Thermodynamics of protein aqueous solutions: From the structure factor to the osmotic pressure

An analytical expression for the structure factor for globular proteins in aqueous solution is presented. This expression was obtained considering a potential given by the sum of a hard core, a van der Waals attractive, and a screened Coulomb contribution. Experimental data of small angle x‐ray scattering for bovine serum albumin (BSA) in aqueous solutions containing sodium salts at different protein concentrations and pH values are also presented. The developed expression for the structure factor describes accurately these experimental data provided a dependence of the attractive parameter on protein concentration is established. An expression for the osmotic pressure was derived from the structure factor. With attractive parameters adjusted from x‐ray scattering data, the osmotic pressure of BSA aqueous solutions could be predicted with very good agreement with experimental data. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2871–2880, 2015     

Biomass estimation using fluorescence measurements in Pichia pastoris bioprocess

The utilisation of tryptophan fluorescence as an indirect biomass measurement for the yeast Pichia pastoris, an excellent host system for the production of heterologous proteins, is presented. Direct fluorescence measurements for cell densities above 3 g dm^?3 presented important interferences due to inner filter effects. To overcome this drawback, a dilution protocol is provided which allows the quenching of the emission signal caused by solid particles to be controlled. The measured tryptophan fluorescence intensities were used to estimate biomass concentration during a P pastoris batch bioprocess growing either on glycerol or methanol. The best measurement model tested was based on the application of a Luedeking–Piret‐based equation to fluorometric measurements. Thus, a linear relationship between the specific fluorescence evolution rate and specific growth rate was applied. The mean absolute relative prediction error (MARE) for biomass concentration was about 6%. Copyright © 2005 Society of Chemical Industry     

Probability bounds analysis for nonlinear dynamic process models

Dynamic process models frequently involve uncertain parameters and inputs. Propagating these uncertainties rigorously through a mathematical model to determine their effect on system states and outputs is a challenging problem. In this work, we describe a new approach, based on the use of Taylor model methods, for the rigorous propagation of uncertainties through nonlinear systems of ordinary differential equations (ODEs). We concentrate on uncertainties whose distribution is not known precisely, but can be bounded by a probability box (p‐box), and show how to use p‐boxes in the context of Taylor models. This allows us to obtain p‐box representations of the uncertainties in the state variable outputs of a nonlinear ODE model. Examples having two to three uncertain parameters or initial states and focused on reaction process dynamics are used to demonstrate the potential of this approach. Using this method, rigorous probability bounds can be determined at a computational cost that is significantly less than that required by Monte Carlo analysis. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Review of the important challenges and opportunities related to modeling of mammalian cell bioreactors

Industrialization of mammalian cell culture has been achieved by integrating knowledge from several applying core concepts of chemical engineering, cellular and molecular biology, and biochemistry. Modeling has been applied to biological and physical processes to gain additional insights into such processes. This article covers modeling of the bioreactor and metabolic processes as it applies to bioprocess. Hydrodynamics of a bioreactor is briefly described while additional focus is given to gas‐liquid mass transfer. Biological modeling is presented in the order of increasing complexity. First steady state models are presented followed by dynamic models, cybernetic models, and finally bioreactor integrated models. The closing discussion summarizes challenges of implementation of model‐based approaches in the biopharmaceutical industry. © 2016 American Institute of Chemical Engineers AIChE J, 63: 398–408, 2017     

Chemical conversion and liquid–liquid extraction of 5‐hydroxymethylfurfural from fructose by slug flow microreactor

A dehydration of fructose in the water/methyl isobuthyl ketone (MIBK) biphasic system can yield 5‐hydroxymethylfurfural (HMF) to be successfully extracted into the organic MIBK phase. The HMF production and yield in MIBK phase was discussed by using a simplified model taking into consideration of the slug flow. The extraction resistance of HMF across the interface between water and MIBK depended on the line velocity and the flow rate ratio. It was likely that the velocity field generated in the slug flow contributed to an increase in the mass transfer of HMF. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2135–2143, 2016     

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.     

Integration of COSMO‐based methodologies into commercial process simulators: Separation and purification of reuterin

The conceptual design of a new process is developed via computer‐aided simulation for separating and purifying reuterin, an antimicrobial substance obtained by bacterial fermentation of glycerol, from its mixture with the nonfermented substrate, the main subproduct of the process (1,3‐propanediol) and water. The nondatabank components included in the simulations are created by using the structures derived from quantum mechanical calculations and the properties (molecular weight, normal boiling point, and mass density) estimated by COSMO‐RS method. The unknown remainder properties are estimated by the methods and models used by default in Aspen Plus (v7.3). The COSMOSAC property model, also implemented in Aspen Plus, is specified with the molecular volumes and sigma profiles obtained by COSMO‐RS. The properties (boiling temperatures, densities, VL equilibria, etc.) predicted for glycerol, 1,3‐propanediol, water, and their mixtures by COSMO‐based methods agree reasonably well with experimental reported values, whereas those obtained for reuterin derivatives are consistent with the behavior of amphoteric compounds having strong capabilities to interact attractively with hydrogen donor and acceptor groups all together. The process consists of a two‐stage distillation operation, the first of which removes the water and the second one separates reuterin as a 99.5 wt %‐pure bottom product. The second column operates at low pressure (ca. 40 kPa) to avoid thermal decomposition of reuterin (over 280°C) and guaranties 99.9% recovery of the desired product. Water removing offers different heat integration and energy‐saving opportunities considering that condenser pressure of the first column can be increased to ～15 bar preserving the thermal integrity of the reuterin. Dimensions of the equipments as well as capital and operating costs are evaluated. © 2012 American Institute of Chemical Engineers AIChE J, 2012     

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。     

功能基因组学与代谢工程：微生物菌种改进与生物过程优化

代谢工程是用现代基因工程技术对细胞性质进行改进.代谢工程包括3个重要步骤：细胞途径的修饰（合成）,修饰后细胞表型的严格评价（表型表征）,根据评价结果设计进一步的修饰（优化设计）.其中“组学”技术（基因组学、转录物组学、蛋白质组学、代谢物组学、代谢通量组学等）在表型表征中起着极为重要的作用.此外,由于细胞的性质不仅与其基因组密切相关,而且也与细胞所处的微观及宏观环境条件（底物种类与浓度、pH、温度、溶氧、生物反应器的混合与传递特性等）密切相关,因此在菌种改进过程中就要密切结合这些实际的环境条件对所得的菌株用上述“组学”技术进行表型表征,从而使所开发的代谢工程菌株满足包括环境条件影响在内的整个生物加工过程优化的需要.本文结合国际上的发展及作者的研究实践,综述了近几年基于功能基因组学的代谢工程研究发展情况.     

甘油连续生物歧化过程的多目标优化

研究了甘油连续生物歧化过程的多目标优化。针对甘油连续生物歧化为1,3-丙二醇过程的还原途径酶催化非线性动力系统,首先考虑目的产物1,3-丙二醇的产率、甘油转化为1,3-丙二醇的转化率、甘油的转化率以及3-羟基丙醛浓度等四个目标函数,构建了六个多目标非线性优化模型,其次应用NBI（Normal Boundary Intersection）方法对其进行求解。为了解决NBI方法可能获得非全局Pareto最优解这一问题,设计了一种过滤算法以去除NBI方法产生的非全局Pareto点。最后对获得的所有多目标优化问题的Pareto最优解集及Pareto前沿进行了分析与讨论,为实现甘油生物歧化为1,3-丙二醇过程的操作优化提供指导。