Non-invasive Glucose Detection Research Articles

Surface plasmon resonance prism coupler for enhanced circular birefringence sensing and application to non-invasive glucose detection.

A surface plasmon resonance (SPR) prism coupler is proposed for the high-resolution non-invasive (NI) measurement of the circular birefringence (CB) properties of turbid media. The feasibility of the proposed device is demonstrated by means of numerical simulations. It is shown that the SPR sensor enables the CB properties to be detected with a resolution of up to 8.9 × 10-7 RIU (refractive index units) for refractive indices in the range of 1.3∼1.4. Moreover, for tissue phantom solutions containing 2% lipofundin, the device has a detection limit of 3.72 mg/dL. This resolution performance satisfies the detection limit of 10 mg/dL stipulated by the U.S FDA for point-of-care glucose monitoring devices. Thus, the proposed SPR sensor has significant potential for NI glucose sensing in such applications as diabetes detection and management.

Non-Invasive Fluidic Glucose Detection Based on Dual Microwave Complementary Split Ring Resonators With a Switching Circuit for Environmental Effect Elimination

In this paper, a microwave fluidic glucose sensor based on dual complementary split ring resonators (CSRRs) with a switching circuit is proposed for non-invasive and continuous glucose concentration detection. A CSRR has been designed to detect subtle changes in the dielectric constant of glucose solutions, and the electric field distribution is utilized to determine the effective sensing region. In a well-controlled environment, the glucose concentration can be detected by tracking the transmission coefficient of the designed CSRR. However, because the variations in dielectric constant with the glucose concentration are very small, the environmental factors (i.e., ambient temperature and relative humidity) can be dominant compared to the glucose concentration. To qualify the effect of the environmental factors, the variation in the transmission coefficient of the CSRR has been measured when the ambient temperature condition is varied from 293 K to 313 K and the relative humidity is varied from 30% to 90% inside temperature- and humidity-controlled chamber. Moreover, the environmental effects are calibrated out using two identical CSRRs with the switching circuit: one detects changes in the glucose concentration, while the other operates as a reference for environmental factors. After the elimination of the environmental effects, glucose concentrations in the range of 0 mg/dL to 400 mg/dL have been measured, and the sensitivity is 0.008dB/(100mg/dL). In addition, the reproducibility of the proposed sensor is verified by repeated measurements. It is demonstrated that the proposed sensor can detect glucose concentrations under practical environmental conditions.

Cotton thread-based wearable sensor for non-invasive simultaneous diagnosis of diabetes and kidney failure

Thread has become a promising substrate for non-invasive wearable sensor. Herein, we create a modified cotton thread-based colorimetric sensor for non-invasive and simultaneous detection of glucose and urea excreted from human sweat. Cellulose nanofiber/chitosan-graphene oxide was selected to modify the cotton thread surfaces for enhancing of enzymatic immobilization efficiency and sensor performance. The modified thread surfaces were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. This sensing platform exhibits a linear range of 0.1–3 mM with a detection limit of 0.1 mM for glucose and a linear range of 30–180 mM with a detection limit of 30 mM for urea. Interestingly, this colorimetric sensor can determine the cut-off levels for both glucose (0.3 mM) and urea (65 mM) in human sweat, thus it can effectively distinguish between normal and abnormal people. Due to the thread flexibility nature, this sensor can be readily integrated with the clothes and accessories for real-time and continuous monitoring of diabetes and kidney failure from the wearer’s sweat. This platform might open a new road for blood-free diagnosis in healthcare applications.

