Ultrasensitive Label-Free Nanosensing and High-Speed Tracking of Single Proteins

: Label-free detection, analysis, and rapid tracking of nanoparticles is crucial for future ultrasensitive sensing applications, ranging from understanding of biological interactions to the study of size-dependent classical-quantum transitions. Yet optical techniques to distinguish nanoparticles directly among their background remain challenging. Here we present amplified interferometric scattering microscopy (aiSCAT) as a new all-optical method capable of detecting individual nanoparticles as small as 15 kDa proteins that is equivalent to half a GFP. By balancing scattering and reflection amplitudes the interference contrast of the nanoparticle signal is amplified 1 to 2 orders of magnitude. Beyond high sensitivity, a-iSCAT allows high-speed image acquisition exceeding several hundreds of frames-per-second. We showcase the performance of our approach by detecting single Streptavidin binding events and by tracking single Ferritin proteins at 400 frames-per-second with 12 nm localization precision over seconds. Moreover, due to its extremely simple experimental realization, this advancement finally enables a cheap and routine implementation of label-free all-optical single nanoparticle detection platforms with sensitivity operating at the single protein level.Peer ReviewedPostprint (author's final draft

Cerebellar Motor Learning Deficits: Structural mapping, neuromodulation and training-related interventions

Movement allows us to interact with our direct environment, manipulate objects and communicate with each other. Moreover, we can adjust our movements to fit a remarkable range of situations and circumstances. The ability to adjust movements in response to changes in the environment and task demands is referred to as motor learning. The cerebellum is a key neural structure for motor learning. As such, disease of the cerebellum, in addition to the clinical symptom of ataxia, results in various motor learning deficits. There is a consensus that supportive therapy (e.g. physiotherapy, occupational therapy or speech therapy) can reduce ataxia symptoms of cerebellar patients, but little is known about the mechanisms underlying the improvements, and how patients can benefit most. Additionally, motor learning deficits are associated with reduced efficacy of supportive therapy. With the work described in this thesis, we sought to unravel the structural components of cerebellar disease and the relationship between cerebellar integrity and motor learning. Furthermore, we investigated whether motor learning deficits in cerebellar patients could be ameliorated with neuromodulation or training-related interventions, under experimental conditions, hoping to support the development of interventions relevant for application in a clinical setting

Distribution and kinematics of atomic and molecular gas inside the Solar circle

The detailed distribution and kinematics of the atomic and the CO-bright molecular hydrogen in the disc of the Milky Way inside the Solar circle are derived under the assumptions of axisymmetry and pure circular motions. We divide the Galactic disc into a series of rings, and assume that the gas in each ring is described by four parameters: its rotation velocity, velocity dispersion, midplane density and its scale height. We fit these parameters to the Galactic HI and CO (J=1-0) data by producing artificial HI and CO line-profiles and comparing them with the observations. Our approach allows us to fit all parameters to the data simultaneously without assuming a-priori a radial profile for one of the parameters. We present the distribution and kinematics of the HI and H2 in both the approaching (QIV) and the receding (QI) regions of the Galaxy. Our best-fit models reproduces remarkably well the observed HI and CO longitude-velocity diagrams up to a few degrees of distance from the midplane. With the exception of the innermost 2.5 kpc, QI and QIV show very similar kinematics. The rotation curves traced by the HI and H2 follow closely each other, flattening beyond R=6.5 kpc. Both the HI and the H2 surface densities show a) a deep depression at 0.5<R<2.5 kpc, analogous to that shown by some nearby barred galaxies, b) local overdensities that can be interpreted in terms of spiral arms or ring-like features in the disk. The HI (H2) properties are fairly constant in the region outside the depression, with typical velocity dispersion of 8.9+/-1.1 (4.4+/-1.2) km/s, density of 0.43+/-0.11 (0.42+/-0.22) cm-3 and HWHM scale height of 202+/-28 (64+/-12) pc. We also show that the HI opacity in the LAB data can be accounted for by using an `effective' spin temperature of about 150 K: assuming an optically thin regime leads to underestimate the HI mass by about 30%.Comment: 23 pages, 24 figures. Accepted by A&

