Bioengineering Seminar Schedule
Fall 2007
Tuesday, August 21, 12:00 - 1:00 p.m., Room 210 Hallowell, CG628 Hershey
Prof. Dr. Axel R. Pries
Institute for Physiology, Charitéé Berlin, and German Heart Center Berlin; Germany
"Vascular Adaptation: An Integrative View"
Abstract
Vessel diameters continuously change in response to feedback signals derived from vascular function including
blood flow (shear stress) blood pressure (circumferential wall stress) and tissue metabolic state. Many components
and mechanisms of angioadaptation have been described. However, the complex interaction of functional stimuli,
molecular mediators, cellular reactions and resulting functional properties of vascular beds is still poorly understood.
Integrative approaches, including the analysis and extrapolation of experimental findings by mathematical models
are thus needed. For the structural adaptation of existing vessels (remodeling), mathematical models have been
presented which allow prediction of realistic vascular properties based on a generic set of adaptation characteristics.
These models allow a quantitative analysis of the relation between vascular reaction patterns to mechanical stimuli
and properties of terminal vascular beds including situations with aberrant adaptive properties or systemic conditions.
In the future, mathematical model simulations of angiogenic processes which include the molecular level will be
useful not only to understand the involved mechanisms in a quantitative fashion, but also to define possible targets
for effective therapeutic interventions and to predict the corresponding effects.
Friday, August 31, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Shile Liang
Ph.D. Thesis Defense
"Hydrodynmic Effects on Intercellular Interactions of Tumor Cells with Leukocyte and Endothelium"
Abstract
One person in the US dies from the metastatic consequences of melanoma every hour. Currently, no effective treatment
exists to prevent metastasis of melanoma cells to the lungs or to inhibit metastatic tumors growing at this site.
This is due, in part, to a lack of therapeutic approaches designed to inhibit melanoma metastasis to the lung.
Cancer metastasis requires that tumor cells detach from a primary site and invade the surrounding stroma, survive
immune defenses and turbulence of the blood circulation after invading into the circulatory system, extravasate
through the endothelial lining of blood vessels and finally form a new colony in the surrounding tissue. A better
understanding of the underlying mechanism of cancer metastasis holds the promise to design effective interventions
for metastatic cancer. The goal of this study is to investigate mechanisms involved in an important step in the
metastatic process - the interactions of melanoma cells with leukocytes within the tumor microenvironment that
results in tumor cell adhesion to the vascular endothelium (EC) and subsequent extravasation in the microcirculation.
Results have indicated that polymorphonuclear neutrophils (PMNs) can facilitate melanoma cell adhesion to the EC
through the binding of b2 integrins on PMNs and intercellular adhesion molecule-1
(ICAM-1) on melanoma cells as well as on the EC. This process is regulated by the hydrodynamic shear rate, which
is inversely proportional to the convection-driven cell-cell contact time (or adhesion on-rate kinetics), rather
than by the shear stress, which is proportional to the force exerted on formed bonds (or adhesion off-rate kinetics).
This may be ascribed to two possible mechanisms which have been shown all to be affected by the fluid transport
and mechanics: First, heterotypic aggregation between melanoma cells and PMNs - a critical step for PMN-facilitated
melanoma adhesion to the EC; Second, the up-regulation of b 2 integrins on
PMNs in response to chemokines endogenously-produced within the tumor microenvironment.
Molecular mechanisms involved in initiating the communications between melanoma cells, PMNs, and the ECs could
be responsible for melanoma adhesion and extravasation, especially which involve inflammatory cytokine communications
under microcirculatory flow conditions. Results have shown that melanoma cells induce PMNs to secrete inflammatory
IL-8 through activation of NFk- B. Melanoma-derived IL-8 is also required, as a primary
factor among many other tumor-released factors, for induction of endogenous IL-8 in PMNs. PMN-derived chemokines
in response to melanoma cells can act through autocrine and/or paracrine mechanisms to enhance PMN inflammatory
activities.The functional significance of IL-8, through the CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) on
PMNs, is that it facilitates the ability of PMNs to enhance melanoma cells to form shear-resisted arrest on the
EC and subsequent extravasation within the circulation. A potential role of B-Raf, the most mutated gene in malignant
melanomas has also been studied. Results have indicated that targeting mutant V600EB-Raf reduces melanoma
metastasis through reductions in melanoma cell extravasation through the EC. Mechanistically, reduced melanoma
extravasation following inhibition of mutant V600EB-Raf is due to the disruption of downstream NFk- B signaling within the melanoma cells linking to the constitutive IL-8 productions and
ICAM-1 expressions, which are essential for PMN-facilitated melanoma extravasation under flow conditions.
