Kidney stone disease is an increasing worldwide issue. There is a current lack of understanding of the exact mechanisms involved, partially due to the need for experimental instrumentation able to mimic the microenvironmental conditions present in vivo. As crystal nucleation often initiates at liquid-solid interfaces, the interface morphology plays a significant role in the rate of nucleation. Within the nephron, the functional unit of the kidney, four distinct segments can be distinguished that contain different surface morphologies. Particularly, the cells lining these segments contain protrusions in the shape of nanopillars that vary in length, diameter and spacing. Exploiting the opportunities provided by organ-on-chip technology, we designed and manufactured a microfluidic device proposed to increase our understanding of the exact mechanisms that drive kidney stone crystallization. We used two-photon polymerization to fabricate surfaces that contain these morphologies in materials possessing a Young’s modulus matching the value of the biological structures. After optimizing design and process parameters like laser power and scanning speed, we manufactured nanopillars with diameters in the range of 150-250 nm and aspect ratios up to 100 with which we can mimic the protrusions in the nephron. Pillar arrays were printed on a glass slide, and assembled with a polydimethylsiloxane (PDMS) microfluidic component (channels 150 um wide). We used high-resolution 3D printing to create master molds used for PDMS soft-lithography. After precise alignment, the two components were brought together and clamped mechanically with a 3D printed holder to ensure a watertight seal between the glass and PDMS. This microfluidic device was used to study crystallization of the most common type of kidney stone, calcium oxalate monohydrate (COM). Because of the chip dimensions combined with a surface morphology this device closely resembles a human nephron.

Acoustic Force Spectroscopy (AFS) is a versatile tool that uses sound waves to manipulate tiny particles such as cells, bacteria, and even zebrafish embryos in microfluidic systems. This kind of acoustic tweezer is gaining increasing attention due to its high throughput capability and non-invasiveness. In addition, this device allows for parallel manipulation of bio-molecules. Therefore, it can provide statistically significant data about the DNA replication process, which is widely considered a stochastic process. Understanding the dynamics of the DNA replication process plays a vital role in developing medicine to cure diseases that are still incurable today. Most single-molecule techniques, such as optical tweezers, magnetic tweezers, and atomic force microscopy, can only manipulate a limited number of particles simultaneously. Therefore, obtaining statistically significant data with these methods is laborious, time-consuming, and expensive. This report describes the design, fabrication, simulation and characterization of an easy-tobuild and cost-effective acoustic tweezer. The trapping stiffness of this device is derived from finite element modelling and experiments. This property is used to benchmark the acoustic tweezer developed in this project against other microparticle manipulation devices found in the literature. The results show that the acoustic tweezer developed in this project provides sufficient trap stiffness for studying DNA replication.

A research gap exists in a targeted drug delivery into the brain with an implant placed on the outer surface of the cerebral cortex. If an implant with spatial control that can release drugs to a target location can be developed, it will provide efficient treatment opportunities for a variety of brain disorders such as strokes. One of the questions in realizing this implant is how to activate the drug release mechanism. Light is a promising activation stimulus due to its spatial precision and flexibility in the optical path. This thesis is a feasibility study into carrying light inside such a brain implant using a photonic crystal waveguide. Such a device must be soft and maintain its functionality during the mechanical bending imposed on the implant by the geometry and movement of the brain. A flexible 2D photonic crystal is simulated using COMSOL Multiphysics with the goal of designing a waveguide that functions with infrared light. The dispersion diagram of the photonic crystal is plotted to design for a bandgap at the operating wavelength. The transmission through a linear waveguide is calculated for the deformed state of the implant in mechanical bending, which is modeled as a 2D strain. A metallo-photonic crystal with photoresist nanopillars coated with a gold thin film and embedded in a flexible PDMS matrix is selected as the prototype for fabrication. The nanopillar arrays that form the photonic crystal waveguide are printed using two-photon polymerization (2PP), deposited with gold then transferred into photosensitive PDMS by drop casting. For characterization, a tapered rib waveguide is designed for light coupling and an optical end-fire test setup is built for transmission measurements on the fabricated device.