Bioengineering Seminar Schedule
Spring Semester, 2003 (For prior semesters, click here: Fall
1999, Spring 2000 , Fall 2000 , Spring
2001, Fall 2001, Spring 2002, Fall
2002 Click here to return to current semester)
Friday, January 17, 12:00 - 1:00 pm, Room 210 Hallowell
Multiphoton Fluorescence Snapshots of Energy Metabolism and Protein Dynamics
Ahmed Heikal
School of Applied and Engineering Physics, Cornell University
Abstract
Molecular level understanding of numerous biological processes can be elucidated using integrated multiphoton
fluorescence microscopy, spectroscopy, and ultrafast dynamics techniques. Multiphoton fluorescence allows noninvasive
visualization of cellular functions within turbid and thick biological samples with high 3D-spatial resolution,
large penetration depth into tissues, minimal out-of-focus cellular photodamage, and high signal-to-noise contrast.
Further, the fluorescence properties of molecular probes play an important role in fluorescence-based techniques
for biological applications. I will discuss using endogenous biomolecules (e.g., reduced pyridine nucleotide, NADH,
and flavin adenine dinucleotide, FAD) as probes for real-time functional imaging of mitochondrial respiratory chain
in neuronal and cardiac tissue. In addition, exogenous fluorophores such as intrinsically fluorescent proteins
(IFPs), isolated from Aequorea victoria jellyfish or Discosoma coral, can be expressed in live cells for non-invasive
visualization of numerous biological processes. I will discuss quantitatively the unique properties of IFP fluorescence
and thermodynamics in both buffered solutions and living cells. Finally, I will present a brief account of innovative
fluorescent markers (e.g., quantum dots, nanoparticles, and efficient two-photon absorbers) and their potential
in biology.
Friday, January 24, 12:00 - 1:00 pm, Room 210 Hallowell
History of Development of Standards for Electrocardiographs
David Gelselowitz
Emeritus Professor of Bioengineering
Friday, January 31, 12:00 - 1:00 pm, Room 210 Hallowell
Colloidal Biology: A Neglected Concept?
Matthew Rosinski
Harvard Medical School
Massachusetts General Hospital
Abstract
Solving the structure of DNA in the 1950s culminated a lengthy search over a period of 50 years for the physical
basis of a gene. The model proposed by Watson and Crick heralded the beginning of the rapid evolution of what became
known as molecular biology. The main reason for this epoch making discovery was the successful union of theory
and technique between disciplines, most importantly physics and biology. Suddenly, the cellular mechanisms underlying
the empirical Mendelian rules of heredity could be explored within a conceptual framework. Despite all these advances,
the fundamental question remains: What is the physical basis of a cell? A vocal minority suggest, much like jello,
living cells are colloidal gels as is the extracellular matrix in which you find them. In the spirit of Martin
H. Fischer's view (1939): Colloid chemistry is the twilight between chemistry and physics - but that is where life
is revealed This century's old hypothesis, elegantly expressed by Fischer, underlies fundamental biological processes.
This recognition, along with advances in polymers, nanotechnology and colloid and interfacial science, suggest
the time is now ripe for students of Colloidal Biology to play a more prominent role. I will discuss the importance
of Colloidal Biology in the context of virus production for biopesticides and gene therapy, models of cell dynamics
and specific applications in modern medicine.
Friday, February 7, 12:00 - 1:00 pm, Room 210 Hallowell
Computational Models of Nitric Oxide Transport in Biological Tissues
Mahendra Kavdia
Johns Hopkins University
Abstract
Nitric oxide (NO) plays a key role in diverse physiological and pathophysiological functions including regulation
of smooth muscle tone, neurotransmission, inhibition of platelet aggregation, host defense, and angiogenesis. Although
intense investigations of the biological effects of NO, in vivo or in vitro, have been carried out in the past
two decades, our quantitative knowledge of NO distribution at the cellular and tissue level is limited. NO reacts
with a wide range of molecules both intracellularly and extracellularly and the biological functions of NO depend
on these interactions. To gain quantitative understanding of NO effects, we have developed mathematical models
of reaction kinetics and diffusion of NO in several biological systems including in tissues in vivo, tissue cultures,
NO delivery devices, and bioartificial substitutes.
I will talk about our recently developed mathematical models of NO in the microcirculation. The mathematical models
incorporated several proposed mechanisms for preservation of NO bioactivity in the microcirculation. Further, I
will elucidate how the NO biotransport models provided a rational basis for the design parameters of hemoglobin
based oxygen carriers (HBOCs), which are currently being developed as blood substitutes for clinical applications
such as resuscitation from hemorrhagic shock, transfusion during surgery, and perioperative hemodilution. Model
predictions also provided an explanation for the experimental and clinical observations of vasoconstriction following
transfusion with HBOC. Finally, these models can be extended to include interaction with reactive oxygen species
and reactive nitrogen species. A quantitative understanding of these molecular interactions at the cellular levels
can give important insights into the mechanisms responsible for many pathological conditions, such as cardiovascular
disorders and ischemic-reperfusion injuries, and can provide potential treatments for these conditions.
