Continuous Glucose Detection Research Articles

A non-enzymatic flexible and wearable sensor based on thermal transfer printing technology for continuous glucose detection in sweat

Non-invasive, flexible wearable sensors are an important method to continuously measure glucose in sweat for diabetes and human health monitoring and management. However, how to create an alkaline environment at any time so that CuO based sensors can be applied to wearable devices to detect sweat glucose while finding a way to efficiently and quickly produce the sensors in small batches have been a challenge. Herein, we report a non-enzymatic thermal transferred flexible and wearable sensor based on CuO/CaTiO3 for continuous glucose detection in sweat. The sensor is manufactured using thermal transfer printing technology, which offers advantages like low cost, ease of operation, and rapid small batch production. CuO is known for its excellent electrocatalytic activity, making it a suitable candidate for glucose oxidation. Meanwhile, CaTiO3 particles provide a large specific surface area, good biocompatibility, and electrical conductivity, which enhance the electron transfer rate during detection and broaden the linear range of glucose detection. Specially designed NaOH/Nafion/PEO blend film make the measurements always in a strong alkali environment without any pretreatment and preparation. The synthesized material with this as-prepared flexible and wearable sensor exhibits superior performance towards glucose monitoring, such as high sensitivity of 487.3 μA mM−1 cm−2 with limit of detection(LOD) 0.75 μM, wide dynamic linear range from 0.01 mM to 2 mM and fast response time of less than 0.1 s. Additionally, the proposed sensor also exhibited excellent biocompatibility, selectivity, reproducibility and flexibility, as well as good stability with about 88 % of its initial activity after 5 weeks’ storage and it has been successfully applied for the detection of glucose concentration in human sweat real samples. This research contributes to the development of flexible and wearable sensors for non-invasive sweat diagnostics, enabling continuous glucose monitoring for various applications in healthcare and wellness.

O13 | The pig as surrogate model for humans for the rational design of an invisible sensor for subcutaneous continuous glucose detection for type 1 diabetes management

Journal of Veterinary Pharmacology and TherapeuticsVolume 46, Issue S1 p. 34-34 ORAL PRESENTATIONS O13 | The pig as surrogate model for humans for the rational design of an invisible sensor for subcutaneous continuous glucose detection for type 1 diabetes management First published: 11 June 2023 https://doi.org/10.1111/jvp.13179Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume46, IssueS1Special Issue: 15th International Congress of the European Association for Veterinary Pharmacology and Toxicology held Bruges, Belgium, July 2–5, 2023June 2023Pages 34-34 RelatedInformation

Biomolecular sensors for advanced physiological monitoring.

Body-based biomolecular sensing systems, including wearable, implantable and consumable sensors allow comprehensive health-related monitoring. Glucose sensors have long dominated wearable bioanalysis applications owing to their robust continuous detection of glucose, which has not yet been achieved for other biomarkers. However, access to diverse biological fluids and the development of reagentless sensing approaches may enable the design of body-based sensing systems for various analytes. Importantly, enhancing the selectivity and sensitivity of biomolecular sensors is essential for biomarker detection in complex physiological conditions. In this Review, we discuss approaches for the signal amplification of biomolecular sensors, including techniques to overcome Debye and mass transport limitations, and selectivity improvement, such as the integration of artificial affinity recognition elements. We highlight reagentless sensing approaches that can enable sequential real-time measurements, for example, the implementation of thin-film transistors in wearable devices. In addition to sensor construction, careful consideration of physical, psychological and security concerns related to body-based sensor integration is required to ensure that the transition from the laboratory to the human body is as seamless aspossible.

Nonenzymatic Glucose Biosensors: Latest Advances and Perspectives

Over the sixty years since glucose biosensor was introduced, development of glucose biosensor had experienced three generations. Considering the increasing demand of glucose biosensor, research and development has been carried out for more promising nonenzymatic glucose biosensor. Compared to the traditional enzyme-based glucose biosensor, nonenzymatic sensor is more capable to continuous glucose detection and has higher stability. Additionally, nonenzymatic glucose biosensor has a lower fabrication cost, which can be beneficial to the wide range of patients with the need for constant checking for blood glucose concentration. This paper introduces two proposed nonenzymatic glucose detection models: activated chemisorption and incipient hydrous oxide adatom mediator. As the developing trend of glucose biosensors is toward wearable and continuous glucose monitoring, two wearable sensors and working principles are introduced. This paper describes the application progress of different types of materials in enzyme-free blood glucose sensors, puts forward the existing problems in the application of enzyme-free blood glucose sensors, and looks forward to its future application prospects.