Identification and characterization of molecular targets related to inflammation and cancer remain a high priority
in cancer research. Results from this study provide new evidence for the complex roles of hydrodynamic forces,
inflammatory factors such as chemokines within the tumor microenvironment, PMN-melanoma adhesion and cancerous
genes in the recruitment of metastatic cancer cells to the EC, which will give insights for the development of
experimental therapeutic approaches to prevent melanoma metastasis.
Friday, September 7, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Herbert H. Lipowsky
"Orientation/Welcome for New Graduate Students and Old Faculty"
Friday, September 14, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Andrew Webb
Keefe Manning
Ahmed Heikal
Ryan Clement
"Research in Progress"
Friday, September 21, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
David Piston
Vanderbilt University
"Imaging the Molecular Mechanisms of Glucose-Stimulated Insulin Secretion"
Abstract
The islet of Langerhans is the functional unit responsible for glucose-stimulated insulin secretion (GSIS), and thus plays a key role in blood glucose homeostasis. The importance of the islet is demonstrated by the proven ability of islet transplants to reverse Type I diabetes pathologies in human patients. Over the last 10 years, we have been interested in understanding the multicellular mechanisms of islet function, and their role in the regulation of blood glucose under normal and pathological conditions. In many ways, the islet appears to function as a syncytium, which exhibits synchronous behavior of membrane action potentials, Ca2+ oscillations, and pulsatile insulin secretion across all b-cells in the islet. In other ways, the islet works as individual cells, especially in the regulation of gene transcription. Using our unique quantitative optical imaging methods and novel microfluidic devices, the dynamics of these molecular mechanisms can be followed quantitatively in living cells within intact islets. These investigations utilize transgenic and tissue-specific knock-out mouse models with demonstrated phenotypes, as well as traditional biochemical and molecular biological approaches.
Friday, September 28, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Wade Reeser
Ph.D. Dissertation Defense
"Intersubject Variability In Ozone Uptake By The Human Lung"
Abstract
Ozone O3 is a major component of the air pollution commonly referred to as 'smog' and inhalation
of O3 causes a decrease in lung function and can initiate inflammatory responses within the lung. Ozone
is a very powerful oxidizing agent. As such, it readily reacts with biological molecules found within the mucous
layer of the respiratory system including glycoproteins, lipids and antioxidants. The reaction of ozone with the
molecules in the mucus layer is so rapid that ozone never diffuses through the mucus layer to directly contact
the underlying endothelial tissue of the lung. The reaction products are frequently toxic and diffuse through the
mucus lining layer and produce inflammatory and neurological responses that result in the observed decrements in
lung function.
Numerous studies have established that while decrements in pulmonary responses are reproducible within subjects,
there exists a large variability between subjects for a given inhaled O3 concentration, ventilation
rate, body surface area and age of the subject. It is hypothesized that this unexplained variability in response
between subjects is due to such factors as differences in local dose to target tissues within the lung that may
depend upon anatomical differences of the subjects and individual biochemistry of the respiratory system. In this
work, the specific objectives were: 1) to determine the uptake efficiency of ozone for a large group of men and
women for a given exposure condition, 2) to use a mathematical model to predict uptake efficiency of ozone for
a given subject and exposure condition and 3) to identify model parameters that can be adjusted for each subject
to match the predicted uptake efficiency of the model to individual subject data.
Sixty subjects were exposed to continuous ozone concentrations of 0.25 parts per million for a 1-hour exposure
at a target ventilation of 30 liters per minute. An apparatus monitored both the respired flow and ozone concentration
at the airway opening from which the overall ozone uptake, tidal volume, breathing frequency and uptake efficiency
were calculated for each minute of the exposure. Physiological measurements were made to determine the total lung
volume and respiratory dead space for each subject.
