This master thesis investigates the potential of vector field stimulation as an innovative technique for enhancing visual cortex stimulation [1]. An algorithm was designed and implemented to evaluate this concept, utilizing COMSOL simulations to model the generated electric fields. The algorithm was validated using Green functions, which serve as analytical approximations to the Poisson equation solved in COMSOL. The interior point method was employed in the algorithm to minimize visual error [2], a concept introduced in the literature and adjusted to our problem. Results indicate that vector field stimulation improves targeted stimulation precision noticeably compared to traditional bipolar stimulation methods. Additionally, it was observed that incorporating the minimization of input current alongside visual error further enhanced the algorithm’s performance. Despite challenges such as numerical errors and the algorithm getting trapped in local minima, the findings highlight the need for future research to improve microstimulation techniques. This report emphasises the promising potential of vector field stimulation and the supporting algorithm in improving visual cortex stimulation.

In recent years, many therapeutic applications for medical ultrasound have arisen, such as ablation of tumors, breaking up kidney stones, and neuromodulation. To localize the target area, often ultrasound imaging methods are used. Conventionally, a different transducer array is used for imaging and therapeutic applications because of their conflicting requirements of transducer damping. If this damping would be done electronically, it can be switched on or off on demand, allowing a single transducer array to be used for both therapeutic and imaging ultrasound. This would allow medical ultrasound devices to be smaller and therapeutic treatments to have reduced overall system complexity. This thesis develops a PCB to compare a combination of existing and novel methods of electronic damping on a single transducer, also called electronic Q-factor control. A maximum damping of 23\% is achieved relative to the undamped transducer mounted on the PCB. This is achieved by a novel method based on a feedback loop around a second 'dummy' transducer. Methods of electronic Q-factor control should eventually be extended to be applied in an Integrated Circuit for damping of entire ultrasound transducer arrays.

The development of neural prostheses, especially those directly targeting the brain, requires extensive research and modelling before clinical trials can be performed. Currently, the resolution of artificial vision is not sufficient for everyday tasks. By studying the expected spatial extent of stimulation, we aim to provide insights to researchers that can be used to improve the resolution of artificial vision. The goal of this MSc thesis was to visualise the shape and intensity of electric fields in the cortex as a response to intracortical microelectrode stimulation to observe the expected regions of neuronal activation considering electrode design parameters. To do this, parameters that can influence the generated electric field and the regions of activated tissue have been defined. Implementing these parameters in a Finite Element Model (FEM) allows the computation of the generated electric field in 3D of a stimulating electrode to observe the spatial extent of activated tissue. The spatial extent of activated tissue can be estimated using simplified methods such as the activating function (AF) or current density threshold. The result is a parameterised framework that creates a Visualisation of Neuronal Activation (VoNA) that can be used to assess activated tissue regions for varying scenarios by defining material properties and dimensions of the model, and allows for the adjustment of the stimulation configuration, electrode contact spacing, customisation of electrode size and modulation of stimulation current. It enables the user to tune the model settings towards their specific needs and explore the possibilities by visualising the results from different angles by defining subsets of the entire solution. In line with expectations, the presented models show that the model parameters can influence factors such as the generated electric field, the current density and electric potential, which are indicators of neuronal activation. The findings support the hypothesis that these parameters should be considered during electrode design to achieve accurate stimulation.

Background
Damage dealt to the central nervous system (CNS) caused by trauma or disease can have detrimental effects on human quality of life because the CNS has limited regenerative capabilities. Efforts to replace lost neural cells require improved knowledge and methods for differentiation of neural stem cells (NSCs).

Objective
In this thesis, I aim to chart our current scientific knowledge and progression of neural differentiation and explore practically the feasibility of continuous ultrasound (US) stimulation on neural progenitor cells (NPCs) differentiating into neurons in vitro.

