This thesis analyzes and describes a wearable pressure sensor to detect intraocular pressure and guide clinician diagnosis of glaucoma. Although glaucoma has many symptoms and risk factors, high intraocular pressure is the most predominant. A method to continuously and accurately record intraocular pressure measurements and fluctuations in a patient could lead to a more reliable glaucoma diagnosis and a better understanding of glaucoma progression. The proposed sensor consists of an ecoflex dielectric layer, between two graphene-silver nanowire spiral antenna electrodes which also act as the membrane structure. The sensor deflection depends on the intraocular pressure fluctuations; higher pressure leads to larger deflection values, therefore, larger capacitance change. The capacitance change leads to a shift of the resonant frequency, which is simulated in this thesis. The sensor must be smaller than 11 mm2 to fit on a commercial lens. Specifically, this thesis analyzes and simulates the effects of electrode thickness and shape on the overall performance of the sensor. The optimum geometry of the capacitive sensor is analyzed to maximize sensor sensitivity and quality factor, with a correlated frequency appropriate for a wearable lens. Using Computer Simulation Technology, the optimized antenna dimensions are spiral-electrodes with a plate thickness of 350µm, and 3 spiral revolutions; leading to an increase in sensitivity of 1.4 MHz/mmHg.

In vitro models are fundamental in the study of cell behaviour, the physiological function of organs, and their response to drugs and toxins. However, the shortage of accurate and reliable in vitro models calls for the development of in vitro lung models that better recapitulate lung physiology and pathology. Lung-on- a-chip models are promising to this end. To date, most membranes used in these models are made of poly(dimethylsiloxane), which has significant disadvantages. Moreover, there is a need to establish adequate membrane pore sizes throughout the cell culture duration. A design of a novel LOC membrane containing a dynamic membrane pore size to recapitulate the pulmonary alveolar-capillary barrier was designed and its viability evaluated. Poly(octamethylene maleate (anhydride) citrate) (POMaC) is evaluated as a membrane material on its cytotoxicity, biodegradability and imaging properties. For creating a thin and porous membrane, spincoating, moulding and 2-photon polymerization were studied. The results provide promising support for fabricating a thin membrane. It was concluded that thin, uniform POMaC layers and a conical micropillar mould could be created. Moreover, stiffness of POMaC was in the expected range, and the bioimaging properties were found to be suitable. The degradation results did not support the hypothesis that a structural pore size could increase, which likely impedes the increase of pore diameter necessary for immune cell transmigration. Therefore, a model of the degradation characteristics of POMaC is proposed.

The dorsal root ganglion (DRG) is an interesting target for neurosurgical pain treatments since it contains the somata of sensory neurons and is relatively accessible, just outside of the central nervous system. Current interventions, such as radiofrequency ablation or neurostimulation, target the DRG with rigid instruments, only tangenting the structure. The goal of this project was to increase the area of influence for neurosurgical instruments by expanding the contact area between the instrument and the DRG. A mechanical solution was designed, consisting of a pre-bend nitinol leaf spring and a rigid injection needle as delivery device. Multiple prototypes were made with various pre-bend diameters and tip shapes. The prototypes with a backbend at the tip and a pre-bend diameter of 5-6 mm were the most successful in curving around a phantom of the L5 DRG in an experimental setup. Future research is needed to incorporate treatment modalities such as neurostimulation and radiofrequency ablation into the mechanical design.

