Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills eventually leading to death from complete brain failure. It is the most common cause of dementia and affects more than 46 million people globally, with 500'000 new cases diagnosed annually in the United States alone. While there is still no cure for AD, there are several prescription drugs approved by the U.S. Food and Drug Administration to treat its symptoms. Recently, there has been growing excitement around treating neurological diseases using neuromodulation techniques. Flickering strobe lights at gamma-frequency of 40 Hz have shown very promising results in mouse models where microglia immune cells could be activated and contributed to degradation of amyloid-β proteins. Invasive neuromodulation methods can target very specific areas in the brain. The current modulation devices, however, are comparable to that of early cardiac pacemakers, leading to fibrotic encapsulation within weeks. This is mainly predicated on the neural probe's mechanical properties, given by the hard platinum/iridium electrodes from the semiconductor industry. Our proposed approach for ten thousand times softer electrodes is based on nano engineered neural interfaces (NENI) - hybrid microstructured polymer pads covered by ultra-thin and soft nanostructured metal/elastomer compounds. Our NENI probes will allow a rapid reconfiguration to pre-selected brain targets for a patient-specific anatomy and therefore enable the activation of microglia immune cells. This project is in collaboration with 5 project partners from around Switzerland: University Hospital Basel, Empa, PSI, FHNW, and University of Basel. In addition, two companies: Invibio Ltd/United Kingdom, a leading provider of polymeric biomaterials which have been used in around 9 million PEEK medical implants with more than 15 years of proven clinical history and Valtronic SA, a global contract manufacturer for the electronics of medical devices, are supporting this project.

AFM for nano-structural and -mechanical studies of dielectric actuators

Multi-modal matching is understood as the automatic (elastic) alignment of data, termed regis-tration, from different imaging techniques using the characteristic anatomical features. While satisfying approaches for two-dimensional (2D) to 2D and three-dimensional (3D) to 3D data sets have been developed during the last two decades, the non-rigid 2D-3D registration belongs to the unsolved problems because of the larger degrees of freedom especially for high-resolution 'big data'. The need for 2D-3D registration, however, becomes more and more obvious, as besides the well-established histology, which highlights the functionality in tissue slices according to the selected stain, magnetic resonance (MR) and computed tomography (CT) 3D data with better and better spatial resolution and contrast have been acquired. The combination of the functional information from 2D images with the local physical quantities in 3D recorded, for example, by means of micro CT (µCT) and MR microscopy has been vital to (i) correct preparation artifacts in the histological slices applying the less detailed 3D data, to (ii) identify the issue types in 3D data using the functional information from histology in quantitative manner and to (iii) determine the optimized location and direction of histological slicing. The aim of the project is the development of algorithms for the automatic non-rigid multi-modal 2D-3D registration. Here, we will concentrate on registering histological sections with µCT-data. In a first stage, we will focus on the development of a sparse image registration approach that has the advantage of being robust and computationally efficient. The second stage uses the sparse registration as anchor points while delivering a dense multimodal registration of the two imaging modalities. Finally, the computational effort and the general usability will be optimized to allow the processing of large data sets that are characteristic for high-resolution 3D imaging in biomedical engineering.

The human body contains 10^14 cells, which are categorized into 200 to 400 cell types. The human brain accounts for about 2% of the weight of an average person. This is a much larger percentage than in other primates. Despite of its size and complexity one can reasonably assume that it is possible to reveal the individual cells within the human brain and describe its three-dimensional structure on the cellular level. To achieve this goal, we will perform grating-based hard X-ray phase tomography using synchrotron radiation facilities. In addition we will expand the available laboratory system phoenix nanotom® m from GE Healthcare by a grating interferometer. An average human cell contains 10^14 atoms, which are categorized in the 118 elements of the periodic table. Thanks to this clarity, one can reasonably expect that it is possible to reveal the nanostructure of selected pieces of brain tissues. To achieve this, we will perform spatially resolved X-ray scattering experiments at the cSAXS-beamline, Swiss Light Source at the Paul Scherrer Institut. The myelinated axons, for example, which stretch for over 10^8 m if aligned end-to-end, exhibit a quasi-periodical arrangement of the lamellar structure of the myelin sheaths repeating less than every 20 nm. This characteristic periodicity will be used to determine the abundance and the orientation of the myelin fiber bundles in projection images similar to histology and in three-dimensional space applying tomographic reconstruction techniques, which are to be further developed. The interdisciplinary project aims to bridge the gap concerning spatial resolution between the tomography data from clinical modalities (CT and MRI) and histological approaches employed by anatomists and pathologists taking advantage of recent developments in physics: X-ray scattering and phase tomography.

The aim of the proposal is to realize prototype devices acting as artificial muscle, termed anal sphincter, to finally treat patients with severe FI. The device should replace the destroyed natural muscle function using low-voltage electrically activated polymers (EAPs) controlled by implemented pressure sensors and the patient. The unique artificial fecal EAP-based sphincter system is driven by an integrated microprocessor, powered by an energy harvesting device and an implantable battery, rechargeable by transcutaneous energy transfer (TCT) controlling the fluid flow intentionally by the patient and automatically with pressure gauges. The remote control will allow the physician to perform patient-specific adjustments.

The three-dimensional vascular structures down to the smallest capillaries have been of vital interest in cancer research because of the demand for alternatives to the established treatments (surgery, medication and radiation). The present research efforts range from in vivo imaging (MRI, US, and PET), via post mortem methods, including micro computed computer tomography. In a previous study, we showed that synchrotron radiation-based necessary spatial resolution and contrast to capture the smallest vessels from casts. Tumors with damaged vessel walls are inappropriate for casting. Therefore, phase tomography was applied to visualize the capillaries. Grating-based tomography yields the necessary contrast but vessels with a diameter smaller than 20 provides the necessary spatial resolution but hardly enough contrast. Consequently, we propose first to improve the spatial resolution of grating-based tomography, second to identify rather simple in-line tomography approaches such as the one introduced by Paganin searching for better contrast, and third to combine tomograms from both approaches to gain additional information toward the smallest capillaries.

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The human body possesses a huge potential for self-healing. In many processes tissue is regularly formed and removed. Our teeth as well are constantly demineralized and remineralized when we ingest. If this equilibrium comes out of balance, the tooth cannot be remineralized and dental caries is the consequence. This process depends on the oral hygiene, preferred type of food, and oral microflora of each individual. In a first step, bacterial acids cause a demineralisation at the weakest point of the tooth. Initial lesions or "white spots" develop. These rarely remineralize spontaneously and normally cannot be regenerated. If caries proceeds, the pseudointact surface breaks down forming a carious cavity. Standard treatment since more than 100 years is to mechanically open the carious area and to fill it with a biocompatible material. Credentis ag has now launched an innovative treatment method that regenerates the affected enamel. Scientists of the University of Leeds have developed a self-assembling peptide that, applied to the carious lesion, diffuses into the initial lesion and forms a supramolecular network inside the carious lesion. As soon as this 3D network exists, the crystallisation of nanocrystals is initated and the regeneration of the white spots is induced. Nowadays, initial lesions can be treated successfully applying this method. For larger cavities the product does not function yet.

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The correct sourse of funding is SATW / Swiss Nanoscience Institute (SNI)