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It also deals with studying various biotechnological processes. Shijie Liu reviews the relevant fundamentals of chemical kinetics-including batch and continuous reactors, biochemistry, microbiology, molecular biology, reaction engineering, and bioprocess systems engineering- introducing key principles that enable bioprocess engineers to engage in the analysis, optimization, design and consistent control over biological and chemical transformations.

The quantitative treatment of bioprocesses is the central theme of this book, while more advanced techniques and applications are covered with some depth. Many theoretical derivations and simplifications are used to demonstrate how empirical kinetic models are applicable to complicated bioprocess systems.

Contains extensive illustrative drawings which make the understanding of the subject easy Contains worked examples of the various process parameters, their significance and their specific practical use Provides the theory of bioprocess kinetics from simple concepts to complex metabolic pathways Incorporates sustainability concepts into the various bioprocesses.

Fundamentals of Modern Bioprocessing addresses this growing demand. Written by experts well-established in the field, this book connects the principles and applications of bioprocessing engineering to healthcare product manufacturing and expands on areas of opportunity for qualified bioprocess engineers and students. The book is divided into two sections: the first half centers on the engineering fundamentals of bioprocessing; while the second half serves as a handbook offering advice and practical applications.

Focused on the fundamental principles at the core of this discipline, this work outlines every facet of design, component selection, and regulatory concerns.

It discusses the purpose of bioprocessing to produce products suitable for human use , describes the manufacturing technologies related to bioprocessing, and explores the rapid expansion of bioprocess engineering applications relevant to health care product manufacturing. It also considers the future of bioprocessing—the use of disposable components which is the fastest growing area in the field of bioprocessing to replace traditional stainless steel.

In addition, this text: Discusses the many types of genetically modified organisms Outlines laboratory techniques Includes the most recent developments Serves as a reference and contains an extensive bibliography Emphasizes biological manufacturing using recombinant processing, which begins with creating a genetically modified organism using recombinant techniques Fundamentals of Modern Bioprocessing outlines both the principles and applications of bioprocessing engineering related to healthcare product manufacturing.

It lays out the basic concepts, definitions, methods and applications of bioprocessing. A single volume. This book discusses the underlying principles of bioseparations engineering written from the perspective of an undergraduate course. It covers membrane based bioseparations in much more detail than some of the other books on bioseparations engineering. Based largely on the lecture notes the author developed to teach the course, this book is especially suitable for use as an undergraduate level textbook, as most other textbooks are targeted at graduate students.

Popular Books. Student Solutions Manual. Solutions Manual for Lehninger Principles of Biochemistry 5ed. Freeman, Student solutions manual for Mathematical methods for physics and engineering.

Instructor's solutions manual to accompany Principles of geotechnical engineering, sixth edition. Encyclopedia of Bioprocess Technology. Modern Physics Instructors Solutions Manual. Power Systems Analysis - Solutions Manual. Recommend Documents. Bioprocess Engineering Principles Biop. Doran Bioprocess Engineering Prin Advanced Engineering Mathematics - Solutions Manual Solutions Manual Therefore, the power requirements without gassing can be determined using Eq.

Answer: W P. Determine the flow regime by calculating the impeller Reynolds number. Substituting parameter values into Eq. If the fermenter is not gassed, the power required is evaluated using Eq. Much of the remainder of the electrical power is converted into heat within the motor housing. The power required without gassing is evaluated using Eq. The stirrer speed required can be determined by rearranging Eq.

Relative to the 1— 2 kW m—3 guideline for large fermenters, the value of kW m—3 is extremely large. It is unreasonable to expect to be able to provide this amount of power; the size of the motor and stirrer assembly required is impractical. Therefore, achieving turbulence with viscosity times greater than that of water is not possible.

Answer: kW m—3; no; an impractically large stirrer motor would be required 8. Assume that both fermenters are operated without sparging. From Table 8.

Answer: W c First, let us assume that flow in the large-scale vessel is turbulent: this is checked below. The stirrer speed under turbulent flow conditions is determined by rearranging Eq. An equation for the gas flow rate Fg required to achieve complete gas dispersion with a Rushton turbine is obtained by substituting the definitions of Eqs 8.

Answer: Yes 8. For a cylindrical tank, the liquid volume VL is: P. From Figure 8. If the power draw of both impellers is reduced by the same percentage with gassing, the results of this comparison remain valid with gassing.

