Online analysis of oxygen inside silicon-glass microreactors with integrated optical sensors

Ehgartner, Josef; Sulzer, Philipp; Burger, Tobias; Kasjanow, Alice; Bouwes, Dominique; Krühne, Ulrich; Klimant, Ingo; Mayr, Torsten

doi:10.1016/j.snb.2016.01.050

Cited by 48 publications

(51 citation statements)

References 38 publications

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“…The synthesis of the oxygen‐sensitive particles as well as their characterization and calibration were described in previous works (Ehgartner, J., Strobl, et al, 2016; Ehgartner, Sulzer, et al, 2016). Oxygen monitoring was carried out at a sampling frequency of 1 Hz using a FireStingO2 optical oxygen meter (Pyroscience, Germany) connected to optical fibers (length 1 m, outer diameter 2.2 mm, fiber diameter 1 mm; Sticker et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction

Totaro

Rothbauer

Steiger

et al. 2020

Biotech & Bioengineering

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A key challenge for bioprocess engineering is the identification of the optimum process conditions for the production of biochemical and biopharmaceutical compounds using prokaryotic as well as eukaryotic cell factories. Shake flasks and bench‐scale bioreactor systems are still the golden standard in the early stage of bioprocess development, though they are known to be expensive, time‐consuming, and labor‐intensive as well as lacking the throughput for efficient production optimizations. To bridge the technological gap between bioprocess optimization and upscaling, we have developed a microfluidic bioreactor array to reduce time and costs, and to increase throughput compared with traditional lab‐scale culture strategies. We present a multifunctional microfluidic device containing 12 individual bioreactors (Vt = 15 µl) in a 26 mm × 76 mm area with in‐line biosensing of dissolved oxygen and biomass concentration. Following initial device characterization, the bioreactor lab‐on‐a‐chip was used in a proof‐of‐principle study to identify the most productive cell line for lactic acid production out of two engineered yeast strains, evaluating whether it could reduce the time needed for collecting meaningful data compared with shake flasks cultures. Results of the study showed significant difference in the strains' productivity within 3 hr of operation exhibiting a 4‐ to 6‐fold higher lactic acid production, thus pointing at the potential of microfluidic technology as effective screening tool for fast and parallelizable industrial bioprocess development.

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Section: Methodsmentioning

confidence: 99%

Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction

Totaro

Rothbauer

Steiger

et al. 2020

Biotech & Bioengineering

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“…Layers can be structured down to a size of 100 micrometres combination with stencils. 43,44 f. Microdispensing and inkjet printing…”

Section: E Spray-coatingmentioning

confidence: 99%

“…During this method, the glass, which has to be a borosilicate glass with a high content of alkali ions, is exposed to an electric field, causing the surface of the glass to bond with the surface of the silicon wafer. This usually happens at high temperatures >300°C, but has been shown to work at temperatures as low as 180°C by Ehgartner et al 43 which is more likely to leave sensing material in a functional state. With the current state of the art in sensor dye and matrix development, anodic bonding will have to be effective at even lower temperatures to allow sensor integration.…”

Section: A Clampingmentioning

confidence: 99%

“…23,43 Instrumentation is inexpensive for lifetimes >1 μs and is miniaturized to the size of a memory stick as used by Ehgartner et al 43 Phase shift measurements show lit-tle cross-sensitivity to ambient light and are applied for single point oxygen measurements in microfluidic devices. 23,43 Dual lifetime referencing DLR enables referenced signals for analyte-sensitive fluorophores with decay times in the nanosecond range (most pH-indicators) with fiber optic instrumentation. A reference dye with overlapping absorption spectra and lifetime in the micro-second range is added to the sensor layer.…”

Section: Time-gated Fluorescencementioning

confidence: 99%

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Integration and application of optical chemical sensors in microbioreactors

et al. 2017

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The quantification of key variables such as oxygen, pH, carbon dioxide, glucose, and temperature provides essential information for biological and biotechnological applications and their development. Microfluidic devices offer an opportunity to accelerate research and development in these areas due to their small scale, and the fine control over the microenvironment, provided that these key variables can be measured. Optical sensors are well-suited for this task. They offer non-invasive and non-destructive monitoring of the mentioned variables, and the establishment of time-course profiles without the need for sampling from the microfluidic devices. They can also be implemented in larger systems, facilitating cross-scale comparison of analytical data. This tutorial review presents an overview of the optical sensors and their technology, with a view to support current and potential new users in microfluidics and biotechnology in the implementation of such sensors. It introduces the benefits and challenges of sensor integration, including, their application for microbioreactors. Sensor formats, integration methods, device bonding options, and monitoring options are explained. Luminescent sensors for oxygen, pH, carbon dioxide, glucose and temperature are showcased. Areas where further development is needed are highlighted with the intent to guide future development efforts towards analytes for which reliable, stable, or easily integrated detection methods are not yet available.

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“…Optical chemical sensors are an attractive format for integration into microfluidic devices due to the following features: they are highly sensitive, inexpensive, and easy to miniaturize; and they are capable of noninvasive and nondestructive monitoring during operation (Ehgartner et al, 2016;Gruber, Marques, Sulzer et al, 2017). Several reviews are published on the integration and application of optical sensor in microfluidic devices Pfeiffer & Nagl, 2015;Sun, Ungerböck, & Mayr, 2015).…”

mentioning

confidence: 99%

A fully online sensor‐equipped, disposable multiphase microbioreactor as a screening platform for biotechnological applications

Maldonado

Panjan

Sun

et al. 2018

Biotech & Bioengineering

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A new disposable, multiphase, microbioreactor (MBR; with a working volume of 550 μl) equipped with online sensors is presented for biotechnological screening research purposes owing to its high-throughput potential. Its design and fabrication, online sensor integration, and operation are described. During aerobic cultivation, sufficient oxygen supply is the most important factor that influences growth and product formation. The MBR is a microbubble column bioreactor (μBC), and the oxygen supply was realized by active pneumatic bubble aeration, ensuring sufficient volumetric liquid-phase mass transfer (k a) and proper homogenization of the cultivation broth. The μBC was equipped with miniaturized sensors for the pH, dissolved oxygen, optical density and glucose concentration that allowed real-time online monitoring of these process variables during cultivation. The challenge addressed here was the integration of sensors in the limited available space. The MBR was shown to be a suitable screening platform for the cultivation of biological systems. Batch cultivations of Saccharomyces cerevisiae were performed to observe the variation in the process variables over time and to show the robustness and operability of all the online sensors in the MBR.

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Online analysis of oxygen inside silicon-glass microreactors with integrated optical sensors

Cited by 48 publications

References 38 publications

Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction

Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction

Integration and application of optical chemical sensors in microbioreactors

A fully online sensor‐equipped, disposable multiphase microbioreactor as a screening platform for biotechnological applications

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