Friday, February 14, 12:00 - 1:00 pm, Room 210 Hallowell
New Approaches in the Understanding, Prevention and Treatment
of Cardiac Arrhythmias
Antonis A. Armoundas
Division of Cardiology, Johns Hopkins
Abstract
Sudden cardiac death (SCD) is stated to have an incidence of 300,000 deaths annually in the United States (US).
This figure underlies the significance of better understanding of the underlying mechanisms of cardiac arrhythmias,
development of effective and low-cost preventive strategies and treatment modalities. My efforts in understanding
the mechanisms of cardiac arrhythmias are focused on patients that suffer from heart failure. Over two million
people in the US suffer from heart failure. Altered electrophysiology of the heart or electrical remodeling is
a common feature of myocardial failure that has been shown to predispose patients with heart failure to an increased
risk of arrhythmic death. My research employs tissues and myocytes isolated from the canine pacing-induced heart
failure model, which recapitulates the depressed left ventricular function and spontaneous ventricular arrhythmias
observed in human cardiomyopathy, to: (i) investigate the role of the enhanced action potential heterogeneity across
the ventricular transmural wall in the failing heart to susceptibility to ventricular arrhythmias, (ii) understand
the molecular basis of heart failure-induced changes in cellular electrophysiology and Ca2+ dynamics, (iii) refine
an existing single canine cell action potential model to incorporate regional changes in ion currents, transporters
and intracellular calcium handling and their effect in action potential dynamics. My efforts in developing preventive
strategies of cardiac arrhythmias are focused in developing signal processing algorithms that will identify patients
that are high risk to SCD Despite the absence of any visible beat-to-beat changes of the T-wave, microvolt level
T-wave alternans (TWA), an alternating pattern in the repolarization phase of the electrocardiogram, has been associated
with patient susceptibility to malignant cardiac arrhythmias. Studies that suggest that TWA is a promising noninvasive
technique for screening patients susceptible to cardiac arrhythmias and SCD will be presented. A novel method for
assessing vulnerability to cardiac arrhythmias and delivery of appropriate therapy will be also presented. My efforts
in treating cardiac arrhythmias are focused on an established clinical procedure that is called catheter ablation.
Catheter ablation, a technique that prevents cardiac arrhythmias from recurring, involves the use of a catheter
to deliver radio-frequency energy from a tip of a catheter placed inside the heart, to the site of origin of these
arrhythmias while the arrhythmia is ongoing. Thus, patients that cannot tolerate this procedure are necessarily
excluded. My research has explored the development and evaluation of an accurate and rapid new algorithm that would
allow the use of body surface electrocardiographic (ECG) signals to both identify the site of origin of the arrhythmia
in the heart, and guide the ablation catheter to the same site. This algorithm can identify cardiac electrical
sources with the resolution required (millimeter) for clinical applications such as radio-frequency catheter ablation
procedures.
Friday, February 21, 12:00 - 1:00 pm, Room 210 Hallowell
High Performance Tangential Flow Filtration: A New Approach for Protein Purification
Andrew Zydney
Chemical Engineering Department, PSU
Abstract
High performance tangential flow filtration (HPTFF) is a new membrane technology that can be used for protein
separations without limit to the relative size of the product and impurity. HPTFF can potentially be used throughout
the downstream purification process to remove specific impurities (e.g., proteins, DNA, or endotoxins), clear viruses,
and/or eliminate protein oligomers or degradation products. HPTFF is unique among available separation technologies
in that it can effect simultaneous purification, concentration, and buffer exchange, allowing several different
separation steps to be combined into a single scalable unit operation. This talk will examine the basic principles
governing protein separations by High Performance Tangential Flow Filtration, with particular emphasis on the importance
of electrostatic phenomena in generating the high selectivities required for bioprocessing applications. Specific
examples will be used to illustrate the importance of solution pH, ionic strength, and the surface charge characteristics
of the membrane in determining the separation performance.
