Bioengineering Seminar Schedule
Spring 2004
Friday, January 16, 12:00 - 1:00 pm, Room 210 Hallowell
Michael Eppihimer
Wyeth Research
"Leukocyte, Platelet and Endothelial Cell Interactions, and Their Role in Mediating
Inflammation and Thrombosis"
Abstract
The accumulation of leukocytes and platelets at sites of vascular injury are hallmarks of the inflammatory and hemostasis responses. In recent years, studies have sought to delineate the relationship between inflammatory and coagulation pathways in the pathogenesis of vascular disease such as thrombosis and atherosclerosis. The initial accumulation of platelets to a damage blood vessel acts as an appropriate substrate whereby circulating leukocytes may attach. The association of leukocytes and platelets, and their proximity to the vascular endothelium permit an array of molecular interactions that may exacerbate platelet aggregation and fibrin deposition, and subsequently the development of thrombi. Thus, inhibition of these cellular interactions may provide a therapeutic benefit in preventing vascular thrombosis. Studies in the lab have delineated the structure activity relationship of protein antagonists to cell adhesion molecules during venous thrombosis. In addition to thrombosis, there is a concentrated research effort within the lab in characterizing the mechanisms associated with T-helper cell recruitment to sites of inflammation, and the relative molecules responsible for T-helper cell activation. In particular, studies have identified novel biological pathways within endothelial cells that may play a role in regulating T-cell activation.
Friday, January 23, 12:00 - 1:00 pm, Room 210 Hallowell
Kavitha Nellore
Final Defense
"Venular Control of Capillary Perfusion in the Presence of Cardiovascular Risk Factors"
Abstract
Evidence has accumulated in recent years that arteriolar tone can be controlled by nearby venules that are often
found in a parallel, countercurrent arrangement in microvascular beds. This mechanism appears to involve venular
production of vasorelaxing factors, which diffuse through interstitial tissue to dilate the closely paired arterioles.
The result of this dilation should be increased capillary flow due to the decrease in arteriolar resistance. Our
own studies in the mesenteric microcirculation have supported this hypothesis: in young healthy rats, we have found
that capillaries branching from venule-paired arteriolar pathways have faster flow; when such pairing is scarce,
capillary flow is relatively slow.
The positive correlation between capillary velocity and arterio-venular pairing was not observed during nitric
oxide (NO) synthase inhibition, or in either hypercholesterolemic or diabetic rats. However, the correlation could
be restored in hypercholesterolemia when the rats were given drinking water supplementation of L-arginine or an
injection of anti-neutrophil serum. In diabetic rats, venular control of capillary perfusion was restored by treatment
with fucoidan, which inhibits venular leukocyte adhesion. These results indicate that dysfunctional venular control
of capillary perfusion in both hypercholesterolemia and diabetes may be a consequence of a neutrophil-mediated
deficiency of NO.
Arteriolar tone is also reported to depend on venular shear and venular leukocyte adherence. Arteriolar and venular
wall concentrations of NO as well as tissue NO were measured in normal and diabetic rat mesentery using fluorescent
diaminofluoresceins. The results from this study indicate that NO levels are much lower in diabetic rats compared
to normal rats. Arteriolar NO is enhanced by venular shear in normal but not in diabetic rats and this might contribute
to dysfunctional venular control of capillary perfusion in diabetes.
Arterio-venular communication is an effective mechanism that can help in feedback control of capillary flow, and
improving this communication in hypercholesterolemia and diabetes would be expected to aid capillary perfusion.
Friday, January 30, 12:00 - 1:00 pm, Room 210 Hallowell
Anupam Pal
Mechanical Engineering, PSU
"Gastric Motility, Mixing and Drug Release, Analyzed Using Computer
Simulation and In Vitro Experiment"
Abstract
Surface shear due to fluid motions in the stomach is a primary mechanism in the release of pharmaceuticals from extended-release tablets in the stomach. Gastric fluid motions in the stomach arise primarily from peristaltic contractions of the stomach wall. We have analyzed these motions and their effects on surface stress and mixing by coupling computer simulations with in vivo data and in vitro experiment. We find that the contraction-induced motions underlie surface stress, drug release and gastric mixing, and contribute in previously unknown ways to gastric emptying. The talk will focus on the unique combination of computer simulation, in vivo data, and in vitro experiment for evaluation of gastric function.
Friday, February 6, 12:00 - 1:00 pm, Room 210 Hallowell
SEMINAR CANCELLED
Friday, February 13, 12:00 - 1:00 pm, Room 210 Hallowell
Keefe Manning
Penn State University
"Understanding the Mechanisms of Mechanical Heart Valve Cavitation"
Abstract
Local fluid mechanics plays an integral role in the development of mechanical heart valve (MHV) cavitation.
