Output stabilization of fermentation processes: A binary control system approach

Two types of continuous fermentation processes for product formation are considered. The processes are described by three nonlinear differential equations with uncertain parameters. Binary control design for theses processes is proposed. The asymptotic output stabilization problems are solved. The control design is carried out with direct use of nonlinear model and microbiological expert knowledge. The good system robustness to parameter uncertainties and external disturbance is demonstrated by simulation investigations.     

Experimental design methods for bioengineering applications

Experimental design is a form of process analysis in which certain factors are selected to obtain the desired responses of interest. It may also be used for the determination of the effects of various independent factors on a dependent factor. The bioengineering discipline includes many different areas of scientific interest, and each study area is affected and governed by many different factors. Briefly analyzing the important factors and selecting an experimental design for optimization are very effective tools for the design of any bioprocess under question. This review summarizes experimental design methods that can be used to investigate various factors relating to bioengineering processes. The experimental methods generally used in bioengineering are as follows: full factorial design, fractional factorial design, Plackett–Burman design, Taguchi design, Box–Behnken design and central composite design. These design methods are briefly introduced, and then the application of these design methods to study different bioengineering processes is analyzed.     

Engineering the Virtual Enterprise: An Architecture-Driven Modeling Approach

The managerial and organization practices required by an increasingly dynamic competitive manufacturing, business, and industrial environment include the formation of “virtual enterprises.” A major concern in the management of virtual enterprises is the integration and coordination of business processes contributed by partner enterprises. The traditional methods of process modeling currently used for the design of business processes do not fully support the needs of the virtual enterprise. The design of these virtual enterprises imposes requirements that make it more complex than conventional intraorganizational business process design. This paper first describes an architecture that assists in the design of the virtual enterprise. Then it discusses business process reengineering (BPR) as a methodology for modeling and designing virtual organizations. While BPR presents many useful tools, the approach itself and the modeling tools commonly used for redesign have fundamental shortcomings when dealing with the virtual enterprise. However, several innovative modeling approaches provide promise for this problem. The paper discusses some of these innovative modeling approaches, such as object-oriented modeling of business processes, agent modeling of organizational players, and the use of ontological modeling to capture and manipulate knowledge about the players and processes. The paper concludes with a conceptual modeling methodology that combines these approaches under the enterprise architecture for the design of virtual enterprises.     

Enzyme stability in downstream processing. Part 2: quantification of inactivation

In biotechnological recovery processes the instability of the product can lead to large losses in the sequence of recovery processes needed to purify the product. As the cost of the final active product is strongly dependent on the recovery yield, this will lead to an increase in product cost. Therefore knowledge of factors that influence stability is important. This Part 2 provides the basic principles for design and operation of processes in which inactivation takes place. Simple kinetics and reactor modelling are discussed. These are applied to a number of unit operations: cell disruption, membrane filtration, drying and reversed micellar extraction. It is thus shown that the basic tools for modeling of biochemical processes provide us with the data needed for optimal process design and operation.     

Sliding-mode control of fermentation processes

Continuous fermentation processes described by two nonlinear differential equations with uncertain parameters are considered. Sliding mode control design for these processes is proposed. The control design is carried out with direct use of nonlinear model, expert knowledge and on-line measurement of output variable only. Chattering phenomena are avoided by realizing the sliding mode with respect to the control input derivative. The excellent performance of presented control is proved through simulation investigations.     

Sustainability indicator development—Science or political negotiation?

The efforts to develop sustainability indicators have strongly increased since the beginning of the 1990s, often led by intergovernmental processes. More recently, a number of sustainability indicator development processes have been initiated within large research projects that aim to design tools for sustainability assessments, funded by the European Union. The development of sustainability indicators provides a particular challenge to scientists, given the essentially normative dimension of the concept of “sustainability”. Thus, we argue, the development of sustainability indicators is a process of both scientific “knowledge production” and of political “norm creation”, and both components need to be properly acknowledged. Based on a respective theoretical framework and comparing five cases of sustainability indicator development processes (three science-led and two led by intergovernmental processes), we find that the political norm creation dimension is not fully and explicitly recognized in science-led processes. The paper concludes by discussing a number of implications for the design of sustainability indicator development processes, in particular with regard to participation and representation as well as adjustment of indicators over time.     

Biofilms and fluidized bed fermentation

The exploitation of biofilms in industrial processes such as wastewater treatment and metabolite production is described. In this way it is intended to highlight the positive aspects of biofilms, and provide a contrast with the negative associations which these microbial aggregations normally have. In particular, the exploitation of adhesive microbes in fluidized bed operation is discussed. A range of processes is outlined, from wastewater treatment to the production of ethanol, enzymes, and antibiotics. These various processes use a range of cell types; which has required the modification of the basic design of FB bioreactor, e.g. for anaerobic or aerobic operation; and for bacteria, actinomycetes, or plant cells. One basic design is illustrated, and reference made to how this is modified for different fermentations.     