382-P: Exhaled Isoprene Products Change during Hypoglycemia in Type 1 Diabetes and Home Breath Capture Is Feasible as a Diagnostic Tool

Detection of hypoglycemia is important to reduce risk and optimize glucose in T1D. Noninvasive glucose detection methods have not been fully explored. Exhaled breath isoprene, a component of sterol metabolism, has been associated with hypoglycemia in controlled studies in a limited population in the laboratory setting. Home-monitoring of breath isoprene levels may permit noninvasive hypoglycemia detection. We conducted an exploratory study measuring exhaled volatile organic compounds (VOCs) in breath samples collected during hypoglycemia (CBG <70 mg/dL) compared to euglycemia (CBG 70-180 mg/dL) under free-living conditions in 10 subjects age 7-74 with T1D. Breath samples were collected using designated breath capture bags and processed 1-4 weeks later by proton-transfer-reaction time-of-flight (PTR TOF) mass spectrometry. Over 100 VOCs were identified in 52 breath samples (25 hypoglycemia, 27 euglycemia). During hypoglycemia, isoprene increased 37% (p<0.05) and its oxidation products methyl vinyl ketone (MVK) and methacrolein (MACR) decreased 59% (p<0.05). However, predictive modelling using metabolite concentration as the input could not reliably predict whether the breath sample was collected during hypoglycemia or euglycemia. All other measured VOCs were not statistically different. This is the first free-living study to evaluate exhaled VOCs in patients with T1D. We successfully replicated findings of a prior study done in a controlled laboratory setting suggesting isoprene concentration in human breath increases during hypoglycemia. We further describe decreased MVK and MACR during hypoglycemia and home breath capture may be feasible for diagnostics in medical conditions. In addition, the physiology of glucose changes on sterol metabolism is worthy of further study. Finally, identification of an exhaled marker of glucose levels hints at a possible mechanism of detection by so-called diabetes alert dogs. Disclosure E.A. Los: Advisory Panel; Self; Medtronic. W.L. Stone: None. G. Ford: None. Funding East Tennessee State University (18-025M)

Enhanced acetone sensing performance in black TiO2 by Ag modification

The application of TiO2 acetone monitor is highly limited by the high operating temperature and poor sensitivity. In this work, black TiO2 (B-TiO2) is produced by Ti3+ self-doping and is followed by Ag modification to form B-TiO2@Ag. It is first demonstrated that the operating temperature and sensitivity of TiO2 to acetone can be promoted evidently. By introducing a Ti3+ self-doped layer on the surface of TiO2, as observed in TEM images, the band gap of TiO2 is reduced to 3.01 eV. Ag surface decoration is carried out for the enhancement of electron generation. Optical absorption and the Hall effect results prove that B-TiO2@Ag exhibits highest photoelectrical properties. As a result, the B-TiO2@Ag gas sensor with a low operating temperature at 250 °C and high response of 68.19 to 50 ppm acetone is realized. The low detection limit of B-TiO2@Ag sensor reaches 887 ppb, which provides an applicable way for non-invasive detection of blood glucose.

Chitosan–Fe3O4 nanoparticle enzymatic electrodes on paper as an efficient assay for glucose and uric acid detection in biological fluids

In this study, two important biomarkers, namely glucose and uric acid, were detected in different biological fluids using a highly sensitive and selective chitosan-/nano-based electrochemical microfluidic paper-based analytical device (µPAD). A graphite/chitosan/polyethylene glycol (PEG) mixture was used as bare working electrode and counter electrode with silver ink being used as quasi-reference electrode. Graphene, multiwall carbon nanotubes, and Fe3O4 nanoparticles were used to improve sensitivity as well as selectivity of the working electrodes. The developed chitosan-/nano-based microfluidic analytical system showed apparent redox peaks, and all the three types of nanomaterials improved the performance of the bare graphite/chitosan/PEG electrode with the Fe3O4-modified electrode exhibiting the sharpest signals with the highest selectivity. The linear ranges of glucose and uric acid were 0.01–30 mM and 0.05–15 mM, respectively, where the limits of detection (LOD) were 5 µM and 20 µM for glucose and uric acid, respectively. In comparison with most of previous data reported on μPADs and due to high surface area/volume ratio of NPs and faster electron transfer promoted by chitosan and NPs, the better LODs were found in the current study. The fast, efficient, and low-cost µPADs were successfully applied to highly sensitive and selective detection of glucose and uric acid in serum and urine samples and noninvasive glucose detection in tear samples.

