Measurement Of Glucose Concentration Research Articles

Method for the Detection of Insulin‐independent Glucose Uptake in Skeletal Muscle

The quantification of glucose uptake into tissues, alongside co‐solutes flux, is essential to advance basic knowledge of glucose transport and metabolism. However, comprehensive understanding of glucose metabolism has been elusive. A major player in this crucial process is muscle tissue ‐ its large mass, high catabolic rate and storage capabilities make a major contribution to glucose homeostasis. The traditional insulin‐dependent model has proven insufficient to explain a well‐documented clinical observation: Type II diabetic, insulin resistant patients can lower their blood sugar levels with frequent exercise. One challenge in studying a complex mechanism like glucose uptake in muscles is the lack of experimental tools with multi‐channel capabilities, able to quantify most of, if not all the possible related solute fluxes within current models, in‐vivo or ex‐vivo. Our goal was to develop a method to measure glucose, K+, Na+, Ca2+, Fe, Cu, Zn2+ and Mn flux in biological samples using Inductively Coupled Plasma – Mass Spectroscopy (ICP‐MS). ICP‐MS is well established as a sensitive and versatile tool for direct detection and quantification of specific elements.In this study, we developed a new ratiometric method, based on stable‐isotope dilution, to quantify 13C‐based molecules using the molar ratio of 13C/12C. This, added to the multi‐metal detection capabilities of ICP‐MS was combined for a multi‐channel ion flux measurement in mouse EDL muscle during contraction‐stimulated glucose uptake. The preliminary results demonstrated a correlation of K+ uptake with glucose uptake. We showed involvement of the Na+K+ATPase (NKA) with this process using ouabain. An isolated EDL muscle was either stimulated at 90 Hz for 5 min or left unstimulated in 11mM 13C glucose uptake solution at 32°C. The muscle was then washed at 0°C for 20 minutes to wash away excess glucose on the surface of the muscle and to inhibit transporter activity. The muscle was then digested in 1:1 HCl and H2SO4 to break it down to inorganic forms. Finally, we used ICP‐MS to quantify glucose and co‐solute transport. The transport rate for glucose (nM/g min) for stimulated tissues was 601 as compared to 9 for unstimulated tissues. The stimulated muscles also took up K+, as measured through Rb+ tracer, indicating that NKA was active during contraction‐stimulated glucose uptake. To determine which isoform of Na,K,ATPase (NKA) the glucose was coupled to, we used 0.75uM ouabain. This concentration is enough to maintain muscle contractions as well as inhibit NKA α2 but not α1. Ouabain reduced the average glucose uptake rate by 81 %. These preliminary results show that NKA α2 may be coupled to a possible novel glucose transporter in skeletal muscle tissue or to GLUT‐4 in an undescribed way. The development of a method to measure glucose concentrations in biological samples together with coupled fluxes of other ions will advance knowledge of glucose handling in health and disease. In addition, our method to reproducibly quantify C‐based organic molecules by ICP‐MS will advance applications of ICP‐MS to many other fields of biomedical research.Support or Funding InformationNIH RO1 AR 063710

Microscale Biosensor Array Based on Flexible Polymeric Platform toward Lab-on-a-Needle: Real-Time Multiparameter Biomedical Assays on Curved Needle Surfaces.

In vivo sensing of various physical/chemical parameters is gaining increased attention for early prediction and management of various diseases. However, there are major limitations on the fabrication method of multiparameter needle-based in vivo sensing devices, particularly concerning the uniformity between sensors. To address these challenges, we developed a microscale biosensor array for the measurement of electrical conductivity, pH, glucose, and lactate concentrations on a flexible polymeric polyimide platform with electrodeposited electrochemically active layers. The biosensor array was then transferred to a medical needle toward multiparametric in vivo sensing. The flexibility of the sensor platform allowed an easy integration to the curved surface (φ = 1.2 mm) of the needle. Furthermore, the electrodeposition process was used to localize various active materials for corresponding electrochemical sensors on the microscale electrodes with a high precision (patterning area = 150 μm × 2 mm). The biosensor array-modified needle was aimed to discriminate cancer from normal tissues by providing real-time discrimination of glucose, lactate concentration, pH, and electrical conductivity changes associated with the cancer-specific metabolic processes. The sensor performance was thus evaluated using solution samples, covering the physiological concentrations for cancer discrimination. Finally, the possibility of in vivo electrochemical biosensing during needle insertion was confirmed by utilizing the needle in a hydrogel phantom that mimicked the normal and cancer microenvironments.

