Flexible and stretchable wearable biomedical devices provide a platform for continues long-term monitoring of biological signals during neutral body movements thus enabling early intervention and diagnostics of various diseases. This thesis evaluates novel flexible and stretchable bio interfacing medical devices based on microneedle patches and split ring resonator for healthcare diagnostics. Flexible and stretchable microneedle patches were realized by integrating a soft polymer substrate with sharp stainless steel microneedles. This was realized using a magnetic assembly technique. Investigations have shown that the flexible microneedle patch can provide conformal and reliable contact with wrinkles and deformations of the skin. In addition, transdermal monitoring of potassium ions using the proposed flexible microneedle patch have been demonstrated by coating the microneedles with a potassium sensing membrane. Ex-vivo test on the microneedle potassium sensor performed on chicken and porcine skin was able to detect change in potassium concentration in the skin. Furthermore, a novel flexible bio-interface spilt ring resonator (SRR) for the monitoring of intera cranial pressure (ICP) is demonstrated. The sensor was fabricated by depositing a 500 nm gold film on a thermoset thiolene epoxy polymer substrate. The flexible sensor was able to clearly detect the pressure variation that might be an indication of increased ICP in the skull. The proposed methodology of heterogeneous integration of hard materials on a soft and flexible substrate demonstrates a first proof of concept of flexible wearable bio-interfacing devices with vastly different material properties with the potential for continuous and real-time health monitoring. / <p>QC 20190306</p>

The field of soft electronics is rapidly growing as there is an increased demand for health monitoring using wearable electronics that conforms to biological tissue. To promote sustainability and reduce electronic waste, it is of interest to find ways to reuse low-value-added commodities, such as protein-rich byproducts, for materials in high-value-added technologies that are degradable at end of use. One recognised byproduct from meat production is the abundant protein collagen, or the hydrolysed derivative gelatine. To overcome the limited mechanical properties of gelatine, it can be functionalised with a polymer with previous use in tissue-engineering and battery encapsulation, namely Poly(Glycerol Sebacate)(PGS), to generate the copolymer PGS-G. The work described in this thesis focuses on PGS and PGS-G polymer characterisation by utilising ATR-FTIR and DSC, but also on material characterisation of mechanical and hydration properties, ionic conductivity, and degradation. The results indicate that the successfully synthesised PGS and PGS-G polymers should not be crosslinked completely to achieve the most flexible mechanical properties, but also that crosslinking density should be tuned to suit the application. Moreover, incorporation of gelatine in PGS resulted in increased hydrophilicity for PGS-G. Finally, it was concluded that PGS is suitable for encapsulation whereas PGS-G could be used as an active component. Future work should include degradation studies in vivo and under environmental aerobic conditions to ensure that the polymers are fully biodegradable. / Mjuk elektronik är ett nytt forskningsområde som utvecklas starkt i takt med den ökade efterfrågan på hälsoövervakning med innovativ elektronik som är mjuk och töjbar vilket möjliggör smidig integrering i biologisk vävnad. För att främja hållbarhet och minska elektroniskt avfall så är det av intresse att återanvända lågt värderade handelsvaror, såsom proteinrika restprodukter från industrin, till att skapa funktionella material för värdeskapande teknologier vilka är nedbrytbara efter användning. En välkänd restprodukt från köttproduktion är proteinet kollagen och dess hydrolyserade derivat gelatin. För att förbättra de mekaniska egenskaperna hos gelatin så kan det funktionaliseras med en polymer, vid namn Poly(Glycerol Sebacate)(PGS), som tidigare har använts för att skapa substitut till biologisk vävnad och batteriinkapsling. Denna reaktion genererar den nya polymeren PGS-G. I det här examensarbetet beskrivs karaktärisering av polymererna PGS och PGS-G, som utfördes med ATR-FTIR och DSC, samt karaktärisering av materialets mekaniska och hydrerande egenskaper men även dess ledningsförmåga och nedbrytbarhet. Resultaten indikerar att polymererna PGS och PGS-G ej bör tvärbindas fullständigt för att uppnå optimala mekaniska egenskaper med avseende på flexibilitet men också att tvärbindningen ska justeras beroende på tillämpningen. Vidare bidrar inkorporeringen av gelatin i PGS till en ökad hydrofilicitet i PGS-G. Slutligen visades det att PGS är lämpligt för inkapsling medan PGS-G kan användas som en aktiv komponent. Innan tillämpning behöver ytterligare studier genomföras med avseende på nedbrytbarhet, dels in vivo, dels i aerobiska förhållanden, för att säkerhetsställa att polymererna är fullständigt nedbrytbara.