Organ-on-Chip (OoC) is a technology that aims to increase the efficiency of drug development processes and organ models by engineering well-defined cell culture environments. Physiological relevant mechanical, chemical, or electrical cues provide in vivo-like microenvironments for realistic cell maturation. Biodegradable technologies have gained attention for the development of novel OoCs by integrating transient features to the culture platforms imitating the ever-changing environment inside the human body. Current efforts to replicate durable brain tissue models from organoids are limited by the lack of sufficient vascularisation introducing cell necrosis inside the 3D cell culture. This report presents the design and fabrication of a 3D-printed OoC-platform that combines two independent cell protocols for a Vessel-on-Chip and a cortical brain organoid. The microfluidic chip is embedded with a biodegradable membrane, that separates the two cell cultures for a strictly defined time period. The membrane, composed of bayberry wax, lanolin, and carbonyl iron particles, enables the controlled opening via alternating magnetic field exposure. The thermal behaviour of the membrane is analysed with DSC and the magnetic particles with a SQUID magnetometer. Inductive heating experiments determine the optimal composite composition and exposure profile to facilitate membrane opening and subsequent communication between neural and vascular cells. The integrated membrane proved to be successful during the injection and evacuation phase. This positive result paves the way for co-culturing two inherently different cell protocols on a single chip. This master project lays the foundation for collaborative efforts towards vascularised brain organoids-on-chip and showcases the potential of additive manufacturing and biodegradable materials in OoC technology.

Atrial fibrillation (AF) is one of the most common heart diseases. Billions of people have suffered from it in the world. Although it can lead to terrible complications such as stroke and heart failure, the underlying mechanisms of it are still under-explored. Besides, there is no so-called optimal therapy for the patients. As the disease is progressive, it is important to detect it in an early stage. To develop methods for understanding and detecting AF, the interpretable parametric model can be an option. This model can provide physiological information at the signal level. In this case, the electrocardiogram, as the most commonly used invasive measurement of cardiac conditions, can be the data to model the heart structure and cardiac activities. This thesis proposes an interpretable parametric model based on P-waves extracted from the ECG signals. Specifically, the autoregressive (AR) model is implemented, which is also known as linear predicting coding (LPC). The goal is to model the atrium and understand the function of the atrium, which can reflect on the varying parameters in the SR and AF cases. In this context, The formant of P-waves is modeled and estimated, which is a representation of the atrium activities. In addition, the parameters of the model are mapped into 2-dimension by the zero-pole plots in order to interpret the differences between SR and AF situations. Based on the differences between parameters and formants, a parametric classifier of high interpretability is developed to detect AF. An alternating searching algorithm is proposed to determine the parameters of the classifier.

An exponential growth in the mobile communications industry over the past decade has raised concerns over it’s energy consumption, especially in light of the current climate crisis. 5G technologies in particular exhibit features that imply high power consumption, such as the densification of 5G base stations. Implementing mitigation measures requires accurate a priori knowledge of the power consumption of 5G array architectures in various scenarios; however, there are large gaps in the literature on this topic, and existing power consumption models for 5G array architectures only address a limited scope of use cases and array topologies. Recent works have focused on the energy efficiency of array architectures, but not on the actual amount of power being consumed. In this thesis, an integrated system-level power consumption model is devised for 5G base station multi-beam transmitter topologies and beamforming schemes, which accounts for the use cases and architectures missing from the literature. The model is then applied to novel use cases in the enhanced urban Mobile Broadband (eMBB) scenario to obtain the estimated power consumption per component, per array and per user for five different beamforming schemes. A thorough parametric analysis is conducted for the optimality and trade-offs of each use case. Recommendations are made on the optimal topology, beamforming scheme and front-end technology from a power consumption perspective. Initial results show that the choice of technology, architecture and topology can lead to an improvement in the per-user power consumption of 41-80%.

