Efficient MILP formulations for the simultaneous optimal peptide tag design and downstream processing synthesis

Novel and efficient linear formulations are developed for the problem of simultaneously performing an optimal synthesis of chromatographic protein purification processes, and the concomitant selection of peptide purification tags, that result in a maximal process improvement. To this end, two formulations are developed for the solution of this problem: (1) a model that minimizes both the number of chromatographic steps in the final purification process flow sheet and the composition of the tag, by use of weighted objectives, while satisfying minimal purity requirements for the final product; and (2) a model that attempts to find the maximal attainable purity under constraints on the maximum number of separation techniques and tag size. Both models are linearized using a previously developed strategy for obtaining optimal piecewise linear approximations of nonlinear functions. Proposed are models to two case studies based on protein mixtures with different numbers of proteins. Results show that the models are capable of solving to optimality all the implemented cases with computational time requirements of under 1 s, on average. The results obtained are further compared with previous nonlinear and linear models attempting to solve the same problem, and, thus, show that the approach represents significant gains in robustness and efficiency. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

Near-infrared spectroscopic monitoring of biomass, glucose, ethanol and protein content in a high cell density baker's yeast fed-batch bioprocess

The use of at-line NIRS to monitor a high cell density fed-batch baker's yeast bioprocess was investigated. Quantification of the key analytes (biomass, ethanol and glucose) and the product quality indicator (percentage protein content) was studied. Biomass was quantitatively modelled using whole matrix samples (as was percentage protein content). The dominance of the whole matrix spectrum by biomass, and its associated light scattering effects, were overcome by use of filtrate samples and adapted (semi-synthetic) filtrate samples, which allowed successful ethanol and glucose modelling, respectively. Calibrations were rigorously challenged via external validation with large sample sets relative to the calibration sample size, ensuring model robustness and potential practical utility. The standard errors of calibration for biomass, glucose, ethanol and total intracellular protein were (g/l) 1.79, 0.19, 0.79 and 0.91, respectively, comparable to those of the primary assays. The calibration strategies necessary to generate quantitative models for this range of analytes in such a complex high cell density bioprocess fluid are discussed.     

甘油间歇生物歧化过程的动态优化

研究了甘油间歇生物歧化过程的动态优化。针对甘油间歇生物歧化过程的非线性过量动力学系统,首先在终端时刻是固定和可变两种情况下,分别以终端时刻产物1,3-丙二醇的浓度、终端时刻产物1,3-丙二醇的产率为目标函数,提出了三个动态优化模型;然后基于有限元配置法将甘油间歇生物歧化过程的状态方程转化为代数方程,从而得到动态优化模型的非线性规划形式。最后对提出的三个动态优化模型进行求解,并对所得优化结果进行了分析与讨论。与已有结果相比,获得了更高的1,3-丙二醇产率。     

甘油生物歧化为1,3-丙二醇过程的H∞控制

A robust controller is designed by using the bilinear transformation and H∞ mixed sensitivity method for bio-dissimilation process of glycerol to 1,3-propanediol. Under the controller the system works near an optimal steady-state for the volumetric productivity of 1,3-propanediol attaining its maximization. The design procedure is carried out by tuning the transformation parameter and DC gain of the performance weighted function, which is an iterative and optimal search process. Simulation results are presented which show that the designed robust controller not only ensures the robust stability of the system in face of the parametric variations in the model, but also makes the system have a favourable robust tracking performance. The validity of the proposed H∞ controller has been tested.     

Fuzzy modeling and control of biological processes

Fuzzy modeling and control based on the fuzzy sets theory have been used in the biotechnology field for the last two decades. Recent studies on fuzzy modeling and control of various biological processes are reviewed. In addition, five applications of fuzzy control to industrial biological processes are summarized, compared and discussed in terms of the system features, control purpose, input and output variables, development of fuzzy rules and effectiveness. Fuzzy modeling and control are regarded as promising methods for automating the bioprocesses in which experienced operators play significant roles in their successful operation.     

