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Diabetes affects 1 in 11 people globally and requires monitoring of blood glucose levels as a part of its treatment. Initial blood glucose monitoring devices involved finger prick testing at regular intervals daily, a self-monitoring strategy reliant on patient compliance. Advances in technology have facilitated continuous glucose monitors (CGMs), (semi-) implantable devices that can monitor glucose levels in vivo and transmit the data to mobile applications. Majority of commercial CGMs are electrochemical in nature and meet the requirements for a commercial sensing implant. There are three main factors that limit CGMs for in vivo use – namely oxygen dependence, low molecular weight (LMW) materials and foreign body response (FBR) – which negatively affect the lifetime and accuracy of CGMs. This thesis aims to detail strategies to combat these issues, building on previous work performed in the field of enzymatic electrochemical glucose sensors. Chapter 2 details the use of design of experiments (DoE) to optimise enzyme electrode components – Osmium complex-based redox polymer, commercial glucose oxidising enzyme (glucose oxidase, GOx) and crosslinker (polyethylene glycol diglycidyl ether, PEGDGE). Previous work established high current and stability of a similar system which also incorporated acid treated multiwalled carbon nanotubes (MWCNTs) as a nanosupport. The MWCNTs enable high currents and surface coverages, but the quantities required were quite high, which can be detrimental for in vivo applications. In this chapter, the grafting of enzyme to nanosupport was carried out to allow minimisation of MWCNT amounts while retaining high currents and operational stability. DoE facilitated the determination of electrode component amounts for optimal current density and stability. The optimised enzyme electrodes show a current density of 3.18 ± 0.30 mA cm−2 , representing a 146% increase in current density in 50 mM phosphate-buffered saline at 37 °C containing 5 mM glucose when compared to similar systems where enzyme and nanosupport are not grafted to each other. Using the predictive DoE model, component amounts were then modified to minimise the quantity of the enzyme-MWCNT nanoconjugate, resulting in a biosensor which showed similar electrochemical behaviour and current density to the optimised system while using 93% less of the nanoconjugate Commercial GOx shows excellent behaviour for glucose oxidation but uses oxygen in its half reaction to regenerate. This is problematic as in vivo oxygen levels can fluctuate resulting in errors in measurement. Additionally, enzyme regeneration by oxygen reduction gives hydrogen peroxide as a product. Peroxide can cause enzyme instability as it oxidises the methionine residues of the enzyme, decreasing its activity. To combat this use, GOx was replaced with engineered cellobiose dehydrogenase (CDH) in Chapter 3. CDH is a dehydrogenase and thus does not use oxygen in its half reactions and has been modified to selectively choose glucose as its substrate. The enzyme electrodes comprising osmium complex-based redox polymer, CDH and PEGDGE were optimised with DoE, while a direct electron transfer (DET) based system was also optimised through conventional methods. The resulting sensors had sensitivities in the same order of magnitude as those in literature. Most importantly, sensor signals showed no difference in the presence and absence of oxygen. The sensors derived from CDH were shown to be specific to glucose over other clinically relevant in vivo sugars and selective, i.e., capable of glucose sensing in the presence of interfering species present in complex media. While no individual species is classified as an interferent in complex media they seemed to exhibit a cooperative effect resulting in a minimisation of current (43%). This is usually overcome with the use of polymer coatings. However, polymer coatings themselves lead to reduced sensor signals on their application, due to the formation of a diffusion barrier. Chapter 4 focuses on the design of polymer coatings to enable protection against biofouling while retaining current density. This was done by designing polymer coatings with a compatible epoxy crosslinking moiety on the polymer backbone that could crosslink with the redox polymer used in the sensing layer. The polymers selected in this study were zwitterionic in nature because of their inherent ability to minimise biofouling. Protein adsorption and cell adhesion studies, using fibrinogen and fibroblasts respectively, allowed a screening to select the most effective of the synthesised polymers for biofouling resistance. This poly(2- methacryloyloxyethyl phosphorylcholine-co-glycidyl methacrylate (MPC)-type polymer showed similar biofouling resistance compared to commercial polymer Lipidure with ~50% reduction in fibrinogen adsorption and ~80% reduction in fibroblast adhesion. When used as coatings for glucose biosensors fabricated in Chapter 3, MPC showed ability to resist protein adsorption while retaining current density similar to a non-coated system with 1.5-fold increase in sensitivity. MPC polymers showed ability to impart biofouling resistance while maintaining current signals. Nevertheless, their ability to resist LMW materials was not proved. In Chapter 5, a series of different protective strategies were explored to determine which approach would be the best to protect from biological and LMW interferences. Enzymatic scavenging using enzymes that target LMW species was investigated but showed inefficient scavenging, likely due to low enzymatic activity. Polymer multilayer approach with successive anionic and MPC polymer layers was utilised and showed the best potential. MPC as the outerlayer showed biofouling resistance whereas an anionic interlayer ([Poly(1-vinylimidazole-co-4-styrene sulfonic acid sodium salt hydrate], P(VI1 -SSNa1 )) inhibited anionic LMW species such as uric acid and ascorbic acid which cause interference. Moreover, due to the compatible crosslinking sites, the layers intermix at the boundary between them, minimising diffusional barrier and allowing current signals similar to a non-coated system. This multilayer protection system extends linear range and enables higher current and stability than a non-coated system in 50 mM phosphate-buffered saline and artificial plasma. Chapter 6 summarises the results from Chapter 2-5 and highlights the significant conclusions that can be drawn from these results. Future directions that can improve on the strategies in this thesis are also discussed.

