Le suivi des petits animaux utilisés dans le cadre de tests de laboratoire et l'analyse de leur comportement à distance, à faible coût et en temps réel suscitent depuis longtemps l’intérêt des chercheurs. Ceux-ci peuvent se faire par l’implantation de capteurs sans fils miniatures qui nécessitent des composants vitaux dont le plus problématique est l’antenne. En effet, la principale difficulté dans la conception d'antennes pour les dispositifs de communication bio-implantables est de fournir une structure rayonnante efficace et ce, malgré les contraintes de volume et le fort impact des tissus biologiques qui l’entourent. Si de nombreuses études ont porté sur l’utilisation d'antennes implantées dans la bande MICS (Medical Implant Communications Service) (402-405 MHz), il faut noter qu’à ces fréquences, la taille des antennes peut être un inconvénient réel dans le cas de petits animaux, d’où une recherche de miniaturisation. Une alternative consiste en l’utilisation de la technologie RFID (Radio-Frequency Identification) dans la bande UHF à 868 MHz. En effet, elle présente deux avantages primordiaux : elle facilite l'implantation du tag et ne nécessite pas l’ajout d'une batterie pour alimenter le périphérique implanté. Ce travail de thèse fait suite à un projet collaboratif financé par l’ANR (Agence Nationale de la Recherche) dans le cadre du Labex UCN@Sophia et qui a pour objectif la conception d’un système sans fils incluant aussi bien les tags RFID implantables, les antennes du lecteur et le lecteur connecté à un ordinateur se chargeant de la gestion centralisée des informations sur un serveur pour le suivi et la collecte de données de souris de laboratoire. Ce mémoire présente la conception d’antennes implantées pour tags RFID dans un modèle homogène représentant le corps d’une souris. Après l’analyse d’un bilan de liaison permettant de calculer les performances minimales de l’antenne implantée à concevoir pour une communication fiable et efficace, des antennes tags RFID passifs en 2D et en 3D ont été optimisées par différentes techniques pour atteindre des structures finales implantables ou injectables au dos d’une souris. Une caractérisation des solutions proposées en termes d’impédance, de champs E et H et de DAS (Débit d'Absorption Spécifique) a ensuite été effectuée dans un fantôme homogène. Enfin, un système d’interrogation permettant d’estimer la position de l’animal via la récupération du RSSI (Received Signal Strength Indicator) est présenté. / The monitoring of small animals in laboratory tests and the remote analysis of their behavior, with low cost and in real time interest researchers for a long time. This can be done by implanting miniature wireless sensors requiring vital components among which the most challenging is the antenna. Indeed, the main difficulty in designing antennas for bio-implantable communication devices is to provide an effective radiating structure, despite the volume constraints and the high impact of the surrounding biological tissues. Although many studies have focused on the use of implanted antennas dedicated to the MICS band (402405 MHz), it should be noted that at these frequencies, the size of the antennas can be a real disadvantage in the case of small animals, requiring miniaturization structures. Another solution consists in the using RFID (Radio-Frequency Identification) technology in the UHF band at 868 MHz. Indeed, it has two major advantages: it facilitates the implementation of the tag and does not require the addition of a battery to power the implanted device. This thesis funded by the ANR (French National Research Agency) within the framework of the Labex UCN@Sophia aims at designing a wireless system, including implantable RFID tags, reader's antennas and the reader connected to a computer that is responsible for the centralized management of information on a server for monitoring and collecting the data of laboratory mice. This thesis presents the design of implanted antennas for RFID tags in a homogeneous model representing the body of a mouse. After an analysis of a link budget allowing to determine the minimum performance of the implanted antenna to be designed for a reliable and an efficient communication, two RFID passive tag antenna designs have been optimized to obtain final structures able to be implanted or injected in the back of a mouse. A characterization of the proposed solutions in terms of impedance, E and H fields and SAR (Specific Absorption Rate) was then performed in a homogeneous phantom. Finally, an interrogation system capable to estimate the position of several animals placed in a cage thanks to the RSSI (Received Signal Strength Indicator) levels is presented.

