Bioprocess Engineering

990 Pages·2013·30.886 MB·1000\990

BIOPROCESS
ENGINEERING
KINETICS, BIOSYSTEMS,
SUSTAINABILITY,
AND REACTOR DESIGN
S L
HIJIE IU
SUNYESF
DepartmentofPaperandBioprocessEngineering,
Syracuse,NY13210,USA
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Preface
All Iknowisjust what Ireadin the papers. area of Biology and Chemical Engineering,
Will Rogers to a discipline that covers the engineering
and engineering science aspects of biotech-
nology, green chemistry, and biomass or
Thequoteaboveisquiteintriguingtome renewable resources engineering. As such,
andreflectiveofthis text.Everything inthis textbooks in the area are needed to cover
text can be found either directly or with the needs of educating the new generation
“extrapolation” or “deduction” from the offinebioprocessengineers,notjustbycon-
books and papers one can find to date. The verting well-versed chemical engineers and
most influential books to this time are engineering-savvy biologists to bioprocess
the“BiochemicalEngineeringFundamentals”by engineers. I hope that this textbook can fill
J.E.Baileyand D.F. Ollis, “Elementsof Chem- thisgapandbringsthematurityofbioprocess
icalReactionEngineering”byH.S.Fogler,“The engineering.Yet,someofthematerialsinthis
Engineering of Chemical Reactions” by L.D. text are deep in analyses that are suited for
Schmidt, “Chemical Reaction Engineering” by graduateworkand/orresearchreference.
O.Levenspiel,“BioprocessEngineeringdBasic The key aspect that makes Bioprocess
Concepts” by M.L. Shuler and F. Kargi, and Engineering special is that Bioprocess Engi-
many others. All these texts and others neering as a discipline is centered around
haveformedpartofthistext.Innointention solvingproblemsoftransformationstemmed
thistextiscompiledtoreplaceallthesegreat from cellular functions and biological and/
textbooksofthetime.Amererearrangement or chemical conversions concerning the
and/orcompilingismadeinthistexttogive sustainable use of renewable biomass. The
youthereaderanopportunitytounderstand mechanism, rate, dynamic behavior, trans-
someofthebasicprinciplesofchemicaland formation performance and manipulations
biological transformations in bioprocess of bioprocess systems are the main topics of
engineering. thistext.
Thecomputeragehastrulyrevolutionized Chapter1isanintroductionofbioprocess
the literature, beyond the literature revolu- engineering profession including green
tion brought about by the mass production chemistry, sustainability considerations and
or availability of paper and distribution of regulatoryconstraints.Chapter2isanover-
books via library. Theexplosion of the shear view of biological basics or cell chemistry
amountofliterature,birthofinterdisciplines including cells, viruses, stem cell, amino
and disciplines or subject areas in the past acids, proteins, carbohydrates and various
decades has been phenomenal. Bioprocess biomass components, and fermentation
Engineeringisonethatbornofbiotechnology media. In Chapter 3, a survey of chemical
andchemicalengineering.Withthematuring reaction analysis is introduced. The basic
of Bioprocess Engineering as a discipline, it knowledge of reaction rates, conversion,
evolves from an interdisciplinary subject yield, stoichiometry and energy regularity
ix
x
PREFACE
for bioreactions are reviewed. The concepts isdiscussed.InChapter9,youwilllearnboth
of approximate and coupled reactions are ideal and non-ideal adsorption kinetics
introduced, providing the basis of under- and adsorption isotherms. Is multilayer
standing for the metabolic pathway repre- adsorptionthetrademarkforphysisorption?
sentations later in the book. Mass and The heterogeneous kinetic analysis theory
energy balances for reactor analyses, as is applied to reactions involving woody
well as the definitions of ideal reactors and biomasswherethesolidphaseisnotcatalytic
commonly known bioreactors are intro- in x9.5. Chapter 10 discusses the cellular
duced before an introduction to reactor genetics and metabolism. The replication of
system analyses. The biological basics and genetic information, protein production,
chemical reaction basics are followed by substrate uptake, and majormetabolic path-
the reactor analysis basics in Chapters 4 waysarediscussed,hintingattheapplication
and 5, including the effect of reaction of kinetic theory in complicated systems. In
kinetics, flow contact patterns and reactor Chapter 11, you will learn how cell grows:
system optimizations. Gasification (of coal cellular material quantifications, batch
andbiomass)isalsointroducedinChapter5. growthpattern,cellmaintenanceandendog-
How the ideal reactors are selected, what enous needs, medium and environmental
flow reactor to choose and what feed conditions,andkineticmodels.Reactoranal-
strategy to use are allcovered in Chapter5. ysesarealsopresentedinChapters8and11.