Friday, February 28, 12:00 - 1:00 pm, Room 210 Hallowell
Lance Munn
Assistant Professor, Chemical Engineering
Massachusetts General Hospital and Harvard Medical School
Abstract
Under normal physiologic conditions, the blood vessel wall consists of an endothelial lining, perivascular cells
and a
basement membrane. During physiologic angiogenesis (e.g. in organogenesis and wound healing) and pathological
angiogenesis (e.g. in tumor growth), the structure of the vessel wall changes as vessels reorganize and endothelial
cells
migrate. Many cell types and growth factors are involved in the various manifestations of angiogenesis, and we
are only
beginning to understand the complex chain of events that destabilizes existing vessels, induces endothelial reorganization
and then restabilizes the new vasculature. In tumors, these processes are apparently dysregulated, as the vasculature
of
tumors is disorganized and inefficient. Using confocal, two-photon and electron microscopy, we find endothelial
cells with
unusual morphology and incomplete staining for common endothelial markers. The basement membrane is often
incomplete or extremely sparse and perivascular cells are not closely associated with the endothelial cells. Further
studies
will elucidate the kinetics of the formation of these abnormal vessels, and may point therapeutic strategies for
targeting
them. It is known that perivascular cells play an important role in vessel formation and stabilization. Using two-photon
microscopy we have analyzed the association between these cells and tumor vessels in a GFP expressing mouse implanted
with a non-GFP tumor. The results suggest that the perivascular cells in tumors, although prevalent, do not associate
as
intimately with the vessel wall as in normal vessels. This could be, in part, responsible for the dysregulation
in tumor
vessel formation, their higher permeability and their apparent lack of structural integrity.
In other research, we focus on how erythrocytes and leukocytes interact in these blood vessels. Leukocytes roll
and arrest
on the vascular endothelium in both normal and pathological immune responses, but the particulate, non-Newtonian
nature of blood renders traditional mathematical models of these processes intractable. We have developed a Lattice-
Boltzmann approach to quantify the fluid dynamics and forces involved as white blood cells interact with red blood
cells in
virtual blood vessels of various geometries. Our results show that the normal force imparted by erythrocytes
is sufficient
to increase leukocyte binding, and that increases in tangential force and torque can promote rolling of previously
adherent
leukocytes. The ratio of cell diameter to vessel diameter is an important determinant of the form of the interaction.
This
novel approach can be applied to a large number of biological and industrial problems involving the complex flow
of
particulate suspensions.
Friday, March 7, 12:00 - 1:00 pm, Room 210 Hallowell
NO SEMINAR
Friday, March 14, 12:00 - 1:00 pm, Room 210 Hallowell
NO Seminar Spring Break
Friday, March 21, 12:00 - 1:00 pm, Room 210 Hallowell
An Engineering Approach to Teaching Microvascular Function: The BIOE 576 Experience
Herbert H. Lipowsky
Department of Bioengineering, Penn State University
Abstract
Graduate level teaching of cardiovascular function to bioengineers poses numerous challenges because of their
limited exposure to physiology. Conversely, teaching engineering concepts to physiology students is equally difficult
because of their lack of engineering fundamentals. To overcome these impediments, a graduate level course was developed
around the Matlab/Simulink program. The class was instructed to create a computer model of the microcirculation.
With a class of 4 bioengineering and 2 physiology students, each was directed to implement a quantitative description
of a physiological process in a template model of microvascular function provided by the instructor. The graphical
interface of Simulink was well suited for rapidly implementing a systems model that was redesigned by students
to incorporate concepts (chosen by students) of shear induced nitric oxide production, myogenic regulation of diameter,
shear induced mechanotransduction, transvascular fluid exchange, thermal regulation of blood flow and orthostatic
tolerance. Following a general overview of microvascular structure and function and a tutorial on Matlab, students
implemented the template model, performed simulations of physiological provocation tests and added their own features.
Both bioengineering and physiology students needed guidance in formulating a systems modeling approach and appeared
to benefit from a team approach to problem solving.
Friday, March 28, 12:00 - 1:00 pm, Room 210 Hallowell
The Detection of Microemboli in Flowing Blood Using Doppler Ultrasound
William Weiss
Hershey Medical Center
Abstract
Microemboli refer to small air bubbles or solid particulate matter (soft and hard plaque or blood clots) which
may be released during open surgical and closed endovascular procedures (such as balloon angioplasty, stenting,
aortic aneurysm repair, heart valve replacement, and coronary bypass surgery), as a result of disease processes
(atherosclerosis, atrial fibrillation, carotid artery stenosis, and deep venous thrombosis), or from prosthetic
devices. The resulting ischemia may result in end organ dysfunction, such as stroke or pulmonary embolism. Doppler
ultrasound is a commonly used technology for measuring blood flow in vessels. Although the ability of Doppler ultrasound
to detect emboli in circulating blood was first described more than 35 years ago, its clinical utility has been
limited to detecting emboli in the cerebral arteries by transcranial Doppler.
Improvements are being investigated in the areas of signal processing and transducer design. The Doppler embolic
signal is characterized as a high-amplitude, periodic waveform, in contrast to the lower amplitude, stochastic
backscatter of the red blood cells. Approaches to maximizing the embolic-to-blood signal power ratio are being
investigated. A type of transducer called the diffraction-grating transducer has been used to detect micro-spheres
in close proximity to a simulated vessel. This transducer produces a narrow, uniform beam which is advantageous
in this application. The development of a transducer specifically for micro-embolization monitoring in carotid
arteries and femoral vessels is also underway.