In-Vivo and Ex-Vivo Measurements of Blood Glucose Using Whispering Gallery Modes.

The permittivity of blood glucose is not a strong function of its concentration in microwave or millimeter-wave frequencies. Measuring glucose concentrations remains a challenge, particularly in the presence of interference caused by the ambient leaky waves. In this paper, however, we demonstrate that a near-linear correlation between the glucose concentration and the blood permittivity was noticeably observed at a whispering gallery mode resonance. Method: the proposed sensor was a vacuum suction aspirator partially wounded with a turn of the Goubau line. This arrangement enabled a fixed cylindrical volume of a skin tissue bump or glucose/water solution to be formed and used as a whispering gallery resonator for in-vivo and ex-vivo measurements. Results: in the in-vivo study, a near-linear correlation between the glucose levels and the S21 parameters was noticeably observed at the fundamental whispering gallery resonance (i.e., at 2.18 GHz). In the ex-vivo study, a similar correlation was observed between the concentration of a glucose/water solution and the S21 parameters 56.6 GHz. Conclusion: the results of both investigations were consistent not only with the invasive measurements using the Accu-checkTM, but also with the conclusion drawn by some other research groups who have successfully measured blood glucose concentrations at millimeter-wave frequencies.

Estimation of MU for Glucose in Human Serum Using Bottom-up Approach

Glucose is an important material in human metabolism. The establishment of glucose reference measurement procedures and to study the uncertainties of measurement is of great significance. Linear fitting and dilution of reference material were used in the measurement of glucose concentration and they are common operations in daily work. Investigation of the measurement uncertainty of these operations will be of important significance to clinical laboratory medicine. However, in the field of laboratory medicine, related research was rarely reported. The spectrometric quantification of glucose is an application of the enzymatic reference method with hexokinase. The sources of uncertainty in the measurement process were analyzed. The measurement uncertainties in the study were evaluated according to GUF method and the method introduced by Quantifying Uncertainty in Analytical Measurement (QUAM) was also applied in the evaluation of the measurement of linear fitting. The standard curve was built successfully according to the measurement procedure recommended by the CDC and the linear equation was y = 0.000807x + 0.001213 (R2 = 0.999179). The measurement uncertainty of glucose in the sample was 0.450,408 mmol/L. The method for the determination of serum glucose concentration by hexokinase in our laboratory has been successfully established. The measurement uncertainty was consistent with the GUF method and the method introduced by Quantifying Uncertainty in Analytical Measurement (QUAM) in the process of linear fitting when the glucose concentration was measured by the reference method (hexokinase method).

An innovative blood plasma separation method for a paper-based analytical device using chitosan functionalization.

This study describes a microfluidic paper-based analytical device (μPAD) for separating plasma from whole blood and measuring glucose concentration. A two-dimensional μPAD was fabricated by wax printing, using chromatographic paper and was functionalized by the incorporation of chitosan into the plasma separation zone. Red blood cells were isolated from whole blood in the plasma separation zone consisting of a chitosan polymer structure and a wax barrier. The separated plasma, with buffer, was injected into the test zone to cause a color change. The colorimetric results were digitized with a scanner, and the concentration was calculated using a calibration curve. This μPAD, which separated the plasma from whole blood without a separation membrane, will be useful for constructing point-of-care testing devices that detect analytes in small sample volumes.

