Biomedical Engineering and Bioengineering Commons^™

Lysosomal Delivery Of Bioactive Proteins To Living Human Cells Via Engineered Exosomes, Daniel Levy

Bioengineering Master's Theses

Exosomes are naturally secreted nanovesicles derived from mammalian cells that are used for intercellular communication in vivo. As a result, they can potentially be used for intracellular delivery of therapeutics for disease treatment. We have developed an exosome pseudotyping approach using vesicular stomatitis virus glycoprotein (VSVG) to produce protein chimeras that optimize production of modified exosomes containing protein therapeutics and facilitate effective delivery to their target cells. To the VSVG transmembrane scaffold, we have fused both fluorescent and luminescent reporters for exosome tracking/visualization and quantification of activity respectively. Through our design, we have shown the biogenesis of VSVG modified exosomes …

Engineering Nanoscale Exosomes For Lysosomal Delivery Of Bioactive Enzymes, Mai Anh Do

Bioengineering Master's Theses

There are at least 50 lysosomal storage diseases that are caused by accumulation of a substrate due to a defective enzyme. Although some treatment options are available, low efficacy, high cost, and immunogenicity are main challenges of current treatments. To overcome those limitations, we use cell-derived nanoparticles to deliver biologically active cargos into lysosomes. Naturally produced exosomes can deliver proteins without triggering an immune response. Additionally, exosome have an intrinsic ability to cross blood brain barrier benefiting patients at a late disease stage that affects the brain. After fusing either Gaussia luciferase (gLuc) or puromycin resistant protein (puro) onto a …

Active Auxetic Heel Support For Achilles Tendon Therapy, Anna Hinrichs, Kseniya Malukhina, Ishaan Sharma, Micaela Vierra

Bioengineering Senior Theses

The Achilles tendon, which stretches from the calf to the ankle, can be injured due to repeated daily activities or overstretching. In severe cases a tear in the tendon can prevent athletes from performing in games as well as individuals from completing their daily tasks. Achilles tendon injuries affect millions of people. The severe pain that occurs upon injury can take months to improve and for the Achilles tendon to heal. Our goal is to design an auxetic support to provide comfort, help heal the tendon, and allow the individual to continue to be active through the natural healing process. …

Modifying The Size Of Nanopores Of Alginate Microcapsules, Andrea Filler, Jordan Levine, Jerard Roniel Madamba, Natalie Ploof

Bioengineering Senior Theses

Alginate hydrogels provide desirable biocompatibility and material properties for various biomedical applications, but are limited by the polymer's natural pore size. With the rise of nanotechnology, the desired crosslinked pore size range of 30 nm to 100 nm has not yet been achieved. This project aimed to develop a method to increase the pore size of alginate-based hydrogels in a reproducible manner without compromising their structural integrity. Experimental methods included altering alginate composition using carboxymethyl cellulose or gelatin and inducing conformational changes via Mach-1TM mechanical compression. Fluorescence microscopy was used to visualize the diffusion of FITC-dextran weight markers and fluorescent …

A 3d Simulation Of Leukocyte Adhesion In Blood Flow, Tai-Hsien Wu

Dissertations

It has been widely acknowledged that further understanding about the dynamics between blood cells and blood flow can help us gain more knowledge about the causes of diseases and discover more effective treatments. Examples of such dynamics include red blood cell (RBC, or erythrocyte) aggregation, white blood cell (WBC, or leukocyte) margination, and WBC extravasation. WBC extravasation is an important multiple-step process in the inflammatory response and therefore has drawn considerable attention over the past two decades. In this multiple-step process, a WBC undergoes at least four steps, including capture, rolling, firm adhesion, and transmigration, and each step is influenced …

Multi-Purpose Heart Valve Therapy Assembly Fixture, Alec John Foster, John Patrick Hofstetter, Emily Lim

Mechanical Engineering

STATEMENT OF CONFIDENTIALITY: The complete senior project report was submitted to the project advisor and sponsors. The results of this project are of a confidential nature and will not be published at this time.

Annuloplasty Mti: Improved Tooling For Annuloplasty Ring Manufacturing, Justin David Smith, Spencer Lee Combs, Luke Edward Maly

Mechanical Engineering

The complete senior project report was submitted to the project advisor and sponsor. The results of this project are of a confidential nature and will not be published at this time.