La bioélectronique est un domaine interdisciplinaire qui étudie les interconnexions et les interactions entre entités biologiques (cellules, tissus, organes) et systèmes électroniques,par l’intermédiaire du transducteur adéquat. Pour des cellules ou des tissus excitables (neurones, muscles, ...), le transducteur prend la forme d’une simple électrode, car ces tissus produisent une activité électrique spontanée ou, dans le sens inverse, peuvent être excités par un signal électrique externe. Cette communication bidirectionnelle donne lieu à deux schémas expérimentaux : l’acquisition et la stimulation. L’acquisition consiste à enregistrer, traiter et analyser les bio-signaux alors que la stimulation consiste à appliquer le courant électrique adéquat aux tissus vivants, pour déclencher une réaction. Cette thèse se concentre sur ce dernier point : deux générations de système de stimulation ont été développées, chacune basée sur un circuit intégré spécifique et adaptée à différents contextes applicatifs.Tout d’abord, le cadre scientifique a été celui du projet CENAVEX, axé sur la stimulation électrique fonctionnelle pour réhabiliter la fonction respiratoire, suite à une lésion de la moelle épinière. Ensuite, les objectifs de conception ont été étendus pour couvrir de nouveaux besoins d’application : la surveillance de l’impédance électrique in situ et l’exploration des formes d’onde de stimulation originales. Le premier pourrait être une solution pour suivre la réaction tissulaire après l’implantation d’une électrode, contribuant ainsi à la biocompatibilité à long terme des implants ; le second propose d’aller au-delà dela conventionnelle impulsion biphasique carrée et d’explorer de nouvelles formes d’ondes qui pourraient être plus efficaces en termes de consommation d’énergie, pour un effet physiologique donné.Le travail présenté dans ce manuscrit contribue à la conception, à la fabrication et au test de dispositifs de stimulation innovants. Cela a conduit au développement de deux circuits intégrés et de deux dispositifs de stimulation permettant une stimulation multicanal.Les caractérisations électriques et les validations biologiques, de la faisabilité in vitro aux expériences in vivo, ont été menées et sont décrites dans ce manuscrit. / Bioelectronics is a cross-disciplinary field that studies interconnections and interactions between biological entities (cells, tissues, organs) and electronic systems, using the adequate transducer. For excitable cells or tissues (neurons, muscles, . . . ), the transducer takes the form of a simple electrode, as these tissues produce a spontaneous electrical activity or,in the opposite way, may be excited by an external electrical signal. This bi-directional communication gives rise to two experimental schemes: acquisition and stimulation. Acquisition consists in recording, processing and analyzing bio-signals whereas stimulation consists in applying the adequate electrical current to living tissues in order to trigger a reaction. This thesis focuses on the latter: two generations of stimulation systems have been developed, both being centered on an Application Specific Integrated Circuit, and adapted to different application contexts. First, the scientific framework was given by the CENAVEX project, focusing on Functional Electrical Stimulation to rehabilitate the respiratory function, following a Spinal Cord Injury. Then, the design objectives were extended to cover new application needs:in situ electrical impedance monitoring and exploration of original stimulation wave forms.The first one could be a solution to follow the tissue reaction after electrode implantation,hence contributing to long-term biocompatibility of implants; the second one proposes to go further the conventional constant biphasic pulse and explore new wave forms that couldbe most efficient in terms of energy consumption, for a given physiological effect.The work presented in this manuscript is a contribution to the design, fabrication and test of innovative stimulation devices. It leaded to the development of two integrated circuits and two stimulation devices permitting multichannel stimulation. Both electrical characterizations and biological validations, from in vitro feasibility to in vivo experiments, have been conducted and are described in this manuscript.

