Cervical Vagus Nerve Stimulation (CVNS) has shown efficacy in treating depression, therapy-resistant epilepsy, and is being explored for conditions such as obesity and migraine. The side effects of whole nerve stimulation, which is currently the only approved method, can be minimized using spatially selective stimulation. This thesis introduces Temporal Current Steering (TCS), a novel stimulation technique aimed at enhancing spatial selectivity for CVNS. TCS introduces a temporal variation to standard current steering, creating an electric field that varies both temporally and spatially. With this study, enhanced spatial selectivity was confirmed through simulations of extracellular stimulation of neurons with time-dependent waveforms on two electrodes located on a single plane. Particle swarm optimization was employed over 2000 iterations and 98 runs to identify a waveform with the highest spatial selectivity. The optimal solution achieved a 30% improvement over a single electrode placed directly in line with the target and a 31% improvement over the standard direct current steering technique, simulated in the same model. The findings of this thesis suggest that TCS can increase spatial selectivity in invasive stimulation, although further simulations are needed for non-invasive applications with greater electrode-to-neuron distances.

Micropumps are essential for providing controlled fluid dynamics in Organ-on-a-Chip (OoC) devices. Additive manufacturing builds up prototypes in several hours with a free-geometry advantage. Therefore, this master's thesis investigates the utilization of additive manufacturing to produce a micropump with a flowrate in the range of several $\mu l/min$ for OoC applications. A ball valve-based piezoelectric micropump was fabricated with a mSLA 3D printer. This micropump generates unidirectional flow through the reciprocating motion of the piezoelectric actuator and the movement of a ball within the conical channel. The virtual mass due to the inertia of the fluid inside the chamber shifts the resonance frequency of the piezoelectric actuator from the 1600 Hz to 43 Hz. The maximum flow rate of $26.5 \mu l/min$ was generated when the applied sinusoidal voltage was 240 Vpp at 5Hz and the maximum back pressure of 36.5 mbar was obtained under this power supply. These results confirm that additive manufacturing provides a promising option for miniature pump manufacturing.

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

Transcranial direct current stimulation (tDCS) is a noninvasive technique, allowing for the reversible modulation of activity in particular brain regions. TDCS has obtained much scientific interest and it promises many potential benefits to the patients.

However, tDCS that is performed today is almost the same with the method that was used 20 years ago (applying 2 mA current, during a 20 min session, using two large surface sponge electrodes). The tDCS module of the future must be characterized by increased portability, battery life and focality.

Many commercially available devices have very low power efficiency, leaving space for the design of low power consumption tDCS devices. Power efficient tDCS modules will also need lower battery capacity and thus lighter batteries, increasing the portability of the system. Regarding focality, there is increased interest from the researchers and physicians for multichannel devices that use small diameter electrodes. These devices can increase the focality and the accuracy of the delivered currents offering more targeted therapies.

In this thesis, the realization of a novel, low power, multichannel stimulation module, made with discrete components, which uses the ultra high frequency (UHF) technique for tDCS applications is implemented. With this approach, the technological benefits of the UHF stimulation technique, regarding increased multichannel power efficiency, are derived, combined with a cost effective, low scale production method. Moreover, contrary to previous integrated circuit (IC) realizations, current control feedback is added to the system.

In this thesis, three prototypes are fabricated, with the last one being an eight channel module that can be supplied from a 3.5 V battery and has a very linear relationship between the selected DAC’s codes and the output delivered current and, at the same time, being able to stimulate a wide range of loads (0.148 - 10.11 kΩ) up to 2 mA. Furthermore, the employed novel boost technique shows 40.57% maximum improvement of the power efficiency, compared to the use of a conventional buck-boost converter. Moreover, the feedback system shows significant robustness, achieving only 7.6% output current divergence for 6731% change of the output load’s impedance. The module has 4 μΑ resolution, which is translated to 0.2% of the maximum delivered current. Except from the high resolution, the system also has a fast transient response, which is less than 2.1 ms. Additionally, when one channel is active, the stimulator shows 43.84% maximum power efficiency. The aforementioned power efficiency is 23.49% higher than the maximum efficiency of state of the art adaptive voltage current source implementations. Additionally, the multichannel system was tested in real life scenarios and its efficiency was compared to a fixed voltage current source module. The system achieved 37.57%, 45.47% and 11.59% power efficiency improvements for two, four and eight channels respectively.