DNA based vaccines offer improved vaccination supply for the developing world

Vaccination is a major line of defense against infectious diseases. However, with many current vaccines production methods can be both time‐consuming and expensive. These characteristics, together with the low number of vaccine manufacturers and the occurrence of region‐specific diseases, prevent the ready availability of vaccines worldwide. These shortcomings particularly affect developing countries and present real vaccine supply concerns in the event of a global pandemic. DNA‐based vaccines are now emerging as a potential alternative that could provide broader access to vaccination around the world. Although this technology is still in its initial research and development stages, production, processing and distribution of these kinds of vaccines could be greatly simplified since DNA is in essence a simple‐to‐handle molecule. With the proper methodologies and protocols, health care efforts around the world could enormously benefit from this technology ensuring better life‐quality standards in less developed regions. © 2013 Society of Chemical Industry     

苏州福星污水厂改造方案的可行性分析

通过数据分析和实践经验,选取多点进水倒置A/A/O工艺作为苏州福星污水处理厂改造的首选方案.同时,利用BioWin软件构建该方案的工艺模型,研究温度、DO和内回流比对工艺运行的影响.模拟结果表明,改造方案的出水水质基本能达到一级A排放标准,但为了确保TP的达标排放需加药除磷.为了克服进水水质、水量波动对工艺稳定运行和达标排放的影响,设计构建了一套生物智能优化控制系统.这套系统的实施,在实现工艺稳定运行、达标排放的同时,还可以降低处理能耗、节约成本.     

A web-enabled software for real-time biogas fermentation monitoring – Assessment of dark fermentations for correlations between medium conductivity and biohydrogen evolution

A web-enabled software was developed for continuous online monitoring of biohydrogen, biomethane and carbon dioxide gas fractions, temperature, Dissolved Oxygen (DO), pH, conductivity and gas volume for biogas fermentations. The cumulative gas volumes are computed recursively at 1 min intervals. Process data streamed into a MySQL database are accessible on a Local Area Network in real-time. This software was evaluated via continuous monitoring of two batches of dark fermentations for biohydrogen production using anaerobic sludge as inoculum and glucose as substrate. The effect of sampling frequency on the accuracy of cumulative hydrogen volume determination and the possible correlations between medium conductivity and biohydrogen evolution were examined. Data showed an erroneous over estimation of biohydrogen production at 12.09% and 16.23% for 12 and 24 h sampling intervals, suggesting the adoption of a high sampling rate to derive reliable key process parameters from the Gompertz model. Partial correlations were observed between medium conductivity and hydrogen gas fractions with maximum conductivity changes of 5.0 and 21.1 S × cm⁻¹, corresponding to peaks of hydrogen concentrations of 33.53% and 44.86%, respectively. Accurate application of conductimetric techniques for real-time monitoring of biohydrogen production requires further understanding of all sources of conductivity changes. The implemented software could generate high throughput actionable information for biohydrogen process development and optimization.     

生物法防治黄曲霉毒素B1研究进展

黄曲霉毒素具有极强的致癌、致畸和致突变作用。受黄曲霉毒素污染的粮食不仅给人体和动物的健康带来严重危害,也给食品、畜牧等行业造成巨大经济损失。目前,黄曲霉毒素降解方法研究已成为各国科研工作者的一个热点。生物法降解黄曲霉毒素较物理、化学等方法具有安全系数高、特异性强、绿色清洁等独特优势,被视为最具发展前景和潜力的降解方法。利用微生物菌体的吸附作用、微生物酶解作用、微生物代谢作用等对黄曲霉毒素进行脱除,已逐渐成为生物法消减黄曲霉毒素的重要研究方向。通过筛选和改造获得可脱除黄曲霉毒素的优良菌株;通过分离、提取、纯化等手段获得高纯度和高活性的微生物源解毒产物;通过改进和优化获得最佳脱除工艺等,已成为研究生物法脱除黄曲霉毒素的重要手段和突破口。本文主要对国内外生物法防治黄曲霉毒素B_1的研究进行综述,并对今后生物防治的发展方向提出一些设想。