Enzyme bioconjugated PAMAM dendrimers for estimation of glucose in saliva

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

Non-invasive detection of glucose via a solution-gated graphene transistor.

Owing to its high sensitivity, a solution-gated graphene transistor has rapidly emerged as a cutting edge technology in electrochemical sensing. In this work, composites of gold nanoparticles and reduced graphene oxide were synthesized on a glassy carbon electrode by using the electrodeposition method. A modified glassy carbon electrode was used as the gate electrode and assembled into the solution-gated graphene transistor device along with the graphene channel for a non-invasive glucose detection. The sensing mechanism was based on the change in current in the channel of the device caused by the addition of glucose, of which electro-oxidation on the surface of the gold nanoparticles and reduced graphene oxide led to a change in equivalent gate voltage, and consequently, affected the channel carrier concentration. The self-amplification effect of transistors was utilized in our sensors, which resulted in a detection limit that was 10 times lower than those of conventional electrochemical sensors. Compared to traditional enzymatic transistor sensors, the novel solution-gated graphene transistor nonenzymatic sensors based on gold nanoparticles and reduced graphene oxide demonstrated significant sensing advantages, such as a simple structure, wide linear range from 10 μM to 400 μM and 400 μM to 31 mM, and low detection limit down to 4 μM. The chemicals coexisting in human sweat e.g. sodium chloride, urea, and lactic acid imposed no distinct interference for the glucose detection. Therefore, we achieved a non-invasive detection of glucose in the artificial sweat samples with satisfactory sensing results. This work demonstrates an effective route for non-invasive glucose testing in practical clinical diagnosis by using nonenzymatic, solution-gated graphene transistor devices.

Simple Glucose Measurement System Based on Uncladded Fiber Bragg Grating Etched with Nitric Acid

The demand for a non-invasive, fast, and accurate glucose detection for diabetic patients is increasing nowadays. It is predicted that diabetic patient will increase from 415 million people at 2018 to 640 million people at 2050. Glucose is also present in saliva, therefore glucose concentration measurement in saliva can be an alternative way during diabetics monitoring. In this study, we measure 0-60% glucose concentration through optical systems. The optical system consists of an erbium-doped fibber laser, uncladded fiber bragg gratings that have been etched with nitric acid (HNO3), and optical spectrum analyser (OSA). The measured parameter is a Bragg wavelength shift due to changes in glucose solution concentration. The results show that the wavelength shifts to lower value (blue shift) as the glucose concentration increases. The sensitivity obtained from this measurement system is 1.2 pm/% in glucose solution. This result is a preliminary study to detect glucose concentration in saliva based on Fibber Bragg Grating which has advantages for diabetic patients such as simple setup, non-invasive, fast, and low cost.

Near-Infrared Light Emitting Diode Based Non-Invasive Glucose Detection System.

Diabetes mellitus is a common disease that has affected people since antiquity. The complexity of diabetes mellitus lies in the fact that it requires continuous management in order to prevent serious complications. Various methods for managing diabetes mellitus through monitoring blood glucose levels have been studied and developed, and the most widely used method includes using an invasive blood glucose meter. Since the invasive blood glucose meter poses a major inconvenience for patients, in this study, we sought to develop a non-invasive blood glucose meter. We therefore proposed the development of a non-invasive blood glucose measurement system that is based on near-infrared spectroscopy. The system developed was composed of a light source for emitting different wavelengths, a light detector unit, and a computing system for recording signals. A prepared glucose solution was injected into a quartz cuvette and light at 780-1650 nm was emitted to pass through the cuvette. The degree of reaction was determined by recording the change in wavelength. The wavelength band used for the experiment was 780-1000 nm and the resolution was 20 nm. The glucose concentration was determined to be between 50 to 400 mg/dl compared to the normal range of 80 to 120 mg/dl. By examining which wavelength bands specifically reacted with glucose, we observed that the wavelength bands that decreased or increased in response to the glucose concentration were at 780 nm and 940 nm. For wavelength bands at 1000 nm or above, light was also absorbed by water and therefore it was difficult to distinguish the results. The most reliable wavelength band was at 940 nm with an R² of 0.9806. In conclusion, the near-infrared light emitting diode based non-invasive glucose detection system performed well and is expected to be a superior method for monitoring blood glucose levels in diabetes mellitus.

