Glucose Monitoring In Interstitial Fluid Research Articles

Wearable hollow microneedle sensing patches for the transdermal electrochemical monitoring of glucose

According to the World Health Organization, about 422 million people worldwide have diabetes, with 1.5 million deaths directly attributed each year. Therefore, there is still a need to effectively monitor glucose in diabetic patients for proper management. Recently, wearable patches based on microneedle (MN) sensors provide minimally invasive analysis of glucose through the interstitial fluid (ISF) while exhibiting excellent correlation with blood glucose. Despite many advances in wearable electrochemical sensors, long-term stability and continuous monitoring remain unsolved challenges. Herein, we present a highly stable electrochemical biosensor based on a redox mediator bilayer consisting of Prussian blue and iron-nickel hexacyanoferrate to increase the long-term stability of the readout coupled with a hollow MN array as a sampling unit for ISF uptake. First, the enzymatic biosensor is developed by using affordable screen-printed electrodes (SPE) and optimized for long-term stability fitting the physiological range of glucose in ISF (i.e., 2.5–22.5 mM). In parallel, the MN array is assessed for minimally invasive piercing of the skin. Subsequently, the biosensor is integrated with the MN array leaving a microfluidic spacer that works as the electrochemical cell. Interestingly, a microfluidic channel connects the cell with an external syringe to actively and rapidly withdraw ISF toward the cell. Finally, the robust MN sensing patch is characterized during in vitro and ex vivo tests. Overall, affordable wearable MN-based patches for the continuous monitoring of glucose in ISF are providing an advent in wearable devices for rapid and life-threatening decision-making processes.

Nonenzymatic Electrochemical Sensor for Wearable Interstitial Fluid Glucose Monitoring

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

Porous Platinum Black-Coated Minimally Invasive Microneedles for Non-Enzymatic Continuous Glucose Monitoring in Interstitial Fluid.

Individuals with diabetes can benefit considerably from continuous blood glucose monitoring. To address this challenge, a proof-of-concept was performed for continuous glucose monitoring (CGM) based on an enzymeless porous nanomaterial (pNM)-modified microneedle electrode array (MNEA). The pNM sensing layer was electrochemically deposited on MNs by applying a fixed negative current of −2.5 mA cm˗2 for 400 s. The pNM-modified MNEA was packed using a biocompatible Nafion ionomer. The fabricated MNEAs were 600 × 100 × 150 µm in height, width, and thickness, respectively. The surfaces of the modified MNs were characterized by scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The fabricated MNEAs showed a wide dynamic range (1–30 mM) in phosphate-buffered saline (PBS) and in artificial interstitial fluid (ISF), with good sensitivities (PBS: 1.792 ± 0.25 µA mM−1 cm−2, ISF: 0.957 ± 0.14 µA mM−1 cm−2) and low detection limits (PBS: 7.2 µM, ISF: 22 µM). The sensor also showed high stability (loss of 3.5% at the end of 16 days), selectivity, and reproducibility (Relative standard deviations (RSD) of 1.64% and 0.70% for intra- and inter-assay, respectively) and a good response time (2 s) with great glucose recovery rates in ISF (98.7–102%).

EFFECT OF USING THE NIGHTSCOUT SYSTEM ON METABOLIC CONTROL, SAFETY, AND INCIDENCE OF COMPLICATIONS IN PATIENTS WITH DIABETES MELLITUS

Introduction: The Nightscout system is a free Do It Yourself solution. This system appeared in Poland in 2016. The concept of the project is to provide insight into measurements from the system of continuous glucose monitoring in interstitial fluid by authorized persons. The aim: The study was carried out to assess the functionality of the Nightscout system and its effect onmetabolic control, safety and the incidence of complications in patients with type 1 diabetes mellitus. Material and methods:The study comprised 98 patients with type 1 diabetes. The study was conducted online using an anonymous questionnaire targeted at members of the "Nightscout Polska (Poland)" group on the Facebook. Results: Severe hypoglycaemic episodes with loss of consciousness were more frequent before using the Nightscout system and were reported by 3 adults (1-2 episodes). No severe hypoglycaemic episodes were reported when using the Nightscout system. The number of ketoacidosis episodes was reduced from 5 before using the Nightscout system to 2 episodes during the use of the system in children, and from 3 to 0 episodes in adults. Levels of glycated haemoglobin were lower in patients using the Nightscout system, both compared to control groups and values before the use it. In people using the Nightscout system glycated hemoglobin values were lower than their values before using this system. It was also shown that people using the Nightscout system had lower glycated hemoglobin than people from the control group. Conclusions: Using the Nightscout system can positively affect the safety of insulin therapy and the treatment process of type 1 diabetes. The Nightscout system can be an improvement of the system of continuous glucose monitoring in interstitial fluid.