Chapters6,7,8,9,10and11arestudieson In Chapters 12 and 13, we discuss the
bioprocess kinetics. In Chapter 6, you will controlled cell cultivation. Continuous
learnthecollisiontheoryforreactionkinetics culture and wastewater treatment are dis-
andapproximationscommonlyemployedto cussed in Chapter 12. Exponential growth
arrive at simple reaction rate relations. is realized in continuous culturing. An
Kinetics of acid hydrolysis, of an important emphasis is placed on the reactor perfor-
unit operation in biomass conversion, is manceanalyses,usingmostlyMonodgrowth
introducedasa casestudy.InChapter7,we model in examples, in both Chapters.
turntodiscussthetechniquesforestimating Chapter 13 introduces fed-batch operations
kinetic parameters from experimental data, andtheiranalyses.Fedbatchcanmimicexpo-
breaking away from the traditional straight nential growth in a controlled manner as
line approaches developed before the opposed to the batch operations where no
computer age. You can learn how to use control (on growth) isassertedbesides envi-
modern tools to extract kinetic parameters ronmentalconditions.
reliablyandquicklywithoutcomplexmanip- Chapter 14 discusses the evolution and
ulation of the data. In Chapters 8 and 9, we genetic engineering, with an emphasis on
discuss the application of kinetic theory to biotechnologicalapplications.Youwilllearn
catalytic systems. Enzymes, enzymatic reac- how cells transform, how cells are manipu-
tions and application of enzymes are exam- lated, and what some of the applications of
ined in Chapter 8, while adsorption and cellular transformation and recombinant
solid catalysis are discussed in Chapter 9. cells are. Chapter 15 introduces the sustain-
The derivation of simplified reaction rate ability perspectives. Bioprocess engineering
relations, such as the MichaeliseMenten principlesareappliedtoexaminethesustain-
equation forenzymatic reaction andLHHW abilityofbiomasseconomyandatmospheric
for solid catalysis, is demonstrated. The CO . Is geothermal energy a sustainable
2
applicabilityofthesesimplekineticrelations or renewable energy source? Chapter 16
xi
PREFACE
discussesthestabilityofcatalysts:activityof masstransferonthereactorperformance,in
chemical catalyst, genetic stability of cells particular with biocatalysis, is discussed.
and mixed cultures, as well as the stability Both external mass transfer, e.g. suspended
of reactor systems. Sustainability and media,andinternalmasstransfer,e.g.immo-
stability of bioprocess operations are dis- bilized systems are discussed, as well as
cussed. A stable process is sustainable. temperature effects. The detailed numerical
Multiple steady states, approach to steady solutionscanbeavoidedorgreatlysimplified
state, conditions for stable operations and byfollowingdirectlyfromtheexamples.Itis
predatoreprey interactions are discussed. recommended that examples be covered in
Continuouscultureischallengedbystability classroom, rather than the reading material.
of cell biomass. In ecological applications, Chapter 18 discusses the reactor design and
sustainability of a bioprocess is desirable. operation.Reactorselection,mixingscheme,
For industrial applications, the ability of the scale-up,andsterilizationandasepticopera-
bioprocess system to return to the previous tionsarediscussed.
