<p>Hydrocephalus is a neurological disease characterized by abnormal accumulation of cerebral spinal fluid (CSF) in ventricle of brain. 1 in 1000 newborns are affected each year and it is life-threatening if left untreated. The golden standard of treatment is to surgically implant a shunt that divert excessive CSF away from ventricle to alleviate intraventricular pressure (ICP) in patient. Unfortunately, shunt failure rate is notoriously high because of obstruction of catheter intake pore. The obstruction is primary caused by normal and inflammatory tissue (biofilm) buildup over time. Shunt replacement surgery is typically required after only 1 year of implantation for 40% of patients. To prolong the lifespan of hydrocephalus shunt, we previously proposed and designed magnetic micro-actuators platform to remove biofilm mechanically. Removal of muscle cells and microbeads were demonstrated from wafer level devices on bench-top.</p><p> </p><p>To examine device efficacy in ventricular catheter, I developed magnetic actuator on polymer substrate. First, polyimide based flexible thin-film devices were microfabricated and integrated into a single-pore silicone catheter. A proof-of-concept self-clearing smart catheter was presented. Removal of microscopic biofilm was evaluated against bovine serum protein (BSA). Detachment of BSA up to 95% was achieved by shear stress from magnetic actuation. Next, I developed resistive deflection sensing using a metallic strain gauge, allowing device alignment with magnetic field for maximum energy delivery. In addition, auxiliary functionalities such as occlusion detection and flow rate measurement were demonstrated on catheter. Moreover, a new serpentine cantilever geometry with increased magnetic volume was proposed for improved delivery of torque and deflection. In a benchtop evaluation, we showed prolonged catheter drainage (7x) in a dynamic fluid environment containing macroscopic blood clots. Finally, using an intraventricular hemorrhage (IVH) porcine model, we observed that self-clearing catheter had longer survival than control catheter (80% vs. 0%) over the course of 6 weeks. Animals treated with magnetic actuation had significantly smaller ventricle size after 1 week of implantation.</p>

Gastrointestinal (GI) septa are pathological entities whereby a wall of tissue is present in the GItract, resulting in symptoms such as dysphagia and regurgitation. They can be associated withconditions such as esophageal diverticula or upper gastrointestinal duplication, or post-surgicalcomplications such as candy cane syndrome. Current treatments involve interventions by eitherhighly skilled endoscopists or invasive surgery. We suggest the use of compression anastomosis toachieve endoscopic septotomy, relieving the patients of their symptoms. Compression anastomosisusing rings, clips, magnets, and wires or rubber bands (though not named as such for these last two)has previously been described in the literature. We propose the use of a combination of MagneticCompression Anastomosis (MCA) and what we have defined as Wire Compression Cutting (WCC),both involving progressive pressure application to induce ischemia, necrosis, inflammation, andfibrosis with regeneration. This PhD thesis describes the development of a novel medical devicedesigned to achieve the aforementioned process, from initial conception to detailed constructionby a specialized company, based on clinical and technical requirements defined in collaborationwith physicians and from latest regulations. This device, the MAgnetic Gastrointestinal UniversalSeptotome (MAGUS), consists of two magnetic boxes linked by a self-retractable wire. The wire isactivated by a spring coil system located inside the two magnetic boxes. This MAGUS MagneticDevice (MMD) is designed to be used with the MAGUS Delivery System (MDS), a catheter to whichit is attached, enabling the physician to mobilize each magnet independently during the procedure.To assess that the MAGUS meets the technical requirements of the procedure, and to mitigateagainst all possible risks that were identified through Failure Mode and Effects Analysis, verificationtests were performed in combination with animal testing. Clinical trials started in February 2020at Erasme Hospital with good preliminary results. Finally, to make the procedure more accessiblefor less experienced physicians, future improvements on the delivery catheter and procedure areproposed. / En gastroentérologie, un septum est défini comme une paroi de tissu séparant deux cavités. Ce typede structure peut être la cause de symptômes tels que de la dysphasie ou des vomissements. Il estcausé soit par des pathologies, comme les diverticules ou duplications de l’oesophage, soit par descomplications chirurgicales, comme le syndrome dit du "candy cane". Le traitement classique estla chirurgie mais celle-ci est liée à un haut taux de mortalité et morbidité. Ces dernières années,de nouvelles techniques endoscopiques ont été proposées, mais la plupart de celles-ci nécessitentl’intervention de médecins très expérimentés. Le travail développé dans cette thèse propose d’utiliserle concept d’anastomose par compression pour réaliser une découpe de ce septum. L’anastomosepar compression a été abondamment traitée dans la littérature. Cette compression est réalisée pardes anneaux, des clips, des aimants, des élastiques, ou du fil. Afin de réaliser cette septotomie,nous proposons donc de combiner l’anastomose par compression magnétique et ce que nous avonsappelé la découpe par compression par fil (Wire Compression Cutting), qui consiste à appliquer unepression, pour induire de l’ischémie, de la nécrose, de l’inflammation, et enfin de la régénérationcombinée à de la fibrose. Deux cahiers des charges, l’un clinique et l’autre technique, ont été réalisés;ceux-ci se basent sur la littérature sur le sujet, des échanges avec des médecins, et les normeset régulation actuellement d’application. Dans la suite du travail, le développement techniquedu MAGUS (MAgnetic Gastrointestinal Universal Septotome) est décrit, de l’idée à la premièreutilisation sur patients. Ce dispositif permet de réaliser cette compression, à l’aide de deux aimantsreliés par un fil rétractable. Cette solution épurée permet ainsi de découper différentes tailles deseptum, en une seule endoscopie, et sans incisions, réduisant le risque de perforation. Le "MAGUSMagnetic Device" a été conçu avec son outil dédié, le "MAGUS Delivery System", permettant defaciliter la mise en place du dispositif par endoscopie. Afin de vérifier que les caractéristiquestechniques définies au préalable sont bien remplies, et de réduire les dangers identifiés par uneanalyse de risque, des tests de vérifications ont été réalisés, en parallèle d’essais de faisabilité sur descochons. Les premières études cliniques ont commencé en février 2020 à l’Hôpital Erasme, donnantdes résultats préliminaires très encourageants. Ces premiers traitements ont notamment permisde prouver la faisabilité de la découpe par compression par fil. Ce travail est conclu en proposantdes améliorations pour le dispositif de pose, afin de faciliter sa prise en main, ainsi que de futuresnouvelles applications cliniques. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished

The inclusion of a new device in clinical practice requires an adequate validation. The original publication which introduced multichannel bioimpedance monitor MBM was focused on discribing its technical parameters and demonstration measurements. Further evaluation desires comparision with other standard measuring device. This thesis describes pulse wave measurement by MBM and by other medical devices used for establishing cardiovascular risk. It proposes the validation experiment with synchronized vascular ultrasonography as a reference method. The process of the experimental measurement, aquired data and following data analysis are described in detail. The outputs of the experiment are statistically evaluated. The MBM’s performance and design of the experiment are discussed.

This thesis deals with electromagnetic compatibility of implantable electro-medical devices using in cardiology. The main aim of this thesis is detection of the resistance of implantable pacemakers (PM) and implantable cardioverter defibrillators (ICD) to the electromagnetic interference. In the first part of this thesis, a function of the heart, which is necessary for understanding of PM and ICD operation, is described. The function and construction of PM and ICD is detailed in the theoretical part as well. The next part is focused on the electromagnetic compatibility. The next part is description of the measurement method and the experimental arrangement used for practical experiments with electromagnetic resistance of PM and ICD.

<p>Intra-Arterial Chemotherapy (IAC) is a preferred treatment for the primary liver cancer, despite its adverse side-effects. During IAC, a mixture of chemotherapeutic drugs, e.g. Doxorubicin, is injected into an artery supplying the tumor. A fraction of Doxorubicin is absorbed by the tumor, but the remaining drug passes into systemic circulation, causing irreversible heart failure. The efficiency and safety of the IAC can be improved by chemical filtration of the excessive drugs with a catheter-based Chemofilter device, as proposed by a team of neuroradilogists. </p> <p>The objective of my work was to optimize the hemodynamic and drug binding performance of the Chemofilter device, using Computational Fluid Dynamics (CFD) modeling. For this, I investigated the performance of two distinct Chemofilter configurations: 1) a porous “Chemofilter basket” formed by a lattice of micro-cells and 2) a non-porous “honeycomb Chemofilter” consisting of parallel hexagonal channels. A multiscale modeling approach was developed to resolve the flow through a representative section of the porous membrane and subsequently characterize the overall performance of the device. A heat and mass transfer analogy was utilized to facilitate the comparison of alternative honeycomb configurations. </p> A multiphysics approach was developed for modeling the electrochemical binding of Doxorubicin to the anionic surface of the Chemofilter. An effective diffusion coefficient was derived based on dilute and concentrated solution theory, to account for the induced migration of ions. Computational predictions were supported by results of <i>in-vivo</i> studies performed by collaborators. CFD models showed that the honeycomb Chemofilter is the most advantageous configuration with 66.8% drug elimination and 2.9 mm-Hg pressure drop across the device. Another facet of the Chemofilter project was its surface design with shark-skin inspired texturing, which improves the binding performance by up to 3.5%. Computational modeling enables optimization of the chemofiltration device, thus allowing the increase of drug dose while reducing systemic toxicity of IAC.