During in vitro high-speed videographic studies, bubble and vortex cavitation have been shown to develop during
valve closure and rebound with the potential for valve and blood element damage in vivo. Using a new single shot
MHV chamber and modified mechanical heart valve, potential flow structures were investigated that might induce
valve cavitation.
Using a Bjork-Shiley Monostrut (BSM) MHV, flow measurement studies were conducted using laser Doppler velocimetry
(LDV) in a modified MHV chamber designed to replicate the mitral annulus geometry. Under normal physiologic conditions,
a detailed, three component velocity map of the regurgitant flow field was constructed 3 mm upstream of the major
orifice, perpendicular to the pivot axis. In addition, a window was cut into the housing of a BSM valve and filled
in with acrylic to retain valve integrity and flow geometry. The window was used to investigate the flow field
within the valve housing during closure on the major orifice side.
LDV measurements revealed flow structures developed during valve closure that may support cavitation. Three-dimensional
flows were visualized including a recirculating flow that developed proximal to the major orifice within the atrium.
This recirculating flow pattern was initiated at the onset of valve closure and decreased in size until it became
a tight vortex at valve impact and briefly enlarged during rebound. Observations from within the BSM housing revealed
the onset of the vortex and velocities within the clearance gap on the order of 20 m/s.
The measurements within the MHV housing suggest a mechanism of heart valve cavitation induced by a tight vortex
forming at valve impact and expanding during rebound. Valve rebound creates a low-pressure tension wave locally,
and coupled with the low pressure core of the vortex, may lead to cavitation inception due to the local pressure
drop within the vortex.
New insight into the development of MHV cavitation has been uncovered in this study. LDV was used to investigate
the flow fields within and near the housing of the BSM MHV. Vortical flow structures were identified that could
lead to pressure reduction and cavitation resulting in blood element and valve damage. The approach described here
may be used to examine the impact that dP/dt, valve design, and valve material have on flow structures underlying
cavitation.
Friday, February 20, 12:00 - 1:00 pm, Room 210 Hallowell
Robert Sainburg
Penn State University
"The Neural Foundations of Handedness: Evidence for Dynamic Dominance"
Abstract
One of the more prominant features of human motor control is the asymmetry that we refer to as "handedness". Because the mechanical characteristics of the limbs are largely symmetric, handedness is thought to arise from lateralization of neural control systems. However, regardless of years of research, consistent performance differences between the arms for performance measures, such as final position accuracy, movement time, peak velocity, and reaction time have yielded equivocal results. Because of this, the neural mechanisms that underlie motor lateralization remain poorly understood. The most prominent hypothesis that has emerged from previous research proposes that the dominant hemisphere/limb system is specialized for planning movements whereas the nondominant system is specialized for errors correction. Our studies have examined asymmetries in coordination between the limb segments. In studies of multijoint reaching, we showed that dominant hand path curvatures are independent of the passive "interaction" torques generated between the segments of the moving limb, whereas, the paths of the nondominant hand is constrained by these interactions. Dominant arm movements are consistently performed with a substantially smaller mean squared torque, which corresponds to reduced muscle activities. Nevertheless, nondominant arm movements consistently show greater final position accuracies. More recent findings have indicated fundemental differences in how each system controls movement distance. The dominant system appears to rely on forward control of distance by specifying initial accelerations prior to movement. The nondominant system does not appear to specify distance in advance, but rather employs feedback to extend movement time in accord with intended distance. In support of this, the nondominant system shows advantages for achieving final positions in the face of unexpected inertial loads. These findings support the idea that dominant and nondominant systems are specialized for different features of control: The dominant system for forward control of limb trajectory and, the nondominant system, for control of limb posture. Because these two goals are mutually competitive, it is easy to imagine why the control systems would be separated in the CNS. We expect that both systems are employed during unilateral movements, but that asymmetry is related to the greater sensori\motor access of each limb to the contralateral cerebral hemisphere.
Friday, February 27, 12:00 - 1:00 pm, Room 210 Hallowell
Lei Sun
Penn State University
"Magnetic Resonance Imaging (MRI) Guided Adaptive Real-Time Temperature Control System
for Ultrasound Thermal Therapy"
Abstract
Thermal therapy, the treatment of tissue by applying heat, is gaining more and more attention as a tumor treatment
modality, especially associated with radiotherapy or chemotherapy. In spite of the advantages, its clinical application
is still limited due to a lack of effective real-time temperature control system to precisely manipulate the target
tissue temperature at therapeutic level by delivering proper amount of acoustic power.
