• Journal of Astronomy and Space Sciences
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• v.32 no.1
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• pp.81-89
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• 2015

In this paper, we describe the development of a bioreactor for a cell-culture experiment on the International Space Station (ISS). The bioreactor is an experimental device for culturing mouse muscle cells in a microgravity environment. The purpose of the experiment was to assess the impact of microgravity on the muscles to address the possibility of long-term human residence in space. After investigation of previously developed bioreactors, and analysis of the requirements for microgravity cell culture experiments, a bioreactor design is herein proposed that is able to automatically culture 32 samples simultaneously. This reactor design is capable of automatic control of temperature, humidity, and culture-medium injection rate; and satisfies the interface requirements of the ISS. Since bioreactors are vulnerable to cell contamination, the medium-circulation modules were designed to be a completely replaceable, in order to reuse the bioreactor after each experiment. The bioreactor control system is designed to circulate culture media to 32 culture chambers at a maximum speed of 1 ml/min, to maintain the temperature of the reactor at $36{\pm}1^{\circ}C$, and to keep the relative humidity of the reactor above 70%. Because bubbles in the culture media negatively affect cell culture, a de-bubbler unit was provided to eliminate such bubbles. A working model of the reactor was built according to the new design, to verify its performance, and was used to perform a cell culture experiment that confirmed the feasibility of this device.

• Journal of the Korean Society for Precision Engineering
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• v.29 no.9
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• pp.946-957
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• 2012

The objective of this paper is to investigate into the development of a thin flat panel photo-bioreactor case with characteristics shapes. The thin flat panel photo-bioreactor case was designed to be manufactured from a plastic thermoforming process. A proper design with a relatively high rigidity was obtained through the structural analyses for different designs of the photo-bioreactor case. The thermoforming analyses were performed. From the results of the thermoforming analyses, a proper forming condition and the formability of the designed plastic photo-bioreactor case were estimated. The thermoforming moulds for the flat panel photobioreactor cases were manufactured. The thermoforming experiments were performed to examine the manufacturability of the designed flat panel photo-bioreactor cases. From the results of the thermoforming experiments, it was shown that thin flat panel photo-bioreactor cases with characteristic shapes can be manufactured from the designed thermoforming mould and process.

• Journal of the Korean Society of Mineral and Energy Resources Engineers
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• v.55 no.6
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• pp.527-537
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• 2018

Column tests of a sulfate reducing bacteria (SRB) bioreactor were conducted to determine the design factors for sulfate-rich mine drainage. Various substrates were applied to the bioreactor, including cow manure and its mixture with a mushroom compost, with rice straw and limestone as subsidiary materials. This procedure provided a removal efficiency of up to 82% of the total sulfur with the mixture of cow manure (70%), mushroom compost (10%) and rice straw (20%), and higher efficiencies were observed after 2 days of retention time. In the downflow condition of the flow direction, oxygen supply and re-oxidation of the sulfates occurred, causing a decrease in sulfate removal efficiency. The addition of an inorganic sludge containing heavy metals, which was intended for production of metal-sulfides in the bioreactor, had a negative effect on the long-term operation owing to arsenic release and toxicity to the SRB. The results thus show that a bioreactor using a mixed substrate with cow manure and operating in the downflow direction could reduce sulfates and total dissolved sulfur content; this process confirms the applicability of the SRB bioreactor to sulfate-rich saline drainage.

• Journal of Microbiology and Biotechnology
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• v.26 no.1
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• pp.139-144
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• 2016

Synthetic oscillators are gene circuits in which the protein expression will change over time. The delay of transcription, translation, and protein folding is used to form this kind of behavior. Here, we tried to design a synthetic oscillator by a negative feedback combined with a positive feedback. With the mutant promoter P_LacC repressed by LacIq and P_Lux activated by AHL-bound LuxR, two gene circuits, Os-LAA and Os-ASV, were constructed and introduced into LacI-deleted E. coli DH5α cells. When glucose was used as the carbon source, a low level of fluorescence was detected in the culture, and the bacteria with Os-ASV showed no oscillation, whereas a small portion of those carrying Os-LAA demonstrated oscillation behavior with a period of about 68.3 ± 20 min. When glycerol was used as the carbon source, bacteria with Os-ASV demonstrated high fluorescence value and oscillation behavior with the period of about 121 ± 21 min.

• KSBB Journal
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• v.6 no.3
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• pp.231-240
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• 1991

Recently, developments of large scale and high density cell culture methods have been the objects of many researches, because the demand of various pharmaceutical products produced by animal cell culture has been rapidly increasing. The cell culture equipment should have the requirements such as sufficient oxygen transfer and mixing, low shear stress and surface tension, and small foaming. In order to develop a proper bioreactor meeting these requirements simultaneously, a perfluorocarbon having high solubility of oxygen was sprayed into the medium as an oxygen carrier instead of air. Also, a new impeller was developed and combined together with the perfluorocarbon spraying system so as to design a new bioreartor for cell cultivation. The new impeller had better characteristics of mixing and oxygen transfer than the paddle and cell-lift impellers based on the same, shear rate. But, it was observed that the volumetric oxygen transfer coefficient of the new bioreactor decreased with increasing cell density during E. coli fermentation.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.39 no.8
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• pp.633-643
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• 2015

In this study, we develop a highly efficient conical-air diffuser that generates fine bubble. By inserting a sufficient number of aerotropic microorganisms with dissolved oxygen from an air diffuser and minimizing the air-channel blockages within the air diffuser, we expect to improve the efficiency and durability of the decomposition process for organic waste. To upgrade the conventional air diffuser, we perform experiments and numerical analysis to develop a conical-type that generates fine bubble, and which is free from nozzle blockage. We complement the air-diffuser design by numerically analyzing the internal air-flow pattern within the diffuser. Then, by applying the diffuser to a mockup bioreactor, we experimentally and numerically study the bubble behavior observed in the diffuser and the 2-phase fluid flow in the bioreactor. The results obtained include statistics of the cord length and increased velocity, and we investigate the mechanisms of the fluid-flow characteristics including bubble clouds. Throughout the study, we systemize the design procedures for the design of efficient air diffusers, and we visualize the fluid-flow patterns caused by bubble generation within the mockup bioreactor. These results will provide a meaningful basis for further study as well as the detection of oxygen transfer and fluid-flow characteristics in real-scale bio-reactors using sets of air diffusers.