Methods
I performed a literature study examining previous studies that investigated electrical stimulation, nanoparticles, or ultrasound to improve in vitro or in vivo differentiation of neural stem cells. Using finite element method (FEM) frequency analyses with COMSOL Multiphysics, I investigated the use of a 24-wells plate with piezoelectric lead zirconate titanate [Pb(ZrxTi1–x)O3] (PZT) US transducers. Additionally, I validated in vitro previous findings on the feasibility of differentiation of NSCs to NPCs.

Results
With the knowledge gained from literature and findings from the experiments, I created a mold for the fabrication of a custom variant of a 24-wells plate made with polydimethylsiloxane (PDMS) to which 2.03 mm thick PZT can be mounted.

Conclusion
Future research efforts should focus on further developing this technique, specifically into electrical schemes to optimize US transmission to NPCs.

Neurological disorders profoundly affect quality of life, impairing essential functions like memory, cognition, and movement. Traditional treatments are often limited due to the complexity of the brain, the invasiveness of procedures, or the poor precision of the treatment. Ultrasound (US) neuromodulation offers a promising and minimally invasive alternative, using ultrasound waves to modulate neural activity in deep brain regions with high spatial resolution. Despite its potential, a technological gap limits preclinical ultrasound neuromodulation studies, as current ultrasound devices are too bulky and imprecise for flexible and continuous neuromodulation in freely moving rodents. Moreover, precise targeting is essential for effective neuromodulation, necessitating fine control over the focal spot location. This thesis aims to discover new system-level and circuit-level approaches to designing a miniaturized, power-efficient, and high-spatial-resolution 2D phased array transmitter application-specific integrated circuit (ASIC). These approaches are guided by the vision of implementing a miniaturized ultrasound transducer device for precise ultrasound neuromodulation in freely moving rodents, ultimately laying the foundation for future clinical applications in neurological disorder treatment.
The thesis begins with a literature review to determine the acoustic parameters required for effective ultrasound neuromodulation. Then, a comprehensive system-level study using the k-Wave Matlab toolbox is conducted, examining factors critical to the design of a 2D phased array transducer. This study highlights how parameters such as driving voltage, phase quantization resolution, frequency, and array length significantly impact the performance of the 2D phased array ultrasound transducer by influencing key acoustic and electrical attributes. Optimizing these parameters is essential to achieving high focal gain and spatial resolution while minimizing power consumption. The study finds that a three-bit phase resolution is optimal for accurate ultrasound beam steering. Additionally, while increasing array length improves spatial resolution and phased array gain, it also increases the overall size of the ultrasound transducer, constrained by the small brain sizes of rodents in preclinical studies. This study demonstrates that higher frequencies enhance spatial resolution and phased array gain. However, due to kerf limitations in the dicing manufacturing process of piezoelectric transducers, increasing frequency reduces the effective area of the transducers. Moreover, the pitch size should be reduced with increasing frequency in order to avoid the appearance of the grating lobes in the beam profile, forming a tradeoff between the frequency and the available area for the beamforming channels. Since higher frequencies are desired, particularly for applications in which higher spatial resolution is needed, high-voltage beamforming channels have been developed to investigate the highest frequency that allows for implementing a high-voltage beamforming channel. In this regard, two beamforming channels have been implemented and validated in TSMC 180-nm BCD technology, allowing for driving the ultrasound transducers with 12-MHz 36-V pulses. On the other hand, the power consumption of the beamforming channels has a crucial impact on the overall power efficiency of the ASIC. Therefore, a power-efficient HV pulser is developed, leading to 40.9% power consumption reduction with respect to the conventional HV pulser.
Utilizing the proposed beamforming channels, a prototype 2D phased array transmitter ASIC is developed to validate the findings of the initial system-level study. The transmitter ASIC includes a 12*12 array of beamforming channels that generate 12-MHz pulses with 20-V amplitude. The phasing circuitry in the ASIC generates the required delay for each beamforming channel, hence allowing the ASIC to steer the ultrasound beam. The measurement results proved the functionality of the phased-array transmitter ASIC in terms of phase quantization, showing a maximum DNL of 0.35 LSB. Furthermore, the ASIC allows for controlling the driving voltage and the burst duration, as needed for US neuromodulation applications. Based on the prototype 2D phased array transmitter ASIC, a US-guided US transmitter ASIC is developed for preclinical US neuromodulation experiments in freely moving rats. Considering the size of the rat's brain, the size of the ASIC is limited to 5*5 mm2. Given the prior discussion, the frequency was set to 12 MHz to achieve higher spatial resolution and phased array gain. Taking into account the proposed 20-V beamforming channel, the size of the 2D array was set to 66*66. According to the author's knowledge, this is the first transmitter ASIC that allows for preclinical US neuromodulation experiments on freely moving animals. Moreover, a temperature sensor was added to the ASIC to monitor the temperature rise in the ASIC. In order to monitor the location of the focal spot during the US neuromodulation, synthetic aperture US imaging capabilities are added to the ASIC to track the tissue displacement caused by the US neuromodulation push. In this regard, the ASIC includes eight groups of receiver channels that will be connected to 96 piezoelectric transducers using an analog multiplexer. To prevent side lobes in the beam profile, a system-level study was conducted to determine the optimal placement of receiver channels within the 2D array. The study revealed that a random distribution of receiver elements among the 2D transmitter elements is the most effective arrangement for minimizing side lobe appearance. To the best of the author's knowledge, this is the first ultrasound neuromodulation ASIC with integrated imaging capabilities. The measurement results proved the functionality of the ASIC in generating 20-V 12-MHz pulses with a programmable burst duration. The simulation results have shown that the receiver channels are capable of recording the echoes required for US imaging to monitor the location of the focal spot.
In summary, this thesis describes innovations in system-level and circuit-level integrated circuit design for developing an ultrasound ASIC that can be integrated with a 2D array of piezoelectric transducers, forming a miniaturized phased array US transducer that allows 3D US beam steering and focusing with the highest combination of spatial resolution and penetration depth in the context of pre-clinical studies. The ASIC includes the receiver channels that can be used for US imaging, allowing for monitoring real-time monitoring of the location of the focal spot during the US neuromodulation. This US ASIC leads to the emergence of miniaturized US transducers compatible with preclinical behavioral experiments in rodents, paving the way for the development of therapies to treat neurological disorders in humans. @en