Time-domain photoacoustic waveform analysis for glucose measurement.

Photoacoustic (PA) effect is the product of light-ultrasound interactions and its time-domain waveform contains rich information. Besides optical absorption, the PA waveform inherently consists of other mechanical and thermal properties of the sample. They also have correlation with the target composition but have not been utilized in conventional PA spectroscopy. In this article, we propose a new concept named time-domain photoacoustic waveform spectroscopy (tPAWS) for chemical component quantification. It employs multiple variables inherently contained in the PA waveform excited by a single wavelength laser to extract informative features. The demonstration of glucose measurement in human blood serum (HBS) shows superior sensitivity and accuracy enhancement, compared to conventional amplitude-based PA measurement and NIR spectroscopy. Thanks to the sensitivity and accuracy of tPAWS, multiple wavelength sources and complex instrumentation used in conventional spectroscopic sensing methods can be avoided. TPAWS, as a novel physics-inspired sensing method, shows great potential for complementing or surpassing the current spectroscopic methods as a new sensing technique for chemical analysis.

Continuous Glucose Monitoring in Conscious Unrestrained Mice.

Measurement of blood glucose concentration is a common end point in studies using animal models of diabetes. Usually a blood glucose meter is used to measure non-fasted blood glucose concentrations, typically at frequencies of between 1 and 7 times per week. This process involves pricking the tip of the tail to collect a small blood sample (0.5-5μL), which could potentially cause a stress response and affect blood glucose concentrations. Moreover, with blood glucose concentrations constantly fluctuating in response to feeding and activity, a single-point measurement can easily misrepresent the actual glycemic control of the animal. In this chapter, we discuss the use of continuous glucose monitoring in mice by radio-telemetry which allows second-by-second changes in blood glucose to be captured without restraining the mouse. Glucose excursions rather than single-point measurements may prove more useful in detecting effects of treatments, and lack of handling may avoid stress responses causing artefacts. We outline what is involved in implanting such devices into mice including some practical tips to maximize success.

Glucose Analyzer Based on Self-made Biosensor for High-performance Glucose Detection

The concentration analyzer with high precision and wide range is the core device for monitoring the fermentation process. In this work, we designed and proposed a lowcost three-electrode glucose analyzer based on a self-made screen-printed enzyme biosensor chip, which has a Prussian blue (PB) nanocubic structure and leads to high sensitivity of 117.31 μAmM-1cm-2. The hardware design of the glucose analyzer can be divided into five critical parts, including digital, signal treatment system, power supply, motor-driven and the host computer. The signal treatment system is used to collect, convert and amplify the weak current signal generated by the biosensor. The digital circuit of the central processing unit of the analyzer is designed using the STM32F407ZET6. Besides, an external analog-to-digital converter is used to achieve high precision A/D conversion. The stability of the potentiostat is ensured by designing the precision power supply, hardware filtering, and algorithm filtering. The experimental results show that the glucose analyzer has a wide linear detection range from 1g/L to 120g/L and the coefficient of variation at 1g/L is 0.038, which exhibits excellent performance in stability and detection accuracy. The analyzer can be applied in the future for in-situ measurement of glucose concentration for its wide-range and high-precision detection capabilities.

The relationship between plasma GIP and GLP-1 levels in individuals with normal and impaired glucose tolerance.

