In the emerging research field of bioelectronic medicine, it has been indicated that neuromodulation of the Vagus Nerve (VN) has the potential to treat various conditions such as epilepsy, depression, and autoimmune diseases. In order to reduce side effects, as well as to increase the effectiveness of the delivered therapy, sub-fascicle stimulation specificity is required. In the electrical domain, increasing spatial selectivity can only be achieved using invasive and potentially damaging approaches like compressive forces or nerve penetration. To avoid these invasive methods, while obtaining a high spatial selectivity, a 2 mm diameter extraneural cuff-shaped proof-of-concept design with integrated Lead Zirconate Titanate (PZT) piezoelectric ultrasound transducers is proposed. For the development of the proposed concept, wafer-level microfabrication techniques are employed. Moreover, acoustic measurements are performed on the device, in order to characterize the ultrasonic beam profiles of the integrated PZT-based piezoelectric ultrasound transducers. A focal spot size of 200 μm by 200 μm is measured for the proposed cuff. Moreover, the curvature of the device leads to constructive interference of the ultrasound waves originating from multiple piezoelectric ultrasound transducers, which in turn leads to an increase of 45% in focal pressure compared to the focal pressure of a single piezoelectric ultrasound transducer. Integrating piezoelectric ultrasound transducers in an extraneural cuff-shaped design has the potential to achieve high-precision ultrasound neuromodulation of the Vagus Nerve without requiring intraneural implantation.

Demand for high density, high bandwidth, and low power Integrated Circuits (ICs) is rapidly increasing even as Moore's Law is starting to plateau. Among the new wave of technologies that are meant to continue the prevalent trend of semiconductor device scaling, 3D System Integration promises many advantages over traditional single-planar designs. This technology enables designers to stack multiple dies and unlock new functionality by reducing the footprint of the final device package. Using 3D Integration, multiple different types of chiplets (Digital IC, Analog IC, MEMS) can be integrated into a single package, potentially bypassing an expensive move to a newer process node and unlocking even more functionality from the same package. These downscaling issues are not limited to traditional CMOS technologies but extend to Quantum Computers. Due to the highly heterogeneous nature of Quantum ICs, and especially their requirement of low qubit decoherence noise, we require high-density connections from the Qubit layer to the Microelectronics Control layer while maintaining appropriate spacial separation between the two. In this project, the qubit layer is comprised of Diamond Colour Centers in a Photonic IC with other optical components such as SNSPDs, and MEMS switches. On the other hand, the microelectronics control layer is a Cryogenic CMOS chip. The main goal of this project is to design an Interposer and related technologies like Through Silicon Vias (TSVs) and Microbumps to successfully integrate these two chiplets in a single 3D assembly. We conduct thermal analysis of multiple 3D assembly designs using Finite Element Modelling to derive optimum fabrication specifications. Subsequently, fabrication recipes are developed and optimised for TSV etching, coating, and patterning with superconductive sidewall liners. Recipes are also developed to fabricate Indium Microbumps using techniques like evaporation, liftoff, and atmospheric reflow. Utilizing these microbumps, we conduct cold-compression flip-chip experiments. Finally, we establish cryogenic measurement setups to electrically characterize these fabricated devices.

This document reports details the development of a solid stool detection system. On behalf of Momo Medical - a TU Delft-based startup company - a device for detecting defecates by elderly people has been designed. The goal of the detection system is to detect solid stools by elderly patients wearing a diaper and to notify the nurses in a nursing home accordingly. The project has been organized and conducted in two groups: Hardware & Software. Our group has been in charge of the hardware. The other group has been responsible for the software. The main focus in this report will be the hardware design of the system. This report contains: the analysis of the problem, the development of a solution, the design and the evaluation of the device in test. The developed device detects methane by means of multiple gas sensors, since methane is the main gas component released while defecating. Several iterations making a suited printed circuit board and case have been carried out, while taking aspects like safety, reliability and noise performance into account. The report concludes with a summary of main results and an outline of future work.

