Abstract: MicroRNAs (miRNAs) are small oligonucleotides (18-25 bases) that play a key role in epigenetic regulation. Since the discovery of miRNAs in 1993, their role in biological processes has been extensively investigated. By now, it has been evidenced that monitoring and detection of miRNAs can improve (early) disease diagnosis. The existing diagnostic approaches have limitations such as the need for complex multistep protocols for sample preparation, analysis, data interpretation, high cost of equipment, the need for highly qualified personnel, and high laboratory standards. As opposed to this, point-of-care biosensors and chips aim to facilitate the procedure and avoid sending samples into centralized laboratories, which saves time, reduces the chance of sample degradation, and enables analysis of patient samples in remote areas, directly at home or primary and secondary care facilities (i.e. general practitioners and specialists). The latter is essential for therapy assessment and follow-up monitoring of patients with chronic diseases and cancer. Nevertheless, the development of such sensors is lagging compared to the projections of 10 – 20 years ago, mainly due to insufficient sensitivity, poor reproducibility, and the complexity of the sensors’ design reported in the research literature. This motivates the development of new detection strategies and technologies such as photoelectrochemical sensors that combine the best features of different sensing approaches. The primary concern when developing detection technologies for miRNA is the need for a highly sensitive and selective platform. This thesis explores a novel photoelectrochemical (PEC) method that is distinctive owing to its sensitive nature and simple and robust design. Firstly, we focused on the usage of recently emerging commercial gold-sputtered electrode systems for the detection of short nucleic acid with enzymatic amplification. Importantly, cleaning such electrodes is a challenge since the standard procedures known for regular disk electrodes such as polishing cannot be employed here, since it will damage the protective layer on the electrode. However, the electrodes can be washed and pretreated chemically and/or electrochemically. Thus, a procedure to effectively clean and modify the gold-sputtered electrode has been developed, resulting in high-performance gold-sputtered nucleic acid sensors. Next, the usage of molecular photosensitizers as an alternative to enzymatic amplification has been evaluated. We took advantage of the singlet oxygen production by photosensitizers upon photoexcitation, leading to a photocurrent response due to the singlet oxygen-induced (electro)chemical conversions. Following the demonstration of the detection strategy, the analytical performance of the sensing system was evaluated using magnetic beads-based nucleic acid assay on disposable electrode platforms, with a focus to enhance the sensitivity and robustness of the technique in detecting complementary nucleic acid targets. Following the fundamental evaluation of the singlet oxygen-based PEC detection of nucleic acids, we further optimized the assay and measurement parameters and employed the sensing strategy for a polymerase chain reaction-free (PCR-free) quantification of miRNAs related to prostate cancer. By successfully detecting and quantifying low-picomolar range concentrations (< 10 pM) in plasma samples from prostate cancer patients, we successfully showed the applicability of the novel sensing strategy. We have also compared and positioned the performance of our developed PEC strategy with an existing state-of-art technique, i.e. electrochemiluminescence (ECL). Our PEC strategy performed on par with ECL, both yielding low-picomolar detection limits in serum matrices, however quicker and cheaper than ECL. Owing to the versatility of this PEC technique, the final study explored its multiplexing capability. As a starting point in this branch of the research, we have investigated two possible ways for multiplexing. To perform multiple measurements at the same time, constructing calibration plots and quantifying unknown miRNA concentrations in patient samples at the same time, we have developed a high-throughput detection with 96X multi-channel electrode systems and in-house designed and constructed 96XLED illumination sources. Secondly, to detect more than one target miRNA in a single measurement, intra-vial multiplexing where the samples were analyzed for different targets in one vial was also explored. Altogether, this thesis presents the fundamentals, development and application of a novel PEC strategy for detecting short (< 25 bases) nucleic acid sequences, in particular, miRNA. With an aim to serve as a distinctive technique to function as a clinical testing platform without any need for PCR, this work adds value to the development of nucleic acid-based sensors for miRNAs and other short-stranded nucleic acid biomarkers, and benefits in the early detection of diseases like cancer.

Abstract: Mechanical deformations and ensuing strain are routinely exploited to tune the band gap energy and to enhance the functionalities of two-dimensional crystals. In this Letter, we show that strain leads also to a strong modification of the exciton magnetic moment in WS2 monolayers. Zeeman-splitting measurements under magnetic fields up to 28.5 T were performed on single, one-layer-thick WS2 microbubbles. The strain of the bubbles causes a hybridization of k-space direct and indirect excitons resulting in a sizable decrease in the modulus of they factor of the ground-state exciton. These findings indicate that strain may have major effects on the way the valley number of excitons can be used to process binary information in two-dimensional crystals.

