Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia, making the study of small vessel hemodynamics vital for advancing diagnostic and therapeutic strategies. This research focuses on fabricating microfluidic devices that replicate the lateral lenticulostriate arteries (LSA) to validate computational flow models of small cerebral vessels. A key challenge in studying CSVD is the lack of experimental validation for computational fluid dynamics (CFD) models, which are widely used to simulate hemodynamics. To address this, additive masked Stereolithography (mSLA) was employed to fabricate a microfluidic model of the LSAs. The study explored the impact of orientation, exposure time, and layer height on the roundness and error of the intended area of printed micro-pores, to optimize the manufacturing of a microfluidic device. The smallest printed pore measured 270 μm in diameter. Pores printed at a larger angle as assessed from the build plate were more likely to remain open, but exhibited a larger decrease in area compared to smaller angles. A lower exposure time exhibited a larger pore area, whereas a larger layer height showed a decrease in area from intended. The layer height and angle did not influence the roundness, whereas an increase in exposure time decreased the roundness of the pores. Additionally, flow experiments were conducted using a 3D printed microfluidic device to compare empirical data with CFD and analytical simulations. The encountered resistance was larger for the experimental results (3.19 ⋅10^11 Pa⋅s/m^3) compared to the analytical result (1.96 ⋅10^11 Pa⋅s/m^3) and the computational result (1.90 ⋅10^11 Pa⋅s/m^3), likely due to deviation from the intended size. Finally, arterial microfluidic devices were printed and flow was induced to showcase their functionality. Achieving precise channel dimensions remains the primary challenge in mSLA printing due to cumulative dosage effects.
This research bridges the gap between computational modeling and experimental validation, providing a platform for studying cerebral microcirculation. The findings demonstrate the feasibility of using commercially available 3D-printed microfluidic devices to replicate small cerebral vessels. The outcomes of this study contribute to the advancement of vascular biomodeling, with implications for future clinical applications in stroke and neurovascular research.

The primary objective of this research is to develop an efficient protocol which can be used to 3D print multi-material microfluidic devices with a high resolution. During this research, the fabrication of multi-material microfluidic valves is discussed as a showcase to verify the multi-material protocol, using a single affordable printer and multiple resin vats. In contrast to single material microfluidic fabrication methods, complex geometries can be created by the use of combinations of stiff and flexible materials in a single 3D print. This protocol aims to streamline the fabrication process while ensuring precise feature reproduction and robust mechanical properties in multi-material 3D printed microfluidic parts.

In this study, the effects of UV light exposure on feature accuracy and mechanical performance is systematically investigated. It is observed that for the rigid material, Anycubic High Clear, sample sizes increase and void features shrink when the exposure to UV light increases. For the soft material, Liqcreate Elastomer-X, shrinkage rates after swelling due to IPA absorption are compared under different conditions, revealing that shrinkage occurs more rapidly with a heat source than at ambient temperature.

Mechanical properties are further evaluated through tensile testing of four sets of printed dogbones, showing that extended UV exposure enhances mechanical properties such as the Young's modulus, ultimate tensile strength and strength at break. Elastomeric materials assessed in this study demonstrate an optimal measurement accuracy within a strain range of 10% to 50%. The influence of print orientation is assessed for the hard material. This experiment is executed for layer thicknesses from 10 µm to 200 µm across horizontal, vertical, and diagonal orientations, with vertically printed samples being closest to the intended dimensions.

A comprehensive multi-material 3D printing protocol based on the existing "print-pause-print" technique and utilizing the software UVTools is presented. Finally, a microfluidic Quake valve is designed and optimized for 3D printing, its performance is analyzed through finite element (FEM) simulation and analytical calculations.

The results of this study offer valuable insights into the optimization of multi-material 3D printing for microfluidic applications, highlighting several critical parameters that affect feature resolution and mechanical performance. The proposed protocol and findings serve as a foundation for future advancements in the fabrication of complex microfluidic devices.

