This report presents a route map and the first steps to the development of a vascularised alveolarcapillary barrier to study the effects of air pollution on lung-health and chronic respiratory diseases. The ultimate goal is to fabricate a vascularised model of an alveolar-capillary barrier, that mimics the physiology of the human lung more closely than currently used models. Current vascularised alveolar-capillary barrier models are limited by the absence of membrane-free designs and the lack of integration of both fluid flow and membrane stretching. The development of a membrane-free, vascularised model that integrates fluid flow and membrane stretching, requires a reproducible vascularisation method with a lifespan sufficient for epithelial cell differentiation and follow-up experiments. Pre-structured vessels provide more control of the structure of the vessel network and improve the reproducibility of a model compared to a model with a self-assembled vascular network. Therefore, the first step in this study is to establish a method for culturing a lung-derived endothelial vessel in a pre-formed channel within hydrogel as extracellular matrix that can last several weeks. Wire moulding is used to create a hollow channel inside a fibrinogenbased hydrogel between two injection needles. Two diameters of wires, 50 μm and 125 μm, and two concentrations, 1% and 2%, of fibrinogen were used for a total of 10 tests. The endothelial cells were seeded using the capillary effect and after four hours, the perfusion of medium through the channels started. A pre-formed channel in the hydrogel containing 2% hydrogel and seeded with lung-derived endothelial cells remained perfusable for 32 days while withstanding flow leading to a significant amount of shear stress on the endothelial cells. To study the phenomena of gas exchange that accur across larger tissue constructs, the hierarchical dimensions and topological complexity of native vascular beds should be better replicated. Another moulding method is needed to create a structure of hollow channels inside a hydrogel to culture a vascular network rather than one vessel. It was found that with carbohydrate glass, varying structures can be printed and it can be embedded within hydrogel prior to cross-linking without blending into one another. This indicates that sacrificial moulding using carbohydrate glass is a promising technique for creating pre-structured vascularised networks. This potential method to create a pre-structured network combined with our cell seeding method and the 2% fibrinogen hydrogel, is the basis for the development of a reproducible, membrane-free vascularised alveolar-capillary barrier model that incorporates flow and stretching of the barrier.

In recent years electronics have not only become smaller but also faster. The resulting integrated circuits (IC) often operate at radiofrequencies (RF). As a result of the small distance between features and the high operating frequencies, parasitic coupling can occur between functional elements impacting the functionality of the circuits. Our research therefore presents a novel contactless probe capable of measuring RF voltages and currents with μm-resolution at a bandwidth of 1 to 23 GHz. The probe is fabricated through a multiscale 3D-printing process where the bulk of the chip is printed using Digital Light Processing (DLP) stereolithography. The rest of the probe is printed through a Two-Photon Polymerisation (2PP) process. At the interface, a two-leged cantilever is 2PP printed on top of the DLP print. At the end of the cantilever, a sensing tip is integrated. It contained a triangular loop with a uniform width, and connects the two legs of the cantilever. On top of the triangular loop, a sharp tip is printed. In the last fabrication step, a thin conductive film is deposited by means of thermal evaporation, resulting in a sharp, conductive tip that sits on top of a conductive triangular loop. The loop is connected to the two legs of the cantilever and, hence, a potential over the loop can be measured.

When the probe is brought in proximity to an electrode carrying a time-varying current it inductively couples to the loop. Similarly, when the probe comes close to an electrode subjected to a time-varying voltage, it capacitively couples to the conductive tip. A model-based approach is applied to increase the spatial resolution of the probe. The sharp tip and cantilever allow the probe to be mounted in a modified AFM setup, which is used to accurately position the tip, and determine the tip-circuit distance. The voltage and current are continuously measured while the tip-circuit distance is increased. Sources directly underneath, hence very close to the probe show a non-linear dependence on the tip-circuit distance, whereas parasitic adjacent sources that are further away show an approximately linear dependence on the tip-circuit distance. By fitting the measured data to a mathematical model, the non-linear components can be isolated from the parasitic contributions to the measurement signal. Applying this technique allows us to conduct contactless RF voltage and current measurements with μm-resolution at a bandwidth ranging from 1 to 23 GHz.