During ultrasound hyperthermia, it is required to maintain the target tissue temperature above 43oC
for about half an hour, and have the temperature less than 41oC outside the region of interest. In this
research, several adaptive feedback control methods have been proposed and evaluated for an intracavitary ultrasound
phased array system for ultrasound hyperthermia. The driving signals (phase and amplitude) of the array elements
are controlled in such a manner that proper amount of acoustic power is deposited in the desired location to compensate
for the dynamic temperatures due to the tissue blood perfusion change.
Using the proton resonant frequency shift, magnetic resonance imaging (MRI) as a technique capable of providing
non-invasive 2-D or 3-D quantitative temperature feedback makes the ultrasound hyerpthermia treatment completely
non-invasive. MRI also provides an alignment of the ultrasound applicator with respect to the target tumor tissue.
In vitro and in vivo MRI-guided adaptive temperature control system are tested with tissue phantom (bovine muscles)
as well as animals (rabbits and canines). In vitro experiments show that starting at an initial temperature of
28oC, the controller achieves the steady state temperature within 6.0 minutes; deviation from the target
profile is no greater than ± 1.37oC. Similar to the in vitro results, in vivo experimental results
indicate that the rabbit thigh muscle is heated initially from 36.5oC to the target temperature 44.5oC
for 25 minutes and the transitional period is within 8.0 minutes. The maximum variation from the desired temperature
profile is - 2.5oC; after reaching steady state, tissue temperature is maintained at 44.5oC
± 1.2oC. The MRI-guided adaptive temperature control system satisfies the requirement for hyperthermia
treatment.
Friday, March 5, 12:00 - 1:00 pm, Room 210 Hallowell
John Hossack
University of Virginia
"Leveraging Improvements in Digital Processing into Ultrasound Transducer Design and
Operation"
Abstract
In ultrasound imaging systems, as in many medical instrumentation systems, overall performance is largely determined by the weakest link in a serial processing chain. Fundamental physics and material properties considerations limit our ability to continuously make significant improvements in transducer performance. However, dramatic improvements in terms of cost and performance are evident in digital electronics and current trends are expected to continue. Therefore, there is a growing opportunity to explore approaches for compensating for the limitations of conventional transducers using digital processing techniques. In this talk, I discuss four methods for improving overall transducer / imaging system performance. All depend on having a versatile programmable transmit waveform generator. In the first of these, phased waveforms are applied to dual active layer transducers to yield true octave bandwidth. (Conventional transducers have a null at the harmonic.) The second method considers how the conventional problem of only being able to obtain a single focal zone for each transmit ‘firing’ can be overcome by programming multiple focal depths for multiple frequency bands within the transmitted waveforms. The third method explores how acoustic crosstalk in ultrasound arrays can be mitigated by characterizing the crosstalk signal and then applying compensating waveforms on adjacent elements to cancel crosstalk effects. In the last method, the spurious harmonic signals normally generated by electrostatic (capacitive) transducers can be reduced by an iterative waveform correction process.
Friday, March 12, 12:00 - 1:00 pm, Room 210 Hallowell
NO Seminar Spring Break
Friday, March 19, 12:00 - 1:00 pm, Room 210 Hallowell
Dorian Liepmann
University of California
"Complex Fluid Flows in Micro-Devices"
Abstract
BioMEMS is a rapidly growing area enabled by new approaches for fluid control and its potential for biomedical applications. Research on the design and development of microfluidic components such as needles, pumps, valves, and mixers and their integration have been on-going for several years aided by substantial funding by DARPA. Many, if not most, biomedical applications will involve fluid control of complex and two-phase fluids including flows containing bubbles or particles as well as polymers. In the MEMS environment, the characteristic length scales of cells, large molecules, and functionalized beads are similar to the length scales of the micro-flow channels. The seminar will present recent research on fundamental fluid mechanics of these types of flows in micro-environments, especially those situations that exhibit unexpected results for which we are still looking for answers.
Friday, March 26, 12:00 - 1:00 pm, Room 210 Hallowell
Mary Elizabeth Williams
Chemistry, Penn State University
"Directed Transport of Functional Nanoparticles"
Friday, April 2, 12:00 - 1:00 pm, Room 210 Hallowell
David GoughCANCELLED
University of California
"Bioengineering of the Implantable Glucose Sensor"
Abstract
The development of an implantable glucose sensor and automated insulin delivery system that would enable people with diabetes to better manage blood glucose has long been an important bioengineering objective. After considerable effort, sensors have been developed that are now being tested in human clinical trials, and the possibility of practical automatic control of blood glucose is in sight. Nevertheless, there are still many important issues to be addressed related to the sensors themselves, the control system, and the physiology of metabolic regulation.
