Subcutaneous Sensor Research Articles

Database testing of a subcutaneous monitor with wireless alarm

Abstract We have tested the accuracy of detection of cardiac arrest in a cardiac event recorder that has the 4x4cm sensor implanted, the recorder external, and the two connected by wireless. Storage and transmission is activated by the patient when symptoms are present or automatically when cardiac arrest is detected, in which case the recorder sounds a loud alarm to alert bystanders. It is the automatic mode that requires database testing of accuracy. Materials We obtained an appropriate database by mapping the chest in 60 ICD patients in sinus rhythm (SR) and induced ventricular fibrillation (VF), and deriving bipolar ECGs from adjacent electrodes located where the electrodes on the subQ sensor would be. (We then implanted the device in 2 dogs and demonstrated the equivalence of ECGs recorded on the skin to subcutaneous ECGs). A blinded selection of 10 of these 60 patients, together with 14 records from the MIT/BIH database, formed a testing set; the others were available for development and training of the detection algorithm. Results In all 60 patients, ECGs from closely-spaced electrodes properly located on the chest appeared suitable for automatic VF detection. Formal testing with the 24-patient database yielded sensitivity and specificity of 100% in detecting VF. Conclusion It appears a 4cm square subcutaneous sensor with electrodes at its corners can reliably monitor cardiac activity, accurately detect the occurrence of cardiac arrest, transmit the ECG to an external receiver, and produce an alarm when a life-threatening arrhythmia is detected.

Model Based Study on Monitoring Ketone Bodies to Improve Safety in Intensive Insulin Therapy

The present study explores new signals (capillary 3betahydroxybutyrate - 3betaOHB) for improving the safety of a closed loop insulin infusion system (external wearable artificial pancreas). Data collected during a clinical trial on diabetic subjects including a period of insulin deprivation were interpreted through mathematical models to simulate the effect of monitoring ketone bodies (capillary 3betaOHB, KB) compared to blood glucose in subjects on Continuous Subcutaneous Insulin Infusion (CSII) treatment. The estimation of model coefficients satisfactorily fits experimental data. The evaluation of dynamic changes of capillary 3betaOHB levels showed a more rapid response than blood glucose. The effect of the combination of monitoring of glucose and ketone bodies can consistently improve the safety and efficacy of the use of a closed loop system for glycemic control in dangerous situations like ketoacidosis. If a subcutaneous glucose-ketone bodies sensor were to become available in the near future it would be a key component of an external artificial pancreas.

Reducing implant-related infections: active release strategies

Despite sterilization and aseptic procedures, bacterial infection remains a major impediment to the utility of medical implants including catheters, artificial prosthetics, and subcutaneous sensors. Indwelling devices are responsible for over half of all nosocomial infections, with an estimate of 1 million cases per year (2004) in the United States alone. Device-associated infections are the result of bacterial adhesion and subsequent biofilm formation at the implantation site. Although useful for relieving associated systemic infections, conventional antibiotic therapies remain ineffective against biofilms. Unfortunately, the lack of a suitable treatment often leaves extraction of the contaminated device as the only viable option for eliminating the biofilm. Much research has focused on developing polymers that resist bacterial adhesion for use as medical device coatings. This tutorial review focuses on coatings that release antimicrobial agents (i.e., active release strategies) for reducing the incidence of implant-associated infection. Following a brief introduction to bacteria, biofilms, and infection, the development and study of coatings that slowly release antimicrobial agents such as antibiotics, silver ions, antibodies, and nitric oxide are covered. The success and limitations of these strategies are highlighted.

