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Shigeo Katoh, Jun-ichi Horiuchi, and Fumitake Yoshida

Biochemical Engineering

A Textbook for Engineers, Chemists and Biologists

Second, Completely Revised and Enlarged Edition

Wiley Logo

Preface to the Second Edition

Bioengineering can be defined as the application of the various branches of engineering, including mechanical, electrical, and chemical engineering, to biological systems, including those related to medicine. Likewise, biochemical engineering refers to the application of chemical engineering to biological systems. This book is intended for use by undergraduates, and deals with the applications of chemical engineering to biological systems in general. In that respect, no preliminary knowledge of chemical engineering is assumed.

In the first edition of Biochemical Engineering, published in 2009, we attempted to demonstrate how a typical chemical engineer would address and solve such problems in order to facilitate an understanding by newcomers to this field of study. In Part I of the book, we outlined some very elementary concepts of chemical engineering for those new to the field, and in Part II, “Unit operations and apparatus for bio-systems” were covered. Although in Part III we described applications of biochemical engineering to bioprocesses and to other areas, this part did not include a chapter for “Bioprocess control.” In bioindustry processes, the control of bioreactors is essential for the production of high-quality products under validated conditions. A fundamental understanding of process control should be very useful for all biochemical engineers, as well as for chemical engineers. Thus, we welcome a new coauthor, Prof. Jun-ichi Horiuchi, who is a leading researcher in the Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology.

Currently, many biopharmaceuticals, which are proteins in many cases, are produced in many bioindustry fields, and the measuring of the concentrations and bioactivities of these products is thus becoming essential in bioindustry. We have added a new section for “Biorecognition assay” in Chapter 11, and we explain the fundamental aspects of biorecognition and its application for the measurement of bioproducts at low concentrations. In this edition, we have included some examples and some new problems to assist in the progress with learning how to solve problem.

We would like to express great thanks to Prof. Michimasa Kishimoto and Prof. Yoichi Kumada for their useful discussion, particularly for Chapters 11–13. We also thank the external reviewers for providing invaluable suggestions and the staffs of Wiley-VCH Verlag for planning, editing, and producing this second edition.

Shigeo Katoh

Preface to the First Edition

Bioengineering can be defined as the application of the various branches of engineering, including mechanical, electrical, and chemical engineering, to biological systems, including those related to medicine. Likewise, biochemical engineering refers to the application of chemical engineering to biological systems. This book is intended for use by undergraduates, and deals with the applications of chemical engineering to biological systems in general. In that respect, no preliminary knowledge of chemical engineering is assumed.

Since the publication of the pioneering text Biochemical Engineering, by Aiba, Humphrey, and Millis in 1964, several articles on the so-called “biochemical” or “bioprocess” engineering have been published. While all of these have combined the applications of chemical engineering and biochemistry, the relative space allocated to the two disciplines has varied widely among the different texts.

In this book, we describe the application of chemical engineering principles to biological systems, but in doing so assume that the reader has some practical knowledge of biotechnology, but no prior background in chemical engineering. Hence, we have attempted to demonstrate how a typical chemical engineer would address and solve such problems. Consequently, a simplified rather than rigorous approach has often been adopted in order to facilitate an understanding by newcomers to this field of study. Although in Part I of the book we have outlined some very elementary concepts of chemical engineering for those new to the field, the book can be used equally well for senior or even postgraduate level courses in chemical engineering for students of biotechnology, when the reader can simply start from Part II. Naturally, this book should prove especially useful for those biotechnologists interested in self-studying chemical bioengineering. In Part III, we provide descriptions of the applications of biochemical engineering not only to bioprocessing but also to other areas, including the design of selected medical devices. Moreover, to assist progress in learning, a number of worked examples, together with some “homework” problems, are included in each chapter.

I would like to thank the two external reviewers, Prof. Ulfert Onken (Dortmund University) and Prof. Alois Jungbauer (University of Natural Resources and Applied Life Sciences), for providing invaluable suggestions. I also thank the staff of Wiley-VCH Verlag for planning, editing, and producing this book. Finally I thank Kyoko, my wife, for her support while I was writing this book.

About the companion website

This book is accompanied by a companion website:

image

http://www.wiley.com/go/katoh/biochem_eng_e2

The website includes detailed solutions to the problems in the book.

Nomenclature

(Some symbols and subscripts explained in the text are omitted.)