This master thesis explores strain-induced quantum emitters in hexagonal boron nitride (hBN) as novel optical nanoprobes for Förster resonance energy transfer (FRET)-based biosensors. These types of emitters could outperform conventionally used fluorophores due to their high brightness, stability in harsh environments, biocompatibility and ease of integration with solid state devices. Ultimately, the aim is to combine optically-active hBN emitters with protein fingerprinting devices, which could impact the field of molecular diagnostics by detecting clinically relevant protein biomarkers.

To date, however, it is unclear which parameters are crucial for the generation of hBN quantum emitters with strain in both CVD grown and exfoliated hBN crystals. To address this gap in the field, this thesis systematically investigates the generation of strain by mechanically exfoliating pristine hBN crystals onto a variety of rigid micro/nanostructures with different aspect ratios, including 5 µm and 10 µm microbeads, femtosecond laser-ablated cavities, and CD/Blu-ray micro-nanostructures. We characterised the samples with fluorescence microscopy and atomic force microscopy in order to correlate the optical properties of the hBN with the topography of the substrate. Among the tested structures, samples displayed clear fluorescent emission at the location where the hBN was deposited on the femtosecond laser-ablated cavities with sharp edges. The presence of strain in these regions was verified with Raman spectroscopy, and the spectral properties of the fluorescent regions were determined with photoluminescence spectroscopy. We additionally studied the temporal behavior of the identified emitters and observed effects such as blinking with intensities reduced up to a 38 % and photobleaching with quantum emitters’ lifetimes between 6.57 s and 44.17 s.

While there were no clear threshold values of curvature, substrate structure height, and thickness of hBN that led to reproducible localized fluorescence, these findings open up further research opportunities for the use of strain engineering to generate quantum emitters in hBN.

Fused filament fabrication (FFF) is the most used additive manufacturing technique that uses a heated nozzle to melt a polymer and a feeder to extrude it on a buildplate. The dependencies of temperature, shear-rate, viscosity and pressure of the melt create complex dynamics within the nozzle, which causes inconsistent extrusion. To improve extrusion control, a better understanding of the dynamics within the nozzle is required. The greatest knowledge gap comes from a lack of experimental data on the pressure inside the nozzle, due to the challenging environment for sensors. This study presents a novel way of monitoring the pressure inside the nozzle of an FFF 3D printer. A pin that is in direct contact with the melt transfers the force applied by the melt through a hole in the nozzle to an externally mounted load cell. The set-up has proven to provide reliable, repeatable pressure data in steady-state, static extrusion. The experimental data on different nozzle geometries and materials, with different flows and temperatures, has been compared to theoretical pressure calculations to identify non-linearities that influence the pressure such as entrance effects, temperature non-uniformity and viscoelastic behaviour of the melt. The proposed design can be used to gain more knowledge on the extrusion process to further develop extrusion control.

Administration of drugs can help in the recovery of the brain for example after a stroke. There are many available delivery routes such as intravenous injection or local injection in the brain. Whereas, the former encounters problems with systemic side effects, the latter requires multiple invasive brain surgery. Local drug administration could be achieved with a drug delivery implant to reduce the amount of invasive procedures and to include useful features such as electrodes for monitoring neural activity. In this study an advancement is made towards spatial control of permeability in a membrane. Porous PDMS membranes were fabricated by replica molding in a 3D-printed mold. The smallest pore diameter was 100 μm and the thinnest membrane thickness was 160 μm. The permeability of such a membrane is tested by a dye which must go through the membrane in order to observe staining in 0.6% agarose gel to simulate diffusion of brain tissue. No staining was detected using pristine PDMS membranes. However, a fast flow from hydrophobic to hydrophilic side was observed in a PDMS membrane recently treated with plasma on a single side. Furthermore, slow diffusion of the dye was present in a less hydrophilic, dextran-modified membrane that received plasma treatment on one side as well. Thus, the permeability was controlled by the wettability of the membrane surface without modification of the entire inner pore. The same experiments were performed on a mouse brain to be compared to the results on agarose gel. The use of agar as a brain phantom material is useful for further investigation of a local drug delivery device, but a few improvements are required to better correspond to the brain.