Editorial: Symposium on Algorithms for Continuous Glucose Monitoring and Control

Diabetes Technology & TherapeuticsVol. 7, No. 1 Symposium on Algorithms for Continuous Glucose Monitoring and ControlEditorial: Symposium on Algorithms for Continuous Glucose Monitoring and ControlB. Wayne BequetteB. Wayne BequetteSearch for more papers by this authorPublished Online:28 Feb 2005https://doi.org/10.1089/dia.2005.7.1AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Editorial: Symposium on Algorithms for Continuous Glucose Monitoring and Control." , 7(1), pp. 1–2FiguresReferencesRelatedDetailsCited bySimulation Environment to Evaluate Closed-Loop Insulin Delivery Systems in Type 1 Diabetes1 January 2010 | Journal of Diabetes Science and Technology, Vol. 4, No. 1 Volume 7Issue 1Feb 2005 InformationCopyright 2005, Mary Ann Liebert, Inc.To cite this article:B. Wayne Bequette.Editorial: Symposium on Algorithms for Continuous Glucose Monitoring and Control.Diabetes Technology & Therapeutics.Feb 2005.1-2.http://doi.org/10.1089/dia.2005.7.1Published in Volume: 7 Issue 1: February 28, 2005PDF download

Clinical Performance of a Continuous Viscometric Affinity Sensor for Glucose

A viscometric affinity sensor has been developed to measure the interstitial glucose concentration continuously. In a pilot clinical study its performance was assessed under conditions close to everyday life. Additionally, different insertion sites were tested for their suitability to apply subcutaneous glucose sensors. Twelve subjects, 10 of whom with type 1 diabetes, were examined for 8 h. Sensors were applied subcutaneously at the forearm and the abdomen of each subject. Capillary blood glucose references were obtained from the finger tip every 30 min. Retrospective calibration was carried out individually with Deming regression. After retrospective calibration the 95% limits of agreement in the plot of the differences between sensor signals and references versus their means were +/-60 mg/dL. The sensitivity of the sensors remained stable over the entire measuring period, without any significant differences between the sensors at forearm and abdomen. Correcting for the observed time delay of 15 min between references and sensor values the limits of agreements were reduced to +/-38 mg/dL. Furthermore, error grid analysis showed 89.3% of the paired values in zone A and 9.6% in zone B. Only 1.1% were clinically unacceptable (zone D). The performance of the viscometric affinity sensor shows the potential of the measuring principle under in vivo conditions. Forearm and abdomen seem to be similarly well suited for the application of subcutaneous sensors. The signal stability over time and the absence of enzymatic, chemical, or electrode reactions are advantages of the viscometric affinity principle.

Evaluation of a continuous glucose monitoring system in diabetic dogs

The generation of a blood glucose curve is important for assessing the response to insulin therapy in diabetic dogs. Disadvantages of this technique include patient discomfort and the potential for missing transient hypo- or hyperglycaemic episodes. The aim of the current study was to evaluate a continuous glucose monitoring system (CGMS) for use in diabetic dogs. Interstitial fluid glucose concentrations were recorded in 10 diabetic dogs, every five minutes for up to 48 hours, using a subcutaneous sensor attached to the CGMS device. Blood glucose concentrations were measured simultaneously using a glucometer. The correlation between interstitial fluid and blood glucose values was 0.81 (P < 0.01). The largest discrepancies between the two sets of data were seen during the one- to three-hour period following feeding, suggesting that postprandial hyperglycaemia might not be reflected in the interstitial fluid. The authors conclude that the CGMS is a potentially valuable tool in the management of canine diabetic patients.

Determination of plasma glucose during rapid glucose excursions with a subcutaneous glucose sensor.

Continuous glucose monitoring has the potential to improve glucose management and reduce the risk of hypoglycemia in individuals with diabetes. Accurate sensors may also allow the development of a closed-loop insulin delivery system. The purpose of this work was to determine the delay time associated with a subcutaneous glucose sensor during rapidly changing glucose excursions. Subcutaneous glucose sensors (Medtronic MiniMed, Inc., Northridge, CA) were inserted in five healthy men. After a 2-h stabilization period, a 3-h hyperglycemic (approximately 11 mM) clamp was performed followed by a 90-min period in which plasma glucose was allowed to decline to as low as 2.8 mM. Sensors were calibrated using two points (basal and hyperglycemia), and the calibrated sensor glucose measurements were compared with those from a reference analyzer (Beckman Instruments, Fullerton, CA). Response time was estimated from a first-order kinetic model. Plasma glucose levels, determined with the subcutaneous sensor, were highly correlated with those obtained with the reference glucose analyzer (r(2) = 0.91, p < 0.001; mean absolute difference of approximately 8%). The half-time for the sensor response was estimated to be 4.0 +/- 1.0 min. The subcutaneous glucose sensor has the potential to facilitate the detection of hypoglycemia and improve overall glycemic control when used in a real-time monitor. The rapid response should be sufficient to allow a fully automated closed-loop insulin delivery system to be developed based on the subcutaneous sensing site.