Friday, April 9, 12:00 - 1:00 pm, Room 210 Hallowell
Student Presentations:
"Kinesin Force Measurements by Optical Trap"
By Kihong Ahn
Abstract
Kinesins are molecular motors that transport intracellular organelles on microtubules. Kinesin motors are consisted
of head domain, which has ATP hydrolysis sites and microtubule binding sites, rod domain, and tail domain that
has cargo binding sites. We performed bead motility assays in an attempt to analyze the properties of kinesin motors,
where kinesin motors are adsorbed to 0.2-micrometer silica beads and microtubules are immobilized on treated surface.
When the motor approaches to a microtubule, it binds to the microtubule through its head domain and starts to move
along the microtubule. We built an optical trap using 633nm He-Ne laser on an inverted microscope and the optical
trap, which can trap a microsphere in solution, was employed to manipulate beads and to measure the force exerted
by kinesin motors, and to aid the bindings of beads to microtubules. Beads trapped in an optical trap, are moved
on a microtubule by kinesin motor, but as soon as the optical trap force overcomes the kinesin motor force the
beads quickly get back to the trap center. The displacements of the microtubule bound beads from the optical trap
center are recorded and used to measure the kinesin run length and the maximum kinesin force.
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"An Alternative Technique To Compare Power Flow Between Non-Pathological Foot-Shank (NPFS)
System and Below-Knee Prostheses (BKP)"
By Prashant Bansal
Abstract
The human foot ankle system is a very sophisticated system of bones, muscles, tendons, ligaments and passive
tissue. Gait analysis studies have suggested that the muscles crossing the ankle joint produce more work (approximately
five times more energy than they absorbed during gait) than any other joint in the body (Winter et al 1983). It
is impossible to get this phenomenal energy generation with existing prostheses because of their passive components.
Studies evaluating Energy Storage and Release (ESAR) in BKP compare prosthesis with prosthesis to evaluate their
performance to aid in prostheses prescription. Biomechanical investigations comparing ESAR in the NPFS system and
BKP are very limited. Most of these studies used the ankle power curve to obtain the ESAR in the normal population.
When a person loses his/her leg they do not just lose the foot but also a part of the shank, tendons, muscles,
ligaments and plantar fascia in the foot. All these structures are elastic in nature and can store and return energy.
The ankle-power curve clearly underestimates the significance of these elastic structures which must be included
in the analysis when calculating the energy storage and release. In order to account for the elasticity of these
structures a novel technique to compute the ESAR in the NPFS system was developed using Scott Delp's lower extremity
model (Delp et al, 1990) in the SIMM modeling environment, which accounts for strain energy that could be stored
in the tendons and other passive structures of the NPFS system. The work of the bone-on-bone force and moment,
elastic strain energy of the tendons and muscle-power was computed to obtain the net power flow in and out of the
NPFS system.
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"Oligonucleotide-Directed Alignment of Cytoskeletal Filaments for Nanoscale Assembly"
By Yi-Chun Chen
Abstract
The goal of this project is to align cellular filaments (microtubules) on engineered surfaces and use motor
proteins (kinesins) attached to nanoparticles or other structures for directed assembly, molecular sorting, or
force generation at nanoscale dimensions. The obstacle to using microtubules and kinesins for this application
is that the motors move undirectionally along the filament tracks and so the microtubules must be properly oriented
to obtain directed motion.
This project uses the specificity and reversibility of double-stranded DNA hybridization to attach microtubules
with desired orientation, onto pattern surface. Oligonucleotides with known sequence will be covalently attached
to one end of a microtubule, and their reverse complements will be attached to specified locations on a lithographically
pattern surface. By conjugating different oligonucleotides to each end of the microtubule and attaching their complements
with proper spacings onto surfaces, microtubules will be affixed to surfaces with defined orientation. Then motors
can move with desired directionality along the microtubule tracks. This technique provide an opportunity of overcoming
a major hurdle in obtaining useful nanoscale work from cellular motor proteins, and should provide a strategy for
creating spatially defined patterns of virtually any protein.
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"ATPase Rates of KIF3A/B and its Chimaeric Homodimers"
By Minki Hwang
Abstract
KIF3A/B is a member of the KinII kinesin subfamily which has naturally two distinct heads. Since the mechanism of the movement of the kinesin along the microtubule is not yet fully understood, it is expected that studying the role of each head of naturally occurring heterodimer will help understanding the interdomain coordination in all kinesins. Kinesins use ATP as the energy source as they move along the microtubule, and it is known that one molecule of ATP is used per each step for conventional kinesin. The goal in this study is to measure the ATPase rates of wild type KIF3 and mutants containing two identical head domains, and compare the ATPase rates to the velocity data from motility assays. The radiometric ATPase assay, which is more sensitive than other assays, was used in this study, and the active motor concentration was determined by radionucleotide binding assay. The ATPase rates were measured as a function of microtubule concentrations, and the data were fitted to the Michaelis-Menten equation. The maximal microtubule stimulated ATPase rate of the most active motor KIF3B/B was 37 ATP/(dimer*sec) consistent with the 50 steps/sec predicted from motility assays. The measured microtubule affinity (Km=0.7uM) is similar to conventional kinesin.
