Harnessing the damping properties of materials for high-speed atomic force microscopy

The success of high-speed atomic force microscopy in imaging molecular motors1, enzymes2 and microbes3 in liquid environments suggests that the technique could be of significant value in a variety of areas of nanotechnology. However, the majority of atomic force microscopy experiments are performed in air, and the tapping-mode detection speed of current highspeed cantilevers is an order of magnitude lower in air than in liquids. Traditional approaches to increasing the imaging rate of atomic force microscopy have involved reducing the size of the cantilever4,5, but further reductions in size will require a fundamental change in the detection method of the microscope6–8. Here, we show that high-speed imaging in air can instead be achieved by changing the cantilever material. We use cantilevers fabricated from polymers, which can mimic the high damping environment of liquids. With this approach, SU-8 polymer cantilevers are developed that have an imaging-in-air detection bandwidth that is 19 times faster than those of conventional cantilevers of similar size, resonance frequency and spring constant

Automaticity in sequence-space synaesthesia: a critical appraisal of the evidence

For many people, thinking about certain types of common sequence - for example calendar units or numerals - elicits a vivid experience that the sequence members occupy spatial locations which are in turn part of a larger spatial pattern of sequence members. Recent research on these visuospatial experiences has usually considered them to be a variety of synaesthesia, and many studies have argued that this sequence-space synaesthesia is an automatic process, consistent with a traditional view that automaticity is a key property of synaesthesia. In this review we present a critical discussion of data from the three main paradigms that have been used to argue for automaticity in sequence-space synaesthesia, namely SNARC-like effects (Spatial-Numerical-Association-of-Response-Codes), spatial cueing, and perceptual incongruity effects. We suggest that previous studies have been too imprecise in specifying which type of automaticity is implicated. Moreover, mirroring previous challenges to automaticity in other types of synaesthesia, we conclude that existing data are at best ambiguous regarding the automaticity of sequence-space synaesthesia, and may even be more consistent with the effects of controlled (i.e., non-automatic) processes. This lack of strong evidence for automaticity reduces the temptation to seek explanations of sequence-space synaesthesia in terms of processes mediated by qualitatively abnormal brain organization or mechanisms. Instead, more parsimonious explanations in terms of extensively rehearsed associations, established for example via normal processes of visuospatial imagery, are convergent with arguments that synaesthetic phenomena are on a continuum with normal cognition. (c) 2012 Elsevier Ltd. All rights reserved

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Development of Implantable Electrodes Based on Polymer Derived Ceramics

The invention of heart pacemakers in the 50's aims to help patients to overcome heart strokes, which represent the first cause of death worldwide. In Europe and in the USA, more than 3000 pacemakers are implanted every day. Despite the constant evolution of the pacemaker system, the lifetime of the implants is limited to several years. State of the art pacemaker electrodes suffer from pacing signal inhibition related to fibrotic tissue growth. This thesis describes the development of novel electrically conductive ceramic based materials, which promise to be more bio-inert than the currently used metals electrodes. Several Polymer Derived Ceramic (PDC) materials (Ceraset, SMP10 and SU8) have been investigated. In order to induce electrical conductance our project partner at EMPA doped the ceramics by an increase in carbon contents. However, for SU8 this step was not necessary. Photolithography and moulding were the two main microfabrication methods used for shaping the PDC materials. Moulding showed to be the most suitable method for shaping Ceraset and SMP10 materials. Thanks to the optimization work of the mould coatings, the main advantage of moulding consists in the possibility to release the PDC from the mould prior the sintering at high temperature. The release can be further facilitated when using elastomeric mould. SU8 was shaped by means of photolithography on top of a water soluble Dextran release layer and released before sintering. The materials were characterized at each fabrication step. The material composition, surface analysis and hardness of the densified ceramic samples have been measured. Furthermore an electrochemical characterization was performed in PBS and 1M KCl solution, by means of cyclic voltammetry and electrochemical impedance spectrometry. The measurements of the new materials show comparable values and behaviours to standard Pt metal electrodes. As the electrodes are meant to be implanted, it was necessary to investigate their cytotoxicity and in vitro biocompatibility for non-conductive and conductive compositions. Low cytotoxicity levels comparable to the state of the art positive reference implant materials have been assessed. To elucidate the fibrosis inhibition, long-term implantation tests (1 week to 6 months) have been carried out without the presence of electric signals. The fibrosis level turned out to be low for the new materials and comparable the reference materials. The pacing functionality of the new electrodes has been experimentally assessed as follows: (a) In vitro pacing of isolated cardiomyocytes by applying an electric potential of 20-40 V between two electrodes. The cell contraction was quantified by correlating the pacing signal with the hemodynamic parameters by means of video recording and image processing; (b) In vivo and ex vivo tests on a rat model were conducted by implanting SU8 micro-electrodes into peripheral muscles and in an isolated and perfused heart, respectively. The analysis confirmed that both muscle tissues were successfully actuated by using typical signal parameters. In conclusion, this thesis presents the successful development, optimisation and fabrication of pacemaker electrodes with new materials, which possess properties that are comparable to state of the art platinum electrode. This work provides a selection of materials for further characterization of long term implanted electrodes, studying the influence of an electric pacing signal on the fibrosis

