Operator training simulators for biorefineries: current position and future directions

Recent technological advances in the development of alternative energy sources, including biofuels, for transportation and energy requirements have demonstrated the need for highly skilled engineers and operators in the biotechnological industries. Although operator training simulators (OTS) used in the traditional chemical process industries may be used to train biorefinery operators and engineers, several distinct aspects of bioprocess operations make their direct application limited. The development and deployment of OTSs for use in biotechnological processes is therefore beginning to gain increasing attention. This review paper examines the present status of OTS development and use in biorefineries, including future considerations on how an OTS may be used to improve operator competence, maximise biorefinery operational efficiencies and protect people and the environment. The general premise of an OTS is that model‐based operator training simulators can be used to verifiably enhance the training of industrial operators to run complex biorefineries. Only a few examples of the design and application of OTSs in large‐scale biorefineries have so far been reported. A discussion of the mathematical models used for OTS development is briefly presented, as well as available OTS design frameworks and vendors, including their benefits and drawbacks. The review concludes by looking at possible future directions of OTS development and use in biorefineries and their contribution in facilitating the transition to a bio‐based economy. © 2018 Society of Chemical Industry     

Nonlinear control of the dissolved oxygen concentration integrated with a biomass estimator for production of Bacillus thuringiensis δ-endotoxins

Bacillus thuringiensis is a microorganism that allows the biosynthesis of δ-endotoxins with toxic properties against some insect larvae, being often used for the production of biological insecticides. A key issue for the bioprocess design consists in adequately tracking a pre-specified optimal profile of the dissolved oxygen concentration. To this effect, this paper aims at developing a novel control law based on a nonlinear dynamic inversion method. The closed-loop strategy includes an observer based on a Bayesian Regression with Gaussian Process, which is used for on-line estimating the biomass present in the bioreactor. Unlike other approaches, the proposed controller leads to an improved response time with effective disturbance rejection properties, while simultaneously prevents undesired oscillations of the dissolved oxygen concentration. Simulation results based on available experimental data were used to show the effectiveness of the proposal.     

Model-based control of titer and glycosylation in fed-batch mAb production: Modeling and control system development

Therapeutic monoclonal antibodies (mAbs) are typically manufactured using mammalian cell cultures in fed-batch bioreactors, with increasing emphasis on meeting productivity and product quality attribute targets that depend strongly on such process variables as nutrient feed rates and bioreactor operating conditions. In this article, we identify, categorize, and address the challenges of achieving both productivity and product quality goals simultaneously, by developing a multivariable, model-based control system that can satisfy multiple production objectives in a fed-batch cell culture process. Here, we discuss model development and present theoretical concepts of observability and controllability that are essential to understanding and handling effectively these intrinsic challenges. Subsequently, we evaluate via simulation the performance of the outer-loop model predictive control and demonstrate the overall capability to satisfy complex production objectives in a laboratory scale bioreactor, as a first step toward the ultimate goal of creating an advanced control system for fed-batch mAb manufacturing processes.     

Predicting in silico bioprocess additive and food additive undesirable outcomes due to utilising cytochrome P450 isoform metallomimics

Up to 2700 isoforms of cytochromes P450 bioconvert components of food bioprocessing. Nutragenomics define the biotransformation abilities of particular cytochromes P450 selected from 57 human isoforms in appropriate tissues such as the liver. Safety predictions solely in silico are unreliable using metallomimics of the Fe‐containing enzymes. Copyright © 2004 Society of Chemical Industry     

An approach to mechanistic event recognition applied on monitoring organic matter depletion in SBRs

A fundamental practice in process engineering is monitoring the state dynamics of a system. Unfortunately, observability of some states is related to high costs, time, and efforts. The mechanistic event recognition (MER) aims to detect an event (defined as a change of the system with specific significance to the operation of the process) that cannot be directly observed but has some predictable effect on the dynamics of the systems. MER attempts to apply fault diagnosis techniques using mechanistic “recognition” models to describe the process. A systematic method for building recognition models using optimal experimental design tools is presented. As proof of concept, the MER approach to detect organic matter depletion in sequencing batch reactors, measuring only ammonia, dissolved oxygen, and nitroxides is applied. The event, that is, consumption of organic matter to a level below 50 gCOD/m³, was successfully detected even though microbial activity is known to continue after organic matter depletion. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3460–3472, 2014     

生物反应池工艺过程控制技术的设计及应用

在安徽芜湖城南污水处理厂(10 ×104 m3/d)的设计中,采用了先进的生物反应池工艺过程控制技术,包括智能优化系统(BIOS)、曝气控制系统(MASC)及在线监测仪表.该控制技术采用前馈控制理念,通过安装在生物池前段的在线仪表并结合工艺数学模型实时优化和控制生物反应池的工艺运行参数(如溶解氧、内回流比或排泥量等).对生物反应池进行工艺过程控制,可提高生物处理效率,在保证污水处理厂出水稳定达标排放(GB 18918-2002一级B标准)的基础上还能节省曝气量,预计该技术的应用可节省20%～40%的曝气能耗.     

Development and monitoring of an integrated bioprocess for production of a potential malaria vaccine with Pichia pastoris

An engineered variant of the yeast Pichia pastoris was used to produce the potential malaria vaccine D1M1. This paper describes the implementation of an expanded bed adsorption chromatography step into a sequential cultivation process of the yeast in order to link protein expression, cell release, and product capture of the secreted protein in a fully automated plant. The process is operated with a semi-continuous strategy for an integrated production. Process improvements have been achieved using design of experiments. Resulting purities of product achieved up to 87% with recoveries of 51% in a single downstream operation. Furthermore, a multivariate analysis of historical batch data was used to develop a golden batch model for process monitoring.     

氯代有机物污染场地的监控自然衰减修复初探

氯代有机物因其高毒性、高富集性、高环境残留的特点及其“致癌、致畸、致突变”效应被美国环保局(EPA)列为优先控制污染物。氯代有机物污染场地的传统物理、化学、生物修复方式修复费用相对较高,对污染场地周边环境影响较大。监控自然衰减(MNA)是一种国际上应用较广的污染场地修复和管理技术,近年来在我国逐渐得到关注,其利用污染物自身的自然衰减作用达到修复目标,从而降低修复成本,规避工程风险。本文重点介绍监控自然衰减技术,并结合氯代有机物自然衰减过程中的生物降解作用、降解途径与机理、主要降解菌和酶等要素对氯代有机物污染场地实施监控自然衰减修复的可行性进行初步探究。     

氧化还原电位调控混合糖为底物的丁醇发酵

控制丁醇发酵过程中的氧化还原电位（oxidoreduction potential, ORP）能够大幅提高丁醇产量和果糖利用率,并降低终点有机酸浓度。实验考察了以葡萄糖和果糖混合糖为底物,通过泵入无菌空气控制ORP分别不低于-490、-460、-430及-400 mV丁醇发酵情况。其中,控制ORP不低于-460 mV时,丁醇和总溶剂产量分别达到13.19 g·L^-1及19.71 g·L^-1,相对于不控制ORP的丁醇自然发酵分别提高了139.38%及117.07%,残糖浓度降低至3.20 g·L^-1,糖利用率高达94.18%。该调控策略有效地解决了以葡萄糖和果糖混合糖为底物的丁醇发酵过程中存在的残糖浓度高、丁醇产量低的问题。