Co3O4 needles on Au honeycomb as a non-invasive electrochemical biosensor for glucose in saliva

While glucose monitoring technology is widely available, the continued prevalence of diabetes around the world coupled with its debilitating effects continues to grow. The significant limitations which exist in the current technology, instils the need for materials capable of non-invasive glucose detection. In this study a unique non-enzymatic electrochemical glucose sensor was developed, utilising a gold honeycomb-like framework upon which sharp Co3O4 needles are anchored. This composite nanomaterial demonstrates excellent sensing performance in glucose concentrations ranging between 20 μM and 4 mM, exceeding the range required for non-invasive glucose sensing. In conjunction with this high sensitivity (2.014 mA mM−1·cm−2), the material possesses excellent selectivity towards glucose for commonly interfering physiological species such as uric acid and ascorbic acid. Glucose detection in synthetic saliva was then performed showing excellent capability in the low concentration range (20 μM–1 mM) for non-invasive sensing performance. Further tests showed good selectivity of the sensor in physiological contaminants commonly found in saliva such as cortisol and dopamine. This development provides excellent scope to create next-generation non-invasive diabetes monitoring platforms, with excellent performance when detecting low glucose concentrations in complex solutions such as saliva.

Eyeglasses-based tear biosensing system: Non-invasive detection of alcohol, vitamins and glucose

We report on a wearable tear bioelectronic platform, integrating a microfluidic electrochemical detector into an eyeglasses nose-bridge pad, for non-invasive monitoring of key tear biomarkers. The alcohol-oxidase (AOx) biosensing fluidic system allowed real-time tear collection and direct alcohol measurements in stimulated tears, leading to the first wearable platform for tear alcohol monitoring. Placed outside the eye region this fully wearable tear-sensing platform addresses drawbacks of sensor systems involving direct contact with the eye as the contact lenses platform. Integrating the wireless electronic circuitry into the eyeglasses frame thus yielded a fully portable, convenient-to-use fashionable sensing device. The tear alcohol sensing concept was demonstrated for monitoring of alcohol intake in human subjects over multiple drinking courses, displaying good correlation to parallel BAC measurements. We also demonstrate for the first time the ability to monitor tear glucose outside the eye and the utility of wearable devices for monitoring vitamin nutrients in connection to enzymatic flow detector and rapid voltammetric scanning, respectively. These developments pave the way to build an effective eyeglasses system capable of chemical tear analysis.

Non-enzymatic and non-invasive glucose detection using Au nanoparticle decorated CuO nanorods

Non-enzymatic electrochemical glucose sensors have been fabricated using hydrothermally grown CuO nanorods on fluorine doped tin oxide (FTO) coated glass substrates. The sensing performance has been increased by several times after attaching Au nanoparticles with CuO nanorods. The formation of CuO nanorods and attachment of Au nanoparticles were confirmed using scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) study. The Au decorated CuO nanorod electrodes demonstrated glucose sensitivity of 2009 μAmM-1 cm-2, in the linear detection range 5 μM to 1.325 mM, with detection limit of 0.17 μM. Such Au decorated sensing electrodes are highly selective and exhibited long-term stability. Non-invasive glucose detection has been demonstrated using human saliva samples. The sensitivity of the sensor for salivary glucose detection was found to be 1740 μAmM-1 cm-2. Our present study demonstrated the promising use of Au decorated CuO NR electrodes for low cost, non-enzymatic, non-invasive diabetes monitoring application.