Ultrasound (US) neurostimulation, the non-pharmacological, reversible excitation or inhibition of the nervous system using ultrasonic waves, is emerging as a high interest topic in neurostimulation research. In the current project, an attempt was made to demonstrate US neuromodulation in a Lumbricus Terrestris model of evoked compound action potentials (eCAP). Hardware and software for the electrophysiological observation of local field potentials were designed and assembled. The resulting system was used to perform mechanical, electrical and both direct and indirect ultrasonic neurostimulation experiments. It was shown electrical stimulation could be performed reliably in-vivo and ex-vivo. Mechanical stimulation only functioned in-vivo. Additionally, power transfer experiments showed that deeply embedded CMUT devices can be used to harvest acoustic power and use this signal to stimulate an explanted Lumbricus Terrestris medial nerve cord. Direct ultrasound neurostimulation was however not observed, likely due to a combination of misalignment and incorrect acoustic pressure profiles. As an additional project, a microfabrication step was designed and performed for the etching of high aspect-ratio silicon bulk structures for the backside venting of low frequency CMUT devices. A two-step process deep reactive ion etch (DRIE) was attempted where smaller features were first introduced into the silicon (phase A) and then advanced using a larger etch frame (phase B). It was shown that phase A etching could be performed adequately, resulting in high quality deep silicon etch profiles with minimal tapering and an excellent etch rate. However, phase B etching resulted in the consumption of side-walls and removal of previously etched features. It is likely some slight adjustments to the passivation stage of the DRIE process would result in successful completion of this fabrication step. Acknowledgements

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.

Atrial fibrillation (AF) is the most commonly occurring arrhythmia in clinical practice and can have a significant impact on the current and future wellbeing of the patient. By placing an unipolar sensor array directly on the epicardium during an open-heart surgery to measure the electrical activity of the atrium, more insight about this disease can be obtained. One method to obtain these insights is by applying common signal processing models to the measured electrogram (EGM). This thesis further investigates this application and argues why the most common array processing signal models are fundamentally incompatible with this application and proposes two different signal models to rectify the identified discrepancies. The proposed signal models are subsequently analyzed and the conclusion is drawn that both novel signal models better fit the EGM signals, but one signal model in particular shows promising results. This potential is exemplified by using this signal model to formulate a novel LAT estimation technique that can compete with state of the art LAT estimation methods in terms of estimation accuracy and execution time. This result shows the potential of the proposed signal model and opens the door to explore more applications in the future.

Cardiorenal Syndrome (CRS) is a multi-organ disease characterized by a reciprocal pathological interaction between the heart and kidneys during acute or chronic injury. Yet, a complete understanding of the underlying bi-directional pathophysiological mechanisms is lacking, hence obscuring effective diagnostic strategies, patient stratification and adequate administering of intervention therapies. Thus far, CRS has only been modelled in in vivo animal models, which are inherently limited in terms of experimental control and translatability of results to humans physiology. This underlines the need to develop more advanced in vitro models that accurately recapitulate the complex inter-organ cross talk responsible for the onset and progression of CRS. However, to date no such disease model system has been reported. This project set out to design, develop and validate a microfluidic set-up, which would then enable the investigation of CRS in a three-dimensional environment. To that end, a theoretical framework covering all aspects related to Multi-Organ-On-Chip (MOoC) design was developed. This framework then formed the foundation for an extensive list of requirements to establish an ideal microfluidic set-up for a heart-kidney disease model. Various conceptual circuit designs were proposed and evaluated on the basis of the set requirements and their associated priority. By executing feasibility studies, simulating computational fluid dynamics, designing specific organoid inserts and eventually setting-up the proposed microfluidic circuits, a better understanding of the technological and biological challenges to be addressed was obtained. Proof-of-principle experiments were promising, but more experimental iterations with a focus on in-depth biological tissue characterization are required to further evolve and fully validate the proposed cardiorenal model. Pressing issues entail establishing physiologically relevant scaling ratios, reducing required medium volume and identifying the exact disease models to incorporate once the physiological organoid system is functional and has been validated.

