Non-invasive Blood Glucose Monitoring Research Articles

Non-invasive Glucose Monitoring at mm-Wave Frequencies

In this paper, we review our recent experimental studies todevelop a non-invasive blood glucose monitoring system at mm-wave frequencies. A robust 60 GHz radar system is used todifferentiate between hemoglobin samples of disparate glucoseconcentrations through detecting minute changes in theirdielectric properties. A new-developed dielectric assessmentsystem (DAK) is used to characterise the electromagneticproperties of the tested samples and identify the amount ofchange in these parameters at different concentrations of interest.

Non-invasive monitoring of blood glucose using optical methods for skin spectroscopy-opportunities and recent advances.

Diabetes mellitus is a widespread disease with greatly rising patient numbers expectedin the future, not only for industrialized countries but also for regions in the developing world. There is aneed for efficient therapy, which can be via self-monitoring of blood glucose levels to provide tight glycemic control for reducing the risks of severe health complications. Advancements in diabetes technology can nowadays offer different sensor approaches, even for continuous blood glucose monitoring. Non-invasive blood glucose assays have been promised for many years and various vibrational spectroscopy-based methods of theskin are candidates for achieving this goal. Due to the small spectral signatures of the glucose hidden among a largely variable background, the largest signal-to-noise ratios and multivariate calibration are essential to provide the method applicability for self-monitoring of blood glucose. Besides multiparameter approaches, recently presented devices based on photoplethysmography with wavelengths in the visible and near-infrared range are evaluated for their potential of providing reliable blood glucose concentration predictions. Graphical abstract ᅟ.

Penerapan Teknik Prapemrosesan Smoothing Spline pada Data Hasil Pengukuran Alat Pemantau Kadar Glukosa Darah Non-Invasif

A non-invasive blood glucose monitoring device is performed without injuring the limbs. One method of measurement in the form of qualitative and relatively simple to use because the process is fast and requires a cheap cost, namely Fourier Transform Infrared (FTIR). Spectroscopic results allow for a shifting of the scatter, since the same object is measured several times incorrectly producing the same spectrum, requiring a preprocessing method to reduce the problem. However, in some cases it is difficult to identify the existing data pattern, so that a nonparametric approach is needed to identify the pattern of data held so that in the process of calibration model obtained accurate results. Smoothing Spline is one nonparametric method is piecewise polynomial, which is a piece of polynomial that has a segmented property on the hose k that formed at knot points, thus providing flexibility in constructing the shape of the curve that we have. The Smoothing Spline method produces an optimum value when the GCV value is minimum on the use of a linear order with sixteen knot points. The resulting varians value after Smoothing Spline method is smaller than before smoothing, this indicates that this method can minimize the effect of liquefaction in the non-invasive blood glucose value spectrum. In addition, Smoothing Spline method can also capture data patterns well.

In vivo Microscopic Photoacoustic Spectroscopy for Non-Invasive Glucose Monitoring Invulnerable to Skin Secretion Products

Photoacoustic spectroscopy has been shown to be a promising tool for non-invasive blood glucose monitoring. However, the repeatability of such a method is susceptible to changes in skin condition, which is dependent on hand washing and drying due to the high absorption of infrared excitation light to the skin secretion products or water. In this paper, we present a method to meet the challenges of mid-infrared photoacoustic spectroscopy for non-invasive glucose monitoring. By obtaining the microscopic spatial information of skin during the spectroscopy measurement, the skin region where the infrared spectra is insensitive to skin condition can be locally selected, which enables reliable prediction of the blood glucose level from the photoacoustic spectroscopy signals. Our raster-scan imaging showed that the skin condition for in vivo spectroscopic glucose monitoring had significant inhomogeneities and large variability in the probing area where the signal was acquired. However, the selective localization of the probing led to a reduction in the effects of variability due to the skin secretion product. Looking forward, this technology has broader applications not only in continuous glucose monitoring for diabetic patient care, but in forensic science, the diagnosis of malfunctioning sweat pores, and the discrimination of tumors extracted via biopsy.

