Transcript Seamlees Integration of Biological and Chemical Engineering In

Integration of Chemical and Biological
Engineering In The Undergraduate
Curriculum: A Seamless Approach
Howard Saltsburg Maria Flytzani-Stephanopoulos
Kyongbum Lee
David Kaplan
Gregory Botsaris
Aurelie Edwards
Department of Chemical & Biological Engineering
Tufts University
Medford MA
ASEE
18 March 2006
The Need For Change
•ChE paradigm useful for more than 100 years
•Response to industry based on
commodity chemicals(20s), petroleum (30s),
polymers (40-70s), traditional pharmaceuticals
•All mature industries- little growth
• Chemical engineering is flexible
new technologies accommodated with same core
material
• Biotechnology is major new growth area
• Chemical Engineering can play an important role
The Role of Chemical Engineering In
Biological Engineering
•All known life forms involve cells.
•A cell is the smallest self-preserving and self-reproducing
unit.
•Many complex chemical reactions and complex
transport processes occur
• A cell looks like a chemical plant
• Chemical engineers routinely work with that type of
system.
ANIMAL
CELL:
A CHEMICAL
Animal Cell:
A Chemical
Factory
FACTORY
How To Optimize Education To Take Advantage Of
The Opportunity
•Biology becomes an integral part of the curriculum
•Enabling sciences go from the
•Traditional three legs
Chemistry, Math, Physics
•To four legs
Chemistry, Math, Physics, Biology
( basic understanding of molecular and
cellular biology)
Some courses must be revised/altered/dropped to make room
Molecular and Cellular Biology
“Biology is complex chemistry that works”
•Chemical engineers will not become biologists
• Must understand molecular biology and cell structures
• Molecular biology is insufficient to understand cell
function
• Interaction of components defines the system.
• A systems approach is necessary
•Welcome to chemical engineering
.
The “Patch” Approach
•Problems in courses inadequate
• Often disguise the real system problem by
oversimplifying:
•Kidney as simple separator
•Body as pump and tubes
•Liver as reactor
•Modules as add-ons tend to be self-contained
• Biological problems can be disconnected from the rest of
the curriculum
• Neither approach adds to the solution of a real problem
Integrating the curriculum
Fermentor System as a Patch
LIQUID
FEED
KOH 5g/l
LIQUID
FEED
LIQUID
PRODUCTS
Fermentor
Yeast Extract 10g/l
Zymomonas
mobilis
Ethanol
1g/l
Sorbitol
MgSO4.7H2O .5g/l
Glucose
KH2PO4
(NH4)2SO4
1g/l
Glucose
XgF g/l
Fructose
XfF g/l
GASEOUS FEED
Fructose
Sterile Air 46.5 l/h
Byproducts
Fermentor Patch Example as a
Generic System
LIQUID
LIQUID
FEED
FEED
LIQUID
PRODUCTS
Reactor
GASEOUS FEED
Another Patch Example
Recycling in the Liver
CO2 + 2NH4+ = urea and byproducts
R
E
C
Y
C
L
E
S
T
R
E
A
M
INPUT FROM
BLOOD
LIVER
OUTPUT
Simple Recycle With Reaction
Methanol Synthesis
R
E
C
Y
C
L
E
FEED CO, H2,N2
REACTOR
S
T
R
E
A
M
PRODUCT STREAM
Methanol
LIVER FUNCTIONS
Urea Recycling in Kidney
EFFERENT BLOOD
FLOW
RENAL BLOOD
FLOW
GLOMERULAR CAPILLARIES
FILTRATE
RECYCLE
STREAM
WATER
NEPHRON
LOOPS
URINE
G
E
N
E
R
A
L
C
I
R
C
U
L
A
T
I
O
N
Separation With Recycle
OUTPUT FLOW
INPUT
FLOW
PRIMARY
SEPARATOR
FILTRATE
RECYCLE
LSTREAM
SOLVENT
SEPARATOR
WASTE
C
O
L
L
E
C
T
O
R
Kidney : Another Factory
Urine Formation: Separation
Transport Processes
Appropriate Approaches for Chemical
Engineering
Ground rule:
•Since future “hot topics” are unknown, we do not want to destroy
the traditional base as there is a fundamental intellectual core to
the subject.
•The biological and biomedical engineering approach is too
narrow as they are derivatives of the chemical engineering core
•Chemical engineers will not become molecular biologists but
must understand it
The Seamless Approach
• A biological system is simply another system
• Usual approach to problem solving by chemical engineers
is applicable
• Traditional approaches and material must be included
• Students must be able to function in a wide variety of
technical situations involving chemistry and biology
• Students will work on both types of systems (biological
and chemical) simultaneously in each core course
• Similarities as well as differences can be exposed.
• We develop an understanding of multiscale issues and
systems.
The Thread
• Comparison between a biological system
•cell, organ, organism and
•traditional chemical plant (specialty, commodity) is
examined in the first course.
• Choice of the chemical system can introduce new material
(polymers, semiconductors). .
• Subsequent courses examine same systems with the
detail appropriate to the new course material.
• The content of the entire curriculum is connected
• The overall program is brought into context.
•Issues of scale and complexity are introduced naturally
Term Projects ChBE 10
.
Chemical Process Calculations
•To what extent can the behavior of a biological cell (as a
chemical manufacturing plant) be described by a series of unit