Fundamental neuronal studies are concerned with the investigation and understanding of the behaviour of cells in response to certain chemical or physical cues. The field of study concerned with physical cues and their effect on neurons is referred to as neuronal mechanobiology or neuromechanobiology. These cues include properties such as the geometry (i.e. 2D vs. 3D substrates), topography (i.e. roughness of the substrate), and stiffness of the substrate, which can affect migration, phenotypic expression, and neurite outgrowth of neurons. In recent years, the study of mechanobiology has witnessed substanrial developments due to our increasing ability to fabricate (physiologically) relevant environments that simulate specific features of the native extracellular matrix (ECM). Specifically, within micro and nano-fabrication techniques, two-photon polymerization (2PP) gained a lot of traction and proved to be a versarile method for the fabrication of microstructures to be used in mechanobiological studies. The technology of 2PP allows indeed the fabrication of specifically designed complex 3D microstructures with a resolution that can reaches down to 50 nm in feature size in a reproducible manner with relative ease.
In this dissertation, I present multiple microfabrication and processing protocols developed specifically for mechanobiological studies of neurons and microglia (part of the glial cells category), two of the most abundant cell types in the brain. @en

Current stroke treatments are limited to acute phase management, and there are few clinically available drugs for neuron protection or damage repair due to restrictions imposed by the blood-brain barrier. This project envisions an implantable DDS for precise drug dispensing to areas of the brain affected by stroke, using light-activated liposomes and microfluidic control to improve therapeutic effectiveness and minimize off-target side effects.

Reviewing literature on microfluidic trap-and-release mechanisms, it became evident that deformable particles often tend to slip out of traps. To accurately predict this behavior, the Young's-Laplace equation and energy stored in the liposome membrane have been assessed. Next, microfluidic devices that were able to manipulate the liposomes to the desired trapping locations were designed and produced. The trapping behavior of liposomes has been assessed by increasing the hydrostatic pressure under a fluorescent microscope. The results show that the experimental pressure of 50-250 Pa is lower than the expected theoretical predictions and that there exists a diameter threshold of 17-18 μm for which the liposomes show lysis behavior. Finally, the entire DDS concept has been demonstrated using a network of traps using the path-of-least-resistance approach.

Each year, stroke claims about 5.5 million lives and leaves around 116 million with lasting disabilities. Current stroke treatments focus on the acute phase, lacking drugs for neuron protection or damage repair due to the blood-brain barrier. This proof-of-concept project presents an implantable drug delivery system (DDS) using microfluidics and light-sensitive liposomes for post-stroke treatment in the affected regions of the brain. This research investigates the synthesis, characterization, and application of giant unilamellar vesicles (GUVs) for potential drug delivery applications. Vesicles synthesized by the gel-assisted swelling method. Dye encapsulation studies identified 5 μM as the optimal concentration, with higher concentrations negatively impacting vesicle formation. Stability assessments showed that PEGylation and cholesterol enrichment improved thermal stability and encapsulation efficiency, with lower temperatures generally enhancing stability. Coating GUVs with gold nanoparticles faced challenges with aggregation, indicating the need for optimized reagent concentrations and reduction processes. Dye release studies demonstrated stable encapsulation up to 39°C, suggesting potential for controlled release via surface plasmon resonance. Pipetting was found to better preserve vesicle integrity in microfluidic platforms compared to syringe introduction. Overall, this thesis provides comprehensive knowledge about the synthesis, lipid formulation optimization, and stability of GUVs, offering practical insights into their handling and application in microfluidic platforms, and laying the groundwork for future innovations in drug delivery systems.

Lung-on-Chip (LoC) are devices that give cells a habitat in vitro that tries to more nearly imitate their natural environment in vivo. This microscale bio-mimetic device is designed to replicate essential features of the human lung within a controlled environment. While advancements in microfluidic technology have been substantial, the lung-on-chip devices presents distinctive challenges. This research mainly deals with eliminating the shortcomings like leakage of the culture media through the cover slips due to improper sealing and detachment of the cover slip. Through an iterative approach during manufacturing and incorporating refinements based on experimental findings, a modified device is designed and fabricated which eliminates the previous shortcomings and ensures miniaturisation. The design includes a clamping mechanism using magnetism and provides enough force to ensure no leakage through the cover slip and avoid its detachment while ensuring precise testing of the device in microscale. The devised clamping mechanism successfully provides a reliable solution for sustaining proper sealing and functionality in Lung-on-Chip microfluidic devices.

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.

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.