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.

Vagus nerve stimulation serves as an approach to manage drug-resistant epilepsy. Focused ultrasound stands out as a unique tool, offering a non-invasive modality for VNS. With its excellent depth of penetration and sub-millimeter focusing capabilities in soft tissue, ultrasound allows for precise targeting of the vagus nerve without the need for surgical intervention. This technology relies on piezoelectric transducers that convert electrical energy into ultrasonic waves. However, the high costs and technical difficulties associated with the production of these arrays have led to limited commercialization of piezoelectric transducer arrays.

This thesis investigates the design, fabrication, and optimization of a small, low-cost phased-array piezoelectric ultrasonic transducer. The transducer is specially designed for non-invasive UVNS applications in the form of a small patch for the neck. The research is dedicated to the fabrication of the transducer array, designing a transducer capable of both transmitter (TX) and receiver (RX) functions, which in the future can be used for simultaneous image-guided neural regulation. Two prototypes were fabricated: one is a 256-element 2MHz rectangular transducer array integrated into an 8-layer stacked rigid printed circuit board (PCB), and the other is a dual-frequency array integrated into a 4-layer flexible PCB substrate, explicitly designed for simultaneous imaging and neural modulation.

The study utilized two key materials, the well-known PZT and the lesser-known but promising <001> oriented PMN-0.3PT piezoelectric single crystal. Through extensive optimization, air-filled PZT transducer arrays were realized, and the cutting parameters for PMN-PT were significantly improved. A unique aspect of the fabrication was the use of flip-chip technology to directly integrate the air-filled 2D array onto the PCB, a method seldom detailed in existing research.

