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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

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slide1

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

slide2

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
slide3

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 factory
ANIMAL CELL: A CHEMICAL FACTORY

Animal Cell: A Chemical Factory

slide5

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

slide6

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
  • .
slide7

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
Fermentor System as a Patch

LIQUID FEED

KOH 5g/l

LIQUID FEED

LIQUID PRODUCTS

Ethanol

Sorbitol

Glucose

Fructose

Byproducts

Fermentor

Zymomonas mobilis

Yeast Extract 10g/l

KH2PO4 1g/l

MgSO4.7H2O .5g/l

(NH4)2SO4 1g/l

Glucose XgF g/l

Fructose XfF g/l

GASEOUS FEED

Sterile Air 46.5 l/h

fermentor patch example as a generic system
Fermentor Patch Example as a Generic System

LIQUID FEED

LIQUID FEED

LIQUID PRODUCTS

Reactor

GASEOUS FEED

another patch example recycling in the liver co 2 2nh 4 urea and byproducts
Another Patch ExampleRecycling in the LiverCO2 + 2NH4+ = urea and byproducts

INPUT FROM BLOOD

RECYCLE

STREAM

LIVER

OUTPUT

simple recycle with reaction methanol synthesis
Simple Recycle With ReactionMethanol Synthesis

RECYCLE

STREAM

FEED CO, H2,N2

REACTOR

PRODUCT STREAM Methanol

urea recycling in kidney
Urea Recycling in Kidney

EFFERENT BLOOD FLOW

RENAL BLOOD FLOW

GENERAL CIRCULATION

GLOMERULAR CAPILLARIES

FILTRATE

RECYCLE STREAM

WATER

NEPHRON LOOPS

URINE

separation with recycle
Separation With Recycle

OUTPUT FLOW

INPUT FLOW

COLLECTOR

PRIMARYSEPARATOR

FILTRATE

RECYCLE LSTREAM

SOLVENT

SEPARATOR

WASTE

slide18

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
slide19

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.
slide20

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
slide21

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?
slide22

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)
slide23

Projects 2003

Biological Cell Type Chemical Process

Archaea

Prokaryote

Eukaryote

Archaea

Procaryote

Eucaryote

Archaea

Ammonia production

Polyethylene

Pennicillin

Sulfuric Acid

Crude Oil to Gasoline

Ethanol

Bakers Yeast

slide24

A PROCESS ANALYSIS OF SULFURIC ACID PRODUCTION & ARCHAEAL CELLS

NUCLEOID

DNA + mRNA

CYTOPLASM

tRNA

tRNA

mRNA

AMINO ACIDS

GLUCOSE

TRANSPORT

PROTEIN

H2S

REACTION UNIT

H2S + O2 H2SO4

RIBOSOME

ATP

O2

PROTEIN

H2SO4

H2SO4

ENZYMES ADP

INORGANIC P

PLASMA MEMBRANE

student projects 2004
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
Fermentor System

LIQUID FEED

KOH 5g/l

LIQUID FEED

LIQUID PRODUCTS

Ethanol

Sorbitol

Glucose

Fructose

Byproducts

Fermentor

Zymomonas mobilis

Yeast Extract 10g/l

KH2PO4 1g/l

MgSO4.7H2O .5g/l

(NH4)2SO4 1g/l

Glucose XgF g/l

Fructose XfF g/l

GASEOUS FEED

Sterile Air 46.5 l/h

macro bioprocessing
Macro Bioprocessing

CONDENSER

GLUCOSE

CO2 STRIPPER

CORN MASH

FERMENTOR

BLOWER

S T

EAM

CO2

RECYCLE

BACK FEED

slide29

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
Ammonia Clearance from BloodThe 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:
rate law
Rate Law
  • Simplified power-law approximation (assumes CO2 is in excess):
reaction order estimate from batch data
Reaction Order Estimate from Batch Data

Culture conditions: 10×106 cells/mL, 1 mL culture volume

n = 1

n = 2

ka = 0.08 min-1

Max rate:

cell mass requirement
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
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 ?

slide35

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
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