Enzyme-Based Glucose Sensor: From Invasive to Wearable Device.

Blood glucose concentration is a key indicator of patients' health, particularly for symptoms associated with diabetes mellitus. Because of the large number of diabetic patients, many approaches for glucose measurement have been studied to enable continuous and accurate glucose level monitoring. Among them, electrochemical analysis is prominent because it is simple and quantitative. This technology has been incorporated into commercialized and research-level devices from simple test strips to wearable devices and implantable systems. Although directly monitoring blood glucose assures accurate information, the invasive needle-pinching step to collect blood often results in patients (particularly young patients) being reluctant to adopt the process. An implantable glucose sensor may avoid the burden of repeated blood collections, but it is quite invasive and requires periodic replacement of the sensor owing to biofouling and its short lifetime. Therefore, noninvasive methods to estimate blood glucose levels from tears, saliva, interstitial fluid (ISF), and sweat are currently being studied. This review discusses the evolution of enzyme-based electrochemical glucose sensors, including materials, device structures, fabrication processes, and system engineering. Furthermore, invasive and noninvasive blood glucose monitoring methods using various biofluids or blood are described, highlighting the recent progress in the development of enzyme-based glucose sensors and their integrated systems.

An Approach for Noninvasive Blood Glucose Monitoring Based on Bioimpedance Difference Considering Blood Volume Pulsation

Noninvasive blood glucose monitoring (NBGM) provides a promising solution for patients with diabetes with the advantages of painless and continuous monitoring. To better characterize the response of glucose to radio-frequency (RF) signals at low frequencies, the conductivity and relative permittivity of aqueous solutions with different glucose concentrations were obtained by the use of an impedance analyzer in the frequency range of 1 kHz to 1 MHz. Furthermore, considering the blood volume pulsation in cardiac cycle, a new approach based on measuring bioimpedance was presented for NBGM in this paper. For this purpose, an inhomogeneous arm model, which consists of three tissue layers (i.e., blood, blood vessel, and other relevant tissues), was proposed to validate the aforementioned approach. Furthermore, the measurements were carried out by means of in vitro experiment and in vivo studies, respectively. The results showed that as the glucose concentration increased, the conductivity of aqueous solutions decreased when the frequency of RF signal was below 1 MHz. However, the relative permittivity was almost insensitive to glucose concentration. The simulation result of the arm model showed that as the glucose concentration increased, the bioimpedance difference of blood volume decreased. This was supported by both in vitro and in vivo experiments. We therefore suggest that the proposed approach for NBGM has potentials in practical applications.

Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring.

Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery-powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface. The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. We conducted in vivo human clinical trials. The noninvasive measurement results for intravascular blood glucose showed a high correlation (>0.9) with clinically measured blood glucose levels. The system opens up new prospects for clinical-grade noninvasive continuous glucose monitoring.

Noninvasive Monitoring of Blood Glucose with Raman Spectroscopy.