A area (m2)
a specific interfacial area (m2 m−3 or m−1)
b width of rectangular conduit (m)
C concentration (kg or kmol m−3, g or mol cm−3)
Cn cell number density (m−3)
Cp heat capacity (kcal °C−1 or kJ K−1)
Cl clearance of kidney or hemodialyzer (cm3 min−1)
cp specific heat capacity (kJ kg−1 K−1 or kcal kg−1 °C−1)
D diffusivity (m2 h−1 or cm2 s−1)
D tank or column diameter (m)
Dl dialysance of hemodialyzer (cm3 min−1)
d diameter (m or cm)
de equivalent diameter (m or cm)
E enhancement factor = k*/k (−)
E internal energy (kJ)
Ea activation energy (kJ kmol−1)
ED, EH, EV eddy diffusivity, eddy thermal diffusivity, and eddy kinematic viscosity, respectively (m2 h−1 or cm2 s−1)
Ef effectiveness factor (−)
F volumetric flow rate (m3 h−1 or cm3 s−1 or min−1)
f friction factor
Gm fluid mass velocity (kg h−1 m−2)
GV volumetric gas flow rate per unit area (m h−1)
g gravity acceleration (=9.807 m s−2)
H henry's law constant (atm or Pa kmol−1 (or kg−1) m3)
H height, height per transfer unit (m)
H enthalpy (kJ)
Hs height equivalent to an equilibrium stage (−)
Ht hematocrit (%)
h individual phase film coefficient of heat transfer (W m−2 K−1 or kcal h−1 m−2 °C−1)
J mass transfer flux (kg or kmol h−1 m−2)
JF filtrate flux (m s−1, m h−1, cm min−1, or cm s−1)
K consistency index (g cm−1 sn−2 or kg m−1 sn−2)
K overall mass transfer coefficient (m h−1)
K distribution coefficient, equilibrium constant (−)
Km michaelis constant (kmol m−3 or mol cm−3)
Kp proportional gain (−)
Kc ultimate gain (−)
k individual phase mass transfer coefficient (m h−1 or cm s−1)
k reaction rate constant (s−1, m3 kmol−1 s−1, etc.)
kM diffusive membrane permeability coefficient (m h−1 or cm s−1)
L length (m or cm)
Lv volumetric liquid flow rate per unit area (m h−1)
m partition coefficient (−)
N mass transfer rate per unit volume (kmol or kg h−1 m−3)
N number of revolutions (s−1)
N number of transfer unit (−)
N number of theoretical plate (−)
Ni number of moles of i component (kmol)
n flow behavior index (−)
n cell number (−)
O output signal (−)
P total pressure (Pa or bar)
P power requirement (kJ s−1 or W)
p partial pressure (Pa or bar)
Q heat transfer rate (kcal h−1 or kJ s−1 or W)
Q total flow rate (m3 s−1)
q heat transfer flux (W m−2 or kcal h−1 m−2)
q adsorbed amount (kmol kg−1)
R gas law constant, 0.08206 atm l gmol−1 K−1, (= 8.314 kJ kmol−1 K−1, etc.)
R hydraulic resistance in filtration (m−1)
R, r radius (m or cm)
r sphere-equivalent particle radius (m or cm)
ri reaction rate of i component (kmol m−3 s−1)
RQ respiratory quotient (−)
T temperature (K)
TI integration time constant (s)
TD differential time constant (s)
T temperature (°C or K)
t time (s)
U overall heat transfer coefficient (kcal h−1 m−2 °C−1 or W m−2 K−1)
U superficial velocity (m s−1 or cm s−1)
u velocity (m s−1 or cm s−1)
V volume (m3)
Vmax maximum reaction rate (kmol m−3 s−1)
v velocity averaged over conduit cross section (m s−1 or cm s−1)
vt terminal velocity (m s−1)
W work done to system (kJ s−1 or W)
W mass flow rate per tube (kg s−1 or g s−1)
W peak width (m3 or s)
w weight (kg)
x thickness of wall or membrane (m or cm)
x mole fraction (−)
x fractional conversion (−)
YxS cell yield (kg dry cells/kg substrate consumed)
y distance (m or cm)
y oxygen saturation (% or −)
Δy effective film thickness (m or cm)
Z column height (m)
z height of rectangular conduit of channel (m or cm)

