Modified Problem-based Teaching of Biotransport Phenomena

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Introductory Bioengineering at UMass
Dartmouth
Sankha Bhowmick, PhD
Mechanical Engineering
University of Massachusetts Dartmouth
Biotransport Education Workshop
ASME 2012 Summer Bioengineering Conference
June 23rd, 2012
Course Information
• MNE 525/BMB 510: Introduction to Bioengineering and
Biotechnology (Prereq: Advanced Math with Differential
Equations)
• Dual-level course for both undergraduate and graduate
• Required introductory course for all BMB Ph. D students
• Diverse student population: Engineering, Chemistry,
Biology
• Difficult to find a good and up-to-date text book
Course History
• Originally designed in the MIT/Harvard system
• BERE Program for Physicians (Whittaker funded)
• Intensive course in engineering principles applied to
biological systems
• Includes quantitative measurement principles,
thermodynamics, solid mechanics, fluid mechanics, heat
and mass transport, chemical kinetics.
Course Syllabus
Course Outline:
1. Overview of basic biological systems and measurement tools.
2. Applications of thermodynamics, fluid mechanics, and transport study
to biological systems.
3. An introduction to chemical kinetics
4. Basic biomechanics
5. Special Topics (Tissue Engineering; Drug delivery, etc)
Emphasis is on engineering with relevance to clinical and research
medical applications.
Grading:
Homework/Assignments: 10%
Discussion of research/technology papers: 10%
Two term exams: 50% (25% each)- Exams are open book (or take
home)
Project: 30%
References:
1. Principles and applications of biomedical engineering, Berthiaume,
Toner, Fowler and Yarmush
2. Physical Chemistry with applications to the Life Sciences,
Eisenburg and Crothers
3. Biomedical Engineering Principles, Cooney.
4. Handouts of papers/articles on specific topics
Project:
Each one of you will select a project
topic to work on. The project can be a
problem that you are working on as a
part of your research or work or it can be
a review of a specific field. In either
case you will talk to the instructor and
develop an outline for your project by
mid-March. You will have to submit an
abstract of what you intend to do as a
part of your project during this time. The
final project requires a report as well as
a presentation. The final project grade
will be distributed equally between the
final report and the presentation.
For undergraduate students who are not
directly involved in research, I am willing
to provide topics, if you cannot find one.
Experimental Homework
You are required to write a report on observation of cells under bright field and fluorescence microscope in Prof. Bhowmick’s
laboratory.
1. Inverted microscope: You will be given a flask of cells in the laboratory. Perform the following tasks:
a) Put the flask under the microscope and turn on the lights. Bring the cells into focus. Then move the flask around to observe
cells under different viewing fields. Draw a sketch of how the cells look under the microscope. If cells assume different
morphologies, you can draw multiple sketches illustrating different morphologies. Identify the cell membrane and the
nucleus in your sketch. How clearly can you see them under the bright field microscope.
b) Draw a schematic of the bright field light path of the inverted microscope. Clearly label the position of the light source,
objective, the sample and the eyepiece. Also under what magnifications (magnification is the product of the magnification of
the objective and eye-piece) did you make your observations? Did you have any different observations under different
magnifications?
2. Upright microscope: You will be given an aliquot of cells. Perform the following tasks:
a) Take 10 microliters of the cells and put them on a glass slide, cover it with a glass coverslip and observe them under the
brightfield microscope. Take pictures using the computer ( put the pictures as a part of a report). How are these pictures
different from your observations under the inverted microscope?
b) Draw a clear schematic of the light path of the upright microscope. How is this different from an inverted microscope?
c) Split the remaining cells into two batches. Heat one of the batches in the water bath at 60 C for 2 minutes. Wait five minutes.
Then label both the batches with Hoechst and Ethidium Homodimer (or Propidium Iodide- depending on which dye is
available). Wait fifteen minutes. Put them separately under the microscope and take pictures under appropriate
fluorescence filters. Show the pictures as a part of the report. What difference in observations do you make for the batch
that you heated up vs. the batch that you did not heat? Can you explain them?
d) Clearly draw the fluorescence light path. What the respective excitation and emission of the Hoecsht and Ethidium
Homodimer dyes?
Projects
Using Microchannels to Solve
the Challenge of Vascularizing
Tissue-Engineered Constructs
Learning Outcome:Finals
You are designing an ex vivo artificial organ. The cells in the organ cannot tolerate
shear stress in excess of 0.5 g/cm s2. You need to design channels to deliver the
nutrients to the cells. The total number of cells in the device is 2x109. The rate of
oxygen metabolism is 7.8 nmol oxygen/min/mg of cells. The cell mass is 33.7 x10-12
g/cell.
a) How much oxygen must be delivered to the device per second?
b) Assume that the dissolved oxygen concentration in media (that is flowing over the
cells) is 0.2 mmol/liter of media. What volume of fluid must be pumped into the device
per second?
c) Assuming the cells are 20 micrometer diameter discs, how much surface area is
required for the plate if they are cultured as a monolayer (single layer- not one on top of
another)?
d) Find the combination of U, H and L (H is the height of the fluid- NOT THE
CHANNEL- ASSUME EXTERNAL FLOW OVER A PLATE; L is the length of the
channel) that do not exceed the shear stress on the cells but delivers the required
oxygen to all the cells. Oxygen transport is given by the flux equation
Jo2= -Do2 dC/dy (Fick’s Law) [Assume a realistic diffusivity value of oxygen in water]
e)Plot shear stress () and oxygen flux (Jo2) as a function of position.
You can assume the properties of media to be that of water and the whole system to
be at 37C.
Clearly state all assumptions made.
(50 POINTS)
Course Evaluation
• Most advanced students find the course material challenging
and stimulating.
• Ph. D students learn about developing a proposal.
• Major challenge in developing Differential equation based
approach for Biology and Chemistry students- scaling arguments
• Engineering students have fared better than
Biology/Chemistry/Medical laboratory science students
Summary and Future
• A course designed to introduce bioengineering principles ( about 50%
biotransport) primarily for non-engineers.
• Course in lecture formant- guest lecturers
• Introduction to measurement techniques in bioengineering (including hands
on experiments)
• Project as immersion into a bioengineering topic
• Need to measure learning outcomes to distinguish between engineers vs.
non-engineers.
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