Bioengineering Seminar Schedule
Spring 2006
Friday, January 13, 2006
Maruti Uppalapati
Bioengineering
"Controlling and Confining Kinesin Driven Microtubules in Capped Microchannels"
Abstract
In eukaryotic cells, kinesin motor proteins transport cargo and provide the mechanical forces underlying mitotic
meiotic spindle morphogenesis and chromosome separation. A continuing challenge in nanoscience is controlling the
manipulation and assembly of materials at the nano-scale, and the kinesin-microtubule system provides a model system
for force generation and nano-scale motion. Here we demonstrate a novel method for microtubule confinement and
for generating a high density ensemble of isopolar microtubules. This approach can be used to concentrate aligned
microtubules for microscale transport applications. ========================================================================================================================================
William Hancock
Bioengineering
"Recent Progress from the Hancock Lab"
Abstract
We are investigating the fundamental mechanism of kinesin molecular motors and their applications in microscale systems. Dr. Hancock will review recent progress from the lab and future directions for the research.
Friday, January 20, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Peter Butler
Bioengineering
"Fundamental Mechanisms of Endothelial Cell Mechanotransduction: Experimental and
Computational Approaches"
Abstract
Blood flow-related shear stress induces biochemical and physiological changes in vascular endothelial cells (ECs), a process termed mechanotransduction. Recent studies support the hypothesis that forces and the resultant biochemical reactions are highly localized and that this localization is regulated by the cell. These observations point to a need for new techniques to spatially and temporally map mechanotransduction events on the subcellular level. To be presented are new engineering analyses and experimental studies of single EC mechanotransduction and molecular dynamics. Comprising our experimental approaches to single cell and single molecule mechanotransduction is the integration on a single microscope platform of DIC, TIRFM, confocal fluorescence imaging, time-resolved fluorescence, and photonic-force microscopy. This infrastructure provides experimentally-determined inputs to advanced 3-D image processing algorithms, computational fluid dynamics solvers, finite element (FE) solid mechanics models, and molecular dynamics simulations enabling time- and position- dependent correlations of cell stresses with signal transduction. Such research supports the goal of developing mechanistic and predictive computational models of endothelial cell mechanotransduction and may point to new molecular level interventions for endothelial cell dysfunction.
Friday, January 27, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Tony Huang
James Henderson Assistant Professor
Department of Engineering Science and Mechanics
"From Biomimetic Molecular Machines to Functional Nanodevices"
Abstract
Biological molecular components, like myosin and actin in skeletal muscle, organize to perform complex mechanical tasks. These components execute nanometer scale interactions, but produce macroscopic effects. Inspired by this concept, we are developing a new class of mechanical nanodevices which employ a group of artificial molecular machines called rotaxanes. As a substantial step towards this long-term objective, we have proven, for the first time that rotaxanes are mechanically switchable in condensed phases on solid substrates. We have further developed a rotaxane-powered microcantilever actuator utilizing an integrated approach that combines "bottom-up" assembly of molecular functionality with "top-down" micro/nano fabrication. By harnessing the nanoscale mechanical motion from artificial molecular machines and eliciting a nanomechanical response in a microscale device, this system mimics natural skeletal muscle and provides a key component for the development of nanoelectromechanical system (NEMS).
Friday, February 3, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Jeff Zahn
Bioengineering
"Microfluidic Devices for Clinical Diagnostics and Health Management"
Abstract
Batch fabricated microfluidic platforms that can mimic conventional sample preparation techniques performed in laboratories hold great potential to enable both research and healthcare advances. Such miniaturized diagnostic devices have been termed micro total analysis systems (mTAS) or biochips and combine sensing mechanisms (physical, optical, electrical or chemical) with microfluidics. While microfluidics promises to have an impact in many research fields, one of the more attractive applications has been towards biomedical and life science diagnostics. There is a growing market for point of care diagnostic devices for both bedside and outpatient monitoring. This seminar will provide an overview of research projects currently underway in the Zahn laboratory which utilize microfluidic technologies for the clinical diagnosis and treatment of disease. First, research on miniaturized hypodermic injection needles and an on-chip microdialysis system for continuous glucose monitoring for diabetes treatment will be discussed. Next, approaches towards developing devices which can separate blood plasma from whole blood and measure the concentration of the clinically relevant proteins in a continuous, real time fashion will be discussed. This is especially important for monitoring inflammatory responses in patients undergoing cardiac surgery when cardiopulmonary bypass (CPB) is used. Finally, an approach for improving DNA purification from cells using a two phase liquid extraction with electrohydrodynamic (EHD) instability micromixing is discussed.