This report details the software part of the development process of the eNose technology. The technology is posed by Momo Medical. Momo Medical is a start-up company located in Delft, it provides and develops non-intrusive monitoring systems in the nursing sector. The project is the next step in an already existing product: BedSense. BedSense enables nurses to check for among others decubritus, whether the patient is out of bed, and even if the patient has passed away. The finished project will be able to detect solid stool and hence, when integrated into the system of BedSense, will greatly assist the nurses. The eNose technology is able to detect solid bowel movement using its gas sensing abilities. It consists of gas sensors that detect the relevant gasses that are related to feces. These sensor values are then fed into an algorithm that is able to interpret them and detect defecation. Besides it includes a communication system that handles the internal and external communication. Finally, the technology supports Over The Air (OTA) updates which allows to update the firmware of the devices remotely. The final prototype functions accurately in certain restrooms and can be regarded as a proof of concept.However more work and data is needed in order to make the eNose work in various environments, with possible integration of machine learning analysis, as it has showed great potential. The project is executed in two groups, hardware and software. This report contains only the software part of the process. It includes the development of the detection algorithm. And the developmentof a communication and OTA programming system.

Pressure ulcers, also known as bedsores, are wounds that form when a person sits or lays in the same posture for an extended period of time. Continued pressure being applied to the same spot causes the skin to decay, possibly continuing into underlaying tissue if the wounds are not treated. A common and proven practice to prevent pressure ulcers from forming is to regularly change the posture of the patient, so that there is not too much pressure on any one part of the skin. Momo Medical is creating a sensor system to assist in preventing pressure ulcers. They already have a prototype using force-sensing resistor (FSR) and piezoelectric sensors to measure changes in posture of the patient. The prototype is able to detect if a patient has moved enough, whether on their own or by the nurses, to prevent pressure ulcers. The prototype works, but they need their system to be more reliable. The research in this thesis focuses on improving the piezoelectric sensors. Momo Medical uses the piezoelectric sensors to measure human bio-signals, mainly respiration and heart rate, through the mattress. Two different printed circuit boards (PCBs) were designed as test set-ups to be able to easily modify the amplifier to measure the piezoelectric sensors separately. Using these test set-ups two common piezoelectric sensors were compared, namely lead zirconate titanate (PZT) and polyvinylidene difluoride (PVDF) sensors. From this comparison it was concluded that the PVDF sensors consistently have a better signal-to-noise ratio (SNR), but that both the PZT and PVDF sensors were able to measure human bio-signals effectively. The PVDF sensors did showed even more promising results when using them in a different mechanical configuration. In the test set-up the amplifier was also changed to improve the read-out of the sensors. Multiple iterations on the amplifier design were tested. In the final design a non-inverting amplifier was chosen to decouple the amplification from the input impedance of the amplifier and a input impedance of 100MΩ was chosen. Because of the high input impedance in the final design the signal was dampened less and less amplification was needed, thus reducing noise.

This thesis treats designing and building a linear generator which is used to power the Battery Free Jogger Light. This harvester needs to be able to generate power from the movement of a jogger. This Battery Free Jogger Light is meant to be used by people while jogging in dark environments to improve their visibility and thus safety. The complete system consists of the energy harvester which is connected to a full-bridge rectifier. This full-bridge rectifier consists of two LEDs and two schottkydiodes. The bridge is connected to a voltage regulator which provides a constant voltage to a super-capacitor while the jogger is moving. After having the super-capacitor charged to a sufficient voltage level, the super-capacitor is able to power three other LEDs using a clocked-decade counter until the voltage level of the super-capacitor becomes to low. A MATLAB model is created to be able to optimise the parameters of the model to comply with the needs of the rest of the system. To this point the model is able to calculate the voltages which are induced in the harvester. Using the model, a prototype was designed and built which was able to deliver plenty of power to the circuitry of the device. A final prototype of the harvester is designed and built, the harvester is tested in combination with the rest of the system and the complete system is proven to be working.