Purpose: Due to the neurological aspects of Parkinson’s Disease (PD) and the sensitivity of eye movements to neurological issues, eye tracking has the potential to be an objective biomarker with higher accuracy in diagnosis than current clinical standards. Currently when PD is diagnosed clinically, there is an accuracy of 74% when diagnosed by a general practitioner and 82% when diagnosed by a movement disorder specialist. This study was designed to: 1. Assess eye movements as a potential biomarker for Parkinson’s Disease. 2. Determine if eye movements can distinguish between Parkinson’s Disease and commonly confounded movement disorders with parkinsonian symptoms. 3. Determine if the eye movements of Rapid Eye Movement Behavior Disorder (RBD) patients who will likely convert to PD are distinguishable from healthy controls and if RBD patients have eye movements with similar features to PD. Methods: The eye movements of 160 subjects (43 healthy controls, 63 PD, 31 REM Behavior Disorder, and 22 Other Parkinsonisms) were recorded at 500 Hz and analyzed. Each subject performed five eye tracking tasks that included reflexive saccades, inhibition of reflexive saccades, predictive saccades, and reading. Based on an analysis of selected eye movement measurement parameters, a multivariable logistic regression model was developed that compared: PD vs. Control, PD vs. “Other”, PD vs RBD, and Control vs RBD. The resulting predictive model was then assessed for accuracy, sensitivity, and specificity. Results: After screening, the most statistically significant predictors that were included in the final multivariate model were: Site, Sex, Age, Age squared, UPDRS Score, mean absolute fixation velocity (Horizontal Step Task), saccadic duration, average saccadic velocity, and mean fixation velocity (Predictive Task). The model predicted with an accuracy of: 92% for Controls, 88% for PD, 86% for RBD, and 68% for Other Parkinsonisms. The model was best at distinguishing between PD and Other Parkinsomisms with an accuracy of 89% and RBD and Controls with an accuracy of 88%. Conclusion: This research found that specific combinations of eye tracking parameters from simple tasks can be used to distinguish between PD and commonly confounded movement disorders with parkinsonism symptoms. The model’s ability to distinguish between groups indicates that in a confirmatory study we should have relatively high accuracy in discriminating between groups. This model is able to accurately distinguish Controls from RBDs, however due to an insufficient number of follow-up visits to date, the current study is unable to confirm if the RBDs tested will convert to PD. With such high error rates in diagnosing PD clinically, this model is a potentially beneficial and could serve as an easy screening tool to add to the suite of diagnostic tests and improve clinician’s ability to diagnose accurately.

The development of treatments for neurological disorders such as Alzheimer’s and Parkinson’s disease begins by understanding what these diseases affect and the consequences of further manifestation. One particular region where these diseases can produce substantial problems is the blood-brain barrier (BBB). The BBB is the selective diffusion barrier between the circulating blood and the brain. The barrier’s main function is to maintain CNS homeostasis and protect the brain from the extracellular environment. The progression of BBB research has advanced to the point where many have modeled the BBB in vitro with aims of further characterizing and testing the barrier. Particularly, the pharmaceutical industry has gained interest in this field of research to improve drug development and obtain novel treatments for patients so the need for an improved model of the BBB is pertinent in their discovery. In the Cal Poly Tissue Engineering lab, an in vitro tissue engineered BBB system has previously been obtained and characterized for the initial investigation of the barrier and its components. However, certain limitations existed with use of the commercial system. Therefore, the focus of this thesis was to improve upon the capabilities and limitations of this commercialized system to allow further expansion of BBB research. The work performed was based on three aims: first to design and develop an in-house bioreactor system that could be used to cultivate the BBB; second, to characterize flow and functional capabilities of the bioreactor; third, to develop protocols for the overall use of the bioreactor, to ultimately allow co-cultures of BAEC and C6 glioma cells, and further the progression toward creating an in vitro model of the BBB. The work of this thesis demonstrates development of an in-house custom bioreactor system that can successfully culture cells. Results showed that the system was reusable, could be sterilized and monitored, was easily used by students trained in the laboratory, and allowed non-destructive scaffold extraction. This thesis also discusses the next set of experiments that will lead to an in vitro model of the BBB.

This study investigated possible solutions to the current wartime problem of junctional hemorrhaging, or massive traumatic hemorrhaging in non-tourinquetable areas such as the neck, groin, or armpit. Junctional hemorrhaging has been identified as a major contributor to potentially survivable deaths seen on the battlefield today and therefore is a priority for the U.S. armed and coalition forces (Kragh et al., 2011a; Bozeman, 2011). Common tourniquets today are standard issue and carried by soldiers in the military, but are limited to distal extremity trauma. As the battlefield has changes however, trauma has transformed from commonly seen gunshot wounds to more extreme trauma such as dismounted complex blast injuries which typically includes loss of one or more appendages. These newly found situations render the traditional tourniquet ineffective. Thus, the development of a new tourniquet to control hemorrhaging from regions such as the neck, armpit, and groin has been deemed necessary. The development of a new tourniquet for hemorrhage control included market research, preliminary testing to determine design restraints, design ideation, finite element analysis, manufacturing a prototype, and prototype testing. Research and comparisons were done of the strengths and weaknesses of tourniquets already approved by the Food and Drug Administration (FDA). Next, design limitations were found using preliminary testing on a blood-flow replicate model developed by Tracey Cheung. The results from this testing provided a framework for designing a new tourniquet. A new approach to control junction hemorrhaging was then designed, built, and tested on the Cheung model. To verify the design, simplified models were analyzed using finite element analysis. The prototype was then tested and compared against the FDA approved tourniquets, listing the advantages and possible shortcomings.