Friday, February 10, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Herbert Meiselman
USC
"Cellular Factors in Red Blood Cell Aggregation"
Abstract
The phenomena of reversible red blood cell (RBC) aggregation (e.g., rouleaux formation) has been observed and
studied for decades: enhanced RBC aggregation increases low shear blood viscosity and markedly affects in vivo
blood flow. There is now general agreement regarding: 1) associations between plasma levels of fibrinogen or other
large proteins (e.g., macroglobulins) and enhanced RBC aggregation; 2) effects of molecular weight and concentration
for neutral polymers such as dextran (e.g., threshold molecular weight for aggregation). Two mechanisms have been
suggested to be involved in the process of RBC aggregation (i.e., bridging, depletion). Experimental data for RBC
in polymer solutions demonstrate the existence of a depletion layer, with recent work by Neu, et al. strongly supporting
depletion-mediated forces as the main mechanism for RBC-RBC attraction.
In spite of recent progress made in understanding aggregation, one area still requires further study: the role
of RBC cellular factors as determinants of red blood cell aggregation. Several examples serve to illustrate this
point: 1) Washed RBC from normal donors re-suspended in an isotonic 70 kDa dextran solution exhibit a > 2-fold
range of aggregation; 2) Age (i.e., density)-separated normal RBC exhibit marked differences in plasma and polymers
(i.e., older>>younger); 3) Neonatal RBC aggregate less than adult cells and show smaller age-specific effects;
4) Increased aggregation in autologous plasma predicts increased aggregation in polymer solutions for all RBC (e.g.,
neonatal, adult, marine mammals). Theoretical analyses suggest that RBC glycocalyx properties (e.g., thickness,
permeability) are likely responsible for these differences, yet additional studies are required to fully define
the specific nature of such cellular factors.
Friday, February 17, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Ahmed Heikal
Bioengineering
"Navigating the Complexity of Biological Systems with Molecular Sensitivity"
Abstract
Biocomplexity is the hallmark of life with its inherent multiple-scale nature, from organized biomolecular structure, signaling and metabolic pathways, cellular functions, and cell-cell interactions in tissues. One of the main challenges is elucidating the general rules and molecular mechanisms that underlie such biological complexity in a non-invasive manner. Our research interests include energy metabolism, mitochondrial anomalies, protein dynamics, protein-protein interactions and lipid phases in biomembranes. I will discuss some of our recent results and how we use integrated biophotonics techniques for in-depth understanding of the underlying molecular mechanisms in those biological processes. Key to our experimental and modeling approaches is the ability to gain molecular information that underlie multiscale biocomplexity and systems (from in vivo, ex-vivo, to in vivo) with high spatial and temporal resolution.
Friday, February 24, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Cheng Dong
Bioengineering
"Inflammation and Cancer: Role of Intercellular and Intracellular Interactions Mediated
by Mechanics and Chemistry"
Abstract
USA Today (Nov. 10, 2004) interviewed leading medical experts about the relationship between inflammation and
cancer. Doctors believe that inflammation is involved in a wide variety of cancers. Scientists say they can't be
sure whether inflammation produces cancer, if cancer leads to inflammation, or the two processes interact. Yet
doctors suspect that long-term inflammation or infection is involved in up to 20% of cancers, including those of
the esophagus, colon, skin, stomach, liver, bladder, breast and some kinds of lymphoma. These unanswered questions
have pointed to a need for new integration in cellular and molecular studies focusing on leukocyte immunology and
cancer biology, which are currently conducted in the Cellular Biomechanics Laboratory at Penn State - Bioengineering.
Attachment of tumor cells to the endothelium under flow conditions is critical for migration of tumor cells out
of the vascular system, a process so-called extravasation, to establish metastases. The interaction of tumor cells
with endothelial cells includes three main events: 1) tumor cell adhesion to the endothelial cell surface; 2) tumor
cell-mediated breaching of endothelial junction; and 3) tumor cell penetration into the sub-endothelial space.
