Cancer metastasis, the spread of cancer cells from a primary tumor to distant organs, is the leading cause of cancer-related deaths. During metastasis, cancer cells undergo significant changes in their mechanical properties, including alterations in cell elasticity. Cancer cells generally exhibit higher elasticity than normal cells, a key feature that may contribute to their ability to migrate and invade other tissues. Although extensive research has focused on cell-substrate interactions, these studies do not fully replicate the physiological environment, where cells are frequently in direct contact with each other. In this study, Atomic Force Microscopy (AFM) in force spectroscopy mode, utilizing a micro-sized cantilever with a hemispherical tip, was used to quantify the Young’s modulus (E) of MCF-7 breast cancer cells in two configurations: cell-substrate and cell-cell. The resulting force-indentation curves were analyzed and fitted to the Hertz contact model to determine the Young’s modulus. The results showed that the Young’s modulus in the cell-cell configuration was Ecc = 205.8 ± 50.88 Pa, while in the cell-substrate configuration, it was Ecs = 187.95 ± 78.26 Pa. These findings suggest that MCF-7 cells are slightly less elastic in the cell-cell configuration. This challenges the expectation of a more significant difference between the two configurations and highlights the importance of considering biological variability and experimental conditions when interpreting cell mechanical properties.

Much research is conducted on the biomechanical properties of cells, particularly in cancer research. Cell stiffness and cell adhesion are two properties often studied, because they are important for the functioning of a cell. To study these properties, atomic force microscopy(AFM) is often used, using nanoindentation for stiffness analysis and fluid force microscopy(FluidFM) for adhesion analysis. However, these techniques often involve different cantilever probes, which complicates the measurement of both properties in a single cell. To make it possible to study cell stiffness and cell adhesion of a single cell, a multifunctional microfluidic AFM cantilever is developed in this research. This cantilever is equipped with a blunted pyramid-shaped tip for nanoindentation enabling the measurement of cell stiffness and imaging. Moreover, it features a channel running through its length, with an aperture on the tip, facilitating fluid force microscopy for determining cell adhesion. The multifunctional cantilever is fabricated using a multiscale 3d-printing technique, where stereo lithography is used for the larger parts, and two-photon polymerisation is used for the cantilever. To demonstrate the capabilities of the cantilever, tests are conducted on various substrates. Nanoindentation is demonstrated on PDMS, hydrogel and endothelial cells to determine the Young’s modulus of these materials. Fluid force microscopy is showcased by examining prostate cancer cells (PCA-3), removing the cells from the substrate while measuring the adhesion forces. The imaging capabilities of the cantilever were also demonstrated by generating a height map and a Young’s modulus map through quantitative imaging of a hydrogel spheroid. This research shows that combining the properties of nanoindentation and FluidFM cantilevers into a single cantilever is possible. Integrating these functionalities into a single cantilever makes doing more mechanical measurements on a single cell possible.

In vitro models are fundamental in the study of cell behaviour, the physiological function of organs, and their response to drugs and toxins. However, the shortage of accurate and reliable in vitro models calls for the development of in vitro lung models that better recapitulate lung physiology and pathology. Lung-on- a-chip models are promising to this end. To date, most membranes used in these models are made of poly(dimethylsiloxane), which has significant disadvantages. Moreover, there is a need to establish adequate membrane pore sizes throughout the cell culture duration. A design of a novel LOC membrane containing a dynamic membrane pore size to recapitulate the pulmonary alveolar-capillary barrier was designed and its viability evaluated. Poly(octamethylene maleate (anhydride) citrate) (POMaC) is evaluated as a membrane material on its cytotoxicity, biodegradability and imaging properties. For creating a thin and porous membrane, spincoating, moulding and 2-photon polymerization were studied.

The results provide promising support for fabricating a thin membrane. It was concluded that thin, uniform POMaC layers and a conical micropillar mould could be created. Moreover, stiffness of POMaC was in the expected range, and the bioimaging properties were found to be suitable. The degradation results did not support the hypothesis that a structural pore size could increase, which likely impedes the increase of pore diameter necessary for immune cell transmigration. Therefore, a model of the degradation characteristics of POMaC is proposed.