Abstract: Using state-of-the-art simulation methods, we optimized the performance of nanoscale superconducting scanning probe tips for advanced spatial imaging of magnetic fields. The systematic studies of the tips’ static properties as a function of the tilted magnetic field, geometric parameters, and material parameters were carried out. The sensitivity of different superconducting quantum interference devices (SQUIDs) to the magnetic field emanating from the magnetic nanoparticle, where the location of a magnetic nanoparticle is considered below the primary loop's center, was examined as a function of the primary and secondary loop dimensions. The main objective of the research was to characterize and optimize the performance of a nano-sized SQUID-on-tip (SOT) device. Optimal SOT sensitivity was sought, for different loop sizes, arm linewidth, and lead dimensions. Moreover, we revealed that a constriction in the loop arms of the SOT can substantially improve the sensitivity of the device. Finally, the properties of the theta-SOT device were examined in the presence of in-plane and out-of-plane magnetic field components, enabling nanoscale imaging of 3D distributions of the magnetic field. Altogether, the obtained results deliver an engineering solution for the optimum performance of the SOT device in desired conditions.

Abstract: According to the World Health Organization, about 422 million people worldwide have diabetes, with 1.5 million deaths directly attributed each year. Therefore, there is still a need to effectively monitor glucose in diabetic patients for proper management. Recently, wearable patches based on microneedle (MN) sensors provide minimally invasive analysis of glucose through the interstitial fluid (ISF) while exhibiting excellent correlation with blood glucose. Despite many advances in wearable electrochemical sensors, long-term stability and continuous monitoring remain unsolved challenges. Herein, we present a highly stable electrochemical biosensor based on a redox mediator bilayer consisting of Prussian blue and iron-nickel hexacyanoferrate to increase the long-term stability of the readout coupled with a hollow MN array as a sampling unit for ISF uptake. First, the enzymatic biosensor is developed by using affordable screen-printed electrodes (SPE) and optimized for long-term stability fitting the physiological range of glucose in ISF (i.e., 2.5–22.5 mM). In parallel, the MN array is assessed for minimally invasive piercing of the skin. Subsequently, the biosensor is integrated with the MN array leaving a microfluidic spacer that works as the electrochemical cell. Interestingly, a microfluidic channel connects the cell with an external syringe to actively and rapidly withdraw ISF toward the cell. Finally, the robust MN sensing patch is characterized during in vitro and ex vivo tests. Overall, affordable wearable MN-based patches for the continuous monitoring of glucose in ISF are providing an advent in wearable devices for rapid and life-threatening decision-making processes.

Abstract: During the past decades, metallic nanoparticles (NPs) have attracted great attention in materials science due to their specific optical properties based on surface plasmon resonances. Because of these phenomena, plasmonic NPs (or nanoplasmonics) are very promising for application in biosensing, photocatalysts, medicine, data storage, solar energy conversion, etc. Currently, colloidal synthesis techniques enable scientists to routinely produce mono and bimetallic NPs of various shapes, sizes, composition, and elemental distribution, with superior properties for plasmonic applications. Two primary directions for further advancing nanoplasmonic-based technologies include synthesizing novel morphologies, such as highly asymmetric chiral NPs, and gaining deeper insights into the factors affecting the stability of produced nanoplasmonics. With the increasing complexity of nanoplasmonics morphologies and higher stability requirements, there is a pressing need for thorough investigations into their 3D structures and their evolution under different conditions, with high resolution. Electron tomography (ET) emerges as an ideal tool to retrieve shape and element-sensitive information about individual nanoparticles in 3D, achieving resolutions down to the atomic level. Moreover, ET techniques can be combined with in situ holders, enabling detailed studies of processes mimicking real applications of nanoplasmonic-based devices. The first part of this thesis will focus on detailed studies of chiral Au NPs, promising for spectroscopy techniques based on the differential absorption of left- and right-handed circularly polarized light. Specifically, I will discuss the primary strategies for wet-colloidal growth of the various types of intrinsically chiral Au NPs. Advanced ET methods will be demonstrated as powerful tools for characterizing the final helical morphologies of the produced Au NPs and for studying the chiral growth mechanisms by examining intermediate structures obtained during chiral growth. The second part will focus on the heat-induced stability of various Au@Ag core-shell NPs. Operating in real conditions, such as elevated temperatures, may cause particle reshaping and redistribution of metals between the core and shell, gradually altering nanoplasmonics properties. Hence, a thorough understanding of the influence of size, shape, and defects on these processes is crucial for further developments. Recently developed techniques, combining fast ET with in-situ heating holders, have allowed me to evaluate the influence of various parameters (size, shape, defect structure) on heat-induced elemental redistribution in Au@Ag core-shell nanoparticles qualitatively and quantitatively. Additionally, I will discuss the prospects of high-resolution ET for visualizing the diffusion of individual atoms within complex nanostructures.