It has become evident from in vivo studies that the mechanisms utilized by leukocytes and metastatic tumor cells
to adhere to a vessel wall prior to extravasation are very different. Human leukocytes, including neutrophils (PMN),
actively participate in the inflammatory response via adhesion to the vascular endothelium. However, recent studies
indicate that PMN may play an important role in communication with tumor cells and affect the interactions between
them within a tumor microenvironment; hence, promote tumor cell extravasation. Such interactions are found to be
mediated by hemodynamic forces, cell deformability, cell adhesion, cell motility, and intercellular or intracellular
signaling.
Friday, March 3, 12 Noon - 1:00 p.m., Room 210 Hallowell, CG624E Hershey
Alex Wright
University of Pennsylvania
"High-Strength Gradients and Cryogenic RF Coils for MRI of Tissue Micro-Architecture"
Abstract:
This talk will focus on some recently developed micro-MRI instrumentation for the evaluation of biological tissue micro-architecture at a length scale 1-50 microns. Application-specific hardware will be presented, including a miniature ultra-high strength gradient coil for diffusion measurements and a novel cryogenic system for cooling an RF coil to increase signal-to-noise ratio. Studies of spinal cord and intervertebral disc will be described, along with methods for quantitative analysis, using lamprey spinal cord and sheep disc as models for human tissue.
Friday, March 10, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
SPRING BREAK NO SEMINAR
Wednesday, March 15, 12 - 1:10 p.m., Room 210 Hallowell, Hershey
Masaaki Sato
Tohoku University, Sendai, Japan
"Biomechanical Responses of Endothelial Cells to Shear Stress and Hydrostatic Pressure"
Abstract
Endothelial cells respond to mechanical stimuli such as shear stress, tensile stress and hydrostatic pressure,
and show changes in cytoskeletal structure, cell shape, cell functions, and so on.
In my talk, I would like to mainly focus on three topics as follows:
(1) Dynamic process of endothelial cell shape change in shear flow conditions (actin filaments, microtubules and
focal adhesional proteins),
(2) Mechanical properties of intracellular components (stress fiber and nucleus),
(3) Effects of hydrostatic pressure on EC shape.
Endothelial cells adhere to extracellular matrix at focal adhesions (FA), which are believed to play an important
role for changing cell shape. To understand the mechanism of cell remodeling by mechanical stimuli, dynamic behavior
of FA and actin filaments in endothelial cells exposed to shear stress was observed. Bovine aortic endothelial
cells obtained from thoracic aortas were used. RFP-FAT (focal adhesion targeting) and GFP-actin were co-transfected
into the cells planted in the glass-base dishes. The confluent endothelial cell monolayer was loaded into a parallel-plate
flow chamber and laminar shear stress of 1.5 - 2 Pa was applied to the cells. Cells expressing RFP-FAT and GFP-actin
were observed under fluid condition using a confocal laser-scanning microscope. Actin filaments locating in orthogonal
direction to flow first started to shrink by exposure to shear stress. FAT also moved with actin filaments along
the shrinking directions. Then, lamellipodia appeared at upstream side. During the cell remodeling process, dynamic
behavior of FAT such as appearance/disappearance, elongation, sliding and aggregation was observed. Within 20 min,
significant changes in the position of FAT were not observed.
Biomechanical properties of stress fibers isolated from cultured smooth muscle cells were measured using an originally
designed micro-tensile testing apparatus. Stress fibers were elongated more than two-fold of the initial length,
and the resistance to elongation increased with strain showing nonlinear stress-strain relation.?The initial elastic
modulus of stress fibers, 2.5 MPa, was much lower than that of synthesized single F-actin, 1.8 GPa. Mechanical
balance in the cell will be discussed among stress fibers, nucleus and internal pressure.
Endothelial cells are also exposed to hydrostatic pressure in vivo and the effect of hydrostatic pressure on morphology
and expression of VE-cadherin of cultured bovine EC was investigated. After confluent endothelial cells were exposed
to hydrostatic pressure of 50, 100 and 150 mmHg for 24 hours, F-actin filaments and VE-cadherin of endothelial
cells were stained. Statically cultured endothelial cells formed a cobblestone pattern of contact-inhibited cells
with thin, short F-actin filaments in monolayer. VE-cadherin was uniformly distributed at the periphery of cells.
In contrast, endothelial cells exposed to hydrostatic pressure exhibited marked elongation without predominant
orientation, together with development of centrally located, thick stress fibers. Pressured endothelial cells also
exhibited multilayered structure unlike monolayer under control conditions. Moreover, VE-cadherin was sparsely
distributed at the periphery of cells, and its expression was lower than that of control. These results suggest
that hydrostatic pressure could inhibit the expression of VE-cadherin, resulting in loss of contact inhibition
followed by formation of multilayered structure.