Answer: The larger impeller. This translates into a smaller overall power draw for operation of the larger impeller. However, if this turbine is operated with downward pumping, we can assume that it will flood at lower gas flow rates than a corresponding Rushton impeller Section 8. Therefore, we will perform the calculations for a Rushton turbine. An equation for the gas flow rate at the flooding—loading transition is obtained by substituting the definitions of Eqs 8. Therefore, according to our assumption, the pitched-blade turbine will also be flooded.

Answer: Flooded, assuming that the pitched-blade turbine is operated with downward flow so that it is likely to be flooded at lower gas flow rates than a same-geometry Rushton turbine operated at the same stirrer speed b Determine the flow regime by calculating the impeller Reynolds number using Eq.

Answer: W d The impeller is flooded and there is a much higher rate of energy input by sparging than by stirring. The vessel is operating virtually as a bubble column with little benefit being obtained from stirring in terms of mixing or gas dispersion. Calculating the power required without gassing from Eq. For just complete solids suspension, the stirrer speed is equal to NJS. Substituting these values into the above equation: P0.

An expression for the gas flow rate Fg under these conditions is obtained by substituting the definitions of Eqs 8. In the turbulent regime, the relationship between P and Di is given by Eq. The stirrer speed required for complete solids suspension is given by Eq.

For different impellers of the same size, all the terms in Eq. Substituting these values into the above equation: PPB 1. Let us assume that flow is turbulent: this is checked below. The stirrer speed is determined by rearranging Eq. This justifies the above application of Eq. Answer: rpm d Eq. This is the same answer as in b. The power P in Eq. The mixing time is calculated using Eq.

Answer: W ii Eq. Assume that flow is turbulent: this is checked below in b iii. An expression for the power required to achieve a given mixing time is obtained by rearranging Eq. This justifies application of Eqs 8.

This justifies the application of Eqs 8. Answer: 27 rpm for the Rushton turbine; 80 rpm for the A hydrofoil 8. This can be calculated from the equation for the volume of a cylindrical tank: P. To avoid having to modify the stirrer motor or drive assembly, impeller retrofitting is carried out so that the power draw and stirrer speed remain the same Section 8. First, calculate the power draw for operation of the Rushton turbine at rpm before retrofitting. Check that this stirrer speed corresponds to turbulent flow by calculating the impeller Reynolds number using Eq.

Therefore, the power requirements can be determined using Eq. For turbulent flow conditions, the impeller diameter can be evaluated by rearranging Eq. This justifies the use of Eq. The value of 0. Therefore, the cost of retrofitting is difficult to justify based on the expected mixing times. Answer: Hydrofoil impeller ii As downward-pumping hydrofoil impellers do not perform well with gassing Section 8. As P. Answer: Curved-blade disc turbine 8. First, calculate the power draw for operation of the three Rushton turbines at 1.

To check whether 1. For the system after retrofitting, calculate the power drawn by the lower curved-blade disc turbine operated at 1.

As the diameter and operating speed of this turbine are the same as those of the Rushton turbines, Rei is equal to 4. Therefore, the curved-blade disc turbine generates turbulent flow and Eq. Therefore, for each hydrofoil, the power draw is The diameter of the hydrofoil impellers is determined by rearranging Eq. For pseudoplastic fluids, Rei is given by Eq. For operation of the viscometer at 2.

The highest operating stirrer speed for laminar flow is obtained by rearranging Eq. This range of shear rates is also considerably broader than that calculated in c for the Rushton turbine. The helical ribbon viscometer allows rheological investigation of fluids over a wider range of shear rates and shear stresses than the Rushton turbine viscometer.

The kinematic viscosity is calculated using Eq. Rearranging Eq. As gassing is provided through the reactor headspace, the culture liquid in the bioreactor is not sparged; therefore, there is no reduction in stirrer power due to gassing. This justifies the application of Eq. Answer: 17 rpm. There is a substantial difference between the answers obtained in a and b.

This illustrates the shortcomings of the Kolmogorov-scale approach for estimating the operating conditions required to avoid shear damage. The calculation depends on the distribution of the rate of turbulence kinetic energy dissipation within the vessel, which is difficult to know accurately.

An equation for the power P is obtained by rearranging Eq. Let us assume that flow in the bioreactor is turbulent: this is checked below.

As the loss of power with gassing is negligible, the stirrer speed can be determined by rearranging Eq. Answer: 42 rpm Chapter 9 Heat Transfer 9. The rate of heat conduction can be calculated using Eq. Their magnitudes are calculated using Eq. For thermal resistances in series, the rate of heat conduction is calculated using Eq. The flow diagram for cocurrent flow is shown below. Answer: 32 m b The rate of heat loss to the atmosphere can be determined using Eq. From energy balance considerations, this rate of heat loss is equal to the rate of reduction in sensible heat of the water as represented by Eq.