Hip replacement surgery, also termed total hip arthroplasty, is a surgical intervention intended to substitute a deteriorated or dysfunctional hip joint with an artificial prosthesis. This procedure is commonly indicated for individuals experiencing severe hip discomfort resulting from conditions like osteoarthritis, rheumatoid arthritis, hip fractures, or other hip-related issues that significantly impair mobility. Globally, more than 1 million total hip replacement surgeries are conducted annually. Given the substantial mechanical loads experienced by hip implants during regular activities, a thorough understanding and early identification of potential issues before implant failure are imperative. Continuous monitoring of strain is crucial to assess how the implant responds to various stresses over time. This monitoring aids in evaluating the implant’s durability and performance under diverse stress conditions, enabling proactive interventions, if necessary, to prevent critical failures. Strain monitoring acts as a diagnostic tool to assess the implant’s status and the surrounding tissues. Deviations in strain patterns may signify problems such as implant loosening, wear, or bone loss around the implant. Moreover, this monitoring technique helps customize rehabilitation programs and recommend specific activities based on individual strain levels. Consequently, this tailored approach enhances recovery outcomes while mitigating associated risks. This project involves the development of a passive wireless resonant circuit that will be used in the future in a sensor designed to detect strain on hip implants for early failure detection. The strain is anticipated to cause fluctuations in the frequency. To evaluate the LC (inductor-capacitor) resonator design at a specific frequency, a simulation model was established using the Computer Simulation Technology (CST) Microwave Studio as the simulation platform. The fabrication of this LC resonant circuit employs cleanroom techniques and protocols to ensure precision and reliability in its structure. Subsequent to fabrication, the resonator underwent characterization employing an antenna to ascertain resonance frequency alterations in accordance with theoretical expectations. The results indicated a detectable shift in resonant frequency corresponding to designs representing different strains.

Atrial Fibrillation (AF) is a cardiac arrhythmia that occurs due to the initiation of electrical impulses in the heart in an uncoordinated manner, giving rise to a disorganized and rapid heartbeat. The progression of AF over time can lead to complications such as stroke and heart failure. Catheter ablation is an established treatment protocol adopted to eliminate AF triggers and restore normal sinus rhythm in patients. To improve the success rates of ablation procedures, mapping and localizing the regions in the heart that give rise to uncoordinated impulses is crucial. This work focuses on obtaining a visual estimate of the location of irregular electrical activity within a volume domain of cardiac tissue using epicardial electrogram measurements. A straightforward, effective, and computationally fast backprojection imaging method is proposed that provides an indication of the regions in a given volume of cardiac tissue that exhibit prominent irregular atrial activity. The chosen volume is subdivided into non-overlapping voxels, and the standard electrogram signal model is discretized to a matrix multiplication form. The inverse problem of reconstructing the transmembrane current distribution in the volume is solved using the epicardial electrogram readings obtained from the surface and the inverse distances matrix containing the inverse of the distances from each electrode to each voxel within the volume domain. The generated backprojection images are visualized to estimate the location (x and y coordinate information) and depth of irregular atrial activity in the volume. To improve the accuracy of localization while maintaining the computationally fast nature of the proposed solution, Singular Value decomposition (SVD) of the inverse distances matrix is proposed for the transmembrane current reconstruction. The obtained visual estimates can guide ablation procedures, making them more targeted, and reducing the need for repeat ablation procedures due to AF recurrence.

Atrial fibrillation is a common cardiovascular disease, affecting the regular beating of the heart through chaotic contraction of the heart's upper chambers. On its own, the condition—increasingly prevalent among the elderly—is not life threatening, but it leads to an increased risk of stroke and heart failure. As of yet, there is no consensus on the physiological mechanisms responsible for initiating and sustaining atrial fibrillation. A more detailed view of cardiac activity would improve understanding of the disease, making earlier diagnosis possible and improving options for treatment. The contraction of the cardiac muscles is governed by electrical signals propagating through the tissue. Cardiac activity can be monitored with a high spatial resolution by measuring the electrical potential directly on the epicardium of the heart during open-heart surgery, using an array of closely spaced electrodes. From these electrograms, estimating the time of local activation of the cardiac tissue underneath each electrode provides a quantitative way of mapping the mechanisms of atrial fibrillation. Various methods exist to estimate the activation times, but the complex signals that are typical of atrial fibrillation make it difficult to obtain accurate results. This thesis proposes combining two existing methods for estimating the local activation times. Based on a model of the electrogram as a spatial convolution of local transmembrane currents, an inverse problem is formulated and solved, resulting in a less opaque view of the cardiac activity at the electrode locations by attenuating distant disturbances and emphasizing local activity. The deconvolution output is fed to the second step, where cross-correlating certain pairs of signals gives an estimate for the mutual time delay in local activation. A graph representation of the electrode array is used to define neighbor order and decide which signal pairs are correlated. The set of pairwise time delays this produces is then converted to an estimate for the local activation times, using a least-squares estimator. The proposed method is evaluated using different simulated cardiac settings. In a setting with one stimulation source, earlier results of the deconvolution and cross-correlation methods are confirmed, and the proposed method is seen to produce a slightly lower mean error than reference methods. In the higher-complexity triple-source setting, the latter effect is again visible. Reinforced by the performance of the different methods in increasingly noisy settings, the main merits of the proposed method for the estimation of local activation times can be said to be found in the form of increased consistency, not significantly improving on the accuracy of existing methods.