Friday,March 17, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Prosenjit Bagchi
Rutgers
"Computational Modeling and Simulation of Blood Flow in Microcirculation"
Abstract
Computational modeling and simulation of blood flow in small vessels of diameter 10-300 micron remain a major
challenge. This is because blood in such vessels behaves as a multiphase suspension.
Individuality of blood cells must be retained in the modeling. Further, the red blood cells (RBC) are highly deformable
particles.Deformability of RBC must be modeled accurately. This talk will present computational fluid dynamic models
and simulation of the hydrodynamics of deformable particles, with specific focus on the hemodynamics of blood cells
in microvessels, typical of microcirculation and microfluidic devices. The motion of a large population of deformable
blood cells (>O(100)) through straight channels/tubes and branched vessels are considered. The simulations are
multiscale, fully three-dimensional, unsteady, and well resolved in space and time, and are performed on multiprocessor
supercomputers. Flow field inside and outside of individual cells, and their dynamic deformation are accurately
resolved. Molecular interaction between the adjacent cells and between cell and vessel wall are also modeled via
a kinetic approach, and coupled to the hydrodynamics. Using the simulation as a tool, we are exploring in detail
various hydrodynamic phenomena related to blood cells in small vessels. In this talk we will present results on
deformation of red blood cells (and, capsules), their lateral migration, formation of the cell-free layer, and
the Fahraeus-Lindqvist effect. Effect of varying deformability, as in case of many blood disorders (sickle cell
disease/malaria), on the microrheology will be discussed. Aggregation between red blood cells, margination and
adhesive rolling of white blood cells under varying hematocrit, vessel diameter, and RBC deformability will also
be discussed.
Friday, March 24, 12 :00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Robert F. Kunz
ARL
"Multi-Scale Human Respiratory System Simulations to Study the Health Effects of Aging,
Disease and Inhaled Substances"
Abtract
This seminar will summarize our recent research in the application of Computational Fluid Dynamics (CFD) in
the analysis of human respiration, and will introduce our recently awarded NIH grant in this area. Specifically,
medical imaging technology and data developed by the third author have been used to obtain detailed geometric representations
of the human lung to the 11th generation. This geometry has been used by the first author and PSU students to develop
single and multiphase CFD models for respiration including gas uptake and particle deposition. Also, a quasi-one-dimensional
model under development by the second author has been used to represent the subgrid scale fluid mechanics in the
respiratory units.
In the current NIH project, a multi-scale strategy is being pursued to develop, couple, apply, and validate medical
imaging and physics modeling of resolvable and sub-resolvable scales in human respiration. Specifically, high-resolution
computed tomography (HRCT) will be used to characterize the "macroscale" convective range of the lung.
Microscopic computed tomography (mCT) and confocal microscopy (CLSM) will be used to
characterize the "microscale" global and cellular architectures of the respiratory units. Multiphase
computational fluid dynamics (CFD), and quasi-one-dimensional (Q1D) functional modeling will be used to simulate
the multi-component fluid mechanics at these macro and micro scales, respectively. Software infrastructure and
two-phase fluid mechanics models will be developed to address the coupling between the physics at these two scales.
Model predictions will be validated against experimental and clinical data from the literature.
A novel and critical component of the present work is that the interfaces between scales will be developed using:
1) dimension reducing coupling strategies, and 2) multidisciplinary data exchange software. The coupling technologies
to be developed between: 1) macro- and microscales, and 2) multimodality imaging and physical modeling, will yield
a system-level model that accommodates the critical two-way coupling between convective respiration physics and
uptake, deposition and disease-state morphology. Such a model will elucidate heretofore inaccessible physical understanding,
dependencies and treatment implications.
Friday, March 31, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
No Seminar Today
Friday, April 7, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Hanako Yamanaka
Final Defense
"Investigation of Thrombosis at the Biomaterial Surface in Left Ventricular Assist Systems"
Abstract
Cardiovascular disease is the leading cause of death in the United States. With heart transplants in short supply,
the use of ventricular assist devices (VADs) is up to almost 20% in patients awaiting heart transplants. Although
the use of VADs has increased, thrombosis remains a major problem, occurring in up to 35% of VAD patients. A thrombus
may obstruct blood flow, alter fluid dynamics causing damage to blood components, or wash off the surface as emboli
and occlude vessels.
