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

Tric, Mircea; Lederle, Mario; Neuner, Lisa; Dolgowjasow, Igor; Wiedemann, Philipp; Wölfl, Stefan; Werner, Tobias

doi:10.1007/s00216-017-0511-7

Cited by 40 publications

(24 citation statements)

References 31 publications

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“…In addition, glucose monitoring has been widely applied in the food industry as a quality control and safety tool [12]. Another application is cell culture: Because glucose is a primary carbon source for proliferating mammalian cells, glucose quantification provides valuable information on metabolism [13][14][15]. Methods for glucose monitoring in cell culture include Raman spectroscopy, liquid chromatography, and other spectroscopic techniques; in general, these techniques are expensive and time-consuming [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Screen-Printed Glucose Sensors Modified with Cellulose Nanocrystals (CNCs) for Cell Culture Monitoring

et al. 2020

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Glucose sensors are potentially useful tools for monitoring the glucose concentration in cell culture medium. Here, we present a new, low-cost, and reproducible sensor based on a cellulose-based material, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized-cellulose nanocrystals (CNCs). This novel biocompatible and inert nanomaterial is employed as a polymeric matrix to immobilize and stabilize glucose oxidase in the fabrication of a reproducible, operationally stable, highly selective, cost-effective, screen-printed glucose sensor. The sensors have a linear range of 0.1–2 mM (R2 = 0.999) and a sensitivity of 5.7 ± 0.3 µA cm−2∙mM−1. The limit of detection is 0.004 mM, and the limit of quantification is 0.015 mM. The sensor maintains 92.3 % of the initial current response after 30 consecutive measurements in a 1 mM standard glucose solution, and has a shelf life of 1 month while maintaining high selectivity. We demonstrate the practical application of the sensor by monitoring the glucose consumption of a fibroblast cell culture over the course of several days.

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Section: Introductionmentioning

confidence: 99%

Screen-Printed Glucose Sensors Modified with Cellulose Nanocrystals (CNCs) for Cell Culture Monitoring

et al. 2020

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“…Furthermore, an optical fiber sensor for glucose was developed by modifying the surface of a commercially available oxygen sensor (OXY-4 mini ® PreSens, Regensburg, Germany) with crosslinked glucose oxidase. The results of the sensor integrated into the BR showed good durability of the sensor for a period of 52 days, linear characteristics up to 20 mM and the sensor's response time lower than 10 min [248].…”

Section: Electrochemical Biosensors For Nutrients and Metabolitesmentioning

confidence: 96%

“…Different principles of glucose sensors based on electrochemical and optical detection were recently proposed in the literature for application in BRs [247][248][249][250][251][252][253][254][255][256][257]. The innovative combination of droplet microfluidics and optical detection methods was proposed by Adams and coworkers for rapid measurements of glucose levels in the µBR systems [247].…”

Section: Electrochemical Biosensors For Nutrients and Metabolitesmentioning

confidence: 99%

Cultivating Multidisciplinarity: Manufacturing and Sensing Challenges in Cultured Meat Production

Djisalov

Knežić

Podunavac

et al. 2021

Biology

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Meat cultivation via cellular agriculture holds great promise as a method for future food production. In theory, it is an ideal way of meat production, humane to the animals and sustainable for the environment, while keeping the same taste and nutritional values as traditional meat and having additional benefits such as controlled fat content and absence of antibiotics and hormones used in the traditional meat industry. However, in practice, there is still a number of challenges, such as those associated with the upscale of cultured meat (CM). CM food safety monitoring is a necessary factor when envisioning both the regulatory compliance and consumer acceptance. To achieve this, a multidisciplinary approach is necessary. This includes extensive development of the sensitive and specific analytical devices i.e., sensors to enable reliable food safety monitoring throughout the whole future food supply chain. In addition, advanced monitoring options can help in the further optimization of the meat cultivation which may reduce the currently still high costs of production. This review presents an overview of the sensor monitoring options for the most relevant parameters of importance for meat cultivation. Examples of the various types of sensors that can potentially be used in CM production are provided and the options for their integration into bioreactors, as well as suggestions on further improvements and more advanced integration approaches. In favor of the multidisciplinary approach, we also include an overview of the bioreactor types, scaffolding options as well as imaging techniques relevant for CM research. Furthermore, we briefly present the current status of the CM research and related regulation, societal aspects and challenges to its upscaling and commercialization.

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“…We previously developed an optical glucose biosensor capable of in‐line glucose measurements [ 9 ] and its manufacture was described in detail. [ 10 ] The ease of handling and disposable feature of this sensor enables integration into various cultivation systems for single‐use glucose monitoring.…”

Section: Introductionmentioning

confidence: 99%

Continuous optical in‐line glucose monitoring and control in CHO cultures contributes to enhanced metabolic efficiency while maintaining darbepoetin alfa product quality

Lederle

Tric

Roth

et al. 2021

Biotechnology Journal

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Great efforts are directed towards improving productivity, consistency and quality of biopharmaceutical processes and products. One particular area is the development of new sensors for continuous monitoring of critical bioprocess parameters by using online or in‐line monitoring systems. Recently, we developed a glucose biosensor applicable in single‐use, in‐line and long‐term glucose monitoring in mammalian cell bioreactors. Now, we integrated this sensor in an automated glucose monitoring and feeding system capable of maintaining stable glucose levels, even at very low concentrations. We compared this fed‐batch feedback system at both low (< 1 mM) and high (40 mM) glucose levels with traditional batch culture methods, focusing on glycosylation and glycation of the recombinant protein darbepoetin alfa (DPO) produced by a CHO cell line. We evaluated cell growth, metabolite and product concentration under different glucose feeding strategies and show that continuous feeding, even at low glucose levels, has no harmful effects on DPO quantity and quality. We conclude that our system is capable of tight glucose level control throughout extended bioprocesses and has the potential to improve performance where constant maintenance of glucose levels is critical.

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

Cited by 40 publications

References 31 publications

Screen-Printed Glucose Sensors Modified with Cellulose Nanocrystals (CNCs) for Cell Culture Monitoring

Screen-Printed Glucose Sensors Modified with Cellulose Nanocrystals (CNCs) for Cell Culture Monitoring

Cultivating Multidisciplinarity: Manufacturing and Sensing Challenges in Cultured Meat Production

Continuous optical in‐line glucose monitoring and control in CHO cultures contributes to enhanced metabolic efficiency while maintaining darbepoetin alfa product quality

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