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    REU Projects for Summer 2011

    These 24 areas for research projects are proposed for 2011 REU Fellows. Descriptions of these project

    areas follow below. The 2011 Application and Project Descriptions are also available by email from theprogram director, Martha Absher, at [email protected]. Please note that these descriptions are generaland describe the research area in which you will be placed, not necessarily the specific project. For thoseproject areas which have been offered previously, brief descriptions of some former Fellows' projects arepresented. The 2011 REU Application and 2011 REU Project Descriptions are available online at:http://www.pratt.duke.edu/about/outreach.php

    Project # 1: Vaccine Engineering Formation of Chemokine Gradients in 3D EnvironmentsAdvisor: Dr. William Reichert, Professor, Biomedical Engineering and Dr. Steve Wallace,Assistant Research Professor, and Brittany Davis

    A key goal of vaccine engineering is to formulate vaccines that generate effective, high-affinity antibody.The currently available vaccine for anthrax calls for five intramuscular injections over 18 months toestablish effective protection. Our motivation is to improve the process of vaccine development, and inparticular, to identify strategies to improve the efficacy of the standard anthrax vaccine. To achieve ourgoal, a collaborative team compromising of labs at Duke University, Yale University, University of Michigan, and North Carolina State University has been assembled to carry out the many phases of thisresearch effort.

    The focus of this project is the many cellular interactions that occur in the germinal center. Germinal

    centers within lymph nodes and the spleen are the epicenter of the adaptive immune system. Within thegerminal centers, B cells migrate to different areas interacting with T cells and experience cellproliferation, mutation, and selection. This process can occur many times to produce a high-affinityantibody to the antigen, such as anthrax. Extracellular gradients of chemokines serve as the signals thatguide cell movement in vivo. However, direct visualization of chemokine gradients is still in its earlystages, largely due to the technical difficulties in detecting extracellular diffusible molecules.

    The purpose of Reichert Lab subproject is to form in vitro models to study the migration of T and Blymphocytes along well-characterized chemokine gradients within 2 and 3D environments. The goal of the REU fellow will be to help optimize and characterize chemokine gradients in a 3D environment.

    Project # 2: Vaccine Engineering: Lymphocyte Migration on Chemokine GradientsAdvisor: Dr. William Reichert, Professor, Biomedical Engineering and Dr. Steve Wallace,Assistant Research Professor

    A key goal of vaccine engineering is to formulate vaccines that generate effective, high-affinity antibody.

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    The currently available vaccine for anthrax calls for five intramuscular injections over 18 months toestablish effective protection. Our motivation is to improve the process of vaccine development, and inparticular, to identify strategies to improve the efficacy of the standard anthrax vaccine. To achieve ourgoal, a collaborative team compromising of labs at Duke University, Yale University, University of Michigan, and North Carolina State University has been assembled to carry out the many phases of thisresearch effort.

    The focus of this project is the many cellular interactions that occur in the germinal center. Germinalcenters within lymph nodes and the spleen are the epicenter of the adaptive immune system. Within thegerminal centers, B cells migrate to different areas interacting with T cells and experience cellproliferation, mutation, and selection. This process can occur many times to produce a high-affinityantibody to the antigen, such as anthrax. Extracellular gradients of chemokines serve as the signals thatguide cell movement in vivo. However, direct visualization of chemokine gradients is still in its earlystages, largely due to the technical difficulties in detecting extracellular diffusible molecules.

    The purpose of Reichert Lab subproject is to form in vitro models to study the migration of T and Blymphocytes along well-characterized chemokine gradients within 2 and 3D environments. The goal of the REU fellow will be to characterize the migration properties of T and B cells when exposed to variouschemokine gradients. At the end of the fellowship, the REU fellow will have gained experience in manyareas, such as surface chemistry, cell culture, and mathematical modeling.

    Project #3: Characterization of peripheral blood endothelial progenitor cells for use in

    prosthetic vascular graftsAdvisor: Dr. William Reichert, Professor, Biomedical Engineering and John Stroncek, andMichael Nichols, Biomedical Engineering Graduate Students

    Cardiovascular disease is the leading cause of death in the US. Blockage of the coronary arteries is themost deadly form of cardiovascular disease and is one of the main causes of sudden cardiac arrest. Onesurgical solution for blocked coronary arteries is coronary artery bypass surgery. These bypass grafts areisolated from a patient's mammary artery or saphenous vein. However, this surgery can only beperformed if autologous vessels are healthy. Not all coronary bypass surgery candidates have healthyvessels available, and thus there is scarcity of suitable small diameter vessels for patients.

    Synthetic grafts made out of ePTFE or Dacron have been looked to for a possible replacement of autologous vessels. However, currently synthetic grafts are limited to vessels with an internal diameterlarger than 6 mm due to the thrombogenicity of the material. Investigators have attempted to improve theperformance of these materials by coating the lumen with endothelial cells, and successful seeding of endothelial cells has been shown to improve the long-term patency of these grafts. Still, major technicalhurtles include finding a relevant autologous cell sources and improving the attachment of endothelialcells to prosthetic grafts.

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    This work focuses on isolating a type of high proliferation potential endothelial cells that are found in anindividual's circulating blood, called endothelial progenitor cells (EPCs). We are currently attempting todetermine whether EPCs represent a viable and easily isolated autologous cell source for the seeding ontosynthetic vascular grants. The strength of adhesion and the antithrombotic properties of the EPCs onsynthetic graft materials will be determined through in vitro assays. Gene therapy will be used to regulatethe expression of antithrombotic molecules. Seeded grafts will eventually be tested in animal models.This project involves cell culture, gene expression analysis, and phase/fluorescent microscopy.

    REU Fellow: Sean McNary, Bioengineering, University of the PacificIntegrin Density in Adherent Fibroblast Cells

    Sean McNary is a bioengineering major from the University of the Pacific. The location anddistribution of RGD-recognition integrins in confluent fibroblasts is important for developing celllayering studies and other investigations involving RGD-recognition integrins. To this end, fibroblastswere incubated with RGD-Streptavidin (SA), with the RGD site being recognized by the cell?s ?v?3and ?5?1 integrins. Through a high affinity ligand-receptor bond, SA was labeled with biotinylated

    Alexa Fluor 488 dye or biotinylated FluoSphere microspheres. Cells and the fluorescent markers wereimaged through confocal microscopy. Control experiments verified that both biotinylated fluorescentmarkers labeled only RGD-SA treated cells. Imaging revealed biotinylated Alexa Fluor 488 penetratedthe cell membrane and remained in the cytosol, preventing analysis of RGD-recognition integrins.Limited experimental evidence suggests biotinylated FluoSphere microspheres bind to selectedfibroblasts. More research is required to fully assess the viability of labeling RGD-recognition integrinswith FluoSphere microspheres.

    PROJECT #4: Three-dimensional drug distributions in solid tumors

    Advisors: Fan Yuan, Ph.D., Assistant Professor, Dept. of Biomedical Engineering

    Anticancer drugs will not be able to cure cancer, if they can not reach every tumor cells. However, it hasbeen shown that drug delivery in solid tumors is non-uniform. The drug concentration is high in someregions but nearly zero in other regions of tumors. This is one of the major problems in cancer treatmentsince local recurrence of tumors can be caused by the residue tumor cells left from the previous treatment.

    The non-uniform drug delivery in solid tumors can be caused by different mechanisms, including non-uniform blood supply, vascular permeability, and interstitial transport. The goal of our research is tounderstand the mechanisms and to improve the delivery of novel therapeutic and diagnostic agents in

    solid tumors. Our research is multidisciplinary, which involves quantification of drug distribution,transport parameters, and vascular morphology in solid tumors. The approach used in our researchinvolves development of animal and cell culture models, application of fluorescence microscopy, imageand data analysis, and mathematical modeling of transport processes in solid tumors. The followingproject will be available for undergraduate students.

    Description: 3D cell culture models will be used to study drug delivery. Students will learn how to

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    prepare the tumor models and quantify 3D distributions of fluorescent molecules in these models. Thedistribution results will be compared with computer simulations, using mathematical models developedfor studying transport of drugs in solid tumors. These mathematical models will integrate the informationof individual experiments, which is crucial for identification of important factors that hindle drug deliveryin solid tumors.

    A description of some REU Fellows projects with Dr. Yuan follows:

    Jason Hallo, Biology Major, Gallaudet UniversityChemotaxis VelocityMentors: Dr.Fan Yuan, Professor of Biomedical Engineering and Dilip Nagarkar, Pratt Fellow,Biomedical Engineering

    Jason Hallo is a biology major from Gallaudet University. Jasons project focuses onchemotaxis velocity of bacteria. Gene therapy might one day cure cancer in our cells.

    Unfortunately, gene therapy when placed into a virus is not able to host into a persons DNA. Analterative method of gene therapy is to use bacteria instead of viruses. Bacteria cant get in thehost but they are able to give proteins that hopefully will regulate cancer cells one day in thefuture. An understanding of bacteria E-colis mobility is required before we can do furtherexperiments on gene therapy. My project aimed to study and understand the mobility of bacteriaE-coli in the presence of four different concentrations of dextrose. Charts of results are madebased on the experimental measurement of the rings of growth of the bacteria on the petri dishes.Our finding was that bacteria move more when there is a lower concentration of dextrose present.These findings will be used in further experiments in the laboratory on the development of genetherapies using bacteria.