The long-range goal of this research is to develop a clinical tool for the detection of micro-emboli in real time,
both as a diagnostic tool and as an aid during surgical interventions or treatments. Such a device could be used
to monitor the carotid artery or femoral artery in an outpatient setting, or to monitor vessels during operative
procedures.
Friday, April 4, 12:00 - 1:00 pm, Room 210 Hallowell
Applications of Neural Engineering in the Development of Neuroprosthetic Technology and Brain-Machine
Interfaces
Ryan S. Clement
Arizona State University
Abstract
Devices that electronically interface with the nervous system to enhance or restore lost function are no longer
science fiction. The cochlear implant is one such device that has shown an amazing ability to restore a sense of
hearing in people with sensorineural hearing loss. While this technology has allowed many to communicate without
lip-reading, significant patient variability and limitations in overall performance still exists. Improving and
developing future neuroprosthetic systems is an exciting, multidisciplinary effort in which biomedical engineers
are poised to have great impact. This seminar will describe several neural engineering research projects along
this effort. First the seminar will describe the development of a new electrophysiological technique that could
be used to objectively fit cochlear implants. The technical details of this approach, based on stapedius muscle
EMG recordings, will be discussed and data from animal studies supporting further development will be presented.
The remaining portion of the seminar will discuss recent research efforts in the area of brain-machine interfaces.
This work has centered on the application of implantable multi-channel micro-electrodes to simultaneously record
from neurons in the auditory or motor cortex of rats. Results will be presented from a set of experiments aimed
at using the rat's cortical signals to provide sensory information to a mobile robot. Preliminary results from
a related study will also be presented that demonstrate the ability to classify motor cortex signals in rats in
real-time that predict intended lever presses. These studies have created useful models for investigating issues
related to the development of brain-machine interfaces that may help individuals who have lost motor control. This
effort, as well as the development of neuroprostheses in general, will require improvements to the neural interface
that makes the electrical connection with the nervous system. The seminar concludes with some thoughts for accomplishing
this through the use of BioMEMS-based technology that could allow for greater interface biocompatibility and long-term
recording/stimulating stability.
Friday, April 11, 12:00 - 1:00 pm, Room 210 Hallowell
Student Presentations:
The Role of Nitric Oxide and Matrix Metalloproteinase-2 in the Shear Stress-Mediated Inhibition
of Smooth Muscle Cell Migration
by Jeff S. Garanich
Abstract
Increased levels of vascular smooth muscle cell (SMC) migration and proliferation are widely recognized as two
of the hallmark processes in intimal hyperplasia (IH) progression. The development of IH has been attributed to,
among other factors, alterations in hemodynamic conditions at the disease site. This knowledge, coupled with the
fact that SMCs are exposed to blood flow in both intact vessels (interstitial flow driven by the transmural pressure
gradient) and denuded vessels (direct contact with flowing blood), necessitates an understanding of the effect
of blood flow and its subsequent shear stress (SS) on SMC migration and proliferation. While numerous in vitro
studies have been done to determine the role of SS in SMC proliferation, the effect of direct SS on SMC migration
remains to be seen. We therefore grew rat aortic SMCs on Matrigel-coated cell culture inserts and quantified their
migration toward a known chemoattractant (platelet-derived growth factor (PDGF)-BB) while subjected to 1, 10, or
20 dyn/cm2 SS for 1-4 hours.
4 hours of both 10 and 20 dyn/cm2 SS acted to significantly suppress SMC migration levels compared to control conditions.
4 hours of 10 dyn/cm2 SS also drastically elevated the SMC production of nitric oxide (NO), which through the use
of a NO donor (500 mM S-nitroso-N-acetylpenicillamine) was shown to inhibit SMC migration by reducing the production
and activation of matrix metalloproteinase (MMP)-2, an enzyme involved in the SMC degradation of the extracellular
matrix during the migration process. This MMP-2 downregulation was also seen in SS experiments, as conditioned
media from cells exposed to 4 hours of 20 dyn/cm2 SS contained significantly lower levels of active MMP-2 compared
to control. Other experiments confirmed a role for MMP-2 in SMC migration as 50 ng/ml active MMP-2 added to inserts
acted to elevate SMC migration levels significantly. Western blotting results showed no effect of 4 hours of 20
dyn/cm2 SS on SMC production of PDGF-AA, another biochemical known to reduce SMC migration. Thus, it appears that
SS inhibits SMC migration through a NO-mediated reduction in MMP-2 activity.
These results agree well with those obtained in vivo in which IH development was attenuated in areas of increased
blood flow and SS and provide the basis for further more physiological 3-dimensional studies into the role of SS
on SMC migratory function.