In vitro models are used for studying the physiological function of an organ, disease modelling and drug testing. Over the last decade, since their first commercial introduction, organ-on-a-chip (OOC) technology has proved to be able to recreate aspects of organ function that conventional in vitro models, such as cell culture wells and cell culture inserts, fail to recreate accurately. OOC devices provide a 3D environment for co-culture of cells, that closely mimics the in vivo environment. They provide mechanical cues that are essential for accurately recreating the behaviour of cells. In this report, a new design for a lung-on-a-chip (LOC) device, along with the manufacturing techniques used to make the device, is presented. The device is designed to cyclically stretch the cultured lung epithelial cells to recreate breathing strains, and allows for flow of culture media to recreate shear stress on endothelial cells due to blood flow in the capillaries. The design process involved coming up with an initial dimensional design with the help of COMSOL models of the device. The dimensions were further tweaked on the basis of test results for membrane stain. In comparison to the state-of-the-art LOC devices, which either fail to recreate the strain type or fail to incorporate media flow in a way that recreates blood flow accurately, the device strikes a balance between providing the cyclic strain and providing shear stress. The design focuses on making the device convenient for the end user to set up and use. It allows for direct seeding of the cells in the chip and live imaging of the cells during the experiments.

Current technology of Organ-on-Chips allows investigation of human cells outside the body including a microfluidic medium flow. Control of oxygen in this microfluidic flow is required to mimic the situation as in the human liver (physiological) or to create temporary low oxygen concentrations (hypoxia). In this research, a gas exchanger module is designed for liver-on-a-chip cell experiments at the Erasmus MC. Based on prototype tests and COMSOL simulations, the gas exchanger module is designed and integrated with a commercial Micronit microfluidic channel. The functioning of the fabricated gas exchanger is validated by measuring an oxygen gradient as well as performing oxygen consumption measurements on a liver cell layer.

The Organ on Chip (OoC) market is fast-growing and has the promise to drastically reduce the cost of developing drugs and the need for animal testing. However, the growth could be obstructed by the difficulties of scaling up production of developed prototypes. Most OoC prototypes are not suited for mass production because of the material used, namely polydimethylsiloxane (PDMS). In this thesis a roadmap for the OoC prototyping process is proposed, which can be carried out in small labs without expensive equipment, and which can be directly scaled up to mass production. In the proposed roadmap the polymer cyclic olefin copolymer (COC) is used instead of PDMS. Expensive etching processes typically used to fabricate a mold are replaced by stereolithography printing and soft lithography. The final parts of the chip are soft embossed and for assembly thermal fusion bonding is suggested. These steps require relatively simple equipment, namely a stereolithography printer, a spin coater, a fume hood, and basic lab ware. Next to that, a press for embossing and bonding is required. Such a press is designed, fabricated, calibrated, and tested in this thesis. The press enables embossing and bonding experiments with high repeatability on a simple desktop and can be fabricated in roughly 2 - 3 days in a workshop with standard materials costing no more than € 250,-. Temperature of the compression platens can be controlled within 0.25oC precise up to 180oC. Compression forces up to 3.5 kN can be applied and an accuracy of ±32 N and ±80 N for forces up to respectively 1.3 kN and 2.0 kN can be reached. The performance of the press is tested by carrying out embossing experiments, which yielded replication accuracies comparable with literature for channels of 170 µm deep and 1 mm wide. Next to that, a protocol is produced for spin coating COC films with controllable thickness between 7.5 and 14 µm on top of a COC substrate.