    REU Fellow: Kelley Bohm, Bioengineering Major, Pennsylvania State UniversityProtocol for Microfluidics Tumor Formation

    Kelley Bohm is a bioengineering major from Pennsylvania State University. Her projectfocuses on Microfluidics, which offers a novel way to observe interactions between therapeuticbacteria and cancer cells. Culturing the cancerous tumors in microscopic conditions allows forprecise manipulation of the cells and the bacteria that will be introduced. Creating these tumors,before the bacteria are even introduced, is a complex process that needed to be worked out inorder to move on to more complex topics. Cells need to aggregate effectively within themicrofluidic chamber and this involves proper flow rates, cell concentrations, and possibly a

    substance to help aggregation. One potential aggregate that was considered was poly-L-lysine.This was first imaged with cells to choose the concentration that yielded the desirable amount of aggregation and then the viability of this mixture was tested using trypan blue stain. The idealamount 20% poly-L-lysine was determined to be too deadly to the cells and will not be used.Collagen will be considered in the future. Many trials were needed to determine the ideal flowrates and cell concentrations. The specific numbers are detailed later in this paper. This data wascompiled and a protocol was made for Dr. Yuans lab and others to use for microfluidic tumor

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    culturing.

    REU Fellow: Danielle F. Garcia, Chemical Engineering, University of New MexicoDeveloping a Multicellular Layer Model for Drug Diffusion in Tumors

    Danielle is a chemical engineering major from the University of New Mexico. Her projectinvolved drug diffusion in tumors. An in-vitro model for drug diffusion through solid tumors has beendeveloped. The development process is comprised of growing a three-dimensional cell culture on acollagen coated Teflon membrane suspended in stirred media for up to 12 days. HT-29 human coloncarcinoma cells and B-16 murine melanoma cells were used to demonstrate the procedure in developingthese multicellular layers (MCLs). HT-29 cells have been shown to produce an MCL thickness of 160mm after 12 days in suspension. A comprehensive investigation was carried out of variablesaffecting growth of B-16 MCLs to achieve maximum reproducibility and comparability to HT-29 MCLs.We aim to generate a sufficient amount of MCLs, and refine the development process to visualizecommon properties of tumors such as necrosis and hypoxia, which affect diffusion properties. TheseMCLs can then be used in further studies of drug transport to aid in cancer treatment research.

    REU Fellow: Rebekah Lee Smith, Biology Major, Gallaudet UniversityProject: Quantification of Electrical Impedance of Tumor Tissues

    Rebekah's project was in biomedical engineering and its application in cancer research. The goal of herproject was to develop a method to determine changes in the volume fraction of cells in tumor tissuesbased on electric impedance measurement. This method can be used directly in the clinic to monitor the

    efficacy of any anticancer treatment. In her experiment, different electrodes were used to measure theimpedance as a function of electric field frequency in tumor tissues. The impedence was then convertedto the resistance, capacitance, and inductance of tumor tissues based on the Cole model. The tissue usedin this experiment was a rat tumor, called rat fibrosarcoma. The volume change of tumor cells wasinduced by a mannitol solution that would in theory shrink tumor cells due to the osmotic effect. The cellshrinkage was detected through electric impedance measurement and data analysis based on the Colemodel. After several sets of experiments on fibrosarcoma, Rebekah did find that the mannitol solutionmade the cells shrink, and the final impedance graph did fit into the Cole model. Rebekah completed theformulas for resistance indicating how the tumor reacted and shrank in the mannitol solution. Therefore,her hypothesis that fibrosarcoma cells would shrink in the mannitol solution was proved true.

    REU Fellow: Daniel LundbergProject: Viscous Polymer Solutions for Sustained Drug Delivery

    Daniel Lundberg is a senior biology major at Gallaudet University. He performed his researchunder Dr. Fan Yuan, Assistant Professor, and Yong Wang, graduate student in the Department of Biomedical Engineering. Daniels research focused on a novel method to treat cancers and tumors via

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    targeted drug delivery systems. As traditional methods and local drug delivery lead to the disseminationof the drug into the systemic circulation, the side effect impact of a cancer treatment increases.Temperature-sensitive polymers offer a possible method in containing the drugs within the tumor,reducing the side effects. In order for a substance to be a successful polymer for this treatment, it has tohave a low viscosity at room temperature yet a high viscosity at body temperature. Polymer solutions,such as alginate, calcium ion/alginate, Poloxamer, PNIPAAM, and methyl cellulose polymer solutionswere tested as potential agents which can reduce drug clearance into the systemic circulation and improvedrug retention in tumors, reducing the side effect of the anti-tumor drugs. From the data, it was clear thatthe alginate and methyl cellulose polymers did not attain the goal, since they were more viscous at roomtemperature than body temperature. Certain concentrations of PNIPAAM and Poloxamer polymersolutions turned out to be promising polymers. Their viscosity had dramatic increases from roomtemperature to body temperature, achieving the goal. The ionic environment variable proved to beeffective in increasing a polymers viscosity at a certain concentration. The next step of this experimentwould be to focus on the addition of the calcium ions to the successful polymers to observe the results.Also, the promising polymers need to be tested in mice with the aid of fluorescent drug markers to

    observe the progression of the polymer/drug markers. Daniel learned challenging new laboratorytechniques in this project.

    Project #5: Tissue-engineered model of muscle diseaseAdvisors: Nenad Bursac, Associate Professor, Biomedical Engineering and Mark Juhas, BiomedicalEngineering Graduate Student

    Duchenne Muscular Dystrophy (DMD) is a debilitating disease that occurs due to lack of the proteindystrophin. The disease effects 1 in every 3500 males and in most cases results in patients beingwheelchair-bound by age 12 and dying before age 30 due to respiratory or heart failure. In this project wewill apply genetic and tissue engineering methodologies to generate novel tissue model of DMD muscleand by altering expression of membrane-matrix binding proteins (integrins) attempt to decrease celldeath, improve force generation capacity, and restore normal myofiber architecture of the DMD muscle.A variety of tissue engineering techniques, gene and protein expression analyses, and physiological testswill be utilized to accomplish goals of this project.

    REU Fellow: Alice Welsh, Biomedical Engineering Major, Senior, North Carolina StateUniversityQuantifying Gap Junctional Coupling between Cardiomyocytes and Other Cell Types

    Mentors: Dr. Nenad Bursac, Assistant Professor, and Luke McSpadden, GraduateStudent, Biomedical Engineering

    Alice Welsh is a senior biomedical engineering major at North Carolina StateUniversity. The purpose of her project was to determine gap junctional couplingbetween cardiomyocytes and other cells types. Cardiac cells are connected to eachother by channels called gap junctions; these channels allow ions and small moleculesto pass between adjacent cells. The presence of these junctions allows for electricalsignals within the heart to propagate from cell to cell, causing the contraction of the

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    heart which pumps blood throughout the body. The formation of gap junctionsbetween other cell types and cardiomyocytes results in slowed conduction of theaction potentials of the heart, leading to unpredictable signal propagation. It washypothesized that gap junctions would only form between cardiomyocytes and othercells that contain connexins, which are important gap junctional proteins. In order toquantify the gap junctional coupling between cardiomyocytes and other loading cells,a technique involving dye transfer followed by fluorescent-activated cell sorting(FACS) analysis was implemented. Donor cells were stained with two dyes: one smallenough to move through gap junctions, calcein AM, and one that was too large, DiI.

    The percentage of cells which uptake the calcein but not DiI can be used as ameasure of gap junctional coupling between the cell types. The appropriate dyeconcentration and absorption times were determined, as was the most effectivestaining procedure and donor to recipient ratio. The initial results were good but thetheory that yielded promising results with human embryonic kidney (HEK) cells didnot hold up for cardiomyocyte donor cells. This study helped clarify what processwould not work for cardiomyocytes, and gives some direction for procedures andapproaches in future studies. procedures. This project let Alice know for sure that shewishes to continue research in biomedical engineering and she is currently applyingto graduate programs, including Duke.

    REU Fellow: Kassandra Thomson, Biomedical Engineering, University of Texasat Austin

    The Visualization and Quantification of CollagenDeposition by Cardiac Cell Cultures

    Kassandra Thomson is a biomedical engineering major from the University of Texas at Austen. Cardiac fibrosis is a major component of heart disease, and canlead to heart failure as the cardiac muscle stiffens. It is important to build models of diseased heart tissue in order to study the effects of fibrosis on the electricalproperties of cardiac cells. The aim of this study was to develop a method to visualizeand quantify collagen deposition by 2D cardiac cell cultures in vitro to determine if collagen was being deposited between cardiomyocytes, thus interrupting electricalpropagation. Collagen deposition was also compared between samples of differentage, with different concentrations of ascorbic acid, and isotropic versus anisotropic.Immunostaining was the primary method of visualization used. A new method wasdeveloped to stain extracellular collagen separately from intracellular collagen. Ahydroxyproline assay was tried in order to quantify the amount of collagen present incell cultures. Extracellular collagen staining was achieved in cardiac fibroblastcultures, but not with cardiomyocytes. For fibroblasts, there is a visible increase inthe amount of collagen deposition with cultures of increasing age and with increasingamounts of ascorbic acid. Changes in collagen deposition with cellular patterninghave not yet been determined. The hydroxyproline assay is currently beingformatted to our cell cultures, and has not yet worked successfully.

