Lab‐scale fermentation tests of microchip with integrated electrochemical sensors for pH, temperature, dissolved oxygen and viable biomass concentration

Krommenhoek, E.E.; Leeuwen, M. van; Gardeniers, Han; Gulik, Walter M. van; Berg, Albert van den; Li, Xiaonan; Ottens, Marcel; Wielen, Luuk A.M. van der; Heijnen, Joseph J.

doi:10.1002/bit.21661

Cited by 56 publications

(57 citation statements)

References 36 publications

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“…Controlling pH may also be important, as it has been demonstrated that small changes, up or down, in the pH of the medium provided to ES cells results in an approximately 50% decrease in the yield of cells capable of forming embryoid bodies (three dimensional spheroids of differentiating ES cells) (83). Ultimately, it is likely that control of oxygen and pH in artificial stem cell niches will require new sensor technologies, capable of cell-level measurement and control (84), enabling prospectively controllable links between cell signaling, gene regulation, and metabolic networks (85).…”

Section: Ecm Microarraysmentioning

confidence: 99%

Enabling stem cell therapies through synthetic stem cell–niche engineering

Peerani

Zandstra²

2010

J. Clin. Invest.

158

122

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Enabling stem cell-targeted therapies requires an understanding of how to create local microenvironments (niches) that stimulate endogenous stem cells or serve as a platform to receive and guide the integration of transplanted stem cells and their derivatives. In vivo, the stem cell niche is a complex and dynamic unit. Although components of the in vivo niche continue to be described for many stem cell systems, how these components interact to modulate stem cell fate is only beginning to be understood. Using the HSC niche as a model, we discuss here microscale engineering strategies capable of systematically examining and reconstructing individual niche components. Synthetic stem cell-niche engineering may form a new foundation for regenerative therapies.

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Section: Ecm Microarraysmentioning

confidence: 99%

Enabling stem cell therapies through synthetic stem cell–niche engineering

Peerani

Zandstra²

2010

J. Clin. Invest.

158

122

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“…Recently, an integrated sensor array has been developed, based on the 96-well microtiter plate format, containing sensors for pH, dissolved oxygen, temperature, and viable biomass concentration. 22,23 Compatibility of a miniaturized bioreactor system to the current high-throughput cell cultivation platforms, i.e. the 24 and 96 (deep)well plates, is highly desirable because of the already available automation equipment.…”

Section: Introductionmentioning

confidence: 99%

“…Taking this into account, we developed a parallelized micro bioreactor system with a working volume of 100 lL based on the 96-well microtiter plate format. In each of the micro bioreactors, a recently developed electrochemical sensor array 22,23 was integrated for the online measurement of temperature, pH, dissolved oxygen concentration, and viable biomass concentration. The cumulative CO 2 production during the cultivations was measured with a conductometric sensor.…”

Section: Introductionmentioning

confidence: 99%

Aerobic batch cultivation in micro bioreactor with integrated electrochemical sensor array

Leeuwen

Krommenhoek

Heijnen

et al. 2009

Biotechnology Progress

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Aerobic batch cultivations of Candida utilis were carried out in two micro bioreactors with a working volume of 100 muL operated in parallel. The dimensions of the micro bioreactors were similar as the wells in a 96-well microtiter plate, to preserve compatibility with the current high-throughput cultivation systems. Each micro bioreactor was equipped with an electrochemical sensor array for the online measurement of temperature, pH, dissolved oxygen, and viable biomass concentration. Furthermore, the CO(2) production rate was obtained from the online measurement of cumulative CO(2) production during the cultivation. The online data obtained by the sensor array and the CO(2) production measurements appeared to be very reproducible for all batch cultivations performed and were highly comparable to measurement results obtained during a similar aerobic batch cultivation carried out in a conventional 4L bench-scale bioreactor. Although the sensor chip certainly needs further improvement on some points, this work clearly shows the applicability of electrochemical sensor arrays for the monitoring of parallel micro-scale fermentations, e.g. using the 96-well microtiterplate format.

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“…Here, the pH-control and fed-batch fermentations could be performed by feedback controlling the opening times of the acid or base microvalve or establishing glucose pulses in response to an increasing DOT. Besides some attempts to measure pH, DOT, and biomass with electronic sensors (Krommenhoek et al, 2008), the common method to monitor the important fermentation parameters in the described microbioreactors is the non-invasive, optical measurement by means of optodes (pH and DOT) or light transmission (OD).…”

Section: Introductionmentioning

confidence: 99%

Microfluidic biolector—microfluidic bioprocess control in microtiter plates

Funke

Buchenauer

Schnakenberg

et al. 2010

Biotech & Bioengineering

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In industrial-scale biotechnological processes, the active control of the pH-value combined with the controlled feeding of substrate solutions (fed-batch) is the standard strategy to cultivate both prokaryotic and eukaryotic cells. On the contrary, for small-scale cultivations, much simpler batch experiments with no process control are performed. This lack of process control often hinders researchers to scale-up and scale-down fermentation experiments, because the microbial metabolism and thereby the growth and production kinetics drastically changes depending on the cultivation strategy applied. While small-scale batches are typically performed highly parallel and in high throughput, large-scale cultivations demand sophisticated equipment for process control which is in most cases costly and difficult to handle. Currently, there is no technical system on the market that realizes simple process control in high throughput. The novel concept of a microfermentation system described in this work combines a fiber-optic online-monitoring device for microtiter plates (MTPs)--the BioLector technology--together with microfluidic control of cultivation processes in volumes below 1 mL. In the microfluidic chip, a micropump is integrated to realize distinct substrate flow rates during fed-batch cultivation in microscale. Hence, a cultivation system with several distinct advantages could be established: (1) high information output on a microscale; (2) many experiments can be performed in parallel and be automated using MTPs; (3) this system is user-friendly and can easily be transferred to a disposable single-use system. This article elucidates this new concept and illustrates applications in fermentations of Escherichia coli under pH-controlled and fed-batch conditions in shaken MTPs.

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Lab‐scale fermentation tests of microchip with integrated electrochemical sensors for pH, temperature, dissolved oxygen and viable biomass concentration

Cited by 56 publications

References 36 publications

Enabling stem cell therapies through synthetic stem cell–niche engineering

Enabling stem cell therapies through synthetic stem cell–niche engineering

Aerobic batch cultivation in micro bioreactor with integrated electrochemical sensor array

Microfluidic biolector—microfluidic bioprocess control in microtiter plates

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