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 Forster 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.

The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein coupled receptor and cAMP - protein kinase A signalling, but the sugar receptor has remained unknown. We show strong expression and co-localization with SGLT1 of the β2-adrenergic receptor (β2-AR) at the enterocyte apical membrane and reveal its role in stimulating glucose uptake from the gut by the sodium/glucose-linked transporter, SGLT1. Upon heterologous expression in different reporter systems, the β2-AR responds to multiple sugars in the mM range, consistent with estimated gut sugar levels after a meal. Most adrenergic receptor antagonists inhibit sugar signaling, while some differentially inhibit epinephrine and sugar responses. However, sugars did not inhibit binding of I125-cyanopindolol, a β2-AR antagonist, to the ligand-binding site in cell-free membrane preparations. This suggests different but interdependent binding sites. Glucose uptake into everted sacs from rat intestine was stimulated by epinephrine and sugars in a β2-AR-dependent manner. STD-NMR confirmed direct physical binding of glucose to the β2-AR. Oral administration of glucose with a non-bioavailable β2-AR antagonist lowered the subsequent increase in blood glucose levels, confirming a role for enterocyte apical β2-ARs in stimulating gut glucose uptake, and suggesting enterocyte β2-AR as novel drug target in diabetic and obese patients. Future work will have to reveal how glucose sensing by enterocytes and neuroendocrine cells is connected, and whether β2-ARs mediate glucose sensing also in other tissues.

Molecularly imprinted polymers (MIPs) have gained growing interest among researchers worldwide, due to their key features that make these materials interesting candidates for implementation as receptors into sensor applications. In fact, MIP-based glucose sensors could overcome the stability issues associated with the enzymes present in commercial glucose devices. Various reports describe the successful development of glucose MIPs and their coupling to a wide variety of transducers for creating sensors that are able to detect glucose in various matrices. In this review, we have summarized and critically evaluated the different production methods of glucose MIPs and the different transducer technologies used in MIP-based glucose sensors, and analyzed these from a commercial point of view. In this way, this review sets out to highlight the most promising approaches in MIP-based sensing in terms of both manufacturing methods and readout technologies employed. In doing so, we aim at delineating potential future approaches and identifying potential obstacles that the MIP-sensing field may encounter in an attempt to penetrate the commercial, analytical market.

Non-enzymatic electrochemical glucose sensors are of great importance in biomedical applications, for the realization of portable diabetic testing kits and continuous glucose monitoring systems. Nanostructured materials show a number of advantages in the applications of analytical electrochemistry, compared to macroscopic electrodes, such as great sensitivity and little dependence on analyte diffusion close to the electrode–solution interface. Obtaining electrodes based on nanomaterials without using expensive lithographic techniques represents a great added value. In this paper, we modeled the chronoamperometric response towards glucose determination by four electrodes consisting of nanostructured gold onto graphene paper (GP). The nanostructures were obtained by electrochemical etch, thermal and laser processes of thin gold layer. We addressed experiments obtaining different size and shape of gold nanostructures. Electrodes have been characterized by field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry, and chronoamperometry. We modeled the current-time response at the potential corresponding to two-electrons oxidation process of glucose by the different nanostructured gold systems. The finest nanostructures of 10–200 nm were obtained by laser dewetting of 17 nm thin and 300 °C thermal dewetting of 8 nm thin gold layers, and they show that semi-infinite linear diffusion mechanism predominates over radial diffusion. Electrochemical etching and 17 nm thin gold layer dewetted at 400 °C consist of larger gold islands up to 1 μm. In the latter case, the current-time curves can be fitted by a two-phase exponential decay function that relies on the mixed second-order formation of adsorbed glucose intermediate followed by its first-order decay to gluconolactone.

Aims: To conduct a pooled analysis to assess the performance of intermittently scanned continuous glucose monitoring (isCGM) in association with the rate of change in sensor glucose in a cohort of children, adolescents, and adults with type 1 diabetes. Material and methods: In this pooled analysis, isCGM system accuracy was assessed depending on the rate of change in sensor glucose. Clinical studies that have been investigating isCGM accuracy against blood glucose, accompanied with collection time points were included in this analysis. isCGM performance was assessed by means of median absolute relative difference (MedARD), Parkes error grid (PEG) and Bland-Altman plot analyses. Results: Twelve studies comprising 311 participants were included, with a total of 15 837 paired measurements. The overall MedARD (interquartile range) was 12.7% (5.9-23.5) and MedARD differed significantly based on the rate of change in glucose (P < 0.001). An absolute difference of -22 mg/dL (-1.2 mmol/L) (95% limits of agreement [LoA] 60 mg/dL (3.3 mmol/L), -103 mg/dL (-5.7 mmol/L)) was found when glucose was rapidly increasing (isCGM glucose minus reference blood glucose), while a -32 mg/dL (1.8 mmol/L) (95% LoA 116 mg/dL (6.4 mmol/L), -51 mg/dL (-2.8 mmol/L)) absolute difference was observed in periods of rapidly decreasing glucose. Conclusions: The performance of isCGM was good when compared to reference blood glucose measurements. The rate of change in glucose for both increasing and decreasing glucose levels diminished isCGM performance, showing lower accuracy during high rates of glucose change. Keywords: continuous glucose monitoring (CGM); type 1 diabetes.