Organ-on-chip (OoC) is invented around 10 years ago which is used to do pre-clinical drug test without live animals. Physiological microenvironment of different cells can be mimicked in OoC. In order to better form of tissue in OoC, mechanical stimulation can offer through different ways including pneumatic, thermal, and electric stimulations. As another way to offer mechanical deformation, magnetic stimulation has high reacting speed and wireless operation.

Conventional techniques for audio monitoring, including Passive Audio Monitoring (PAM), often call for the use of environmentally unsustainable and challenging equipment. This among other limitations can disrupt the very environment that is meant to be studied and may also limit the ability to observe an ecosystem in its natural state. This thesis explores the possibility of a passive wireless biodegradable microphone for the purpose of audio monitoring in fragile environments. This project introduces the "The BioThing - A biodegradable microphone for monitoring biodiversity". The BioThing uses a biodegradable material, to address the current challenges of state-of-art monitoring techniques. The design utilises a resonant cavity to function as a listening device through the implementation of the backscatter wave modulation technique and with a primary working resonant frequency of around 1.7 GHz. This report presents a detailed analysis of the device's design and function to optimize its geometry for various frequencies, operational ranges, and functionalities by investigating the effect of critical parameters such as the variable capacitances namely the distance between the diaphragm and the tuning post, and the distance between the tuning post and the antenna. Additionally, it also analyses the effect of device geometry on resonance properties by investigating the impact of parameters such as tuning post height, membrane thickness, and cavity height. The report also investigates the possibilities for device enlargement for long-distance operation and device miniaturisation to facilitate faster degradation. This optimization process aims to achieve improved performance, ultimately leading to a more effective listening device. A prototype was fabricated using commercially available Zinc and plant-based resin. This research works towards a new generation of ecologically sustainable audio monitoring equipment that will allow a deeper insight into the soundscapes of fragile environments without disturbing the ecosystems.

Conventional techniques for audio monitoring, including Passive Audio Monitoring (PAM), often call for the use of environmentally unsustainable and challenging equipment. This among other limitations can disrupt the very environment that is meant to be studied and may also limit the ability to observe an ecosystem in its natural state. This thesis explores the possibility of a passive wireless biodegradable microphone for the purpose of audio monitoring in fragile environments. This project introduces the "The BioThing - A biodegradable microphone for monitoring biodiversity". The BioThing uses a biodegradable material, to address the current challenges of state-of-art monitoring techniques. The design utilises a resonant cavity to function as a listening device through the implementation of the backscatter wave modulation technique and with a primary working resonant frequency of around 1.7 GHz. This report presents a detailed analysis of the device's design and function to optimize its geometry for various frequencies, operational ranges, and functionalities by investigating the effect of critical parameters such as the variable capacitances namely the distance between the diaphragm and the tuning post, and the distance between the tuning post and the antenna. Additionally, it also analyses the effect of device geometry on resonance properties by investigating the impact of parameters such as tuning post height, membrane thickness, and cavity height. The report also investigates the possibilities for device enlargement for long-distance operation and device miniaturisation to facilitate faster degradation. This optimization process aims to achieve improved performance, ultimately leading to a more effective listening device. A prototype was fabricated using commercially available Zinc and plant-based resin. This research works towards a new generation of ecologically sustainable audio monitoring equipment that will allow a deeper insight into the soundscapes of fragile environments without disturbing the ecosystems.