A High-Linearity Glucose Sensor Based on Silver-Doped Con A Hydrogel and Laser Direct Writing

A continuous glucose monitoring (CGM) system is an ideal monitoring system for the blood glucose control of diabetic patients. The development of flexible glucose sensors with good glucose-responsive ability and high linearity within a large detection range is still challenging in the field of continuous glucose detection. A silver-doped Concanavalin A (Con A)-based hydrogel sensor is proposed to address the above issues. The proposed flexible enzyme-free glucose sensor was prepared by combining Con-A-based glucose-responsive hydrogels with green-synthetic silver particles on laser direct-writing graphene electrodes. The experimental results showed that in a glucose concentration range of 0-30 mM, the proposed sensor is capable of measuring the glucose level in a repeatable and reversible manner, showing a sensitivity of 150.12 Ω/mM with high linearity of R2 = 0.97. Due to its high performance and simple manufacturing process, the proposed glucose sensor is excellent among existing enzyme-free glucose sensors. It has good potential in the development of CGM devices.

Pt/MXene-Based Flexible Wearable Non-Enzymatic Electrochemical Sensor for Continuous Glucose Detection in Sweat.

Wearable non-invasive sensors facilitate the continuous measurement of glucose in sweat for the treatment and management of diabetes. However, the catalysis of glucose and sweat sampling are challenges in the development of efficient wearable glucose sensors. Herein, we report a flexible wearable non-enzymatic electrochemical sensor for continuous glucose detection in sweat. We synthesized a catalyst (Pt/MXene) by the hybridization of Pt nanoparticles onto MXene (Ti3C2Tx) nanosheets with a broad linear range of glucose detection (0-8 mmol/L) under neutral conditions. Furthermore, we optimized the structure of the sensor by immobilizing Pt/MXene with a conductive hydrogel to enhance the stability of the sensor. Based on Pt/MXene and the optimized structure, we fabricated a flexible wearable glucose sensor by integrating a microfluidic patch for sweat collection onto a flexible sensor. We evaluated the utility of the sensor for the detection of glucose in sweat, and the sensor could detect the glucose change with the replenishment and consumption of energy by the body, and a similar trend was observed in the blood. An in vivo glucose test in sweat indicated that the fabricated sensor is promising for the continuous measurement of glucose, which is essential for the treatment and management of diabetes.

Effect of Electrode Modification with Chitosan and Nafion® on the Efficiency of Real-Time Enzyme Glucose Biosensors Based on ZnO Tetrapods.

Noninvasive, continuous glucose detection can provide some insights into daily fluctuations in blood glucose levels, which can help us balance diet, exercise, and medication. Since current commercially available glucose sensors can barely provide real-time glucose monitoring and usually imply different invasive sampling, there is an extraordinary need to develop new harmless methods for detecting glucose in non-invasive body fluids. Therefore, it is crucial to design (bio)sensors that can detect very low levels of glucose (down to tens of µM) normally found in sweat or tears. Apart from the selection of materials with high catalytic activity for glucose oxidation, it is also important to pay considerable attention to the electrode functionalization process, as it significantly contributes to the overall detection efficiency. In this study, the (ZnO tetrapods) ZnO TPs-based electrodes were functionalized with Nafion and chitosan polymers to compare their glucose detection efficiency. Cyclic voltammetry (CV) measurements have shown that chitosan-modified ZnO TPs require a lower applied potential for glucose oxidation, which may be due to the larger size of chitosan micelles (compared to Nafion micelles), and thus easier penetration of glucose through the chitosan membrane. However, despite this, both ZnO TPs modified with chitosan and Nafion membranes, provided quite similar glucose detection parameters (sensitivities, 7.5 µA mM−1 cm−1 and 19.2 µA mM−1 cm−1, and limits of detection, 24.4 µM and 22.2 µM, respectively). Our results show that both electrodes have a high potential for accurate real-time sweat/tears glucose detection.