Herein, we reported a self-assembled fabrication of a network nanozyme (TMPyP-pSC4@GNPs) and a glucose-recognition molecule (APBA) for highly stable and selective glucose sensing. By involving the ...

Herein, a two-dimensional (2D) Co(OH)2 nanosheet (NS) was prepared by reacting Co(II) acetate with 2-ethylimidazole and trimethylamine at room temperature. The as-prepared Co(OH)2 NS-modified screen-printed electrode enabled glucose sensing in human blood plasma samples (HBP) diluted with phosphate buffer saline (PBS, pH 7.4) and NaOH (0.1 M, pH 13.0) solutions. The electrocatalytic activity of Co(OH)2 NS for glucose oxidation in a wide pH range can be ascribed to the enriched oxygen vacancies with a high surface area of the porous NS, which enabled the facile formation of CoII/CoIII redox pair. The oxidation current response as a function of glucose concentration displayed two straight lines in the ranges 55.12–117.50 μM and 180–12055 μM in PBS diluted HBP, and 62.80–180 μM and 305–12055 μM in NaOH diluted HBP with the sensitivity of 430 and 98.18 μA/cm2/mM and the limit of detection of 0.082 and 2.2 μM, in PBS and NaOH diluted HBP solutions, respectively. The sensor also exhibited good long-term stability, repeatability, and interference-free signals. The good analytical performance of the proposed sensor demonstrates the suitability of Co(OH)2 NS as a material to fabricate disposable systems for the direct detection of glucose in human body fluids at physiological pH.

Purpose The purpose of this study is to develop a non-enzymatic based glucose-sensing platform composed of Bodipy-BBV dual system which can be monitored by a photodetector under the blue LED excitation. Design/methodology/approach The sensor has been developed from a dual system including a fluorescent dye, an aldehyde derivative of boron dipyrromethene (Bodipy) and a quencher, orto-boronic acid linked viologen (o-BBV) where their combination resulted in a ratiometric fluorescence quenching in ethanol: PBS (1:1, pH:7.4) solution under UV light excitation. By glucose addition, o-BBV has been released from the Bodipy and binded to cis-diol groups of glucose, thereby fluorescence emission of Bodipy has been regained. Furthermore, a setup consisting of a light emitting diode (LED) and a photodiode (PD) was used to prove electrical detection of glucose without the need for expensive and bulky optical equipment, enabling the development of a miniaturized and low-cost glucose-sensing platform. Findings The fluorescence intensity of the Bodipy derivative in the solution (2 × 10−6 M) was diminished by 93% in the presence of o-BBV solution (5 × 10−3 M). Upon the glucose addition, 81% of the Bodipy fluorescence intensity has been recovered after introduction of 30 mM of glucose, where the ratio of o-BBV/Bodipy was 35:1. A linear response between 10 and 30 mM glucose concentration was obtained, which covers the biologically significant range. A high correlation between the photodiode current and Bodipy fluorescence intensity was achieved. Originality/value Even though Bodipy molecules are known with their superior optical properties and applied to the fluorescence-based detection of glucose, to the best of the authors’ knowledge, no work has been reported on Bodipy-BBV dual system to detect glucose molecules as a non-enzymatic based method. This design enables the dye and the quencher to independently coexist in the solution, allowing for tuning of their individual concentrations to optimize the glucose sensitivity. Furthermore, an electrical light detection scheme consisting of a LED and a photodiode has been implemented to eliminate the bulky optical equipment from the measurement setup and further this work for the development of a compact and inexpensive sensor. The results presented here demonstrate the feasibility of this system for the development of a novel glucose sensor.

It is shown here that microwave sensors can be used to monitor glucose in serum concentration with minimum detectable as well as resolution of 1 mMol $\cdot \text{L}^{{-1}}$ ( $\approx 18$ mg $\,\cdot $ dL−1). The ultrasensitive detection technique relies on a split ring resonator, operating at the frequency of 1.156 GHz, as the core of the sensor where its loss is compensated to enhance the quality factor from $\sim 190$ (passive mode) to $\sim 3850$ (active mode) to enable high resolution (modified frequency detection error from ±12 kHz down to ±2.5 kHz) frequency-shift sensing. Initially, glucose concentrations of 100–1000 mMol $\,\cdot \text{L}^{{-1}}$ (1800–18000 mg $\,\cdot $ dL−1) in water were detected within 250 kHz of dynamic range (between two spectrum ends). Selectivity of the sensor to glucose is verified with respect to common interstitial fluid ingredients with biological levels. Finally, to enhance the resolution of the proposed sensor, its loss–compensation is further improved leading to increased accuracy of measuring glucose samples in a 0.9 % NaCl solution containing 10 % horse serum that closely resembles blood plasma and interstitial fluid. This allows exploration of lower concentrations in the physiological range 1–30 mMol $\,\cdot \text{L}^{{-1}}$ (18–540 mg $\,\cdot $ dL−1) with improved frequency detection error down to ±0.75 kHz for two cases of with/without serum solutions with dynamic range of 30 kHz/38 kHz. The highly accurate glucose monitoring technique could be utilized for developing noninvasive glucose sensors for biomedical applications in real–time glucose monitoring.