Elucidating The Mechanisms Of Two Unique Phenomena Governed By Particle-Particle Interaction Under Dep: Tumbling Motion Of Pearl Chains And Alignment Of Ellipsoidal Particles, Yu Zhao, Jozef Brcka, Jacques Faguet, Guigen Zhang

Biomedical Engineering Faculty Publications

Particle-particle interaction plays a crucial role in determining the movement and alignment of particles under dielectrophoresis (DEP). Previous research efforts focus on studying the mechanism governing the alignment of spherical particles with similar sizes in a static condition. Different approaches have been developed to simulate the alignment process of a given number of particles from several up to thousands depending on the applicability of the approaches. However, restricted by the simplification of electric field distribution and use of identical spherical particles, not much new understanding has been gained apart from the most common phenomenon of pearl chain formation. To enhance …

Identification System For Heart Valve Manufacturing, Nicholas Robert Jensen, Edgar Davis Nix, Judith Evelyn Gonzalez, Albert Austin Liddicoat

Mechanical Engineering

Abstract withheld due to NDA constraints

Foot Stress And Blood Flow Sensing Under High-Loading During Hip Surgery, Chris Cardenas, Esther Chen, Claire Kingston, Katie Paswaters, Brianna Rodebaugh

Mechanical Engineering

The PolyHIPS team was tasked with integrating sensors into Stryker’s hip arthroscopy boot that monitor blood flow and heel slip during hip surgery. During hip arthroscopy, the femur head is distracted from the acetabulum to create space in the joint for the surgeon to operate. This requires the use of up to 200 lbf. In order to maintain this space, the foot is held tightly in the boot. Complications can result from the foot being held too tightly in the boot during the procedure. The most common complication is neuropraxia, or temporary nerve damage. PolyHIPS proposes a solution that utilizes …

Transcatheter Heart Valve Leaflet Assembly Tooling Improvement Final Design Report, James Craig Sherman, Zachary Robert Dicks, Luke Edward Williams

Mechanical Engineering

Statement of Confidentiality: The complete senior project report was submitted to the project advisor and sponsor. The results of this project are of a confidential nature and will not be published at this time.

Dynamic Model For Simulating Motion Of The Right Ventricle, Brian Michael Larsen, Sam Koopman Porter, John Francis D'Ambrosio

Mechanical Engineering

This report documents all the research, ideation, and mockups used to determine right ventricle motion and develop a system capable of reproducing that motion on a tissue sample. The model is intended for evaluating anchoring systems being developed by Edwards Lifesciences for use with tricuspid valve therapies. Several design solutions were considered for the primary functions of recreating motion of the right ventricle and attaching tissue to the device. From these ideas a primary means of producing motion and attaching tissue was selected. These ideas were then developed over the course of a school year to become the final system …

Detection Method Of Subclinical Atherosclerosis Of The Carotid Artery With A Hemodynamics Modeling Approach, Marisa Peressini

Master's Theses

Subclinical atherosclerosis is an important area of research to evaluate stroke risk and predict localization of plaque. The current methods for detecting atherosclerosis risk are insufficient because it is based on The Framingham Risk Score and carotid intima media thickness, therefore an engineering detection model based on quantifiable data is needed. Laminar and turbulent flow, dictated by Reynolds number and relative roughness, was modeled through the carotid artery bifurcation to compare shear stress and shear rate. Computer-aided design and fluid flow software were used to model hemodynamics through the carotid artery. Data from the model was derived from governing equations …

Comparison Of Autonomic Control Of Blood Pressure During Standing And Artificial Gravity Induced Via Short-Arm Human Centrifuge, Ajay K. Verma, Da Xu, Michelle Bruner, Amanmeet Garg, Nandu Goswami, Andrew P. Blaber, Kouhyar Tavakolian

Electrical Engineering Faculty Publications

Autonomic control of blood pressure is essential toward maintenance of cerebral perfusion during standing, failure of which could lead to fainting. Long-term exposure to microgravity deteriorates autonomic control of blood pressure. Consequently, astronauts experience orthostatic intolerance on their return to gravitational environment. Ground-based studies suggest sporadic training in artificial hypergravity can mitigate spaceflight deconditioning. In this regard, short-arm human centrifuge (SAHC), capable of creating artificial hypergravity of different g-loads, provides an auspicious training tool. Here, we compare autonomic control of blood pressure during centrifugation creating 1-g and 2-g at feet with standing in natural gravity. Continuous blood pressure was acquired …

Powering A Biosensor Using Wearable Thermoelectric Technology, Anneliese Bals, Noah Barnes, Rafael Bravo, Nicolas Garcia, Joseph O'Bryan, Dylan Santana

Interdisciplinary Design Senior Theses

Wearable medical devices such as insulin pumps, glucose monitors, hearing aids, and electrocardiograms provide necessary medical aid and monitoring to millions of users worldwide. These battery powered devices require battery replacement and frequent charging that reduces the freedom and peace of mind of users. Additionally, the significant portion of the world without access to electricity is unable to use these medical devices as they have no means to power them constantly. Wearable thermoelectric power generation aims to charge these medical device batteries without a need for grid power.