Hence, a novel, multichannel module, with current feedback, is created that offers both high accuracy and improved multichannel power efficiency. The proposed system offers significant benefits compared to the existing solutions. Therefore, the system can be used for future implementations of power efficient multichannel tDCS devices.

Optogenetics is a biological technique that uses light to control cells in living tissues, typically neurons, that have been genetically modified to express light-sensitive ion channels. Using this technique, neuroscientists can investigate the neural circuits underlying neurological diseases with a higher spatio-temporal resolution when compared to other known neuromodulation methods.

As employed today, optogenetics requires methods for guiding sufficiently strong and precisely timed light to specific brain regions, while the experimental subject carries out behaviors of interest. For this role, miniaturized devices (namely optrodes) shall be properly engineered to hold the required components (e.g. light source, recording electrodes, etc) whilst complying with some surgical and biocompatibility issues.

In this work, an optrode was designed and fabricated using an in-house MEMS microfabrication technology. The custom-made device featured (a) low impedance level with TiN-coated microelectrodes, (b) sufficient optical power delivery through on-chip-uLEDs, and (c) miniaturized dimensions with tolerable tissue damage during long-term animal experiments. In addition, different optrodes were fabricated to allow different experiment conditions (i.e. chronic or acute implantation, multi-site or multi-layer studies). A MEMS cavity for the on-chip-uLED was engineered on the optrode's shaft in order to further minimize the induced tissue damage during the surgical implantation. Last but not least, this customized optrode is also compatible with our in-house CMOS technology and can be further upgraded with additional electronic functionalities, as well as with the deposition of novel materials.

After the microfabrication and system integration, in-vitro experiments on three different designs were performed to characterize electrically the electrode impedance, the control of uLED's light intensity and pulse frequency.

Close collaboration between the Bioelectronics department at Delft University of Technology and the Neuroscience department at the Erasmus Medical Centre has resulted in a successful tethered design for a real-time epileptic seizure detection and suppression method for mice. The goal of the Neuromate project is to develop this method into a wireless setup containing group-housed freely moving and interacting mice for use in behavioural studies. The system will include continuous monitoring and stimulation at set points in time. The Neuromate project comprises three links, two of which have previously been established.

The main goal of this study was to find and evaluate a technique to complement the current Neuromate project with a wireless downlink, channelling the communication from the researchers towards the mice.

This new downlink should fit in the ongoing project and meet particular specifications. The most critical requirements are that it should be lightweight and small-scale and should allow simultaneous multi-user communication. Also crucial are the prevention of interference with the two other links, reliability and low power consumption. The three most promising techniques, power source keying, optical wireless transmission and terahertz torching are elaborated.

Terahertz (THz) torching, covering the high thermal part of the THz band (10 to 100 THz), was chosen as the technique to be developed in this thesis. This decision was based on the fundamental limitations of power source keying and optical wireless transmission, which appear in the weighted criteria evaluation of the requirements. The challenges of THz torching are mainly practical, while fundamentally it provides the opportunity to form a reliable non-interfering wireless link. The feasibility of THz torching for our specific application was tested by creating a proof-of-principle and conducting five different experiments.

The prototype includes two components. The first is a thermal source, which in the final design will be placed above the cage, and the second is a pyroelectric detector, which will later be positioned on top of the head module of each of the mice. During the experiments, communication with the recently developed THz torch was proven to be feasible. Experiment 1 resulted in an optimum data rate of 35.71 bps, allowing for the simultaneous stimulation of the mice. And the divergence of the source was sufficient to cover the entire cage, as it was found in experiment 3 that an angle of 50° was the maximum misalignment still allowing reliable transfer of the data. However, the prototype did fail to reach the required distance. In experiment 2 only 8 cm could reliably be bridged. The source was not strong enough to overcome the attenuation in the air. A more powerful source will allow an increased reachable distance, making sure the entire cage is covered.

In this work, an innovative and promising proof-of-concept has been realized for the wireless downlink of the Neuromate project.