A single-path model of the respiratory system was used to calculate the internal ozone distribution and uptake
efficiency for a given inhaled ozone concentration, tidal volume, minute volume, lung volume and respiratory dead
space. Physical parameters were identified in the single-path model as likely candidates to explain the between-subject
variation, including mucus layer thickness, hydraulic diameter, longitudinal dispersion constant and reaction rate
constant. Parameters that could effectively explain the differences in uptake efficiency between the model and
the data are identified by sensitivity analysis using physiologically relevant variation of the parameters.
It is demonstrated that ozone reaction rate constants with substrates within the mucus layer can be adjusted for
each subject to match the predicted uptake efficiency of the single-path model to individual subject data. For
the 60 experimental subjects it is shown that the large majority of individual reaction rate constants are in the
range reported in the literature.
Monday, October 1, 4:00 - 5:00 p.m., Room 210 Hallowell, CG624E Hershey
Sowmya Ballakur
Ph.D. Dissertation Defense
"The Detection of Microemboli in Blood Using Doppler Ultrasound:
Signal Analysis and Detector Performance"
Abstract
Micro-embolization in chronic vascular disease and asymptotic patients has been poorly studied due to a lack
of suitable technology. Micro-embolization has been known to result in fatal or severely debilitating conditions
such as stroke, post-operative renal failure and pulmonary embolism, among others. We envision that an accurate,
widely-available system for detecting micro-embolization will have a significant clinical impact in the following
ways --in identifying patients at the risk of a stroke and improving their therapeutic management; optimizing the
anti-platelet and anti-thrombotic therapy of patients with vascular disease, prosthetic devices and grafts, and
deep-venous thrombosis and improving the peri-operative management of patients undergoing vascular procedures.
Upon determination of the feasibility of using a high-frequency continuous wave diffraction grating transducer
for micro-emboli detection in close proximity (peripheral applications) as opposed to the frequently used clinical
low frequency TCD ultrasound units, the first objective was to develop a signal-processing algorithm incorporating
an automated method of detection of micro-emboli using the spectral content of the Doppler backscattered signals
and statistically determined decision criteria. The algorithm is intended to automatically track changes in the
Doppler signal strength that occur due to flow pulsatility and possible movement of the transducer. The detection
accuracy is measured using an in-vitro flow phantom, designed to be capable of simulating physiological flow profiles
(pulsatile and continuous flow) and emboli of known size, composition and density. Specifically, the aims are to
investigate joint time-frequency, parametric-estimator based and joint time-scale based signal processing strategies
(optimization of the parameters of the Short-time Fourier transform used, development of an adaptive-width window
based STF method of spectrum generation, parametric methods of spectral analysis, use of Continuous Wavelet Transform)
for use in the detection algorithm and the comparison of the three approaches to spectrum generation as viewed
from the emboli-detection efficacy standpoint. The goal is to arrive at the most optimum signal-processing strategy
to be adopted for increased accuracy of detection weighed against the imposed computation load on the real-time
operating monitoring device.
Wednesday, October 3, 12:00 - 1:00 pm, Room 210 Hallowell, CG623 Hershey
Igor Aronson
Argonne National Laboratory
"Self-Organization of Microtubules interacting with Molecular Motors"
Abstract
A central question in biology concerns the origin of highly-organized self-assembled macroscopic structures
from initially disordered states.
The mixture of long and rigid microtubules and dynamic molecular motors constitutes a unique well-controlled system
where the fundamentals of self-assembly process can be studied in a great detail. In vitro experiments on self-assembly
of motors and microtubules in quasi-two-dimensional geometry revealed a variety of spontaneous large-scale patterns:
ray-like asters, rotating vortices and filament bundles. Motivated by these experiments, we derive from microscopic
interaction rules a model describing spatio-temporal organization of an array of microtubules interacting with
dynamic molecular motors and static cross-links. Starting from a generic stochastic microscopic model of inelastic
polar rods, we obtain a set of equations for the local rods concentration and orientation. Above certain critical
density of rods the model exhibits spontaneous orientational phase transition and the onset of large-scale coherence.
We demonstrate that this orientational transition leads to the formation of vortices, asters, and bundles seen
in recent experiments.
Friday, October 5, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Kaushik Chatterjee
Ph.D. Dissertation Defense
"Surface-Mediated Molecular Events in Material-Induced Blood-Plasma Coagulation"
Abstract
Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical
devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing
on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials.