Radio-Frequency Biosensors for Real-Time and Continuous Glucose Detection.

This review paper focuses on radio-frequency (RF) biosensors for real-time and continuous glucose sensing reported in the literature, including our recent research. Diverse versions of glucose biosensors based on RF devices and circuits are briefly introduced, and their performances are compared. In addition, the limitations of the developed RF glucose biosensors are discussed. Finally, we present perspectives on state-of-art RF biosensing chips for point-of-care diagnosis and describe their future challenges.

Nonenzymatic Electrochemical Sensor for Wearable Interstitial Fluid Glucose Monitoring

AbstractWe report on a nonenzymatic electrochemical sensor for wearable glucose monitoring in interstitial fluid. The sensor exhibited acceptable selectivity and reliability for continuous glucose detection for up to 30 days. The sensor tip is coated with polyurethane, and the biocompatibility of the tip is investigated by tissue staining. A fully integrated wearable glucose monitoring system is developed with a wireless connection with a smartphone. The test results are in agreement with reference methods. So, we believe the sensor is promising for the development of a continuous glucose monitoring system and diabetes management.

A fluorescence sandwich immunoassay for the real-time continuous detection of glucose and insulin in live animals.

Real-time biosensors that can continuously measure circulating biomolecules in vivo would provide valuable insights into a patient’s health status and their response to therapeutics, even when there is considerable variability in pharmacokinetics and pharmacodynamics across patient populations. Unfortunately, current real-time biosensors are limited to a handful of analytes (e.g. glucose and blood oxygen) and are limited in sensitivity (high nanomolar). In this work, we describe a general approach for continuously and simultaneously measuring multiple analytes with picomolar sensitivity and sub-second temporal resolution in a device with an incubation time of 30 s. As exemplars, we report the simultaneous detection of glucose and insulin in live diabetic rats. Using our system, we demonstrate the capacity to resolve inter-individual differences in the pharmacokinetic response to insulin, and discriminate profiles from different insulin formulations at high temporal resolution. Critically, our approach is general and could be readily modified to continuously and simultaneously measure other circulating analytes in vivo, thus making it a versatile tool for biomedical research.

V2O5 Nanobelts Mimick Tandem Enzymes To Achieve Nonenzymatic Online Monitoring of Glucose in Living Rat Brain.

The continuous detection of glucose is significant for revealing its role in neuron protection and for diagnosis of various diseases. In this study, for the first time, a nonenzymatic online optical detection platform (OODP) for glucose measurement in rat brain utilizing the tandem enzyme activity of V2O5 nanobelts is developed. V2O5 nanobelts were synthesized via a facile solvothermal strategy, and for the first time it is found that the V2O5 nanobelts possess dual enzyme-like activity, i.e., glucose oxidase (GOx)-like and peroxidase-like activity, and can act as a "tandem nanozyme". To investigate the mechanisms of the GOx-like property, we built an adsorption model, and the RPBE density functional calculations indicate that the glucose molecule can be adsorbed on the V2O5 plane. Based on the ability of V2O5 nanobelts to mimick tandem enzymes, a nonenzymatic online optical detection platform (OODP) for the continuous monitoring of glucose in rat brain was designed, which exhibits excellent stability, high selectivity, and a wide linear detection range from 0.2 to 5 mM and records cerebral glucose alterations in the calm/ischemia model. This facile but reliable nonenzymatic online optical glucose measurement compares favorably with natural enzyme-based online electrochemical glucose analytical systems, and its ready adoption by physiologists and pathologists will facilitate the understanding of brain function and the pathogenesis of diabetes.

Near-Infrared Optical Nanosensors for Continuous Detection of Glucose.