Glucose-dependent insulinotropic polypeptide (GIP) is released primarily from the proximal small intestine and glucagon-like peptide-1 (GLP-1) from the more distal small intestine and colon. Their relative importance to the incretin effect in health has been contentious in the past, although it now appears that GIP has the dominant role. It is uncertain whether there is a relationship between GIP and GLP-1 secretion. We aimed to evaluate the relationship between plasma GIP and GLP-1 responses to a 75-g oral glucose load in individuals with normal (NGT) and impaired glucose tolerance (IGT). One hundred healthy subjects had measurements of blood glucose, serum insulin, plasma GIP and GLP-1 concentrations for 240min after a 300mL drink containing 75g glucose. Fifty had NGT and 41 IGT; 9 had type 2 diabetes and were excluded from analysis. In both groups, there were increases in plasma GIP and GLP-1 following the glucose drink, with no difference in the magnitude of the responses between t = 0-240min. There was a weak relationship between the iAUC0-240min for GIP and GLP-1 in the combined (r = 0.23, P = 0.015) and in the IGT (r = 0.34, P = 0.01), but not in the NGT (r = 0.15, P = 0.14) group. There is a weak relationship between oral glucose-induced GIP and GLP-1 secretions in non-diabetic subjects.

Measurement Uncertainty Impacts Diagnosis of Diabetes Mellitus: Reliable Minimal Difference of Plasma Glucose Results.

IntroductionThe diagnosis of diabetes mellitus is based on suitable cut-off values of specific biomarkers, such as the concentration of glucose in plasma. The German Diabetes Association has very recently published a clinical practice guideline on the definition, classification and diagnosis of diabetes mellitus that recommends measurements of plasma glucose concentration have an imprecision defined as a minimal difference (MD) of at a fasting plasma glucose concentration of 7.0 mmol/L. To obtain reliable values for the MD, we investigated long-term and short-term measurement uncertainty.MethodsThe imprecision was determined by two approaches: (1) a long-term dataset with imprecision based on the Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations (Rili-BAEK), in a medical laboratory operating 24/7, using internal quality control (IQC) data for four concentrations during a 10-year period; and (2) a detailed short-term dataset with imprecision assessed by hourly measurements of control materials. These datasets were used to calculate the MD cut-off (MDcut-off) as: {text{MD}}_{text{cut-off}} = k times {text{SD}} = 2 times {text{SD}} , where SD is the standard deviation and k = 2 represents a confidence level of 95%.ResultsThe MDcut-off of ≤ 0.7 mmol/L at a fasting plasma glucose concentration of 7.0 mmol/L (MDcut-off 7.0) for the long-term and the short-term approaches were 0.44 and 0.40 mmol/L, respectively. The MDcut-off 7.0 from both approaches was therefore below the recommended value of 0.7 mmol/L. It was noted that the variability in performance within and between instruments can be covered by reporting the long-term MDcut-off 7.0 across all connected instruments. In this study, stable results for the MDcut-off 7.0 were obtained after 1 year.ConclusionImprecision as measured by IQC data is remarkably stable over many years of operation. Current imprecision assessment usually focuses on only single instruments, whereas clinicians perceive the measurement as the result of the combined analytical performance of all instruments used for a certain assay. In the clinical setting, the MD may be a more useful measure of imprecision, and we suggest deriving the MDcut-off combined from all instruments and control cycles that are used in the patient care setting for a given analyte.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00740-w) contains supplementary material, which is available to authorized users.

Real-Time Noninvasive Measurement of Glucose Concentration Using a Modified Hilbert Shaped Microwave Sensor.

We developed a microwave glucose sensor based on the modified first-order Hilbert curve design and measured glucose concentration in aqueous solutions by using a real-time microwave near-field electromagnetic interaction technique. We observed S21 transmission parameters of the sensor at resonant frequencies depend on the glucose concentration. We could determine the glucose concentration in the 0–250 mg/dL concentration range at an operating frequency of near 6 GHz. The measured minimum detectable signal was 0.0156 dB/(mg/dL) and the measured minimum detectable concentration was 1.92 mg/dL. The simulation result for the minimum detectable signal and the minimum detectable concentration was 0.0182 dB/(mg/dL) and 1.65 mg/dL, respectively. The temperature instability of the sensor for human glycemia in situ measurement range (27–34 °C for fingers and 36–40 °C for body temperature ranges) can be improved by the integration of the temperature sensor in the microwave stripline platform and the obtained data can be corrected during signal processing. The microwave signal–temperature dependence is almost linear with the same slope for a glucose concentration range of 50–150 mg/dL. The temperature correlation coefficient is 0.05 dB/°C and 0.15 dB/°C in 27–34 °C and 36–40 °C temperature range, respectively. The presented system has a cheap, easy fabrication process and has great potential for non-invasive glucose monitoring.