While exhaustive testing on phase-delayed beam-forming and imaging capabilities could not be conducted due to equipment limitations, preliminary evaluations of the capacity to generate plane waves were made. The properties of the bulk PZT and PMN-PT transducers were characterized. It was observed that the PMN-PT transducer generated significantly lower ultrasonic pressure compared to the PZT transducer, which aligns with expectations due to the fragile nature of PMN-PT. The first prototype of the PZT array transducer was successfully fabricated and assessed, achieving a pressure of 176 kPa at its 10 mm natural focal point. Subsequently, the internal array second of the prototype was fabricated and evaluated, registering a pressure of 1.14 MPa at the 1.2 mm natural focus point.

The results demonstrate the feasibility of building complex piezoelectric arrays using optimized fabrication methods. This lays the foundation for future prototypes to test beam-forming capabilities and for fabrication of the complete equipment afterwards.

Micro-Doppler (µDoppler) ultrasound imaging is a high frame rate ultrasound imaging modality that provides high spatiotemporal resolution ultrasound images of blood flow. It is sensitive to slow blood flow and particularly suitable for capturing fast-changing phenomena like rapid blood flow. Clutter filtering is an essential step in µDoppler data processing to reject tissue clutter signals and keep blood flow information as much as possible. 3D freehand µDoppler imaging is an emerging ultrasound technique that can construct full spatial vasculature images with a panoramic view that conventional 2D ultrasound is not able to provide. As freehand implies the continuous and nonuniform movement of the probe, it becomes more challenging for clutter filtering to acquire high-quality images.

This thesis explores and compares different state-of-art clutter filtering techniques on freehand in-vivo µDoppler imaging of the human brain. Specifically, Singular Value Decomposition (SVD), Robust Principle Component Analysis (Robust PCA), and Independent Component Analysis (ICA) clutter filtering techniques have been investigated. The aim is to test and compare their performance on in-vivo µDoppler ultrasound data with freehand probe movement and understand how freehand motion affects the threshold selection criteria. Besides that, a newly proposed method that combines ICA clutter filtering and clustering is included in this thesis to bring another perspective for sorting independent components corresponding to blood flow and rejecting unwanted ones consisting mostly of tissue clutter signals.

This thesis report, one of a set of two reports, describes a novel way to detect incidents that could occur in the daily life of the elderly. Unlike most systems already implemented in this field, this system does not use any wearable (positioning) sensors and works off an Single Board Computer (SBC).Independent of both of these systems is a system for reassurance to alleviate distress.

In vitro neuromodulation studies play a crucial role in understanding the underlying interaction mechanisms between cells and ultrasound, which is important in the development of new therapies for various neurological disorders. Acoustic focusing, the ability to focus ultrasound at a specific focal length with high spatial resolution, provides a precise and effective way to stimulate cell cultures. In this way, researchers are able to stimulate specific cells or regions within a cell culture, leading to a better understanding of cellular behaviour and responses to ultrasound stimulation.

This thesis focuses on designing and developing a microfabricated acoustic Fresnel lens to focus ultrasound at a pre-determined focal length to fit into currently used Microelectrode Array (MEA) devices. Polydimethylsiloxane (PDMS) is used as lens material and microfabrication technologies are employed for the fabrication of a silicon mold. Experimental measurements have been conducted in an underwater configuration to evaluate the performance of the acoustic lens. The research highlights the potential of using acoustic Fresnel lenses on ultrasound transducers for in vitro neuromodulation. The results of the study demonstrate their capability to effectively focus ultrasound waves at the desired focal length. This advancement has significant implications for the field of in vitro neuromodulation, as it offers a cost-effective and promising method for achieving more accurate stimulation of cell cultures and for studying the impact of various acoustic parameters on cells.

Ultrasound (US) neuromodulation is a widely-used technique in the field of neuroscience and medical therapy that uses ultrasound waves to non-invasively modulate neural activity. The miniaturization of modern ultrasonic systems has an intimate relation with system power consumption. As the advancement of Integrated Circuits (ICs) represents a powerful stride in achieving the compactness and integration of ultrasound systems, power efficiency is always a challenge in ICs. The pulser is a power-consuming part in the transmitter stage, because a considerable power should be used to charge and discharge the parasitic capacitor of the US transducer.