Friday, April 16, 12:00 - 1:00 pm, Room 210 Hallowell
Student Presentations:
"Scaled Interfacial Activity of Proteins at the Liquid-Vapor Interface"
By Anandi Krishnan
Abstract
A principal conclusion drawn from observations of time- and concentration-dependent liquid-vapor (LV) interfacial
tension glv of a diverse selection of proteins ranging from albumin to ubiquitin is that concentration scaling
substantially alters perception of protein interfacial activity, as measured by the amount adsorbed to the hydrophobic
LV surface. Proteins appear more similar than dissimilar on a weight/volume basis whereas molarity scaling reveals
a "Traube-rule" ordering by molecular weight, suggesting that adsorption is substantially driven by solution
concentration rather than diversity in protein amphilicity. Scaling as a ratio-to-physiological-concentration demonstrates
that certain proteins exhibit the full possible range of interfacial activity at-and-well-below physiological concentration
whereas others are only weakly surface active within this range, requiring substantially higher solution concentration
to achieve maximum adsorption to the LV interface. Important among this latter category of proteins are the blood
factors XII and XIIa, assumed by the classical biochemical mechanism of plasma coagulation to be highly surface
active, even in the presence of overwhelming concentrations of other blood constituents such as albumin and immunoglobulin
that are shown by this work to be among the class of highly-surface-active proteins, at physiologic concentration.
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"Numerical Evaluation of Power Radiated and Dissipated by a Loaded Surface Coil at High
Field"
By Wanzhan Liu
Abstract
The evaluation of radiation power loss of a RF coil has been an interest particularly for high field MRI engineering.
The radiation power of an antenna is proportional to the square of the antenna-length-to-wavelength ratio. Thus,
the decrease of the wavelength in high field MRI systems may increase the radiation power loss of a coil to a significant
degree. To theoretically or experimentally assess the radiation power loss of a given RF coil is difficult because
of the complicated geometry and the near-field characteristics of the sample-coil system. In this report, we examine
the radiation loss in a surface coil loaded with different samples at different frequencies using a computer modeling
method. It is found that the radiation loss by a surface coil remains small in the frequency regime that corresponds
to the field strength available for human imaging. The high dielectric constant of the human sample reduces radiation
loss.
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"Influence of Substratum Surface Characteristics on Osteoblast Adhesion and Morphology "
By Xiaomei Liu
Abstract
Time-varying interactions of human fetal osteoblastic cells (hFOB 1.19) with materials of diverse chemical composition
and surface energy were assessed using a combination of assays sensitive to different phases of cell-substratum
compatibility. Short-term (minutes to hours) cell-attachment-rate assays were used to measure the earliest stages
of cell-surface interactions leading to adhesion. Proliferation-rate assays quantifying viability of attached cells
were applied as a measure of medium-term (hours to days) cytocompatibility. Both attachment- and proliferation-rate
assays were found to strongly correlate with material surface energy, with the exception of a reproducible and
significant adhesion preference for fully water-wettable quartz over glass. No such adhesion/proliferation preference
was observed for hydrophobized counterparts, and attachment to water-wettable glass was significantly less than
that to control tissue culture polystyrene. These results suggest that the amorphous SiOx surface was inhibitory
to hFOB 1.19 growth whereas putatively crystalline quartz stimulated bioadhesion. Moreover, SEM and immunofluorescent
image analysis have been used to monitor cell morphological changes with time on substratum surface energy extremes
from hydrophilic to hydrophobic ones, and TCPS controls. The results from these two analyses are consistent and
indicate that hFOB cells had precise response and adjustment to the substratum surfaces with showing large morphological
differences at the early stage of cell growth. Once cells adapt to the growth environment, they begin to proliferate.
