Bioresorbable scaffolds (BRS) were thought to represent the next cardiovascular interventional revolution in relief of obstructive coronary atherosclerosis, yet they failed in comparison to metal stents. They were expected to provide mechanical support non-inferior to metal stents in short-term and gradually degrade to eliminate long-term complications associated with permanent implants. However, their clinical performances at all times were inferior to metal stents, including increased rate of thrombosis and myocardial infraction. These problems evaded detection, emerging only in clinical trials, leading one to wonder if BRS were appropriately characterized during the preclinical testing. We specifically questioned whether methods designed for metal stents could detect issues with BRS or hide potential areas of concerns. This work sought to determine how to define mechanical failure modes of BRS distinct from metal stents, and if such definition might have predicted clinical failure of the 1st generation BRS and if implemented now enable optimization of the design of next generation scaffolds. We developed a BRS-specific integrated approach involving benchtop mechanical testing, computational modelling, material characterization, and animal model validation evaluating de novo intact devices or those in which control defects were introduced. We performed mechanical characterizations with variable working environments and parameters. Micro-cracks and localized deformations were identified as a form of accelerated wear and challenge to structural integrity. We designed and built a high-throughput multimodal fatigue tester to generate deformation modes evident in arterial deformations in vivo, and test scaffold durability during acute and subacute timeframes. We reproduced fracture rates and locations seen in animal models, and revealed the relationship between loading modes, scaffold design, and fracture initiation and propagation. Finally, we utilized Raman spectroscopy to identify heterogeneities in material microstructures, which induced non-uniform degradation and severe localized deformations that could explain early structural failures and late clinical complications. Failure modes of BRS are distinct from those of bare metal stents and techniques designed to detect the one are not readily appropriate for the other. Characterization of device performance matched to device design might enable more appropriate device design. / 2020-10-22T00:00:00Z

abstract: Magnetic Resonance Imaging (MRI) is an efficient non-invasive imaging tool widely used in medical field to produce high quality images. The MRI signal is detected with specifically developed radio frequency (RF) systems or "coils". There are several key parameters to evaluate the performance of RF coils: signal-to-noise ratio (SNR), homogeneity, quality factor (Q factor), sensitivity, etc. The choice of coil size and configuration depends on the object to be imaged. While surface coils have better sensitivity, volume coils are often employed to image a larger region of interest (ROI) as they display better spatial homogeneity. For the cell labeling and imaging studies using the newly developed siloxane based nanoemulsions as 1H MR reporter probes, the first step is to determine the sensitivity of signal detection under controlled conditions in vitro. In this thesis, a novel designed 7 Tesla RF volume coil was designed and tested for detection of small quantities of siloxane probe as well as for imaging of labeled tumor spheroid. The procedure contains PCB circuit design, RF probe design, test and subsequent modification. In this report, both theory and design methodology will be discussed. / Dissertation/Thesis / Masters Thesis Bioengineering 2014

abstract: Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on bulk cell analysis, which results in averaging out the results acquired from a group of cells and hence missing important information about individual cells and their behavior. Understanding the cellular behavior at the single-cell level can help in obtaining a complete profile of the cell and to get a more in-depth knowledge of cellular processes. For example, measuring transmembrane fluxes oxygen can provide a direct readout of the cell metabolism. The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density. / Dissertation/Thesis / Masters Thesis Engineering 2014

abstract: Through decades of clinical progress, cochlear implants have brought the world of speech and language to thousands of profoundly deaf patients. However, the technology has many possible areas for improvement, including providing information of non-linguistic cues, also called indexical properties of speech. The field of sensory substitution, providing information relating one sense to another, offers a potential avenue to further assist those with cochlear implants, in addition to the promise they hold for those without existing aids. A user study with a vibrotactile device is evaluated to exhibit the effectiveness of this approach in an auditory gender discrimination task. Additionally, preliminary computational work is included that demonstrates advantages and limitations encountered when expanding the complexity of future implementations. / Dissertation/Thesis / Defense Presentation / Masters Thesis Bioengineering 2015

