• KSBB Journal
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• 제15권5호
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• pp.423-427
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• 2000

바이오센서의 구조와 기능 그리고 종류에 대해 소개하였다. 이 분야의 연구가 과거 15년간 각국에서 경쟁적으로 연 구하였으나 glucose sensor가 상품화되 었을 뿐 연구결과를 상 품화한 것은 극히 적은 수였다. 그러나 최근 몇 년간 특히 포켓용 i-STAT point-of-care system의 도입 그리고 surface plasmon resonance와 evanescent wave 측정 장치 의 출현으로 상품화된 바이오샌서의 수가 크게 증가하는 추세에 었다. 이들 중 의료임상과 생물공정 그리고 환경오염 측정용으로 응 용되고 있는 몇 가지 상품에 대하여 약술하였다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권3호
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• pp.156-165
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• 2004

Concentrations of substrates, glucose, and ammionia in biological processes have been on-line monitored by using glucose-flow injection (FIA) and ammonia-FIA systems. Based on the on-line monitored data the concentrations of substrates have been controlled by an on-off controller, a PID controller, and a neural network (NN) based controller. A simulation program has been developed to test the control quality of each controller and to estimate the control parameters. The on-off controller often produced high oscillations at the set point due to its low robustness. The control quality of a PID controller could have been improved by a high analysis frequency and by a short residence time of sample in a FIA system. A NN-based controller with 3 layers has been developed, and a 3(input)-2(hidden)-1(output) network structure has been found to be optimal for the NN-based controller. The performance of the three controllers has been tested in a simulated process as well as in a cultivation process of Saccharomyces cerevisiae, and the performance has also been compared to simulation results. The NN-based controller with the 3-2-1 network structure was robust and stable against some disturbances, such as a sudden injection of distilled water into a biological process.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권4호
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• pp.304-308
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• 2005

The response of IPTG induction was investigated through the monitoring of the alkali consumption rate and buffer capacity during the cultivation of recombinant E. coli BL21 (DE3) harboring the plasmid pRSET-LacZ under the control of lac promoter. The rate of alkali consumption increased along with cell growth, but declined suddenly after approximately 0.2 h of IPTG induction. The buffer capacity also declined after 0.9 h of IPTG induction. The profile of buffer capacity seems to correlate with the level of acetate production. The IPTG response was monitored only when introduced into the mid-exponential phase of bacterial cell growth. The minimum concentration of IPTG for induction, which was found out to be 0.1 mM, can also be monitored on-line and in-situ. Therefore, the on-line monitoring of alkali consumption rate and buffer capacity can be an indicator of the metabolic shift initiated by IPTG supplement, as well as for the physiological state of cell growth.

• KSBB Journal
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• 제17권4호
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• pp.326-332
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• 2002

크로마토그래피 공정 성능 검증의 한 항목인 담체의 수명 검증을 위해 자동화된 미니 크로마토그래피 시스템(MiniValChrom)을 개발하였다. 이 시스템은 크로마토그래피공정의 자동화된 반복수행, 크로마토그래피 각 step의 작동순서 및 공정조건의 자유로운 구성, on-line 실시간 모니터링 및 제어, 여러 담체 수명 검증법의 method file 저장기능 등을 갖추었다. MiniValChrom을 사용하여 BSA와 Cibacron Blue 3G-A를 각각 모델 단백질과 담체로 담체 수명 검증실험을 사례연구로 수행하였다. 담체 수명의 감소는 크로마토그래피 공정을 반복수행하면서 5 cycle 마다 변화하는 HETP값을 측정하여 HETP 값이 1 cm 이상 될 때까지 반복 수행함으로써 담체 수명을 결정할 수 있었다. 본 연구를 통해 개발된 MiniValChrom은 다른 검증 항목이나 multi-product 생산공장 내 크로마토그래피 공정 검증에도 유용하게 쓰일 수 있을 것으로 기대된다.

• KSBB Journal
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• 제16권5호
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• pp.452-458
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• 2001

생물공정에서 암모니아 농도를 제거하기 위해 NN 제어기를 개발하였고 기존의 PID 제어기와 비교하였다. 특히, 생물반응기내 암모니아 농도를 온라인 모니터링하기 위해 암모니아-FIA 장치를 사용하였으며, 이 장치의 분석 오차, 분석 시료의 체류 시간 등의 제어 특성에 대한 영향 computer simulation을 통해 비교, 고찰하였다. 또한 computer simulation에 의해 생물공정에 적합한 인공 신경망 제어구조를 고찰하였고, 3-2-1 구조의 NN 제어기가 PID 제어기보다 우수함을 알수 있었다. 3-2-1 구조의 NN 제어기를 이용하여 모사 생물공정 및 yeast 발효공정에서 암모니아 농도를 제어하여 그 특성을 고찰하였다. 본 연구로부터 미생물의 비선형성장 특성을 가진 생물공정에서 기질의 농도를 제어하기 위해서는 3-2-1 구조의 인공 신경망 제어기가 적합함을 알 수 있었다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권4호
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• pp.351-356
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• 2006

This study developed an artificial neural network (ANN) to estimate the growth of microorganisms during a fermentation process. The ANN relies solely on the cumulative consumption of alkali and the buffer capacity, which were measured on-line from the on/off control signal and pH values through automatic pH control. The two input variables were monitored on-line from a series of different batch cultivations and used to train the ANN to estimate biomass. The ANN was refined by optimizing the network structure and by adopting various algorithms for its training. The software estimator successfully generated growth profiles that showed good agreement with the measured biomass of separate batch cultures carried out between at 25 and $35^{\circ}C$.