Not much morphological difference can be observed then. ======================================================================================================================================
"Monitoring Lipid-Order Fluctuations in Biomembranes with High Spatial and Temporal Resolution"
By Deepti Mudaliar
Abstract
The role of biomembranes in various cellular functions like signal transduction and intracellular trafficking cannot be understated. The lipid order and specialized domains 'rafts' in plasma membranes play an important role in such functions with implications in neurodegenerative diseases such as Parkinson's, Alzheimer's and prion diseases, and serve as portals of entry for various pathogens such as the HIV AIDS virus. Lateral diffusion within biomembranes has been studied in both model biomembranes and living cells using various techniques, but much less attention has been devoted to the rotational diffusion within these two systems. Currently we are developing the Fluorescence Polarization Cross-Correlation Spectroscopy (FPCCS) technique to elucidate the dynamics of rotational mobility and translational diffusion of fluorescent markers impeded within biomembranes. Our long-term plan is to gain quantitative and real-time assessments of the role played by lipid order and orientations in various cellular responses with both spatial and temporal resolution.
Friday, April 23, 12:00 - 1:00 pm, Room 210 Hallowell
Student Presentations
"Interlimb Differences in the Control of Movement Speed"
By Pratik Mutha
Abstract
Recent results from our laboratory indicate interlimb differences in the mechanisms that control movement extent: the dominant system appears to rely on acceleration impulse-height control, whereas, the nondominant system relies more extensively on pulse-width control. The former mechanism of control is employed prior to the opportunity for closed loop mechanisms, whereas the latter has been associated with feedback mediated events. We now employ two different tasks to specifically investigate interlimb differences in feedforward and feedback mediated control mechanisms. In the first study, subjects were to make elbow extension movements that achieved different peak velocities, in the absence of a spatial target. Because peak speed is determined early in the movement, and because the movement had no spatial accuracy requirement, we expected this condition to reflect largely open-loop mechanisms In contrast to our previous studies, the differences between the limbs were drastically reduced. Both systems employed pulse height control, emphasizing the similarities in open loop control. However, the nondominant arm showed a greater variation of acceleration impulse width with movement speed, supporting a nondominant system reliance on pulse width control. Our second task, emphasized control of three target speeds, but also required accuracy to a single spatial target. Both limbs continued to utilize similar pulse height strategies at movement onset. Whereas, the dominant limb showed little variation in acceleration impulse duration, the non-dominant arm system showed substantial reductions in acceleration impulse width at increasing target speeds. Whereas, both arms showed similar movement accuracies, the nondominant arm utilized acceleration impulse width control to regulate movement distance. In contrast, the dominant arm adjusted deceleration amplitude and width in accord with distance requirements of the task. These differences support our previously identified interlimb differences in reliance on pulse height and pulse width control mechanisms, respectively. Taken together, these findings suggest that control of movement speed through open loop mechanisms is fairly similar for both dominant and nondominant limb systems. However, spatial accuracy appears to be controlled through different mechanisms for the dominant and nondominant systems: The former controls movement amplitude largely through pulse height mechanisms, whereas, pulse width mechanisms do not emerge until the deceleration phase of motion. The nondominant system, in contrast, relies more heavily on pulse width control mechanisms, which emerge early in the initial acceleration phase of motion. These differences likely reflect differences in reliance on open and closed loop control mechanisms, respectively.
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"Functionalization of Microtubules with DNA and Quantum Dots for Directed Assembly of Nanoparticles"
By Gayatri Muthukrishnan
Abstract
Microtubules are 25 nm biopolymers that act as tracks for intracellular transport by the motor protein kinesin. We seek to employ microtubules and kinesin for directed assembly of nanoparticles, which requires being able to functionalize them with molecules like DNA and quantum dots. Functionalizing with single stranded DNA allows binding of microtubules to surfaces patterned with complementary DNA strands. Quantum dots function as fluorescence probes that overcome photobleaching property of current fluorophores. They can be modified for biological labeling and can function as protein carriers. Our approach to functionalization has been to employ biotin-streptavidin chemistry: both the microtubule and the functionalizing molecule are covalently biotinylated and streptavidin is used as molecular glue to bridge them. At present, we have observed motility of quantum dot functionalized microtubules and binding of DNA functionalized microtubules on a complementary surface.
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"Pressure-Volume Characteristics of Electroactive Polymer Laminates for Blood Pump Applications"
By Kimberly Pope
Abstract
Electroactive polymers are materials that change shape in the presence of an electric field. A subset of electroactive
polymers is dielectric elastomers, thin films that change in thickness under electrostatic
pressure from an applied electric field. Previous research has demonstrated the potential for dielectric elastomer
diaphragms for use in pumping applications. This testing focused on small volume, single
layer diaphragms that operated at very low pressures. Organizing the thin films into laminates increases operating
pressures, making the technology more suitable for blood pump applications.