Myocardial ischaemia induced by cardioplegia is the most prominent risk during open-heart surgery. To achieve adequate protection of the cardiomyocytes during surgery, the cardioplegia must arrive at all cardiomyocytes. Local obstruction can lead to regional ischaemia. For surgeons and perfusionist, the arrested heart is a black box. They know how much cardioplegia they are administering to the heart. However, they do not know if cardioplegia is reaching all cells. This work describes which parameters can be measured during cardioplegia induced cardiac arrest and compares the methods used in the literature to detect these parameters. Following this, it is the goal to create a proof-­of-­concept sensor for the detection of myocardial ischaemia. A literature review indicated that a fluorescent optochemical pH sensor has the most potential. To be able to develop a proof-­of-­concept, optical, chemical, and medical knowledge needs to be combined. This is necessary to map what is required and what is possible for optochemical in vivo sensing. First, a framework is designed and used to select the best technique and material suited for this project. In this framework, the medical requirements and the resources available are combined. As a result, this thesis work will use a dual wavelength pH­-sensitive fluorescent dye encapsulated in a biocompatible hydrogel. In preparation for the proof-­of-­conceptsensor, multiple samples are fabricated and extensively tested to achieve the optimal sensing layer. Using the optimised concentrations, a proof-­of-­conceptsensor is created using a miniature reflection probe and an USB spectrometer. This proof-­of-­conceptsensor shows that it can measure the changes in pH and can be corrected for multiple interferences. It also shows the potential to be further miniaturised and to be used during cardiac surgery. Before this can happen, chemical optimisation of the sensing layer is needed, and the consistency of the sensing layer needs to be improved. However, besides this, the work succeeded in selecting an optochemical sensing technique and material which shows the potential to be used in cardiac surgery

Until now parameter analysers for Organ-on-Chips (OoCs) have needed bulky multi-probe setups that do not fit in biological research labs. For this reason a bachelor graduation project was proposed to get one of the sensors designed by the Electronic Components, Technology and Materials group (ECTM) out of the lab and into the hands of potential end users. This thesis is one of three from that project, and describes the calibration and user interface components of the portable parameter analyzer that is developed for the OoC sensor. First, an analysis is performed on the amplifier design that was given with the sensor. The analysis showed that the biggest sources of error in the overall gain are the offset and gain error, while non-linearity was not significant. Therefore, a two-point calibration method was deemed sufficient for the amplifier calibration. It is performed by taking two reference voltages as input of the amplifier, and measuring the corresponding output. With those points the actual gain and offset voltage can be calculated and corrected in measurements. Because of circumstances it was not possible to test in a lab environment whether the amplifier and the two-point method would meet the requirements. Therefore a second calibration method is proposed, the `sweep' method. For each input voltage step the corresponding output voltage is measured. This mapping can be stored in memory, and any future measurement can be looked up to find the correct voltage. The sweep method can also be used with a slight modification of the current hardware in order to simply plot the gain of the amplifier, to verify that it is linear as intended. Because the portable parameter analyzer is operated remotely, there was a need to develop a communication protocol on top of the Bluetooth link, in order to allow for parallel development of the GUI and embedded software on the analyzer. Once the communication between GUI and analyzer was defined, it was also possible for the other group to calculate the power consumption of the communication module. Finally, a Graphical User Interface (GUI) needs to be developed that can interact with the analyzer (connect, change settings, retrieve data, etc.) and it should display and store the measured data. A framework called Qt is chosen for developing the GUI, and a graphical design was made. Two modules are implemented in the GUI: A Bluetooth scanner to connect to the analyzer, and a way to plot data from the analyzer.

In this thesis, the realization and qualification of an anechoic dome chamber for 5G antenna’s is discussed. As with audio, where no echoes or noise from outside is wanted when listening to music, when characterizing an antenna it must be prevented to get internal reflections or electromagnetic (EM) radiation from outside. For this reason, a measurement setup was simulated, using that setup, different absorbers were tested and characterized. And a Faraday cage shielding is designed and evaluated, to remove EM interference. To make the anechoic chamber physically possible, rebuilding the minidome was also required, so that the absorber and Faraday cage could be mounted on the inner wand of the dome. Eventually, a suitable test environment for 5G antenna’s is build. In the end, the assessment of the absorbing materials was completed, and the chamber achieved all requirements. Despite the space of improvement, the idea of building an anechoic chamber is successfully verified.

Problems in drug development and personalised disease treatments are the main impulse for the development of OoCs. At the Electronic Components, Technology and Materials (ECTM) group at TU Delft an OoC sensor has been developed and the design is now at a stage where a system can be developed to take the sensor out of the initial research environment, into a complete product that incorporates the sensor. In this thesis a design is proposed for a portable parameter analyser based around the STM32L4 microcontroller platform. It contains an instrumentation amplifier and a communication module to connect to an external device. A power consumption estimation is made for individual system components as well as for the system as a whole. From this it is concluded which components contribute the most to the power consumption and recommendations are made on how to decrease this power consumption.