abstract: Tracking microscale targets in soft tissue using implantable probes is important in clinical applications such as neurosurgery, chemotherapy and in neurophysiological application such as brain monitoring. In most of these applications, such tracking is done with visual feedback involving some imaging modality that helps localization of the targets through images that are co-registered with stereotaxic coordinates. However, there are applications in brain monitoring where precision targeting of microscale targets such as single neurons need to be done in the absence of such visual feedback. In all of the above mentioned applications, it is important to understand the dynamics of mechanical stress and strain induced by the movement of implantable, often microscale probes in soft viscoelastic tissue. Propagation of such stresses and strains induce inaccuracies in positioning if they are not adequately compensated. The aim of this research is to quantitatively assess (a) the lateral propagation of stress and (b) the spatio-temporal distribution of strain induced by the movement of microscale probes in soft viscoelastic tissue. Using agarose hydrogel and a silicone derivative as two different bench-top models of brain tissue, we measured stress propagation during movement of microscale probes using a sensitive load cell. We further used a solution of microscale beads and the silicone derivative to quantitatively map the strain fields using video microscopy. The above measurements were done under two different types of microelectrode movement – first, a unidirectional movement and second, a bidirectional (inch-worm like) movement both of 30 μm step-size with 3min inter-movement interval. Results indicate movements of microscale probes can induce significant stresses as far as 500 μm laterally from the location of the probe. Strain fields indicate significantly high levels of displacements (in the order of 100 μm) within 100 μm laterally from the surface of the probes. The above measurements will allow us to build precise mechanical models of soft tissue and compensators that will enhance the accuracy of tracking microscale targets in soft tissue. / Dissertation/Thesis / Masters Thesis Bioengineering 2015

abstract: Prosthetic joint infection (PJI) is a devastating complication associated with total joint arthroplasty that results in high cost and patient morbidity. There are approximately 50,000 PJIs per year in the US, imposing a burden of about $5 billion on the healthcare system. PJI is especially difficult to treat because of the presence of bacteria in biofilm, often highly tolerant to antimicrobials. Treatment of PJI requires surgical debridement of infected tissues, and local, sustained delivery of antimicrobials at high concentrations to eradicate residual biofilm bacteria. However, the antimicrobial concentrations required to eradicate biofilm bacteria grown in vivo or on tissue surfaces have not been measured. In this study, an experimental rabbit femur infection model was established by introducing a variety of pathogens representative of those found in PJIs [Staphylococcus Aureus (ATCC 49230, ATCC BAA-1556, ATCC BAA-1680), Staphylococcus Epidermidis (ATCC 35984, ATCC 12228), Enterococcus Faecalis (ATCC 29212), Pseudomonas Aeruginosa (ATCC 27853), Escherichia Coli (ATCC 25922)]. Biofilms of the same pathogens were grown in vitro on biologic surfaces (bone and muscle). The ex vivo and in vitro tissue minimum biofilm eradication concentration (MBEC; the level required to eradicate biofilm bacteria) and minimum inhibitory concentration (MIC; the level required to inhibit planktonic, non-biofilm bacteria) were measured using microbiological susceptibility assays against tobramycin (TOB) and vancomycin (VANC) alone or in 1:1 weight combination of both (TOB+VANC) over three exposure durations (6 hour, 24 hour, 72 hour). MBECs for all treatment combinations (pathogen, antimicrobial used, exposure time, and tissue) were compared against the corresponding MIC values to compare the relative susceptibility increase due to biofilm formation. Our data showed median in vitro MBEC to be 100-1000 times greater than the median MIC demonstrating the administration of local antimicrobial doses at MIC level would not kill the persisting bacteria in biofilm. Also, administering dual agent (TOB+VANC) showed median MBEC values to be comparable or lower than the single agents (TOB or VANC) / Dissertation/Thesis / Masters Thesis Bioengineering 2017

abstract: The pathophysiology of Alzheimer’s disease (AD) remains difficult to precisely ascertain in part because animal models fail to fully recapitulate many aspects of the disease and postmortem studies do not allow for the study of the pathophysiology. In vitro models of AD generated with patient derived human induced pluripotent stem cells (hiPSCs) could provide new insight into disease mechanisms. Although many protocols exist to differentiate hiPSCs to neurons, standard practice relies on two-dimensional (2-D) systems, which do not accurately mimic the complexity and architecture of the in vivo brain microenvironment. This research aims to create three-dimensional (3-D) models of AD using hiPSCs, which would enhance the understanding of AD pathophysiology thereby, enabling the generation of effective therapeutics. / Dissertation/Thesis / Masters Thesis Bioengineering 2017