Our team has developing a wristband prototype that uses body heat, ambient …

Urinalysis Screening For Rural Communities, Dana Bren-Cardali, Lilian Dao, Jeffrey Destruel, Ryan Fernandez

Interdisciplinary Design Senior Theses

Access to medical care and health screenings is a necessity for patients around the globe, but it can be difficult to provide this without screenings becoming costly or convoluted. In rural and underdeveloped areas, patients are often disadvantaged when it comes to finding reliable and affordable healthcare. The isolation provided by their location and the rising costs of physicians makes it impossible for most impoverished communities to attain personalized care. Because of this, treatable diseases often go unaddressed, allowing diseases to progress to a critical condition. Mortality rates have shown to be higher in communities located in rural areas and …

Enhancing Mobility And Independence Of Wheelchair Users, Briar Blake, Paul Nauleau

Interdisciplinary Design Senior Theses

Conditions as simple as a leg fracture or more severe impairments such as paralysis and stroke may confine a person to a wheelchair. Wheelchairs help people with limited mobility transport themselves to different locations, but do not help the person leave the wheelchair. Users would need to do this to enter a car, use the restroom, take a shower, and sit at a table comfortably with family. The following design is a wheelchair attachment that serves to provide the user with increased mobility and independence. Wheelchair users struggle to get into and out of their chairs due to the unassisted …

The Human Keyboard, Derek Char, Thomas Chung, Alexander Mckee, Allen Pai

Interdisciplinary Design Senior Theses

Most products that implement features for user interactions utilize buttons or switches for the user to command to select actions to perform. Such designs are typically controlled with direct motions, such as touch or voice and are seldom designed in consideration of those unable to utilize direct control. In this project, we designed technology that reads naturally occuring biosignals from the body, which then can be apply those signals with any interface. For our specific application in this project, we decided to implement a keyboard. Instead of teaching the fingers how to type on a mechanical keyboard, the body can …

Cervis: Cervical Cancer Early Response Visual Identification System, Evangelia Bouzos, Ivy Fernandes, Marina Predovic

Bioengineering Senior Theses

Our goal is to make a positive impact in the cervical cancer diagnostic space through the development of an accurate, cost effective solution that enables women in low resource settings to test for cervical cancer on a frugal and effective platform. In developed countries, we rely on regular preventive care, such as pap smears, to identify any cellular abnormalities that may indicate the disease state. However, due to the high cost and laboratory requirements of this procedure, women in low resource settings typically do not have access to this procedure. Since they are not regularly screened and often have little …

Engineered Living Nanoparticles For The Treatment Of Inflammatory Diseases, Annie Brown, Alex Campanelli, Adarsh Tantry

Bioengineering Senior Theses

Rheumatoid arthritis (RA) is a widespread, debilitating autoimmune disease characterized by painful inflammation of the joints. Current treatments for RA are either ineffective, expensive, or have undesirable effects, such as an adverse immune response. To mitigate these effects, we have designed an exosome-based treatment for inflammation. We chose to utilize exosomes for their longer half-life in the body, better penetrative capacity, and biocompatibility, thus improving upon previous RA treatments. To do this, we created a stable cell line to produce exosomes modified at the surface to express a tumor necrosis factor receptor (TNFR), which possesses the ability to act as …

Meshr: A Modular, Economical Skin Graft Hand Roller, Maggie Alt, Josée Fournier, Madeline Krenek, Will Paton

Bioengineering Senior Theses

In South Africa and around the world, the rates of severe burns are a significant health issue. Skin grafts are used to improve the function and appearance of the burned area and reduce the amount of time a patient is in the hospital. To minimize the amount of skin needed and maximize the coverage of the graft, the harvested sample is meshed in a lattice pattern so it can expand and graft a much larger surface area. Unfortunately, the current methods and devices used in both high and low-income countries have been optimized for hospitals with larger budgets and more …

Assessing The Photoprotective Effects Of Fluorescent Sphingomyelin Against Uvb Induced Dna Damage In Human Keratinocytes, Rebecca Marie Kandell

Master's Theses

Non Melanoma Skin Cancer (NMSC) affects 3.3 million Americans each year and results from Ultra Violet Radiation (UVR) damage to DNA in the form of pyrimidine dimers and photoproducts [1]–[5]. Cells directly detect the damage and initiate apoptosis, cell cycle arrest, or DNA repair by modulating p53 and p21 levels [6]–[9]. Current methods of photoprotection include sunscreen, but controversy over safety of some active ingredients necessitates research into more natural alternatives [10]–[12]. In particular, 24 hour incubation with bovine milk sphingomyelin (BSM) has demonstrated photoprotective potential by reducing p21 and p53 levels in keratinocytes (KRTs) after UV radiation [13], [14]. …

Extended-Use Ecg Monitor, Daniel Aaron Soski

Master's Theses

In this thesis, a prototype ECG monitor was developed that is integrated into an elastic shirt and takes a 3-lead ECG for over 5 days. The high-quality measurements can be used to identify markers indicative of various detrimental heart conditions. Measurements recorded by the device are encrypted and stored onto a micro-SD card. Current Holter monitors are expensive and have functional lives less than 48 hours; however, extended duration monitoring has been proven more useful in diagnosis. The device designed demonstrates that ECG measurements can be taken over longer durations without sacrificing quality, comfort, or device cost.