Surface thrombosis in a left ventricular assist system (LVAS) and the individual and collective effects of biomaterial
properties and anticoagulation on thrombosis at the biomaterial surface, with time in vivo and in vitro were addressed.
LVAS were implanted in a bovine model for 3 and 30 days, n = 3, 4 and 4, 5, with and without anticoagulation, respectively.
Surface thrombosis was assessed on the polyurethane blood sacs in the LVAS pumps by macroscale examination and
multiple microscopy techniques. Platelet adhesion to polymers of different chemistry and activation of bulk platelet
suspension were assessed in vitro by immunofluorescence techniques over a range of low shear stresses relevant
to pediatric pumps.
Surface thrombosis at the macroscale was lower in the 30-day study compared to the 3-day study. Anticoagulation
had no effect on surface coverage by macroscopic thrombi. Differences in surface topography of blood sacs with
implantation time were observed by SEM and confocal microscopy. Although anticoagulation appeared to reduce adhesion
of platelet-like structures in the 30-day study, anticoagulation seemed to be ineffective in reducing biologic
deposition in the 3-day study. Region-dependent surface topography correlating with high and low shear stress regions
was observed by SEM.
In vitro studies of platelet adhesion were performed on candidate polymers for a pediatric VAD, Biospan® MS/0.4
(n = 3) and Biospan-P® (n = 4), for shear stresses from 0 to 10 dynes/cm2. Low platelet adhesion
was observed on both polymers at all shear stresses, except in regions with possible disturbed flow from the experimental
setup. No significant difference in platelet adhesion between Biospan MS/0.4 and Biospan-P was observed at all
shear stresses except at 5.5 and 8.9 dynes/cm2.
Friday, April 14, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Student Presentations:
"Gray Matter Thinning Demonstrated in ALS Using Novel Thickness Maps"
by: Don Bigler
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating disease that preferentially attacks motor functions. Currently,
there is no non-invasive method to identify and evaluate pathological changes in the brain in ALS. Our resent study
on nine ALS subjects revealed a conspicuous loss of T1 contrast in the focal area within the primary motor cortex
(PMC), in addition to atrophy. These findings suggest a potential utility of using gray matter (GM) thickness as
a quantitative and sensitive method to assist diagnosis of ALS.
Method
Nine ALS subjects and eight age/sex-matched controls received a whole brain T1-weighted 3D MDEFT scan on a Philips
Intera 3.0 T system with isotropic 1mm voxel size. Mean symptom duration for ALS subjects was 42 months. Five subjects
had mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement and the remaining four subjects showed
LMN signs only. Images were smoothed and segmented into GM, white matter, and cerebrospinal fluid. GM thickness
was calculated from the segmented GM images using a novel method based on the Euclidian distance filter. To highlight
brain areas with significant thinning, the GM thickness maps were displayed such that 1mm areas were marked in
red, 2mm areas marked in yellow, and everything greater than 2mm was marked as blue.
Results
All ALS patients with primarily LMN signs showed extensive thinning of the PMC. Two of the five patients with mixed
symptoms also showed thinning. Figure 1 shows a comparison of an age/sex-matched control and ALS thickness maps
in three orthogonal plans cutting through the PMC. The pathological change associated with the disease is detected
and clearly presented in the thickness maps. These preliminary results suggest that thinning in the PMC may be
useful for diagnosis of ALS and its progression.
===================================================================================
"The Role of Biomaterial Surfaces in Activation and Propagation of the Blood Coagulation
Cascade"
by: Kaushik Chatterjee
Abstract
Despite the widespread use of blood-contacting medical devices, there is little understanding of the surface-mediated molecular events that occur when a biomaterial interacts with blood plasma, an important consideration towards engineering hemocompatible materials. In this study, three model surfaces with different water-wettability were prepared by silanization of 0.5 mm diameter glass beads. Surface area titration plots in platelet poor plasma (PPP) generated using an in vitro coagulation assay supported previous observations of the scaling of coagulation efficiency with water-wettability. FXIIa was immobilized onto these surfaces and the procoagulant efficiency was assayed in vitro by titrating in FXII-deficient-PPP (dPPP). Quantitative parameters from fit of the data to a previously established mathematical model indicate that the procoagulant activities of FXIIa in all forms- soluble or immobilized on any surface- are similar. In contrast to previous theories of blood coagulation, it appears that repeated adsorption-desorption of the enzyme is not essential for coagulation suggesting and the surface is necessary for activation to the enzymatic form but is not a requirement for subsequent propagation of the cascade.