Organ-on-a-chip (OoC) technology has revolutionized the biomedical research field by offering dynamic platforms which accurately mimic physiological environments of human tissue. This technology has become a promising option to study human biology in vitro, including disease modeling, drug screening and personalized medicine. Organoids, 3D cell cultures derived from human stem cells, represent a promising tool to investigate 3D tissue growth in vitro. However, integration of vasculature in these organoids remains a significant challenge. Establishment of vasculature is essential to enable significant organoid growth, allowing nutrient and oxygen supply and waste removal. This report aims to develop a Pluronic F127 based hydrogel as a transient barrier in an OoC-platform that combines cell cultures of Vasculature-on-a-Chip and cortical brain organoids. This transient barrier separates the two cell cultures until sufficient maturation of the cortical organoid. Due to thermoreversible gelation, the Pluronic F127 hydrogel barrier can be removed from the barrier channel by a decrease in temperature. Pluronic F127 and di-acrylated Pluronic F127 hydrogels were synthesizes and characterized using rheometry, differential scanning calorimetry and degradation testing to determine the optimal Pluronic F127 hydrogel. Simultaneously, optimization of the OoC-platform was done by fabrication of the platform using Polydimethylsiloxane (PDMS). It was shown that the OoC platform for Vascularized Organoids-on-a-Chip could effectively by fabricated using PDMS molding. This was achieved through both PDMS-PDMS and PDMS-glass bonding. Pluronic F127 hydrogels were shown to be a viable option to function as a transient barrier for Vascularized Organoids-on-a-Chip. Pluronic F127 hydrogels effectively blocked fluid flow through the barrier channel for seven days. To increase this time, di-acrylated Pluronic F127 was synthesizes. A degree of acrylation of 57% was achieved. This was shown to be insufficient to significantly increase the longevity of Pluronic F127 hydrogels. Further research needs to be done to find the optimal synthesis and photo-polymerization conditions of di-acrylated Pluronic F127 hydrogels. Ideally, di-acrylated Pluronic F127 hydrogels exhibit a low degradation rate while maintaining the thermoreversible properties of Pluronic F127 hydrogels.

Organ-on-a-chip (OoC) technology has revolutionized the biomedical research field by offering dynamic platforms which accurately mimic physiological environments of human tissue. This technology has become a promising option to study human biology in vitro, including disease modeling, drug screening and personalized medicine. Organoids, 3D cell cultures derived from human stem cells, represent a promising tool to investigate 3D tissue growth in vitro. However, integration of vasculature in these organoids remains a significant challenge. Establishment of vasculature is essential to enable significant organoid growth, allowing nutrient and oxygen supply and waste removal. This report aims to develop a Pluronic F127 based hydrogel as a transient barrier in an OoC-platform that combines cell cultures of Vasculature-on-a-Chip and cortical brain organoids. This transient barrier separates the two cell cultures until sufficient maturation of the cortical organoid. Due to thermoreversible gelation, the Pluronic F127 hydrogel barrier can be removed from the barrier channel by a decrease in temperature. Pluronic F127 and di-acrylated Pluronic F127 hydrogels were synthesizes and characterized using rheometry, differential scanning calorimetry and degradation testing to determine the optimal Pluronic F127 hydrogel. Simultaneously, optimization of the OoC-platform was done by fabrication of the platform using Polydimethylsiloxane (PDMS). It was shown that the OoC platform for Vascularized Organoids-on-a-Chip could effectively by fabricated using PDMS molding. This was achieved through both PDMS-PDMS and PDMS-glass bonding. Pluronic F127 hydrogels were shown to be a viable option to function as a transient barrier for Vascularized Organoids-on-a-Chip. Pluronic F127 hydrogels effectively blocked fluid flow through the barrier channel for seven days. To increase this time, di-acrylated Pluronic F127 was synthesizes. A degree of acrylation of 57% was achieved. This was shown to be insufficient to significantly increase the longevity of Pluronic F127 hydrogels. Further research needs to be done to find the optimal synthesis and photo-polymerization conditions of di-acrylated Pluronic F127 hydrogels. Ideally, di-acrylated Pluronic F127 hydrogels exhibit a low degradation rate while maintaining the thermoreversible properties of Pluronic F127 hydrogels.