The successful development of a noninvasive blood glucose sensor that can operate reliably over sustained periods of time has been a much sought after but elusive goal in diabetes management. Since diabetes has no well-established cure, control of elevated glucose levels is critical for avoiding severe secondary health complications in multiple organs including the retina, kidney and vasculature. While fingerstick testing continues to be the mainstay of blood glucose detection, advances in electrochemical sensing-based minimally invasive approaches have opened the door for alternate methods that would considerably improve the quality of life for people with diabetes. In the quest for better sensing approaches, optical technologies have surfaced as attractive candidates as researchers have sought to exploit the endogenous contrast of glucose, notably its absorption, scattering, and polarization properties. Vibrational spectroscopy, especially spontaneous Raman scattering, has exhibited substantial promise due to its exquisite molecular specificity and minimal interference of water in the spectral profiles acquired from the blood-tissue matrix. Yet, it has hitherto been challenging to leverage the Raman scattering signatures of glucose for prediction in all but the most basic studies and under the least demanding conditions. In this Account, we discuss the newly developed array of methodologies that address the key challenges in measuring blood glucose accurately using Raman spectroscopy and unlock new prospects for translation to sustained noninvasive measurements in people with diabetes. Owing to the weak intensity of spontaneous Raman scattering, recent research has focused on enhancement of signals from the blood constituents by designing novel excitation-collection geometries and tissue modulation methods while our attempts have led to the incorporation of nonimaging optical elements. Additionally, invoking mass transfer modeling into chemometric algorithms has not only addressed the physiological lag between the actual blood glucose and the measured interstitial fluid glucose values but also offered a powerful tool for predictive measurements of hypoglycemia. This framework has recently been extended to provide longitudinal tracking of glucose concentration without necessitating extensive a priori concentration information. These findings are advanced by the results of recent glucose tolerance studies in human subjects, which also hint at the need for designing nonlinear calibration models that can account for subject-to-subject variations in skin heterogeneity and hematocrit levels. Together, the emerging evidence underscores the promise of a blood withdrawal-free optical platform-featuring a combination of high-throughput Raman spectroscopic instrumentation and data analysis of subtle variations in spectral expression-for diabetes screening in the clinic and, ultimately, for personalized monitoring.

The dynamics of invasive and noninvasive blood glucose monitoring methods: Recent trends

Improved prognoses of patients with type 2 diabetes are primarily determined by the extent of blood glucose control (correction of both hyper- and hypoglycemia and normalization of blood glucose levels). The proper identification and timely correction of abnormal blood glucose levels require frequent blood glucose monitoring by the patient. Currently used methods for the self-monitoring of blood glucose have significant drawbacks that limit their use. The most significant problems with these methods include insufficient accuracy, invasiveness and high cost, leading to noncompliance and difficult assessment of disease status. Such factors underscore the need for a noninvasive, cost-effective and highly accurate method to measure blood glucose levels. There are several different approaches for the noninvasive measurement of blood glucose levels, including optical analysis, ultrasound and bioimpedance. The concept of a noninvasive glucometer was launched more than 30 years ago. Nevertheless, most noninvasive technologies are still in early stages of development and are not used in clinical practice. This review describers the most promising developments in this area.

Non-invasive blood glucose monitoring is an elusive goose

Non-invasive blood glucose monitoring is an elusive goose

Fundamentals of microwave technology for non-invasive blood glucose monitoring and review of the most significant works developed

A retrospective review of the most important researches made regarding non-invasive blood glucose monitoring is presented, and bases for further investigation in this field are offered. The problem of diabetes disease on its two known types as well as its consequences and its management is discussed, and the need for this kind of glucose monitoring to avoid the painful procedures is shown. Fundamentals of microwave technology concerning relative permittivity measurement and tissue characterization are provided to understand the operating principles of non-invasively measuring, and theory review on this concern is presented. Variations of the relative permittivity in some zones of the body as the blood glucose level changes are studied to assess the feasibility of this kind of glucose monitoring. Literature references of electrical properties of biological tissues are studied, and the most relevant researches made regarding non-invasive blood glucose monitoring are discussed, focusing on the systems based on microwave resonators.

Noninvasive blood glucose monitoring in the terahertz frequency range

Human skin optical properties were studied in vivo using terahertz (THz) time-domain spectroscopy. For the attenuated total internal reflection (ATR) the silicon Dowe prism was used. The measurements were carried out on six volunteers with normal blood glucose concentration and in good health. A standard oral glucose tolerance test was also performed. The ATR spectra of palm skin were consecutively measured at 0–90 min after glucose intake. The variations of the ATR spectra of human skin were correlated with the changes in blood glucose level. The amplitude of ATR signal of human palm skin increased and the phase decreased when glucose concentrations in blood rose above the normal level. Our results demonstrate the possibility of a non-invasive real-time measurement of blood glucose concentration.