La bioélectronique est un domaine transdisciplinaire qui oeuvre, entre autres, àl’interconnexion entre des systèmes biologiques présentant une activité électrique et le mondede l’électronique. Cette communication avec le vivant implique l’observation de l’activitéélectrique des cellules considérées et nécessite donc une chaine d’acquisition électronique.L’utilisation de Multi/Micro Electrodes Array débouche sur des systèmes devantacquérir un grand nombre de canaux en parallèle, dès lors la consommation etl’encombrement des circuits d’acquisition ont un impact significatif sur la viabilité dusystème destiné à être implanté.Cette thèse propose deux réflexions à propos de ces circuits d’acquisition. Une ces desréflexions a trait aux circuits d’amplification, à leur impédance d’entrée et à leurconsommation ; l’autre concerne un détecteur de potentiels d’action analogique, samodélisation et son optimisation.Ces travaux théoriques ayant abouti à des résultats concrets, un ASIC a été conçu,fabriqué, testé et caractérisé au cours de cette thèse. Cet ASIC à huit canaux comporte doncdes amplificateurs et des détecteurs de potentiels d’action analogiques et constitue le principalapport de ce travail de thèse. / Bioelectronics is a transdisciplinary field which develops interconnection devicesbetween biological systems presenting electrical activity and the world of electronics. Thiscommunication with living tissues implies to observe the electrical activity of the cells andtherefore requires an electronic acquisition chain.The use of Multi / Micro Electrode Array leads to systems that acquire a large numberof parallel channels, thus consumption and congestion of acquisition circuits have asignificant impact on the viability of the system to be implanted.This thesis proposes two reflections about these acquisition circuits. One of thesereflections relates to amplifier circuits, their input impedance and consumption; the otherconcerns an analogue action potentials detector, its modeling and optimization.These theoretical work leading to concrete results, an ASIC was designed,manufactured, tested and characterized in this thesis. This eight-channel ASIC thereforeincludes amplifiers and analogue action potentials detector and is the main contribution of thisthesis.

The aim was to develop a sensing platform on the base of organic electrochemical transistor (OECT). The focus was on the preparation of proper electrode system and on optimalization of properties of thin layer of organic semiconductor. As a base, commercial glass substrates with integrated indium-tin oxide electrodes were chosen. Thin layers were prepared from organic semiconductor poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) by spin-coating. Four formulations of material were studied. Layers with different thickness were prepared and the dependence of transconductance on the thickness of the layer and ratio of width and length was observed. The degradation of electrode system was solved by galvanic plating with gold. Attention was also paid to modifications to PEDOT: PSS. It has been found that the optimal layer thickness for use in sensors is approximately 150 nm. By reducing the series resistance by using a silver paste, the transconductance of 23 mS was obtained for the Ink 2, for the Ink 3 the transconductance was 44 mS. Sensoric platforms with these transconductances can be used for detection of physiological functions of electrogenic cells, e.g. cardiomyocytes.

