Preclinical In Vivo Study of a Fluorescence Affinity Sensor for Short-Term Continuous Glucose Monitoring in a Small and Large Animal Model

Dutt-Ballerstadt, Ralph; Evans, Colton; Gowda, Ashok; McNichols, Roger J.

doi:10.1089/dia.2008.0033

Cited by 6 publications

(9 citation statements)

References 36 publications

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“…31 Our main conclusion is that the very low dose of ConA used in sensor implants in the adipose and subcutaneous tissue is safe. Various other in vivo studies in small and large animals were performed 20,32 that further demonstrated safety and feasibility of our technology for continuous glucose sensing under in vivo conditions. The goal of this study was to investigate the performance, overall mechanical robustness, safety, and comfort level of the FAS for glucose in a pilot study under acute in vivo conditions (4 h).…”

Section: Introductionmentioning

confidence: 78%

A Human Pilot Study of the Fluorescence Affinity Sensor for Continuous Glucose Monitoring in Diabetes

Dutt-Ballerstadt

Evans

Pillai

et al. 2012

J Diabetes Sci Technol

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We report results of a pilot clinical study of a subcutaneous fluorescence affinity sensor (FAS) for continuous glucose monitoring conducted in people with type 1 and type 2 diabetes. The device was assessed based on performance, safety, and comfort level under acute conditions (4 h). Research Design and Methods:A second-generation FAS (BioTex Inc., Houston, TX) was subcutaneously implanted in the abdomens of 12 people with diabetes, and its acute performance to excursions in blood glucose was monitored over 4 h. After 30-60 min the subjects, who all had fasting blood glucose levels of less than 200 mg/dl, received a glucose bolus of 75 g/liter dextrose by oral administration. Capillary blood glucose samples were obtained from the finger tip. The FAS data were retrospectively evaluated by linear least squares regression analysis and by the Clarke error grid method. Comfort levels during insertion, operation, and sensor removal were scored by the subjects using an analog pain scale. Results:After retrospective calibration of 17 sensors implanted in 12 subjects, error grid analysis showed 97% of the paired values in zones A and B and 1.5% in zones C and D, respectively. The mean absolute relative error between sensor signal and capillary blood glucose was 13% [±15% standard deviation (SD), 100-350 mg/dl] with an average correlation coefficient of 0.84 (±0.24 SD). The actual average "warm-up" time for the FAS readings, at which highest correlation with glucose readings was determined, was 65 (±32 SD) min. Mean time lag was 4 (±5 SD) min during the initial operational hours. Pain levels during insertion and operation were modest. Conclusions:The in vivo performance of the FAS demonstrates feasibility of the fluorescence affinity technology to determine blood glucose excursions accurately and safely under acute dynamic conditions in humans with type 1 and type 2 diabetes. Specific engineering challenges to sensor and instrumentation robustness remain. Further studies will be required to validate its promising performance over longer implantation duration (5-7 days) in people with diabetes.

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Section: Introductionmentioning

confidence: 78%

A Human Pilot Study of the Fluorescence Affinity Sensor for Continuous Glucose Monitoring in Diabetes

Dutt-Ballerstadt

Evans

Pillai

et al. 2012

J Diabetes Sci Technol

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“…Several receptors for glucose have been investigated for fluorescence-based glucose sensing 4 including boronic acid derivatives, 4 concanavalin A 4,17,19,21 and other lectins, 8 glucose oxidase 4,13,16 and bacterial glucose/galactose-binding protein (GBP).…”

Section: 20mentioning

confidence: 99%

A fluorescence lifetime-based fibre-optic glucose sensor using glucose/galactose-binding protein