    Project #6: Design and development of an LED-based optical spectrometer to detect

    intrinsic fluorescence signals from biological tissues.Advisors: Nimmi Ramanjam, Associate Professor, Biomedical Engineering, and Karthik

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    Vishwanath, Postdoctoral Fellow

    Background and Motivation: Optical spectroscopy has shown considerable promise in being ablenon-invasively detect pre-cancerous changes in various different tissues in humans. First-generationproptotypes of these optical spectrometers were bulky (~ 70x70x50 cm), used high power lamps and usedmechanical motion to collect optical signals from biological tissues. Recent engineering advances solid-state technologies now allows one to design optical instrumentation which are much smaller in size(~10x10x6 cm) are use light sources that can be powered using laptops.

    Project Description: We are looking for motivated students who will help design and construct anoptical spectrometer that can rapidly collecting fluorescence spectra from biological tissue. The studentwill then characterize and test the performance of this device and participate in preclinical studies whichwill use the developed instrument to collect optical fluorescence in ongoing studies. These projects willinvolve designing innovative solutions to improve upon the existing instrumentation, developing bettercomputational models/interfaces for faster and better extraction of tissue optical properties.Skills and Prerequisites: Pre-requisites include knowledge of basic chemistry, physics, and/or electronics.

    Familiarity with tissue optics and programming experience with C/C++/Matlab/LABVIEW are highly

    preferred.

    Project #7: Cardiac Ablation Imaging with ARFI UltrasoundAdvisor: Patrick Wolf, Associate Professor, Department of Biomedical Engineering

    The overall goal of the project is to develop a multimodality imaging system to guide cardiac ablationtherapy. The system will exploit catheter based acoustic radiation force impulse imaging to characterizelesion growth during ablation. This technology will be integrated into the standard clinical catheterguidance paradigm yielding a complete tool for ablative therapy of cardiac tachyarrhythmias. A studentworking on this project would be performing ablation experiments in vitro and assisting with in vivoexperiments and imaging the outcome with ultrasound.

    A description of a former REU Fellows project follows:

    Clarissa Shephard, Biomedical Engineering Major, North Carolina State UniversitySubdermal EEG Recorder for Lifelong MonitoringMentors: Dr. Patrick Wolf, Associate Professor, Department of Biomedical Engineeringand Thomas Jochum, Biomedical Engineering Graduate Student and Zachary Abzug,Pratt Fellow in Biomedical Engineering

    Clarissa Shephard is a biomedical engineering major from North Carolina StateUniversity. Her research focused on the Subdermal EEG Recorder for LifelongMonitoring, which will provide a low cost alternative to currently available EEG

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    monitoring devices. The Recorder will be a thin cylindrical device implanted along thetop of the skull, below the scalp. Because the device is fully implanted, charging of thedevice and data transmission will occur transcutaneously. To test the transcutaneouscapabilities of the device, a saline phantom model of the human head was created using

    acrylic, saline, and copper wires to mimic the electrical properties of the human head.This model was built using the HEALPix (Hierarchical Equal Area isoLatitudePixelation) model as a conformal mapping model for the scalp and skull. The scalp andbrain were represented by saline layers and the skull was represented by a perforatedacrylic sheet. These materials gave the desired electrical properties and resistivity ratios.The copper wires were used to electrically connect the physical discontinuities present inthe HEALPix model. The completed model was tested and the results were compared to acomputer simulation to determine the relative error. Initial findings show that the modelhas limited error when compared to the computer simulation, but future work must bedone to determine if this is an accurate representation of an anatomical human head.

    Renee Miller, Biomedical Engineering Major, Marquette UniversityIn Vitro Differentiation Between Multiple Cardiac Ablation Lesions using Acoustic RadiationForce Impulse (ARFI) Imaging

    Renee Miller is a biomedical engineering major from Marquette University. Her projectfocused on acoustic radiation force impulse (ARFI) imaging, which may be an effective methodof imaging cardiac ablation therapy in real-time. Many cardiac ablation treatments, used to treatarrhythmias, require doctors to make multiple lesions in a line or ring. Consequently, ARFIimaging must enable doctors to distinguish between separate lesions and show gaps betweenthem. In this study, a V shaped lesion was made in porcine and ovine myocardial tissue samplesand imaged using ARFI imaging. A digital picture of the image was also taken. The imageswere aligned using needles which were visible in the digital and bmode images. Then, athresholding algorithm was used to determine lesion from non-lesion in the ARFI image. Andfinally, at the point of separation, the distance between the actual lesions was calculated in orderto determine the relative resolution between lesions using ARFI imaging. The average distancebetween distinguishable lesions was 0.22 cm. With this information, doctors can potentiallyperform cardiac ablations with greater accuracy. In addition, a standardized method for creatingthe V shaped lesions was determined. Ablating endocardial tissue at 30 W for 60 sec proved tobe most effective in creating a defined V shaped lesion visible on both the surface and ARFIimages.

    Emily Dingmore, Biomedical Engineering Major, North Carolina State UniversityPreliminary Investigation of the Feasibility of a Graphite Radio-frequencyAblation Catheter

    Emily Dingmore is a senior biomedical engineering major from North Carolina State University.Developments in Acoustic Radiation Force Impulse (ARFI) imaging have provided useful imaging of

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    lesions during cardiac Radio-frequency ablation procedures. By measuring stiffness in soft tissue, ARFIimaging can determine the effectiveness of procedures to treat cardiac arrhythmias. This imagingtechnique, however, cannot take place while a metal catheter is in the imaging window due to noisecreated on the ARFI image. Alternate catheters were tested by placing various carbon materials onporcine heart tissue and producing ARFI images at incremental distances. It was predicted that by usinga graphite coated radio-frequency ablation catheter instead of a metal tip catheter there would be areduction of noise present in the Acoustic Radiation Force Impulse image. This reduction of noisewould allow for improved imaging of lesions created during clinical cardiac ablation procedures. Byusing MATLAB computer code to analyze the average amount of noise produced by each material it wasdetermined that the graphite samples produced less noise on the ARFI image than that produced by themetal catheter. The region of tissue affected is also smaller for the graphite materials. It is also possiblethat the transducer used for capturing the ARFI images can be closer to the catheter placement site forthe graphite materials than it can be while imaging the metal catheter. Further testing may provide moreinsight into the benefits of using various materials for the ablation catheter.

    Project #8: Implanted Biopotential RecorderAdvisor: Patrick Wolf, Ph.D., Associate Professor, Department of Biomedical Engineering andThomas Jochum, Biomedical Engineering Graduate Student

    A student involved in the Implanted Biopotential Recorder project will partake in thedevelopment of an implanted medical device to measure, store, and telemeter biopotentials suchas electroencephalograms. The long range goal of the research is a novel medical systemcomprised of a miniature electronic device implanted beneath the skin that measures and storesbiopotentials and a desktop device that extracts the data stored in the implanted device. An

    important piece of this project is discovering how the devices electrically and thermally interactwith the body. The student will design, construct, and apply measurement systems that quantifythe electrical or thermal performance of prototypes or emulations of the Implanted BiopotentialRecorder. The ideal student should have an interest in electronics and computer-controlledmeasurement systems. Experience with or prior course work in these areas is a real plus.

    A description of some former REU Projects follow:

    Erin Lewis, Mechanical Engineering Major, Junior, University of Kansas

    Encapsulation Methods for a Neural Data Acquisition System

    Erin Lewis is a junior mechanical engineering major at the University of Kansas. Her projectfocused around neural data acquisition, which translates neural signals into digital signals that can beinterpreted by a computer to perform specific motions such as moving a prosthetic arm. Currenttechnology is progressing toward a three-component system that can be considered for completeimplantation. However, the system must be encapsulated in appropriate materials that will protect the

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    human body and the electronic components, as well as meet the governments standards and Erinsproject was to research and begin testing on this encapsulation methodology. She created a handbook outlining each detail of the encapsulation procedure and outlining the methods and materials of twocomponents of the system: the Transcutaneous Energy Transmission System (TETS) coil and the InternalCentral Communications Module (ICCM). In the process learned about properties of several materials:compatibility, durability, flexibility, and water-vapor permeability, as well as FDA approval. Sheperformed many compatibility tests, learning which materials worked well together. Through herresearch and lab testing, encapsulation methods and materials for two of the components have beendocumented. The Transcutaneous Energy Transmission System (TETS) coil is encapsulated in SiliconeAdhesive and Silicone Dispersion to create a flexible, durable, and water-vapor preventative coating. TheInternal Central Communications Module (ICCM) is coated first with Parylene-C, a pin-hole freecovering, and then by a mold of Hysol Medical Grade Epoxy; the combination provides durability andwater vapor permeation protection. The procedure for the encapsulation of each component will help theneural data acquisition system be one step closer to the market.