Evaluation of conventional blood glucose monitoring as an indicator of integrated glucose values using a continuous subcutaneous sensor.

To use a portable continuous glucose monitoring system (CGMS) to evaluate how well the customary intermittent self-monitoring of blood glucose (SMBG) correlates with integrated values during the surrounding time periods in ambulatory patients with type 1 diabetes. In the study, 18 young patients with type 1 diabetes were monitored with CGMS for up to 72 h, during which they continued to perform the four standard SMBG tests (preprandial and bedtime). Correlations were examined between each of the four standard SMBG tests and the mean CGMS values from defined periods that preceded and followed. We also tested how well a low bedtime SMBG predicted nocturnal hypoglycemia. Strong correlations were found between 1) SMBG at breakfast and the mean CGMS value for the preceding 8 h (r = 0.7514), 2) SMBG at dinner and the CGMS from lunch to dinner (r = 0.7538), 3) SMBG at bedtime and the CGMS from dinner to bedtime (r = 0.8145), and 4) SMBG at bedtime and the CGMS from bedtime to breakfast (r = 0.6463). The remaining correlations were weak and not statistically significant. These correlations seem independent of insulin-delivery method as virtually identical results were obtained when data from patients on conventional versus intensive regimes were separately analyzed. A bedtime SMBG <7 mmol/l did not predict nocturnal hypoglycemia (defined as at least one CGMS value <3). -The breakfast and dinnertime SMBG values are good indicators of integrated glucose values in the time period preceding them, while the bedtime test correlates well with the integrated values both preceding and following it. This information should aid in the meaningful use of SMBG to evaluate glycemic control and make insulin dose adjustments.

Defining the period of recovery of the glucose concentration after its local perturbation by the implantation of a miniature sensor.

At the wound caused by implanting a subcutaneous glucose sensor, the concentration of glucose differs transiently from that in the subcutaneous fluid near non-wounded skin. The period of recovery differs for different wounds and is difficult to predict. A diabetic patient implanting a subcutaneous sensor needs to know whether the transient difference subsided sufficiently for the sensor readings and the sensor's in vivo calibration to be valid. The miniature amperometric glucose sensor has a compound membrane including a layer of glucose oxidase the reaction centers of which are electrically connected to the electrode through a redox polymer; layers excluding interferents and poisons of the electrocatalytic oxidation of glucose; and a layer reducing fouling by components of the biological fluids. We show that the sensor maintains its in vitro sensitivity after its implantation for four hours in the jugular vein and in the peritoneal fluid of the rat. For a diabetic patient who implants the sensor the four-hour period is long enough for the insertion-trauma-caused local perturbation of the glucose concentration to subside and to safely rely on the readings of the implanted sensor.

Covalent surface chemical modification of electrodes for cardiac pacing applications.

We report the covalent surface modification of active-fixation pacemaker electrodes with butanethiol or dodecanethiol self-assembled monolayers (SAMs) using a platinum or gold metal-thiolate bond (i.e., changing the chemical identity of the exposed metal electrode from metal to organic) in such fashion that (a) the surface is organic in functionality with lipophilic physicochemical characteristics, (b) a possible degradation product is gold (I)-alkanethiolate with putative anti-inflammatory actions, and (c) current density/electric field strength is increased. Superior acute and chronic pacing performance with dodecanethiol-modified, gold-coated, platinum-iridium alloy pacemaker electrodes was observed with inferential evidence of reduced inflammation and scar. This approach may have applicability in other areas of bioelectrodes with practical applications in clinical cardiology, surgery, neuroscience, and subcutaneous sensors.

New developments in type 1 (insulin-dependent) diabetes.