===================================================================================
Ultrasound Mediated Transdermal in vivo Transport of Insulin with Low Profile Cymbal Arrays
by Seungjun Lee
Abstract
The purpose of this study is to determine the feasibility of ultrasonic transdermal insulin delivery with the
light-weight (< 22 g), low-profile (37 x 37 x 7 mm3) ultrasound transducer (f = 20 kHz). For these experiments,
30 rats (350-450 g) were divided into six groups: two controls, four insulin-ultrasound exposures. Each rat was
anesthetized, shaved and a 1 mm water tight standoff was arranged between the rat's abdomen and the array with
insulin (4 mL). Prior to beginning the experiment, 0.3 mL of blood was collected from the jugular vein for a baseline
glucose analysis from each rat. For comparison between the rats, the change in the glucose level for each rat was
normalized to an initial baseline (i.e. 0 mg/dL). Blood samples were taken from each rat every 30 minutes up to
90 minutes. For the two insulin with ultrasound exposure groups, the array at Isptp = 100mW/cm2 was shut off after
either 60, 20, 10 or 5 minutes of exposure to examine. Blood samples taken after 90 minutes indicated that glucose
level decreased 296.7 ± 52.8, 247.5 ± 32.5, 231.8 ± 68.9 and 239.7 ± 19.1 mg/dL from
the baseline for the 60, 20, 10 and 5 minute ultrasound exposure groups, respectively. Compared to the 60 minute
exposure results, only 5 minutes of ultrasound exposure was necessary to deliver a clinical dose of insulin to
reduce hyperglycemia. Hyperglycemia was also reduced using a rabbit model. The results indicate the feasibility
of using a low profile, light weight cymbal array for noninvasive transdermal insulin delivery.
=====================================================
Construction of a Confocal, Laser-Scanning Molecular Dynamics Microscope
(CLS-MDM) for Mechanotransduction Investigations.
by Tristan Tabouillot
Abstract
Mechanical forces induce changes in molecular-scale signaling events in endothelial cells which are related
to vascular health and disease. Molecular dynamics measurements with high spatial (nm) and temporal (ms) resolution
will allow us to better understand how cells transduce mechanical force into changes in cell biology. The process
by which cells convert mechanical stimulation to chemical signaling is called mechanotransduction. To measure molecular
dynamics in cells, we have integrated time-resolved fluorescence spectroscopy and confocal, laser-scanning microscopy
to perform fluorescence lifetime as well as fluorescence correlation spectroscopy (FCS). By coupling high numerical
aperture objectives, a confocal pinhole, and a 3-D
piezoelectric nanopositioner we record fluorescence data in three dimension and time. The temporal dimension is
given by pulsed-laser excitation and a time-correlated single photon counting board in the computer which allows
us to measure the arrival time of each photon emitted from the fluorescent sample relative to the laser pulse time
and the experimental start time. Two main available timescales, microscale and macroscale, give us a chance to
investigate a variety of cellular dynamic processes. The microscale in the nanoseconds range is used to record
fluorescence decay curves after pulsed-laser excitation; and the macroscale in the seconds range is used to
record FCS measurements. FCS refers to the temporal autocorrelation of fluorescence fluctuations to recover information
about lateral diffusion of fluorescent molecules.
To be described are details of the setup, such as system components and computer interfacing, system testing and
calibration.
======================================================
Thermoresponsive and Biodegradable Dendrimer for Drug Delivery
by Young Shin Kim
Abstract
A dendrimer was synthesized by coupling reaction of poly(L-lysine) (PLL) dendron and poly(N-isopropylacrylamide)
(PNIPAAM) grafted with poly(L-lactic acid) (PLLA). The chemical structure of the dendrimer was confirmed by FTIR
and 1H-NMR spectroscopy. The molar mass of the dendrimer was 4200 (gmol-1), measured by matrix assisted laser desorption
ionization time of flight mass spectrometry (MALDI-TOF). The analysis of transmission electron microscopy revealed
the particle size of the dendrimer was 20-40 nm. The dendrimer showed thermoresponsive property with the lower
critical solution temperature (LCST) in the range of 32o to 39oC at the concentration of
0.5-0.05 mg/ml, measured by UV-VIS spectroscopy. The LCST of the dendrimer increased with decreasing the concentration
of the dendrimer. The dendrimer also illustrated degradable property with deterioration in molar mass and viscosity
in PBS at 37o C with time. The nano-sized dendrimer has great potential in sustained and targeted release
of therapeutic agents across the blood brain barrier and significant clinical impact on the treatment of Alzheimer's
disease and other neurological disorders.
Friday, April 18, 12:00 - 1:00 pm, Room 210 Hallowell
Student Presentations
Quantifying Shear Stress-Induced Changes in the Dynamics of the Endothelial Cell Cytoplasm
Using Single Particle Tracking of Endogenous Markers.
