Optical biosensor optimized for continuous in-line glucose monitoring in animal cell culture

Biosensors for continuous glucose monitoring in bioreactors could provide a valuable tool for optimizing culture conditions in biotechnological applications. We have developed an optical biosensor for long-term continuous glucose monitoring and demonstrated a tight glucose level control during cell...

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Veröffentlicht in:Analytical and bioanalytical chemistry 2017-09, Vol.409 (24), p.5711-5721
Hauptverfasser: Tric, Mircea, Lederle, Mario, Neuner, Lisa, Dolgowjasow, Igor, Wiedemann, Philipp, Wölfl, Stefan, Werner, Tobias
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container_issue 24
container_start_page 5711
container_title Analytical and bioanalytical chemistry
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creator Tric, Mircea
Lederle, Mario
Neuner, Lisa
Dolgowjasow, Igor
Wiedemann, Philipp
Wölfl, Stefan
Werner, Tobias
description Biosensors for continuous glucose monitoring in bioreactors could provide a valuable tool for optimizing culture conditions in biotechnological applications. We have developed an optical biosensor for long-term continuous glucose monitoring and demonstrated a tight glucose level control during cell culture in disposable bioreactors. The in-line sensor is based on a commercially available oxygen sensor that is coated with cross-linked glucose oxidase (GOD). The dynamic range of the sensor was tuned by a hydrophilic perforated diffusion membrane with an optimized permeability for glucose and oxygen. The biosensor was thoroughly characterized by experimental data and numerical simulations, which enabled insights into the internal concentration profile of the deactivating by-product hydrogen peroxide. The simulations were carried out with a one-dimensional biosensor model and revealed that, in addition to the internal hydrogen peroxide concentration, the turnover rate of the enzyme GOD plays a crucial role for biosensor stability. In the light of this finding, the glucose sensor was optimized to reach a long functional stability (>52 days) under continuous glucose monitoring conditions with a dynamic range of 0–20 mM and a response time of t 90  ≤ 10 min. In addition, we demonstrated that the sensor was sterilizable with beta and UV irradiation and only subjected to minor cross sensitivity to oxygen, when an oxygen reference sensor was applied. Graphical abstract Measuring setup of a glucose biosensor in a shake flask for continuous glucose monitoring in mammalian cell culture
doi_str_mv 10.1007/s00216-017-0511-7
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We have developed an optical biosensor for long-term continuous glucose monitoring and demonstrated a tight glucose level control during cell culture in disposable bioreactors. The in-line sensor is based on a commercially available oxygen sensor that is coated with cross-linked glucose oxidase (GOD). The dynamic range of the sensor was tuned by a hydrophilic perforated diffusion membrane with an optimized permeability for glucose and oxygen. The biosensor was thoroughly characterized by experimental data and numerical simulations, which enabled insights into the internal concentration profile of the deactivating by-product hydrogen peroxide. The simulations were carried out with a one-dimensional biosensor model and revealed that, in addition to the internal hydrogen peroxide concentration, the turnover rate of the enzyme GOD plays a crucial role for biosensor stability. 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ispartof Analytical and bioanalytical chemistry, 2017-09, Vol.409 (24), p.5711-5721
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subjects Analysis
Analytical Chemistry
Beta rays
Biochemistry
Bioreactors
Biosensors
Biotechnology
Blood sugar monitoring
Cell culture
Cells
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Computer simulation
Crosslinking
Darbepoetin alfa
Deactivation
Dextrose
Dynamic range
Dynamic stability
Food Science
Glucose
Glucose monitoring
Glucose oxidase
Hydrogen peroxide
Irradiation
Laboratory Medicine
Mathematical models
Membrane permeability
Monitoring
Monitoring/Environmental Analysis
Oxidases
Oxygen
Oxygen probes
Permeability
Research Paper
Response time
Sensors
Turnover rate
Ultraviolet radiation
title Optical biosensor optimized for continuous in-line glucose monitoring in animal cell culture
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