Spatially dependent photoluminescence and atomic-resolution images confirm the high crystallinity of the monolayers and the seamless lateral connectivity between the different TMD domains. These findings could be extended to other families of 2D materials, and creates the foundation towards the development of complex and atomically thin in-plane super-lattices, devices and integrated circuits. 17 2 A key step for the fabrication of TMD-based heterostructures is to control the relative amount of precursors in the gaseous phase from the solid sources during a one-pot synthesis strategy. In general, compounds based on MX2 (where: M= [W, Mo] and X= [S, Se]) have high melting points. Therefore, they are not a common choice as precursors for vapor transport synthesis, although dissociation has been observed by mass spectroscopy at temperatures ranging between 930 and 1090 o C. 18 The presence of water vapor can significantly influence their physicochemical properties, such as oxidation and the formation of volatile species. 15, 16 The enhanced volatility of Mo/W, and of their known oxides above 1000 o C, in the presence of water vapor, has already been reported in the early 1950s. 16,19,20 Reaction of MoS2 and water vapor was initially reported by Cannon et al. 15 which indicates that MoS2 undergoes quick oxidation above 450 o C. However, a minimum temperature of 1000 o C is required to generate an equilibrium concentration of H2S in the reactive environment relative to the concentration of H2O. 21 In this report, MoX2-WX2 lateral heterostructures were grown using a solid source composed of MoX2 and WX2 powders placed side-by-side within the same boat at high temperatures. The selective growth of each material was controlled independently only by switching the carrier gas, i.e. from N2+H2O (v) to Ar+H2 (5%). N2+H2O (v) promotes the growth of MoX2. Switching to Ar+H2(5%) stops the growth of MoX2 and promotes the growth of WX2. Figure 1a and 1b (left panels) show optical images of a lateral heterostructure containing a core composed of monolayer MoSe2 (darker contrast) and a WSe2 monolayer shell (lighter), both grown on SiO2/Si substrate, containing different shell lateral sizes (Extended data Fig. 1a-1h). The sizes of both the core and the shell were controlled by choosing the growth time of each individual section. These MoSe2-WSe2 single-junction monolayers predominantly display, an equilateral triangle geometry. Noticeably, the nucleation of the consecutive material (WSe2) happens mainly at the edges of the MoSe2 triangular monolayers resulting in a lateral epitaxial growth, as shown below by the Scanning Transmission Electron Microscopy (STEM) analysis.In general, the typical sample area is at least 5 x 5 mm 2 but hundreds of similar monolayer lateral heterostructures can be found on the same substrate. The average size of the heterostructure islands varies with their position on the substrate due to the temperature profile of the furnace (Fig. 1l); and hence is a function of the substrate temperature for ...

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of haematological cancers and is currently being investigated for solid tumours, including high-grade glioma brain tumours. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumours. In this work, we use a mathematical model of predator–prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor T-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, proliferation, exhaustion, and persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyser to parametrize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted when compared with higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumour growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumour characteristics including tumour growth rate and antigen level to maximize therapeutic benefit.

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Electrically active field-effect transistors (FET) based biosensors are of paramount importance in life science applications, as they offer direct, fast, and highly sensitive label-free detection capabilities of several biomolecules of specific interest. In this work, we report a detailed investigation on surface functionalization and covalent immobilization of biomarkers using biocompatible ethanolamine and poly(ethylene glycol) derivate coatings, as compared to the conventional approaches using silica monoliths, in order to substantially increase both the sensitivity and molecular selectivity of nanowire-based FET biosensor platforms. Quantitative fluorescence, atomic and Kelvin probe force microscopy allowed detailed investigation of the homogeneity and density of immobilized biomarkers on different biofunctionalized surfaces. Significantly enhanced binding specificity, biomarker density, and target biomolecule capture efficiency were thus achieved for DNA as well as for proteins from pathogens. This optimized functionalization methodology was applied to InP nanowires that due to their low surface recombination rates were used as new active transducers for biosensors. The developed devices provide ultrahigh label-free detection sensitivities ∼1 fM for specific DNA sequences, measured via the net change in device electrical resistance. Similar levels of ultrasensitive detection of ∼6 fM were achieved for a Chagas Disease protein marker (IBMP8-1). The developed InP nanowire biosensor provides thus a qualified tool for detection of the chronic infection stage of this disease, leading to improved diagnosis and control of spread. These methodological developments are expected to substantially enhance the chemical robustness, diagnostic reliability, detection sensitivity, and biomarker selectivity for current and future biosensing devices.

Venous system pathologies have increasingly been linked to clinically relevant disorders of CSF circulation whereas the exact coupling mechanisms still remain unknown. In this work, flow dynamics of both systems were studied using real-time phase-contrast flow MRI in 16 healthy subjects during normal and forced breathing. Flow evaluations in the aqueduct, at cervical level C3 and lumbar level L3 for both the CSF and venous fluid systems reveal temporal modulations by forced respiration. During normal breathing cardiac-related flow modulations prevailed, while forced breathing shifted the dominant frequency of both CSF and venous flow spectra towards the respiratory component and prompted a correlation between CSF and venous flow in the large vessels. The average of flow magnitude of CSF was increased during forced breathing at all spinal and intracranial positions. Venous flow in the large vessels of the upper body decreased and in the lower body increased during forced breathing. Deep respiration couples interdependent venous and brain fluid flow—most likely mediated by intrathoracic and intraabdominal pressure changes. Further insights into the driving forces of CSF and venous circulation and their correlation will facilitate our understanding how the venous system links to intracranial pressure regulation and of related forms of hydrocephalus.