    Patrick Conway, Computer Science Major, Gallaudet UniversityBrain-Machine Interface

    Patrick Conway is a computer science major from Gallaudet University. His project involved aportable neural interface developed by Dr. Iyad Obeid for his Ph.D. under the supervision of Dr. Patrick Wolf, which has been undergoing some revisions and needed a new software program to run it.Specifically, there are two data processing boards operating in tandem rather than a single one and the6533 Digital I/O data acquisition card from National Instruments is being used for the first time to collectthe data from the data processing boards. At this point, the program is also being transferred from acommand line interface to a graphical user interface. The software is capable of acquiring data from the

    FIFOs of the brain-machine interface, converting the data from the packed 8 bit word formats to theunpacked 16 bit word format, saving the data to a selected file, and graphing all channels simultaneously.The software uses parallel processing to improve speed and dynamic queues to allow the threads toproceed at their own pace. There are a few software and hardware bugs to work out yet, but nearlyeverything is fully functional at the time of this writing.

    Eric Turevon, Biology and Computer Science Major, Gallaudet UniversitySoftware for a Brain Machine Interface

    Eric Turevon is a biology and computer science major from Gallaudet University. His project

    focuses on the Brain Machine Interface, and his research was performed in collaboration with Patrick Conway, also an REU Fellow, with Dr. Patrick Wolf, Associate Professor of Biomedical Engineering, astheir mentor. Erics task was to learn to program software to accompany the Brain Machine Interface.The three components of a brain machine interface are are: a 16 channel headstage module, an analogfront end and mezzanine,a personal computer with a National Instruments NI-DAQ PXI-6533 PXIinterface onboard. The software programmed to interact with these components was written in aLabWindows/CVI environment. Eventually, the purpose of this brain machine interface will be to assist

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    severely disabled people to lead a more productive, independent life.

    Project #9: Fabrication of Nanopatterned Surface to Study Stem Cell DifferentiationAdvisors: Kam W. Leong, Professor, BME, and Lab Mentors: Dr. Karina Kulangara and Dr.

    Yong Yang

    Native extracellular matrix comprises many nanoscaled features in the form of nanofibers, nanopores,and nano-ridges. In creating an optimal microenvironment for the expansion and differentiation of embryonic and adult stem cells, it would be important to include these nanotopographical cues intoconsideration. We have evidence showing that bone-marrow derived stem cells differentiate into theneuronal and muscle lineages when cultured on nanogratings. A significant effort in our lab is tounderstand the mechanism of this phenomenon of nanotopography-mediated differentiation. Weenvision that the student will assist in the following aspects of the project:1) 1. Fabricate different nanopatterned samples of poly(dimethylsilosane) (PDMS) by cast molding;

    2) 2. Characterize the nanopatterned PDMS by SEM and AFM;3. Functionalize the PDMS surface with cell-specific ligands by soft stamping.

    A description of some former REU Fellows projects follows:

    Krystian Kozek, Materials Science and Engineering Major, North Carolina State UniversitysiRNA Delivery Into LNCaP Cells Using a Novel, Multivalent NanocomplexMentors: Dr. Kam Leong, James B. Duke Professor, Department of Biomedical Engineering andDr. Hanying Li, Postdoctoral Associate, Department of Biomedical Engineering

    Krystian Kozek is a materials science and engineering major from North Carolina State

    University. His research focues on short interfering ribonucleic acid (siRNA) delivery intoprostate cancer (LNCaP) cells, which was attempted using a novel and multivalent nanocomplex.The complex was a three-armed deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)hybrid structure, where the arms were connected through dithio-bismaleimidoethane (DTME) bydisulfide bonding. The disulfide bonding of the arms was not as efficient as desired; however,conjugation was successful, although with a low yield. A three-armed and fully formed complexhas not yet been completely successful proven; however, preliminary data points towardsassembly of the full nanocomplex. Application of this nanocomplex for the receptor-mediatedendocytosis into the LNCaP cells has been preliminarily successful, with the aptamer guidinguptake and the siRNA knocking down chosen genes; future research will aim to prove the

    efficiency and study the application in cancer research.

    Nevija Watson, Chemical Engineering Major, North Carolina A&T State UniversityFabrication of Nanopatterned Surfaces to Study Stem Cell DifferentiationNevija Watson is a junior chemical engineering major from North Carolina A & T StateUniversity. The hypothesis of her research project over the summer was that cells react tonanotopographic cues under static conditions and flow alters the cells behavior. We wanted to

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    engineer a synthetic surface with topographic cues in the nanoscale to mimic a stem cell niche.We want to use this synthetic niche to expand and differentiate human mesanchymal stem cellsfor cellular therapies. In my time here over the summer, we found that the topographic cues onthe synthetic patterned surface we created do affect the cells. Cells seeded on the patternedsurfaces grew and moved along the ridges of the pattern compared to cells seeded on a flatsurface which spread out along the surface in a normal fashion. We have found that flowincreases the elongation of the cells on the patterned surface and the cells become oriented in theflow direction on the flat surface. Our findings from the duration of my project are stillpreliminary; there is still extensive research to be done on the reaction of the cells to flow and thenanotopographic cues

    Project # 10: Neuronal circuits in the primate brain and their implications for roboticsAdvisor: Marc A. Sommer, Dept. of Biomedical Engineering and the Center for CognitiveNeuroscience

    The primate brain is a network of highly interconnected areas. Most of the areas havebeen studied at this point, and we know much about them. Little is known, however, about howthe areas talk to each other. Somehow their connections form highly synchronized, widespreadcircuits that mediate our perception, cognition, and movements. The overall goal of mylaboratory is to study the interaction of brain areas at the circuit level. Our primary method is torecord from single neurons in behaving rhesus monkeys. The animals perform tasks similar tovideo games that involve visual stimulation, decision-making, and eye movement responses. Westudy the signals carried by neurons between brain areas while the animals perform the tasks,analyze what the signals represent, and design computer models that help us to interpret ourfindings and apply them to technology. We are currently designing a model of the visual systemthat rotates a video camera in a way that approximates real eye movements. Input from thecamera guides a robotic arm, and the bioengineering challenge is to design the system so that thearm makes accurate visually-guided manipulations even as the video camera moves around -- justlike we are able to inspect and manipulate tools even as we move our eyes around. A goodundergraduate candidate for a position in our laboratory would have studied biology (including abasic understanding of neurons), would be comfortable with animal research, and should havefamiliarity with computer programming (e.g. Matlab or C), engineering, or both.

    PROJECT #11; Application of Endothelial Progenitor Cells for Vascular Repair

    Advisor: Dr. George Truskey, Professor and Chair, Biomedical Engineering

    Endothelial progenitor cells derived from adult and umbilical cord blood represent apromising source of cells for applications in tissue engineering, repair of blood vessels and

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    seeding of vascular grafts, stents and ventricular assist devices. Work in our lab is focused upondetermining the properties of these cells when cultured with smooth muscle cells under flowconditions, understanding ways to optimize the dynamic adhesion of the cells and furthering thedevelopment of tissue engineering applications.

    REU FELLOW: Kristen Hambridge, Biomedical Engineering Major, North Carolina StateUniversityResponse of Human Umbilical Vein Endothelial Cells in Co-culture With Aortic Smooth Muscle Cells

    In vitro cell culture systems are important for modeling diseases such asAtherosclerosis. Atherosclerosis is a disease of the intima, resulting in plaqueformation on the inner lining of the artery walls. Low Density Lipoprotein (LDL)accumulation within the vessel wall leads to an immunological response withinflammatory attributes. The increased permeability of the endothelial layer to LDLshas played a major role in Atherosclerosis. The study aims to research the role of human umbilical vein endothelial cells (HUVECs) in co-culture with aortic smoothmuscle cells (AoSMCs). Specifically, it aims to discover whether the inclusion of

    smooth muscle cells will improve the physiological nature of endothelial cells. Thiswas tested by performing albumin permeability tests on a HUVEC monolayer, AoSMCmonolayer, co-culture, and the membrane containing no cells. Cells were grown inmedia containing 3.3% and 10% Human Serum (HS). Permeability was tested ondays 2,3, 5, and 7 post seeding. Days 5 and 7 were found to be optimal days.Average albumin permeability for HUVECs was 1.35 +/- 0.47 for 10% HS at Day 5,0.75 +/- .04 for 3.3% HS at Day 5, 1.95 +/- 0 for 10% HS at Day 7, and 1.34 +/- 0 for3.3% HS at Day 7. Average albumin permeabilities for AoSMCs at Day 5 were 4.05+/- 0.69 and 1.72 +/-0.62 for 10% and 3.3% HS respectively while Day 7 were 4.95+/- 1.33 and 5.2 +/- 0.93 for 10% and 3.3% HS respectively. Lastly, the co-cultureaverage albumin permeabilities were found to be 1.97 +/- 0.35 and 0.83 +/- 0.4 atDay 5 for 10% and 3.3% HS respectively while values for Day 7 were .089 +/- 0.34and 1.77 +/- 0.66 for 10% and 3.3 % HS respectively. Overall, most permeabilityvalues at 3.3% HS were lower than at 10% HS. At day 7, the permeability of the co-culture was lower than the ECs at 10% but not for 3.3% HS. It can be concluded thatwith time, the ECs respond better in co-culture than alone when in 10% HS.