The Diabetes Control and Complications Trial has conclusively demonstrated that improved metabolic control leads to reduction in the rate of microvascular complications of diabetes. In order to allow patients to achieve improved metabolic control, much research has focused on improved methods of glucose monitoring and more physiologic ways of insulin delivery. The 2 most promising methods of minimally invasive blood glucose monitoring are the Glucowatch, using the technique of reverse iontophoresis to measure interstitial fluid glucose levels every twenty minutes and an implantable sensor, in which a catheter resembling that used for insulin delivery through a pump is impregnated with glucose oxidase at the tip. This device monitors blood sugars every few minutes, but like a holter monitor, must be downloaded in the physician's office. Still under development are (1) implantable subcutaneous sensors with a high and low blood glucose alarm and (2) sensors in which the patient will be able to download the data using a home PC. Advances in insulin delivery have included the availability of new insulin analogs which more closely simulate endogenous insulin release, with rapid acting analogs simulating the increase in insulin production that normally occurs after meals. Phase III clinical trials are in progress of a long-acting basal insulin without peak actions to simulate the low dose continuous production of the insulin which normally inhibits hepatic glucose production. In addition, use of the insulin pump has increased markedly since publication of the DCCT with the greatest increase being among adolescents. In addition to advances in treatment of diabetes, research has continued on curing the disease using islet cell transplantation and preventing the disease with agents such as insulin (DPT-1 Trial) and nicotinamide (ENDIT). This article provides an overview of recent advances in diabetes management and prevention.

Amperometric biosensors

Over the past 18 months, our understanding of the chemistry and engineering principles of amperometric biosensors, including bioaffinity sensors, has deepened. In addition, several novel amperometric biosensors have been commercialized and progress has been made in the design of subcutaneous sensors, particularly those for glucose.

On line continuous monitoring of subcutaneous tissue glucose in men by combining portable glucosensor with microdialysis.

For the normalisation of blood glucose levels in diabetic patients by feedback controlled insulin delivery, a self-manageable and reliable method for continuous glucose estimation is still not available. By combining a commercially available needle type dialysis probe (molecular cutoff 20,000 Da) with a sensitive glucose sensor, we obtained a device for continuous glucose measurement in dialysate. This device was tested in healthy volunteers during a 75-g oral glucose tolerance test and in Type 2 (non-insulin-dependent) diabetic patients. Venous glucose and subcutaneous sensor signal were followed for 300 min (ten healthy subjects), 21 h (three healthy subjects) or 9 h (seven Type 2 diabetic patients). The recovery of the microdialysis was interindividually different, but after calibration, glucose levels in the dialysate and subcutaneous glucose sensor signal correlated well (r = 0.84-0.95). Under the assumption of a physiologic and technical delay between intravenous and subcutaneous glucose, correlation coefficient between intravenous glucose and subcutaneous sensor signal ranged from 0.60 to 0.93. We conclude that changes in blood glucose could be monitored in the subcutaneous tissue by the microdialysis technique in a continuous on line manner.

In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer

Miniature, amperometric glucose sensors were constructed for implantation in the subcutaneous tissue of normal and insulin-dependent diabetic subjects. To minimise dependence on fluctuating tissue oxygen tension, we employed the technology of mediated electron transfer, with 1,1'-dimethylferrocene acting as the redox shuttle between immobilized glucose oxidase and a platinum base electrode. In 6 normal subjects, the subcutaneous sensor responses mirrored the simultaneously-measured changes in blood glucose concentration after a 75 g oral glucose load and after intravenous injection of 0.15 U/kg short-acting insulin, though increases and decreases in the sensor output were slower than the glycaemic changes. The mean peak delay in sensor response after the oral glucose was 40 min (range 0-45 min) and the delay in the hypoglycaemic nadir was 4 min (range 0-15 min). In 5 insulin-dependent diabetic subjects, spontaneous and induced hypoglycaemia was detectable by the implanted sensor. In addition, marked and frequent oscillations in the sensor current occurred in several normal and diabetic individuals as the blood glucose fell below about 1.9 mmol/l. These oscillations were present in a diabetic subject who had lost adrenergic warning symptoms to hypoglycaemia. Continuous metabolic monitoring in diabetes, particularly the detection of hypoglycaemia, may be possible with implanted sensors based on this technology.