shuler and kargi bioprocess engineering pdf

Shuler And Kargi Bioprocess Engineering Pdf

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Bioprocess Engineering-Basic Concepts by Shuler and Kargi

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Start by pressing the button below! Doran Bioprocess Engineering Prin The ability to manipulate DNA has already changed our perceptions of medicine, agriculture and management. Scientific breakthroughs in gene engineering and cell fusion are being strengthening biotechnology industry into products and services.

Many a student has been enticed by the promise ofbiotechnology and the excitement of being near the cutting edge of scientific advancement. However, the value of biotechnology is more likely to be assessed by business, government and consumers alike in terms of commercial applications, impact on the marketplace and financial success. Graduates trained in molecular biology and cell manipulation soon realise that these techniques are only part of the complete picture; bringing about the full benefits of biotechnology requires substantial manufacturing capability involving large-scale processing of biological material.

For the most part, chemical engineers have assumed the responsibility for bioprocess development. However, increasingly, biotechnologists are being employed by companies to work in co-operation with biochemical engineers to achieve pragmatic commercial goals. Yet, while aspects of biochemistry, microbiology and molecular genetics have for many years been included in chemical-engineering curricula, there has been relatively little attempt to teach biotechnologists even those qualitative aspects of engineering applicable to process design.

The primary aim of this book is to present the principles of bioprocess engineering in a way that is accessible to biological scientists. It does not seek to make biologists into bioprocess engineers, but to expose them to engineering concepts and ways of thinking.

The material included in the book has been used to teach graduate students with diverse backgrounds in biology, chemistry and medical science. While several excellent texts on bioprocess engineering are currently available, these generally assume the reader already has engineering training.

On the other hand, standard chemical-engineering environmental expression, protein translated by a texts do not revolutionary often considernew examples from bioprocessing and are written almost exclusively with the petroleum and chemical industries in mind. There was a need for a textbook which explains the engineering approach to process analysis while providing worked examples and problems about biological systems.

In this book, more than problems and calculations encompass a wide range of bioprocess applications involving recombinant cells, plant- and animal-cell cultures and immobilised biocatalysts as well as traditional fermentation systems.

It is assumed that the reader has an adequate background in biology. One of the biggest challenges in preparing the text was determining the appropriate level of mathematics.

In general, biologists do not often encounter detailed mathematical analysis. However, as a great deal of engineering involves formulation and solution of mathematical models, and many important conclusions about process behaviour are best explained using mathematical relationships, it is neither easy nor desirable to eliminate all mathematics from a textbook such as this. Mathematical treatment is necessary to show how design equations depend on crucial assumptions; in other cases the equations are so simple and their application so useful that non-engineering scientists should be familiar with them.

Derivation of most mathematical models is fully explained in an attempt to counter the tendency of many students to memorise rather than understand the meaning of equations. Nevertheless, in fitting with its principal aim, much more of this book is descriptive compared with standard chemicalengineering texts. The chapters are organised around broad engineering subdisciplines such as mass and energy balances, fluid dynamics, transport phenomena and reaction theory, rather than around particular applications ofbioprocessing.

That the same fundamental engineering principle can be readily applied to a variety of bioprocess industries is illustrated in the worked examples and problems. Although this textbook is written primarily for senior students and graduates ofbiotechnology, it should also be useful in food-, environmental- and civil-engineering Preface xiY , courses. Because the qualitative treatment of selected topics is at a relatively advanced level, the book is appropriate for chemical-engineering graduates, undergraduates and industrial practitioners.

I would like to acknowledge several colleagues whose advice I sought at various stages of manuscript preparation. Sections 3. Hall who provided lecture notes on this topic. Thanks are also due to Jacqui Quennell whose computer drawing skills are evident in most of the book's illustrations. Pauline M. Bioprocess operations make use of microbial, animal andplant cells and components of cells such as enzymes to manufacture newproducts and destroy harmful wastes.

Use of microorganisms to transform biological materials forproduction offermented foods has its origins in antiquity. Since then, bioprocesseshave been developedfor an enormous range of commercialproducts, from relatively cheap materials such as industrial alcohol and organic solvents, to expensive specialty chemicals such as antibiotics, therapeuticproteins and vaccines. Industrially-useful enzymes and living cells such as bakers'and brewers'yeast are also commercialproducts of bioprocessing.

Table 1. Typical organisms used and the approximate market size for the products are also listed. The table is by no means exhaustive; not included are processes for wastewater treatment, bioremediation, microbial mineral recovery and manufacture of traditional foods and beverages such as yoghurt, bread, vinegar, soy sauce, beer and wine.

Industrial processes employing enzymes are also not listed in Table 1. Large quantities of enzymes are used commercially to convert starch into fermentable sugars which serve as starting materials for other bioprocesses. Our ability to harness the capabilities of cells and enzymes has been closely related to advancements in microbiology, biochemistry and cell physiology.

Knowledge in these areas is expanding rapidly; tools of modern biotechnology such as recombinant DNA, gene probes, cell fusion and tissue culture offer new opportunities to develop novel products or improve bioprocessing methods. Visions of sophisticated medicines, cultured human tissues and organs, biochips for new-age computers, environmentally-compatible pesticides and powerful pollution-degrading microbes herald a revolution in the role of biology in industry.