A new detection reagent that could possibly augment or replace antibodies research and diagnosis methods are aptamers. Aptamers are ssDNA, RNA or polypeptide constructs that function like active antibodies. Antibodies and aptamers both specifically bind to selected target molecules, and as such they enable the detection or targeting of the presence or absence of a specific antigen. In order to ensure that ssDNA aptamers perform similarly to antibodies, anti-VEGF-A polyclonal antibody and anti-VEGF-A ssDNA aptamer were evaluated against vascular endothelial growth factor A (VEGF-A) using Surface Plasmon Resonance (SPR). It was hypothesized that the anti-VEGF-A aptamer had the same, if not better, binding kinetics than the anti-VEGF-A polyclonal antibody, and as such offers an ideal replacement for use in in field, real-time testing assays. SPR revealed that both the polyclonal antibody and ssDNA aptamer bound the target antigen, VEGF-A. Additionally, from the SPR kinetic analysis, the anti-VEGF-A aptamer had KD values of 20-28 nM and the anti-VEGF-A antibody had KD values of 16-127 uM. The binding efficacy of the aptamer was several orders of magnitude better than that of the antibody. The aptamer was also stable in solution for a longer amount of time than the antibody, which denatured in solution after two weeks.

Microfluidics refers to manipulation, precise control, and behavior of fluids at the micro and nanoliter scales. It has entered the realm of science as a way to precisely measure or mix small amounts of fluid to perform highly controlled reactions. Glass and polydimethylsiloxane (PDMS) are common materials used to create microfluidic devices; however, glass is difficult to process and PDMS is relatively hydrophobic. In this study, SU-8, an epoxy based (negative) photoresist was used to create various electrokinetic microfluidic chips. SU-8 is commonly used in microelectromechanical design. Spin coating of various SU-8 formulations allows for 1 μm to 100 μm thick layers with aspect ratios reportedly as high as 50:1. Case studies were performed to understand the curing/crosslinking process of SU-8 by differential scanning calorimetry. Supplier (MicroChem) recommended parameters were then altered to allow for adequate development of microfluidic channels, while maintaining enough molecular mobility to subsequently bond the SU-8 to a secondary substrate. Three SU-8 layers were used to create fully (SU-8) enclosed microfluidic channels. An (1) SU-8 2050 fully cured base layer was used as a platform on silicon to build from, (2) an SU-8 2050 partially cured layer for developing microfluidic channels , and (3) an SU-8 2007 uncured layer for bonding a secondary substrate to enclose the microfluidic channels. Bond quality was verified by optical and scanning electron microscopy, which resulted in a nearly 100% bond with little to no reflow of SU-8 into channels. Working pressures (ΔP across the capillary) of 15.57 lb/in2 (max detection) were obtained with no fluid leaks. Electroosmotic flow and steaming potential measurements failed. Electrophoretic behavior of glass particles was observed and particle velocities were compared by the application of 200 volts and 300 volts, across a channel length of 2 cm. Particle velocities obtained ranged from 100 μm/s to 1500 μm/s.

Impedance spectroscopy (IS) is an important tool for cell detection and characterization in medical and food safety applications. In this thesis, the Cal Poly Biofluidics Lab’s impedance spectroscopy system was re-evaluated and optimized for single-cell impedance spectroscopy. To evaluate the IS system, an impedance spectroscopy bioMEMS chip was fabricated in the Cal Poly Microfabcrication lab, software was developed to run IS experiments, and studies were run to validate the system. To explore IS optimization, Maxwell’s mixture theorem and the Schwartz-Christoffel transform were used to calculate an analytic impedance solution to the co-planar electrode system,a novel volume fraction to account for the non-uniformity of the electric field was developed to increase the accuracy of the analytic solution and to investigate the effect of cell position on the impedance spectrum, a software program was created to allow easy access to the analytic solution, and FEA models were developed to compare to the analytic solution and to investigate the effect of complex device geometry.