This project aims to design a power-efficient pulser for an ultrasound transducer, which is adopted in a 2D ultrasound phased-array transmitter (TX). The area of the TX circuit in a 2D phased array is limited to half of the sound wavelength, requiring an area limitation for the circuit. The transducer element used in this case has an area of 100*100 um^2. Thus, the area occupation is also considered as an important aspect through the design process.

This work designs a power-efficient 3-level high-voltage pulser with TSMC 180-nm BCD Technology. The proposed pulser interfaces an ultrasound PZT transducer with a resonant frequency of 8.15 MHz. A bootstrap structure is utilized in this design to double the 10-V supply voltage. Five switches are controlled open and close to determine the voltage level at the output node, where three control signals are needed. The design adopts stacked standard CMOS transistors instead of HV transistors for the switches. As the transistors inevitably act as one of the power-hungry parts in the circuit, a smart design of shortly close one of the switches is proposed to save more energy. The 3 levels of the output voltage level from the proposed pulser are near 0, 8 V and 15 V. Thus, as a reference for comparison, a conventional class-D pulser with a supply voltage of 15 V is also presented. It is worth mentioning that to make the comparison as fair as possible, the conventional pulser is also designed in its most power-efficient condition. The simulation result shows a 35.4% power efficiency enhancement of the proposed design compared with the conventional class-D pulser.

Noninvasive brain stimulation plays an essential role in diagnosing and treating diseases of the brain. This stimulation can affect disease-related changes in brain activation, inhibition, or connectivity. Ultrasound neuromodulation is a rapidly growing field of noninvasive brain stimulation. In a form of acoustic pressure waves, ultrasound can transmit mechanical forces to modulate neurons. The acoustic waves can be focused on a particular location with a spatial resolution that depends on the set frequency. Compared to other noninvasive brain stimulation methods, ultrasound neuromodulation is a safe and reversible method that can be used to accurately simulate neuronal circuits for the treatment of neurological diseases.

New medical ultrasound solutions, from ultrasound imaging to ultrasound neuromodulation and ultrasonic powering of medical implants, require a wearable form factor and low power consumption. In these applications, pulsers are the most power-hungry block since they deliver high voltages to the ultrasound transducers and transducers contain massive parasitic capacitance. The ultrasound transducer needs to be driven by a high voltage (HV) square wave so that it can generate desired pressure for ultrasound brain stimulation. Therefore, improving the power efficiency of the driver part is very important for the whole system.

The purpose of this thesis is to design an energy-efficient driver within a limited area. There are two energy-consuming parts in the driver circuit. One is the parasitic capacitance of HV transistors, and the other is the capacitance of the transducer. In order to achieve HV operations, the driver part is typically implemented with HV transistors which have massive parasitic capacitance and also consume large areas. To solve this problem, stacked 5 V CMOS transistors are implemented to replace HV transistors. As for the energy loss due to charging and discharging the ultrasound transducer, many energy-saving methods are introduced in the literature such as energy-replenishing technique, charge redistribution method, and multi-level pulse-shaping technique. The proposed design compared the advantages and disadvantages of these methods and made some improvements on the basis of these techniques.

This work presents a power-efficient high-voltage pulser to drive integrated lead zirconate titanate (PZT) ultrasound transducers for ultrasound medical applications. The proposed pulser employs charge redistribution technique by utilizing a storage capacitor to save part of the charges before discharging the transducer. Furthermore, HV transistors are replaced by stacked 5V CMOS transistors that allow delivering 10 V to the piezo transducer. The pulser is designed and simulated in 180nm CMOS technology with 10 V power supply and 15 MHz operating frequency. The simulation results demonstrate that the proposed circuit improves the power efficiency by 30.55$\%$ compared to the traditional class-D pulser.