===================================================================================
"Shear-Induced Changes in the Nano-Scale Dynamics of the Endothelial Cell Cytoplasm"
by: Jhanvi Dangaria
Abstract
Hemodynamic forces induce changes in vascular endothelium which are important determinants of vascular health
and disease. While long term (hours) shear-induced morphological changes have been described previously, rapid
shear-induced changes (sec-min) in the dynamics of the endothelial cell cytoplasm remain unexplored. Furthermore,
dissecting out passive versus active responses of cells to applied forces has been limited by the spatial and temporal
resolution of force activation and biological readouts. In this study, Single particle tracking with nanometer-scale
precision using image correlation methods and machine vision algorithms were used to track the rapid dynamics of
endogenous particles in endothelial cells before the onset of a step change in fluid shear stress, during steady
shear of 10 dynes/cm2, and after the removal of shear stress. Results show that shear stress induces
nm-scale deformation in the cell cytoplasm after flow onset may be a direct result of decrease in cell stiffness.
Thus, shear-induced changes in the nano-scale dynamics of cytoplasmic constituents is a novel assay for both passive
deformation and mechanoactivation of endothelial cells. ===================================================================================
"Flow Field Measurements in the Penn State 50 cc Left Ventricular Assist Device Using Particle
Image Velocimetry (PIV)"
by James Kreider
Abstract
Bleeding, hemolysis, thrombus formation, infection and device durability have been common problems affecting blood pumps since their introduction. As hemolysis and thrombus formation in a device are closely tied to its fluid mechanics, in vitro investigations into these flow characteristics have accompanied clinical work. Particle image velocimetry (PIV) is a viable tool for this task. The ability of PIV to rapidly acquire global planar flow field data has been primarily responsible for the incorporation of this in vitro work into the device design process. The Penn State 50 cc left ventricular assist device is a pulsatile blood pump designed to serve smaller patients for whom successful larger pumps are not suitable. Two pump designs were tested. The cylindrical chamber of device v0 has a flat front face. The front face of device v1 is modified into a dome shape, and the inlet and outlet ports are flared outward in this version. Previous studies have shown the diastolic inflow jet to be a strong determinate of the overall flow patterns in these devices. Here the Bjork-Shiley Monostrut mitral valve through which this jet is formed is rotated in order to alter the properties of the jet. Device v0 shows strong sensitivity to valve orientation, with the 45° orientation exhibiting superior flow characteristics over the other angles tested. The study is repeated in device v1 with less sensitivity noted, as general flow characteristics in the device are inferior to those observed in device v0. Device v1 is also tested with Newtonian and non-Newtonian blood analog fluids. The shear thinning characteristics of the non-Newtonian analog are a close match to those of 40% hematocrit blood, yielding more clinically relevant results. The inlet jet is slightly more coherent in the non-Newtonian analog, probably contributing to the small improvement in the rotational pattern which is observed. The differences between the two analog fluids are consistent with those seen in other devices.
Friday, April 21, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Student Presentations:
"The Viscoelasticity of Pediatric Blood and Its Implications for the Testing of a Pulsatile
Pediatric Blood Pump"
by: Jennifer Long
Abstract
Red blood cell hematocrit, aggregation and deformability as well as plasma protein concentration influence the
viscosity and elasticity of whole blood. These parameters affect the flow properties, especially at low shear rates
(< 50 s-1). In particular, we have previously shown that the viscoelasticity of fluid affects the
inlet filling characteristics and regions of flow separation in small pulsatile blood pumps. Although the viscosity
of pediatric blood has been thoroughly studied, its elasticity has not been previously measured. Here we present
the viscosity and elasticity of pediatric blood against shear rate for hematocrits from 19-56, measured using an
oscillatory rheometer. There is little effect of patient age on blood viscoelasticity. A statistical analysis shows
that, when compared at constant hematocrit, adult and pediatric blood have quite similar viscoelastic properties.
We present blood analog solutions, as a function of hematocrit, constructed on the basis of the pediatric measurements.
Flow field results for viscoelastic analogs of 20, 40 and 60% hematocrit and a Newtonian analog will be compared
in the initial, in vitro testing of the Penn State pediatric blood pump, to determine the importance of incorporating
a viscoelastic analog into the design interaction.
