• Journal of Microbiology and Biotechnology
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• v.31 no.3
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• pp.349-357
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• 2021

Monoclonal antibodies are widely used as diagnostic reagents and for therapeutic purposes, and their demand is increasing extensively. To produce these proteins in sufficient quantities for commercial use, it is necessary to raise the output by scaling up the production processes. This review describes recent trends in high-density cell culture systems established for monoclonal antibody production that are excellent methods to scale up from the lab-scale cell culture. Among the reactors, hollow fiber bioreactors contribute to a major part of high-density cell culture as they can provide a tremendous amount of surface area in a small volume for cell growth. As an alternative to hollow fiber reactors, a novel disposable bioreactor has been developed, which consists of a polymer-based supermacroporous material, cryogel, as a matrix for cell growth. Packed bed systems and disposable wave bioreactors have also been introduced for high cell density culture. These developments in high-density cell culture systems have led to the monoclonal antibody production in an economically favourable manner and made monoclonal antibodies one of the dominant therapeutic and diagnostic proteins in biopharmaceutical industry.

• Journal of the Korean Society of Industry Convergence
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• v.27 no.2_2
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• pp.357-361
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• 2024

Halloysite nanotube (HNT) has a nanotube structure with the chemical formula of Al₂Si₂O₅(OH)₄·nH₂O and is a natural sediment of aluminosilicate. HNT has been used as additive to improve the mechanical properties of epoxy composites with exchange of amine group as a terminal functional group using huge amount of organic solvents. In order to save time and simplify complicated procedures, a dry coating machine was designed and used for amine group exchange in previous research. For better applications, it was conducted with different parameters and with scale up settings. Best condition was found to reduce usage of solvent, time and man power.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04a
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• pp.27-31
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• 2002

Samyang Genex succeeded in commercialization of anticancer agent-paclitaxel by plant cell culture technology. The core technology of Samyang Genex relating paclitaxel production includes cell line development, cell line preservation, cell culture, scale-up technology, and purification technology. On the basis of the research, Samyang Genex built the factory operated by CGMP (current good manufacturing practice). The $paclitaxel-Genexol^{TM}$ is commercially available in Korea, and it will be launched to world market including USA after approval US FDA.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04b
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• pp.27-31
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• 2002

Samyang Genex succeeded in commercialization of anticancer agent-paclitaxel by plant cell culture technology. The core technology of Samyang Genex relating paclitaxel production includes cell line development, cell line preservation, cell culture, scale-up technology, and purification technology. On the basis of the research, Samyang Genex built the factory operated by CGMP (current good manufacturing practice). The $paclitaxel-Cenexol^{TH}-is$ commercially available in Korea, and it will be launched to world market including USA after approval of US FDA.

• Journal of Plant Biotechnology
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• v.29 no.1
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• pp.59-62
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• 2002

Samyang Genex succeeded in commercialization of anticancer agent-paclitaxel by plant cell culture technology. The core technology of Samyang Genex relating paclitaxel production includes cell line development, cell line preservation, cell culture, scale-up technology, and purification technology. On the basis of the research, Samyang Genex built the factory operated by CGMP (current good manufacturing practice). The paclitaxel-Genexol$^{TM}$-is commercially available in Korea, and it will be launched to world market including USA after approval of US FDA.

• Microbiology and Biotechnology Letters
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• v.48 no.3
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• pp.344-357
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• 2020

Strain improvement and bioprocess development were undertaken to enhance hyaluronic acid(HA) production by Streptococcus zooepidemicus cells. Using a high-yielding mutant strain, statistical medium optimization was carried out in shake flask cultures, resulting in 52% increase in HA production (5.38 g/l) at the optimal medium composition relative to the parallel control cultures. For sufficient supply of dissolved oxygen (DO), which turned out to be crucial for enhanced production of HA, agitation system and speed were intensively investigated in 5 L bioreactor cultures. Increase in oxygen mass transfer coefficient (k_La) through increment of agitation speed (rpm) and 35% expansion of diameter of the newly-designed impellers showed significantly positive effects on HA production. By installing an expanded Rushton-turbine impeller for efficient break-down of sparged air, and an extended marine impeller above the Rushton-turbine impeller for efficient mixing of the air-born viscous fermentation broth, maximum amount of HA (9.79 g/l) was obtained at 450 rpm, 1.8 times higher level than that of the corresponding flask culture. Subsequently, the possibility of bioprocess scale-up to a 50 L bioreactor was investigated. Despite almost identical maximum HA production (9.11 vs 9.25 g/l), the average HA volumetric productivity (r_p) of the 50 L culture turned out only 74% compared to the corresponding 5 L culture during the exponential phase, possibly caused by shear damages imposed on the producing cells at the high stirring in the 50 L culture. The scale-up process could be successfully achieved if a scale-up criterion of constant oxygen mass transfer coefficient (k_La) is applied to the 50 L pilot-scale bioreactor system.

