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Microdialysis-coupled enzymatic microreactor for in vivo glucose monitoring in rats.
Anal Chem. 2013 Nov 19; 85(22):10949-55.AC

Abstract

Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemic control and to prevent long-term complications. However, current CGM devices need further miniaturization and improved functional performance. We have coupled a previously described microfluidic chip with enzymatic microreactor (EMR) to a microdialysis probe and evaluated the performance of this system for monitoring subcutaneous glucose concentration in rats. Nanoliter volumes of microdialysis sample are efficiently reacted with continuously supplied glucose oxidase (GOx) solution in the EMR. The hydrogen peroxide produced is amperometrically detected at a (polypyrrole (PPy)-protected) thin-film Pt electrode. Subcutaneous glucose concentration was continuously monitored in anesthetized rats in response to intravenous injections of 20% glucose (w/v), 5 U/kg insulin, or saline as a control. In vitro evaluation showed a linear range of 2.1-20.6 mM and a sensitivity of 7.8 ± 1.0 nA/mM (n = 6). The physical lag time between microdialysis and the analytical signal was approximately 18 min. The baseline concentration of blood glucose was 10.2 ± 2.3 mM. After administering glucose to the rats, glucose levels increased by about 2 mM to 12.1 ± 2.3 mM in blood and 11.9 ± 1.5 mM in subcutaneous interstitial fluid (ISF). After insulin administration, glucose levels decreased by about 8 mM relative to baseline to 2.1 ± 0.6 mM in blood and 2.1 ± 0.9 mM in ISF. A microfluidic device with integrated chaotic mixer and EMR has been successfully combined with subcutaneous microdialysis to continuously monitor glucose in rats. This proof-of-principle demonstrates the feasibility of improved miniaturization in CGM based on microfluidics.

Authors+Show Affiliations

Biomonitoring and Sensoring, Groningen Research Institute of Pharmacy, University of Groningen , Antonius Deusinglaan 1, P.O. Box 196, 9700 AD Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24199633

Citation

Moon, Byeong-Ui, et al. "Microdialysis-coupled Enzymatic Microreactor for in Vivo Glucose Monitoring in Rats." Analytical Chemistry, vol. 85, no. 22, 2013, pp. 10949-55.
Moon BU, de Vries MG, Cordeiro CA, et al. Microdialysis-coupled enzymatic microreactor for in vivo glucose monitoring in rats. Anal Chem. 2013;85(22):10949-55.
Moon, B. U., de Vries, M. G., Cordeiro, C. A., Westerink, B. H., & Verpoorte, E. (2013). Microdialysis-coupled enzymatic microreactor for in vivo glucose monitoring in rats. Analytical Chemistry, 85(22), 10949-55. https://doi.org/10.1021/ac402414m
Moon BU, et al. Microdialysis-coupled Enzymatic Microreactor for in Vivo Glucose Monitoring in Rats. Anal Chem. 2013 Nov 19;85(22):10949-55. PubMed PMID: 24199633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microdialysis-coupled enzymatic microreactor for in vivo glucose monitoring in rats. AU - Moon,Byeong-Ui, AU - de Vries,Martin G, AU - Cordeiro,Carlos A, AU - Westerink,Ben H C, AU - Verpoorte,Elisabeth, Y1 - 2013/11/07/ PY - 2013/11/9/entrez PY - 2013/11/10/pubmed PY - 2014/7/9/medline SP - 10949 EP - 55 JF - Analytical chemistry JO - Anal Chem VL - 85 IS - 22 N2 - Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemic control and to prevent long-term complications. However, current CGM devices need further miniaturization and improved functional performance. We have coupled a previously described microfluidic chip with enzymatic microreactor (EMR) to a microdialysis probe and evaluated the performance of this system for monitoring subcutaneous glucose concentration in rats. Nanoliter volumes of microdialysis sample are efficiently reacted with continuously supplied glucose oxidase (GOx) solution in the EMR. The hydrogen peroxide produced is amperometrically detected at a (polypyrrole (PPy)-protected) thin-film Pt electrode. Subcutaneous glucose concentration was continuously monitored in anesthetized rats in response to intravenous injections of 20% glucose (w/v), 5 U/kg insulin, or saline as a control. In vitro evaluation showed a linear range of 2.1-20.6 mM and a sensitivity of 7.8 ± 1.0 nA/mM (n = 6). The physical lag time between microdialysis and the analytical signal was approximately 18 min. The baseline concentration of blood glucose was 10.2 ± 2.3 mM. After administering glucose to the rats, glucose levels increased by about 2 mM to 12.1 ± 2.3 mM in blood and 11.9 ± 1.5 mM in subcutaneous interstitial fluid (ISF). After insulin administration, glucose levels decreased by about 8 mM relative to baseline to 2.1 ± 0.6 mM in blood and 2.1 ± 0.9 mM in ISF. A microfluidic device with integrated chaotic mixer and EMR has been successfully combined with subcutaneous microdialysis to continuously monitor glucose in rats. This proof-of-principle demonstrates the feasibility of improved miniaturization in CGM based on microfluidics. SN - 1520-6882 UR - https://www.unboundmedicine.com/medline/citation/24199633/Microdialysis_coupled_enzymatic_microreactor_for_in_vivo_glucose_monitoring_in_rats_ L2 - https://doi.org/10.1021/ac402414m DB - PRIME DP - Unbound Medicine ER -