Sub micrometer ceramic structures fabricated by molding a polymer-derived ceramic

This paper describes the fabrication of sub micrometer silicon oxycarbide (SiCO) ceramic structures. The method consists in replicating silicon micro/nanostructures in polydimethylsiloxane (PDMS), followed by a micro/nano molding of liquid polymer derived ceramic precursor (PDC). A dense ceramic SiCO replicated structure is obtained. In order to replicate the original structures with the highest fidelity possible, we applied a combination of coatings on the PDMS mold, in order to improve both filling and releasing. It was possible to fabricate reproducibly arrays of ceramic tips with a radius of 120 nm

Transflective holographic film for head worn display

A display panel assembly comprises a transflective holographic screen, i.e., a transparent screen that reflects light from a projection system, comprising at least a volume hologram, a first protective element and a second protective element, each arranged in contact with the volume hologram such that the volume hologram is sandwiched between the first protective element and the second protective element. The display panel assembly further comprises a projection system focusing an image on the volume hologram comprising at least projection optics, mounting means arranged to fixedly mount the projection system relatively to the transflective holographic screen. The volume hologram comprises a plurality of diffractive patterns disposed in sequence across the volume hologram, each of the plurality of diffractive patterns being configured to diffuse the light rays from the projection system in a determined direction corresponding to the specific diffractive pattern and oriented towards a position of an intended eye of a user wearing the display panel assembly

On the micrometre precise mould filling of liquid polymer derived ceramic precursor for 300-µm-thick high aspect ratio ceramic MEMS

This paper describes a novel and scalable method for the fabrication of polymer derived ceramics (PDC) structures with high aspect ratio and micrometre scale features. Elastomeric micro-moulds composed of a filling pot are used to deliver via sacrificial micro-channels a precise amount of the liquid ceramic precursor to the target location with the micro-scale functional structures. To improve the filling properties of the mould and to ease the de-moulding of the fragile green body parts, we investigated various channel and mould coating materials, such as carbon and Teflon®-like C4F8. The coating properties were characterised by measuring the contact angle and the advancing speed of the PDC inside micro-channels. We found that, the C4F8 Teflon®-like coating yields the best de-moulding results for high aspect ratio moulds, whereas the carbon coating yields a two-fold increase in filling speed compared to bare PDMS. The fabricated samples and their side-wall properties were characterised in detail by means of optical and scanning electron microscopy. We present process parameters for well-defined ceramic samples containing micrometric features fabricated with this new approach opening the use of this outstanding material for new MEMS applications where resistance to harsh environment such as mechanical wear, high temperatures or corrosion is required. The presented fabrication method has the potential to be scalable up to cost-efficient mass production