A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster
than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular
mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade
because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially
“benign” because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only
activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification
and propagation reactions that ultimately lead to clot formation.
In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed
sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These
studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces
attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger
procoagulants relative to hydrophobic surfaces.
Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model
surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through
the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme
at the procoagulant surface.
Calculations for the amounts of FXIIa generated at material surfaces in plasma using a mathematical model for measured
coagulation responses indicate that the relative contributions of the individual pathways of enzyme generation
are similar at both hydrophilic and hydrophobic surfaces, only the amounts of enzyme generated scale with surface
energy and area of the activating surface.
Further, from direct measurement of enzyme activation at test surfaces we observed that contact activation reactions
are not specific to negatively-charged hydrophilic surfaces. Rather, the molecular interactions are attenuated
at hydrophobic surfaces due to protein adsorption so that poorly-adsorbent hydrophilic surfaces exhibit an apparent
specificity for contact activation reactions.
Preliminary studies were preformed to assay the plasma coagulation response to low-fouling surfaces prepared by
either grafting poly(ethylene glycol) chains or using zwitterions. Results indicate that poly(ethylene glycol)-modified
surfaces are significantly weaker procoagulants than surfaces containing zwitterions underscoring a need to specifically
evaluate the coagulation response despite similarities in observed protein adsorption to both surfaces.
In summary, our studies demonstrate protein adsorption to the material surface lies at the core of contact activation
of the intrinsic blood coagulation cascade and must be incorporated in any proposed underlying molecular mechanism.
Friday, October 12, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Ghassan S. Kassab CANCELLED
Purdue Univeristy
"Biomechanics of Coronary Circulation"
Abstract
Our research interests encompass the biomechanics of the coronary circulation in health and disease. One of our goals has been to develop a computational hemodynamic model of the entire coronary circulation based on a detailed set of anatomical and rheological data of the coronary blood vessels. We have previously obtained the necessary set of anatomical and rheological data of the coronary vasculature which serve as the foundation for the large scale analysis. We are also studying the remodeling of the coronary circulation in disease such as hypertrophy and heart failure. Specifically, we are focusing on the structural and mechanical remodeling of the coronary blood vessels in response to physical factors (i.e., principal and shear stresses). The experimental aspects of our investigations encompass the collection of morphological and mechanical data on the coronary blood vessels as well as measurements of the hemodynamic parameters of interest. The theoretical aspects focus on expressing the remodeling data mathematically in order to formulate and solve significant boundary-value problems of the heart.
Friday, October 19, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Charla Triplett
BME Career Alliance
"Essential Job Search Skills for the BME"
Abstract
Ms. Triplett has over 12 years of experience working with scientists and engineers in the biomedical field, holds a B.S. in Microbiology and a M.S. in Bioengineering. She has an established reputation in the career development area of Biomedical Engineering with strong ties to academic institutions and professional societies. In addition, she has extensive connections within the medical device and biotechnology industry. Her background includes building several Biomedical Engineering Internship Programs and consulting with The Biomedical Engineering society. Charla currently serves as the President of the BME Career Alliance, a non-profit organization that helps connect biomedical engineering students with industry. She will discuss how to create a winning resume with a specific focus on the BME student, types biomedical companies that hire BMEs, careers that biomedical engineers pursue, and how to market the BME degree and skills.
Friday, October 26, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
John Fricks
Dept of Statistics, Penn State
"Diffusion in Biofluids: Microbeads in Mucus"
Abstract
High speed microscopy has enabled experimentalists to track individual microscopic particles in complex biofluids. While traditional rheology can give insights into the bulk properties of these fluids, it may not be sufficient for understanding the diffusion of the microscopic particle in the biofluid including the interaction between the surface of the particle and the fluid. These microscopy experiments attempt to understand diffusion through the paths of individual particles. As an example of such diffusion, an experiment will be introduced in which microbeads are tracked in human lung mucus (in vitro) from both healthy patients and patients with cystic fibrosis with the goal of understanding the diffusion of microscopic pathogens. The dynamics of a bead is modeled using the generalized Langevin equations. A maximum likelihood method to estimate parameters for a certain class of generalized Langevin equations will be presented along with an improved stochastic simulation method for this class of models.
