For this Master thesis the possibility was explored to use a monolayer of graphene as conductive layer, instead of sputtered titanium nitride (TiN), on 25 nm thick aluminium oxide and magnesium oxide membranes. These membranes will be used in a new and faster variant of a vacuum electron multiplier (e.g. the Photo Multiplier Tube (PMT)). These membranes should act as transmission dynodes, or tynodes, where electrons are multiplied while interacting when they travel through the membrane and leave the membrane on the other side instead of being multiplied by hitting the surface of a dynode, where secondary electrons are released on the same side. These membranes are constructed using insulators and can charge up, as more electrons leave the membrane than enter. To circumvent this issue a conductive layer is applied on these membranes. The advantage to use graphene over TiN as conductive layer would be that the maximum transmission electron yield is higher and occurs at a lower incoming (primary) electron energy due to the reduced total thickness of the membrane. In order to get graphene on the membranes a wet transfer method of graphene was used where a layer of Poly(methyl methacrylate) (PMMA) was applied to support and the graphene sheet and to make it buoyant. The adhesion of graphene to alumina membranes proved to be very difficult and on many occasions the graphene was washed away during the removal of the polymer by acetone. The few remaining samples that were produced on both alumina and magnesium oxide membranes, where the conductive layer was successfully applied, had a lower transmission electron yield than the samples coated with a sputtered TiN layer. Sputtered TiN was used as conductive material in this project, before graphene was researched for this thesis. The reason for the lower yield is that the adhesion between the conductive graphene and the membranes was not good enough to conduct electrons vertically in the membranes causing them to charge up. One of the reasons for the poor adhesion is that the membranes are wrinkled and curved due to internal stresses that are caused by the production process. The graphene layer cannot follow these curves due to the way it is applied and only makes contact at the tops of the wrinkles. The primary electron energy, where the (lower) maximum yield was observed, was higher than samples with TiN, while the expectation was that graphene as the conductive layer would lower this energy, due to the reduced thickness. These observations lead to the conclusion that graphene is not a viable replacement for TiN as the conductive layer on these membranes. The use of TiN deposited by Atomic Layer Deposition (ALD) instead of sputtering was also tested. The samples produced with this method conducted electrons well enough to prevent charging effects in the membranes. The added benefit is that the TiN can be deposited with the alumina layer in a single ALD run and that its thickness can be controlled more precisely. The positive results make ALD TiN a viable replacement for sputtered TiN, but more research should be done to find the minimum thickness of this layer where it is still conductive enough to prevent charging of the membranes. In order to circumvent the abovementioned adhesion issues, a transfer-free method was developed to create graphene-alumina membranes, where the alumina was deposited on the graphene through ALD, instead of transferring graphene on the alumina. Since copper is used as a catalyst to grow the graphene, this put a lot of constraints on suitable wet etching techniques. This resulted in chemical baths where the temperature control was not ideal, which lead to much longer silicon etch times and loss of wafers. Near the end of the process a silicon oxide layer needed to be removed, but this step was most likely not performed correctly, leaving a thin layer of silicon oxide that blocked chemicals that should remove a deeper layer to release the membranes. Further testing of these samples fell out of the scope of this thesis and could be researched in the future. In conclusion, it is advisable to etch the silicon earlier in the process when the copper has not been deposited yet. In general the flowchart of this process needs a revision.

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.