This report presents a proof-of-concept for a sensor measuring the ionic concentrations in sweat using cyclic voltammetry. Development is focused on feasibility of the sensor. Theoretical evaluations of voltammetry as a working principle and its physical and electrochemical foundations are guiding principles of the design. The sensor is then implemented using commercial components. Experiments show that the sensor has good sensitivity and linearity for single ions in the physiological range. For the measurement of multiple ions the voltammogram is characterized in-depth. A matrix of different ionic fluids with multiple ions is prepared and two independent parameters for the concentration of two ions (sodium and potassium) are found, proving the concept of the sensor for more complex solutions. The usability of the sensor is verified using a sweat sample. Different influencing factors are researched and their impact characterized. Varying electrode materials are evaluated considering durability and sensitivity. Conclusions are drawn and an outlook for future research on this type of sensor is given. The concept of the sensor is proven to work within certain limitations.

60 million people around the world have epilepsy, which is a neurological disorder that severely impacts their day to day life negatively. Currently available methods to reduce the effects of epilepsy are either ineffective or require expensive and invasive surgery. A new method has been found that can suppress epilepsy without the need of surgery, called Transcutaneous Vagus Nerve Stimulation (t-VNS). Detecting epileptic seizures is important for this method, as the stimulation should only be used during a seizure. Traditionally, detecting epilepsy is done using scalp-Electroencephalography (EEG), which requires a controlled environment and is hard to use in day to day life. Recently, advancements have been made in ear-EEG, which allows for EEG outside a controlled environment. This study focuses on detecting epilepsy using ear-EEG. Ear-EEG was simulated using scalp-EEG channels close to the ear. After low-pass filtering and downsampling the results were obtained using features obtained from the Wavelet Transform (WT) and Fourier Transform (FT) in combination with several Machine Learning (ML) models; these being a random forest, a Support Vector Machine (SVM), and a Neural Network (NN). Furthermore PCA was also applied to the features, with a threshold of 0%, 95% and 99%. The results clearly show that using the WT outperforms features from the FT. Furthermore, out of the three models, the NN consistently has the best sensitivity for detecting seizures. The best sensitivity was achieved using WT features with a NN and a threshold of 99% for the PCA. The accuracy and sensitivity are 99.3% and 83.5% respectively, which is comparable to previous ear-EEG based research detecting epileptic seizures.

Several studies have illustrated that Transcutaneous Vagus Nerve Stimulation (t-VNS) is an effective method for epileptic treatment. In contrast to the classical invasive Vagus Nerve Stimulation (VNS) which is already a Food and Drug Administration (FDA) approved therapy for epileptic treatment, t-VNS does not require surgical intervention. However, t-VNS has still not been evolved into an application which can be used in clinical practise due to a lack of power efficiency or size constraints. In this bachelor graduation project, an electrical circuit has been designed and implemented for stimulating the auricular branch of the vagus nerve. This circuit is part of a larger project where an ear piece is developed which is able to process Electroencephalogram (EEG) signals as well. The main design goals of the stimulator were power
efficiency and safety. Furthermore, a design for an integrated circuit has been proposed resulting in an power efficient method for controlling the electrical stimulation circuit. The integrated circuit has, among other things, built in safety features and closed loop stimulation capabilities. Simulations showed that the designed circuit is able to successfully stimulate with current amplitudes up to 8 mA when taking worst case values for an impedance model of the electrode-skin interface. However, the implemented physical design was planned to be tested after the thesis submission. In other words, this thesis only contains the design and simulation phase of the stimulator. The design was found to be safe and power-efficient and could lay the basis for future development in the field of wearable in-ear stimulation devices.

DEEP brain stimulation is currently the only technique used in the clinical setting, capable of stimulating the deep brain nuclei. Recently, low intensity focused ultrasound has been shown to reversibly modulate brain activity. At present, ultrasound neuromodulation is performed through the transcranial pathway. This requires the ultrasound waves to pass through the skull, thus attenuating the ultrasound waves. To reduce the effect of attenuation, lower frequencies are used of around 0.5 MHz, however, with decreasing frequency the focal region in which the stimulation occurs also increases. Therefore, a stent with an array of ultrasound transducers operating at high frequencies of around 5 MHz has been proposed to bypass the skull, thus significantly
reducing the attenuation. Moreover, such a device would require a minimally invasive procedure removing the need for open brain surgery as currently performed for deep brain stimulation. This research was performed to evaluate the feasibility of using ultrasound arrays within the brain vasculature to stimulate deep brain nuclei using the finite elementmethod.