    REU Fellow: Viet Le, Chemistry Major, Gallaudet UniversityProject: Interactions between the Endothelial Cells and the Smooth Muscle Cells inCo-Culture: The Endothelial Cells Confluency in Co-CultureThe overall project in Dr. Truskeys laboratory, in which Viet worked, aims to construct a tissue-engineered blood vessel and a synthetic (polymer) vessel, so it can be put into a human body that has aclotted vessel. The tissue-engineered blood vessels are made from cells that grow into tissue on adegrading scaffold. Current tissue-engineered blood vessel form clots over relatively short periods of timebecause the endothelial cells tend to rip off synthetic vessel that clots easier. The endothelial cells need toadhere and function properly in the tissue-engineered blood vessel to prevent clotting. After the smoothmuscle cells have grown to a confluent layer on the slideflask, the endothelial cells were seeded andcultured for several day for growth. Antibody Labeling was used to specifically stain cell junctionproteins so that the visible cell junction protein appear under the fluorescent microscope. In Vietsresearch, attempts were made to stain three type of cell junction proteins: VE-Cadherin, -catenin, and

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    PECAM. VE-Cadherin and -catenin were specifically localized to the inter-endothelial cell junction andPECAM was specifically localized to the outer-endothelial cell junction. Two variables for staining thecell junction proteins which must be considered are (1) the concentration of antibody labeling solution tospecifically stain for cell protein and (2) the incubation time. The VE-Cadherin and -catenin antibodydid not stain the cell effectively in the endothelial cells monolayer, under all the varying concentrationsand incubation times. VE-cadherin and -catenin antibody did not show its visible borders where twocells had merged together under the fluorescent microscope. PECAM was considered as the next cell

    junction protein and the results show that PECAM successfully stained the cell borders alone withconcentration of 20 L to 50 L PECAM antibody solution in the endothelial cells monolayer. Dapi wasadded to the PECAM protocol that stains cell nuclei to indicate the visible stained nuclei within eachvisible PECAM border under the fluorescent microscope. The isotype was used as a control group thatshould not show any visible cell junctions protein with the same PECAM protocol. Viet hypothesized thatthe PECAM antibody will stain the endothelial cell borders on the smooth muscle cell. His results showedthe PECAM protein did not stain effectively the endothelial cells monolayer at low concentration. Forstaining the PECAM protein in future investigation, Viet concluded that an increasing concentration of

    PECAM antibody solution should stain the entire cells in co-culture, and the incubation time must varywith the antibody concentration.

    Project #12: Engineering Bacteria for Medical ApplicationsAdvisor: Lingchong You, Assistant Professor of Biomedical Engineering

    We are engineering bacteria for medical applications by constructing synthetic gene circuits. Theseprojects involve development of genetic sensors that can detect changes in the environment, andcontainment modules that limit un-intended bacterial proliferation. These projects will expose students toboth mathematical modeling and experimentation. The summer student will primarily participate indesign, construction, or characterization of synthetic gene circuits. Prior experience in mathematicalmodeling, cloning, or bacterial growth experiments is preferred.

    Project #13: Early Cancer Detection with BiophotonicsAdvisor: Adam Wax, Associate Professor, Biomedical Engineering

    My research is based on using non-invasive optical techniques to measure the features of biological cellsin a way that is not possible with traditional methods. We have developed a new technique capable of diagnosing cancer at the cellular level based on using scattered light and interferometry. Currently, we aredeveloping these techniques for application to detecting cancer in vivo. Research in my lab involvesdesigning and implementing electronic and optical systems, programming in Labview for instrumentcontrol, as well as computer modeling of light scattering using C++ and Fortran. This project can includehardware (optical and electrical systems) and/or software (Labview and/or C++) components

    A description of some REU Fellows projects follow:

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    Jenna Woodburn, Chemistry Major, Gallaudet UniversityPolarization effects on plasmonic coupling of gold nanosphere pairs

    Jenna Woodburn is a chemistry major from Gallaudet University. Her project hypothesis waswill parallel polarization direction show a strong redshift of the surface Plasmon peak? or willorthogonal polarization show a strong redshift of the surface Plasmon peak? She studied and workedwith gold nanoparticles by taking many images of gold nanoparticles in order to find and measureinterparticle distance. She learned to use a Scanning Electron Microscipe (SEM) as part of her training,and also learned many laboratory techniques which were new to her. While using the SEM (ScanningElectrons Microscope) for her project, she realized that she still could not find the measure of theinterparticle distance. She found that the difficulty was due to the very hard problem of keeping the goldcoating on the slides. Instead of the gold coating, she then used Indium tin oxide coating, which workedwell. The laboratory is still working on this project and this work will continue. Her mentor and otherworkers in biomedical engineering will continue to work towards results for this research.

    Matthew Meleski, Chemistry Major with Minors in Biology and History, Gallaudet UniversityLow Coherence Interferometry (LCI) for Microbicide Gel Measurements: Optical Signal to Noise Ratio(OSNR) and Resolution

    Matthew Meleski is a senior chemistry major and biology and history minor at GallaudetUniversity. Everyday, the cases of HIV and AIDS are rapidly increasing due to unprotected sexualactivities, especially in third world countries in Africa. In order to prevent the rising cases of HIV andAIDS, scientists around the world are developing many different preventative methods against HIV andAIDS. One method being developed to prevent the spreading of HIV/AIDDS is by using microbicidegels. These gels are topical products that act as a physical barrier and as a carrier of an active drug.

    Based on the Michelson Interferometer geometry, the 6-channel low coherence interferometry (LCI) willbe used, and the optical signal-to-noise ratio (OSNR) and axial resolution of each channel will bedetermined. LCI uses broadband light to perform depth ranging measurements of layers in a sample. If improvements are made to the LCI device, particularly in optical signal-to-noise ratio (OSNR) and axialresolution, then there will be increased accuracy of measurements using the device. In order to obtain theOSNR data of each channel, a Matlab routine program was developed to calculate the OSNR for an inputsignal. Also, a Matlab routine was made that plots the data as an a-scan graph and calculates theresolution of each channel. The resultant resolution values were then compared to the predictedresolution of 6.2 micronmeters. All of the actual resolutions are higher than the theoretical resolution(6.2), which means that all these channels are not optimized due to possible contamination (dirt and dust),

    or the channels are not aligned well. It is therefore concluded that more work and adjustments need to bedone on the 6-channel LCI device in order to reduce the actual resolution as close as possible to 6.2microns.

    Ryan Kobylarz, Chemistry Major, Junior, Gallaudet UniversityEarly Detection of Cancer with Biophotonics

    Ryan Kobylarz is a junior chemistry major from Gallaudet University. The objective of Dr.

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    Waxs research project was to develop a biomedical tissue imaging technique. In this research Ryanlearned about how optics can affect the properties of light and how interferometry is based on thephysical principle of light waves; two light waves in phase amplify while those in opposite phases cancelout. Ryan and the research team developed a non-invasive optical technique, Digital HologramMicroscopy, which utilizes both interferometry and microscopy. They used a modified Mach-Zehnderinterferometer type, adding acoustic-optical modulators to create a frequency offset. The frequency offsetthen caused a phase shift and allowed insight on the sample analyzed through the microscope. Theresulting images provided a three-dimension informative view of the sample. Images from stationaryobjects were obtained and analyzed, and the next step will be to complete the dynamic cell imagingtechnique.

    Michele Patterson, Biosystems Engineering Major, Clemson UniversityEarly Cancer Detection with Biophotonics

    Michele Patterson is a Biosystems Engineering Major from Clemson University. Her project

    focused on low coherence interferometry, which allows information to be gathered concerning nuclear sizeand depth resolution. When light is directed at a spherical particle it will demonstrate characteristicreflection patterns. A new system named Fourier-domain Low Coherence Interferometry (fLCI) isintroduced to detect the size and location of cell nuclei. It is hypothesized this information can potentiallyoffer a noninvasive cancer diagnostic system since it has been determined that malignant cells display anabnormally large nucleus compared to benign cells.

    Upon reaching a spherical particle, such as a cell nucleus, light waves will both reflect off andtravel through the particle. Of the light that passes through the lower boundary of the particle, again somewill reflect off the upper layer of the particle and some will pass through. The reflected rays will meet anddisplay a distinctive interference pattern. This scattered spectrum is then Fourier transformed to determine

    particle size and also depth resolution. The fLCI system provides a non-invasive, cost effective techniquefor noticing nuclear irregularities at various depths within tissues.