To control fluid transport, microfluidic systems often make use of pressure driven flow and pneumatically actuated valves. However these require bulky external instrumentation. An integrated fluid control mechanism would make microfluidic systems more portable, closed and automated. The aim of this project was to create a pH-responsive membrane for integrated fluid control in microfluidic systems. pH-responsiveness will allow the membrane to interact directly with analytes in a microfluidic system.
First pH-responsive materials and fluid control mechanisms to create a pH-responsive membrane were reviewed. Cross-linked polymer hydrogels with pH-dependent volumetric swelling were identified as the most suitable material for the membrane. These materials respond to changes in pH by large volumetric transitions, which creates potential for control over a wide range of flow rates. Furthermore they have an inherent interaction with water and are permeable to small molecules such as H+ ions. The material is synthesized from a liquid precursor that can be cured through photo-initiated free radical polymerization.
We tested a system for measuring the pH response of the material that consisted of a hydrogel disk that was vertically constrained inside a fluidic channel. Due to this constraint, expansion only occurred in the lateral direction and could be measured using an optical microscope. Furthermore, we developed a method for manufacturing macro-porous hydrogel membranes that gives control over pore size, shape and position. A photo-lithography approach was used to pattern the membranes and thereby create pores, using a photo-mask that was manufactured on an office printer in a very fast and low-cost process.
The resulting membranes had a thickness of 140-190 um and pore diameters of 100-400 um. The pore size was measured for environmental pH of 1.6 and 7.1, within this range the pores doubled in diameter. Furthermore the pH-responsive deformation ratio of the pores increased significantly with increasing curing time and decreasing pore diameter. The results suggest that there is a difference in material properties around the pores that develops due to a local difference in received exposure dose during curing.
The fluidic properties and pH-response of the membrane can be adjusted to suit a specific application by changing the design, the curing time or the chemical composition of the membrane. The constrained disk system can then be used to measure and compare the pH-response of different potential materials.

A manufacturing technology is proposed to manufacture polymeric membrane scaffolds for culturing of cells, tissues, and organoids with integrated sensor capabilities and fluidic functionalities. A multilayer substrate is imprinted with a soft mold to manufacture polymeric membrane scaffolds for culturing of cells, tissues, and organoids with integrated sensor capabilities and fluidic functionalities. Aside from exploiting the well characterized, simple and low cost techniques that can be employed in polymer manufacturing, the use of solely polymeric materials increases the opportunities for functional integration, while at the same time allowing for the translation of complex cleanroom fabrication processes into mold-based replication techniques. With this developed manufacturing technology, it is demonstrated that it is possible to manufacture membrane scaffolds with integrated porous electrode up to 1mm by 1mm in effective surface area, with a thickness of 10 µm, with control over the pore diameter (as small as 400 nm), the porosity, and the location of the pores. The morphological characterization is done by scanning electron microscopy. The integrated porous electrode’ performance is characterized electrically by a 4-point probe and electrochemically by cyclic voltammetry and electrochemical impedance spectroscopy. Showing the possibility to use the conductive layer to give cells electrical stimuli and for the use as a biosensor.

The structuring of polymers on the micro and nanoscale is performed largely by lithographic techniques, which require complex steps and suffer from geometrical and scaling limits. Techniques such as Nanoimprint Lithography and Hot Embossing are attractive alternatives as they can produce high quality nanoscale structures with a high throughput. Colloidal building blocks offer a way to self-assemble the masters required for these replication steps. However, the difficulty with self-assembly lies in the creation of stable structures with little defect that are well controlled. This work sets out to provide a
comprehensive overview of the aspects of the fabrication of colloidal crystals, the most influential parameters and how they can be qualified. Offering a basis for future research on microscale replication by colloidal crystals and resulting in development of a method for the fabrication of colloidal crystal, which can be used as a master to replicate microscale patterns through Hot Embossing.