Saxl

Khan

Ferla

et al. 2011

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This version is available at https://strathprints.strath.ac.uk/30189/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Alternative, non-electrochemistry-based technologies for continuous glucose monitoring are needed for eventual use in diabetes mellitus. As part of a programme investigating fluorescent glucose sensors, we have developed fibre-optic biosensors using glucose/galactose binding protein (GBP) labelled with the environmentally sensitive fluorophore, Badan. GBP-Badan was attached via an oligohistidine-tag to the surface of Ni-nitrilotriacetic acid (NTA)-functionalized agarose or polystyrene beads. Fluorescence lifetime increased in response to glucose, observed by fluorescence lifetime imaging microscopy of the GBP-Badan-beads. Either GBP-Badan agarose or polystyrene beads were loaded into a porous chamber at the end of a multimode optical fibre. Fluorescence lifetime responses were recorded using pulsed laser excitation, high speed photodiode detection and time-correlated singlephoton counting. The maximal response was at 100 mM glucose with an apparent K d of 13 mM (agarose) and 20 mM (polystyrene), and good working-day stability was demonstrated. We conclude that fluorescence lifetime fibre-optic glucose sensors based on GBP-Badan are suitable for development as clinical glucose monitors.

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“…Few attempts to develop fluorescent sensors were also executed during the past years. Among them, Biotex ( http://www.biotexmedical.com/index.html ) reported on developing a fiber-enclosed ConA-dextran FRET-based sensor [ 10 – 12 ]. However, the accuracy of the device (tested in rats and pigs) was moderate, and the development of an improved device was, apparently, ceased.…”

Section: Introductionmentioning

confidence: 99%

Generation of an immortalized mesenchymal stem cell line producing a secreted biosensor protein for glucose monitoring

Siska

Weisman²,

Romano³

et al. 2017

PLoS ONE

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Diabetes is a chronic disease characterized by high levels of blood glucose. Diabetic patients should normalize these levels in order to avoid short and long term clinical complications. Presently, blood glucose monitoring is dependent on frequent finger pricking and enzyme based systems that analyze the drawn blood. Continuous blood glucose monitors are already on market but suffer from technical problems, inaccuracy and short operation time. A novel approach for continuous glucose monitoring is the development of implantable cell-based biosensors that emit light signals corresponding to glucose concentrations. Such devices use genetically modified cells expressing chimeric genes with glucose binding properties. MSCs are good candidates as carrier cells, as they can be genetically engineered and expanded into large numbers. They also possess immunomodulatory properties that, by reducing local inflammation, may assist long operation time.Here, we generated a novel immortalized human MSC line co-expressing hTERT and a secreted glucose biosensor transgene using the Sleeping Beauty transposon technology. Genetically modified hMSCs retained their mesenchymal characteristics. Stable transgene expression was validated biochemically. Increased activity of hTERT was accompanied by elevated and constant level of stem cell pluripotency markers and subsequently, by MSC immortalization. Furthermore, these cells efficiently suppressed PBMC proliferation in MLR transwell assays, indicating that they possess immunomodulatory properties. Finally, biosensor protein produced by MSCs was used to quantify glucose in cell-free assays. Our results indicate that our immortalized MSCs are suitable for measuring glucose concentrations in a physiological range. Thus, they are appropriate for incorporation into a cell-based, immune-privileged, glucose-monitoring medical device.

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Preclinical In Vivo Study of a Fluorescence Affinity Sensor for Short-Term Continuous Glucose Monitoring in a Small and Large Animal Model

Abstract: Overall, the fiber-coupled FAS was safe, and its performance during 4-h and 3-day testing compared favorably to the commercially available Medtronic Minimed CGMS, indicating its potential value for diabetes management.

Cited by 6 publications

References 36 publications

A Human Pilot Study of the Fluorescence Affinity Sensor for Continuous Glucose Monitoring in Diabetes

A Human Pilot Study of the Fluorescence Affinity Sensor for Continuous Glucose Monitoring in Diabetes

A fluorescence lifetime-based fibre-optic glucose sensor using glucose/galactose-binding protein

Generation of an immortalized mesenchymal stem cell line producing a secreted biosensor protein for glucose monitoring

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