Human Civilization is no stranger to infectious diseases, throughout the abundance of time infectious diseases, famine and wars have been a major threat to human existence and progress. These disease are caused by micrometer to nanometer sized microorganisms like bacteria, pathogens, and viruses. They are of various types, with each having its own unique effect on the infected host. It becomes self evident that only early detection, quarantine and treatment of the infected can curtail a possible exonential growth rate of infections and the possibility of mutation of a given virus to a more virulent strain. The emergence of SARS-CoV-2 in december 2019 has brought about a unified global effort to characterise and curtail the virus. This effort has met with some difficulties, the inability to contain the rapid spread of COVID-19 proceeds from the unavailability of simple, reliable, cheap and rapid testing methods. Lab based testing during epidemics cannot cater for the overwhelming number of test to be done. In such a Pandemic situation, an interplay of the above situational dynamics, begs the need for very sensitive and efficient point of care device that simplifies diagnoses of SARs-CoV-2 virus. The WHO stipulates that all such point of care devices should meet with following standards: (i) affordable; (ii)sensitive; (iii) specific; (iv) user-friendly; (v) rapid and robust; (vi)equipment-free;and (vii) deliverable to end-users. In this thesis, an immunoassay based on surface enhanced Raman spectroscopy (SERS) was used to investigate SARs-CoV-2 antibody for its characteristic Raman finger print. Characterization of SERS substrate like Nanoporous gold, gold nanoparticles deposited on topaz and sputtered on borosilicate glass showed a decent enhancement factor of about 10^3 to 10^4 , it was also observed on all SERS substrate that a 1µm height of deposited nanoparticles was sufficient for SERS enhancement. The immobilization of the Genetex SARs-CoV-2 was done using Cysteamine hydrochloride and Lomants reagent, linkage was only possible only after sufficient cleaning was effected on the SERS substrates, the Raman spectrum obtained was same for both protocols, however noise and substrate instability was observed. The presence of Cysteamine Hydrochloride monolayers was confirmed by the Raman peaks 510, 643, 726, 938, 1015, 2557, 2928, and2962cm−1 each respectively assigned to ν(S − S), ν(C − S), ν(C − S), ν(C − C(−N)), ν(C − C(−N)), ν(S − H), νas(CH2) and ν2(CH2) . The characteristic disufide band, Aliphatic and Aromatic bands, Amide I and Amide III bands were identified for both linking protocols and tentatively assigned. since adsorption of the thiol monolayers was from solution a Langmuir growth model is proposed as the means of thiol growth and orientation.

Since the discovery of the photovoltaic properties of metal halide perovskites in 2009, the material has rapidly gained interest in the scientific community. In less than 10 years, the power conversion efficiency of perovskite solar cells (PSC) has increased from 3.9% to over 25%, reaching levels of conventional silicon cells. PSCs have multiple favorable properties, such as low manufacturing costs, thin film flexibility, and a tunable bandgap, which is promising for tandem solar cells that can surpass the Shockley-Queisser efficiency limit of conventional (single-junction) solar cells. Other applications are color-tunable LEDs and super sensitive (x-ray) photodetectors. However, there are still mysteries surrounding perovskites that need to be solved in order to fully understand the extraordinary properties of the material. For a specific perovskite, CH3NH3PbI3 (MAPI), it is debated whether it has a direct or indirect bandgap. In this work, a new Photothermal Deflection Spectroscopy (PDS) setup is designed and build that can perform sensitive below-bandgap absorption measurements under hydrostatic pressure (up to 400 MPa). Measurements performed with this setup resulted in absorption spectra of MAPI at different pressures, showing a transition from a primarily indirect bandgap at ambient pressure to a more direct bandgap at 375MPa. The data provides new empirical evidence indicating an indirect-to-direct bandgap transition at 325MPa, which opens a novel perspective on unraveling the nature of the bandgap of metal halide perovskites.

The exceptional material properties of bulk diamond like high stiffness, high thermal conductivity, wide optical transparency, chemical inertness and bio-compatibility make it the material of choice in many high-end applications. Most present-day diamond micro-devices are fabricated by costly and time-consuming top-down methods, such as focussed ion beam milling or reactive ion etching. Hence, bottom-up methods that incorporate selective seeding and chemical vapour deposition (CVD) to produce micro-patterned poly-crystalline diamond are of interest. The present work introduces two novel methods for the bottom-up synthesis of nanocrystalline diamond micro-structures. The first method is based on the precise dispensing of nanodiamond dispersions from a hollow AFM cantilever and is used to manufacture freestanding diamond micro-resonators which are analysed on their frequency response. The second method incorporates maskless lithography to create stencils for selective seeding and enables patterned diamond growth on the single digit micrometer scale. A future step of growing such micro-structures in electrically conductive diamond could open up a vast new range up applications.

The suspended microchannel resonator is one of the most reliable devices for the mass measurement of biological and chemical specimens. Since it works in vacuum, the energy dissipation is decreased to the minimum. In this case, the instability related to the thermoelastic coupling effect has become a major source of uncertainty and a main hindrance for higher mass precision. In order to explore methods to control the thermoelastic coupling effect, we investigated factors that are relevant to the instability in eigenfrequency measurements, including the thickness of metal coating on the top of the resonator, and the position of the detecting laser spot on the resonator. We found that this instability-induced error is 1 to 2 orders of magnitude lower on resonators without coating than on those with coating, and 3 to 4 orders of magnitude lower if the measurement is done with the first flexural eigenmode than with the first torsional mode. The minimum mass error is achieved when measuring the first flexural eigenmode on an uncoated suspended microchannel resonator. It is in the magnitude of zeptogram (10e-21g), and can be smaller than the minimum detectable mass change which is limited by the minimum detectable frequency change in the measurement.

