In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue

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Devices for continuous glucose monitoring (CGM) are currently a major focus of research in the area of diabetes management. It is envisioned that such devices will have the ability to alert a diabetes patient (or the parent or medical care giver of a diabetes patient) of impending hypoglycemic/hyperglycemic events and thereby enable the patient to avoid extreme hypoglycemic/hyperglycemic excursions as well as minimize deviations outside the normal glucose range, thus preventing both life-threatening events and the debilitating complications associated with diabetes. It is anticipated that CGM devices will utilize constant feedback of analytical information from a glucose sensor to activate an insulin delivery pump, thereby ultimately realizing the concept of an artificial pancreas. Depending on whether the CGM device penetrates/breaks the skin and/or the sample is measured extracorporeally, these devices can be categorized as totally invasive, minimally invasive, and noninvasive. In addition, CGM devices are further classified according to the transduction mechanisms used for glucose sensing (i.e., electrochemical, optical, and piezoelectric). However, at present, most of these technologies are plagued by a variety of issues that affect their accuracy and long-term performance. This article presents a critical comparison of existing CGM technologies, highlighting critical issues of device accuracy, foreign body response, calibration, and miniaturization. An outlook on future developments with an emphasis on long-term reliability and performance is also presented.

Section: Continuous Glucose Monitoring Device Size and Miniaturizationmentioning

confidence: 99%

Technologies for Continuous Glucose Monitoring: Current Problems and Future Promises

Vaddiraju

Burgess

Tomazos

et al. 2010

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224

“…25 The current ORS configuration had an overall MARD of 10.5% versus meter, and meal FST MARD 8.1% versus PG. This compares favorably to an independent assessment of three nonredundant electrochemical CGMs on the market (MARDs versus PG: Dexcom G4 Platinum 10.8%, Abbott Freestyle Navigator 12.3%, and Medtronic Enlite 17.9%).…”

Section: Discussionmentioning

confidence: 99%

Feasibility of an Orthogonal Redundant Sensor incorporating Optical plus Redundant Electrochemical Glucose Sensing

McAuley

Dang

Horsburgh

et al. 2016

For people with type 1 diabetes (T1D), matching insulin delivery to their varying insulin requirements is central to maximizing quality of life and minimizing diabetes complications.1,2 In contrast to glucose meters, 3 continuous glucose monitoring (CGM) systems measuring interstitial fluid (ISF) glucose provide near-continuous real-time glucose information. 4 CGM improves glycemia for adults with T1D 5,6 and provides a vital component in artificial pancreas development. 7 However, CGM technology remains less accurate than the most accurate glucose meters, 8 with mean absolute relative differences (MARDs) of current generation CGM between 10 and 18%. 9 To replace fingerstick measurement, and to achieve sufficient functionality for use in an artificial pancreas system, CGM needs improved accuracy and reliability.629982D STXXX10.1177/1932296816629982Journal Abstract Background: Orthogonal redundancy for glucose sensing (multiple sensing elements utilizing distinct methodologies) may enhance performance compared to nonredundant sensors, and to sensors with multiple elements utilizing the same technology (simple redundancy). We compared the performance of a prototype orthogonal redundant sensor (ORS) combining optical fluorescence and redundant electrochemical sensing via a single insertion platform to an electrochemical simple redundant sensor (SRS).Methods: Twenty-one adults with type 1 diabetes wore an ORS and an SRS concurrently for 7 days. Following sensor insertion, and on Day 4 with a standardized meal, frequent venous samples were collected for reference glucose measurement (laboratory [YSI] and meter) over 3 and 4 hours, respectively. Between study visits reference capillary blood glucose testing was undertaken. Sensor data were processed prospectively.Results: ORS mean absolute relative difference (MARD) was (mean ± SD) 10.5 ± 13.2% versus SRS 11.0 ± 10.4% (P = .34). ORS values in Clarke error grid zones A and A+B were 88.1% and 97.6%, respectively, versus SRS 86.4% and 97.8%, respectively (P = .23 and P = .84). ORS Day 1 MARD (10.7 ± 10.7%) was superior to SRS (16.5 ± 13.4%; P < .0001), and comparable to ORS MARD for the week. ORS sensor survival (time-averaged mean) was 92.1% versus SRS 74.4% (P = .10). ORS display time (96.0 ± 5.8%) was equivalent to SRS (95.6 ± 8.9%; P = .87). Conclusions:Combining simple and orthogonal sensor redundancy via a single insertion is feasible, with accuracy comparing favorably to current generation nonredundant sensors. Addition of an optical component potentially improves sensor reliability compared to electrochemical sensing alone. Further improvement in optical sensing performance is required prior to clinical application. 10,11,13 Nonelectrochemical CGM modalities including optical technologies have been explored, 10,11 though none are currently commercially available. One promising optical methodology is fluorescence-based sensing involving reversible competitive binding between a fluorophore-labeled glucose receptor and a glucose analog. Keywords14 Relative to ele...

“…As a cost-effective alternative to mice and rats, rabbits have also been employed due to their increased size (2-6 kg) and available blood volume, which permits the evaluation of multiple sensors for short periods (1-2 days). 18,19 Still, the ability to accommodate multiple implanted sensors in a single animal represents a significant advantage in situations where the performance of one sensor type is compared to that of another, as heterogeneity between individual animals is eliminated.…”

Section: Animal Model Selectionmentioning

confidence: 99%

“…Simply feeding the animal is often not reproducible enough to accomplish this goal. Direct administration of glucose via intraperitoneal (IP) injections 16 or through an intravascular (IV) catheter [18][19]31 results in BG changes of appreciable magnitude. Glucose delivery via an IV catheter, either as a bolus 18,31 (0. )…”

Section: Experimental Considerations and Data Collectionmentioning

confidence: 99%

Preclinical Performance Evaluation of Percutaneous Glucose Biosensors

Soto

2015

The utility of continuous glucose monitoring devices remains limited by an obstinate foreign body response (FBR) that degrades the analytical performance of the in vivo sensor. A number of novel materials that resist or delay the FBR have been proposed as outer, tissue-contacting glucose sensor membranes as a strategy to improve sensor accuracy. Traditionally, researchers have examined the ability of a material to minimize the host response by assessing adsorbed cell morphology and tissue histology. However, these techniques do not adequately predict in vivo glucose sensor function, necessitating sensor performance evaluation in a relevant animal model prior to human testing. Herein, the effects of critical experimental parameters, including the animal model and data processing methods, on the reliability and usefulness of preclinical sensor performance data are considered.Keywords animal model, biocompatibility, blood glucose, blood glucose meter, foreign body response, in vivo glucose sensor