Tissue vitality monitoring is a crucial process to preserve patients’ health during post-surgical recovery or to ensure full adaptation and healing of transplanted organs. Among the many local factors for vitality assessment, tissue oxygenation gives an insight into entire tissue recovery and is directly linked to cell metabolism. To be able to assess oxygenation at the cellular level, NADH fluorescence sensing is used due to its contribution to the cellular respiratory cycle and high sensitivity to oxygen concentration. The current devices for NADH fluorescence sensing are limited to external measurements, where they are suitable for hospital use. This raises the need for a device that is implantable and bioresorbable so that it can stay in the body after the surgery and does not require secondary surgery for removal that puts the patient at risk. The goal of this master’s thesis is to introduce the design of a bioresorbable optical filter and photodetector for the measurements of oxygen through the detection of NADH fluorescence. The design consists of an absorption layer, a Fabry-Perot filter, and a wavelength-specific photodetector; where the overall response is designed to have high sensitivity to the emission wavelength of NADH (470nm) and low sensitivity to the excitation of NADH (350nm). ZnO nanoparticles are chosen to be the absorption layer due to their high absorption properties to 350nm and biodegradability, where the optical response is then tested through spectroscopy measurements. For the Fabry-Perot filter, a design with SiO2 and SiNx layers has been created with simulation and tested with optical measurements. The complete design consists of 15 layers and has a total thickness of approximately 1μm. Lastly; for the photodetector, Spectra simulations have been conducted for the determination of the optimal design properties. The choices are then adapted to a mask design for the fabrication, in which the back side etching of the silicon wafer is required for biodegradability and optical performance. The fabrication of the photodetector has not been completed due to the time frame of the project. The measurements on the combination of ZnO and Fabry-Perot filter show that the transmission of 470nm is 2.5-4 times larger than the transmission of 350nm, which is expected to increase to at least an order of magnitude when combined with the photodetector. For future experiments, it is recommended to conduct more tests on the filters and ZnO to ensure repeatability and consistency.

Tissue vitality monitoring is a crucial process to preserve patients’ health during post-surgical recovery or to ensure full adaptation and healing of transplanted organs. Among the many local factors for vitality assessment, tissue oxygenation gives an insight into entire tissue recovery and is directly linked to cell metabolism. To be able to assess oxygenation at the cellular level, NADH fluorescence sensing is used due to its contribution to the cellular respiratory cycle and high sensitivity to oxygen concentration. The current devices for NADH fluorescence sensing are limited to external measurements, where they are suitable for hospital use. This raises the need for a device that is implantable and bioresorbable so that it can stay in the body after the surgery and does not require secondary surgery for removal that puts the patient at risk. The goal of this master’s thesis is to introduce the design of a bioresorbable optical filter and photodetector for the measurements of oxygen through the detection of NADH fluorescence. The design consists of an absorption layer, a Fabry-Perot filter, and a wavelength-specific photodetector; where the overall response is designed to have high sensitivity to the emission wavelength of NADH (470nm) and low sensitivity to the excitation of NADH (350nm). ZnO nanoparticles are chosen to be the absorption layer due to their high absorption properties to 350nm and biodegradability, where the optical response is then tested through spectroscopy measurements. For the Fabry-Perot filter, a design with SiO2 and SiNx layers has been created with simulation and tested with optical measurements. The complete design consists of 15 layers and has a total thickness of approximately 1μm. Lastly; for the photodetector, Spectra simulations have been conducted for the determination of the optimal design properties. The choices are then adapted to a mask design for the fabrication, in which the back side etching of the silicon wafer is required for biodegradability and optical performance. The fabrication of the photodetector has not been completed due to the time frame of the project. The measurements on the combination of ZnO and Fabry-Perot filter show that the transmission of 470nm is 2.5-4 times larger than the transmission of 350nm, which is expected to increase to at least an order of magnitude when combined with the photodetector. For future experiments, it is recommended to conduct more tests on the filters and ZnO to ensure repeatability and consistency.