===================================================================================
"Collagenase-aided Insertion of Cortical Microelectrode Arrays: Evaluation of Insertion
Force and Chronic Recording Performance"
by: Kunal Paralikar
Abstract
One possible mechanism for deterioration in recordings from chronically implanted microelectrode arrays is related
to the mechanical impedance mismatch that may allow for micromotion at the electrode/tissue interface. While hybrid
polymer-metal electrode arrays have optimal mechanical characteristics once implanted, they often can not withstand
the insertion forces required to successfully penetrate the pia-mater especially when multiple shanks are employed.
The primary goal of this study was to quantify the insertion forces experienced during multi-shank electrode insertions
through the pia into the cortex. Effect of collagenase application was explored using a custom designed force sensing
and acquisition system.
Our results indicate as much as a 30% reduction in peak insertion force and dimpling due to collagenase application.
We have also carried out chronic recording experiments to compare the electrode performance in sites implanted
with and without the collagenase treatment. Preliminary results indicate comparable recording characteristics that
strengthen a case for the inclusion of collagenase application as part of the standard implant protocol.
===================================================================================
"Regulation of Interleukin-8 Expression in Melanoma-Stimulated Neutrophil Inflammatory Response"
by: Hsin-Hsin Peng
Abstract
Inflammation facilitates tumor progression including metastasis. Interleukin-8 (IL-8) is a chemokine that regulates polymorphonuclear neutrophil (PMN) mobilization and activity and we hypothesize this cytokine influences tumor behavior. We have demonstrated that IL-8 is crucial for PMN-mediated melanoma extravasation under flow conditions. In addition, IL-8 is up-regulated in PMNs upon co-culturing with melanoma cells. Melanoma cells induce IkB degradation indicating that NF-kB signaling is active in PMNs. Furthermore, the production of IL-8 in PMNs is NF-kB dependent. We have further identified that IL-6 and IL-1b from PMN-melanoma co-cultures synergistically contribute to IL-8 synthesis in PMNs. Taken together, these findings show that melanoma cells induce PMNs to secrete IL-8 through activation of NF-kB and suggest a model in which this interaction promotes a microenvironment that is favorable for metastasis.
Friday, April 28, 12:00 - 1:10 p.m., Room 210 Hallowell, CG624E Hershey
Student Presentations:
"An Intravital Microscopic Study on Glycocalyx Dynamics"
by: Lujia Gao
Abstract
The techniques of indicator-dilution were applied to study the hydraulic conductivity of the endothelial surface
layer. Using a variant of the Stewart-Hamilton method, the hydraulic conductivity in the polysaccharide layer (glycocalyx)
on the endothelium was obtained by calculation of a virtual transit time (VTT) from a bolus of fluorescent dye
injected upstream. Simulation of the transit of a bolus of solutes in the axial direction using CFD techniques
established a theoretical basis for the observations. Experimental measurements of the transit of a bolus of small
fluorescent molecules (FITC) permitted comparison with the theory to elucidate the permeability of the glycocalyx.
The surprisingly sensitive transient dye bolus provide temporal resolution down to 10-msec level, which enabled
quantitation of changes of the glycocalyx structure in response to 10-7 M formal-Met-Leu-Phe (fMLP),
which simulates the effect of peptides normally liberated during the inflammatory process.
====================================================================================
"Analysis of Cortical Responses to Cochlear Stimulation in a Rat Model"
by: Lavanya Krishnan
Abstract
The cochlear implant is one of the most successful commercial neural prosthesis today. It directly activates
the auditory nerve fibers using electrical current, bypassing the damaged hair cells. While the devices provide
good functional recovery, there is a significant difference between the response of the auditory system to this
electrical stimulation and to the acoustic stimulation that a normal ear encounters. These differences likely contribute
to deficits in temporal processing and the narrowing of dynamic range. A current thrust of research, focuses on
improving the nature of the electrical stimuli to the auditory nerve to ensure a more spontaneous and close to
normal response of the auditory system. Many of these techniques have been based on the phenomenon of stochastic
resonance which has played a major role in achieving a 'pseudo spontaneous' response very similar to that of a
healthy ear.