Hydrogen storage in porous media is a potential solution to the energy distribution problems we might face in the future. Intermittent energy sources such as solar and wind energy need to be accompanied with temporary energy storage to accomodate the times when production and demand do not match. Hydrogen is an energy carrier with a large mass energy density as it can be made completely green through electrolysis and it will not release greenhouse gasses when used to produce energy through combustion process. However it has to be stored in large enough volumes to reach the required energy demand. The storage can be done in the subsurface in either aquifers, depleted hydrocarbon reservoirs or salt caverns which are giant porous or cave volumes available to store compressed gases. At this moment, there is a lack of knowledge for safe and efficient hydrogen storage at reservoir (continuum cm and above) scale and pore scale (micrometer-scale). In a reservoir model the relative permeability and capillary pressure are key parameters to characterise flow behaviour and capacity. These are upscaled parameters we can find through pore-network modelling, among other approaches. For a pore-network model, the contact angle and accompanying wettability characteristics (i.e., interfacial tension) are important to obtain reliable upscaled functions and parameters.
Through the use of a captive bubble method, in this thesis work, we have been able, for the first time, to characterize the contact angle of a hydrogen/brine/rock system at different pressures, temperatures, salinity's and rock compositions. It was found that the contact angle of a hydrogen/brine/rock system is in the range of between 21.1 and 43 degrees. Moreover, for the studied range of varying parameters, the contact angle stayed remained relatively constant. The results of this study are published in the Journal of Advances In Water Resources (https://doi.org/10.1016/j.advwatres.2021.103964).

In this study, we introduce the Delft Advanced Research Terra Simulator (DARTS), which employs the Operator-Based Linearization (OBL) approach to provide efficient and precise solutions for non-linear discretized equations, to simulate the polymer flooding process. This compositional simulation framework is feasible for describing complex physical phenomenon with high nonlinearity because detached functional operators have been developed to release the calculation load while maintaining a high degree of stability and accuracy. The main contributions and innovations are shown below: i. A two-phase and three-component chemical flooding mathematical model with some reasonable assumptions was developed to investigate the enhanced-oil-recovery (EOR) mechanism of polymer flooding. A finite volume discretization scheme and a fully implicit method (FIM) are implemented to approximate the conservation equations. The OBL approach is used to reduce the complexity of the simulation framework. The correctness of the model is verified by comparison with analytical model. ii. In addition to shear thinning effect, polymer viscoelasticity has also been taken into account. This mathematical model is able to handle high shear rates during field displacement as well as low to medium shear rates in laboratory experiments. iii. A new model for porosity reduction caused by polymer adsorption is formulated. The effect of polymer concentration on the effective pore volume is incorporated in numerical simulations based on Langmuir adsorption model.

Organ on a Chip (OoC) systems are of high interest through its use for medicine testing in a small time scale without the need for animal testing. Membranes used in OoCs form a base to grow cells on and need to be suitable for cell-attachment and porous. Fouling is the 'Achilles heel' in membrane performance. Research shows that as a result of fouling the viability of the skin cells grown in the chip decreased to zero after 3 weeks. If research on organs is to extend and research on cell- or tissue growth will include longer time spans, the influence of membrane fouling with conditions similar to the OoC is an important factor to understand.
In this research a microfluidic flow cell is produced and used to explore fouling within the OoC. Static and dynamic fouling experiments are executed on membranes having pore sizes ranging from 0.4 to 5 μm.
Scanning electron microscope (SEM) images indicate that standard blocking and cake layer formation are dominating fouling mechanisms.
Membranes with 1 μm pore size are the most susceptible to standard blocking. Further a decrease in pore area of 0%, 11% and 20% and a decrease in uncovered amount of pores of 27%, 34% and 80% for Glycine, BSA and λ-DNA respectively are measured after one week of fouling.
Cake layer formation is seen after fouling for a shorter duration for BSA (one day) than for Glycine (one hour) and a higher concentration of BSA particles is permitted through all tested membranes than Glycine, therefore the conclusion is drawn that BSA causes less fouling than Glycine.