• Biotechnology and Bioprocess Engineering:BBE
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• 제2권2호
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• pp.69-72
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• 1997

The pH of microbial culture medium was calculated from equations of equilibrium, meterial balances for ionic components and electro-neutrality theory. Ammonium ion consumption and Acetic acid production are found out to be the major contributors for the alteration of the pH as well as the buffer capacity of the medium. By measuring the buffer capacity on-line, levels of acetic acid were estimated by a software sensor using pH signal in a fermentation process of E.coli growing in a minimal medium. The measured values of acetic acid showed good correlation to those of estimated by the software sensor.

• Biotechnology and Bioprocess Engineering:BBE
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• 제7권6호
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• pp.331-334
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• 2002

Culture conductivity and on-line NADH fluorescence were used to measure cellular growth in plant cell suspension cultures of Podophyllum hexandrum. An inverse correlation between dry cell weight and medium conductivity was observed during shake flask cultivation. A linear relationship between dry cell weight and culture NADH fluorescence was obtained during the exponential phase of batch cultivation In a bioreactor under the pH stat (pH 6) conditions. It was observed that conductivity measurement were suitable for biomass characterisation under highly dynamic uncontrolled shake flask cultivation conditions. However, if the acid/alkali feeding is done for pH control the conductivity measurement could not be applied. On the other hand the NADH fluorescence measurement allowed online-in situ biomass monitoring of rather heterogenous plant cell suspension cultures in bioreactor even under the most desirable pH stat conditions.

• Biotechnology and Bioprocess Engineering:BBE
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• 제8권6호
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• pp.338-348
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• 2003

In the past decade, considerable progress has been made in developing the appropriate biotechnology for microalgal mass cultivation aimed at establishing a new agro-industry. This review points out the main biological constraints affecting algal biotechnology outdoors and the requirements for making this biotechnology economically viable. One of them is the availability of a wide variety of algal species and improved strains that favorably respond to varying environmental conditions existing outdoors. It is thus just a matter of time and effort before a new methodology like genetic engineering can and will be applied in this field as well. The study of stress physiology and adaptation of microalgae has also an important application in further development of the biotechnology for mass culturing of microalgae. In outdoor cultures, cells are exposed to severe changes in light and temperature much faster than the time scale re-quired for the cells to acclimate. A better understanding of those parameters and the ability to rapidly monitor those conditions will provide the growers with a better knowledge on how to optimize growth and productivity. Induction of accumulation of high value products is associated with stress conditions. Understanding the physiological response may help in providing a better production system for the desired product and, at a later stage, give an insight of the potential for genetic modification of desired strains. The potential use of microalgae as part of a biological system for bioremediation/detoxification and wastewater treatment is also associated with growing the cells under stress conditions. Important developments in monitoring and feedback control of the culture behavior through application of on-line chlorophyll fluorescence technique are in progress. Understanding the process associated with those unique environmental conditions may help in choosing the right culture conditions as well as selecting strains in order to improve the efficiency of the biological process.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권1호
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• pp.54-60
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• 2006

In this paper, we describe a bio-fluidic device for adaptive sample pretreatment, in order to optimize the conditions under which absorbance assays can be conducted. This device can be successfully applied to the measurement of Escherichia coli (E. coli) concentrations using adaptive dilution, with which the dilution ratio can be adjusted during the dilution. Although many attempts have been previously made to miniaturize complex biochemical analyses at the chip scale, very few sample pretreatment processes have actually been miniaturized or automated at this point. Due to the lack of currently available on-chip pretreatments, analytical instruments tend to suffer from a limited range of analysis. This occasionally hinders the direct and quantitative analysis of specific analyses obtained from real samples. In order to overcome these issues, we exploit two novel strategies: dilution with a programmable ratio, and to-and-fro mixing. The bio-fluidic device consists of a rectangular chamber constructed of poly(dimethylsiloxane) (PDMS). This chamber has four openings, an inlet, an outlet, an air control, and an air vent. Each of the dilution cycles is comprised of four steps: detection, liquid drain, buffer injection, and to-and-fro mixing. When using adaptive sample pretreatment, the range in which E. coli concentrations can be measured is broadened, to an optical density (O.D.) range of $0.3{\sim}30$. This device may prove useful in the on-line monitoring of cell concentrations, in both fermenter and aqueous environments.