S-shaped long period fiber grating glucose concentration biosensor based on immobilized glucose oxidase

In this study, we fabricated an S-shaped long period fiber grating (S-shaped LPFG) using the lithography process and then used alkylation technology to immobilize glucose oxidase for glucose concentration measurements. The principles of the associated experiment suggest that this phenomenon is caused by the use of glucose oxidase and glucose-specific binding characteristics for testing. The combination of glucose oxidase with glucose alters the external refractive index of the optical fiber, changing the refractive index and thereby changing the transmission loss. The experimental results show that the transmission varied in a linear manner with differing glucose concentrations. The best sensitivity of the S-shaped LPFG glucose concentration sensor was 6.229 dB/wt% from 0 ∼ 1 wt%, and the linearity (R2) was 0.949. The results demonstrate that the proposed S-shaped LPFG has good potential for high-sensitivity glucose concentration sensor applications.

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.

Mathematical model experimental verification for non-invasive method of glucose concentration in blood determination

The mathematical model of the device which provides performance of the non-invasive measurements of glucose concentration in blood has been created. The model includes composition and solution of the system (or the set of systems) of linear equations in which the concentrations of different absorbing components are variables. This model has some problems from the point of view of the equation system solution convergence, and it was necessary to perform some experiments for the model verification. The present paper is devoted to the experiments performance methods and results for the mentioned mathematical model verification. The study allowed us to determine the working wavelengths in the spectral ranges that are optimal for measuring the concentration of glucose in the blood, and to establish the correlation of the measured and calculated values according to the developed mathematical model.

Microwave reflective biosensor for glucose level detection in aqueous solutions

This article presents the design and analysis of a real-time non-invasive microwave microfluidic sensor for measuring glucose concentration in aqueous solutions. The sensor is made of an open-ended microstrip transmission line loaded with a complementary split-ring resonator (CSRR). The CSRR shows a very intense electric field concentration at resonance, which is highly sensitive to the dielectric sample loading. A microfluidic channel is designed to deliver the glucose solutions to the sensitive area of the device. By applying liquid samples to the channel, a resonance frequency shift is detectable in the reflection coefficient (S11) of the device. This in turn leads to a change in the |S11|. Both of the frequency shift and Δ|S11| can be used to measure the glucose level in the solution. Mathematical models are developed based on the measurement results of the glucose-water solutions using the resonance frequency shift and Δ|S11|. The developed sensing models are then used for detecting the glucose levels down to physiological values using the designed biosensor. The results prove the potential compatibility of the proposed biosensor for human glycaemia monitoring.

Double-knotted U-shaped spiral optical fiber probe for measuring glucose solutions

The study focuses on the glucose concentrations by an U-shaped spiral fiber optical probes device. In this article, we used zero-knotted and double-knotted U-shaped spiral fiber optical probes with 0.6 mm bending radius for measuring glucose solutions was investigated. The fiber optical probe is worked on the different concentrations of the glucose solution and obtain the effective refractive index changes. The principle theory underlying the probe is the whispering gallery mode (WGM). The experimental results show that the double-knotted transmission loss sensitivity can achieve 0.061 dB/% and the highest linearity was 0.99 at the same time. The indicated that the double-knotted U-shaped spiral optical fiber probe with small radius has good the resolution of glucose concentration measurements.