Subscripts

G gas
i interface, inside, inlet
L liquid
O outside, outlet
0 initial

Superscripts

* value in equilibrium with the other phase

Greek letters

α thermal diffusivity (m2 h−1 or cm2 s−1)
α specific cake resistance (m kg−1)
γ shear rate (s−1)
ϵ void fraction (−)
ϵ gas holdup (−)
ϵ deviation (−)
φ thiele modulus (−)
κ thermal conductivity (W m−1 K−1 or kcal m−1 h−1 °C−1)
μ viscosity (Pa s or g cm−1 s−1)
μ specific growth rate (h−1)
ν kinematic viscosity = μ/ρ (cm2 s−1 or m2 h−1)
ν specific substrate consumption rate (g-substrate g-cell−1 h−1)
Π osmotic pressure (atm or Pa)
ρ density (kg m−3)
ρ specific product formation rate (g-product g-cell−1 h−1)
σ surface tension (kg s−2)
σ reflection coefficient (−)
σ standard deviation (−)
τ shear stress (Pa)
τ residence time (s)
ω angular velocity (s−1)

Dimensionless numbers

(Bo) = (g D2ρ/σ) bond number
(Da) = (−ra,max/kLA Cab) damköhler number
(Fr) = [UG/(g D)1/2] froude number
(Ga) = (g D3/ν2) galilei number
(Gz) = (W cp/κL) graetz number
(Nu) = (h d/κ) nusselt number
(Nx) = (F/D L) unnamed
(Pe) = (v L/ED) peclet number
(Pr) = (cp μ/κ) prandtl number
(Re) = (d v ρ/μ) reynolds number
(Sc) = (μ/ρ D) schmidt number
(Sh) = (k d/D) sherwood number
(St) = (k/v) stanton number

Part I:
Basic Concepts and Principles

1
Introduction

1.1 Background and Scope

Engineering can be defined as “the science or art of practical applications of the knowledge of pure sciences such as physics, chemistry, and biology.”

Compared with civil, mechanical, and other forms of engineering, chemical engineering is a relatively young branch of the subject that has been developed since the early twentieth century. The design and operation of efficient chemical plant equipment are the main duties of chemical engineers. It should be pointed out that industrial-scale chemical plant equipment cannot be built simply by enlarging the laboratory apparatus used in basic chemical research. Consider, for example, the case of a chemical reactor – that is, the apparatus used for chemical reactions. Although neither the type nor size of the reactor will affect the rate of chemical reaction per se, they will affect the overall or apparent reaction rate, which involves effects of physical processes, such as heat and mass transfer and fluid mixing. Thus, in the design and operation of plant-size reactor, knowledge of such physical factors – which is often neglected by chemists – is important.

G. E. Davis, a British pioneer in chemical engineering, described in his book, A Handbook of Chemical Engineering (1901, 1904), a variety of physical operations commonly used in chemical plants. In the United States, such physical operations as distillation, evaporation, heat transfer, gas absorption, and filtration were termed “unit operations” in 1915 by A. D. Little of the Massachusetts Institute of Technology (MIT), where the instruction of chemical engineering was organized via unit operations. The first complete textbook of unit operations entitled Principles of Chemical Engineering by Walker, Lewis, and McAdams of the MIT was published in 1923. Since then, the scope of chemical engineering has been broadened to include not only unit operations but also chemical reaction engineering, chemical engineering thermodynamics, process control, transport phenomena, and other areas.

Bioprocess plants using microorganisms and/or enzymes, such as fermentation plants, have many characteristics similar to those of chemical plants. Thus, a chemical engineering approach should be useful in the design and operation of various plants that involve biological systems, if differences in the physical properties of some materials are taken into account. Furthermore, chemical engineers are required to have some knowledge of biology when tackling problems that involve biological systems.

Since the publication of a pioneering textbook [1] in 1964, some excellent books [2, 3] have been produced in the area of the so-called biochemical or bioprocess engineering. Today, the applications of chemical engineering are becoming broader to include not only bioprocesses but also various biological systems involving environmental technology and even some medical devices, such as artificial organs.

1.2 Dimensions and Units

A quantitative approach is important in any branch of engineering. However, this does not necessarily mean that engineers can solve everything theoretically, and quite often they use empirical rather than theoretical equations. Any equation – whether theoretical or empirical – that expresses some quantitative relationship must be dimensionally sound, as stated below.