operations comparable to those considered in traditional
chemical industry.
•You are to describe a traditional chemical process in terms of
relevant unit operations and do the same type of analysis for a
biological cell.. Then, compare the two analyses.
•What are similarities and dissimilarities? What do you need to
know to carry out such an analysis? Include both material and
energy balance considerations. What is the role of
thermodynamics in this discussion?
Types of Cells
•Prokaryotes: single-celled organisms without nucleus (e.g.
bacteria)
1-10 microns,
very few cytoplasmic structures
•Eukaryotes: organisms whose cells have membrane bound nuclei
that contain their genetic material, single cells to higher organisms
10-100 microns
highly structured (intercellular membranes, cytoskeleton)
•Archaea: prokaryotes often living in extreme environments
(geysers; alkaline, salty, or acid water)
Unusual biochemistry (CO2 to CH4; H2S to H2SO4)
Projects 2003
Biological Cell Type
Chemical Process
Archaea
Ammonia production
Prokaryote
Polyethylene
Eukaryote
Pennicillin
Archaea
Sulfuric Acid
Procaryote
Crude Oil to Gasoline
Eucaryote
Ethanol
Archaea
Bakers Yeast
A PROCESS ANALYSIS OF SULFURIC ACID PRODUCTION & ARCHAEAL CELLS
NUCLEOID
DNA + mRNA
CYTOPLASM
tRNA
GLUCOSE
TRANSPORT
PROTEIN
H2S
REACTION UNIT ATP
O2
H2SO4
m
R
N
A
H2S + O2 H2SO4
H2SO4
ENZYMES
AMINO
ACIDS
t
R
N
A
RIBOSOME PROTEIN
ADP
INORGANIC P
PLASMA MEMBRANE
Ethanol Production
EUKARYOTIC CELLS: A SYSTEMS ANALYSIS (COMPARISON WITH AN
ETHANOL PLANT)
Raw
Materials
Plasma Membrane
SEPARATOR
CYTOSKELETON
L
Y
S
O
S
O
M
E
M
I
T
O
C
H
O
N
D
R
I
A
Lysosome
Membrane
Microfilaments
Cytoplasm
Intermediate
filaments
Microtubules
Interior of
Lysosome
Outer
Membrane
Inner
Membrane
Mitrochondrial
Matrix
NUCLEUS
Nuclear Envelope
(Nuclear Pore)
Nuclear
Lamina
Chromatin
Nucleolus
Ribosomes
Rough
Endoplasmic
Reticulum
Smooth
Endoplasmic
Reticulum
(Lumen)
E
R
R
I
B
O
S
O
M
E
S
G
O
L
G
I
A
P
P
A
R
A
T
U
S
Cis
Region
Lumen of
The
Golgi
Apparatus
Trans
Region
P
E
R
O
X
I
S
O
M
E
V
A
C
U
O
L
E
S
Student Projects 2004
Ethanol production
Biological:
Zymomonas mobilis CP4
Chemical(macro):
Continous fermentation of corn mash
with the product stream processed
Ammonia Synthesis
Biological
ADS positive bacteria
Chemical
Haber process
Fermentor System
LIQUID
FEED
KOH 5g/l
LIQUID
FEED
LIQUID
PRODUCTS
Fermentor
Yeast Extract 10g/l
Zymomonas
mobilis
Ethanol
1g/l
Sorbitol
MgSO4.7H2O .5g/l
Glucose
KH2PO4
(NH4)2SO4
1g/l
Glucose
XgF g/l
Fructose
XfF g/l
GASEOUS FEED
Fructose
Sterile Air 46.5 l/h
Byproducts
Macro Bioprocessing
CONDENSER
GLUCOSE
CO2 STRIPPER
CORN
MASH
FERMENTOR
B
L
O
W
E
R
RECYCLE
BACK
FEED
S
T
E
A
M
C
O
2
Details of Thread
•As students proceed to the next course, they will take on a
new “pair”, one previously studied in the previous class by
another group.
•To avoid a new start, the student team responsible for this
previous study will tutor the new group just as they will be
tutored for their new project
•This insures teamwork and peer instruction
•After three years, students will have seen a variety of
chemical and biological systems. The sequence will form the
thread connecting the components of the curriculum and
placing it in context.
Ammonia Clearance from Blood
The Reactor Analysis
• Free ammonium ion (NH4+) is toxic at high
concentrations
• In the body, the liver removes NH4+ by forming
urea (CO(NH2)2); this process is not an elementary
reaction; it involves multiple enzyme-catalyzed
steps.
• Net stoichiometry:
2 NH3  CO2  urea
Rate Law
Simplified power-law approximation (assumes
CO2 is in excess):
dC A
n
 rA 
 kaC A
dt
A : Ammonia
Reaction Order Estimate from Batch Data
Culture conditions: 10×106 cells/mL, 1 mL culture volume
n=1
t,
min
n=2
CA, µM
0
350
10
210
25
50
40
31
55
4
Max rate: kaC A0
ka = 0.08 min-1
umol
 28
L  min
 103 L
 7
 10 cells
 60 min

 1 hr
umol

  0.17 6
10 cells  hr

Cell Mass Requirement
• Elimination of nitrogen through urine in average
adult: 10 g/day
– NH3 elimination: 12 g/day (assuming 100 % association
with urea)
Possible liver bioreactor
perfusion configurations:
Are there any limitations on bioreactor size and density
(cell-to-volume ratio)?
Caveats
From a Molecular Biologist
Shape counts
Simple decomposition into units will not provide all
answers
From a Chemical Engineer
Is this biology or what engineers think is biology ?
Summary
•A “ new” approach to integrating biology into chemical
engineering based on a “threaded” curriculum is described
•This approach provides integration of material over all four
years coupling content with context
•Students discover that they can learn new material not taught
in courses even at the sophomore level
•As we provide a general chemistry background, we also
provide a general biology background
•Details of curriculum development workshops on web
http://ase.tufts.edu/chemical//
Supported by an NSF Curriculum Planning Grant