Non-contact active microwave sensor for glucose concentration measurement

A non-contract microwave sensor with a common emitter amplifier circuit for glucose concentration sensing is developed and investigated in this article. The geometries and materials of the designed sensor are optimized and analyzed by the full-wave electromagnetic simulation. The microwave prototype was created using a printed circuit board based on dry film techniques. The microwave sensor was connected to a vector network analyzer (VNA) and the electromagnetic interaction between the samples and sensor was analyzed. The proposed sensor was tested for its electromagnetic response to glucose at various concentrations ranging from 0 to 16 % (W/V) with steps of 4 % (W/V) in the frequency range from 2.0 to 4.0 GHz through the measurement of the transmission coefficient (S21) and quality factors (Q-factor) based on non-contact detection. The experimental results confirmed that the magnitude of S21 and Q-factor were changed when the concentration of glucose was changed. The magnitude of S21 and Q-factor were reduced when the glucose concentration is increased. Based on the results of the study, the proposed microwave sensor will be further developed to measure the concentration of soluble glucose and can be used as a sensor for chemical solution measurement and biometrics without damaging the structure of the substance.

Gaussian beam with high spherical aberration focused by a singlet lens-shaped container for glucose measurements.

We describe a highly sensitive optical technique for glucose concentration measurements in liquid samples based on measuring the heights of the primary sidelobes of the normalized intensity profiles of a focused Gaussian beam with high spherical aberration. A singlet lens-shaped container, filled with the sample under test, is used to focus the beam at an observation plane placed close to the focusing region. The normalized intensity profile of the aberrated beam allows for accurate measurement of the sample glucose concentration.

Biopsy needle integrated with multi-modal physical/chemical sensor array

A biopsy needle integrated with a multi-modal physical/chemical sensor array for electrical conductivity, pH, and glucose concentration measurement was developed. A flexible device with an electrical conductivity sensor, a pH sensor, and a glucose sensor was fabricated on a flexible polyimide substrate with thickness less than 20 μm. Then, the sensor was directly integrated onto the surface of biopsy needle by attaching with a pressure sensitive adhesive. The performance factors of the sensor were examined, showing that it could properly measure the parameters in the ranges of human body conditions (conductivity = 0.0265 S/m - 1.027 S/m, pH = 6.6–7.4, and glucose concentration = 2 mM–13 mM). The capabilities of dual-modal and multi-modal sensing were demonstrated by tests with a liver cancer mimicking hydrogel phantom, a solution sample, and porcine liver tissue with exchanged parameters by perfusion of the phosphate buffer saline. Based on these results, we expect that the biopsy needle integrated with the multi-modal sensor array could help to increase the accuracy of the image-guided biopsy process by providing the information of tissue types at the needle tip.

Study of a noninvasive blood glucose detection model using the near-infrared light based on SA-NARX

Accumulated attempts have been made to develop models for near-infrared noninvasive measurement of human blood glucose concentration. Most of them focus on the relationship between near-infrared absorbance and blood glucose concentration, but do not consider the fluctuation regularity of blood glucose concentration and the influence of environmental factors and human physiological state on near-infrared absorption. In order to improve the performance of prediction model, a hybrid method is proposed in this paper. The nonlinear autoregressive model with exogenous input (NARX) was introduced as prediction model. 7 variables, including 1550 nm near-infrared absorbance, ambient temperature, ambient humidity, systolic pressure, diastolic pressure, pulse rate and body temperature were introduced as initial input variables. The sensitivity analysis (SA) method was employed to select the relative important input variables for NARX model. Based on the result of SA, a robust and accurate NARX model with 4 input variables (1550 nm near-infrared absorbance, systolic pressure, pulse rate and body temperature) was derived. Compared with the back propagation neural network (BPNN) with the same selected 4 input variables and the BPNN with initial 7 input variables, the NARX model developed there showed better prediction performance, of which the root mean square error and correlation coefficients were 0.72 mmol/L and 0.85 respectively for the 10-fold cross validation set. The percentages of the 10-fold cross validation set samples falling in region A and B of the Clarke error grid analysis were 90.27% and 9.73% respectively. These results demonstrate the potential of our model for noninvasive measurement of blood glucose concentration.