Transfemoral amputees around the world experience increased difficulty in climbing stairs due to lack of muscle, balance, and other factors. The loss of a lower limb greatly diminishes the amount of natural force generation provided that is necessary to propel oneself up stairs. This study investigated possible solutions to the problem of stair ascension for transfemoral amputees by the means of designing and developing an externally attachable device to a prosthesis. The number of amputations from military service has greatly increased since 2008, which shows there is a clear need for assistive devices (Wenke, Krueger, & Ficke, 2012). With the number of amputations rising and no current externally attachable products on the market to aid in stair ascension for transfemoral amputees, the need for this specific device has become more prominent. Research, previous work, and preliminary testing provided a basis for design and development of a new prototype. Bench top testing was conducted to review concepts in the prototype and provide data for further modifications. Results from testing of previous work, as well as testing of new concepts and modifications, provided a framework for designing a new externally attachable device for assistance in stair ascension. A new prototype was then designed, manufactured, and tested with bench models as well as real-time testing with amputees. Success of the device’s performance was based on bench top results and feedback from amputees, noting both the advantages and shortcomings of the new prototype. Testing provided results and feedback that the device was well built and functioned properly, but did not perform satisfactorily, particularly in the categories of force generation and balance.

As implantable medical devices are being used more often to treat medical problems for which pharmaceuticals don’t suffice, it is important to understand their interactions with commonly used medical modalities. The interactions between medical implants and Magnetic Resonance Imaging machines have proven to be a risk for patients with implants. Implanted medical devices with elongated metallic components can create harmful levels of local heating in a Magnetic Resonance Imaging (MRI) environment [1]. The heating of a biological medium under MRI is monitored via the Specific Absorption Rate (SAR). SAR, defined as power absorbed per unit mass (W/kg), can be calculated as , where σ is electrical conductivity of the medium in units of , |E| is the magnitude of the applied electric field in units of , and ρ is the density of the medium in units of . For continuous, uniform power deposition this can be measured experimentally as a rise in temperature over time (∆T/t), where c is the specific heat capacity of the medium in units of. To understand the SAR induced in-vivo, a phantom (Figure 2.10) is used to conduct in-vitro experiments, as it provides a controllable and repeatable experimental setup. In order to experiment in the phantom, an understanding of the background SAR distribution and in turn the exposure field distribution of the phantom is required as per the ASTMF2182-09 standard [2]. In this work, the background SAR distribution of an ASTM standard torso phantom is measured and studied via fiber optic thermometry. The measurements are compared with an electromagnetic model simulated via FDTD, demonstrating agreement between 10-25%. A custom exposure and data collection setup (including oscilloscope, function generator, RF amplifier, directional coupler, and Neoptix Omniflex Fiber Optic Thermometry system) was integrated and automated using NI LabView. The purpose of this thesis is to map the field distribution in a torso phantom under RF exposure from a 64 MHz MRI RF Birdcage, compare the results to an electromagnetic simulation, and finally conclude the accuracy of this method for field measurements in a standard torso phantom. Understanding the capabilities and accuracy of the fiber optic thermometry method will ultimately allow researchers to successfully apply this method to monitor background fields in their respective experimental setups (related to MRI implant heating) and understand its limitations.

Cerebral ischemia leading to an ischemic stroke is a possible complication of a transcatheter aortic valve replacement (TAVR) procedure. This is because embolic debris can become dislodged and travel through the aortic arch, where they either continue to the descending aorta and join the systemic circulation or travel into the cerebral vasculature through the three daughter vessels that branch off the top of the aortic arch. These three vessels are the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. These three vessels lead either directly or indirectly to the cerebral vasculature, where the diameter of vessels become very small. If a large enough embolus travels into the cerebral vasculature, it can become stuck in the small cerebral vessels, blocking blood flow and cutting off the supply of oxygen to brain cells. The purpose of this study is to expand upon previous work in order to 1) create a more accurate physics simulation of blood and debris flow through the aortic arch 2) report on embolic debris distribution through the aortic arch and 3) analysis on which physical parameters affect embolic debris distribution. The physical parameters analyzed were particle diameter and particle density. This study was performed by creating a finite element model in COMSOL Multiphysics™ using a SolidWorks model of an aortic arch, with dimensions taken from a patient’s CT scan. Computational fluid dynamics was performed using a pulsatile pressure waveform throughout the aortic arch with a non-constant viscosity model. Once the velocity profile through the aortic arch matched with value ranges from literature, the particle tracing study was implemented. Both a pulsatile pressure waveform and a constant pressure model were analyzed, as well as a constant viscosity model and a non-constant viscosity model. The pulsatile pressure waveform influenced particle distribution and is recommended for future studies since this model leads to pulsatile flow, which is representative of flow through the aorta. It was seen that the non-constant viscosity model did not have a large effect on the velocity profile, but more than doubled the surface average value of viscosity. It also had an effect on the particle distribution through the aortic arch. Small diameter emboli were more likely to flow into the descending aorta, the brachiocephalic artery, and the left subclavian artery; larger emboli were more likely to flow into the left common carotid. Lower density emboli were more likely to flow into the descending aorta and the brachiocephalic artery. Averaging all densities and sizes, it was determined 44.8% of emboli flow into the three daughter vessels, but ultimately only 30.61% of emboli flow into the cerebral vasculature and have the potential to cause an ischemic stroke.