Organ-on-chip (OoC) devices are increasingly used for biomedical research and to speed up the process of bringing a medicinal drug from the lab to the market. The technology also addresses ethical issues linked to animal testing as it offers a reduction in animal experiments through its possibility to mimic the environment in the human body. Hence, it produces more relevant results than plain cell-culture experiments, while still sharing the possibility of high-throughput testing by simultaneously operating many devices in parallel. The main components of an OoC device are microfluidic channels and porous membranes. Current chips are often assembled from several parts. In the development phase a small change in design will cause a delay in the research because a new prototype has to be built again step-by-step. This research addresses this problem by targeting the fabrication of a microfluidic device in a single lithography and development step. A device consisting of two crossed channels at different heights separated by a membrane was chosen. The manufacturing method used was two-photon lithography (TPL) on positive photoresist AZ 4562. TPL exploits the fact that two-photon absorption non-linearly depends on the light intensity. The required intensity is only achieved in a small volume around the focal point, called the voxel. By positioning and moving this voxel inside the resist, 3D manufacturing is possible. Therefore the technique can be used for the single step fabrication of a closed channel. By vertically moving the voxel through the resist, pores can be manufactured. In literature an ellipsoidal voxel shape is assumed, leading to the assumption that the maximum voxel, and therefore pore diameter is found at the focal plane, i.e. at z = 0. However, this research shows that the voxel may also have an hourglass-shape for a high enough laser intensity. In this case the maximum voxel diameter is found at a distance z from the focal plane. For the production of pores, therefore the maximum voxel diameter instead of the diameter at the focal plane has to be taken into account. The smallest pores produced measured 250 nm - 290 nm. AZ 4562 was used as a stamp and a mold for the manufacturing of 3D topographical features on a PDMS surface. Finally the microfluidic device was successfully produced in a layer of 50 µm thick resist. The channel width was 100 µm and the height was 10 µm. The channels were separated by 10 µm in height. The sizes of the input and output holes were adapted to the diameter of the smallest available blunt needle, which is 210 µm.

The integration of luminescent nanoparticles into transparent polymer matrices opens the way to affordable, scalable and efficient luminescent solar concentrators. A key challenge in the fabrication is to prevent agglomeration of the nanoparticles as this will drastically reduce the performance due to scattering effects. The incompatibility of inorganic nanoparticles with organic media typically leads to irreversible agglomeration upon direct mixing. In this study, inorganic luminescent Y3Al5O12:Ce3+ nanoparticles are transferred from a polar to a nonpolar solvent without any noticeable agglomeration using amphiphilic statistical copolymers as stabilizing agents. The process parameters that determine the success of stabilization are studied both theoretically and experimentally and a general procedure is proposed to find the optimal conditions for the phase transfer process. The importance of compatibility between the amphiphilic copolymers and the polymer matrix was demonstrated by integrating the stabilized nanoparticles into various polymer matrices. Fully transparent polymer nanocomposite thin films were prepared without any sign of agglomeration. The simple, universal and scalable method presented in this report allows for the fabrication of nanocomposite luminescent solar concentrators using a wide variety of luminescent materials and polymers.

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.

Since its invention, the Atomic Force Microscope has emerged into one of the most useful tools in
nanotechnology due to its acclaimed abilities in exploring surface topography, micro- and nanoscale manipulation
and characterization. The nonlinear interaction between the cantilever tip and the sample surface
has been studied in great detail and a thorough understanding of the cantilever dynamics can improve
measurements and lead to new methods for identification, manipulation and characterization. One of the
biggest challenges in the field of AFM is related to the identification of the cantilever tip size. The accuracy of
measurements in AFM is directly related to the size and geometry of this tip. It is desired that the tip condition
can be continuously monitored in between or even throughout measurements in order to provide high
quality measurements. In this thesis project, a methodology for tip assessment is introduced based on the
nonlinear dynamic response of the cantilever. The method consists of the acquisition of frequency response
curves in the attractive regime where the influence of the tip radius is predominant. Experimental frequency
response curves are fitted to the tip-sample interaction model that includes the van der Waals forces. It is
found that exploiting the nonlinear dynamic response of the cantilever is a safe and accurate method for tip
assessment.