Continuous glucose monitors (CGMs) enable people with diabetes to proactively manage their blood glucose and reduce the risk of hypoglycemia. Commercially available CGMs utilize percutaneous electrodes that, after days to weeks of implantation, are subjected to the foreign body response that severely reduces sensor accuracy. The previous work demonstrated the use of hydrogels containing a glucose-responsive viologen that quenches a nearby fluorophore. Here, we investigate the immobilization of this sensing motif onto a nanoparticle surface and optimize local surface concentrations for optical glucose sensing. A viologen quencher-fluorescent dye system was incorporated into poly(2-hydroethyl methacrylate) hydrogels in varying quantities to assess the effect of quencher-fluorophore concentration on glucose responsiveness. The sensing motif was then immobilized onto silica nanoparticles by carbodiimide chemistry. Nanosensors with a range of dye and quencher concentrations were challenged for glucose responsiveness to determine the optimal sensor formulation. When incorporated into a hydrogel, high concentrations of viologen quencher and fluorophore were required to permit electron transfer between the two components and yield a detectable glucose response. Immobilization of this glucose-responsive system onto a silica nanoparticle facilitated this electron transfer to yield detectable responses at even low concentrations. Increasing quencher concentration on the nanoparticle, relative to the fluorophore, resulted in the greatest apparent glucose response. The nanoparticle sensors demonstrated excellent glucose response in the physiological range and are a promising tool for real-time glucose tracking.

Noninvasive Glucose Monitoring with a Contact Lens and Smartphone.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

Microarray Needle Sensor Composite Conducting Polymer Coated on Au/Zn Oxide Layer for Continuous Glucose Detection in Cells

Diabetes mellitus is a serious metabolic disease that may pose a threat to life owing to various complications. Therefore, patients are required the tight and accurate monitoring of blood glucose level to prevent and reduce complications [1]. In this regard, the continuous glucose monitoring system is most desirable to the efficient management of diabetes, which especially provides painless, and accuracy glucose level. Hence, we report for the development of a robust and simple enzymatic glucose sensor using Au coated microneedle arrays.The AuZn layer was electrochemically grown on Au coated microneedle arrays in Na2SO4 containing HAuCl4·4H2O and ZnCl2 using normal pulse voltammetry method. Electrochemical oxidation of the AuZn was performed in 0.1 M PBS (pH 7.4) using chronoamperometry method. Then, glucose oxidase bound on a conductive polymer precursor monomer (GOx-TCA) was formed on the AuZnOx through cyclic voltammetry method in TCA-GOx solution [2]. To prepare the TCA-GOx, TCA monomer was dissolved in CH3CN containing 0.1 M TBAP. GOx was added in distilled water containing 10 mM EDC/NHS. After that, the solutions were mixed with stirring and incubated at 40oC for 3 h that result in GOx couple on TCA through the amide bond formation. Finally, GOx-pTCA/AuZnOx probe was dipped into Nafion solution and dried for 4 hours at CaCl2 atmosphere. The polymer/enzyme composite stably produced H2O2 by the enzyme reaction. The produced H2O2 was catalytically reduced by the AuZnOx layer. We oxidized AuZn alloy nanostructured layer, which increased the surface area, and the catalytic activity towards hydrogen peroxide [3]. The sensitivity of the AuZnOx probe shows four times higher than AuZn layer. This indicates that AuZnOx layer improves the sensitivity for glucose detection. The reproducibility was examined using ten different sensors, and a relative standard deviation of 1.89 % at 10mM glucose was achieved. The sensitivity was 0.43 μA mM-1with a linearity of 0.998, and within 1 sec, in glucose concentrations ranging from 0.1 to 50 mM. The calibration plots for the glucose were obtained between 0.1 to 5.0 mM and 5.0 to 50.0 mM. The glucose sensor achieved a low detection limit of 90.0 ± 1.6 μM. In order to assess the possibility of interference, the chronoamperometric response of the modified micro needle sensor was measured for ascorbic acid (AA), uric acid (UA), acetaminophen (AP) and dopamine at a concentration of 0.1 mM. Amperometric responses show that, approximately 5% response for AA, UA, AP, and dopamine compared with the glucose signal. The sensitivity of the sensors retained 95% of its initial sensitivity for up to seven days of continuous monitoring at 10 mM glucose concentration. For the determination of glucose concentration inside and outside a single cell we have used PC - 12 and Vero cell lines and isolated and grown a single cell of each in a 60 × 15 mm petri dish for ease of access. Then at first we have measured the voltammogramms for glucose by placing the microneedle adjacent to the cell in culture, followed by insertion of the needle electrode into the cell by piercing the plasma membrane. We have observed the glucose oxidation peaks both inside and outside the single cell using a needle electrode. The result showed that the glucose concentration inside the cells is comparatively higher than the external environment and the cancer cells show almost double the concentration of intracellular glucose as compared to normal cells. Conclusively, the response of the modified micro needle type sensor was very selective, and it could be extended for use in glucose detection in medical diagnosis.[1] Wang, J.; et al., Chem. Rev., 2008, 108, 814.[2] Lee, T.-K.; Shim, Y.-B.; et al., Anal.Chem., 2001, 73, 5629-5632[3] Kim, D.-M.; Shim, Y.-B.; et al., Biosens.Bioelectron., 2016 , 79, 165–172.