Abstract: Hoofd-halskanker vormt een aanzienlijke uitdaging met bijna 900.000 nieuwe diagnoses per jaar, waarbij de jaarlijkse incidentie blijft stijgen. Vaak wordt de diagnose pas in een laat stadium gesteld, wat complexe behandelingen noodzakelijk maakt. Terugval van patiënten is helaas een veelvoorkomend probleem. De gemiddelde overlevingsduur is beperkt tot enkele maanden. Daarom is er een dringende behoefte om nieuwe, veelbelovende behandelingen te ontwikkelen voor patiënten met hoofd-halskanker. Voor het bereiken van deze vooruitgang spelen innovatieve studiemodellen een cruciale rol. Het ontwikkelen van deze nieuwe behandelingen start met laboratoriumonderzoek, waarbij traditionele tweedimensionale celculturen hun beperkingen hebben. Daarom verschuiven onderzoekers hun aandacht meer en meer naar geavanceerdere driedimensionale modellen, met hoofd-halskankerorganoïden als beloftevol nieuw model. Dit model behoudt immers zowel het genetische profiel als de morfologische kenmerken van de originele tumor van de hoofd-halskankerpatiënt. Hoofdhalskankerorganoïden bieden daarom de mogelijkheid om innovatieve behandelingen te testen en kunnen mogelijk zelfs de respons van een patiënt op bepaalde therapieën voorspellen. Hoewel tumororganoïden als ‘patiënt-in-het-lab’ veelbelovend zijn, zijn er uitdagingen te overwinnen, zoals de ontwikkelingstijd en de toepasbaarheid bij alle tumortypes, evenals het ontbreken van immuuncellen en andere micro-omgevingscomponenten. Er is daarom een grote behoefte aan gestandaardiseerde protocollen voor de ontwikkeling van organoïden en verkorting van de ontwikkelingstijd. Concluderend bieden driedimensionale hoofd-halskankerorganoïden een veelbelovend perspectief voor de toekomst van kankerbehandelingen. Ze hebben het potentieel om bij te dragen aan de ontwikkeling van gepersonaliseerde behandelingen en zo de overlevingskansen van kankerpatiënten te verbeteren. Het is echter belangrijk om hun voorspellend vermogen en toepassingsmogelijkheden verder te onderzoeken, voordat ze op grote schaal worden geïmplementeerd.

Abstract: Carbon dioxide electrochemical reduction (CO2ER) has attracted considerable attention as a technology to recycle CO2 into raw materials for chemicals using renewable energies. We recently found that Zn-Al layered double hydroxides (Zn-Al LDH) have the CO-forming CO2ER activity. However, the activity was only evaluated by using the liquid-phase CO2ER. In this study, Ni-Al and Ni-Fe LDHs as well as Zn-Al LDH were synthesized using a facile coprecipitation process and the gas-phase CO2ER with the LDH-loaded gas-diffusion electrode (GDE) was examined. The products were characterized by XRD, STEM-EDX, BF-TEM and ATR-IR spectroscopy. In the ATR-IR results, the interaction of CO2 with Zn-Al LDH showed a different carbonates evolution with respect to other LDHs, suggesting a different electrocatalytic activity. The LDH-loaded GDE was prepared by simple drop-casting of a catalyst ink onto carbon paper. For gas-phase CO2ER, only Zn-Al LDH exhibited the CO2ER activity for carbon monoxide (CO) formation. By using different potassium salt electrolytes affording neutral to strongly basic conditions, such as KCl, KHCO3 and KOH, the gas-phase CO2ER with Zn-Al LDH-loaded GDE showed 1.3 to 2.1 times higher partial current density for CO formation than the liquid-phase CO2ER.