    Particles of different sizes were measured to optimize the data collection technique. First uniformmicrospheres were used to mimic nuclear size. The 1.0 micron beads produced credible results with thefLCI system yielding an average size of 1.099 microns. Second, E. coli cells were measured. Althoughthese cells are much smaller than human cells, they display the natural variations in size unlike the uniformmicrospheres. Several different samples were tested; the average sizes, in microns, were 0.398, 0.423,0.819, 0.828, 0.753, and 0.429. E.coli cells are known to range in size from around 0.5 microns to 1.0microns, so these results were very accurate. Finally, yeast cells were measured since these displayroughly the same shape as cell nuclei.

    Since the readings from the fLCI system consistently provided convincing results, hopefully thisdevice can be used in a clinical setting to identify cell dysplasia.

    REU Fellow: David H. Wagner, Biomedical Engineering Major, North Carolina State UniversityEarly Cancer Detection using Photonics: Removal of Noise in Angle Resolved Low CoherenceInterferometry due to Spatial Correlation via a Low-Pass Filter

    Advisors: Dr. Adam Wax, Assistant Professor, Biomedical Engineering and

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    John Pyhtila, Biomedical Engineering Graduate StudentPrevious research has established angle-resolved low coherence interferometry (a/LCI) as

    an accurate tool for measuring the average nucleus size and fractal dimension (FD) of a sample of cancerous tissue. As signals are acquired from the interferometer they must be modified via signalprocessing before determinations can be made concerning the average nucleus size of a sample. Thisstudy examined the low-pass filter used to alleviate the effects of the spatial correlation of nuclei withinthe tissue. Using fibroblasts in a microarray palette a spatial relationship between each nucleus in thesample was established and based on Mie Theory the frequency due to this relationship was determined.The low-pass filter was then used to determine the spatial relationship among the nuclei and remove thenoise components of the data. Since data is still being collected, at this point it is hard to draw anydefinitive conclusions, but this study seems to support the use of the low-pass filter and the effectivenessof a/LCI in determining particle size and distribution.

    Project #14: Advanced Biophotonic Structured Illumination Imaging System Design

    Advisor: Joseph Izatt, Professor, Biomedical Engineering

    Professor Izatts laboratory has REU opportunities in a project sponsored by the National ScienceFoundation entitled Advanced Biophotonic Structured Illumination Imaging System Design. The goalof this project is to apply cutting-edge signal and image processing techniques to improve the resolutionof conventional optical imaging devices such as microscopes and ophthalmoscopes. This will be done bydesigning novel laser lighting patterns to illuminate cells and tissues with special patterns of light whichare designed to reveal fine structures upon collection and image processing. This approach will contributedirectly to the design of diagnostic instruments capable of imaging individual photoreceptor cells in theliving human retina. Students involved in this project will gain experience in medical imaging laboratorypractice, optical system design and prototyping, computer interfacing with laboratory instrumentation,and image processing algorithm design and programming. Students will also work directly withphysicians on identifying requirements for instrument design and in testing of prototypes.

    Project #15: Engineering Gene Expression Systems for Tissue RegenerationAdvisor: Charles Gersbach, Assistant Professor, Biomedical Engineering

    The Gersbach laboratory is dedicated to applying molecular engineering to thedevelopment of novel approaches to gene therapy and regenerative medicine. A central focus of this research involves engineering proteins that coordinate changes in cellular gene expression orgenome sequence. This work involves enhancing the activity of proteins that occur naturally orengineering entirely artificial proteins to perform these functions. These proteins are thendelivered to cells, either by genetic engineering or other drug delivery vehicles, to coordinatecomplex changes that control cell behavior. One example of this work involves using theseproteins to engineer readily available cell types, such as skin cells, to regenerate diseased ordamaged tissues, including bone, muscle, or blood vessels. Another example involves using the

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    engineered proteins to correct the genetic mutations associated with hereditary diseases, such asmuscular dystrophy and hemophilia.

    In this project, the student will be challenged to design these new proteins withadvisement from the advisor and graduate students. The student will then build the DNAsequences that encode the gene for the protein, including the appropriate gene expression system.If successful, the student will have the opportunity to test the activity of the engineered protein incultured human cells. Through this work, the student will gain expertise in important laboratorymethods, including plasmid DNA propagation and purification, molecular cloning and DNArecombination techniques, electrophoresis, and potentially mammalian cell culture includingliposomal transfection for genetic engineering. Additionally, they will gain exposure to the fieldsof molecular medicine, gene therapy, and regenerative medicine.

    A description of some REU Fellows projects follows:

    Lauren Cosby, Chemical Engineering Major, University of Dayton

    Engineering Synthetic Enzymes for Targeted Gene ModificationMentors: Dr. Charles Gersbach, Assistant Professor, Department of Biomedical Engineering andDave Ousterout, Graduate Student, Biomedical Engineering

    Lauren Cosby is a chemical engineering major from the University of Dayton in Ohio.The objective of her research project was to identify a safe and efficient means of expressingtherapeutic genes using zinc finger nucleases (ZFN). Utilizing the modular approach, a series of six ZFN pairs consisting of five to six fingers each were created. The cleavage of the NeomycinR (NeoR) gene by ZFNs will facilitate reverting NeoR back to the endogenous exon byhomologous recombination. ZFNs were ligated into FRT vectors containing green fluorescentprotein (GFP) and transfected into mammalian cells. Flow Cytometry was employed to

    characterize ZFN activity through fluorescent intensity of GFP. Activity was found to be (acertain percentage higher/lower) compared to a vector only background control of (). It is notedthat zinc finger activity increases with an increase in individual fingers, but at this time researchis still continuing with regard to further results.

    Project #16: Enhancing Light Absorption in Hybrid Nanocomposite IR Photodetectors by using

    Metallic NanoparticlesAdvisor: Adrienne Stiff Roberts, Assistant Professor, Electrical and Computer Engineering

    Hybrid nanocomposites refer to composite material systems in which inorganic compound semiconductornanomaterials are dispersed within organic conducting polymers. Such materials have been used todemonstrate a variety of optoelectronic devices, including light emitting diodes (LEDs), photodetectors,and photovoltaic solar cells. Key advantages of these materials systems include low-cost and room-temperature operation. This research project will focus on the application of infrared (IR) photodetection.More specifically, the goal is to demonstrate enhanced absorption of IR light by incorporating metallicnanoparticles in a photodetector. Such metal structures provide enhancement of the incident electric fieldsuch that device performance could be improved. This project will involve demonstrating the feasibility

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    of this approach to increasing the responsivity of hybrid nanocomposite IR photodetectors, and will havea strong emphasis on modeling and design.

    Project #17: RF and Antenna Design for Communication and ImagingAdvisor: Qing H. Liu, Professor of Electrical & ComputerEngineering (660-5440) [email protected]

    The objective of this project is to design and fabricate smallantennas for communication and imaging applications. The studentwill utlize computer software to design antennas, build antennas inthe laboratory, and perform communication and imaging measurements.

    A description of some REU Fellows projects with Dr. Liu follows:

    Ugonna Ohiri, Computer Engineering Major, University of Maryland- Baltimore CountyUltra Wideband AntennasMentors: Dr. Qing Liu, Professor, Department of Electrical and Computer Engineering and LuisTobon Llano, Graduate Student, Department of Electrical and Computer Engineering

    Ugonna Ohiri is a computer engineering major from the University of Maryland-Baltimore County. His research focused on antennas with both multiple frequencies of resonance and widebroadband performance which have played a major role in the functionalitiesof wireless communication systems. In his project, he used the Sierpinski Carpet Mod-Pfractal antenna based on fractal geometry. In our experiment, we constructed three iterationsusing both software simulations and experimental validation as measurements to test variousparameters. The effect of further fractal iterations on the overall efficiency of the antenna isstudied. Both the simulations and experiments show consistent results when weighed against eachother. Overall, the results show the third iteration as being the most efficient iteration, whencompared to the preceding three.

    Wesley D. Sims, Physics Major, Morehouse CollegeUsing Microwave Imaging for Breast Cancer Detection

    Wesley Sims is a senior physics major from Morehouse College.Microwave imaging for breast cancer detection is based on the contrast inelectrical properties of healthy breast tissues and malignant tumors. My projectcontributed to the research of breast cancer detection using microwaveimaging as an REU Fellow at the Pratt School of Engineering at DukeUniversity. The purpose of this project is to assist in the ability to detect breastcancer by using microwave imaging. Microwave imaging is a much healthiermethods for breast cancer detection than current methods in use. I assisted inthe proposed design of a clinical system to be used at Duke University to dotesting through multiple clinical trials. I helped to design the bed-like structurewith an integrated chamber that will collect images of a patients breast tissue.In addition, I helped to design and simulate major components of the proposed

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    switching system. Part of my research involved making schematic drawings of a proposed clinical system and a single pad of a circuit board layout. I alsoperformed tests and obtained results from simulations done in AgilentAutomated Design System to be used in refining the system for future use.