Implementation of an integrating sphere for the enhancement of noninvasive glucose detection using quantum cascade laser spectroscopy

An integrating sphere is used to enhance the collection of backscattered light in a noninvasive glucose sensor based on quantum cascade laser spectroscopy. The sphere enhances signal stability by roughly an order of magnitude, allowing us to use a thermoelectrically (TE) cooled detector while maintaining comparable glucose prediction accuracy levels. Using a smaller TE-cooled detector reduces form factor, creating a mobile sensor. Principal component analysis has predicted principal components of spectra taken from human subjects that closely match the absorption peaks of glucose. These principal components are used as regressors in a linear regression algorithm to make glucose concentration predictions, over 75% of which are clinically accurate.

Naked-eye point-of-care testing platform based on a pH-responsive superwetting surface: toward the non-invasive detection of glucose

Herein, we demonstrate a contact angle (CA)-based naked-eye point-of-care testing platform with rapid pH-responsive superwettability that can switch between superhydrophilic and superhydrophobic properties for quantitative biosensing. The CA of the droplet on the pH-responsive surface approached ~0° at pH 1 and conversely reached 161.4° ± 6.2° at pH 13. We realized the sensitive detection of the pH, urea, and glucose by monitoring the changes in the CA. The traditional invasive diagnosis of diabetes causes pain and brings the risk of infections, such as acquired immune deficiency syndrome (AIDS), hepatitis B, hepatitis C, and syphilis, to the user. To address this issue, we implemented a method for the non-invasive diagnosis of diabetes in human saliva and urine, which avoided the significant drawbacks mentioned above. The accuracy of this method was demonstrated by comparing the results with those from commercial glucometers and theoretical calculations. Interestingly, we successfully monitored glucose levels in sweat before, during, and after cycling. The sensing performance was barely influenced by the temperature, elevation, and droplet color, illustrating promise for expansion to hundreds of millions of potential customers, especially those with color blindness or color weakness. Given its low cost, lack of instruments, and rapid response (within 1 s), this strategy might overcome the limitations of the mechanical stability and durability of superwettable materials and thus might extend the industrial-scale application of bioinspired superwettable systems.

Electrospun CuO-Nanoparticles-Modified Polycaprolactone @Polypyrrole Fibers: An Application to Sensing Glucose in Saliva.

A non-invasive method for detecting glucose is pursued by millions of diabetic patients to improve their personal management of blood glucose. In this work, a novel CuO nanoparticles (NPs) decorated polycaprolactone@polypyrrole fibers modified indium-tin oxide (denoted as CuO/PCL@PPy/ITO) electrode has been fabricated by electrospinning combined with the electrodeposition method for non-enzymatic detection of glucose in saliva fluid. The electrospun composite fibers exhibit high sensitivity for the glucose detection. The synergistic effect between CuO and PPy together with the unique three-dimensional net structure contributes the reliable selectivity, good test repeatability, large-scale production reproducibility in massive way, the reasonable stability and a high catalytic surface area to the sensor. Quantitative detection of glucose is determined in the linear range from 2 μM to 6 mM and the lowest detection limit is 0.8 μM. The CuO/PCL@PPy/ITO electrode shows potential for the non-invasive detection of salivary glucose.

ZIF-67 derived porous Co3O4 hollow nanopolyhedron functionalized solution-gated graphene transistors for simultaneous detection of glucose and uric acid in tears

Biomarkers in tears have attracted much attention in daily healthcare sensing and monitoring. Here, highly sensitive sensors for simultaneous detection of glucose and uric acid are successfully constructed based on solution-gated graphene transistors (SGGTs) with two separate Au gate electrodes, modified with GOx-CHIT and BSA-CHIT respectively. The sensitivity of the SGGT is dramatically improved by co-modifying the Au gate with ZIF-67 derived porous Co3O4 hollow nanopolyhedrons. The sensing mechanism for glucose sensor is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate, while the sensing mechanism for uric acid is due to the direct electro-oxidation of uric acid molecules on the gate. The optimized glucose and uric acid sensors show the detection limits both down to 100nM, far beyond the sensitivity required for non-invasive detection of glucose and uric acid in tears. The glucose and uric acid in real tear samples was quantitatively detected at 323.2 ± 16.1μM and 98.5 ± 16.3μM by using the functionalized SGGT device. Due to the low-cost, high-biocompatibility and easy-fabrication features of the ZIF-67 derived porous Co3O4 hollow nanopolyhedron, they provide excellent electrocatalytic nanomaterials for enhancing sensitivity of SGGTs for a broad range of disease-related biomarkers.