Electrochemical Biosensor Based on Bienzyme and Carbon Nanotubes Incorporated into an Os‐complex Thin Film for Continuous Glucose Detection in Human Saliva

AbstractSaliva opens a door for noninvasive and painless glucose testing since it reflects changes in the body physiology of diabetic individuals as compared to healthy ones. In this paper, a unique, disposable saliva biosensor has been developed for accurate, low cost, and continuous glucose monitoring. The biosensor exhibits linear dependence of the catalytic current upon glucose bulk concentration over the 0.05–1.5 mM range (R=0.998). A detection limit of 0.003 mM can be calculated considering three times the standard deviation of the blank signal divided by the sensitivity of the sensor. The selectivity of the biosensor was evaluated by adding the interferent species of lactate, ascorbic acid and uric acid into in 0.5 mM glucose; the nearly negligible interference current indicates its good selectivity. The operational stability of the biosensor was measured in 1 mM glucose over a 2 h period (RSD=3.27 %). A clinical trial on real‐time noninvasive salivary glucose monitoring was carried out on 30 individuals by measuring subjects’ salivary glucose and blood glucose in parallel. The results show that there is a good correlation of glucose levels in saliva and in blood 2 h after breakfast. Thus, the disposable biosensor would be a potential alternative for continuous glucose detection in human saliva.

A continuous glucose monitoring device by graphene modified electrochemical sensor in microfluidic system.

This paper presents a continuous glucose monitoring microsystem consisting of a three-electrode electrochemical sensor integrated into a microfluidic chip. The microfluidic chip, which was used to transdermally extract and collect subcutaneous interstitial fluid, was fabricated from five polydimethylsiloxane layers using micromolding techniques. The electrochemical sensor was integrated into the chip for continuous detection of glucose. Specifically, a single-layer graphene and gold nanoparticles (AuNPs) were decorated onto the working electrode (WE) of the sensor to construct a composite nanostructured surface and improve the resolution of the glucose measurements. Graphene was transferred onto the WE surface to improve the electroactive nature of the electrode to enable measurements of low levels of glucose. The AuNPs were directly electrodeposited onto the graphene layer to improve the electron transfer rate from the activity center of the enzyme to the electrode to enhance the sensitivity of the sensor. Glucose oxidase (GOx) was immobilized onto the composite nanostructured surface to specifically detect glucose. The factors required for AuNPs deposition and GOx immobilization were also investigated, and the optimized parameters were obtained. The experimental results displayed that the proposed sensor could precisely measure glucose in the linear range from 0 to 162 mg/dl with a detection limit of 1.44 mg/dl (S/N = 3). The proposed sensor exhibited the potential to detect hypoglycemia which is still a major challenge for continuous glucose monitoring in clinics. Unlike implantable glucose sensors, the wearable device enabled external continuous monitoring of glucose without interference from foreign body reaction and bioelectricity.

Facile one-pot synthesis of organic dye-complexed microgels for optical detection of glucose at physiological pH

With a rational design of functional co-monomers, low-cost dye-complexed microgels, capable of continuous glucose detection at physiological pH, were readily synthesized in one-pot via precipitation polymerization in water.