By Jhanvi Dangaria
Abstract:
Hemodynamic forces induce changes in vascular endothelium and thus are important determinants of vascular health
and disease. Understanding the underlying processes and events occurring at the cell surface and the mechanism
by which cells transduce hemodynamic forces to their interior (cytoplasm) will provide valuable insight into factors
affecting vascular pathology. Our goal is to study the changes taking place in the cytoplasm of endothelial cells
(ECs) induced by fluid shear stress. We developed novel single particle tracking software to monitor changes taking
place in the cytoplasm before and after the onset of flow. Cultured bovine aortic endothelial cells were subjected
to physiological hemodynamic shear stress in a flow chamber using a pump interfaced with the computer. Flow rates
could be continually monitored with the help of a pressure transducer in the flow loop using feedback control of
the pump. High resolution differential interference contrast (DIC) images were obtained continuously during the
entire experiment. These images were subjected to a series of image processing steps to track vesicles in the cells
with nanometer-precision. Modeling these movements as active transport or Brownian motion will help establish the
contribution of cytoskeletal components in EC's subjected to fluid shear stress and thus elucidate the role of
the dynamics of cytoplasmic organelles in endothelial cell adaptation to shear stress.
====================================================================================
Microdevices for Microdialysis and Membrane Separations
Yi-Cheng Hiseh
Abstract
Microdialysis is a commonly used technique for separating small biomolecules. This technique is based upon controlling
the mass transfer rate of small biomolecules diffusing across a semipermeable membrane into a dialysis fluid while
excluding larger molecules such as proteins. Dialysis is also used commonly in biological laboratories to desalt
high ionic strength protein solutions. Using a dialysis membrane is also a quick and inexpensive way of removing
salt. Microfluidic channels have the advantage of having an extremely high surface to volume ratio to promote more
efficient dialysis. Thus, an on-chip dialysis system is useful for desalting protein solutions. The microfluidic
channels were produced on glass using SU-8 thick photoresist. Once the channels were fabricated, they would be
integrated with a cellulose membrane. Commercially available cellulose sheets were obtained. This work demonstrates
the ability to integrate polymer microdialysis membranes with microfluidic systems. Devices were placed in a solution
of rhodamine dye, and dialysis fluid was allowed to flow through the microchannels. The concentration of rhodamine
dye at the microchannel outlet was recorded at different flow rate.
======================================================================================Lack of
Reperfusion-Induced Venular Leukocyte Adherence Following Local Arteriolar Ischemia
By Neeraj Kulkarni
Abstract
Leukocyte adhesion in postcapillary venules has been implicated as a primary determinant of microvascular dysfunction
that occurs following ischemia-reperfusion (I/R). The mechanisms of leukocyte recruitment have not been fully established.
The present study concerns evidence in the literature that I/R in one organ may initiate a systemic effect that
results in inflammatory consequences in another. In this investigation, we used a model of mesenteric I/R in the
rat. In one group (N=13), I/R was induced by temporarily occluding the superior mesenteric artery (SMA) for 30
minutes. In the another group (N=9), localized I/R was induced by micropipette occlusion of a mesenteric arteriole
(for 30 minutes) that perfused the monitored venule(s).
The responses of the two groups were different. No increase in venular leukocyte adherence was observed with local
I/R; instead, there was a trend for a small decrease. In contrast, a significant increase in adherence (p<0.001)
was observed with SMA I/R. Also of interest, both local and SMA I/R similarly prevented the decrease in leukocyte
rolling that occurs in time control experiments following mesenteric exteriorization (N=8). These results suggest
that mesenteric I/R-induced leukocyte adherence (but not rolling) may be dependent on a mediator released into
the systemic circulation
======================================================================================
Pressure-Volume Characteristics of Dielectric Elastomer Diaphragms
By Alyson Tews
Abstract
Electroactive polymers (EAP) are materials that change shape in the presence of an electric field. This research
focuses on dielectric elastomers, which are soft polymers whose shape change occurs due to electrostatic attraction
between charges applied to opposite sides of a film. We measured pressure-volume (P-V) characteristics of single-layer
dielectric elastomer diaphragms, in order to predict their performance in diaphragm-type pumps. Circular diaphragms
of 3M VHB 4905 polyacrylate were cut and biaxially pre-strained, and diaphragms of NuSil's CF19-2186 silicone rubber
were spin cast and left unstretched or modestly pre-strained. Films were mounted to a sealed chamber having a 3.8
cm diameter opening, and P-V characteristics were measured at voltages that provided field strengths before film
deformation of up to 80 MV/m in VHB films and 150 MV/m in silicone films. The most highly pre-strained VHB diaphragms
were found to have linear P-V characteristics whose slope (diaphragm compliance) depended sensitively upon applied
field. Compliance of unstretched silicone diaphragms was nearly independent of field strength at the fields tested
but displayed a notable volume shift in P-V characteristic. For both materials, pressure-volume work loops of significant
size can be obtained for specified operating pressures. Each type of diaphragm may have advantages in certain applications.