The development of responsive materials in a predictable manner is high on the list of the material industry’s trends. In this work, responsive Ag@NiCo2O4 nanowires were, firstly, anchored on N-doped carbon cloth (NC) and, then, employed as array electrodes for a nonenzymatic glucose-sensing application. The results showed that the highly conductive NiCo2O4 nanowires supported Ag nanoparticles and exhibited high conductivity and electrocatalytic properties. The fully exposed crystalline planes of Ag nanoparticles provided more active surface sites. As a result, the assembled Ag@NiCo2O4-NC electrodes for the glucose-sensing evaluation delivered a selectivity of 2803 μA mM−1 cm−2 and a detection limit of 1.065 μM, which outperformed the literature-reported Ag- and NiCo2O4-based glucose-sensing catalysts.

Developing a simple and convenient approach for glucose sensing is crucially important in disease diagnosis and health monitoring. In this work, a glucose sensor based on plasmonic nanostructures was developed using gold–silver core–shell nanoparticles as the sensing platform. Based on the oxidative etching of the silver shell, the concentration of hydrogen peroxide and glucose could be determined quantitatively via the spectral change. This spectral change could also be observed with the naked eye or with a phone camera, realizing colorimetric sensing. To demonstrate this, glucose solutions at different concentrations were quantitatively detected in a wide concentration range of 0–1.0 mM using this colorimetric sensor. Importantly, shell thickness could significantly affect the sensitivity of our colorimetric sensor. This work provides a deeper understanding of the plasmonic sensing of glucose, which will help to realize its real applications. Based on this strategy, the non-invasive sensing of metabolites may be realized for disease diagnosis and health monitoring.

Artificial pancreas enhances the life experience for diabetic patients by allowing them to live normally with their glucose levels controlled automatically with minimal or no intervention. For closed-loop glucose controllers to be approved for clinical practice, they have to prove safety under all potential scenarios. One of the biggest challenges of closed-loop glucose control is to handle the distortion caused by meal intake. This challenge becomes more problematic when taking into account the imperfections and limitations of glucose sensors. In this article, we propose new Proportional-Integral-Derivative (PID)-based control strategies for robust glucose control under varying meal conditions. The proposed approaches aim at counteracting the challenges imposed by the large delays incurred in glucose sensing and insulin action. Statistical model checking was utilized to analyze the performance figures and safety properties as compared with existing closed-loop techniques. The results have shown that one of the proposed approaches provide substantial enhancements towards safe and robust glucose control especially under sensor noise. Where, under a typical relative meal size between 75 and $125\:(g/100Kg)$ , the proposed approach can satisfy hypoglycemia safety property for 90% of the patients compared to lower than 50% of the patients for the other investigated techniques. These enhancements can be achieved without additional personalized tuning beyond the standard PID control.

Insulin‐independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6‐phosphofructo‐2‐kinase‐fructose‐2,6‐biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High‐Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate‐response element‐binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose‐sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin‐independent glucose metabolism.

The development of chemosensors to detect analytes in biologically relevant solutions is a challenging task. We report the synthesis of a fluorescent receptor that combines vibration‐induced emission (VIE) and dynamic covalent chemistry for the detection of glucose in aqueous media. We show that the bis‐2‐(N‐methylaminomethyl)phenylboronic acid‐decorated N,N′‐diphenyl‐dihydrodibenzo[a,c]phenazine (DPAC) receptor 1 can detect glucose and discriminate between closely related monosaccharides including those commonly found in blood. Preliminary studies suggest monosaccharides bind to the DPAC‐receptor with a 1:1 stoichiometry to produce pseudomacrocyclic complexes, which in turn leads to distinct optical changes in the fluorescent emission of the receptor for each host. Moreover, the complexation‐induced change in emission can be detected visually and quantified in a ratiometric way. Our results highlight the potential of VIE‐type receptors for the quantitative determination of saccharides in biological samples., A novel sugar fluorescent chemosensor which combines a vibrational‐induced‐emission (VIE)‐active DPAC core and two N‐methylaminomethylphenylboronic acid moieties can detect glucose within seconds and discriminate between closely related monosaccharides including those commonly found in blood.