An unresolved problem in research in the field of bioelectronics is the connection between the electrical signals coming from different parts of the cell, and the processes occurring within cells. In this regard, the aim of this work was the development of the method of dynamic speckle interferometry, which allows to determine the parameters characterizing the physical processes in different parts of a single cell. Object of research is living L-41 cell culture in the form of defrosted cells precipitated on a glass substrate. Literature review on the use of cell cultures in the bioelectronic field, methods cell culture studies conducted. Optical properties of cells are shown. The theory of the method of averaging in dynamic speckle interferometry is briefly considered. Speckle interferometric installation allowing at high optical magnifications to analyze intracellular processes assembled, adjusted and tested. Attestation of samples carried by optical microscopy. Dependences of the time average digital value of the intensity from pixel number and the time inside the cells are obtained. Dependences of the correlation coefficient of speckle imaging from time for different parts of the cell found. It is shown that the method allows to detect the difference in the processes occurring in the nutrient solution (outside cells) and in cells and also in different parts of the cell. / При исследованиях в области биоэлектроники нерешенной проблемой является установление связи между электрическими сигналами, идущими из разных частей клетки, и процессами, происходящими внутри клетки. В связи с этим, целью работы являлось развитие метода динамической спекл-интерферометрии, позволяющего определять параметры, характеризующие физические процессы в разных частях одной клетки. Объектом исследований являлась живая клеточная культура Л-41 в виде размороженных клеток, посаженных на стеклянную подложку. Проведен литературный обзор работ по использованию клеточных культур в области биоэлектроники, методам исследования клеточных культур, приведены оптические свойства клеток. Кратко рассмотрена теория метода усреднения в динамической спекл-интерферометрии. Собрана, налажена и апробирована спекл-интерферометрическая установка, позволяющая при больших оптических увеличениях анализировать процессы, происходящие внутри клеток. Проведена аттестация образцов методом оптической микроскопии. Получены зависимости среднего по времени цифрового значения интенсивности от номера пикселя и от времени внутри клетки. Для разных участков клетки найдены зависимости коэффициента корреляции спекловых изображений от времени. Показано, что метод позволяет обнаруживать различие в процессах, происходящих в питательном растворе (вне клетки) и в клетке, а также в разных частях клетки.

D. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology. / In this study, few layer graphene (Gr) and heteroatom graphene (HGr) were synthesized by chemical vapour deposition (CVD) method. Acetylene gas was used as carbon source for the synthesis of graphene, while a mixture of nitrobenzene and dichloromethane (ratio 1:1) were used as both carbon and dopant sources for the synthesis of the heteroatom graphene (HGr). A mixture of argon and nitrogen gases were carefully combined and used as carrier gasses and purge for both the synthesis of graphene and the synthesis of heteroatom graphene. X-ray diffraction (XRD) characterized showed that the as synthesized materials were crystalline materials, Raman spectroscopy indicated that the synthesized materials consist of sp2 hybridized carbon atoms, while scanning electron microscopy (SEM) and atomic force microscopy (AFM) results showed that the synthesized materials possess regions of 2 to 7 nm of thickness. Transmission electron microscopy (TEM) characterization also showed that the synthesized heteroatom graphene possesses about 5 to 7 layers with about 2 nm thickness, and x-ray photoelectron spectroscopy (XPS) result showed the presence of nitrogen, oxygen and chlorine in the lattice of the synthesized heteroatom graphene while the synthesized material still retained about 80% sp2 hybridization. The synthesized materials were used in the fabrication of modified bioelectrodes for electrobiocatalytic biosensing of glucose and hydroquinone. The fabricated bioelectrodes were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The CV characterization showed a diffusion-controlled electrode processes in al modified electrodes, while the EIS characterization showed the presence of both diffusion controlled and kinetic controlled impedance at the electrode-electrolyte interface. The fabricated GC/PEDOT-PSS/HGr/Lac modified bioelectrode exhibited a kinetic controlled impedance of 3150 Ω, while the fabricated GC/PEDOT-PSS/Gr/Lac modified bioelectrode exhibited a kinetic controlled impedance of 4138 Ω. Chronoamperometric experiments showed that the fabricated bioelectrodes exhibited swift electrobiocatalytic activity towards glucose and hydroquinone sensing respectively for graphene and heteroatom graphene. The graphene modified bioelectrode exhibited a linear response of 0.2 to 9.8 mM glucose concentration and a sensitivity of 87.0 μA/mM/cm2, while the heteroatom modified bioelectrode also exhibited a swift response to step by step addition of hydroquinone with a limit of detection of 2.07 μM and dynamic range of 2.07μM to 2.97 mM, thus indicating the tremendous potential of the materials in a wide range of electrobiocatalytic and bioelectronics applications.