With the increasing demand in home-care service to provide early intervention at the homes of seniors suffering from early stage dementia, the Smart Teddy prototype offers a technological solution to disburden caregivers, to promote and track the health and conditions of the senior and to prolong their independent life at home. The Smart Teddy is a project founded in 2018 by a research team of the Hague University of Applied Sciences. It is an interactive, companion robot - disguised as a toy dog - that serves as a therapeutic promoter while simultaneously monitoring the quality of life of the senior with pre-determined indicators. It consists of a Teddy to provide the interaction with the user and a Base Station for data processing and charging of the mount-in battery of the Teddy. The Power Operations and Distribution group carried out research on and developed suitable solutions to supply power to the Teddy with rechargeable batteries, to integrate controlled wireless charging of the battery for user-friendliness and to provide a streamlined power distribution throughout the Smart Teddy’s system. Based on an iterated program of requirements and a power budget analysis on the set of installed electronics, a design is implemented for the power system of the Smart Teddy. A design sequence is followed consisting of four stages: (1) battery selection, (2) charger selection, (3) power conversion and distribution, and (4) safety and failure protection. A power system is developed for the Smart Teddy that is able to supply power with lithium-ion batteries with a battery life of at least 12 hours providing a battery capacity of 25.16 Wh. Thereafter, the installed batteries located in the Teddy can be charged wirelessly by placing the Teddy on the Base Station (a dog bed) to reinforce the less robot-like and a more natural look of the Teddy. Furthermore, this system ensures that all electronic modules with different operating voltages and current draws are provided with the necessary power specifications through power-sharing paths and the usage of power converters. Lastly, safety measures and failure protection methods are developed to ensure the safety of the user through the usage of fuses, switches and, cable and PCB management. The design has been verified using the appropriate verification methods where the program of requirements is used as a guideline and assessment tool. The Power Operations and Distribution is largely complying with the program of requirements and is performing according to the predetermined functionalities. Consequently, the power system of the Smart Teddy is integrated in a real, spatial prototype, namely in a toy dog (the Teddy) and its dog bed (the Base Station).

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.

Modular quantum computer chip based on spin qubits in diamond will enable an increased connectivity, a high fidelity, and a low error-rate when the number of qubits increases. The high-quality diamond substrates have the maximum size in the order of mm2, preventing use of advanced semiconductor manufacturing line. Therefore, for a large-scale integration of qubits, there is a need for a wafer-scale diamond for scalable nanofabrication. Here, diamond-on-insulator structure will enable self-standing diamond structure by under-etching the insulator. Hydrophilic direct bonding of single crystalline diamond substrate on silicon is a promising approach. In this research, a process is developed and optimized for hydrophilic direct bonding of (100)-oriented diamond on a low-temperature deposited SiO2 on silicon substrate. The process condition involves treating a (100) CVD diamond substrate in a Piranha solution. A 300-nm-thick SiO2 is PECVD deposited on a (100) silicon wafer which afterwards undergoes a surface activation process by oxygen plasma. The two substrates were contacted in an ambient without applying pressure, cooled, and then annealed. It should be noted that there was no pressure applied during the annealing. By die shear testing, a strong shear strength was measured and further elongating the Piranha cleaning time provided more shear strength bonding.

Drug efficacy and side effects are significantly impacted by the first-pass metabolism, a sequence of events that occurs in the stomach and the liver after oral ingestion. Accurate prediction of this mechanism is crucial for a faster and more cost-efficient drug development process. Replicating the first-pass metabolism in vitro using standard cell culture techniques is challenging due to its complexity involving simultaneous transport and organ-organ interactions in both the gut and liver tissue. A more precise in vitro to in vivo translation of drug distribution, efficacy, and toxicity may be provided by organ-on-a-chip (OoC) models, thereby creating the ability to partially replace currently-used animal models. More specifically, gut-liver-on-a-chip models can aid with in vitro predictions of oral drug administration and the first-pass metabolism. Therefore, the aim of this thesis was to develop an OoC system that could accommodate both intestinal and hepatic cell sources. A hollow fiber membrane (HFM) as a cell scaffold was a critical component of the chip design in order to more accurately reproduce the three-dimensional native environment of the cells. Additionally, the system would need to exhibit the ability to be interconnected quickly and easily, thereby creating the possibility to develop a MOoC system in a plug-and-play manner in a later stage of development, enabling the ultimate realization of organ-organ interactions.