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"Particle Separation in Microchannels Using Flow Rate Control"
By Sung Yang
Abstract
In many miniaturized total analysis systems, sample preparation still remains a critical challenge. Most of biological cell analyses require the ability to either remove cells from a biological fluid, such as the removal of blood cells from plasma, or to concentrate the cells for downstream processing. In this study, microfluidic channels to enhance particle separation are designed based on the Zweifach-Fung effect. In the microcirculation, when erythrocytes flow through a bifurcating region of the capillary blood vessel, they have tendency to travel into the daughter vessel which has the faster flow rate resulting almost zero cells traveling to the slower flow rate channel. The critical flow rate ratio between the daughter branches for this separation is on the order of 2.5:1 when the cell-to-vessel diameter ratio is of the order of 1. The main reason for this phenomenon is that the cell facing a higher flow rate vessel is subjected to higher pressure gradient inducing it to be drawn into faster flow rate vessel. In addition, asymmetric distribution of shear force due to the different flow rate at the surface of particle reinforces it to travel into the faster flow rate vessel. Microfluidic channels have been fabricated on PolyDiMethylSiloxane (PDMS) using the soft-lithography process. The inlet channel width was 35 mm and the daughter channels have different channel widths and lengths to introduce different flow rate ratios (1 to 8) between two daughter channels by changing the downstream flow resistance of each daughter branch. The separation efficiencies were obtained with respect to the flow rate ratio and compared with the estimated flow percentage in the fast daughter branch. The long-term goal of this study is to quantify the separation efficiency with geometric factors including particle diameter/channel width ratio, bifurcating angle and flow rate ratio of each daughter channels. We believe that this mechanism can allow us to develop highly efficient and cost effective microfluidic devices for Lab-On-a-Chip (LOC) including cell concentration, cell-free biological sample preparation devices because of its simple structure and simple control mechanism.
Friday, April 30, 12:00 - 1:00 pm, Room 210 Hallowell
Tim Baldwin
NIH
"The Past, Present, and Future of NHLBI's Artificial Heart Program"
Abstract
The Artificial Heart Program at the National Heart, Lung, and Blood Institute (NHLBI) began in 1964 after Congress recommended moving forward on total artificial heart (TAH) research and after the institute's council recognized the high priority of artificial heart development. In the 40 years since, pneumatic and electro-mechanical TAH devices have been developed and used with intermediate success to treat patients requiring chronic left and right heart support. Also during that time, left ventricular assist devices (LVADs) were recognized as an attractive alternative therapy for bridging patients to transplant. With the results of the recent REMATCH clinical trial, LVADs are now approved and used for long-term permanent circulatory support. However, with the substantial rate of adverse events which occur in patients supported with the current generation of devices, better devices are needed. As such, the NHLBI continues to fund research to improve current devices and to develop next generation devices. Other NHLBI activities in this area include funding the development of VADs for children with congenital heart disease and interest in supporting investigations of cardiac recovery in circulatory support patients.
Thursday, June 10, 10:00 a.m. - 12:00 p.m., Room 210 Hallowell
Khaldon Saleh
Final Defense
"Design and Evaluation of Multi-Dimensional Ultrasound Phased Arrays for Thermal Treatment
of Prostate Diseases"
Abstract
The design and construction of multi-dimensional ultrasound phased arrays, to be used for the treatment of prostate
cancer and benign prostatic hyperplasia, present many challenges for design engineers. Many design issues, sometimes
contradicting each other, must be looked at in order to have a reliable design. The resonance frequency has to
be high enough in order to prevent cavitation and have a sharp focus, and low enough in order to be able to generate
a focus and go deep in tissue. A compromise resonance frequency of 1.2 MHz was chosen for the proposed designs.
The array must also have a lot of tiny elements in both directions in order to pin point the target, but at the
same time the elements must be large enough to be possible to manufacture. Electrical matching, acoustical matching
and appropriate cabling, must also be taken into consideration in order to efficiently deliver the required acoustical
energy to the target volume.
In this study, two multi-dimensional ultrasound phased array designs have been considered, a 64-element two-dimensional
and a 63-element 1.75-dimensional phased arrays. One l/4 silver epoxy matching layer
has been used for the first array, and two l/4 matching layers, the first being silver
epoxy and the second was SPURR-4, were used in the second one. The matching layer(s) ensured the delivery of maximum
acoustical power to tissue. Matching circuits and low capacitance coaxial cables have been used in both designs
to ensure delivering maximum electrical power to the arrays. Both designs were constructed, and then tested using
exposimetry and ex vivo bovine experiments.