set point after a minor disturbance is an
expectation. In Chapter 17, the effect of
Shijie Liu
Nomenclature
a Catalyst activity D Diffusivity, m2/s
a Specific surfaceor interfacial area, D Dilution rate, s(cid:1)1
m2/m3 De Chirality oropticalisomers:
a Thermodynamic activity right-hand ruleapplies
a Dimensionless dispersion DO Concentrationofdissolvedoxygen,
d
coefficient g/L
a Constant DNA Deoxyribonucleic acid
A Chemical species e electron
A Adenine E Enzyme
A Constant E Energy,kJ/mol
A Heattransferarea,m2 EMP Embden-Meyerhof-Parnas
Ac Acetyl f Fractional conversion
ADP Adenosine diphosphate f Fanning friction factor
AMP Adenosine monophosphate F Flow rate, kg/s or kmol/s
ATP Adenosine triphosphate F Faradyconstant
B Chemical species FAD Flavin adenine dinucleotide in
B Constant oxidized form
BOD Biological oxygen demand FADH Flavin adenine dinucleotide in
reducedform
BOD Biological oxygen demand
5
measuredfor5 days FDA Food and Drug administration
c constant FES Fastequilibrium step (hypothesis)
C Chemical species g Gravitational acceleration,
C Concentration, mol/L orkg/m3 9.80665m2/s
C Constant G Gibbs free energy, kJ/mol
G Guanine
C Cytosine
C Heatcapacity, J/(mol$K), GRAS Generally regarded as safe
P
or kJ/(kg$K) GMP Good manufacturepractice
CoA Coenzyme A GTP Guanosine triphosphate
CHO Chinese hamsterovarycell h height or length
COD Chemical oxygen demand H Enthalpy, kJ/molor kJ/kg
CSTR Continuously stirredtank reactor HC Harvesting cost
d Diameter, m HMP HexoseMonophosphate(pathway)
D Diameter, m J Total transferflux,kmol/sor kg/s
xiii
xiv
NOMENCLATURE
J Transferflux, kmol/(m2$s) P Productivity orproduction rate of
X
or kg/(m2$s) biomass
k Kinetic rate constant P Probability of the vanishing ofthe
0
k Mass transfercoefficient, m/s entirepopulation
K Thermodynamic equilibrium P1 Probabilityoftheentirepopulation
constant not vanishing
K Saturationconstant,mol/Lorkg/L PCR Polymerase chain reaction
K Overallmasstransfercoefficient PEP Phosphoenolpyruvate
L
(from gas to liquid) PFR Plug flow reactor
L Length PP Pentose phosphate (pathway)
L- Chirality oropticalisomers: left PSSH Pseudo-steady-state hypothesis
hand rule applies P/O ATP formation peroxygen
m Amount of mass, kg consumption
m_ Mass flow rate, kg/s q Thermal flux,J/s or W
m Maintenance coefficient Q Volumetric flow rate, m3/s
S
M Molecular weight, Darton(D) Q_ Thermal energytransfer rate into
or kg/kmol the system
MC Molar(or mass) consumptionrate r Radial direction
MG Mass generation rate r Rateofreaction, mol/(m3$s)
MR Mass removal rate or kg/(L$s)
MS MolarorMass supplyrate R Correlation coefficient
MSS Multiple steady state R Ideal gas constant, 8.314 J/
n Total matters in numberof moles (mol$K)
N Mass transferrate, kJ/(m2$s) R Product, or productconcentration
or kg/(m2$s) R Recycleratio
N Numberof species Re Reynolds number
NAD Nicotinamideadenine RNA Ribonucleic acid
dinucleotide s Selectivity
NADP Nicotinamideadenine S Entropy
dinucleotide phosphate S Overallselectivity
OR Orderof reaction S Substrate (or reactant)
OTR Oxygen transfer rate S Substrate concentration, g/L
OUR Oxygen utilizationrate S Surface area,m2
p Pressure Sh Sherwood number
P Probability SMG Specific mass generation rate
P Pressure SMR Specific mass removal rate
P Product, or Productconcentration, t Time,s
kg/m3, org/L, or mol/L T Temperature,K
P Power (ofstirrerinput)
T Thymine
xv
NOMENCLATURE
TCA Tricarboxylic acid b Chiralityoropticalisomers:two
u superficial velocity, m/s chiralcenters with the same hand
U Averagevelocityorvolumetricflux gestures
U Internal energy c Fraction
U Overall heat transfercoefficient, g Thermodynamic activity coefficient
kJ/m2 g Activation energy parameter
U Uracil gDR Degreeof reduction
CoQ Co-Enzyme ubiquinone d Thickness ordistance
n