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Neuro-Silicon Interface Of A Hirudo Medicinalis Retzius Cell Integrated With Field Effect Transistor, Kurt Christian Sjoberg

Master's Theses

The focus of this thesis was to measure the intracellular voltage of a living neural cell using a silicon transistor. The coupling of neurological tissues with silicon devices is of interest to the fields of neurology, neuroscience, electrophysiology and cellular biology. In previous work by Peter Fromherz, single neurons were successfully coupled to transistors [1]. This thesis aims to show proof of concept of the fabrication of a simple neuro-silicon interface using wafer processing methods currently available at Cal Poly. The types of transistors and cells used, the methods for dissecting and preparing the cells, the electrophysiology methods for validating …

Characterization Of Arterial Flow For Junctional Bleeding Control, Nick Bosio

Master's Theses

This study investigated reducing volumetric flowrate under steady flow conditions by varying lengths of compression with constant cross-sectional area and varying cross-sectional area reduction with constant length in order to better understand how to control junctional hemorrhaging. The hypotheses of this study were that length reduction will have little effect on volumetric flowrate and that cross-sectional area reduction would need to be approximately 80 percent in order to obtain bleeding control. The study found that length reduction has little effect on changing the flowrate. However, in order to obtain at least 80 percent reduction in flow, the area needs to …

Validation Of A 1d Algorithm That Measures Pulse Wave Velocity To Estimate Compliance In Blood Vessels, James Leung

Master's Theses

The purpose of this research is to determine if it is possible to validate the new 1D method for measuring pulse wave velocity in the aorta in vivo and estimate compliance. Arterial pressure and blood flow characterize the traveling of blood from the heart to the arterial system and have played a significant role in the evaluation of cardiovascular diseases. Blood vessel distensibility can give some information on the evolution of cardiovascular disease. A patient’s aorta cannot be explanted to measure compliance; therefore we are using a flow phantom model to validate the 1D pulse wave velocity technique to estimate …

Comparative Analysis Of Physiological Measurements And Environmental Metrics On Predicting Heat Stress Related Events, Mckenzie Lee Barlow

Master's Theses

Exposure to high heat and humidity can lead to serious health risks, including heat exhaustion and heat stroke. Wet Bulb Globe Temperature (WBGT) and heat index have historically been used to predict heat stress events, but individualized factors are not included in the measurement. It has been shown that there is a relationship between cardiovascular measurements and heat stress, which could be used to measure heat stress risk on an individual level. Research has been done to find relationships between cardiovascular metrics in a workplace environment, however the study did not include the use of a controlled environment as a …

Posterior Cervical Spine Crisscross Fixation: Biomechanical Evaluation, Joseph F. Cusick, Frank A. Pintar, Joseph S. Cheng, Jason I. Lifshutz, Narayan Yoganandan

Biomedical Engineering Faculty Research and Publications

Background

Biomechanical/anatomic limitations may limit the successful implantation, maintenance, and risk acceptance of posterior cervical plate/rod fixation for one stage decompression-fusion. A method of posterior fixation (crisscross) that resolves biomechanical deficiencies of previous facet wiring techniques and not reliant upon screw implantation has been devised. The biomechanical performance of the new method of facet fixation was compared to the traditional lateral mass plate/screw fixation method.

Methods

Thirteen human cadaver spine segments (C2-T1) were tested under flexion-compression loading and four were evaluated additionally under pure-moment load. Preparations were evaluated in a sequence of surgical alterations with intact, laminectomy, lateral mass plate/screw …

Diffusion Tensor Imaging In A Large Longitudinal Series Of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome, Avinash Rao, Hesham Soliman, Mayank Kaushal, Olesya Motovylyak, Aditya Vedantam, Matthew D. Budde, Brian D. Schmit, Marjorie C. Wang, Shekar N. Kurpad

Biomedical Engineering Faculty Research and Publications

BACKGROUND

Fractional anisotropy (FA) of the high cervical cord correlates with upper limb function in acute cervical cord injury. We investigated the correlation between preoperative FA at the level of maximal compression and functional recovery in a group of patients after decompressive surgery for cervical spondylotic myelopathy (CSM).

OBJECTIVE

To determine the usefulness of FA as a biomarker for severity of CSM and as a prognostic biomarker for improvement after surgery.

METHODS

Patients received diffusion tensor imaging (DTI) scans preoperatively. FA values of the whole cord cross-section at the level of maximal compression and upper cervical cord (C1-2) were calculated. …