This dissertation revolves around the design and implementation of novel instrumentation and related measurement techniques, at the single molecule level, for use in biophysical research. Chapter 1 presents an introduction to the field of fluorescence-based single molecule measurements. In particular,…

Single-Molecule Microscopy (SMM) techniques constitute a group of powerful imaging tools that enable researchers to study the dynamic behavior of individual molecules.

Detecting nanoscopic objects plays an important role in nanoscience in particular, in the rapidly growing field of nanobiology. The forebear to modern super-resolution microscopy for single molecule investigation, is fluorescence microscopy.

The sequence-dependence of biomolecular interactions involving nucleic acids and proteins is essential for numerous processes inside the cell. Insights into the underlying molecular mechanisms have been obtained using various biochemical and biophysical methods on two different levels — bulk and sin…

In this thesis we investigated the ability of two-photon multifocal microscopy for single-molecule microscopy in live cells and organisms.

This thesis is a collection of experimental attempts to enhance photoluminescence of fluorescent molecules and quantum dots with single gold nanorods (GNRs) and relevant applications.

Viral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge…

Spectroscopic studies on fluorescent single molecules in organic condensed matter does not only provide information about the molecule itself, but also its near environment. By suppression of phonon-induced broadening of spectral lines through cooling to low temperatures, small changes in the spectral…

Promotor: Prof.dr. M.A.G.J. Orrit

Promotores: Prof.dr. G.W. Canters, Prof.dr. T.J. Aartsma

In human cells, a meter-long DNA is condensed inside a micrometer-sized cell nucleus. Simultaneously, the genetic code must remain accessible for its replication and transcription to functional proteins.

Single-molecule spectroscopy has become a powerful method for using organic fluorescent molecules in numerous applications.

Early time-resolved experiments by Frauenfelder on the ensemble of the kinetic rebinding of CO to myoglobin molecules resulted in a stretched exponential relaxa-tion due to a very large spread of the reaction rates of individual molecules.

This thesis aims to improve the detection from ultra-weak single emitter by enhancing their emission properties with plasmonic nanostructures. We exploit the wet-chemically synthesized single crystalline gold nanorods (GNRs) as our basic frameworks in the whole studies, simply because of their unique…

Promotor: M.A.G.J. Orrit

Promotor: T. Schmidt, Co-promotor: S. J.T. van Noort

In this work, we investigate the minute circular dichroism effects of single nanoparticles.To this aim, we apply photothermal imaging with a polarization-modulated heating beam.

Promotores: Prof.dr. D. Bouwmeester, Prof.dr. A. Fiore (TU Eindhoven)

In this thesis, we study different curved single crystals because of the diversity of surface structures across their curvature.

Menselijke cellen beschermen hun eiwitten tegen ontvouwen en samenklonteren. Dat ontdekten biofysicus Alireza Mashaghi en zijn team na zeven jaar diepgaand onderzoek naar de vouwmechanismen van eiwitten. Met een nieuwe, baanbrekende methode slaagde het team erin om een afzonderlijk eiwit te vouwen en…

Curved single crystals provide variable, but well-defined surface structures.

Promotor: Thomas Hankemeier, Co-promotores: Heiko van der Linden, Paul Vulto

Complex Organic Molecules (COMs) have been detected in objects across different stages of stellar evolution.

Gold nanorods are biocompatible nanoparticles that present an excellent two-photon signal that can be used to get high spatial resolution inside living cells. Gold nanorods are photostable and therefore can be followed inside cells for long time, with possible applications as trackers in live cells.

A single self-assembled semiconductor quantum dot in a high-finesse optical microcavity - the subject of this thesis - is an interesting quantum-mechanical system for future quantum applications. For instance, this system allows trapping of an extra electron and thus can serve as a spin quantum memory,…

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription.

Promotor: Prof.dr. E. F. van Dishoeck

This thesis revolves around the electronic spectroscopy of molecules in the laboratory and the search for the carriers of the diffuse interstellar bands (DIBs).

Acute cardiovascular syndromes, including myocardial infarction or stroke, are the principal cause of death in the Western society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in…

Viral diseases constitute one of the major challenges in modern medicine. Membrane-targeting have broad-spectrum potential and could distinguish viral membranes from the host cell plasma membrane by the difference in membrane curvature.

Large areas of space are filled by molecular clouds that consist of gas and dust grains that are the remnants of dead stars. When these clouds start collapsing, the decreasing temperature and increasing density cause gas particles to start accreting onto dust grain surfaces.

Promotor: Prof.dr. G.J. Kroes

Promotores: G.W. Canters, T.J. Aartsma

The main focus of the thesis is the discovery and development of novel inhibitors of bacterial metallo-β-lactamases (MBLs).

Promotor: Prof.dr. T. Schmidt, Co-Promotor: S.J.T. van Noort

The deeper understanding of an organism's pathology is important for developing treatments. Over centuries of systematic research, clinical researchers have demonstrated that the more information they acquire about the cellular properties and their organisation in the tissue, the better they can understand…

This thesis consists of two main parts. The first part (Chapters 2 and 3) deals with a class of Markov process called Quasi-Skipfree (QSF) processes.

Despite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we probably only know a subset.

I will give a general introduction to the field of molecular electronics, its history, methods and challenges. I will also introduce the subject of my investigation and provide a brief outlook to the remainder of our thesis.

Heterogeneous catalyzed processes are highly significant to the chemical industry. Dissociative chemisorption (DC) of molecules on surfaces is always considered as a step with a high degree of rate control for heterogeneous catalysis.

Promotor: Prof.dr. T. Hankemeier

Het is nog nooit gelukt om een enkel elektron te detecteren met zichtbaar licht via slechts één molecuul. Leids natuurkundige Michel Orrit en zijn onderzoeksgroep hebben nu een molecuul geïdentificeerd dat gevoelig genoeg is om een elektron te detecteren op een afstand van honderden nanometers. De resultaten…

Promotor: Prof.dr. M. Ubbink, Co-promotor: G. Siegal

In this thesis, we describe the potential of cell mechanical phenotyping for immune cell characterization, diagnosis, drug testing, as well as treatment of disease.

Several techniques are explored for going beyond the born-oppenheimer static surface model for molecule-surface reactions.

De H. D. Landahl Mathematical Biophysics Award van 2017 is toegekend aan Lisanne Rens. Zij is als promovendus bij het CWI (Centrum Wiskunde & Informatica) in Amsterdam tevens verbonden aan het Mathematisch Instituut van de Universiteit Leiden.

Promotor: J.M. van Ruitenbeek, Co-Promotor: S.J. van der Molen

This thesis examines the link between simple molecules and the underlying structure and chemistry within protoplanetary disks - the birthplaces of planets.