The Nightscout system - description of the system and its evaluation in scientific publications.

Nightscout is a non-commercial Do-It-Yourself (DIY) system, developed in 2014 by the parents of children with type 1 diabetes. In Poland it has been available and supported since 2016. The Nightscout system is not an officially registered solution and patients use it at their own responsibility. The idea of the project is to give authorized users online access to data on continuous glucose monitoring in interstitial fluid. Data are stored on external servers. Glucose data can be read on any number of devices with access to the Internet. This article describes the Nightscout system - required components, operating costs, and other usage options. It also presents the current evaluation of the Nightscout system in scientific publications.

Minimally Invasive Enzyme Microprobes: An Alternative Approach for Continuous Glucose Monitoring

Continuous glucose monitoring has been shown to improve glycemia in diabetes.1,2 To minimize the pain, inconvenience, and discomfort associated with long-term implanted sensors, minimally invasive technologies are being developed, including microneedles that remove small volumes of subcutaneous interstitial fluid (ISF).3 We describe here an alternative approach for continuous monitoring of glucose in ISF that involves using solid microprobes that access the interstitium in a minimally invasive and less painful manner than using a lancet to draw capillary blood. The glucose sensor is a small (∼1 cm2) wearable patch covered with arrays of solid microprobes, which penetrate the stratum corneum and monitor glucose in ISF within the epidermis. Unlike microneedles, solid microprobes are not susceptible to clogging and their minimally invasive nature may be less traumatic than existing subcutaneous sensors, reducing the risk of sensor drift and protein adsorption that degrades performance.4,5 The microprobes were made by photolithography using backside illumination6 adapted to create 500–750 mm long structures with tip diameters of 10 mm. Sensitivity to glucose was achieved by assembling glucose oxidase (GOx; EC 1.1.3.4) on the gold-coated microprobes using 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling followed by a Nafion membrane incorporating tetrathiafulvalene (TTF) as an electron transfer mediator. In vitro studies with these devices have demonstrated that they perform well in the clinically relevant range (2–20 mM; Figure 1), with a linear response to increasing glucose and measured currents in the microampere domain. Figure 1 (A) Scanning electron microscope image showing 600 μm high microprobe array. (B) Calibration of TTF/GOx-modified gold microprobes performed in 0.1 M phosphate-buffered saline pH 7.4 background solution; each step represents an increase of 2 mM ... Data are presented for glucose measurement, but the platform may be employed with other enzymes such as lactate oxidase or beta-hydroxybutyrate dehydrogenase. It is also possible to partition the microprobe array and immobilize different enzymes across multiple subarrays for continuous multianalyte sensing. Partitioning may also allow multiple sensors to be used in a “voting” system for the same analyte, thus improving sensor reliability.

Continuous glucose monitoring in interstitial fluid using glucose oxidase-based sensor compared to established blood glucose measurement in rats

Glucose monitoring is of importance for success of complex therapeutic interventions in diabetic patients. Its impact on treatment and glycemic control is demonstrated in large clinical trials. Up to eight blood glucose measurements per day are recommended. Notwithstanding, a substantial number of diabetic patients cannot or will not monitor their blood glucose appropriately. Considerable progress in control of disturbed metabolism in diabetic patients can be expected by continuous glucose monitoring. The aim of the study was to evaluate the performance of a new amperometric glucose oxidase-based glucose sensor in vitro and in vivo after subcutaneous implantation into rats. For in vitro testing current output of sensors was measured by exposure to increasing and decreasing glucose concentrations up to 472 mg dL −1 over a time period of 7 days. After subcutaneous implantation of sensors into interscapular region of male rats glucose in interstitial fluid was evaluated and compared to glucose in arterial blood up to 7 days. Hyper- and hypoglycaemia were induced by intravenous application of glucose and insulin, respectively. Current of each implanted sensor was converted into glucose concentration using the first blood glucose measurement only. A change of current with glucose of 0.35 nA mg −1 dL −1 indicates high sensitivity of the sensor in vitro. The response time (90% of steady state) was calculated by approximately 60 s. Test strips for blood glucose measurement as reference for sensor readings was found as an appropriate and rapidly available method in rats by comparison with established hexokinase method in an automated lab analyzer with limits of agreement of +32.8 and −25.7 mg dL −1 in Bland-Altman analysis. In normo- and hypoglycaemic range sensor readings in interstitial fluid correlated well with blood glucose measurements whereas hyperglycaemia was not reflected by the sensor completely when blood glucose was changing rapidly. The data given characterize a sensor with high sensitivity, long term stability and short response time. A single calibration of the sensor is required only in measurement periods up to 7 days. The findings demonstrate that the sensor is a highly promising candidate for assessment in humans.