"Integrating Multi-Scale Studies of Cardiac Biomechanics using a Tissue Engineering Approach"
Abstract
Relating ventricular chamber function to underlying cardiac cell and tissue properties is a problem of fundamental importance in clinical cardiology and cardiac mechanics research. This seminar presents our ongoing research efforts aimed at understanding the multi-scale mechanics of ventricular myocardium. Projects range from mapping spatiotemporal variations in mechanics of individual beating myocytes using atomic force microscopy to organ-level studies of ventricular mechanics using medical imaging and finite element modeling. A major challenge arises when attempting to bridge these micro- and macro-scale studies. One solution is to develop increasingly sophisticated computational models that try to incorporate the myriad complexities of natural myocardium. An alternative approach is to engineer model tissues that retain relevant aspects of cardiac physiology, yet are consistent with a more simplified theoretical analysis. Toward this end, we have developed living, beating, cylindrical "trabeculae" and spherical "ventricles" for studying cardiomyocyte function and mechanics. By allowing improved experimental control and long-term viability not possible with natural heart tissue, these surrogate cardiac organoids are helping to delineate the effects of chamber geometry versus cell and matrix properties on global cardiac pump function, offering an exciting new tool for the multi-scale investigation of cardiac biomechanics.
Friday, November 9, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Bruce Gluckman
Engineering Science & Mechanics
"Neuronal Modulation with Electric Fields for Seizure Control"
Abstract
Low frequency (f<<100Hz) electric fields can be applied to neuronal networks to modulate their excitability. The primary effect arises from a polarization of the highly asymmetric pyramidal neurons. We've applied such fields to control propagating waves and seizures in brain slices. We have now developed the instrumentation for applying such stimulation in chronically implanted animals while simultaneously recording neural activity with minimal artifact. We are testing this now as a prototype seizure control system.
Friday, November 16, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Kostas Konstantopoulos
Johns Hopkins University
"Integrating Engineering and Biology in Cancer Research"
Abstract
This seminar will provide an example of a multidisciplinary approach integrating engineering fundamentals with concepts and techniques from biochemistry, molecular biology and biophysics in order to better understand aspects of pathological processes, which occur within the vascular system, such as cancer metastasis. More specifically, it will emphasize the importance of the fluid dynamic environment in regulating the adhesion process of colon carcinoma cells to host cells. In view of the critical role of vascular selectins in metastasis, the seminar will discuss our approach for the identification of selectin ligands on colon carcinoma cells, their biochemical and biophysical characterization, and also outline how computational modeling could guide the design of an effective drug delivery method for targeting cancerous cells in the circulatory system.
Friday, November 23, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Thanksgiving Holiday - No Classes
Friday, November 30, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Student Presentations
"Quantitative Analysis of Gastrointestinal (GI) Motion In An Animal Model Using Dynamic
MRI "
by: Amit Ailiani
Abstract
The gastrointestinal (GI) tract functions via deformations of the intestinal wall resulting from the neurophysiologically
induced changes in the muscle fiber tone. The peristaltic contractions underlie transport, while the segmental
contractions facilitate macro mixing in the bulk flow. . Absorption and secretion processes, which rely on the
contractile activity of the lumen, are significantly affected by digestive disorders such as irritable bowel syndrome,
celiac disease and diarrhea. The main aim of this study is to quantify details of intestinal (gut) motility to
learn the predominant classes of gut motion. Dynamic and gadolinium based contrast enhanced MRI was used to quantify
the motions of the small intestine in the rats using using a horizontal bore animal scanner (7 Tesla). A 3D spatial
multi-slice data set of the entire GI tract was acquired to aid in mapping the individual small intestine of each
model. Dynamic images (~ 1000 images at 7.44 frames per second) of the localized small intestine were acquired
using gradient echo pulse sequence to capture the gut motion. A semi-automated 2D spatial + time image segmentation
algorithm based on 3D live wire and gradient vector flow snakes was implemented to accurately segment the dynamically
acquired images. MR experiments were performed on six animals and revealed that the complex gut motion can be represented
by a single motion, constriction of the boundary points along the length of the gut. Thus, our aim is to locate
the constriction along the length of the gut from the segmented boundary of the small intestine. The spatiotemporal
plot of the location of the gut with respect to time is a simplified and a compact representation of the complex
gut motion. These plots have shown that in peristalsis, the constriction propagates along the length of the gut
in contrast to the segmental, where constrictions are approximately at the same location with specific spatial
and temporal patterns. These plots can be used to quantify parameters (period, frequency, amplitude and speed of
the constriction) which can be associated with the physiological activity of the small intestine. The distance
between the adjacent constrictions varied from 1 to 2 cm and it can help us understand the pattern of neuronal
circuitry. The average period of oscillation and speed of contraction for different segments of the bowel quantified
were: a) small bowel mid jejunum, 3.0 ± 0.4 s and 0.5 ± 0.15 mm/s, b) small bowel lower section,
2.3 ± 1.1 s and 0.54 ± 0.16 mm/s and c) large bowel 2.3 ± 1.1 and 0.15 ± 0.07 mm/s
. The results for the "oscillation" period and speed of contraction showed significant differences between
the contractile motion in the large and small bowels. These are the first invivo results where dynamic MRI can
be used non-invasively to quantify the motion of the small intestine. The results from this study could be coupled
with the continuous fluid dynamic (CFD) to predict the change in fluid motions within the small intestine.