Initially, a literature review was conducted to identify the optimal ultrasound parameters for achieving neuromodulation. For stimulation, a PRF ranging from 500 to 1500 Hz and a DC of around 50 to 70% were found to be optimal. Whereas for suppression, a PRF of<100 Hz and a DC of around >=10% were found to be ideal. The intensity for both suppression and stimulation was found to greatly depends on the target region and individual as well as anaesthesia for stimulation, nonetheless, for 5 MHz an intensity of around 1W/cm2 was required to achieve neural excitation.

Next, the brain nuclei were studied and the subthalamic nucleus, ventral intermediate nucleus and globus pallidus internus were identified to be the most commonly targeted nuclei for deep brain stimulation. Brain vasculature was then examined in terms of the blood vessel inner diameter, shape, orientation with respect to the nuclei and the distance to the nuclei. Basal vein of Rosenthal, internal cerebral vein and internal carotid arterywere found to be most suitable to target the subthalamic nucleus, ventral intermediate nucleus and globus pallidus internus respectively.

Afterwards, two-dimensional simulationswere performed usingCOMSOLMultiphysics to identify the minimum required array width and length for stimulating each nucleus from its respective blood vessel. However, when compared to 3D counterparts it was found that 2D significantly overestimated the size of the focal region.

Finally, 3D simulations of 100 x 100 x 262 ¹m transducers in a 104 (2D 26 x 4) and 105 (Checkered [3 x 2] x 21) arrays within the BVR were analysed targeting the STN. These arrays were found to produce a focal region of full width half intensity within the subthalamic nucleus model boundaries while reaching intensities and pressures of 0.558 W/cm2 or 0.140 MPa and 0.311 W/cm2 or 0.101 MPa with a 1 V terminal for 2D and checkered array respectively. Therefore, these arrays are capable of reaching the neural excitation threshold of 1 W/cm2 with terminal input of less than 2 V . Additionally, a maximum input of 9.2 V is required to reach 1 MPa pressure threshold that has been reported by other studies. Nonetheless, these values do not take into account the fully unused length of the stents, as the arrays can be designed to be longer. In conclusion, finite element method result are promising for deep brain stimulation via a vascular stent with ultrasound transducers for high-spatial neuromodulation. Nonetheless, further work is required to develop an initial prototype as well as initially test the prototype and array within a phantom.

Medical technology has seen great progress over the last centuries, developing increasingly more specialised therapy to benefit human health. The rise of the pharmaceutical industry and the research it drives are contributors to this success. However, in humanity's attempt to tackle more and more complex health issues, the conventional methods used require adaptation. This is also true in the case of neurological disorders and diseases, which stem from the body's nervous system. While the nervous system possesses high responsiveness to chemical devices, these same devices can often not target specific locations at the required time. Therefore, solely depending on chemical delivery stagnates progress in overcoming the ailments' negative effects on both health and quality of life. It is here that an argument is made for therapeutic delivery through another modality. Manufacturing such technology creates complex engineering challenges and demands close cooperation between engineers and clinicians.

In this thesis, fundamental research is done to aid the investigation of efficient acoustic delivery with focused ultrasound. It is part of an ongoing effort to make therapy for neurological disorders and diseases less invasive and more effective. The modality of ultrasonic waves promises great potential in this respect, being able to image and modulate neural activity.

The work presented here shows the development of a research platform to effectively study the biophysical mechanisms that are responsible for ultrasonic neuromodulation. Using microfabrication techniques and 3D printing the basic elements of the platform could be manufactured. During electrodeposition, silver layers were grown to construct the Ag/AgCl electrode and insight was gained into the process. Electrophysiological measurements show the platform's capability to measure bilayer lipid membranes, which were manually prepared and suspended.