In this article, we present a free-standing terahertz metasurface based on asymmetric S-shaped complementary resonators under normal incidence in transmission mode configuration. Each unit cell of the metasurface consists of two arms of mirrored S-shaped slots. We investigate the frequency response at different geometrical asymmetry via modifying the dimensions of one arm of the resonator. This configuration enables the excitation of asymmetric quasi-bound states in the continuum resonance and, hence, features very good field confinement that is very important for biosensing applications. Moreover, the performance of this configuration as a biosensor was examined for glucose concentration levels from 54 mg/dL to 342 mg/dL. This range covers hypoglycemia, normal, and hyperglycemia diabetes mellitus conditions. Two sample coating scenarios were considered, namely the top layer when the sample covers the metasurface and the top and bottom layers when the metasurface is sandwiched between the two layers. This strategy enabled very large resonance frequency redshifts of 236.1 and 286.6 GHz that were observed for the two scenarios for a 342 mg/dL concentration level and a layer thickness of 20 μm. Furthermore, for the second scenario and the same thickness, a wavelength sensitivity of 322,749 nm/RIU was found, which represents a factor of 2.3 enhancement compared to previous studies. The suggested terahertz metasurface biosensor in this paper could be used in the future for identifying hypoglycaemia and hyperglycemia conditions.

Porous materials are currently the basis of many optical sensors because of their ability to provide a higher interaction between the light and the analyte, directly within the optical structure. In this study, mesoporous TiO2 layers were fabricated using a bottom-up synthesis approach in order to develop optical sensing structures. In comparison with more typical top-down fabrication strategies where the bulk constitutive material is etched in order to obtain the required porous medium, the use of a bottom-up fabrication approach potentially allows increasing the interconnectivity of the pore network, hence improving the surface and depth homogeneity of the fabricated layer and reducing production costs by synthesizing the layers on a larger scale. The sensing performance of the fabricated mesoporous TiO2 layers was assessed by means of the measurement of several glucose dilutions in water, estimating a limit of detection even below 0.15 mg/mL (15 mg/dL). All of these advantages make this platform a very promising candidate for the development of low-cost and high-performance optical sensors.

The rapid detection of postprandial hyperglycaemia (PPHG) is imperative for the diagnosis of diabetes and the assessment of health risks for nondiabetics. Battery-free flexible glucose sensors are a promising tool for glucose sensing with a relatively low burden on biological tissues and living bodies because they are more lightweight and flexible than conventional battery-driven glucose sensors. However, existing battery-free glucose sensors are unsuitable for the practical detection of hyperglycaemia because of their long response time (>1 h) and response fluctuation. In this research, we demonstrated a unique combination of materials and device design—phenylboronic acid (PBA) hydrogel integrated with an inkjet-printed interdigitated capacitor (IDC)—that enabled rapid response to the change in the glucose concentration. In particular, the following three essential capabilities have been demonstrated: (1) quick response time (

Hierarchical spinel NiCo2O4 microflowers have been successfully designed and synthesized by a successive mild spray-thermal treatment method via bimetallic NiCo-metal-organic framework formation. R...

Glucose is an analyte of great importance, both in the clinical and sports fields. As an alternative to standard blood analysis, sweat arises as an easily accessible, non-invasive biofluid, as well as a great candidate to monitor human health and sport performance of athletes. However, there is a current need for the fabrication of low cost, easy to use technologies capable of sequential analysis of sweat biomarkers at different times. In this research, we developed a chrono-sampling microfluidic platform integrated with an alginate/TiO2 biosystem for sweat glucose determination. Glucose concentrations ranging from 10 to 1000 µM in artificial sweat were detected and quantified, both in a bead format and in the device, where the whole system was calibrated and verified. The PDMS microfluidic platform allowed chrono-sampling over more than 42 min. This research is oriented towards the development of a miniaturized device for fast analysis at the point and place of need. The integration of the chrono-sampling capacity opens the possibility for a continuous monitoring of sweat biomarkers during exercise, allowing a personalized-oriented training to improve the performance of athletes. This research was funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 778001 (DNASurf), the European Union’s Horizon 2020 research and innovation program under grant agreement No. 766007 (MAMI), the “Ministerio de Ciencia y Educación de España” under grant PID2020–120313 GB-I00 / AIE / 10.13039/501100011033 and the Basque Government (Grant IT1633–22).

MnO2 based electrochemical enzyme-free glucose sensors remain significantly limited by their low electronic conductivity and associated complex preparation. In this paper, an MnO2 nanosheet array supported on nickel foam (MnO2 NS/NF) was prepared using a simple hydrothermal synthesis and employed as a 3D integrated electrode for enzyme-free glucose detection. It was found that MnO2 NS/NF shows high performance with a wide linear range from 1 μM to 1.13 mM, a high sensitivity of 6.45 mA mM-1 cm-2, and a low detection limit of 0.5 μM (S/N = 3). Besides, MnO2 NS/NF shows high selectivity against common interferences and good reliability for glucose detection in human serum. This work demonstrates the promising role of MnO2 NS/NF as an efficient integrated electrode in enzyme-free glucose detection with high performance.

Technology in Diabetes Mellitus has been available in the form of insulin pump delivery systems for almost 40 years and glucose sensing technology for over 20 years. It is just the last 10 years there have been broad adoptions of both pumps and personal sensors and more recently integrated delivery systems that are bringing us closer to physiologic dynamic control of diabetes that strives to replicate glucose control similar to persons without diabetes (who have normal glucose control mechanisms). Data from this technology is part of routine clinical practice in anyone caring for persons with diabetes especially in the type 1 space. This is a new avenue for clinical research but also a new area of challenge for providers and staff caring for patients with this technology. There is slowly emerging research that focuses on this clinical data specifically available from personal sensors. This discussion will briefly review what this looks like in clinical practice and a sampling of data from research in this new technology. Then we will discuss how providers, educators, patients, and other stakeholders should work as a team to focus on critical thinking as an essential skill set.