New tools for the genetic manipulation of filamentous fungi

Filamentous fungi have a long-standing tradition as industrial producers of primary and secondary metabolites. Initially, industrial scientists selected production strains from natural isolates that fulfilled both microbiological and technical requirements for economical production processes. Subsequently, genetically modified strains with novel properties were obtained through traditional strain improvement programs relying mostly on random mutagenesis. In recent years, however, recombinant technologies have contributed significantly to improve the capacities of production and have also allowed the design of genetically manipulated strains. These major advances were only made possible by basic research bringing deeper and novel insights into cellular and molecular fungal processes, thus allowing the design of genetically manipulated strains. This better understanding of fundamental genetic processes in model organisms has resulted in the design and generation of new experimental transformation strategies to manipulate specifically gene expression and function in diverse filamentous fungi, including those having a biotechnical significance. In this review, we summarize recent developments in the application of homologous DNA recombination and RNA interference to manipulate fungal recipients for further improvement of physiology and development in regards to biotechnical and pharmaceutical applications.     

Optimizing green design using ant colony-based approach

Purpose

In response to the increasing concerns on the environmental conservation and energy saving, manufacturers are more aware of proving the ‘green’ performance of their products. Some qualitative eco design tools are used to support the development of greener products; however, most of these tools require subjective judgement during the evaluation processes. This paper is therefore to propose an alternative approach that is objective, systematic and efficient, by integrating the ant colony optimization (ACO) and life cycle assessment (LCA), to facilitate the decision-making process.

Methods

The proposed integrative LCA-ACO approach aims to support the simultaneous thorough evaluations of multiple design options. A sequence of options of the lowest corresponding environmental impact value can be obtained. A case application example of various design combinations is presented to demonstrate the applicability of the proposed approach.

Results and discussion

The proposed approach offers decision makers a preliminary fast-track approach for screening decisions without lengthy processes of LCA studies. This approach helps the decision makers, especially during the early design selection stages, identifying the most appropriate design combination from the environmental perspective. The proposed approach is proved a significant contribution to the field of LCA and green product design.

Conclusions

Since full-scale LCA studies require significant effort in data collection processes and experts for result interpretations, it would be time consuming and costly to conduct a full-scale LCA during early product development processes. The proposed approach offers a more convenient way for decision makers to assess multiple design options regarding the environmental considerations. The case example presented in this paper proves the practicality of the proposed approach.

     

雨水花园设计的生态表达

雨水花园设计的生态表达是对雨水花园设计中有雨水花园特色的生态性要素和有雨水生态特征的设计表达方法的探讨。雨水花园设计中有特色的生态过程主要有雨水处理的生态过程、花园生态系统中植物生态过程以及人感知雨水生态的精神生态过程。基于现阶段雨水花园设计实践,在生态综合效应下,建构了由有特征的生态性要素、生态显露设计和生态技术联盟组成的雨水花园设计生态表达图式。     

Fuel ethanol production: process design trends and integration opportunities

Current fuel ethanol research and development deals with process engineering trends for improving biotechnological production of ethanol. In this work, the key role that process design plays during the development of cost-effective technologies is recognized through the analysis of major trends in process synthesis, modeling, simulation and optimization related to ethanol production. Main directions in techno-economical evaluation of fuel ethanol processes are described as well as some prospecting configurations. The most promising alternatives for compensating ethanol production costs by the generation of valuable co-products are analyzed. Opportunities for integration of fuel ethanol production processes and their implications are underlined. Main ways of process intensification through reaction-reaction, reaction-separation and separation-separation processes are analyzed in the case of bioethanol production. Some examples of energy integration during ethanol production are also highlighted. Finally, some concluding considerations on current and future research tendencies in fuel ethanol production regarding process design and integration are presented.     

Membrane processes in biotechnology: an overview

Membrane processes are increasingly reported for various applications in both upstream and downstream technology, such as the established ultrafiltration and microfiltration, and emerging processes as membrane bioreactors, membrane chromatography, and membrane contactors for the preparation of emulsions and particles. Membrane systems exploit the inherent properties of high selectivity, high surface-area-per-unit-volume, and their potential for controlling the level of contact and/or mixing between two phases. This review presents these various membrane processes by focusing more precisely on membrane materials, module design, operating parameters and the large range of possible applications.     

Designing Food Structure to Control Stability, Digestion, Release and Absorption of Lipophilic Food Components

The bioavailability of dietary lipophilic components may be either increased or decreased by manipulating the microstructure and/or physicochemical properties of the foods that contain them. This article stresses how knowledge of the molecular, physicochemical, and physiological processes that occur during lipid ingestion, digestion, and absorption can be used to rationally design food structures to control these processes and therefore impact the rate or extent of lipid digestion and/or absorption. These approaches include controlling the molecular characteristics of the lipid molecules, altering lipid droplet size or interfacial properties, and manipulating food matrix structure and composition. Improved knowledge of the molecular, physicochemical, and physiological processes that occur during lipid ingestion, digestion, and absorption will facilitate the rational design and fabrication of functional foods for improved health and wellness.     