The seminar will deal with these issues and also discuss preliminary studies that were conducted toward developing
an animal model to evaluate the effectiveness of various stimulation techniques in enhancing dynamic range and
temporal processing. These studies have utilized microelectrode array recording technology to monitor responses
of neurons in primary auditory cortex of rats stimulated with cochlear implants. This should enable a new look
at central processing of alternative stimulation strategies aimed at creating more natural responses, and at ultimately
improving the performance of cochlear implants. ====================================================================================
"Monitoring Mechanotransduction in Cells Using Multimodal Microscopy and Single Molecule
Spectroscopy"
by: Tristan Tabouillot
Abstract
Endothelial cells (ECs) are known to convert mechanical stimuli into chemical signaling pathways which regulate their functions and properties. It is hypothesized that perturbation of cellular structures and molecular-scale signaling are each accompanied by changes in molecular dynamics. We constructed an integrated multimodal microscope with the ability to obtain nanometer scale spatially resolved information of the dynamics of single fluorescent probe molecules with simultaneous force application. Special imaging techniques such as total internal reflection microscopy (TIRFM), epi-fluorescence microscopy, and differential interference contrast (DIC) microscopy are used in conjunction with single molecule spectroscopy techniques such as fluorescence correlation spectroscopy (FCS) and time resolved fluorescence to obtain dynamic information in different parts of a single cell. Some of the structures hypothesized to be involved in the phenomenon of mechanotransduction include the glycocalyx, plasma membrane, actin cytoskeleton and focal adhesions among others. Using our setup, it is possible to study molecular scale events occurring within these structures in three dimensions in response to the imposed forces such as micropipette aspiration, optical bead trapping and fluid shear flow in a controlled, quantitative manner. We describe the construction of our multi-modal microscope in detail and demonstrate calibrations for various potential readouts of the system.
====================================================================================
"Investigation of the Flow in the Penn State Pediatric Ventricular Assist Device Using Newtonian
and Non-Newtonian Blood Analogs"
by: Brandon Wivholm
Abstract
Previous in vitro studies suggest that areas of flow stasis, attributed to poor rotational flow development, contribute to thrombus formation observed in vivo in the first 50cc Penn State left ventricular assist device (LVAD) and the early 15cc pediatric LVAD. Although a Newtonian blood analog is often used to carry out in vitro studies, we believe we can more accurately predict the potential for thrombus formation by using a Non-Newtonian blood analog. Particle image velocimetry was performed to capture flow in the devices. With the new 12cc pediatric device, the inlet jets are observed further from the wall when using a Non-Newtonian fluid. The valves have a more marked effect on the flow in the device. Separation occurs upstream of the aortic valve during systole, the degree being a function of viscoelasticity. Based on these results, the Non-Newtonian blood analog, which is a better representation of blood, will remain an essential part of our device testing.
Tuesday, May 2, 10:00 - 11:00 a.m., Room 210 Hallowell, CG623 Hershey
Rui Zhou
Final Defense
"Contact Activation of Human Plasma Coagulation"
Abstract
Development of fully hemocompatible materials remains a substantially unrealized objective of applied biomaterials.
Unfavorable cell-and-protein interactions with biomaterial surfaces leading to thrombus formation are major obstacles
that modern surface engineering seeks to overcome. Future advances in the surface-engineering of blood contacting
biomaterials are critically dependent on a detailed understanding of how blood "processes" in presence
of an artificial material at a molecular level. Toward this understanding, our research aims at establishing structure-property
relationships that links material characteristics with the propensity to activate blood coagulation.
In our previous study, we proposed that the propensity of scales exponentially with surface energy, which is in
general agree with anticipated biochemistry that anionic surface is required for contact activation and hydrophobic
surfaces have very low catalytic potential.
However when we focused on the contact activation complex , we discovered that surface activation of Factor XII,
the principal protein reaction initiating plasma clotting, occurs with equal efficiency at hydrophilic and hydrophobic
surfaces. This observation stands in contrast with anticipated biochemistry mentioned above. Further investigation
reveals that activation rate is substantially attenuated at hydrophobic surfaces in the presence of plasma proteins.
This in part explains the discrepancy between two experiment observations and leads to our central hypothesis that
autoactivation of blood factor FXII in protein mixtures and plasma is moderated by competitive-protein adsorption
occurring at surfaces.
The outcome of this work would lay ground-work for further studying of FXII autoactivation mechanism which may
lead to a new paradigm for the interpretation of hemocompatibility and guide the development of advanced hemocompatible
biomaterials.
For additional information, contact Ms. Doretta Garvey, Dept of Bioengineering,
Tel: 814.865.1407 or E-Mail: bioe@engr.Professor, Biomedical Engineering
psu.edu