===================================================
"Microfluidic Drifting - Implementing Three-Dimensional Hydrodynamic Focusing with
a Single-Layer Planar Microfluidic Device"
by: Xiaole Mao
Abstract
Conventional two dimensional (2D) hydrodynamic focusing is intrinsically problematic for on-chip single molecule detection and flow cytometry because the lack of focusing in vertical direction causes the sample to spread over the entire depth of channel, leaving a large number of molecules or particles undetected. Three dimensional (3D) microfludic devices provide additional focusing in vertical direction; however, tedious assembly process or complex lithography procedure is required. In this work, we prove that by combining state-of-the-art fluid dynamic manipulation with standard soft lithography fabrication, 3D hydrodynamic focusing can be accomplished with a simple 2D planar microfluidic device. The hydrodynamic focusing is realized in a two-step scheme. The first step (the focusing in vertical direction) is accomplished using what we call the "microfluidic drifting" technique. Sample flow and sheath flow are co-infused into a 90-degree curve. The centrifugal effect stretches the sample flow into a thin slice parallel to the substrate, and thus accomplishes the focusing in vertical direction. The second focusing step is performed with two side channels as the conventional 2D focusing. The combined effects of the two focusing steps result in a 3D hydrodynamic focused sample flow with a simple 2D microfluidic channel design. This method is effective, robust, and most of all, does not require any extensive fabrication technique other than standard soft lithography. We believe microfluidic drifting may permit many applications that would otherwise not be possible, due to the current limitations of impractical and specialized 3D microfabrication techniques required for 3D hydrodynamic focusing.
Friday, December 7, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Student Presentations
"Ultrasound Mediated Transdermal Insulin Delivery in Pigs Using a Lightweight Transducer"
By: Eun Joo Park
Abstract
In previous studies, ultrasound mediated transdermal drug delivery has shown a promising potential as a method
for noninvasive drug administration. For prospective future human application, this study was designed to determine
the feasibility of lightweight cymbal transducer array as a practical device for noninvasive transdermal insulin
delivery in large pigs. Six Yorkshire pigs (100-140 lbs) were divided into two groups. As the control (n = 3),
the first group did not receive any ultrasound exposure with the insulin. The second group (n = 3) was treated
with ultrasound and insulin at 20 kHz with an Isptp = 100 mW/cm2 at a 20% duty cycle for 60 min. With the pigs
in lateral recumbency after anesthesia, the ultrasound transducer with insulin was placed on the axillary area
of the pig. At the beginning and every 15 min up to 90 min, the blood glucose level was determined using a glucose
monitoring system. To compare the results of individual animals, the change of blood glucose level was normalized
to each animal's initial glucose value at the start of the experiment. Although each animal had a different initial
glucose level, the mean and standard error for the six animals was 146 ± 13 mg/dl. For the control group,
the blood glucose level increased to 31 ± 21 mg/dl compared to the
initial baseline over the 90 min experiment. However for the ultrasound with insulin treated group, the glucose
level decreased to -72 ± 5 mg/dl at 60 min (p < 0.05) and continued to decreased to -91 ± 23 mg/dl
in 90 min (p < 0.05). The results indicate the feasibility of ultrasound mediated transdermal insulin delivery
using the cymbal transducer array in animal with a similar size and weight to a human. Based on these result, the
cymbal array has potential as a practical ultrasound system for noninvasive transdermal insulin delivery for diabetes
management.