v Molar volume, m3/kmol D Difference
V Volume, m3 ε Voidratio
W_ Rateof work input to thesystem f Thiele modulus
W_ s Rateof shaft work doneby the h Effectiveness factor
system q Fractional coverage (on available
x Variable active sites)
x Axialdirection m Specific rate offormation,or rate of
reactionnormalizedbythecatalystor
X Cellor biomass
X Cellbiomass concentration,L(cid:1)1, cge$lgl(cid:1)b1i$osm(cid:1)1ass concentration, s(cid:1)1 or
org/L
m Specific biomass growthrate, s(cid:1)1 or
XSU Biomass storage for managed g$g(cid:1)1$s(cid:1)1
forest
m Dynamic viscosity of fluid, Pa$s
X Biomass storage for undisturbed f
SU
n Stoichiometric coefficient
unmanaged forest
y Molefraction nf Kinematic viscosity of fluid or
medium, m2/s
y Variable
r Density,kg/m3
Y Yields
s Active site
YF Yield factor, or ratio of
s Variance
stoichiometric coefficients
z Vertical direction s Space time, s
u Mass fraction
z Variable
u Rotational speed
Z Collision frequency
u Weightingfactor
Z Valence of ionic species
Subscript
Greek Symbols
ads Adsorption
a Constant
app Apparent
a Chirality oroptical isomers:two
chiral centers with differenthand A Species A
gestures b reversereaction
b Heat of reactionparameter B Batch
b Constant c Combustion
xvi
NOMENCLATURE
cat Catalyst obs Observed
C Species C out Outlet
C Cold stream p Particle
C Concentration based P Product
C Calculated basedon model P Preparation
d Death R Reaction; Reactor
d Doubling R Reference;Reduced
des Desorption s Solid
D Diffusion coefficientrelated S Sterilization
e Endogenous (growthneeds) S Saturation
e External (mass transfer) S Substrate
e In effluent stream S Surface
eq Equilibrium S Total species
eff Effective t Tube, orreactor
f Final or atend T Tube
f Fluid ormedium T Total
f Formation U Unloading
f Forwardreaction 0 Initial
F In feed stream 0 In feed
G Growth 0 Pre-exponential
H Heatof reaction + Plasmid-containing
H Hotstream (cid:1) Plasmid-free
i Reaction i N maximum or at far field
i Initial S Total or sum
i Impeller
Superscript
in Inlet
I Inhibition 0 (Thermodynamic)Standard
j Species j conditions
m Maximum * Equilibrium
max Maximum * Basedon transitional state
0
net Net Catalyst mass based
0
OPT Optimum Variant
C H A P T E R
1
Introduction
O U T L I N E
1.1. Biological Cycle 1 1.7. The Story ofPenicillin: the Dawn
ofBioprocess Engineering 12
1.2. Green Chemistry 3
1.8. Bioprocesses: Regulatory
1.3. Sustainability 5
Constraints 15
1.4. Biorefinery 6
1.9. The Pillarsof Bioprocess Kinetics
1.5. Biotechnology andBioprocess and Systems Engineering 17
Engineering 9
1.10. Summary 18
1.6. Mathematics, Biology, and
Problems 20
Engineering 11
1.1. BIOLOGICAL CYCLE
Figure 1.1 illustrates the natural biological processes occurring on Earth. Living systems
consist of plants, animals and microorganisms. Sunlight is used by plants to convert CO
2
andH Ointocarbohydratesandotherorganicmatter,releasingO .Animalsconsumeplant
2 2
matter, converting plant materials into animal cells, and using the chemical energy from
oxidizing plant matter into CO and H O (H O also serves as a key substrate for animals),
2 2 2
finishing the cycle. Microorganisms further convert dead animal and/or plant biomass
into other form of organic substances fertilizing the growth of plants, releasing CO and
2
H O,andthecycleisrepeated.EnergyfromtheSunisusedtoformmoleculesandorganisms
2
thatwecalllife.Materialsormatterparticipatinginthebiologicalcyclearerenewablesolong
as the cycle is maintained. Bioprocess engineers manipulate and make use of this cycle by
designing processes to make desired products, either by training microorganisms, plants,
and animals or via directchemical conversions.
BioprocessEngineering
http://dx.doi.org/10.1016/B978-0-444-59525-6.00001-9 1 (cid:1)2013ElsevierB.V.Allrightsreserved.