Non-invasive Continuous Glucose Monitoring System Research Articles

Power and Sensitivity Management of Carbon Nanotube Transistor Glucose Biosensors.

Continuous glucose monitoring (CGM), which is significant for the daily management of diabetes, requires a low-power-consumption sensor system that can track low nanomolar levels of glucose in physiological fluids, such as sweat and tears. However, traditional electrochemical methods are limited to analytes in micromolar to millimolar ranges and entail high power consumption. Carbon nanotube (CNT) film field-effect transistors (FETs) are promising for constructing extremely sensitive biosensors, but their wide applications in CGM are limited by the strong screening effect of physiological fluids and the zero charge of glucose molecules. In this study, we demonstrate a glucose aptamer-modified CNT FET biosensor to realize a highly sensitive CGM system with sub-nW power consumption by applying a suitable gate voltage. A positive gate voltage can enlarge the effective Debye screening length at the double layer to reduce the local ion population nearby and then improve the sensitivity of the FET-based biosensors by 5 times. We construct CNT FET sensors for CGM with a limit of detection of 0.5 fM, a record dynamic range up to 109, and a power consumption down to ∼100 pW. The proposed field-modulated sensing performance scheme is applicable to other aptamer-based FET biosensors for detecting neutral or less charged molecules and opens opportunities to develop facilely modulated, highly sensitive, low-power, and noninvasive CGM systems.

Noninvasive Blood Glucose Monitoring Systems Using Near-Infrared Technology-A Review.

The past few decades have seen ongoing development of continuous glucose monitoring (CGM) systems that are noninvasive and accurately measure blood glucose levels. The conventional finger-prick method, though accurate, is not feasible for use multiple times a day, as it is painful and test strips are expensive. Although minimally invasive and noninvasive CGM systems have been introduced into the market, they are expensive and require finger-prick calibrations. As the diabetes trend is high in low- and middle-income countries, a cost-effective and easy-to-use noninvasive glucose monitoring device is the need of the hour. This review paper briefly discusses the noninvasive glucose measuring technologies and their related research work. The technologies discussed are optical, transdermal, and enzymatic. The paper focuses on Near Infrared (NIR) technology and NIR Photoplethysmography (PPG) for blood glucose prediction. Feature extraction from PPG signals and glucose prediction with machine learning methods are discussed. The review concludes with key points and insights for future development of PPG NIR-based blood glucose monitoring systems.

Evaluation of a Continuous Blood Glucose Monitor: A Novel and Non-Invasive Wearable Using Bioimpedance Technology.

Frequent blood glucose level (BGL) monitoring is essential for effective diabetes management. Poor compliance is common due to the painful finger pricking or subcutaneous lancet implantation required from existing technologies. There are currently no commercially available non-invasive devices that can effectively measure BGL. In this real-world study, a prototype non-invasive continuous glucose monitoring system (NI-CGM) developed as a wearable ring was used to collect bioimpedance data. The aim was to develop a mathematical model that could use these bioimpedance data to estimate BGL in real time. The prototype NI-CGM was worn by 14 adult participants with type 2 diabetes for 14 days in an observational clinical study. Bioimpedance data were collected alongside paired BGL measurements taken with a Food and Drug Administration (FDA)-approved self-monitoring blood glucose (SMBG) meter and an FDA-approved CGM. The SMBG meter data were used to improve CGM accuracy, and CGM data to develop the mathematical model. A gradient boosted model was developed using a randomized 80-20 training-test split of data. The estimated BGL from the model had a Mean Absolute Relative Difference (MARD) of 17.9%, with the Parkes error grid (PEG) analysis showing 99% of values in clinically acceptable zones A and B. This study demonstrated the reliability of the prototype NI-CGM at collecting bioimpedance data in a real-world scenario. These data were used to train a model that could successfully estimate BGL with a promising MARD and clinically relevant PEG result. These results will enable continued development of the prototype NI-CGM as a wearable ring.

885-P: Evaluation of a Novel Continuous Glucose Monitoring System in Insulin-Treated Patients with Diabetes: A Pilot Study

Continuous glucose monitoring has been shown to be an effective tool in management of type 1 and type 2 diabetes. Non-invasive techniques may provide a convenient alternative to current invasive methods but their precision is lacking. We evaluated the accuracy of “LabPatch”, a non-invasive continuous glucose monitoring system that uses micropipette technology to sip interstitial fluid in comparison to YSI® (laboratory reference glucose analyzer) and 2 glucose meters (Onetouch Verio® and Freestyle Lite®) in 30 insulin-treated patients with diabetes at multiple points over 6 hours. LabPatch glucose readings significantly correlated with those of YSI (R-square=0.23, p<0.0001). Moreover, 85.69% of LabPatch glucose readings were within zones A and B of the Clarke Error Grid albeit B>A. LabPatch had an absolute relative difference (ARD) of 35.5% compared with YSI indicating wide variation in glucose readings. For glucose values between 70-180 mg/dL, LabPatch readings were within +/-15% of YSI values with a lower one-sided 95 % confidence bound of 75.25%. Estimated average glucose value (eAGV) were the closest between LabPatch and YSI than between either of the 2 glucose meters and YSI. We conclude that first-generation LabPatch Precision technology has potential to identify glucose trends in situations that require close monitoring of diabetes over shorter intervals such as gestational diabetes, pre-pregnancy planning and patients preparing for elective surgery. Additionally, LabPatch has the potential to be used for diabetes screening due to its non-invasive nature. Larger sample size and more precision of manufacturing technology may make it a valid non-invasive and wireless glucose monitor. Disclosure S. Tomah: Stock/Shareholder; Self; Amarin Corporation. A.H. Eldib: None. M. Tasabehji: None. V. Bhatia: None. H. Gardner: None. O. Hamdy: Consultant; Self; Abbott, AstraZeneca, Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Healthimation, LLC. Funding Cambridge Medical Technologies, LLC

Sensor Monitoring of Physical Activity to Improve Glucose Management in Diabetic Patients: A Review.

