropower source for portable and onsite quick glucose detections.The integrated glucose sensor(GS)and ZIMB(iGS-ZIMB)systempossesses a high areal energy density of 247.3μWh/cm^(2) and power density of 1193μW/cm^(2) and exhibits high sensitivity up to 464.2μA/mM/cm^(2),wide linear range of 0.5-6.0 mM,and good reproducibility in glucose detections.Through a simple amplification circuit design,the glucose concentration signals could be displayed within a short response time of 1.6 s without the need of external auxiliary equipment.Such iGS-ZIMB microsystem has prominent advantages in efficiency and cost and is promising for onsite medical and healthcare applications.

A toolkit of thread-based microfluidics,sensors,and electronics for 3D tissue embedding for medical diagnostics

Threads,traditionally used in the apparel industry,have recently emerged as a promising material for the creation of tissue constructs and biomedical implants for organ replacement and repair.The wicking property and flexibility of threads also make them promising candidates for the creation of three-dimensional(3D)microfluidic circuits.In this paper,we report on thread-based microfluidic networks that interface intimately with biological tissues in three dimensions.We have also developed a suite of physical and chemical sensors integrated with microfluidic networks to monitor physiochemical tissue properties,all made from thread,for direct integration with tissues toward the realization of a thread-based diagnostic device(TDD)platform.The physical and chemical sensors are fabricated from nanomaterial-infused conductive threads and are connected to electronic circuitry using thread-based flexible interconnects for readout,signal conditioning,and wireless transmission.To demonstrate the suite of integrated sensors,we utilized TDD platforms to measure strain,as well as gastric and subcutaneous pH in vitro and in vivo.

Construction of highly accessible single Co site catalyst for glucose detection

The development of high-performance glucose sensors is an urgent need, especially for diabetes mellitus diagnosis. However, the glucose monitoring is conventionally operated in an invasive finger-prick manner and their noninvasive alternatives largely suffered from the relatively poor sensitivity, selectivity, and stability, resulted from the lack of robust and efficient catalysts. In this paper, we design a concave shaped nitrogen-doped carbon framework embellished with single Co site catalyst(Co SSC) by selectively controlling the etching rate on different facet of carbon substrate, which is beneficial to the diffusion and contact of analyte. The Co SSC prompts a significant improvement in the sensitivity of the solutiongated graphene transistor(SGGT) devices, with three orders of magnitude better than those of SGGT devices without catalysts. Our findings expand the field of single site catalyst in the application of biosensors, diabetes diagnostics and personalized health-care monitoring.

Highly sensitive glucose sensor based on hierarchical CuO

The fabrication of high performance CuO based glucose sensors remains a great challenge due to the "trade-off effect" between sensitivity and linear range. In this study, a hierarchical CuO nanostructure with a great number of firecracker-shaped nanorods along the ligament and three-dimensional interconnected nanoporous is obtained by dealloying and post oxidation process of Al-33.3 wt% Cu eutectic alloy ribbons. Because of the precise structural design, not only the number of active sites for glucose electro-oxidation is significantly increased but also the glucose diffusion under high concentration is greatly accelerated, leading to a high sensitivity of 1.18 mA cm^(-2) mM^(-1) and a wider linear range up to 5.53 mM for glucose detection. This work provides a potential approach to design hierarchical nanostructure for other metal oxides with desirable properties for electrocatalytic applications.

HEXOKINASE1 forms a nuclear complex with the PRC2 subunits CURLY LEAF and SWINGER to regulate glucose signaling

The glucose sensor HEXOKINASE1(HXK1)integrates myriad external and internal signals to regulate gene expression and development in Arabidopsis thaliana.However,how HXK1 mediates glucose signaling in the nucleus remains unclear.Here,using immunoprecipitationcoupled mass spectrometry,we show that two catalytic subunits of Polycomb Repressive Complex 2,SWINGER(SWN)and CURLY LEAF(CLF),directly interact with catalytically active HXK1 and its inactive forms(HXK1^(G104D) and HXK1^(S177A))via their evolutionarily conserved SANT domains.HXK1,CLF,and SWN target common glucose-responsive genes to regulate glucose signaling,as revealed by RNA sequencing.The glucose-insensitive phenotypes of the Arabidopsis swn-1 and clf-50 mutants were similar to that of hxk1,and genetic analysis revealed that CLF,SWN,and HXK1 function in the same genetic pathway.Intriguingly,HXK1 is required for CLF-and SWN-mediated histone H3 lysine 27(H3K27me3)deposition and glucose-mediated gene repression.Moreover,CLF and SWN affect the recruitment of HXK1 to its target chromatin.These findings support a model in which HXK1 and epigenetic modifiers form a nuclear complex to cooperatively mediate glucose signaling,thereby affecting the histone modification and expression of glucoseregulated genes in plants.

Uniform and Homogeneous Growth of Copper Nanoparticles on Electrophoretically Deposited Carbon Nanotubes Electrode for Nonenzymatic Glucose Sensor

The multiwalled carbon nanotubes thin-film-based electrode was fabricated by electrophoretic deposition and modified with copper （Cu） nanoparticles to fabricate Cu/CNTs nanocomposite sensor for nonenzymatic glucose detection. The expensive glassy carbon electrode was replaced by fluorine-doped tin oxide glass containing CNTs film to confine the Cu nanoparticles growth by electrodeposition through cyclic voltammetry （CV）. The ultraviolet visible and X-ray diffraction analysis revealed the successful deposition of Cu nanoparticles on the CNTs-modified electrode. The atomic force microscopy images confirrqed the morphology of electrodeposited Cu on CNTs film as uniformly dispersed particles. The electrocatalytic activity of electrode to the glucose oxidation was investigated in alkaline medium by CV and amperometric measurements. The fabricated sensor exhibited a fast response time of less than 5 s and the sensitivity of 314 μA rnM^-1 cm^-2 with linear concentration range （0.02-3.0 mM） having detection limit 10.0 μM. Due to simple preparation of sensor, Cu/CNTs nanocomposite electrodes are a suitable candidate for reliable determination of glucose with good stability.

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

Lifestyle interventions,including dietary adjustments and exercise,are important for obesity management.This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism improvement.Forty-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 weeks.After the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance.Triglycerides decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group.Various glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD group.Only CV slightly decreased after exercise.This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance.Compared with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.