• KSBB Journal
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• v.22 no.2
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• pp.91-96
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• 2007

The saccharogenic liquid (SFW) obtained by the enzymatic saccharification of food wastes was used as a medium for production of bacterial cellulose (BC). The enzymatic saccharification of food wastes was carried out by the cultivation supernatant of Tricoderma inhamatum KSJ1 culture. Acetobacter xylinum KJ1 was employed for the BC production culture. Under the scaled-up aeration condition of 1.0 vvm, 5.64 g/L of BC was produced in 3 days cultivation in 50 L air circulation bioreactor using SFW medium with addition of 0.4% agar. The productivity was similar to that of 10 L air circulation bioreactor (5.84 g/L). This cultivation method with 50 L air circulation bioreactor decreasing shear stress and increasing oxygen transfer coefficient ($k_La$) was very useful in BC mass production. The physical properties, such as morphology, molecular weight, crystallinity, and tensile strength of BC produced by the static culture (A), the air circulation culture using 10 L bioreactor (B) and 50 L bioreactor (C) were investigated. The number average molecular weight of BCs produced under the different culture conditions (A-C) showed 2,578,000, 1,975,000, and 1,809,000, respectively. Tensile strength was 1.72 $kg/mm^2$, 1.19 $kg/mm^2$, and 1.18 $kg/mm^2$, respectively. All of the BCs had a form of cellulose I representing pure cellulose. The relative degree of crystallinity showed the range of 86.2$\sim$87.8%. BC production by the air circulation culture mode brought more favorable results in terms of the physical properties and its ease of scale-up. Therefore, it is expected that the new BC production method, the air circulation culture using SFW, would contribute greatly to BC-related manufacturing.

• Environmental Engineering Research
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• v.17 no.1
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• pp.3-8
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• 2012

A scaled-up bioconversion of fishmeal wastewater (FMW) into liquid fertilizer was performed five times in a $1m^3$ reactor in order to examine the feasibility of commercialization. The importance of aeration was marked. Analyses indicated that dissolved oxygen (DO) level was closely related to the value of oxidation-reduction potential (ORP) and it was crucial to achieve high-quality liquid fertilizer. When pure oxygen was supplied through four diffusers into the reactor, DO levels and ORP values were maintained over 1.2 mg/L and 0.2 mV, respectively all the time during 52 hr of bioconversion. The pH changed from 6.8 to 5.9. The average removal percentages of chemical oxygen demand ($COD_{Cr}$) and total nitrogen (TN) were 75.0% and 71.6%, respectively. Compared to the result acquired in a 5-L reactor, bioconversion of FMW into liquid fertilizer was achieved in a shorter time under the same removal percentages of $COD_{Cr}$ and TN. The 52-hr culture of inoculated FMW was phytotoxic-free and it possessed comparable fertilizing ability to a liquid fertilizer made from the fish waste in hydroponic culture with amino acid contents of 5.93 g/ 100 g sample. From all the above results, transferring lab-scale data to large-scale production appeared to be successful. As a result, the commercialization of a liquid fertilizer made from FMW was feasible.

• Journal of Microbiology and Biotechnology
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• v.23 no.9
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• pp.1308-1321
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• 2013

The emergence of microcarrier technology has brought a renewed interest in anchorage-dependent cell culture for high-yield processes. Well-known in vaccine production, microcarrier culture also has potential for application in other fields. In this work, two types of microcarriers were evaluated for small-scale monoclonal antibody (mAb) production by CHO-K1 cells. Cultures (5 ml) of microporous Cytodex 3 and macroporous CultiSpher-S carriers were performed in vented conical tubes and subsequently scaled-up (20 ml) to shake-flasks, testing combinations of different culture conditions (cell concentration, microcarrier concentration, rocking methodology, rocking speed, and initial culture volume). Culture performance was evaluated by considering the mAb production and cell growth at the phases of initial adhesion and proliferation. The best culture performances were obtained with Cytodex 3, regarding cell proliferation (average $1.85{\pm}0.11{\times}10^6$ cells/ml against $0.60{\pm}0.08{\times}10^6$ cells/ml for CultiSpher-S), mAb production ($2.04{\pm}0.41{\mu}g/ml$ against $0.99{\pm}0.35{\mu}g/ml$ for CultiSpher-S), and culture longevity (30 days against 10-15 days for CultiSpher-S), probably due to the collagen-coated dextran matrix that potentiates adhesion and prevents detachment. The culture conditions of greater influence were rocking mechanism (Cytodex 3, pulse followed by continuous) and initial cell concentration (CultiSpher-S, $4{\times}10^5$ cells/ml). Microcarriers proved to be a viable and favorable alternative to standard adherent and suspended cultures for mAb production by CHO-K1 cells, with simple operation, easy scale-up, and significantly higher levels of mAb production. However, variations of microcarrier culture performance in different vessels reiterate the need for optimization at each step of the scale-up process.

• Transactions of the Korean hydrogen and new energy society
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• v.18 no.4
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• pp.458-463
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• 2007

An experimental study on scale-up of Electro-electrodialysis(EED) to increase the efficiency of HI decomposition section in the IS(Iodine-Sulfur) process was carried out. The EED stack extends the effective area of the membrane to 20 times of that formerly used in a single EED unit cell. The experiment was carried out using HIx solution($HI:H_2O:I_2=1:8.4{\sim}9:1.85{\sim}1.9$) at $100^{\circ}C$ and various solution flow rates of 20, 30, 40 and 50 cc/min. The increased HI molality in catholyte after one-pass throughout from the EED stack was 3 mol/kg-$H_2O$, 2.2 mol/kg-$H_2O$, 2 mol/kg-$H_2O$ and 1.37 mol/kg-$H_2O$ at 20, 30, 40 and 50 cc/min, respectively. These values satisfied the target of HI molality(the increase of HI molality: 2 mol/kg-$H_2O$) in the IS process for hydrogen production of 20 L/hr.