In engineering calculations, a clear understanding of dimensions and units is very important. Dimensions are the basic concepts in expressing physical quantities. Dimensions used in chemical engineering are length (L), mass (M), time (T), the amount of substance (n), and temperature (θ). Some physical quantities have combined dimensions; for example, the dimensions of velocity and acceleration are L T−1 and L T−2, respectively. Sometimes, force (F) is also regarded as a dimension; however, as the force acting on a body is equal to the product of the mass of that body and the acceleration working on the body in the direction of force, F can be expressed as M L T−2.

Units are measures for dimensions. Scientists normally use the centimeter (cm), gram (g), second (s), mole (mol), and degree centigrade (°C) as the units for the length, mass, time, amount of substance, and temperature, respectively (the CGS (centimeter–gram–second) system), whereas the units often used by engineers are m, kg, h, kmol, and °C. Traditionally, engineers have used the kilogram as the unit for both mass and force. However, this practice sometimes causes confusion, and to avoid this, a designation of kilogram-force (kgf) is recommended. The unit for pressure, kg cm−2, often used by plant engineers should read kgf cm−2. Mass and weight are different entities; the weight of a body is the gravitational force acting on the body, that is, (mass) (gravitational acceleration g). Strictly speaking, g – and hence weight – will vary slightly with locations and altitudes on the Earth. It would be much smaller in a space ship.

In recent engineering research papers, units with the International System of Units (SI) are generally used. The SI system is different from the CGS system often used by scientists or from the conventional metric system used by engineers [4]. In the SI system, kilogram is used for mass only, and newton (N), which is the unit for force or weight, is defined as kg m s−2. The unit for pressure, Pa (pascal), is defined as N m−2. It is roughly the weight of an apple distributed over the area of 1 m2. As it is generally too small as a unit for pressure, kPa (kilopascal) (i.e., 1000 Pa), and MPa (megapascal) (i.e., 106 Pa) are more often used. One bar, which is equal to 0.987 atm, is 100 kPa = 0.1 MPa = 1000 hPa (hectopascal).

The SI unit for energy or heat is the joule (J), which is defined as J = N m = kg m2 s−2 = Pa m3. In the SI system, calorie is not used as a unit for heat, and hence no conversion between heat and work, such as 1 cal = 4.184 J, is needed. Power is defined as energy per unit time, and the SI unit for power is W (watt) = J s−1. Since W is usually too small for engineering calculations, kilowatt (=1000 W) is more often used. Although use of the SI units is preferred, we shall also use in this book the conventional metric units that are still widely used in engineering practice. The English engineering unit system is also used in engineering practice, but we do not use it in this text book. Values of the conversion factors between various units that are used in practice are listed in Appendix A, at the back of this book.

Empirical equations are often used in engineering calculations. For example, the following type of equation can relate the specific heat capacity cp (J kg−1 K−1) of a substance with its absolute temperature T (K).

1.1 equation

where a (kJ kg−1 K−1) and b (kJ kg−1 K−2) are empirical constants. Their values in the kcal, kg, and °C units are different from those in the kJ, kg, and K units. Equations such as Equation 1.1 are called dimensional equations. The use of dimensional equations should preferably be avoided; hence, Equation 1.1 can be transformed to a nondimensional equation such as

1.2 equation

where R is the gas law constant with the same dimension as cp and Tc is the critical temperature of the substance in question. Thus, as long as the same units are used for cp and R and for T and Tc, respectively, the values of the ratios in the parentheses as well as the values of coefficients a′ and b′ do not vary with the units used. Ratios such as those in the above parentheses are called dimensionless numbers (groups), and equations involving only dimensionless numbers are called dimensionless equations.

Dimensionless equations – some empirical and some with theoretical bases – are often used in chemical engineering calculations. Most dimensionless numbers are usually called by the names of person(s) who first proposed or used such numbers. They are also often expressed by the first two letters of a name, beginning with a capital letter; for example, the well-known Reynolds number, the values of which determine conditions of flow (laminar or turbulent) is usually designated as Re, or sometimes as NRe. The Reynolds number for flow inside a round straight tube is defined as dvρ/μ, in which d is the inside tube diameter (L), v is the fluid velocity averaged over the tube cross section (L T−1), ρ is the fluid density (M L−3), and μ is the fluid viscosity (M L−1 T−1) (this is defined in Chapter 2). Most dimensionless numbers have some significance, usually ratios of two physical quantities. How known variables could be arranged in a dimensionless number in an empirical dimensionless equation can be determined by a mathematical procedure known as dimensional analysis [5], which is not described in this text. Examples of some useful dimensionless equations or correlations appear in the following chapters of the book.