Glucose performs many essential functions associated with metabolic processes in the living system, and is closely related to many diseases such as diabetes and hypoglycemia. Most of the existing glucose concentration detection methods require complex instruments, which undoubtedly limit its widespread use. Here, we have designed a glucose colorimetric detection system composed of glucose, glucose oxidase (GOD), manganese dioxide nanosheets (MnO2 NSs) and 3,3',5,5'-tetramethylbenzidine (TMB) to achieve colorimetric detection with the naked eye. Compared with the single-color change of the colorimetric method in previous studies, multiple-color changes have been realized. MnO2 NSs, as a kind of nanomaterial imitating oxidase, can directly oxidize TMB to oxTMB. Because oxTMB showed a dark yellow color when strongly oxidized and light blue when weakly oxidized, this feature can achieve multiple-color changes rather than a single-color change, which is helpful for colorimetric observation with the naked eye. Finally, we successfully used MnO2 NSs for colorimetric detection of glucose and realized multiple-color changes, making it easier to achieve colorimetric observation with the naked eye. The linear detection range is 0-4000 μM and limit of detection is 5.0 μM. This is not only useful for glucose, but also has an important significance for other experiments considering colorimetric experiments with the naked eye.

Numerous studies have demonstrated that the construction of heterojunctions in electrode materials resulted in a significant improvement of electrochemical glucose sensing. However, there have so far been rare studies on the underlying relationship between heterojunctions and glucose sensing, and the mechanism for enhancing the glucose sensing ability is still elusive. Herein, with the aid of experimental and theoretical studies, the Cu2O–CuS heterostructure was constructed as a proof of concept to illustrate the role that heterojunctions play in the glucose sensing process. Density functional theory (DFT) calculations revealed that Cu2O–CuS heterojunctions possessed a decreased formation energy of electroactive Cu(III) species along with a lower adsorption energy of glucose molecules, enabling more favorable reaction kinetics for glucose electrooxidation. As expected, the Cu2O–CuS electrode shows superior electrochemical glucose sensing performance with respect to the Cu2O electrode. This work provides significant implications for designing advanced electrochemical sensors in the future.

The present research work is the part of the feasibility study to implement non-invasive blood-glucose sensing using microwave-based sensor. The one-port microstrip patch antenna sensor developed to exhibit variation in its electromagnetic response with respect to blood-glucose level. It has been demonstrated through in vitro controlled experiment under laboratory conditions. The novel multi-parameter-based sensitivity factor termed as GlucoSense was also defined to evaluate the sensitivity of sensor towards the change in glucose concentration. It was established that there was a good correlation between sensor’s reflection properties and glucose concentration. The findings of the controlled experiment convincingly proved that the sensor has the potential to be effectively used for developing a suitable device for non-invasive blood-glucose sensing.

In the present study, a rational two-step strategy is employed for the green, fast, very simple and highly controllable synthesis of the bimetallic nickel-cobalt based metal-organic frameworks on g...

The hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders. While mouse models have been extensively employed for understanding mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and high-sucrose diet (HFHSD) for 7 days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.

This work demonstrates a non-contact diffuse reflectance approach with a working distance of ∼1.1 meters for the potential of glucose sensing. Non-contact diffuse reflectance over 1.1–1.3 µm was developed according to a center-illumination-area-detection (CIAD) geometry. The modeled response of diffuse reflectance in the CIAD geometry was examined with phantoms by altering independently the size of the collection geometry and the reduced scattering and absorption properties of the medium. When applied to aqueous turbid medium containing glucose control solutions with the cumulative volume varying over three orders of magnitude, a linear relationship expected for the diffuse reflectance as a function of the medium absorption/reduced-scattering property was observed for four conditions of the glucose-medium composition that differed either in the effective glucose concentration or the host medium scattering property. The cumulation of glucose up to 17.8 mg/dL and 8.9 mg/dL in the host medium having the same optical properties resulted in linear regression slopes of 0.0032 and 0.0030, respectively. The cumulation of the glucose up to 17.8 mg/dL in an aqueous host medium that differed two folds in the reduced scattering property caused the linear regression slope to differ between 0.0032 and 0.0019. The R2 values of all cases were all greater than 0.987.

The saturation of nonenzymatic blood glucose sensors at lower than normal blood glucose levels has blocked their practical applications. The mechanistic understanding of the saturation, however, has long been under debate. Employing cyclic voltammetry, amperometry, and FTIR with various electrolytes of varying concentrations, we were able to uproot the saturation cause. It was found to be related to the hydroxide ion concentration, which must be 11 times greater than that of the glucose concentration, contrary to the prior understanding. Together with the satisfactory sensitivity at high pH, nonenzymatic blood glucose sensing has finally been achieved, eliminating the usual problem of electrochemical current saturation as well as the need for enzyme found in the present technology.