The heat transfer area A is the area of the wall of the pipe given by Eq. Calculating gives: Estimated values of Tho are used to calculate the left-hand side; successive estimates are then determined depending on whether the calculated value deviates from This is close enough to The dimensionless numbers in this equation are Re, Pr and Nu. Re is given by Eq. Pr is given by Eq. As fractional units are not available, four units must be purchased. The rate of heat loss to the atmosphere is evaluated using Eq.

Therefore, the mass of water in the storage heater is kg. Answer: Turning off the heater is more economical 9. Assuming that A is roughly the same throughout the thickness of the film and fouling layers Section 9. The results for the copper pipe with fouling are used to determine the hot- and cold-film resistances that apply also with the stainless steel pipe. The steady-state energy balance equation for the cooling coil is Eq. However, this equation cannot be solved analytically; therefore an iterative solution is required.

Rearranging gives: The heat transfer area required is obtained from Eq. The rate of heat transfer before cleaning is evaluated using Eq. A is the area of the wall of the pipe given by Eq. The outlet cooling water temperature after cleaning is determined from Eq. From Table 9. The parameters in this equation are Re, Pr and Nu. Pr for the medium is given by Eq. The heat transfer coefficient for water flowing in the shell of the heat exchanger is calculated using the empirical correlation, Eq.

The parameters in this equation are F, Remax, m, Pr and Nu. Remax is given by Eq. Pr for the water is calculated using Eq. The power input by stirring is 1 metric horsepower per l. Multiplying by the liquid volume and applying unit conversion factors from Tables A.

From the energy balance equation for the cooling water, Eq. The dimensionless numbers in this equation are Rei, Pr and Nu. Rei is given by Eq.

Substituting values gives: P. Answer: No 9. Applying the definition of density Section 2. The cooling requirements are determined from the energy balance equation, Eq.

First, check that flow in the fermenter is turbulent by calculating the impeller Reynolds number using Eq. Assume that the fermenter is not gassed. Rei has already been calculated; Pr is given by Eq. From Section 5. As the tube-side heat transfer coefficient hc can be ignored, Eq. From the calculation in a , Rei is greater than the threshold of for turbulent flow Section 8.

This is a long cooling coil, representing a considerable expense when fabricated from stainless steel. Converting the units of qO: P. The maximum cell concentration supported by the heat transfer system 4.

Therefore, the heat transfer system does not allow complete consumption of the substrate. The dependence of Rei on stirrer speed is given by Eq. The range of stirrer speeds to be investigated is 0. We can determine the flow regime corresponding to the maximum value of Ni by calculating the impeller Reynolds number using Eq. Therefore, flow for the stirrer speed range of interest is either laminar or in the transition regime.

Under these conditions, the stirrer power without gassing is evaluated using Eq. Alternatively, NP values can be obtained from the original reference J. Rushton, E. Costich and H. Everett, , Power characteristics of mixing impellers. Answer: About 4 s—1 e From Eq.

Accordingly, at high stirrer speeds, the system has limited capacity to handle exothermic reactions. Answer: Limited by mass transfer As the pressure in the fermenter is 1. The kLa required to achieve this cell concentration under conditions allowing the maximum rate of mass transfer is estimated using Eq. Answer: No The gas flow rate is 0. PT can be expressed in terms of uG using Eq. Using the above expression for PT together with values for kLa and VL in the appropriate units, the expression for kLa becomes: 0.

Starting with an estimate for uG of 0. Converting this result to a volumetric gas flow rate using the definition of superficial gas velocity Section HL m xmax g l—1 1. Multiplying xmax by VL gives the maximum mass of cells produced, Xmax. As all the Pmax values in b are smaller than the corresponding Pmax achieved in the absence of mass transfer limitations, we can conclude that protease production is limited by oxygen transfer at all the liquid heights tested.

Therefore, operation at this liquid height is recommended. In drawing this conclusion, we assume that the higher antifoam consumption and increased antifoam cost for operation at this liquid height is off-set by the greater mass of protease produced compared with operation at lower heights. The rate of oxygen transfer is determined using Eq.

Answer: By a factor of 6. The mole fraction of oxygen yAG in the gas phase corresponding to 7 P. Therefore, oxygen-enriched air containing For E. This problem highlights the very high demands on oxygen transfer inherent in microbial cell culture relative to plant and animal cell systems.

Similarly: 2 2 PT E. The oxygen transfer rate for kLa determination by the oxygen balance method is calculated using Eq. The inlet air flow rate Fg is 1 vvm or l min—1.