Thursday, June 17, 9:00 a.m. - 12:00 p.m., Room 210 Hallowell
Jonathan Cannata
Final Defense
"High Frequency (>20 MHz) Ultrasonic Arrays for Medical Imaging Applications"
Abstract
High frequency (>20 MHz) ultrasound is currently used for various imaging applications in ophthalmology,
dermatology, and small animal studies. At present there are several commercial ultrasound systems available for
use in the 25 MHz to 50 MHz frequency range. These systems rely on single element transducers that are mechanically
scanned in a line or arc to form an image slice. Array systems, on the other hand, are desired because they use
electronic scanning to form an image slice. Arrays also lack movable parts the can be patient hazards, can be steered
and dynamically focused in the image plane, and can achieve higher frame rates. Unfortunately at the present time
array systems are not yet available at frequencies above 20 MHz due mainly to fabrication issues, as well as, a
lack of quality high frequency materials and electronics.
This presentation discusses the development of a 64 element 35 MHz ultrasonic array. This array was designed primarily
for ocular imaging applications, and features 2-2 composite elements mechanically diced out of a fine grain high
density Navy Type VI ceramic. Array elements were spaced at a 50 micron pitch, interconnected via a custom flexible
circuit and matched to the 50 Ohm system electronics via a 78 Ohm transmission line coaxial cable. Elevation, or
off axis, focusing was achieved using a cylindrical epoxy lens.
A finite element model was used to study the effects of array element geometry on performance. This model showed
that array element sub-dicing was required to suppress unwanted acoustic cross-talk between elements and improve
the angular response of the array. The final array design was based upon tradeoffs between the ease of fabrication,
level of array encapsulation, and performance.
Several prototype arrays were fabricated and tested, yielding promising results. An average center frequency of
35 MHz was achieved with and average -6 dB bandwidth of 55% and 20 dB pulse length of less than 110 ns. A maximum
combined electrical and acoustical crosstalk between adjacent or next adjacent elements was less than -23 dB. These
results indicate that the 35 MHz array developed is capable of resolving structures in the human body that are
smaller than 0.1 mm.
Tuesday, June 22, 10:00 a.m. - 12:00 p.m., Room 210 Hallowell
Seungjun Lee
Final Defense
"Ultrasound-Mediated Transdermal Insulin Delivery and Glucose Measurement Using the Cymbal
Array"
Abstract
Recent studies have shown that ultrasound mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to demonstrate ultrasonic transdermal delivery of insulin and glucose measurement with a novel, low profile two-by-two ultrasound array based on the cymbal transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 x 37 x 7 mm3 in size and weighed less than 22g. To evaluate the efficacy of the array as a practical insulin delivery and glucose measurement device, one in vitro and three in vivo experiments have been designed for this study. For in vitro experiment, human cadaver skin from skin bank were used while hyperglycemic rats and rabbits were used for in vivo experiments. Human skin was placed in a Franz diffusion cell and exposed to the ultrasound for an hour. The increased concentration of insulin in the receiver chamber of a Franz diffusion cell was measured in a spectrophotometer. The concentration of insulin in the chamber after ultrasound exposure increased 10-fold. For an in vivo test, thirty Sprague Dawley rats were divided in six groups. Each animal was anesthetized with a combination of ketamine and xylazine. The abdominal area of the rats were shave and the array was placed on the surface of the shaved skin. With 5 minutes of ultrasound exposure (Isptp = 100 mW/cm2, 20% duty cycle), blood glucose level decreased 233.3 ± 22.2 mg/dL in 90 minutes compared to the glucose level of untreated control groups. To explore the efficacy of the array in larger animal, sixteen New Zealand White rabbit experiments were performed in three groups: two controls and one ultrasound with insulin exposure. The rabbits were anesthetized and their thigh area was shaved for the exposure area. After one hour of ultrasound and insulin exposure, the glucose level was decrease to -132.6 ± 35.7 mg/dL compared to the levels of glucose of control groups. For noninvasive glucose measurement, nine Sprague Dawley rats were used. The array was placed on the shaved abdominal skin of the rats and the skin was exposed to ultrasound for twenty minutes. The device was removed and the electrochemical glucose sensor was placed on the skin. The glucose level was measured by the electrochemical sensor and compare to the results from a commercial glucose meter. The difference between two results was about 11.9 ± 58.3 mg/dL. These results indicate the feasibility of the cymbal array for ultrasound enhanced transdermal insulin delivery and glucose measurement.
Friday, July 9, Room 210 Hallowell
David Gough
University of California
"Bioengineering of the Implantable Glucose Sensor"
Abstract
The development of an implantable glucose sensor and automated insulin delivery system that would enable people with diabetes to better manage blood glucose has long been an important bioengineering objective. After considerable effort, sensors have been developed that are now being tested in human clinical trials, and the possibility of practical automatic control of blood glucose is in sight. Nevertheless, there are still many important issues to be addressed related to the sensors themselves, the control system, and the physiology of metabolic regulation.
For additional information, contact Ms. Doretta Garvey, Dept of Bioengineering, Tel: 814.865.1407 or E-Mail: bioe@psu.edu