Glucose monitoring is an important clinical procedure, especially for dialysis patients who need consistent monitoring of their glucose levels. Currently, the most extensively used method for glucose monitoring involves pricking the finger and sampling a small amount of blood. Given that this procedure is inconvenient and can cause pain and potential infection, there is demand for the development of alternative glucose sensing methods. This study introduces a methodology for improved glucose sensor specificity based on a calibration scheme. One microwave and one capacitive glucose sensor were designed and placed on a prosthetic vascular graft. Each sensor yielded a finite variation in the measured glucose concentrations based on its capacity to sense permittivity changes in aqueous D-glucose solutions. However, as blood components other than glucose—such as proteins, erythrocytes and haemoglobin—may affect the measurements, the authors also introduced a calibration scheme to adjust and calibrate each measurement to ensure accuracy. The measurement data yielded a maximum error of

Conjugated hybrid nanostructured Cu2O-ZnO has been grown via the single-step coelectrodeposition (CED) technique. Though ZnO nanostructures grown alone by electrodepostion technique do not exhibit any glucose sensing, the CED-grown Cu2O-ZnO nanostructures show non-enzymatic glucose sensing and amperometric behavior with a good sensitivity of 441.2 μ A mM− 1 cm− 2, linear range of 0.02–1 mM and low detection limit of 0.13 μ M (S/N = 3) along with a fast response time (less than 3 s). The CED growth process leads to development of conjugated hybrid nanostructured Cu2O-ZnO that presents an excellent template for non-enzymatic glucose sensing.

In this work, we have successfully proclaimed the importance of defect prone nanostructure on to the electrode surface for the promising glucose sensing applications. Oxygen-deficient W18O49 moieti...

A rhombicuboctahedral (26-facet) Cu2O single crystal, generally with well-developed {100}, {110} and {111} crystallographic planes, has attracted considerable attention due to its faceted synergistic effects in catalysis, sensing, and energy conversion. However, the electrocatalytic performance of the 26-facet Cu2O single crystal can be severely limited by its large size and low-active smooth surface, since it is quite difficult to prepare high-active 26-facet Cu2O nanocrystals exposed with rough surfaces. In this article, we successfully prepared jagged 26-facet Cu2O nanocrystals with clean facets at room temperature via a facile Mn2+ mediated aqueous phase reduction method. The shape-evolution and growth mechanism of rhombicuboctahedral Cu2O nanocrystals enclosed by jagged surfaces are also proposed, which might be attributed to a sequential dissolution–precipitation–surface reforming mechanism. These unique jagged 26-facet nanocrystals exposed with more active sites can exhibit superior glucose-sensing performance than those of the traditional 26-facet Cu2O microcrystals enclosed by smooth surfaces. With the merits of facile control as well as relatively high activity, it could provide a good prospect for the surfactant-free synthesis of other metal oxides with well-defined crystal planes.

A recent paper by Oh et al. identified a single pair of neurons in the fruit fly brain that directly senses ‘blood’ glucose levels and reciprocally regulates the secretion of insulin and glucagon. This study provides insight into how the brain regulates the circulation and storage of glucose.

Non-enzyme glucose sensors constructed using transition metal oxides present several advantages such as their low cost, high stability, and high sensitivity. Herein, a kind of porous nanosphere-stacking CuO structure has been synthesized by optimizing the thermal decomposition atmosphere, which was derived from Cu-metal–organic framework (Cu-MOF) microrods. Such hierarchical CuO structures, with controllable porosity and adjustable surface area, are efficient catalytic materials for glucose sensing. Benefiting from structural advantages, the obtained porous hierarchical CuO nanospheres exhibit enhanced sensing performance compared to hierarchical CuO clusters. Based on CuO, the effects of surface and morphology on the sensing performance of glucose are also discussed. The sensitivity of CuO porous hierarchically nanospheres for glucose is found to be 1806.1 μA cm−2 mM−1 in the wide linear range of 0–6.535 mM with a low detection limit (S/N = 3) of 0.15 μM. Glucose detection in artificial saliva is then performed, which shows excellent capability in the low concentration range (5 μM–1.165 mM) for non-invasive sensing performance. The sensor also demonstrates a good recovery in real saliva. The novel MOF-templated CuO hierarchical nanospheres are expected to be effective sensing materials for developing non-enzyme and non-invasive glucose sensors.

This work demonstrates a non-contact diffuse reflectance approach with a working distance of ~1.1 meters for the potential of glucose sensing. Non-contact diffuse reflectance over 1.1-1.3 μm was developed according to a center-illumination-area-detection (CIAD) geometry. The modeled response of diffuse reflectance in the CIAD geometry was examined with phantoms by altering independently the size of the collection geometry and the reduced scattering and absorption properties of the medium. When applied to aqueous turbid medium containing glucose control solutions with the cumulative volume varying over three orders of magnitude, a linear relationship expected for the diffuse reflectance as a function of the medium absorption/reduced-scattering property was observed for four conditions of the glucose-medium composition that differed either in the effective glucose concentration or the host medium scattering property. The cumulation of glucose up to 17.8 mg/dL and 8.9 mg/dL in the host medium having the same optical properties resulted in linear regression slopes of 0.0032 and 0.0030, respectively. The cumulation of the glucose up to 17.8 mg/dL in an aqueous host medium that differed two folds in the reduced scattering property caused the linear regression slope to differ between 0.0032 and 0.0019. The R2 values of all cases were all greater than 0.987.