Real-time cell culture media monitoring can be conducted by Organ-on-Chip (OoC) ion-sensitive floating-gate field-effect transistor based sensors (ISFGFET). A method of modelling the sensor is described and implemented in the Advanced Design System (ADS) design and simulation software. The model is validated using measurement data of the sensor when exposed to an aqueous solution and in a 'dry' scenario. The model is utilized for an overall sensitivity analysis and the effect of the sensor dimensions on the sensitivity to charge variation that are immobilized on the sensing area surface. In addition to a SPICE compatible floating gate, level 3 MOSFET parameters are extracted, along with a sensing area model that links changes in the floating gate voltage to changes in the pH of the solution. Subsequently, a bias point is determined based on measurement data and limiting factors. Finally, the sensitivity of the ISFGFET is analysed. Our results characterize the effect that the sensing area dimensions, control gate capacitance and bias point have on the sensitivity.

In the last few years organ-on-chip (OoC) has been emerging as a new method for more reliable research to screen the effects of new drugs on the body. This is a novel technology mimicking the in vivo environment of tissue cells, making it a more suitable candidate for experimentation than traditional 2D cell cultures. However, in order to ensure smooth and swift implementation of this technique, some issues must be addressed first. One of these issues concerns perfusion: most OoC devices require external equipment to provide the necessary dynamic flow that makes the OoC unique, so that cells experience continuous fluid shear and are perfused sufficiently. In this thesis a model of an on-chip electro-polymeric pump is designed for application on an OoC. From a background study the design aims are defined: a membrane actuated pump with a nozzle-diffuser channel providing pump action. The membrane is made from ionic polymer-metal composite (IPMC), a material that deforms under electric current which is produced at TU Delft with the intention to use it in OoC applications. Its low voltage operating range and its biocompatibility make it an excellent candidate for this. Furthermore, the nozzle-diffuser elements avoid the need for moving elements inside the channel, instead providing pump action based on a pressure gradient over the nozzle elements. Finally, three design aims are defined, being: high flowrate, high flow pulse and low flow rate and pulse applications, corresponding to various needs in the OoC field. A base model is designed using COMSOL Multiphysics software, using similar devices described in literature. The model consists of a combination of solid mechanics (for membrane movement), fluid mechanics (for flow movement) and a fluid-structure interaction module to combine the two. This model is then tested for a range of parameters, first independently and later in pairs. General conclusions drawn from these simulations include: - Between the membrane displacement and -frequency (which can both be varied after fabrication), the membrane displacement magnitude affects the output more significantly than actuation frequency - The membrane width is positively correlated with flow rate output and pulse amplitude - The channel depth is positively correlated with flow rate output, but only if the membrane displacement scales along with it - A long slender nozzle yields lower flow output than a short, squat nozzle - The results from this model are consistent with nozzle-diffuser theory, stating that nozzle resistance and membrane movement affect the flow most significantly. This leads to three designs according to the three application wishes expressed earlier. The pump is designed such that it can be manufactured on a silicon wafer using electronics cleanroom equipment. The combination with the process developed for IPMC provides a novel pumping mechanism that has the potential to fully integrate an important aspect of an OoC on-chip, greatly increasing user friendliness and allowing for wider implementation of this technology.

This document describes the design process and implementation of the lighting and casing of a battery free jogger light. This light is meant to increase the safety of joggers in dark environments. The most effective way of increasing the jogger's conspicuity will be researched by considering different light sources and driver circuits to efficiently power the light source in a blinking manner. A casing will be designed to encapsulate the components. Light emitting diodes were chosen as a light source due to their energy efficiency, colour optimisation and small size. Two LEDs are part of a rectifier, while three other LEDs are powered by a driver circuit that uses a clocked decade counter 4017 IC that receives its clock signal from a NAND based oscillator circuit. The casing is designed with 3D modelling software and a prototype is 3D printed. The intended light intensity was not reached, but the brightness in dark environments was deemed suitable for the project's goals. The casing has bigger dimensions than intended; however these can be optimised for mass production.