Self-Interest and the Design of Rules

Rules regulating social behavior raise challenging questions about cultural evolution in part because they frequently confer group-level benefits. Current multilevel selection theories contend that between-group processes interact with within-group processes to produce norms and institutions, but within-group processes have remained underspecified, leading to a recent emphasis on cultural group selection as the primary driver of cultural design. Here we present the self-interested enforcement (SIE) hypothesis, which proposes that the design of rules importantly reflects the relative enforcement capacities of competing parties. We show that, in addition to explaining patterns in cultural change and stability, SIE can account for the emergence of much group-functional culture. We outline how this process can stifle or accelerate cultural group selection, depending on various social conditions. Self-interested enforcement has important bearings on the emergence, stability, and change of rules.     

大规模生产制备质粒DNA技术进展

质粒DNA疫苗或基因治疗剂是生物制品的新品种。鉴于质粒DNA表达效率低、持续时间短,需建立一套大规模生产制备质粒DNA的工艺,即发酵、碱性裂解、分离纯化及质量控制。目前质粒DNA大规模生产已经达到千克级水平,一些产品正在进行临床实验。     

Engineering-Based Contributions in Cryobiology

Over the past three decades there has been an increasing number of engineering-trained researchers who have made the field of cryobiology a primary focus of their work. In prior times the advances in cryobiology were accomplished nearly exclusively by members of the life and medical science communities. In general, the practice of engineering may be distinguished by two features: an emphasis on rigorous quantitative measurement and analysis of processes and the synthesis of an understanding of fundamental principles of nature into the design of novel devices and processes for specific applications. One area of focus in cryobiology that engineers have emphasized is the design of new apparatus, including both experimental instrumentation and clinical diagnostic and therapeutic devices. There has been a broad spectrum of new apparatus invented to enable the quantitative control and measurement of the fundamental phenomena that govern processes in cryobiology. Among these are low-temperature cryomicroscopy stages and mass diffusion chambers, which now are often used in conjunction with digital image analysis algorithms to quantify changes to individual cells and tissues elicited during the process being studied. Other applications include the development of novel measurement techniques for assessing system properties and states during freezing and thawing. In cryosurgery and in cryopreservation new probes and apparatus have been designed to provide more accurate and effective processes to achieve clinical objectives. Equally important and complementary to the design of hardware is the development of analytical models which can be applied to understand and interpret experimental data and to predict the behavior of systems for operation in domains beyond those for which empirical data are available. Perhaps the most critical role of these models is for inverse solution techniques with experimental data to obtain values for the intrinsic constitutive properties of tissues which govern their response to freezing and thawing processes.     

Strategies for developing design spaces for viral clearance by anion exchange chromatography during monoclonal antibody production

The quality‐by‐design (QbD) regulatory initiative promotes the development of process design spaces describing the multidimensional effects and interactions of process variables on critical quality attributes of therapeutic products. However, because of the complex nature of production processes, strategies must be devised to provide for design space development with reasonable allocation of resources while maintaining highly dependable results. Here, we discuss strategies for the determination of design spaces for viral clearance by anion exchange chromatography (AEX) during purification of monoclonal antibodies. We developed a risk assessment for AEX using a formalized method and applying previous knowledge of the effects of certain variables and the mechanism of action for virus removal by this process. We then use design‐of‐experiments (DOE) concepts to perform a highly fractionated factorial experiment and show that varying many process parameters simultaneously over wide ranges does not affect the ability of the AEX process to remove endogenous retrovirus‐like particles from CHO‐cell derived feedstocks. Finally, we performed a full factorial design and observed that a high degree of viral clearance was obtained for three different model viruses when the most significant process parameters were varied over ranges relevant to typical manufacturing processes. These experiments indicate the robust nature of viral clearance by the AEX process as well as the design space where removal of viral impurities and contaminants can be assured. In addition, the concepts and methodology presented here provides a general approach for the development of design spaces to assure that quality of biotherapeutic products is maintained. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

Process and technoeconomic analysis of leading pretreatment technologies for lignocellulosic ethanol production using switchgrass

Six biomass pretreatment processes to convert switchgrass to fermentable sugars and ultimately to cellulosic ethanol are compared on a consistent basis in this technoeconomic analysis. The six pretreatment processes are ammonia fiber expansion (AFEX), dilute acid (DA), lime, liquid hot water (LHW), soaking in aqueous ammonia (SAA), and sulfur dioxide-impregnated steam explosion (SO(2)). Each pretreatment process is modeled in the framework of an existing biochemical design model so that systematic variations of process-related changes are consistently captured. The pretreatment area process design and simulation are based on the research data generated within the Biomass Refining Consortium for Applied Fundamentals and Innovation (CAFI) 3 project. Overall ethanol production, total capital investment, and minimum ethanol selling price (MESP) are reported along with selected sensitivity analysis. The results show limited differentiation between the projected economic performances of the pretreatment options, except for processes that exhibit significantly lower monomer sugar and resulting ethanol yields.     

Directed evolution of (betaalpha)(8)-barrel enzymes

Natural molecular evolution supplies us with manifold examples of protein engineering. The imitation of these natural processes in the design of new enzymes has led to surprising and insightful results. Well-suited for design by evolutionary methods are enzymes with the common and versatile (betaalpha)(8)-barrel fold. Studies of enzyme stability, folding and design as well as the evolution of (betaalpha)(8)-barrel enzymes are discussed.