Diabetic individuals need to tightly control their blood glucose concentration. Several methods have been developed for this purpose, such as the finger-prick or continuous glucose monitoring systems (CGMs). However, these methods present the disadvantage of being invasive. Moreover, CGMs have limited accuracy, notably to detect hypoglycemia. It is also known that physical exercise, and even daily activity, disrupt glucose dynamics and can generate problems with blood glucose regulation during and after exercise. In order to deal with these challenges, devices for monitoring patients’ physical activity are currently under development. This review focuses on non-invasive sensors using physiological parameters related to physical exercise that were used to improve glucose monitoring in type 1 diabetes (T1DM) patients. These devices are promising for diabetes management. Indeed they permit to estimate glucose concentration either based solely on physical activity parameters or in conjunction with CGM or non-invasive CGM (NI-CGM) systems. In these last cases, the vital signals are used to modulate glucose estimations provided by the CGM and NI-CGM devices. Finally, this review indicates possible limitations of these new biosensors and outlines directions for future technologic developments.

Non-invasive continuous glucose monitoring: improved accuracy of point and trend estimates of the Multisensor system

Non-invasive continuous glucose monitoring (NI-CGM) sensors are still at an early stage of development, but, in the near future, they could become particularly appealing in diabetes management. Solianis Monitoring AG (Zurich, Switzerland) has proposed an approach for NI-CGM based on a multi-sensor concept, embedding primarily dielectric spectroscopy and optical sensors. This concept requires a mathematical model able to estimate glucose levels from the 150 channels directly measured through the Multisensor. A static multivariate linear regression model (with order and parameters common to the entire population of subjects) was proposed for such a scope (Caduff et al., Biosens Bioelectron 26:3794-3800, 2011). The aim of this work is to evaluate the accuracy in the estimation of glucose levels and trends that the NI-CGM Multisensor platform can achieve by exploiting different techniques for model identification, namely, ordinary least squares, subset variable selection, partial least squares and least absolute shrinkage and selection operator (LASSO). Data collected in human beings monitored for a total of 45 study days were used for model identification and model test. Several metrics of standard use in the diabetes scientific community to measure point and clinical accuracy of glucose sensors were used to assess the models. Results indicate that the LASSO technique is superior to the others shrinking many channel weights to zero thus leading to smoother glucose profiles and resulting in a more robust model to possible artifacts in the Multisensor data. Although, as expected, the performance of the NI-CGM system with the LASSO model is not yet comparable with that of enzyme-based needle glucose sensors, glucose trends are satisfactorily estimated. Considering the non-invasive nature of the multi-sensor platform, this result can have an immediate impact in the current clinical practice, e.g., to integrate sparse self-monitoring of blood glucose data with an indication of the glucose trend to aid the diabetic patient in dealing with, or even preventing in the short time scale, the threats of critical events such as hypoglycaemia.

Minimally-Invasive and Non-Invasive Continuous Glucose Monitoring Systems: Indications, Advantages, Limitations and Clinical Aspects

Accurate and reliable devices sensing glucose on a (near)-continuous basis may facilitate specific therapeutic adjustments that need to be made to avoid hypo- and hyperglycaemic excursions, thereby improving metabolic control. Current continuous glucose monitoring (CGM) systems indicate the glucose level, the direction and magnitude of change of glucose levels, and can be used to assess glycaemic variability. In addition, real-time CGM sensors can serve as a tool to predict impending glucose excursions, thereby providing alarm signals of hypo- and hyperglycaemic values warning the patient to take preventative actions. Quality of life may also improve by using CGM via reducing the fear of hypoglycaemia. Particularly patients with brittle diabetes, hypoglycaemia unawareness, gastroparesis, pregnant women, or pump users, who are motivated to participate in their diabetes care and are technologically adept, may benefit from CGM. However, to successfully implement CGM in daily practice, these devices must be accurate and reliable, and one must be aware of the limitations of current CGM systems, that originate from physiological and technical aspects. Whether CGM succeeds in improving metabolic control, reducing hypoglycaemic episodes, and improving quality of life in the majority of patients remains to be proven. Should this be the case, real-time CGM may reduce chronic diabetic complications, and avoid hospitalisations, thereby reducing health care costs. In this article we will review indications, advantages, limitations, clinical and technical aspects of current minimally-invasive and non-invasive CGM sensors.

First human experiments with a novel non-invasive, non-optical continuous glucose monitoring system

This paper describes a non-invasive continuous glucose monitoring system based on impedance spectroscopy. Changes in the glucose concentrations can be monitored by varying the frequency in the radio band over a range, optimised to measure the impact of glucose on the impedance pattern. A number of clinical-experimental studies (hyperglycaemic excursions) were performed with healthy subjects in order to prove the applicability of this approach. The sensor used in these experiments is the size of a wristwatch and holds an open resonant circuit coupled to the skin and a circuit, performing an impedance measurement. In most cases, the experiments showed a good correlation between changes in blood glucose and the sensor recordings. A detailed description of the trials is presented. The results of this first series of experiments can be considered as a proof of concept for this novel non-invasive monitoring approach. Nevertheless, partly due to the indirect measurement, a considerable number of questions remain to be clarified.