Abstract: Our scientific and technological worldviews are largely dominated by the concepts of entropy and complexity. Originating in 19th-century thermodynamics, the concept of entropy merged with information in the last century, leading to definitions of entropy and complexity by Kolmogorov, Shannon and others. In its simplest form, this worldview is an application of the normal rules of arithmetic. In this worldview, when tossing a coin, a million heads or tails in a row is theoretically possible, but impossible in practice and in real life. On this basis, the impossible (in the binary case, the outermost entries of Pascal's triangle xn and yn for large values of n) can be safely neglected, and one can concentrate fully on what is common and what conforms to the law of large numbers, in fields ranging from physics to sociology and everything in between. However, in recent decades it has been shown that what is most improbable tends to be the rule in nature. Indeed, if one combines the outermost entries xn and yn with the normal rules of arithmetic, either addition or multiplication, one obtains Lamé curves and power laws respectively. In this article, some of these correspondences are highlighted, leading to a double conclusion. First, Gabriel Lamé's geometric footprint in mathematics and the sciences is enormous. Second, conic sections are at the core once more. Whereas mathematics so far has been exclusively the language of patterns in the sciences, the door is opened for mathematics to also become the language of the individual. The probabilistic worldview and Lamé's footprint can be seen as dual methods. In this context, it is to be expected that the notions of information, complexity, simplicity and redundancy benefit from this different viewpoint.

Abstract: Natural listening involves a constant deployment of small head movement. Spatial listening is facilitated by head movements, especially when resolving front-back confusions, an otherwise common issue during sound localization under head-still conditions. The present study investigated which acoustic cues are utilized by human listeners to localize sounds using small head movements (below ±10° around the center). Seven normal-hearing subjects participated in a sound localization experiment in a virtual reality environment. Four acoustic cue stimulus conditions were presented (full spectrum, flattened spectrum, frozen spectrum, free-field) under three movement conditions (no movement, head rotations over the yaw axis and over the pitch axis). Localization performance was assessed using three metrics: lateral and polar precision error and front-back confusion rate. Analysis through mixed-effects models showed that even small yaw rotations provide a remarkable decrease in front-back confusion rate, whereas pitch rotations did not show much of an effect. Furthermore, MSS cues improved localization performance even in the presence of dITD cues. However, performance was similar between stimuli with and without dMSS cues. This indicates that human listeners utilize the MSS cues before the head moves, but do not rely on dMSS cues to localize sounds when utilizing small head movements.

Abstract: Today, illicit drugs are omnipresent in society. Clandestine markets are growing faster than ever before, record amounts of cocaine are seized in seaports and airports, while the associated violence is spiralling out of control. In addition, drug monitoring centres worldwide are warning for the increasing complexity of the drug markets, as the traditionally popular drugs are joined by countless new synthetic variants, while medical drugs are also increasingly being abused. In order to provide services confronted with illicit drug samples (police, customs, forensic scientists, first responders, …) with important information on the identity of an unknown sample, suitable analytical tests are required. While these exist for laboratory environments, on-site applicable tests are important to accelerate the decision-making process. Electrochemical sensors have all the advantages required for such on-site tests: they are fast, portable, easy-to-use and reliable. Furthermore, they are not influenced by colours, which are frequently added to drug samples to deceive the existing tests. Previous work has mainly focussed on the detection of a single drug per analysis. However, many drugs could be encountered due to the diversity of the drug markets. Therefore, this project developed electrochemical strategies for the detection of multiple drugs simultaneously. First, the electrochemical behaviour of the individual drugs was studied in different measuring conditions (assessing the influence of pH, concentration and temperature). Then, all findings and strategies were combined to detect multiple targets simultaneously. An electrochemical sensor was developed for the four most popular drugs at music festivals: cocaine, MDMA, amphetamine and ketamine. This sensor generates a so-called ‘superfingerprint’ of the sample, which is then automatically interpreted by a developed algorithm in order to produce a straightforward output. Finally, a pill analysis sensor was developed in the context of drug checking services, where a consumer can anonymously have a sample chemically analysed to obtain information on the composition, dose and potentially harmful additives. The sensor achieved an outstanding accuracy in identifying the main component and provided the option to quantify, as well as an indication on the presence of other substances in the sample. The project’s findings demonstrate the potential for electrochemistry in illicit drug detection and provide a basis for the development of new sensors, targeting other drug combinations.