abstract: Heart transplantation is the final treatment option for end-stage heart failure. In the United States, 70 pediatric patients die annually on the waitlist while 800 well-functioning organs get discarded. Concern for potential size-mismatch is one source of allograft waste and high waitlist mortality. Clinicians use the donor-recipient body weight (DRBW) ratio, a standalone metric, to evaluate allograft size-match. However, this body weight metric is far removed from cardiac anatomy and neglects an individual’s anatomical variations. This thesis body of work developed a novel virtual heart transplant fit assessment tool and investigated the tool’s clinical utility to help clinicians safely expand patient donor pools. The tool allowed surgeons to take an allograft reconstruction and fuse it to a patient’s CT or MR medical image for virtual fit assessment. The allograft is either a reconstruction of the donor’s actual heart (from CT or MR images) or an analogue from a health heart library. The analogue allograft geometry is identified from gross donor parameters using a regression model build herein. The need for the regression model is donor images may not exist or they may not become available within the time-window clinicians have to make a provisional acceptance of an offer. The tool’s assessment suggested > 20% of upper DRBW listings could have been increased at Phoenix Children’s Hospital (PCH). Upper DRBW listings in the UNOS national database was statistically smaller than at PCH (p-values: < 0.001). Delayed sternal closure and surgeon perceived complication variables had an association (p-value: 0.000016) with 9 of the 11 cases that surgeons had perceived fit-related complications had delayed closures (p-value: 0.034809). A tool to assess allograft size-match has been developed. Findings warrant future preclinical and clinical prospective studies to further assess the tool’s clinical utility. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2018

abstract: Ionizing radiation, such as gamma rays and X-rays, are becoming more widely used. These high-energy forms of electromagnetic radiation are present in nuclear energy, astrophysics, and the medical field. As more and more people have the opportunity to be exposed to ionizing radiation, the necessity for coming up with simple and quick methods of radiation detection is increasing. In this work, two systems were explored for their ability to simply detect ionizing radiation. Gold nanoparticles were formed via radiolysis of water in the presence of Elastin-like polypeptides (ELPs) and also in the presence of cationic polymers. Gold nanoparticle formation is an indicator of the presence of radiation. The system with ELP was split into two subsystems: those samples including isopropyl alcohol (IPA) and acetone, and those without IPA and acetone. The samples were exposed to certain radiation doses and gold nanoparticles were formed. Gold nanoparticle formation was deemed to have occurred when the sample changed color from light yellow to a red or purple color. Nanoparticle formation was also checked by absorbance measurements. In the cationic polymer system, gold nanoparticles were also formed after exposing the experimental system to certain radiation doses. Unique to the polymer system was the ability of some of the cationic polymers to form gold nanoparticles without the samples being irradiated. Future work to be done on this project is further characterization of the gold nanoparticles formed by both systems. / Dissertation/Thesis / M.S. Bioengineering 2012

abstract: In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb representation. In a previous study, Shi et al. (2013) examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and held their arm at various target locations in a frontal plane. Visual feedback was withheld in half the trials, though non-visual (i.e. somatic) feedback was available in all trials. Previous analysis showed that some of the neurons were tuned to limb position and that some neurons had their response modulated by the presence or absence of visual feedback. This modulation manifested in decreases in firing rate variability in the vision condition as compared to nonvision. The decreases in firing rate variability, as shown through decreases in both the Fano factor of spike counts and the coefficient of variation of the inter-spike intervals, suggested that changes were taking place in both trial-by-trial and intra-trial variability. I sought to further probe the source of the change in intra-trial variability through spectral analysis. It was hypothesized that the presence of temporal structure in the vision condition would account for a regularity in firing that would have decreased intra-trial variability. While no peaks were apparent in the spectra, differences in spectral power between visual conditions were found. These differences are suggestive of unique temporal spiking patterns at the individual neuron level that may be influential at the population level. / Dissertation/Thesis / M.S. Bioengineering 2013