===================================================
"Penn State 12 cc Pulsatile Pediatric Ventricular Assist Device: Flow Field Observations
at a Reduced Beat Rate With Application to Weaning"
By: Breigh Roszelle
Abstract
Ventricular assist devices (VADs) have become a viable option for adult patients with end-stage heart failure during the bridge-to-transplant period and have recently shown promise in aiding in myocardial recovery. Because of the low number of available organs, mechanical circulatory support systems such as VADs are also being developed for use in pediatric patients. After myocardial recovery, the system must be removed from the patient and for pulsatile devices this often includes a reduction in flow rate, which can change the fluid dynamics of the device. These changes need to be monitored because strong diastolic rotational flow, no areas of blood stasis, low blood residence time and wall shear rates above 500 s-1, can help prevent thrombus deposition. Particle image velocimetry (PIV) was used to observe the planar flow patterns and wall shear rates of the 12 cc Penn State Pneumatic Pediatric Ventricular Assist Device (PVAD) at both a normal operating condition and a reduced beat rate. At the reduced beat rate, the PVAD showed a loss of rotational pattern, increased blood residence time, and an overall reduction in wall shear rate at the outer walls. Because this reduction in flow rate could lead to a possible increase in thrombus deposition, it may be necessary to look into other options for weaning a patient from the PVAD.
Friday, December 14, 12:00 - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Student Presentations
"Regional Average Brain Cortical Thickness and Cognitive Exams in ALS"
By: Don Bigler
Abstract
Increasing evidence suggests that ALS is not simply a motor neuron disease, but a more widespread neurodegenerative
process. In this study average thickness in select brain regions was measured and correlated to a cognitive screen
exam sensitive to the three recognized FTD syndromes. Significant negative correlation between subtests scores
and average thickness were found in temporal and occipital brain regions. These results support the evidence that
ALS is a more widespread neurodegenerative disease. Furthermore, MRI validation of this FTD screen exam contributes
to the success of approaches to facilitate ALS-FTD decision-making during discussions of treatment planning and
end-of-life issues.
====================================================
"Conservative Electric Fields Can Dominate Sample Loss in High Field Microimaging"
By: Bu-Sik Park
Abstract
Recently there has been compelling evidence that sample loss can be a significant factor in SNR for high field
microimaging in MRI . Because the magnetically-induced electrical fields and related power loss within the sample
are expected to be negligible in comparison to power loss in the coil , it has been proposed that conservative
electric fields and related power loss in the sample may have a significant role. Here we perform Full-Maxwell
numerical calculations of the electromagnetic fields within a solenoid under several different loading conditions
and analyze the results to evaluate the contribution of conservative electric fields (Ec) and magnetically-induced
electric fields (Ei) to the total electric fields (Etotal) within a solenoidal microimaging coil. The methods we
present may be valuable for other MR applications as well.
====================================================
"The Effects of Cholesterol Depletion on Osteoblast Response to Oscillatory Fluid
Flow"
By: Yanghui Xing
Abstractt
A lipid raft is a cholesterol-enriched microdomain in cell membranes. It consists of various membrane proteins and lipids. Previous literatures showed that lipid raft is associated with several signaling pathways. Cholesterol is an essential part of lipid raft structure and it can be removed from cell membrane by addition of M- CD in cell culture medium. Cholesterol depletion can cause lipid raft structure disruption, thus may affect related proteins and signaling pathways. To examine the involvement of lipid raft in cell response to fluid flow, we will use cell culture medium containing 5mM M- CD to treat cells for 60 minutes before fluid flow while other cells will maintain in normal cell culture medium. Subsequently, both groups were exposed to fluid flow for 5, 15 and 30 minutes. We found that ERK activation level is significantly reduced after cholesterol removal. Additionally, ERK activation level depends on both drug concentration and number of cells. From our previous experiments, we believe ATP, P2Y2 purinergic receptor and Src are also involved in ERK activation pathway.
For additional information, contact Ms. Doretta Garvey, Dept of Bioengineering, Tel: 814.865.1407 or E-Mail: bioe@engr.psu.edu