Nanostructured biosensor using bioluminescence quenching technique for glucose detection

BackgroundMost methods for monitoring glucose level require an external energy source which may limit their application, particularly in vivo test. Bioluminescence technique offers an alternative way to provide emission light without external energy source by using bioluminescent proteins found from firefly or marine vertebrates and invertebrates. For quick and non-invasive detection of glucose, we herein developed a nanostructured biosensor by applying the bioluminescence technique.ResultsLuciferase bioluminescence protein (Rluc) is conjugated with β-cyclodextrin (β-CD). The bioluminescence intensity of Rluc can be quenched by 8 ± 3 nm gold nanoparticles (Au NPs) when Au NPs covalently bind to β-CD. In the presence of glucose, Au NPs are replaced and leave far from Rluc through a competitive reaction, which results in the restored bioluminescence intensity of Rluc. A linear relationship is observed between the restored bioluminescence intensity and the logarithmic glucose concentration in the range of 1–100 µM. In addition, the selectivity of this designed sensor has been evaluated. The performance of the senor for determination of the concentration of glucose in the blood of diabetic rats is studied for comparison with that of the concentration of glucose in aqueous.ConclusionsThis study demonstrates the design of a bioluminescence sensor for quickly detecting the concentration of glucose sensitively.

A Highly Sensitive Nonenzymatic Glucose Biosensor Based on the Regulatory Effect of Glucose on Electrochemical Behaviors of Colloidal Silver Nanoparticles on MoS₂†.

A novel and highly sensitive nonenzymatic glucose biosensor was developed by nucleating colloidal silver nanoparticles (AgNPs) on MoS2. The facile fabrication method, high reproducibility (97.5%) and stability indicates a promising capability for large-scale manufacturing. Additionally, the excellent sensitivity (9044.6 μA·mM−1·cm−2), low detection limit (0.03 μM), appropriate linear range of 0.1–1000 μM, and high selectivity suggests that this biosensor has a great potential to be applied for noninvasive glucose detection in human body fluids, such as sweat and saliva.

Noninvasive and Painless Urine Glucose Detection by Using Computer-based Polarimeter

Diabetes kills millions of people worldwide each year. It challenges us as researchers to give contribution in early diagnosis to ensure a healthy life. As a matter of fact, common glucose testing devices that have been widely used so far are, at least, glucose meter and urine glucose test strip. The glucose meter ordinarily requires blood taken from patient’s finger. The glucose test strip uses patient’s urine but records unspecific urine glucose level, since the strip only provides the glucose level in some particular ranges. Instead of detecting the glucose level in blood and using the non-specific technique, a noninvasive and painless technique that can detect glucose level accurately will provide a more feasible approach for diabetes diagnosis. The noninvasive and painless urine glucose level monitoring by means of computer-based polarimeter is presented in this paper. The instrument consisted of a power source, a sample box, a light sensor, a polarizer, an analyzer, an analog to digital converter (ADC), and a computer. The concentration of urine glucose concentration was evaluated from the curve of the change in detected optical rotation angle and output potential by the computer-based polarimeter. Statistical analyses by means of Gaussian fitting and linear regression were applied to investigate the rotation angle and urine glucose concentration, respectively. From our experiment, the urine glucose level, measured by glucose test strips, of the normal patient was 100 mg/dl, and the diabetic patient was 500 mg/dl. Our polarimeter even read more precise values for the urine glucose concentrations of those normal and diabetic of the same patients, i.e. 50.61 mg/dl and 502.41 mg/dl, respectively. In other words, the results showed that our polarimeter was able to quantitatively measure the urine glucose level more accurate than urine glucose test strips. Hence, this computer-based polarimeter could be used as an alternative for early detection of urine glucose with noninvasive and painless characteristics.