Objective: Diabetes patients are increasingly using a continuous glucose sensor to monitor blood glucose and an insulin pump connected to an infusion cannula to administer insulin. Applying these devices requires two separate insertion sites, one for the sensor and one for the cannula. Integrating sensor with cannula to perform glucose sensing and insulin infusion through a single insertion site would significantly simplify and improve diabetes treatment by reducing the overall system size and the number of necessary needle pricks. Presently, several research groups are pursuing the development of combined glucose sensing and insulin infusion devices, termed single-port devices, by integrating sensing and infusion technologies created from scratch. Methods: Instead of creating the device from scratch, we utilized already existing technologies and introduced three design concepts of integrating commercial glucose sensors and infusion cannulas. We prototyped and evaluated each concept according to design simplicity, ease of insertion, and sensing accuracy. Results: We found that the best single-port device is the one in which a Dexcom sensor is housed inside a Medtronic cannula so that its glucose sensitive part protrudes from the cannula tip. The low degree of component modification required to arrive at this configuration allowed us to test the efficiency and safety of the device in humans. Conclusion: Results from these studies indicate the feasibility of combining commercial glucose sensing and insulin delivery technologies to realize a functional single-port device. Significance: Our development approach may be generally useful to provide patients with innovative medical devices faster and at reduced costs.

Strenuous efforts have been made to develop nanozymes for achieving the performance of natural enzymes to broaden their application in practice, but the fabrication of high-performance and biocompatible nanozymes via facile and versatile approaches has always been a great challenge. Here, sponge-like casein-CuS hybrid has been facilely synthesized in the presence of amphiphilic protein-casein through a simple one-step approach. Casein-CuS hybrid exhibits substrates-dependent peroxidase-like activity. Casein-CuS hybrid exhibits well peroxidase-like activity with 3,3′,5,5′-tetramethylbenzidine (TMB) and 1,2-diaminobenzene (OPD) as substrates, and the affinity of OPD towards the hybrid nanozyme is much higher than that of TMB. More importantly, due to the high affinity of OPD and the well biocompatibility of the hybrid nanozyme, a superior enzyme cascade for glucose based on the well cooperative effect of casein-CuS hybrid and glucose oxidase is developed. The proposed glucose sensor exhibits a wide linear range of 0.083 to 75 μM and a detection limit of 5 nM. This suggests the promising utilization of protein–metal hybrid nanozymes as robust and potent peroxidase mimics in the medical, food and environmental detection fields.

While over half a century has passed since the introduction of enzyme glucose biosensors by Clark and Lyons, this important field has continued to be the focus of immense research activity. Extensive efforts during the past decade have led to major scientific and technological innovations towards tight monitoring of diabetes. Such continued progress toward advanced continuous glucose monitoring platforms, either minimal- or non-invasive, holds considerable promise for addressing the limitations of finger-prick blood testing toward tracking glucose trends over time, optimal therapeutic interventions, and improving the life of diabetes patients. However, despite these major developments, the field of glucose biosensors is still facing major challenges. The scope of this review is to present the key scientific and technological advances in electrochemical glucose biosensing over the past decade (2010-present), along with current obstacles and prospects towards the ultimate goal of highly stable and reliable real-time minimally-invasive or non-invasive glucose monitoring. After an introduction to electrochemical glucose biosensors, we highlight recent progress based on using advanced nanomaterials at the electrode-enzyme interface of three generations of glucose sensors. Subsequently, we cover recent activity and challenges towards next-generation wearable non-invasive glucose monitoring devices based on innovative sensing principles, alternative body fluids, advanced flexible materials, and novel platforms. This is followed by highlighting the latest progress in the field of minimally-invasive continuous glucose monitoring (CGM) which offers real-time information about interstitial glucose levels, by focusing on the challenges toward developing biocompatible membrane coatings to protect electrochemical glucose sensors against surface biofouling. Subsequent sections cover new analytical concepts of self-powered glucose sensors, paper-based glucose sensing and multiplexed detection of diabetes-related biomarkers. Finally, we will cover the latest advances in commercially available devices along with the upcoming future technologies.

On-site and instant glucose sensing is essential for objectively monitoring the change of glucose content that has decisive effects on the normal regulation of carbon metabolism. Colorimetric synergy based on indicators for real-time sensing seemed to be the potential route, but so far it has remained quite challenge to shift down the detection limit in a stable manner. Also, the lack of a direct identification of the underlying detection mechanism especially on the exhibited color change limited their practical use. In this study, the strategy is to employ the carbon nanodots with silver shells functioning as the highly sensitive indicators that enabled realization of the colorimetric sensing of glucose which is caused by oxidation of the surface silver shell observed by the naked eye. These were based on the robust core/shell architectures that allowed an ultralow limit of detection of 87.3 nM for glucose detection through the formation of Ag2O that led to the obvious particle aggregations, and the resu...