Determination of the Pressure Coefficient of Optical Attenuation in Different Layers of In-Vivo Human Skins With Optical Coherence Tomography

We use optical coherence tomography (OCT) to systematically study the dependence of the optical attenuation coefficient μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> upon the applied pressure P in different depth regions of the human skin in vivo. We find that the same OCT data can be used to estimate thicknesses of the epidermis layer and the epidermis-dermis junction and obtain the thickness changes in these skin layers induced by the pressure. We further propose and demonstrate using the correlation map to identify depth regions in which μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> has positive and negative correlations with the applied pressure and study in detail the changes of μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> in dermis with the applied pressure. By using a low-cost thin-film pressure sensor to monitor the applied pressure accurately, we are able to quantitatively obtain the pressure dependence of μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> in different skin layers in vivo with the following interesting findings: When a pressure ranging from 0 to 20 kPa is applied on the volar side of the forearm skin, μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> increases with the applied pressure in the epidermis layer, which coincides with the thickness decrease and increase of the epidermis and the epidermis-dermis junction, respectively. In contrast, μ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> decreases with applied pressure in the upper dermis but increases again in the deeper dermis with applied pressure. Our results demonstrate that the OCT correlation map and the thin-film sensor are effective tools to study the optical scattering properties of human skin under pressure. We anticipate that our experimental and analytical methods reported in this paper can be useful for clinical diagnostic applications, such as noninvasive blood glucose monitoring.

Non-invasive blood glucose monitoring with Raman spectroscopy: prospects for device miniaturization

The number of patients with diabetes has reached over 350 million, and still continues to increase. The need for regular blood glucose monitoring sparks the interest in the development of modern detection technologies. One of those methods, which allows for noninvasive measurements, is Raman spectroscopy. The ability of infrared light to penetrate deep into tissues allows for obtaining measurements through the skin without its perforation. This paper presents the limitations and possibilities of non-invasive blood glucose monitoring with Raman spectroscopy. Especially focusing on the possibilities for device miniaturization. Such device incorporates a Raman spectrometer, a fiber-optical probe, and a computing device (microcontroller, smartphone, etc.) which calculates the glucose concentration using specialized algorithms. Simplification of device design, as well as turbidity correction technique and a new proposed method of synchronized detection are described.

Design and In Vitro Interference Test of Microwave Noninvasive Blood Glucose Monitoring Sensor

A design of a microwave noninvasive continuous blood glucose monitoring sensor and its interference test results are presented. The novelty of the proposed sensor is that it comprises two spatially separated split-ring resonators, where one interacts with the change in glucose level of a sample under test while the other ring is used as a reference. The reference ring has a slightly different resonant frequency and is desensitized to the sample owing to its location, thus allowing changes in temperature to be calibrated out. From an oral glucose tolerance test with two additional commercially available sensors (blood strip and continuous glucose monitor) in parallel, we obtained encouraging performance for our sensor comparable with those of the commercial sensors. The effects of endogenous interferents common to all subjects, i.e., common sugars, vitamins (ascorbic acid), and metabolites (uric acid) have also been investigated by using a large Franz cell assembly. From the interference test, it is shown that the change in sensor response is dominated by changes in glucose level for concentrations relevant to blood, and the effects of interferents are negligible in comparison.

A Microwave Metamaterial Inspired Sensor for Non-Invasive Blood Glucose Monitoring

In this paper, a microwave sensor based on an ar- tificial transmission line is proposed for non-invasive blood glucosemonitoring. Acorrespondingnumericalmodelofthe sensorimplementedinmicrostriptechnologyiscreatedinthe commercial full-wave numerical simulation tool COMSOL Multiphysics and virtually tested by means of numerical sim- ulations. Blood-glucose solution models with various blood glucose concentrations are used as a model of a biological tissue under test. Furthermore, a possible methodology for performing non-invasive tests is proposed. Sensitivity of the sensor developed here is compared to a sensor based on a section of a conventional microstrip transmission line of the same length and width.

Modelling, verification, and calibration of a photoacoustics based continuous non-invasive blood glucose monitoring system.