Therefore, the partial pressure of oxygen in the exit gas is 0. This calculation illustrates the sensitivity of the oxygen balance method to the accuracy of the measured parameters used in Eq. This sensitivity arises from the subtraction of two numbers of similar magnitude for the moles of oxygen in and out of the system.

When errors in both Fg terms are taken into account, the error in the final kLa value can be very large. From Tables C. The parameter values for application in Eq. Values of Hi and Kj are taken from Table SO42— 0. From Table However, if the gas phase in the fermenter is well mixed, the mole fraction of oxygen in the bubbles is equal to that in the off-gas, 0.

The mole fraction of oxygen in the incoming air is 0. The mole fraction of oxygen in the off-gas is 0. Using the result in a for the effect of medium solutes, air 11 P. CAL in this equation depends on the medium composition and the gas-phase oxygen partial pressure. We will assume that the oxygen partial pressure in the bubbles is 0.

For complete conversion of 20 g l—1 glucose and 8. Answer: Substrate availability The inlet air contains The mole fraction of oxygen in the off-gas leaving from the top of the vessel is 0. Therefore, air saturation at the bottom of the fermenter means an oxygen concentration of 1. Using the definition of QO in Eq. Therefore, using the result for ps from b , the pressure at the top of the tank is 2. The effect of the electrode response time and boundary layers should be determined at a range of stirrer speeds using the techniques described in Section The effect of gas-phase dynamics should be tested using different methods of deoxygenation as described in Section Although the dynamic pressure method reduces the influence of gas-phase dynamics on kLa measurement Section This suggests that boundary layer effects were eliminated at 50 rpm.

As the kLa measurements were conducted at 60 rpm, we can conclude that significant boundary layers were not present during the measurement procedure. In the absence of boundary layers, the time taken for the electrode to record CAL for operation with a mixture of air:oxygen:nitrogen at 1 atm. The oxygen mole fraction yAG in the gas mixture is determined using 0.

Recalculating kLa using Eq. In surface aeration, the term a in kLa represents the surface area of liquid at the liquid—gas interface. Assuming that the value of kL is unchanged, i. This 19 P. Therefore, DT must be increased from 8. A vessel diameter of This calculation shows that increasing DT is not a practical approach for obtaining surface aeration kLa values similar to those achieved using air sparging. The assumptions involved in the simple dynamic method apply as described in Section The calculated value for kLa is not reliable unless electrode response and liquid boundary layer effects can be shown to be negligible.

Because bubbles and gas hold-up are not involved in shakeflask aeration, gas-phase dynamics is not a significant issue in this case. Answer: 49 s, assuming that electrode and boundary layer effects are negligible b The closures have cylindrical geometry.

Therefore, the proportion of the total resistance due to the flask closure is 4. From the equation for kLa as a function of shake-flask operating parameters, increasing the shaker speed from 80 rpm to rpm increases kLa by a factor of: 1.

If the liquid volume VL remains constant, VF must be increased 6. Answer: 16 ml 21 Chapter 11 Unit Operations Applying the result for the overall fractional product recovery from a , the mass of purified anti-thrombin III recovered per week is 0. According to Eqs The data after converting the units to s and m3 are listed and plotted below. Calculating the numerator of Eq.

K2 is the same for the new filtration; however, K1 is changed as the value of c is changed. The new value of K1 is obtained from Eq. Answer: 23 g l—1 The time required to collect this volume of filtrate is determined from Eq.

These values are listed below. For the pelleted cells: 1. Similarly, for the filamentous cells: 1. Pressure drop kg m—1 s—2 1. Therefore, the compressibility is 0. The filtration equation for a compressible filter cake is Eq. Assuming that the filter medium resistance Rm is negligible, Eq. We have assumed in this calculation that the filter medium resistance is negligible and that the filter cake characteristics measured at pressures between and mmHg apply at the much higher pressure of mmHg.

Therefore, Eq. Substituting this value for t into the left-hand side of the equation in e : 0. N 1h The sedimentation velocity is determined using Eq. Answer: By a factor of The sigma factor for the disc stack centrifuge is calculated using Eq.

Predicting centrifuge performance depends strongly on accurate measurement of the particle and fluid densities.

For this system, Eq. An assumption in this calculation is that the homogenisation characteristics measured at pressures between and kgf cm—2 apply at the higher pressure of kgf cm—2.

Rewriting Eq. According to this equation, a plot of ln S versus CS should give a straight line. The measured solubility results are listed and plotted below. Therefore, the mass of cellulase recovered in the precipitate is 20, — Therefore, the solubility S after the second treatment is Applying this result in 1 and solving for CS: ln 0.