========================================================================================
Surface Evaluation of Thrombosis in Left Ventricular Assist Systems
By Hanako Yamanaka
Abstract
Thrombosis is an aggregation of blood factors including proteins, platelets and cells. Biomaterial surface-induced
thrombosis currently limits the success of cardiac assist pumps and in particular, the development of reduced size
pumps. Flow dynamics are critical in thrombosis since they affect the biological responses to biomaterial surface
contact. The flow dynamics in left ventricular assist systems (LVAS) vary with device dimensions as well as location
within the device. Therefore, understanding the complex relationship between fluid flow, biomaterials and an altered
biological environment is a key element in device design. In this study, experimental parameters were varied to
observe their effects on thrombosis in the poly(urethane urea) (PUU) blood sacs of LVAS.
Ten LVAS were implanted in calves with combinations of four parameters: (1) Sac dimensions 70cc LVAS, 50cc LVAS,
or 70cc Innovative Ventricular Assist System (IVAS); (2) Duration 3 or 30 days; (3) Postoperative anticoagulation
warfarin sodium or no anticoagulation; and (4) Mean flow rate low (2.2 L/min) or high (6.0 L/min). Upon removal
of the sacs, macroscopic thrombi at the blood sac surface were photographed and mapped by location and size. Scanning
electron microscopy (SEM) provided topographical information at the microscopic level. Fluorescent labeling using
antibodies for key players in thrombosis, the protein fibrinogen and platelets, was utilized to obtain functional
information on thrombogenesis at the sac surface.
Macroscale thrombosis was most prominent in regions expected to have lower blood flow rates and occurred least
in the 70cc LVAS. Macroscale thrombi were commonly observed in both the 50cc LVAS and the 70 cc IVAS. Microscale
assessment by SEM revealed topographical structures resembling fibrin, platelets, and red blood cells. The surface
topography appeared dependent on location within the sac, anticoagulation, and flow rate. Immunofluorescence microscopy
revealed fibrin and platelet adhesion throughout the sac. The structures observed by SEM and fluorescence microscopy
were present regardless of presence or absence of macroscopic thrombi.
Multi-scale analysis of the PUU blood sac surfaces showed thrombosis to be dependent on flow rate, device dimensions,
anticoagulation, and implantation time. Integration of these data into future circulatory support devices has the
potential to minimize surface-induced thrombosis by defining key design parameters.
Friday, April 25, 12:00 - 1:00 pm, Room 210 Hallowell
Student Presentations
Myogenic Constriction in the absence of Vascular Stretch is Controlled by
Transvascular Filtration
by Min Ho Kim
Abstract
Myogenic constriction follows vascular stretch due to a step increase in hydrostatic pressure, but also occurs
in the absence of stretch during a ramp increase in pressure. Besides stretch, we hypothesize an alternative
control mechanism of myogenic response to involve shear forces of transvascular fluid filtration from plasma across
smooth muscle cells. We recently found a role for this mechanism in a step increase in pressure and hypothesize
the same to be present during a ramp increase. Arteriolar diameters in the rat mesentry were monitored prior to
and following gradual (3 min) vascular occlusion with a glass micropipette. Fluid filtration rate was measured
with a modified Landis technique during simultaneous
measurement of arteriolar diameter. As we have previously found with a step increase in pressure, myogenic constriction
due to a ramp increase in pressure was attenuated when an osmotic solution of albumin and Ficoll was infused into
the bloodstream to decrease fluid filtration. These results are consistent with the hypothesis that shear stress
on arteriolar smooth muscle, induced by transvascular fluid filtration, is a contributing factor that helps control
myogenic tone.
===========================================================================================
The Acoustic Emission from Mechanical Heart Valve Cavitation Bubble
By Kwanghyun Sohn
Abstract
Mechanical heart valves are widely used for the replacement of natural valves as well as in ventricular assist devices and artificial hearts. Under certain operation condition vapor cavitation bubbles can be generated by mechanical heart valve movement, and collapse of these bubbles cause blood element and valve material damage. Quantification of mechanical heart valve cavitation level is necessary for further heart valve cavitation research. For this, mechanical heart valve cavitation was generated in the degassed water, and image and acoustic data was analyzed. A high speed CCD camera with 3000 frames/sec was used for the image data, and a hydrophone with 100 kHz to 500 kHz linear frequency range was used for the acoustic data. The acoustic signal was used for the cavitation quantification and compared with the image data. The main problem using pressure data for cavity quantification is separating the cavitation signal from vibration generated by valve closure. Two possibilities were investigated. The first one is based on the assumption that the bubbles generate sound wave randomly in time domain but that the sound wave has typical range in frequency domain. The second one is based on the assumption that the bubbles generate sound wave during very short time at collapse and the sound wave has no typical range in frequency domain.