Airspeed information plays a crucial role in the takeoff, flight, and landing processes in animal flyers and aerial vehicles. Among the aerial vehicles, Flapping Wing Micro Air Vehicles (FWMAVs) represent the novel engineering approach of learning and mimicking animal flyers in the past two decades. A few prototypes of various sizes and functionalities of FWMAVs have been developed by MAVLab in the TU Delft Aerospace department since 2005. For these small and lightweight platforms, stable control under disturbances remains a challenge, and could further benefit from integrating effective airflow sensing into control system design. Current commercial products are either not suitable due to size, weight, and power (SWaP) restrictions of the drone platform, or have very limited low-speed sensitivity. Therefore, to facilitate this, this thesis aims to develop a MEMS-based capacitive airflow sensor for a miniaturized and low-power implementation. Inspired by the filiform hair structure of arthropods, the sensor design comprises two key parts: the hair structure, whose displacement is governed by the drag force induced by the incident airflow, and the sensing base, located at the hair structure's base, which translates the structural displacement into a change in capacitance. The sensor exhibits the capability to sense airflow in one dimension and can be further adapted for omnidirectional sensing. This thesis predominately focuses on the design and reliable fabrication of the sensing base. It is comprised of a suspended membrane supported by corner beams, supplemented by a pivoting dimple and anti-stitching dimples to facilitate robust hair movement and ensure optimal sensor functionality. The sensing base is fabricated at the TU Delft EKL cleanroom facility, equipped with sophisticated machinery that enables fabrication at micro and nano scales. Furthermore, the membrane suspension is achieved through the implementation of Vapor HF etching of a sacrificial layer beneath the membrane. In conclusion, the devised sensors aspire to optimize flight control for FWMAVs within the constraints of SWaP, by drawing profound inspiration from the intricate workings of nature.

Drug development is a complex, time-consuming (10 - 15 years) and expensive process. For a new medicine to reach the market, the net expenses covered by the pharmaceutical industry have been estimated to be around $2.6 billion. Nevertheless, the risk of finding adverse effects or toxicity cases once the drug is already on the market is still high. Thus, pharmaceutical companies have been keenly looking forward to means to eliminate this at an early stage of the development process. Recently, Organs-on-Chips (OOCs) emerged as a potential alternative to traditional drug screening. These devices, promise, in the middle-term, to enhance the in vitro screening and, in the long term, to reduce and eventually eliminate animal models in safety and efficacy essays. Nevertheless, the fabrication methods for most of these devices are hardly adaptable to scalable fabrication processes for in vitro screening application, as they rely strongly on manual techniques. This thesis demonstrates the successful development of diverse microstructures for Organ-on-Chip applications by using scalable IC and MEMS-based fabrication techniques. Chapter 3 demonstrates the development of microfabricated porous PDMS membranes for barrier modelling. A simple and reproducible method to fabricate and transfer porous PDMS membranes with a high control on pore size, porosity, thickness, is shown. Very thin (thickness <10 ¹m) porous membranes with small features sizes down to 2 ¹mand porosity up to 65% can thus be fabricated and successfully transferred with high reproducibility. The presented results on cell transmigration, topology and barrier formation demonstrated the biocompatibility of the porous PDMS membranes. Chapter 4 shows further efforts towards the realization of manufacturable OOCs. A monolithically microfabricated OOC device, an alternative to the available devices capable to address many more applications, was demonstrated. Preliminary biological experiments indicate its biocompatibility as cells (HUVEC, Cardyomyocites) are successfully cultured and maintained viable in the microchannels and the silicon cavity. Finally, Chapter 5 demonstrates other possibilities allowed by the use of IC and MEMS techniques. The integration of microstructures that enable transduction mechanisms to monitor the cell microenvironment, is shown. Specifically, strain gauges for stress sensing as an alternative to monitor in situ strain in microfabricated OOCs, are presented. Relative resistance changes of approximately 0.008% and 1.2% for titanium and polymeric strain gauges have been observed, respectively. The technological advances shown in this thesis form a significant contribution towards manufacturable fabrication of Organs-on-Chips and the standardization of OOCs as routinely used tools for drug development. @en