<p>  </p> <p>Cavitation, liquid slosh, and splashes are ubiquitous in science and engineering. However, these phenomena are not fully understood. Yet to date, we do not understand when or why sometimes the splash seals, and other times does not. Regarding cavitation, a high temporal resolution method is needed to characterize this phenomenon. The low temporal resolution of experimental data suggests a model-based analysis of this problem. However, high-fidelity models are not always available, and even for these models, the sensitivity of the model outputs to the initial input parameters makes this method less reliable since some initial inputs are not experimentally measurable. As for sloshing, the air-liquid interface area and hydrodynamic stress for the liquid slosh inside a confined accelerating cylinder have not been experimentally measured due to the challenges for direct measurement.</p>

Le travail présenté dans le manuscrit concerne la conception d'un dispositif médical de classe III pour des applications en ingénierie tissulaire du derme et du disque intervertébral.Il s'agit d'une solution aqueuse de chitosane, stérilisée par autoclave, et dont le pH et l'osmolarité ont été ajustés selon un procédé de dialyse classique. Cette solution possède des propriétés de gélification in situ innovantes, ce qui lui confère de très bonnes propriétés mécaniques quelques minutes après l'injection, sans l'utilisation d'agents de réticulation mais de façon modulable en fonction de la concentration en polymère. De plus, cette solution possède une bonne injectabilité favorisant le développement d'une technique d'implantation mini-invasive pour la régénération du derme et du disque intervertébral. Un critère de performance rhéologique a notamment été mis au point afin de relier l'injectabilité aux propriétés mécaniques de l'injectât (dermal filler).Les propriétés mécaniques de l'injectât gélifié doivent être comparables au tissu natif en particulier pour le dermal filler mais aussi pour le disque intervertébral. Le comportement mécanique viscoélastique du disque intervertébral a été évalué par des essais de relaxation de contraintes et modélisé avec un modèle de Maxwell solide à trois branches. Ces essais ont été conduits sur des disques sains, ayant subi une altération de structure (fenestration) et après l'injection de biopolymères.La solution de chitosane a été injectée (i) dans le tissu cutané de deux modèles animaux : le porc et le rat et (ii) dans le disque intervertébral de deux modèles animaux : le porc et le lapin. La biocompatibilité ainsi que la réponse biologique de solutions/gels physique de chitosane in vivo ont été validées pour tous ces modèles animaux / This work deals with the conception of a class III medical device for applications in tissue engineering of dermis and intervertebral disc.This device consists in an aqueous chitosan solution, sterilized by autoclaving, with pH and osmolality adjusted by a dialysis process. This chitosan solution shows in situ gelation ability with a post-injection increase of mechanical properties. This feature is related to polymer concentration, gelation time, and is performed without external cross-linking agent. In addition, the solution exhibits a good injectability allowing the development of minimally invasive techniques to treat dermis and intervertebral disc diseases. A rheological performance criterion was defined linking injectability to mechanical properties of the implant (dermal filler).Mechanical properties of gel implant formed in contact with body fluids, in situ, have to be similar to that of native tissues. The viscoelastic behavior characterization of intervertebral disc was performed using stress relaxation and was modeled using a generalized solid Maxwell model (composed of three Maxwell elements). The tests were performed on healthy disc, fenestrated discs and after biopolymers injection.Chitosan solutions were injected into (i) porcine and rat cutaneous tissue and (ii) porcine and rabbit intervertebral discs. The biocompatibility and biofunctionality of chitosan solutions and physical hydrogels was evidenced in vivo for all animals

Indiana University-Purdue University Indianapolis (IUPUI) / The link between volatile organic compounds (VOCs) from breath and various diseases and specific conditions has been identified since long by the researchers. Canine studies and breath sample analysis on Gas chromatography/ Mass Spectroscopy has proven that there are VOCs in the breath that can detect and potentially predict hypoglycemia. This project aims at developing a smart nanosensor system to detect hypoglycemia from human breath. The sensor system comprises of 1-Mercapto-(triethylene glycol) methyl ether functionalized goldnanoparticle (EGNPs) sensors coated with polyetherimide (PEI) and poly(vinylidene fluoride -hexafluoropropylene) (PVDF-HFP) and polymer composite sensor made from PVDF-HFP-Carbon Black (PVDF-HFP/CB), an interface circuit that performs signal conditioning and amplification, and a microcontroller with Bluetooth Low Energy (BLE) to control the interface circuit and communicate with an external personal digital assistant. The sensors were fabricated and tested with 5 VOCs in dry air and simulated breath (a mixture of air, small portion of acetone, ethanol at high humidity) to investigate sensitivity and selectivity. The name of the VOCs is not disclosed herein but these VOCs have been identified in-breath and are identified as potential biomarkers for other diseases as well. The sensor hydrophobicity has been studied using contact angle measurement. The GNPs size was verified using Ultra-Violent-Visible (UV-VIS) Spectroscopy. Field Emission Scanning Electron Microscope (FESEM) image is used to show GNPs embedded in the polymer film. The sensors sensitivity increases by more than 400\% in an environment with relative humidity (RH) of 93\% and the sensors show selectivity towards VOCs of interest. The interface circuit was designed on Eagle PCB and was fabricated using a two-layer PCB. The fabricated interface circuit was simulated with variable resistance and was verified with experiments. The system is also tested at different power source voltages and it was found that the system performance is optimum at more than 5 volts. The sensor fabrication, testing methods, and results are presented and discussed along with interface circuit design, fabrication, and characterization. / 2022-05-8

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