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Design and Evaluation of a 64 Elements Two Dimensional Ultrasound Phased Array for Treating Benign
Prostatic Hyperplasia
by Khaldon Saleh
Abstract
Focused ultrasound surgery (FUS) is a clinical method for treating benign prostatic hyperplasia with which tissue
is noninvasively necrosed by elevating the temperature at the focal point above 60 °C using short sonications
(10-30 seconds). Previous effective prostate ultrasound devices include both mechanically and electrically steered
designs. The drawbacks behind these designs are that they can only steer the focus in the radial and longitudinal
directions or require complex mechanisms to move the focus. With two dimensional phased arrays, the focal point
position can be controlled by changing the electrical power and phase to the individual elements for focusing and
electronically steering in a three dimensional volume. This research describes the design, construction and evaluation
of a two dimensional ultrasound phased array to be used in the treatment of prostate cancer. The array was designed
with a steering angle of 14° in both transverse and longitudinal directions. A piezoelectric ceramic (PZT-8)
was used as the material of the transducer since it can handle the high power needed for tissue ablation and a
matching layer was used for maximum acoustic power transmission to tissue. Analysis of the transducer ceramic and
cable impedance has been designed for high power transfer. For this prototype, the final construction used magnet
compatible housing and cabling for future application in a clinical magnetic resonance imaging system for temperature
mapping of the focused ultrasound. To verify the capability of the transducer for focusing and steering, exposimetry
was performed and the results correlated well with the calculated field. Ex vivo experiments were performed and
indicated the capability of the transducer to ablate tissue using short sonications. For sonications with exposure
time of 10, 15 and 20 seconds, the lesion size was roughly 1.8, 3.0 and 4.3 mm in diameter, respectively, which
indicates the feasibility of this device.
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Adaptive Control Methods for Ultrasound Prostate Cancer Treatment
by Lei Sun
Abstract
Prostate cancer is second only to lung cancer as a cause of cancer-related death among men in the United States.
The American Cancer Society estimated that 189,000 new cases were diagnosed and 30,200 men died of the disease
in 2002. Although surgery is currently the major choice, prostate cancer patients are often aged men, who also
have additional health problems as well, which rule out surgery as a viable option. Recent research has found out
that hyperthermia, raising the tumor temperature to 43-45oC for 30-60 minutes, can enhance the effects
of radiotherapy and chemotherapy by preventing the cellular repair of the tumor tissues. Combination of hyperthermia
with radiotherapy or chemotherapy will greatly increase the effective of radiotherapy or chemotherapy alone. Ultrasound
has been proven to be able to conduct hyperthermia treatment effectively. The goal of this research is to design
adaptive control systems capable of raising as well as maintaining the tissue temperature to 45oC for
30 minutes, at the same time capable of keeping the temperature outside interested region close to normal temperature
by controlling the amplitudes and phases of the driving signals of the ultrasound array in the face of the tissue
inhomogeneity and perfusion rate change.
Friday, May 2, 12:00 - 1:00 pm, Room 210 Hallowell
Design of a High Frequency Annular Array for Medical Imaging
Kevin Snook
Penn State University
Abstract
Technology has improved the precision and reduced the scale of surgical procedures, however, there is a lack
of noninvasive imaging tools to help diagnose pathologies on this scale. Much research is also being done on small
animal models, such as with knock-out mice, though it is difficult to determine changes in the internal structures
in vivo.
A 50 MHz annular array for medical imaging has been fabricated. This device addresses key issues of single element
and linear array transducers which preclude them from providing very high resolution while maintaining good tissue
penetration and a real-time frame rate. The annular array incorporated six elements which were made of a novel,
fine-grain ceramic. The material was fully characterized using low frequency resonance techniques, and was found
to exhibit electromechanical coupling properties which were more desirable than those from commercial materials.
Methods of fabrication adapted from single element and linear array design, including application of a lens to
focus the acoustic energy. Laser micromachining was used to dice the circular kerfs. Electrical interconnect is
a significant factor in design of high frequency devices since elements are often tens of microns in width. A method
of patterning gold lines was developed for the interconnection scheme between the elements and coaxial cables.
Performance of the array was tested to determine center frequency, bandwidth and sensitivity. Imaging was done
using a synthetic aperture technique. A wire phantom was imaged, and the axial and lateral resolutions were determined
to be less than 80 and 130 microns, respectively, throughout a depth of 6 mm. This resolution is good for imaging
structures of the anterior eye.
For additional information, contact Ms. Doretta Garvey, Dept of Bioengineering, Tel: 814.865.1407 or E-Mail: bioe@psu.edu