Finding faint HI structure in and around galaxies: scraping the barrel

Soon to be operational HI survey instruments such as APERTIF and ASKAP will produce large datasets. These surveys will provide information about the HI in and around hundreds of galaxies with a typical signal-to-noise ratio of $\sim$ 10 in the inner regions and $\sim$ 1 in the outer regions. In addition, such surveys will make it possible to probe faint HI structures, typically located in the vicinity of galaxies, such as extra-planar-gas, tails and filaments. These structures are crucial for understanding galaxy evolution, particularly when they are studied in relation to the local environment. Our aim is to find optimized kernels for the discovery of faint and morphologically complex HI structures. Therefore, using HI data from a variety of galaxies, we explore state-of-the-art filtering algorithms. We show that the intensity-driven gradient filter, due to its adaptive characteristics, is the optimal choice. In fact, this filter requires only minimal tuning of the input parameters to enhance the signal-to-noise ratio of faint components. In addition, it does not degrade the resolution of the high signal-to-noise component of a source. The filtering process must be fast and be embedded in an interactive visualization tool in order to support fast inspection of a large number of sources. To achieve such interactive exploration, we implemented a multi-core CPU (OpenMP) and a GPU (OpenGL) version of this filter in a 3D visualization environment ($\tt{SlicerAstro}$).Comment: 17 pages, 9 figures, 4 tables. Astronomy and Computing, accepte

3-D interactive visualisation tools for HI spectral line imaging

Upcoming HI surveys will deliver such large datasets that automated processing using the full 3-D information to find and characterize HI objects is unavoidable. Full 3-D visualization is an essential tool for enabling qualitative and quantitative inspection and analysis of the 3-D data, which is often complex in nature. Here we present $\tt{SlicerAstro}$, an open-source extension of 3DSlicer, a multi-platform open source software package for visualization and medical image processing, which we developed for the inspection and analysis of HI spectral line data. We describe its initial capabilities, including 3-D filtering, 3-D selection and comparative modelling

The Westerbork HI Survey of Spiral and Irregular Galaxies I. HI Imaging of Late-type Dwarf Galaxies

Neutral hydrogen observations with the Westerbork Synthesis Radio Telescope are presented for a sample of 73 late-type dwarf galaxies. These observations are part of the WHISP project (Westerbork HI Survey of Spiral and Irregular Galaxies). Here we present HI maps, velocity fields, global profiles and radial surface density profiles of HI, as well as HI masses, HI radii and line widths. For the late-type galaxies in our sample, we find that the ratio of HI extent to optical diameter, defined as 6.4 disk scale lengths, is on average 1.8+-0.8, similar to that seen in spiral galaxies. Most of the dwarf galaxies in this sample are rich in HI, with a typical M_HI/L_B of 1.5. The relative HI content M_HI/L_R increases towards fainter absolute magnitudes and towards fainter surface brightnesses. Dwarf galaxies with lower average HI column densities also have lower average optical surface brightnesses. We find that lopsidedness is as common among dwarf galaxies as it is in spiral galaxies. About half of the dwarf galaxies in our sample have asymmetric global profiles, a third has a lopsided HI distribution, and about half shows signs of kinematic lopsidedness.Comment: Accepted for publication in A&A. 18 pages. 39 MB version with all figures is available http://www.robswork.net/publications/WHISPI.ps.g

Nanoscale mapping and control of antenna-coupling strength for bright single photon sources

Cavity QED is the art of enhancing light-matter interaction of photon emitters in cavities, with opportunities for sensing, quantum information and energy capture technologies. To boost emitter-cavity interaction, i.e. coupling strength , ultrahigh quality cavities have been concocted yielding photon trapping times of µs to ms. However, such high-Q cavities give poor photon output, hindering applications. To preserve high photon output it is advantageous to strive for highly localised electric fields in radiatively lossy cavities. Nanophotonic antennas are ideal candidates combining low-Q factors with deeply localised mode volumes, allowing large , provided the emitter is positioned exactly right inside the nanoscale mode volume. Here, with nanometre resolution, we map and tune the coupling strength between a dipole nanoantenna-cavity and a single molecule, obtaining a coupling rate of max ~ 200 GHz. Together with accelerated single photon output, this provides ideal conditions for fast and pure non-classical single photon emission with brightness exceeding 10E9 photons/sec. Clearly, nanoantennas acting as “bad” cavities offer an optimal regime for strong coupling , to deliver bright on-demand and ultrafast single photon nanosources for quantum technologies.Peer ReviewedPostprint (author's final draft