    Jack Skinner is an electrical engineering major from Ohio Northern University.Microwave Imaging (MWI) is an emerging technique for the detection of breast cancerand other biomedical anomalies. The success of microwave imaging is due to thedistinct differences in electrical properties between malignant tumors and healthymammary tissue. This new imaging technique uses non-ionizing radiation to producea full 3-D image of the anomaly based on scattered microwave energy. This paperfocuses on the research and construction of an experimental 3-D MWI system, as wellas some of the theory behind microwave imaging. The MWI system will use a 3-Darray of folded patch antennas to send and receive an RF signal. The transmittedsignal will be scattered by an object (tumor) and then recorded by various antennacombinations. These measurements, known as S21 parameters, will be used in aninversion algorithm to reconstruct the inverted dielectric constant and conductivity of the medium and the target itself. This research discusses the major components of the MWI system: the antenna array, imaging chamber, switching system, networkanalyzer, and PC used to run LabVIEW software and record the data. The conclusionof Jacks research has resulted in a functional 3-D MWI system, with only issues of theswitching system and matching fluid to be resolved before a series of tests will be runto reconstruct sample images. In addition, another new imaging technique,microwave-induced thermoacoustic imaging (MITI), was discussed and reviewed. Thisimaging technique will use short pulsed, high power microwave energy to irradiatethe mammary tissue and possible tumors. The tissue and tumor will then heat up andexpand, causing a variation in fluid pressure. The difference in pressure will induce anacoustic signal that will be recorded by an ultrasonic transducer and amplified. Theamplified signal will be converted to a digital signal to be used in imagereconstruction.

    Project #18: Design-for-Testability Methods for Multicore Integrated CircuitsAdvisor: Krishnendu Chakrabarty, Professor Electrical and Computer Engineering

    Multicore integrated circuits (or muticore chips) are being used today in microprocessors toachieve high performance under power constraints. Processor chips with four cores fromcompanies such as Intel and AMD are now common, and up to 16 cores are going to becomemainstream quite soon. These multicore chips are giving us unprecedented computing power forscientific applications, gaming and entertainment, control systems, and business software. Forgraphics applications and graphics processors (GPUs) from companies such as Nvidia, manymore cores are integrated in a single chip. This project is focused on cutting-edge design-for-testability (DFT) techniques for multicore chips. We are developing DFT solutions that canreduce manufacturing cost and make these chips more dependable for user applications. Ourresearch involves collaboration with Intel and AMD.

    Desired skillset: A first course in logic design and computer hardware, basic knowledge of

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    electronic circuits, some understanding of computer architecture/organization, programming inC/C++.

    Project #19: Optimization Methods, Chip Design, and Software Development for Digital

    Microfluidic BiochipsAdvisor: Krishnendu Chakrabarty, Professor Electrical and Computer Engineering

    Advances in digital microfluidics have led to the promise of biochips for applicationssuch as point-of-care medical diagnostics. These devices enable the precise control of nanoliterdroplets of biochemical samples and reagents. Therefore, integrated circuit (IC) technology canbe used to transport and process biochemical payload in the form of nanoliter/picoliter droplets.As a result, non-traditional biomedical applications and markets are opening up fundamentallynew uses for ICs. In this interdisciplinary research project, we are studying ways to designbiochips that can produce accurate results for clinical diagnostics in the shortest possible time andwith minimum chip area. We are collaborating with other faculty and a start-up company inResearch Triangle Park.

    Desired skillset: A first course in logic design and computer hardware, high-school or freshmenChemistry lab work, programming in C/C++, basic knowledge of optimization and computeralgorithms.

    Project #20: Earthquake Response Reduction with Electromechanical Transduction NetworksAdvisor: Jeff Scruggs, Assistant Professor, Civil and Environmental Engineering

    One of the most challenging problems in structural engineering concerns the protection of buildings andbridges from damage during earthquakes and heavy winds. Recently, this has led civil engineers toconsider the prospect of placing controllable devices in structures, which are designed to respond duringthese seismic events, and which are controlled explicitly to reduce the deformation of the structure. Asimple example of such a device is a hydraulic dashpot (similar to, but much larger than, the ones foundin automotive suspensions) with a controllable return valve. Through control of this valve, the amount of energy this device dissipates can be regulated by an automatic control system, in such a manner as toachieve very favorable structural response. A more complicated, but potentially much more versatile,way to accomplish this kind of response regulation is through the use of electromechanical transducers.These devices can be used to remove vibration energy from a shaking structure by converting it toelectrical energy. This converted energy can in turn be used to power the response controller, resulting inan intelligent vibration control system which is entirely "self-powered." This project will involve anexperimental investigation of a self-powered vibration control system for a scale model of a civilstructure. This structure will be built on the hydraulic shake table in the Structural Dynamics and SeismicResponse Laboratory at Duke. The primary objectives will be to validate the general concept, as well asto develop a better understanding of the optimal use of this technology in civil systems.

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    A description of some REU Fellows projects with Dr. Scruggs follows:

    Edwina Jones, Mechanical Engineering Major, Vanderbilt UniversityEarthquake Response Reduction with Electromechanical Transduction NetworksMentor: Dr. Jeff Scruggs, Assistant Professor, Department of Civil and EnvironmentalEngineering

    Edwina Jones was a mechanical engineering major from Vanderbilt University. Herresearch focused on the use of power electronics in electromechanical transduction networks. Theproposed network will structural damper in civil structures to help reduce the vibrations causedby earthquakes. Depending on the magnitude, time duration, and design of buildings, earthquakescan cause a large amount of damage to the affected areas. Moreover, any life within the affectedstructures is at risk of being harmed by the debris that may fall during the earthquake. Byintroducing a power electronic circuit into the electromechanical transduction network theamount of energy from the vibrating structure that is dissipated by the network through electronicswitching can be regulated. More specifically, varying the duty cycle of the switches in the power

    electronic circuit controls the amount of energy absorbed by the electrical part of the network anddamps the response of other components within the entire network. Thus, the duty cycle acts as adamper for the entire network.

    Moises Rivera Santoyo, Civil Engineering Major, California State Polytechnic UniversityPomonaOptimal Structural Damping Using Regenerative Force Actuation NetworksMentor: Dr. Jeff Scruggs, Assistant Professor, Department of Civil and EnvironmentalEngineering

    Moises Rivera Santoyo is a civil engineering major from California State Polytechnic

    University Pomona. His research focused on a regenerative force actuation (RFA) network consisting of an array of electromechanical forcing devices distributed throughout a structuralsystem and whose purpose is to reduce the response of the structure when subjected to avibration. These force actuators are connected in such a way that allows them to share electricalpower. These electromechanical actuators are devices that convert mechanical energy intoelectrical energy and vice versa. This conversion allows for the actuators to absorb mechanicalenergy from the vibrating structure, convert it into electrical energy and re-inject a portion of thisenergy back into the structure at another location. Absorbing energy from the structure allows forthese devices to obtain almost self-powered capabilities for which their operation requires only asmall amount of external power. Additionally, the power-sharing ability of these devices provides

    them with forcing network capabilities unattainable by conventional passive, active or semiactivedamping systems. Furthermore, RFA networks contain the capacity to apply supplemental linearstructural damping where as semiactive and passive devices can only provide local dampingforces. In this paper, it is shown that these systems can be used to produce nonlocal damping, inother words creating virtual forces between distant degrees of freedom, and asymmetric dampingmatrices. In perspective, RFA networks are capable of two-way power flow, like in activedamping systems, and external power supply demands in orders of magnitude below their power

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    capabilities, like in semiactive damping systems. Nevertheless, RFA networks are set apart bytheir energy storage and reuse capabilities as well as by their power coupling in actuationnetworks. Usage of RFA networks in a civil structural system under stochastic base excitation hasshown to yield significant improvements in linear-quadratic optimal performance in stationaryresponse.

    Project #21: Planning for CLEANER ( C ollaborative L arge-scale E ngineering A nalysis N etwork for E nvironmental E ngineering) River Basins Across the United StatesAdvisor: J. Jeffrey Peirce, Associate Professor, Department of Civil and EnvironmentalEngineering

    The National Science Foundation is planning and preparing for a nationwide system of environmental quality sensors and information to be networked among university researchers, publichealth officials, industry representatives, public interest groups, environmental policy experts and K-12educators. Under the direction of Professor Peirce Duke University is in the process of planning andpreparing for one of the eight river basin components, the Neuse River in Eastern North Carolina, inthis nationwide network. Pratt Fellows will collaborate on all aspects of this research project includingthe study of:

    1. environmental sensors and sensor networks to monitor, record and analyze environmentalquality2. cyberinfrastructures (computer networks) to link all CLEANER participants within NC andacross the nation3. methods to model and remediate environmental pollution on a regional and national scale4. business management plans to enhance the operation of Dukes CLEANER facility

    Undergraduate students with interests and training in engineering, science, business management,public policy, and public health are encouraged to consider joining this research program.