Although new products and processes can be conceived and partially developed in the laboratory, bringing modern biotechnology to industrial fruition requires engineering skills and know-how. Biological systems can be complex and difficult to control; nevertheless, they obey the laws of chemistry and physics and are therefore amenable to engineering analysis.

Substantial engineering input is essential in many aspects of bioprocessing, including design and operation of bioreactors, sterilisers and product-recovery equipment, development of systems for process automation and control, and efficient and safe layout of fermentation factories.

The subject of this book, bioprocessengineering, is the study of engineering principles applied to processes involving cell or enzyme catalysts.

As an example, consider manufacture of a new recombinant-DNA-derived product such as insulin, growth hormone or interferon. As shown in Figure 1. The first stages ofbioprocess development Steps are concerned with genetic manipulation of the host organism; in this case, a gene from animal DNA is cloned into Escherichia coil Genetic engineering is done in laboratories on a small scale by scientists trained in molecular biology and biochemistry.

Tools of the trade include Petri dishes, micropipettes, microcentrifuges, nano-or microgram quantities of restriction enzymes, and electrophoresis gels for DNA and protein fractionation. In terms of bioprocess development, parameters of major importance are stability of the constructed strains and level of expression of the desired product.

Shuler, , Bioprocess engineering. Meyers, Ed. Solution can be achieved in many different ways; usually it is a good idea to express each variable as a function of only one other variable, b is already written simply as a function of cin 4 ; let us try expressing the other variables solely in terms of c. From 1 : d- c. Using this result for cin 8 , 4 , 6 and 9 gives: a - Check that these coefficient values satisfy Eqs 1 - 5.

Although elemental balances are useful, the presence of water in Eq. Because water is usually present in great excess and changes in water concentration are inconvenient to measure or experimentally verify, H and O balances can present difficulties.

Instead, a useful principle is conservation of reducing power or available electrons, which can be applied to determine quantitative relationships between substrates and 4 Material Balances 78 products. An electron balance shows how available electrons from the substrate are distributed in reaction. The number of available electrons found in organic material is calculated from the valence of the various elements: 4 for C, 1 for H , - 2 for O, 5 for P, and 6 for S.

The number of available electrons for N depends on the reference state if ammonia is the reference, 0 for molecular nitrogen N 2, and 5 for nitrate. The reference state for cell growth is usually chosen to be the same as the nitrogen source in the medium. In the following discussion it will be assumed for convenience that ammonia is used as nitrogen source; this can easily be changed if other nitrogen sources are employed [5]. Degree o f reduction, ', is defined as the number of equivalents of available electrons in that quantity of material containing 1 g atom carbon.

Electrons available for transfer to oxygen are conserved during metabolism. In a balanced growth equation, number of available electrons is conserved by virtue of the fact that the amounts of each chemical element are conserved. Applying this principle to Eq. Note that the available-electron balance is not independent of the complete set of elemental balances; if the stoichiometric equation is balanced in terms of each element including H and O, the electron balance is implicitly satisfied.

However, one electron balance, two elemental balances and one measured quantity are still inadequate information for solution of five unknown coefficients; another experimental quantity is required. As cells grow there is, as a general approximation, a linear relationship between the amount of biomass produced and the amount of substrate consumed.

Biomass yield is greater in aerobic than in anaerobic cultures; choice of electron acceptor, e. When Yxs is constant throughout growth, its experimentally-determined value can be used to determine the stoichiometric coefficient c in Eq. However, before applying measured values of Yxs and Eq. For example, we must be sure that substrate is not used to synthesise extracellular products other than CO 2 and H One complication with real cultures is that some fraction of substrate consumed is always used for maintenance activities such as maintenance of membrane potential and internal pH, turnover of cellular components and cell motility.

These metabolic functions require substrate but do not necessarily produce cell biomass, CO 2 and H 2 0 in the way described by Eq. It is important to account for maintenance when experimental information is used to complete stoichiometric equations; maintenance requirements and the difference between observed and true yields are discussed further in Chapter For the time being, we will assume that available values for biomass yield reflect substrate consumption for growth only.

Product synthesis introduces one extra unknown stoichiometric coefficient to the equation; thus, an additional relationship between coefficients is required. It means that if we know which organism YB ' substrate wand Ys and product j and YI, are involved in cell culture, and the yields of biomass c and product f , we can quickly calculate the oxygen demand. Of course we could also determine a by solving for all the stoichiometric coefficients of Eq. In these cases, independent reaction equations must be used to describe growth and product synthesis.

In Eq. This relationship can be used to obtain upper bounds for the yields of biomass and product from substrate. Oxygen demand is represented by the stoichiometric coefficient a in Eqs 4.

Oxygen requirement is related directly to the electrons available for transfer to oxygen; the oxygen demand can therefore be derived from an appropriate electron balance. When product synthesis occurs as represented by Eq.

Therefore, even if we do not know the stoichiometry of growth, we can quickly calculate an upper limit for biomass yield from the molecular formulae for substrate and product. If the composition of the cells is unknown, YBcan be 4 Material Balances 80 taken as 4. Maximum biomass yields for several substrates are listed in Table 4. These quantities are sometimes known as thermodynamic maximum biomass yields.

Table 4.

Bioprocess Engineering by Shuler and Kargi

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Bioprocess Engineering Principles

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