Accordingly, considerable further processing of the precipitate is likely to be required to increase the product purity. As the mass of antibody in solution before the second treatment was 3. This may be responsible for some deviation between the predicted and experimental antibody recoveries. In addition, solubility in protein mixtures such as culture broth is generally less than that predicted by the Cohn relationship, due to co-precipitation of other proteins Section If the antibody solubility is lower than that predicted by the equation, this would explain the higher than expected antibody content in the precipitate.

For well-mixed operation Section Applying the equation provided for the resistance due to concentration polarisation: P. The flux with fouling is evaluated using Eq. The mass transfer coefficient k in the plate-and-frame modules is determined using the empirical correlation, Eq.

Sc is given by Eq. Answer: Yes The permeate flux under gel polarisation conditions is determined using Eq. Interpolating Figure After the protein concentration step, V0 for diafiltration is 1 m3. Taking the logarithm of both sides and applying Eq. Applying 1 : 3 0. If the column length, linear flow velocity and packing particle size are kept the same on scale-up Section Therefore, as the toxoid stays in the column for the shorter time, it must be the larger molecule.

Answer: Toxoid b The internal pore volume in the gel in the laboratory reactor is calculated using Eq. If the large-scale column is operated with the same packing and flow conditions, the partition coefficients can be assumed to be the same as those in the laboratory column.

Therefore, for toxoid in the large column, from Eq. The liquid flow rate is scaled up in proportion to the column cross-sectional area. The volumetric flow rate Q is 0. The value of H is determined by rearranging Eq. The average particle size Lav retained on each screen is calculated by taking the average of the aperture sizes of that screen and the one above it. The mass density m is determined by combining Eqs Results calculated from the data provided are listed below.

The mass of the crystals is represented as a slurry density Section From the form of Eq. The results are shown below. If the crystalliser is well mixed, the total mass of crystals per unit volume in the sieved sample taken from the vessel outlet is equal to the operating magma density. Adding together the masses retained at each screen and in the pan gives a total crystal density in the sample of This result can be compared with that calculated using the equation in Table The discrepancy may be attributed to the strong dependence of the MSMPR equation on the fourth power of the slope obtained from the measured data.

A relatively small variation in the slope obtained from fitting the data results in a large change in the calculated magma density. Answer: 69 kg m—3 A plot of n versus Lav on semi-logarithmic coordinates is shown below. In 1 mole of moist air, from the result in b , there are 0. The rate of drying during the constant rate period is given by Eq. The mass of completely dry solid Ms is obtained from the cake volume and the density of the dry material.

Substituting values gives: 1h As the mass of the sample also remains the same, from Eq. The rate of drying Nc is given by Eq. Answer: ; irreversible b From Eq. The values are listed and plotted below. Also from Eq. Whereas the vmax values of the variant and rat enzymes are not very different, the variant enzyme Km is an order of magnitude smaller than that of the rat enzyme. Therefore, the reaction at very low substrate concentrations can be expected to proceed at a significantly higher rate using the variant compared with the rat enzyme.

The kinetic properties of the variant enzyme are therefore more suited for application to cancer patients. Similarly, the catalytic efficiency of the variant enzyme is The efficiency of the variant enzyme is almost an order of magnitude greater than that of the rat enzyme. T is converted to kelvin using Eq.

The parameter values are listed and plotted below. From Table B. From Section Answer: With xylose as substrate, the catalytic efficiency of the enzyme is 6.

Therefore, this enzyme has a greater specificity for xylose as substrate than for glucose. Answer: The enzyme has a greater specificity for xylose as substrate compared with glucose The parameter values are listed and plotted below; T is converted to kelvin using Eq.

Answer: The activation energy E is Answer: mmol l—1 min—1 The concentration of fat is reduced from 45 gmol m—3 to 0. Combining Eqs Grouping terms and solving for t: The equation for first-order enzyme deactivation is Eq. Answer: Yes b The equations for each of the straight lines in the plots in a are listed below.

The values of the deactivation rate constant kd in Eq. The average rate—equal area construction is used to determine growth rates from the concentration data.

The data and calculations are tabulated below. Time, t h x kg m—3 0. Time, t h s kg m—3 0. The instantaneous biomass yield coefficients calculated using Eq. The mid-point slope method is used to determine growth rates from the biomass concentration data. The growth data are listed and plotted below according to the method described in Section Answer: Near the beginning of the culture b The mid-point slope method is used to determine the rate of substrate uptake as a function of time. The sugar concentration data are plotted below according to the method described in Section



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