Abstract: The foodborne pathogens and microorganisms have played a prevalent role in the ebb and flow of the economy worldwide. The increasing population has strained the food processing industry to produce food in large quantity, which in turn has affected the quality of food. To curb this issue, there is immense pressure to produce and maintain quality food within a short time frame. Hence, high throughput technology is used to determine and timely assess the safety and hygiene of food. Further, the revolution of the food industry has also seen an upsurge of new pathogens and microorganisms, thereby increasing the risk of exposure towards rarest diseases to a larger population. This chapter sheds light on the different types of foodborne pathogens affecting the food industry and its social impact. It further emphasizes the safety measures to be taken on the prevention of the disease from the farm to the processing industries and in turn to the household.

Abstract: Generalized Möbius-Listing surfaces and bodies generalize Möbius bands, and this research was motivated originally by solutions of boundary value problems. Analogous to cutting of the original Möbius band, for this class of surfaces and bodies, results have been obtained when cutting such bodies or surfaces. The results can be applied in a wide range of fields in the natural science, and here we propose how they can serve as a model for the heart and the circulatory system.

Abstract: Electron tomography is essential for investigating the three-dimensional (3D) structure of nanomaterials. However, many of these materials, such as metal-organic frameworks (MOFs), are extremely sensitive to electron radiation, making it difficult to acquire a series of projection images for electron tomography without inducing electron-beam damage. Another significant challenge is the high contrast in high-angle annular dark field scanning transmission electron microscopy that can be expected for nanocomposites composed of a metal nanoparticle and an MOF. This strong contrast leads to so-called metal artifacts in the 3D reconstruction. To overcome these limitations, we here present low-dose electron tomography based on four-dimensional scanning transmission electron microscopy (4D-STEM) data sets, collected using an ultrafast and highly sensitive direct electron detector. As a proof of concept, we demonstrate the applicability of the method for an Au nanostar embedded in a ZIF-8 MOF, which is of great interest for applications in various fields, including drug delivery.

Abstract: In present work, we have performed the Grand Canonical Monte Carlo (GCMC) simulations to quantify CO2 capture inside porous silica at high operating temperatures of 673.15 K and 873.15 K; and over a operating pressure range of 500 kPa – 4000 kPa that are methane steam reforming process parameters. Related chemical potential values at these thermodynamic conditions are obtained from the bulk phase simulations in the Canonical ensemble in conjunction with Widom’s insertion technique, where the CO2 has been accurately represented by TraPPE force field. Present structure of the porous silica is a single slit pore geometry of various heights (H = 20 Å, 31.6 Å, 63.2 Å and 126.5 Å), dimensions in which possible vapour-liquid equilibria for generic square well fluids has been reported in literature. Estimation of the pore-fluid interactions show a higher interaction between silica pore and adsorbed CO2 compared to the reported pore-fluid interactions between homogeneous carbon slit pore and adsorbed CO2; thus resulting in an enhancement of adsorption inside silica pores of H = 20 Å and H = 126.5 Å, which are respectively 3.5 times and 1.5 times higher than that in homogeneous carbon slit pores of same dimensions and at 673.15 K and 500 kPa. Estimated local density plots indicate the presence of structured layers due to more molecular packing, which confirms possible liquid-like and vapour-like phase coexistence of the supercritical bulk phase CO2 under confinement.

Abstract: It is standard practice in virtual reality applications to synthesize binaural audio based on a discrete set of directionally-dependent head-related impulse responses (HRIRs). This set of HRIRs is often time-aligned in a pre-processing step, to allow for high-fidelity interpolation between HRIRs corresponding with neighbouring directions. The fidelity of this operation depends on the similarity of neighbouring aligned HRIRs. The pairwise quality of similarity makes it a difficult criterion to optimize globally and consequently one often resorts to alignment methods based on a specific feature that can be extracted for each HRIR separately, e.g., the first-onset of the peak or the group delay. However, such proxies for similarity are very sensitive to noise and therefore require a high signal-to-noise ratio, which makes them less suitable for processing HRIRs acquired outside an anechoic room. In this paper, we advance a novel alignment method, which maximizes the similarity – defined as the correlation between the full-length HRIRs – between neighbouring aligned HRIRs for all directions at once. We show that this correlation-based alignment procedure outperforms the first-onset alignment with regards to the fidelity of the spherical harmonics representation of both the spectral and interaural time difference (ITD) information, when tested on the KEMAR HRIR and six human HRIRs. Finally, we show that the correlation-based alignment is more robust to noise.