This paper examines the use of photoacoustic spectroscopy (PAS) at an excitation wavelength of 905 nm for making continuous non-invasive blood glucose measurements. The theoretical background of the measurement technique is verified through simulation. An apparatus is fabricated for performing photoacoustic measurements in vitro on glucose solutions and in vivo on human subjects. The amplitude of the photoacoustic signals measured from glucose solutions is observed to increase with the solution concentration, while photoacoustic amplitude obtained from in vivo measurements follows the blood glucose concentration of the subjects, indicating a direct proportionality between the two quantities. A linear calibration method is applied separately on measurements obtained from each individual in order to estimate the blood glucose concentration. The estimated glucose values are compared to reference glucose concentrations measured using a standard glucose meter. A plot of 196 measurement pairs taken over 30 normal subjects on a Clarke error grid gives a point distribution of 82.65% and 17.35% over zones A and B of the grid with a mean absolute relative deviation (MARD) of 11.78% and a mean absolute difference (MAD) of 15.27 mg/dl (0.85 mmol/l). The results obtained are better than or comparable to those obtained using photoacoustic spectroscopy based methods or other non-invasive measurement techniques available. The accuracy levels obtained are also comparable to commercially available continuous glucose monitoring systems.

Noninvasive Blood Glucose Measurement Based on NIR Spectrums and Double ANN Analysis

This paper presents a new noninvasive blood glucose monitoring method based on four near infrared spectrums and double artificial neural network analysis. We choose four near infrared wavelengths, 820 nm, 875 nm, 945 nm, 1050 nm, as transmission spectrums, and capture four fingers transmission PPG signals simultaneously. The wavelet transform algorithm is used to remove baseline drift, smooth signals and extract eight eigenvalues of each PPG signal. The eigenvalues are the input parameters of double artificial neural network analysis model. Double artificial neural network regression combines the classification recognition algorithm with prediction algorithm to improve the accuracy of measurement. Experiments show that the root mean square error of the prediction is between 0.97 mg/dL - 6.69 mg/dL, the average of root mean square error is 3.80 mg/dL.

Phantoms for Development of Microwave Sensors for Noninvasive Blood Glucose Monitoring

A suitability of two different liquid phantoms of blood-glucose solutions as phantoms for development of microwave sensors for noninvasive blood glucose monitoring is compared. The two phantoms are physiological saline-glucose and pig blood-glucose solutions. For this purpose a simple microwave sensor is developed for in vitro monitoring of blood glucose levels. The sensor consists of a microstrip antenna and of a small rectangular container on the top of the antenna. The container is filled with one of the liquid phantoms. Both phantoms with different glucose concentrations ranging from 0 to 500 mg/dL are considered. Dependence of sensor’s resonant frequency on glucose concentration of LUTs is both estimated by aid of numerical simulations and measured. The results are discussed and compared with some results reported in the literature.

The Utilization of Ultrasonic Standing Waves for Predicting Glucose Concentration Levels in Dextrose Mixed Intralipid Based Tissue Phantom

This paper represents the effect of amplitude modulated ultrasonic standing waves in determining the glucose concentration in dextrose mixed intralipid based tissue phantom. The intralipid exhibits biological tissue related light absorption, reflection, scattering properties. The intralipid act as a suitable substitute medium for tissue related lab based experimentations. The ultrasonic waves were produced here using two sinusoidal waves. Phase of the ultrasonic waves were controllable in nature. The piezoelectric crystal based ultrasonic transmitter and receiver of 40 kHz were used here. The ultrasound produced here causes series of vibrating pattern on the area of its applications. Molecules usually vibrate specifically based on their structural orientations and physical properties. The vibration patterns of glucose molecule were observed here using infrared LED of 940nm. The experimental design and resultant output in Fast Fourier Transform Domain for glucose prediction in dextrose mixed intralipid phantoms had been described and discussed in this paper. This technology can be utilized to design and improve noninvasive blood glucose monitoring devices.