1.7 Energy Balance

Energy balance is an expression of the first law of thermodynamics – that is, the law of conservation of energy.

For a nonflow system separated from the surroundings by a boundary, the increase in the total energy of the system is given by

1.6 equation

in which Q is the net heat supplied to the system and W is the work done by the system. Q and W are both energy in transit and hence have the same dimension as energy. The total energy of the system includes the total internal energy E, potential energy (PE), and kinetic energy (KE). In normal chemical engineering calculations, changes in (PE) and (KE) can be neglected. The internal energy E is the intrinsic energy of a substance including chemical and thermal energy of molecules. Although absolute values of E are unknown, ΔE, the difference from its base values, for example, from those at 0 °C and 1 atm, is often available or can be calculated.

Neglecting Δ(PE) and Δ(KE) we obtain from Equation 1.6

1.7 equation

The internal energy per unit mass e is an intensive (state) function. Enthalpy h, a compound thermodynamic function defined by Equation 1.8, is also an intensive function.

1.8 equation

in which p is the pressure and v is the specific volume. For a constant pressure process, it can be shown that

1.9 equation

where cp is the specific heat at constant pressure.

For a steady-state flow system, again neglecting changes in the PEs and KEs, the energy balance per unit time is given by Equation 1.10.

1.10 equation

where ΔH is the total enthalpy change, Q is the heat supplied to the system, and Ws is the so-called shaft work done by moving fluid to the surroundings, for example, work done by a turbine driven by a moving fluid.

Problems

1.1 What are the dimensions and SI units for the following physical quantities?

a. Pressure

b. Power

c. Heat capacity

1.2 Is the following equation dimensionally sound?

equation

where p is the atmospheric pressure, z is the height above the sea level, ρ is the specific density of air, and g is the gravity acceleration.

1.3 Convert the following units.

a. energy of 1 cm3 bar into J

b. a pressure of 25.3 lbf in−2 into SI units.

1.4 Explain the difference between mass and weight.

1.5 The Henry constant H′ = p/x for NH3 in water at 20 °C is 2.70 atm. Calculate the value of H = p/C, where C is kmol m−3, and m = y/x where x and y are the mole fractions in the liquid and gas phases, respectively.

1.6 It is required to remove 99% of CH4 from 200 m3 h−1 of air (1 atm, 20 °C) containing 20 mol% of CH4 by absorption into water. Calculate the minimum amount of water required (m3 h−1). The solubility of CH4 in water H′ = p/x at 20 °C is 3.76 × 104 atm.

1.7 A weight with a mass of 1 kg rests at 10 m above ground. It then falls freely to the ground. The acceleration of gravity is 9.8 m s−2. Calculate

a. the PE of the weight relative to the ground

b. the velocity and KE of the weight just before it strikes the ground.

1.8 100 kg h−1 of ethanol vapor at 1 atm, 78.3 °C is to be condensed by cooling with water at 20 °C. How much water will be required in the case where the exit water temperature is 30 °C? The heat of vaporization of ethanol at 1 atm, 78.3 °C is 204.3 kcal kg−1.

1.9 In the milk pasteurization plant of Example 1.3, what percentage of the heating steam can be saved, if a heat exchanger is installed to heat fresh milk at 75–95 °C by pasteurized milk at 132 °C?

References

  1. 1. Aiba, S., Humphrey, A.E., and Millis, N.F. (1964, 1973) Biochemical Engineering, University of Tokyo Press.
  2. 2. Lee, J.M. (1992) Biochemical Engineering, Prentice Hall.
  3. 3. Doran, P.M. (1995) Bioprocess Engineering Principles, Academic Press.
  4. 4. Oldeshue, J.Y. (1977) Chem. Eng. Prog., 73 (8), 135.
  5. 5. McAdams, W.H. (1954) Heat Transmission, McGraw-Hill.
  6. 6. Perry, R.H., Green, D.W., and Malony, J.O. (eds) (1984, 1997) Chemical Engineers' Handbook, 6th and 7th edn, McGraw-Hill.

Further Reading

  1. Hougen, O.A., Watson, K.M., and Ragatz, R.A. (1943, 1947, 1947) Chemical Process Principles, Parts I, II, III, John Wiley & Sons.