• Environmental Engineering Research
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• v.21 no.2
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• pp.196-202
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• 2016

Membrane bioreactor (MBR) technology has previously been used by water industry to treat high salinity wastewater. In this study, an anoxic-oxic biofilm-membrane bioreactor (AOB-MBR) system has been developed to treat mustard tuber wastewater of 10% salinity (calculated as NaCl). To figure out the effects of operating conditions of the AOB-MBR on membrane fouling rate ($K_V$), response surface methodology was used to evaluate the interaction effect of the three key operational parameters, namely time interval for pump (t), aeration intensity ($U_{Gr}$) and transmembrane pressure (TMP). The optimal condition for lowest membrane fouling rate ($K_V$) was obtained: time interval was 4.0 min, aeration intensity was $14.6 m^3/(m^2{\cdot}h)$ and transmembrane pressure was 19.0 kPa. And under this condition, the treatment efficiency with different influent loads, i.e. 1.0, 1.9 and $3.3kgCODm^{-3}d^{-1}$ was researched. When the reactor influent load was less than $1.9kgCODm^{-3}d^{-1}$, the effluent could meet the third discharge standard of "Integrated Wastewater Discharge Standard". This study suggests that the model fitted by response surface methodology can predict accurately membrane fouling rate within the specified design space. And it is feasible to apply the AOB-MBR in the pickled mustard tuber factory, achieving satisfying effluent quality.

• Journal of Microbiology and Biotechnology
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• v.27 no.8
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• pp.1461-1471
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• 2017

Escherichia coli heat-labile enterotoxin (LT) and its non-toxic mutant (LTm) are well-known powerful mucosal adjuvants and immunogens. However, the yields of these adjuvants from genetically engineered strains remain at extremely low levels, thereby hindering their extensive application in fundamental and clinical research. Therefore, efficient production of these adjuvant proteins from genetically engineered microbes is a huge challenge in the field of molecular biology. In order to explore the expression bottlenecks of LTm in E. coli, we constructed a series of recombinant plasmids based on various considerations and gene expression strategies. After comparing the protein expression among strains containing different recombinant plasmids, the signal sequence was found to be critical for the expression of LTm and its subunits. When the signal sequence was present, the strong hydrophobicity and instability of this amino acid sequence greatly restricted the generation of subunits. However, when the signal sequence was removed, abundantly expressed subunits formed inactive inclusion bodies that could not be assembled into the hexameric native form, although the inclusion body subunits could be refolded and the biological activity recovered in vitro. Therefore, the dilemma choice of signal sequence formed bottlenecks in the expression of LTm. These results reveal the expression bottlenecks of LTm, provide guidance for the preparation of LTm and its subunits, and certainly help to promote efficient preparation of this mucosal adjuvant protein.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.3
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• pp.163-170
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• 2002

This report describes the use of a transtubular bioreactor to study the relative effects of diffusion versus perfusion of medium on antibody production by a hybridoma cell line. The study was performed with a high-density cell culture maintained in a serum-free, low-protein medium for 77 days. It was determined that the reactor possessed a macro-mixing pattern residence time distribution similar to a continuous stirred tank reactor (CSTR), However, due to the arrangement of the medium lines in the reactor, the flow patterns for nutrient distribution consist of largely independent medium path lengths ranging from short to long. When operated with cyclic, reversing, transtubular medium flow, some regions of the reactor (with short residence times) are more accessible to medium than others (with long residence times). From this standpoint, the reactor can be divided into three regions: a captive volume, which consists of medium primarily delivered via diffusion; a lapped volume, which provides nutrients through unilateral convection; and a swept volume, which operates through bilateral convection. The relative sizes of these three volumes were modified experimentally by changing the period over which the direction of medium flow was reversed from 15 min (larger captive volume) to 9 h (larger swept volume). The results suggest that antibody concentration increases as the size of the diffusion-limited (captive) volume is increased to a maximum at around 30 min with a sharp decrease thereafter. As reflected by changes in measured consumption of glucose and production of lactate, no significant difference in cellular metabolism occurred as the reactor was moved between these different states. These results indicate that the mode of operation of the transtubular bioreactor may influence antibody productivity under serum-free, low-protein conditions with minimal effects on cellular metabolism.

• Biotechnology and Bioprocess Engineering:BBE
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• v.4 no.1
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• pp.41-45
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• 1999

Microbial cellulose has many potential applications due to its excellent physical properties. The production of cellulose from Acetobacter xylinum in submerged culture is, however, beset with numerous problems. The most difficult one has been the appearance of negative mutants under shaking culture conditions, which is deficient of cellulose producing ability. Thus genetic instability of Acetobacter xylinum under shaking culture condition made developing a stable mutant major research interest in recent years. To find a proper type of bioreactor for the production of microbial cellulose, several production systems were developed. Using a reactor system with planar type impeller with bottoms sparging system, it was possible to produce 5 g/L microbial cellulose without generating cellulose minus mutants, which is comparable to that of static culture system.