Oxygen transfer characteristics of miniaturized bioreactor systems

Abstract

Since their introduction in 2001 miniaturized bioreactor systems have made great advances in function and performance. In this article the dissolved oxygen (DO) transfer performance of submilliliter microbioreactors, and 1–10 mL minibioreactors was examined. Microbioreactors have reached kLa values of 460 h-1, and are offering instrumentation and some functionality comparable to production systems, but at high throughput screening volumes. Minibioreactors, aside from one 1,440 h-1 kLa system, have not offered as high rates of DO transfer, but have demonstrated superior integration with automated fluid handling systems. Microbioreactors have been typically limited to studies with E. coli, while minibioreactors have offered greater versatility in this regard. Further, mathematical relationships confirming the applicability of kLa measurements across all scales have been derived, and alternatives to fluorescence lifetime DO sensors have been evaluated. Finally, the influence on reactor performance of oxygen uptake rate (OUR), and the possibility of its real-time measurement have been explored. Biotechnol. Bioeng. 2013; 110: 1005–1019. © 2012 Wiley Periodicals, Inc.

Intelligent Automation Platform for Bioprocess Development

“…The microscale fermentation in Figure 11 was oxygen limited as the DOT falled to 0% after 45 min when the early exponential phase begun, and remained at 0% until the stationary phase. This is in agreement with recently published works that the limitation of dissolved oxygen plays an import role for final biomass growth in microscale fermentation (Kirk & Szita 2013). …”

Real‐time pH monitoring of industrially relevant enzymatic reactions in a microfluidic side‐entry reactor (μSER) shows potential for pH control

“…The importance of online monitoring has been described among the development needs for microbioreactors [40,41], and timecourse profiles of process parameters have been shown for fermentation [42] and stem cell culture [43]. Therefore, further applications of this approach are not only of interest for analytical and synthetic enzymatic reactions, enzyme stability studies or bioprocess development, but for a variety of biotechnological applications where continuous flow microreactors can be envisioned.…”

“…Optical sensors are more frequently applied in miniaturized and microfluidic devices than electrochemical sensors [7]. Optical pH sensors [8] were applied to observe a pH gradient in free-flow electrophoresis [9]; to detect pH in segments used for cell cultivation [10]; and to control the pH of microbial fermentations in a batch microbioreactor [11].…”

“…And they have also been developed for monitoring pH and potassium [5]. Recently, Welch et al [6] combined ISFETs and microfluidic valves to demonstrate controlled increase and decrease of pH in 0.14 pH increments inside a 90 nL chamber filled with a weak acid and a strong base, but the control of a reaction was not shown.Optical sensors are more frequently applied in miniaturized and microfluidic devices than electrochemical sensors [7]. Optical pH sensors [8] were applied to observe a pH gradient in free-flow electrophoresis [9]; to detect pH in segments used for cell cultivation [10]; and to control the pH of microbial fermentations in a batch microbioreactor [11].…”

Soluble compound screening using microfluidic gradients for regenerative medicine research

“…Micronit, microLIQUID) or are mainly meant for PDMS cell culture devices. [250][251][252] To overcome these issues, a platform was developed in which entirely closed microfluidic systems made from gas-impermeable materials can be used for cell culture under varying physiological conditions (Fig. 3.1).…”