    A description of some REU Fellows project follows:

    Catie Bishop, Civil Engineering Major, University of ConnecticutOptimizing Wireless Sensor Networks in VineyardsMentors: Dr. Jeff Peirce, Associate Professor of Civil Engineering, and Adam Price-Pollak, PrattResearch Fellow in Civil Engineering

    Catie Bishop is a civil engineering major from the University of Connecticut. Herproject focuses on the fact that The optimal location of a few wireless environmental sensors canhelp viticulturists monitor water and air in the vineyard and promote grape growth. The cost of the system can be offset by reduced expenses and increased production. Vineyards are especiallysuitable for the use of an environmental sensor network due to grape sensitivity to microclimateswithin the vineyard. The methods presented in this paper for identifying the optimal sensor

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    locations are general enough to be applied to many different sized vineyards. In addition tomaximizing healthy grape production, smart viticulture can be used for other objectives, such asreducing water consumption and intervention to prevent frost damage

    Lizz Michael, Chemistry Major, Grove City CollegePlanning for CLEANER River Basins across the United States

    Elizabeth Michael is a chemistry major from Grove City College. Her project was onPlanning for CLEANER River Basins across the United States, which is a means to ensure thesuccess of a Collaborative Large-Scale Engineering Analysis Network for EnvironmentalResearch (CLEANER) facility to monitor water quality, pollution problems, and otherenvironmental issues in the Neuse River Basin through careful and systematic planning. Inconjunction with Associate Professor Dr. Jeff Peirce, two journal articles were written:Innovative Approaches for Managing Public-Private Academic Partnerships in Big Science andEngineering for publication in Public Organizational Review and Progression of the Size,Management, and Motivation of Big Science and Engineering Projects for publication in

    History of Science . Innovative Approaches for Managing Public-Private Academic Partnershipsin Big Science and Engineering analyzes public-private academic partnerships (PPAPs) in termsof management, organization, funding, and partner relationships; three case studies are presented,selected to display a range of partnership models. The increasing challenges of Big Science seemto demand the merging of the public, private, and academic sectors into a single collaboration.Three conclusions are drawn: (1) complex PPAPs can be successful if partners roles are clearlydefined; (2) Big Science needs PPAPs to achieve results; and (3) the management style forCLEANER should make use of a hierarchical PPAP organizational style. Progression of theSize, Management, and Motivation for Big Science and Engineering Projects tracks theevolution of Big Science and Engineering to allow recent and ongoing Big Science to be viewed

    as the product of a gradual shift in human motivations, capacity to explore and experiment, andcompetition between nations. The dissemination of Big Science and Engineering from culture toculture is examined; findings indicate that Big Science could continue to spread and that moreBig Science and Engineering projects may arise in the next several decades as scientific researchcontinues to evolve. The new applications and complexities presented by Big Science andEngineering are analyzed to determine the future of Big Science and the most efficient approachto its management and finance. This analysis of the evolution of Big Science and Engineeringconcludes that the scope of Big Science and Engineering may continue to grow, along with thenumber of possible management approaches for it, and that the motivating forces driving BigScience have changed through the ages.

    Lauren Raup Civil and Environmental Engineering Major, Geosciences Minor, Virginia PolytechnicInstitute and State UniversityFluorescence in-situ Hybridization (FISH)Applications in Complex Soil Systems: Emerging Countingand Analysis Techniques

    Lauren Raup is a civil and environmental engineering major and a geosciences minor fromVirginia Polytechnic Institute and State University. The purpose of her research was to facilitate the

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    development of counting and analysis techniques for results given by Fluorescence in-situ Hybridization(FISH) applications in complexly engineered soil systems. The FISH method and a ChemiluminescenceNO x analyzer are used in laboratory experiments to study soil microbial populations and the NOemissions levels from the amended soil samples. NO emissions are examined for two other reasons: first,NO plays a significant role in lower-tropospheric Ozone (O 3) production, and secondly, NO is a commonbyproduct of agricultural soil enhancements. In order to supervise the amount of NO emissions from soil,bioremediation monitoring techniques are employed. The examination of microbial-NO relationships isneeded to develop better approaches to bioremediation. In order to insure the relevance and contiguity of the data in question, the soil samples are checked for integrity and consistency using NO emissions datataken from the NO analyzer and results from previous research. This same previous research shows thatFISH is much more efficient than other methods in so far as it is used to monitor the effectiveness of bioremediation; however, it is also evident that FISH does not have an expedient, existing method forcounting and analysis. This research specifically focuses on the construction of a counting and analysistechnique, with the eventual aim being the creation of a more efficient experimental procedure that wouldeffectively utilize; FISH. The development of a precise counting and analysis method for Fluorescence in

    situ Hybridization in soil compounds can firmly establish the full capacity of FISH for future usage inbioremediation processes. The experimental design calls for 3 Mineral Fertilize (MF) amendments(.0004, .0008, and .0016 g/g soil) with 3 different glucose amendment levels for each MF amount (0, 3, 6mg/g soil); all samples are given a 1 day incubation period. Three replicates of each treatmentcombination are used, thus creating a total of 27 individual experiments. The consequent data from theNO emissions tests shows that the soil properties are acceptable. Two accurate, simple counting methodsthus result from these experiments. The first is designed to count microbes in a slide well being viewedthrough a microscope; the method created cuts the counting time in half. A second method wasdeveloped for counting microbial colonies that have been photographed using a digital camera. Theseimages are often cluttered by the presence of other microbial species or are unclear due to the

    fluorescence of the samples. By using a combination of IrfanView and Microsoft Paint software thecolonies become more accurately mapped. These new methods increase the experimental utility of FISHwith respect to bioremediation, environmental, and agricultural research sciences.

    Janelle Heslop, Environmental and Chemical Engineering, Columbia UniversityEnvironmental Science and Engineering for CLEANER WATERS in the Neuse River Basin: DesigningLaboratory Procedures for Sensing Water Quality

    Janelle Heslop is a junior environmental and chemical engineering major at ColumbiaUniversity. In a response to the need for environmental science and engineering outreach programs inearly education, activities for water quality sensing protocols were created as a part of the CLEANERWATERS network. For the program to be successful, it was determined that it must integrate thelaboratory research work of scientist and engineers with academic merit. In order to select water qualitysensing procedures that would be successful in these two areas two set of criteria, one for research andthe other for education, were developed. Using the two established criteria, from a wide gamut of waterquality tests, five procedures were selected to be developed for middle school students. After theirdevelopment, the criteria for both success in research and education, were used to evaluate each

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    protocol in order to determine if expectations were met. From the assessment, it was determined thatthe protocols do successfully integrate research and education. Furthermore the two sets of criteria aresufficient in determining the success of any educational scientific activity.

    Project: #22: Nonlinear AeroelasticityAdvisor: Earl Dowell, Professor & Dean Emeritus, Mechanical Engin.& Materials Science

    Our research is concerned with the dynamic interaction of a fluid and an elastic structure, a fieldtermed aeroelasticity, i.e., aerodynamics plus elasticity. Recent work has emphasized nonlinearaspects of the phenomena. Research has often been motivated by aerospace applications such asthe oscillations of aircraft wings, turbine blades in jet engines, and the wind loading on missilesduring their launch. However, we also study applications to biomedical engineering, e.g., bloodflow through arteries or airflow through the mouth; civil engineering, e.g., wind loads on bridgesand buildings; electrical engineering, e.g., wind induced oscillations of power lines; and to manyother aspects of engineering. Current projects involve either theoretical or experimental work.These include the following: (1) dynamic response of airfoils and wings due to self-excitation andexternal forces; (2) high performance airfoils; (3) delta wing planforms that deform as plates; (4)long span, highly flexible wings typical of uninhabited air vehicles; (5) novel geometries that leadto enhanced aeroelastic performance including oblique wings and folding wings; (6) control of

    and energy harvesting from such systems; (7) investigation of nonlinear effects such asfreeplay, structural stiffness and damping changes due to large deflections, shock wave motionand viscous effects in the aerodynamic flow.

    Project #23: Experiments in Cooperative Control of Multiple Robots

    Advisor: Devendra P. Garg, Professor of Mechanical Engineering, Mechanical Engineering &Materials Science

    These summer undergraduate projects involve cooperative control of robots of two differentvarieties. In one case, there are two industrial robots working cooperatively for carrying outspecific tasks that are beyond the capability of a single robot. We have acquired two state-of-the-art ABB IRB-140 industrial robots that have been installed in the Robotics and ManufacturingAutomation (RAMA) Laboratory (029G Hudson Hall). In addition, we have purchased andinstalled a conveyor system to transport objects around the two robots, and a six-positionindexing table located in the common workspace of the two robots. The research project dealswith controlling these industrial robots to operate in a collaborative mode for performing avariety of tasks. Examples of such tasks include nut and bolt assembly, transporting a heavyobject from one location to another, playing board games such as chess, or balancing a toy walkeron a beam grasped at its end by each of the two robots. In the other case, we have designed andfabricated a test bed for carrying out sensor fusion and swarming motion control of a group of several Swiss made small (size of a hockey puck) KheperaII robots. The mobile robot testbed is

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    located in the Robot Control Laboratory (030D Hudson Hall). Digital vision cameras locatedabove the robot workspace in the two laboratories can guide the motion of the Khepera and ABBindustrial robots. In a new robotics laboratory, we are conducting experiments to control a groupof mobile robots and aerial vehicles using a variety of sensors to emphasize surveillance andsituation awareness. The summer undergraduate project involves the designi