Probe Tips Functionalized with Colloidal Nanocrystal Tetrapods for High-Resolution Atomic Force Microscopy Imaging

The performance and resolution of atomic force microscopy (AFM) imaging depends mainly on the quality and shape of the probe tip, since the obtained AFM image is a convolution of the tip profile and the sample structure. Therefore, tip radii that are smaller and aspect ratios that are higher than the sample features are desirable in order to obtain good images. Progress in the ability to design, fabricate, and assemble nanostructures in the size range of a few nanometers has raised the demand for probe tips with a corresponding resolution. Standard commercially available tips made of Si or SiN have a pyramidal shape with a tip radius of the order of 10 nm or larger and therefore do not image nanostructures with features in the few nanometer range adequately. One solution to this problem is the commercially available super-sharp Si probes with tip radius of 2 nm, which, however, obtain their high resolution at a price: the sharp tip can break easily during an experiment. These limitations have stimulated many efforts to enhance the resolution of AFMby functionalizing the probe tips with high-aspect-ratio nanostructures. Carbon nanotubes have demonstrated excellent properties in this respect. Different approaches for the attachment of the carbon nanotubes to the AFM cantilever have been developed, and a spatial resolution of only a few nanometers has been demonstrated. However, the attachment of carbon nanotubes to theAFM tip is still a time consuming and very difficult task, and often results in non-reproducible nanotube configuration and placement. The optimal attachment geometry, with the tip perpendicular to the sample under investigation, is particularly hard to realize. Also, the inherent thermal vibration of long nanotubes can cause difficulties when they are used for AFM imaging. Recent approaches to overcome these difficulties comprise the growth of multiwalled carbon nanotubes and the electron beam induced deposition of carbon nanocones on tipless cantilevers. For a recent review on AFM probes see elsewhere. Shape-controlled semiconductor nanocrystals are another very interesting family of nanostructures that can enhance the spatial resolution of AFM. Tetrapod-shaped nanocrystals are especially appealing for functionalizing AFM tips. Their ability to align on a surface with three supporting base arms, and the fourth arm pointing straight up, resembles an optimal geometry for the sensing of topography with the fourth, vertical arm. Recent advances in colloidal chemical synthesis have led to tetrapod samples with arm lengths of the order of several hundred nanometers and a diameter at the arm extremity well below 10 nm. Moreover, the optoelectronic properties of shape-controlled nanocrystals can extend the functionality of AFM beyond the probing of topography. Banin and coworkers, for example, showed that AFM probes functionalized with spherical core/shell nanocrystals can be used for near field optical imaging. Here, we report the positioning of single CdTe tetrapods on flattenedAFM tips and demonstrate the feasibility of these tips, via the vertical tetrapod arm, for high resolution AFM imaging. Withour tippreparationweachieve anoptimal probingangle of 908, due to the use of contactmode scanning for the preparation of the tip flat. This inherently leads to a tip geometrywith the flat parallel to thesampleplane,which, combinedwiththecapability of tetrapods to self-align with three arms contacting the surface and the fourth pointing vertically upward, results in a geometry where the vertical arm probes the topography at a 908 angle to the sample surface. The high aspect ratio shape of the tetrapod arms, with diameters ranging from 5 to 10nm and lengths ranging from 100 to 300 nm, provides excellent properties for high-resolution topography scanning. In particular, we find that the tetrapod-functionalized tips work very well for imaging surfaces that are covered with nanocrystal samples. Furthermore, our tip fabrication technique could open the way for the fabrication of high aspect ratio optically and electronically sensitive probe tips due to the semiconductor properties of the tetrapods. Large aspect ratio colloidal nanocrystal CdTe tetrapods with arm lengths ranging from 100 to 300 nm and diameters around 10 nm were fabricated by chemical synthesis as reported elsewhere and dissolved in toluene (see Supporting Information Fig. S2 for a TEM image of these very large tetrapods). The rapid growth of the tetrapod arms led to a pointed shape (i.e., to a decreasing arm diameter toward the arm extremity), which is advantageous for our purpose of high spatial resolution imaging (see Fig. 1b). Figure 1(b and c) show transmission electron microscopy (TEM) images of tetrapods deposited by drop casting onto a carbon coated TEM grid. The images show that the tetrapods self-align, with three arms contacting the substrate and the fourth arm pointing straight upward, appearing as a dark circular spot in the image. A sketch of the tetrapod-functionalized AFM probe is shown in Figure 1a. [!] Dr. R. Krahne, C. Nobile, A. Fiore, R. Mastria, Prof. R. Cingolani, Dr. L. Manna National Nanotechnology Laboratory of CNR-INFM Distretto Tecnologico ISUFI Via per Arnesano, Lecce 73100 (Italy) E-mail: [email protected]

Meeting report : 1st international functional metagenomics workshop May 7–8, 2012, St. Jacobs, Ontario, Canada

This report summarizes the events of the 1st International Functional Metagenomics Workshop. The workshop was held on May 7 and 8 in St. Jacobs, Ontario, Canada and was focused on building a core international functional metagenomics community, exploring strategic research areas, and identifying opportunities for future collaboration and funding. The workshop was initiated by researchers at the University of Waterloo with support from the Ontario Genomics Institute (OGI), Natural Sciences and Engineering Research Council of Canada (NSERC) and the University of Waterloo

Personalised profiling to identify clinically relevant changes in tremor due to multiple sclerosis

Background: There is growing interest in sensor-based assessment of upper limb tremor in multiple sclerosis and other movement disorders. However, previously such assessments have not been found to offer any improvement over conventional clinical observation in identifying clinically relevant changes in an individual's tremor symptoms, due to poor test-retest repeatability. Method: We hypothesised that this barrier could be overcome by constructing a tremor change metric that is customised to each individual's tremor characteristics, such that random variability can be distinguished from clinically relevant changes in symptoms. In a cohort of 24 people with tremor due to multiple sclerosis, the newly proposed metrics were compared against conventional clinical and sensor-based metrics. Each metric was evaluated based on Spearman rank correlation with two reference metrics extracted from the Fahn-Tolosa-Marin Tremor Rating Scale: a task-based measure of functional disability (FTMTRS B) and the subject's self-assessment of the impact of tremor on their activities of daily living (FTMTRS C). Results: Unlike the conventional sensor-based and clinical metrics, the newly proposed ’change in scale’ metrics presented statistically significant correlations with changes in self-assessed impact of tremor (max R2>0.5,p< 0.05 after correction for false discovery rate control). They also outperformed all other metrics in terms of correlations with changes in task-based functional performance (R2=0.25 vs. R2=0.15 for conventional clinical observation, both p< 0.05).Conclusions: The proposed metrics achieve an elusive goal of sensor-based tremor assessment: improving on conventional visual observation in terms of sensitivity to change. Further refinement and evaluation of the proposed techniques is required, but our core findings imply that the main barrier to translational impact for this application can be overcome. Sensor-based tremor assessments may improve personalised treatment selection and the efficiency of clinical trials for new treatments by enabling greater standardisation and sensitivity to clinically relevant changes in symptoms

Dissociated Representations of Pleasant and Unpleasant Olfacto-Trigeminal Mixtures: An fMRI Study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO2 alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli

Similar or Different? The Role of the Ventrolateral Prefrontal Cortex in Similarity Detection

Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., “both have peel”), while others continue to look for differences between these objects (e.g., “one is yellow, the other is orange”). These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC). We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI) study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1) Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2) Abstraction per se activates the left dorsolateral PFC

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination