Interaction of nanoparticles with lipid films: the role of symmetry and shape anisotropy.

The bioactivity, biological fate and cytotoxicity of nanomaterials when they come into contact with living organisms are determined by their interaction with biomacromolecules and biological barriers. In this context, the role of symmetry/shape anisotropy of both the nanomaterials and biological interfaces in their mutual interaction, is a relatively unaddressed issue. Here, we study the interaction of gold nanoparticles (NPs) of different shapes (nanospheres and nanorods) with biomimetic membranes of different morphology, i.e. flat membranes (2D symmetry, representative of the most common plasma membrane geometry), and cubic membranes (3D symmetry, representative of non-lamellar membranes, found in Nature under certain biological conditions). For this purpose we used an ensemble of complementary structural techniques, including Neutron Reflectometry, Grazing Incidence Small-Angle Neutron Scattering, on a nanometer lengthscale and Confocal Laser Scanning Microscopy on a micrometer length scale. We found that the structural stability of the membrane towards NPs is dependent on the topological characteristic of the lipid assembly and of the NPs, where a higher symmetry gave higher stability. In addition, Confocal Laser Scanning Microscopy analyses highlighted that NPs interact with cubic and lamellar phases according to two distinct mechanisms, related to the different structures of the lipid assemblies. This study for the first time systematically addresses the role of NPs shape in the interaction with lipid assemblies with different symmetry. The results will contribute to improve the fundamental knowledge on lipid interfaces and will provide new insights on the biological function of phase transitions as a response strategy to the exposure of NPs.

Revealing the interfacial nanostructure of a deep eutectic solvent at a solid electrode.

Deep eutectic solvents (DESs) are both green and sustainable, making them an increasingly attractive alternative to conventional solvents. One of their applications is the electrochemical deposition of metals that cannot be deposited from aqueous solution because of the limited electrochemical window of water. The electrodeposition process is influenced by the structure and dynamics of the solvent at the solid-liquid interface. Therefore,the nanoscale structure of the interface between a silicon substrate and deep eutectic solvent (choline chloride-ethylene glycol) was studied by neutron reflectometry (NR) and molecular dynamics (MD) simulations. It is not possible to model NR measurements of this system without simulating a dense DES layer at the solid-liquid interface. This study used an MD simulation trajectory to extract the density, thickness, and roughness of this DES layer. With this input, the model reproduces the reflectometry data at all measured H/D contrasts very well. The thickness of the layer does not change appreciably when applying charge or at higher temperatures. Further analysis revealed a reorganization of ions and reorientation of the choline cations in the interface layer when the electrodes are charged. These changes in ion orientation are not observed with the NR technique since they do not influence the neutron scattering length density profile due to the high number of ethylene glycol molecules at the interface. However, the agreement between measured neutron reflectometry data and model parameters obtained from MD simulations justified subnanoscale analysis of the MD trajectory and confirmed that these two complementary techniques can be successfully combined to reveal the solid/DES interface structure.

Probing the Interface Structure of Adhering Cells by Contrast Variation Neutron Reflectometry.

Cellular adhesion is a central element in tissue mechanics, biological cell-cell signaling, and cell motility. In this context, the cell-substrate distance has been investigated in the past by studying natural cells and biomimetic cell models adhering on solid substrates. The amount of water in the membrane substrate gap, however, is difficult to determine. Here, we present a neutron reflectivity (NR) structural study of confluent epithelial cell monolayers on silicon substrates. In order to ensure valid in vitro conditions, we developed a cell culture sample chamber allowing us to grow and cultivate cells under proper cell culture conditions while performing in vitro neutron reflectivity measurements. The cell chamber also enabled perfusion with cell medium and hence allowed for contrast variation in situ by sterile exchange of buffer with different H2O-to-D2O ratio. Contrast variation reduces the ambiguity of data modeling for determining the thickness and degree of hydration of the interfacial cleft between the adherent cells and the substrate. Our data suggest a three-layer interfacial organization. The first layer bound to the silicon surface interface is in agreement with a very dense protein film with a thickness of 9 ± 2 nm, followed by a highly hydrated 24 ± 4 nm thick layer, and a several tens of nanometers thick layer attributed to the composite membrane. Hence, the results provide clear evidence of a highly hydrated intermediate region between the composite cell membrane and the substrate, reminiscent of the basal lamina.

Hydration and Solvent Exchange Induced Swelling and Deswelling of Homogeneous Poly(N-isopropylacrylamide) Microgel Thin Films.

The investigation of the response kinetics of smart colloidal microgel films is crucial for their optimization to enable advanced applications. We study the classical thermoresponsive microgel model system N-isopropylacrylamide cross-linked with N,N'-methylenebisacrylamide. Without the typically used polyelectrolyte coating of the substrate, thin microgel films are prepared in a single spin-coating step. Atomic force microscopy measurements reveal an extremely dense packing, resulting in a homogeneous compact thin film of microgel particles. The hydration kinetics of these films in H2O and D2O atmospheres as well as the kinetics of the solvent exchange between both water species are investigated with in situ time-of-flight neutron reflectometry (TOF-NR) and in situ Fourier-transform infrared (FTIR) spectroscopy. With accounting for a nonconstant humid atmosphere, the intrinsic diffusion dynamics of water molecules into the thin microgel film are modeled and the specific time constant τ and the effective Flory-Huggins interaction parameter χeff are determined. Comparing the results in H2O and D2O atmospheres, TOF-NR and FTIR spectroscopy results show an increased affinity of the microgel films toward H2O as compared to D2O. From the FTIR spectroscopy data, we further identify different kinetics of intermolecular processes and order them according to their temporal evolution.

Density profile in thin films of polybutadiene on silicon oxide substrates: a TOF-NR study.

We have investigated thin films from fully deuterated polybutadiene (PB-d6) on silicon substrates with the aim of detecting and characterizing a possible interphase in the polymer film near the substrate using time-of-flight neutron reflectometry (TOF-NR). As substrates, thermally oxidized silicon wafers were either used as such or they were coated with triethylethoxysilyl modified 1,2-PB prior to deposition of the PB-d6 film. TOF-NR reveals that, for both substrates, the scattering length density (SLD) of the PB films decreases near the solid interface. The reduction of SLD is converted to an excess fraction of free volume. To further verify the existence of the interphase in PB-d6, we attempt to model the TOF-NR curves with density profiles which do not feature an interphase. These density profiles do not describe the TOF-NR curves adequately. We conclude that, near the solid interface, an interphase having an SLD lower than the bulk of the film is present.

Advice on describing Bayesian analysis of neutron and X-ray reflectometry.

As a result of the availability of modern software and hardware, Bayesian analysis is becoming more popular in neutron and X-ray reflectometry analysis. The understandability and replicability of these analyses may be harmed by inconsistencies in how the probability distributions central to Bayesian methods are represented in the literature. Herein advice is provided on how to report the results of Bayesian analysis as applied to neutron and X-ray reflectometry. This includes the clear reporting of initial starting conditions, the prior probabilities, the results of any analysis and the posterior probabilities that are the Bayesian equivalent of the error bar, to enable replicability and improve understanding. It is believed that this advice, grounded in the authors' experience working in the field, will enable greater analytical reproducibility in the work of the reflectometry community, and improve the quality and usability of results.

Selective growth of α-sexithiophene by using silicon oxides patterns.

A process for fabricating ordered organic films on large area is presented. The process allows growing sexithiophene ultra-thin films at precise locations on patterned Si/SiO(x) substrates by driving the orientation of growth. This process combines the parallel local anodic oxidation of Si/SiO(x) substrates with the selective arrangement of molecular ultra-thin film. The former is used to fabricate silicon oxide arrays of parallel lines of 400 nm in width over an area of 1 cm(2). Selective growth arises from the interplay between kinetic growth parameters and preferential interactions with the patterned surface. The result is an ultra-thin film of organic molecules that is conformal to the features of the fabricated motives.

Mutually Beneficial Combination of Molecular Dynamics Computer Simulations and Scattering Experiments.

We showcase the combination of experimental neutron scattering data and molecular dynamics (MD) simulations for exemplary phospholipid membrane systems. Neutron and X-ray reflectometry and small-angle scattering measurements are determined by the scattering length density profile in real space, but it is not usually possible to retrieve this profile unambiguously from the data alone. MD simulations predict these density profiles, but they require experimental control. Both issues can be addressed simultaneously by cross-validating scattering data and MD results. The strengths and weaknesses of each technique are discussed in detail with the aim of optimizing the opportunities provided by this combination.

Advance Approval of Outpatient Chemotherapy via Phone Call Optimizes Healthcare Delivery without Compromising Patient Satisfaction with Care.

Patient satisfaction is linked to the amount of time spent with the physician. At the same time, long waiting times in hospitals are a major source of patient dissatisfaction. The aim of this study was to determine whether advance approval of outpatient chemotherapy (CT) via phone call can optimize healthcare delivery without compromising patient satisfaction with care. Between 2013 and 2016, 343 patients with breast/gynecological cancer scheduled to undergo CT on day 8 and/or day 15 of the CT cycle were enrolled in a before-after study conducted in a French comprehensive cancer center. In the control group, 168 patients received a face-to-face consultation with an oncologist on the day of CT for approval of the upcoming CT session. In the intervention group, 175 patients received a phone call from a healthcare provider the day before CT, where assessment of toxicity from the previous CT session was recorded and submitted to an oncologist for approval of the upcoming CT session. At the end of the 6th CT cycle, patient satisfaction was evaluated using EORTC IN-PATSAT32. A total of 233 questionnaires were analyzed (response rate: 77.7%). Satisfaction with care was similar between the two groups. No differences in perceived health status were observed, but self-reported time in hospital was lower in the intervention group than in the control group (p = 0.007). Advance approval of outpatient CT via phone call is feasible and particularly relevant in the current context of immunotherapy development.

Surface distortion of Fe dot-decorated TiO2 nanotubular templates using time-of-flight grazing incidence small angle scattering.

Physical properties of nanoclusters, nanostructures and self-assembled nanodots, which in turn are concomitantly dependent upon the morphological properties, can be modulated for functional purposes. Here, in this article, magnetic nanodots of Fe on semiconductor TiO2 nanotubes (TNTs) are investigated with time-of-flight grazing incidence small-angle neutron scattering (TOF-GISANS) as a function of wavelength, chosen from a set of three TNT templates with different correlation lengths. The results are found corroborating with the localized scanning electron microscopy (SEM) images. As we probe the inside and the near-surface region of the Fe-dotted TNTs with respect to their homogeneity, surface distortion and long-range order using TOF-GISANS, gradual aberrations at the top of the near-surface region are identified. Magnetization measurements as a function of temperature and field do not show a typical ferromagnetic behavior but rather a supermagnetic one that is expected from a nonhomogeneous distribution of Fe-dots in the intertubular crevasses.

Morphology Tuning of ZnO/P3HT/P3HT- b-PEO Hybrid Films Deposited via Spray or Spin Coating.

Hybrid films of zinc oxide (ZnO) and poly(3-hexylthiophen-2,5-diyl) (P3HT) show promising characteristics for application in hybrid bulk-heterojunction solar cells (HBSCs). However, the incompatibility of ZnO and P3HT may lead to a reduced interface area, thus reducing the probability of exciton separation and consequently lowering solar cell efficiencies. Here, a diblock copolymer P3HT- b-poly(ethylene oxide) (PEO) is introduced to improve the interface between ZnO and P3HT. ZnO is synthesized via a block copolymer assisted sol-gel approach, and the used zinc precursor is directly incorporated into the PEO blocks. Thus, the possibility of aggregation is reduced for both the inorganic and the organic components, and a good intermixing is ascertained. Two deposition methods, namely, spray and spin coating, are compared with respect to the resulting film structure, which is investigated with scanning electron microscopy and time-of-flight grazing-incidence small-angle neutron scattering measurements. Both the surface and inner morphologies reveal that the spin coated samples possess smaller and less diverse domain sizes than the sprayed films. Due to the advantage of spray coating in large-scale production, the morphology of the sprayed samples is tailored more meticulously by changing the weight fraction of ZnO in the films. The sprayed hybrid films show smaller domains and less aggregation with decreasing the amount of ZnO. This reveals that both the deposition method and composition of the ZnO/P3HT/P3HT- b-PEO hybrid films play an important role for tailoring the film morphology and thus for improving the performance of HBSCs in future application.

Outpatient Cancer Care Delivery in the Context of E-Oncology: A French Perspective on "Cancer outside the Hospital Walls".

In oncology, the treatment of patients outside of hospitals has become imperative due to an increasing number of patients who are older and live longer, along with issues such as medical desertification, oncologist hyperspecialization, and difficulties in financing mounting health expenditures. Treatments have become less "invasive", with greater precision and efficiency. Patients can therefore receive most of their care outside of hospitals. The development of e-health can address these new imperatives. In this letter, we describe the different e-health tools and their potential clinical impacts in oncology, as already reported at every level of care, including education, prevention, diagnosis, treatment, and monitoring. A few randomized studies have yet demonstrated the clinical benefit. We also comment on issues and limits of "cancer outside the hospital walls" from the point of view of patients, health care professionals, health facilities, and public authorities. Care providers in hospitals and communities will have to adapt to these changes within well-coordinated networks in order to better meet patient expectations regarding increasing education and personalizing management. Ultimately, controlled studies should aim to definitively demonstrate areas of interest, benefits, and incentives, for not only patients, but also caregivers (formal and informal) and health care providers, health care facilities, and the nation.

[The role and use of Patient Reported Outcomes in the management of cancer patients]. / Rôle et utilisation des Patient reported outcomes (PROs) dans la prise en charge des patients en oncologie.

Therapeutic innovations in the field of oncology allow to manage cancer as a chronic illness with treatments being administered over prolonged periods of time. In this context, it is now acknowledged that it is important to complete the assessment of benefit based on purely clinical endpoints using outcome measurement evaluated by patients themselves. The Patient reported outcome (PRO) concept has then emerged and there is an increasing interest in using the PROs as an indicator of the benefit of new therapeutic strategies. In this paper, we aim to illustrate the potential use and value of using PROs in the management of cancer patients. After a brief review of the PRO concept and it's link with the quality-of-life concept, this paper describes the actual implementation of PROs, first in clinical research, then in routine clinical practice. We then will focus on the difficulties in the French context to promote a larger use of PROs in the routine clinical practice. This paper will show how the PROs are a useful tool to improve the management of cancer patients.

Monitoring the Swelling Behavior of PEDOT:PSS Electrodes under High Humidity Conditions.

Polymer electrodes made of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) are used in many applications but are also sensitive to humidity. We study humidity-induced changes of PEDOT:PSS electrodes as monitored with in situ time-of-flight neutron reflectivity (TOF-NR) measurements under high humidity conditions. The influence of the solvent additive Zonyl and a post-treatment of PEDOT:PSS films with ethylene glycol (EG) serving as electrodes are analyzed with respect to the swelling ratio and water uptake. Depending on the applied PEDOT:PSS treatment, PEDOT and PSS enrichment layers are clearly identified with TOF-NR at the substrate-polymer and polymer-air interface, respectively. The additive Zonyl reduces the water uptake and limits film swelling. EG post-treatment further increases hydrophobicity and thereby water incorporation into the PEDOT:PSS film is strongly suppressed. The characteristic time constants and effective interaction parameters extracted from the kinetic NR data show that additive and post-treatment reduce the sensitivity of the PEDOT:PSS electrodes to humidity.

Effects of surface chemical composition on the early growth stages of alpha-sexithienyl films on silicon oxide substrates.

In organic field effect transistors, charge transport is confined to a narrow region next to the organic/dielectric interface. It is thus extremely important to determine the morphology and the molecular arrangement of the organic films at their early growth stages. On a substrate of technological interest, such as thermally grown silicon oxide, it has been recently found that alpha-sexithienyl aggregates made of flat-lying molecules can simultaneously nucleate besides islands made of molecules standing vertical. In this paper, we investigate the effects due to variations in surface chemical composition on alpha-sexithienyl ultrathin film formation. Flat-lying molecules are no longer detected when Si-OH groups present at the surface are chemically removed but also when the Si-OH or Si-H group density is maximized. This gives evidence that variations in the surface chemical composition can largely affect the nucleation and growth processes of organic/dielectric interfaces. We hypothesize that isolated OH groups can interact with alpha-sexithienyl molecules and anchor them down flat with respect to the surface.

Effect of alcohol treatment on the performance of PTB7:PC71BM bulk heterojunction solar cells.

The effect of an environmentally friendly alcohol treatment on bulk heterojunction (BHJ) polymer solar cells using the low-bandgap copolymer based on thieno[3,4-b]thiophene-alt-benzodithiophene units and [6,6]-phenyl-C71-butyric acid methyl ester is systematically investigated. Different alcohols are tested, and besides the most commonly used methanol treatment, other alcohols such as ethanol, 2-propanol, and 1-butanol also improve the device performance to certain extents as compared to the untreated solar cells. Changes of the surface structure caused by the alcohol treatment are probed with atomic force microscopy, and the modification of inner film morphology is probed by time-of-flight-grazing incidence small-angle neutron scattering (TOF-GISANS). UV/vis measurements show that the thickness of all BHJ films remains unchanged by the different solvent treatments. Thus, the enhanced device performance induced by the alcohol treatments is correlated to the reconstruction of the inner film structures probed with TOF-GISANS and the modified energy levels at the interfaces between the BHJ layer and the aluminum electrodes, evident by the enhanced short-circuit current and open-circuit voltage of the I-V curves.

Loss of heterozygosity at microsatellite markers from region p11-21 of chromosome 8 in microdissected breast tumor but not in peritumoral cells.

Alterations of chromosomal region 8p11-21 are very frequent in human cancers, and especially in breast cancer; yet, most of the genes involved have not been identified. We performed laser capture microdissection in a series of 52 consecutive breast tumor samples to obtain pure tumor cells without surrounding normal breast. To determine genomic subregions in which some of the cancer genes may be located, we conducted a search for loss of heterozygosity (LOH) at 13 microsatellite markers from this region. Two-thirds of the tumors showed LOH at least at one marker. Microdissection of pure tumor samples was helpful to precisely define four LOH subregions. No LOH was observed in the corresponding peritumoral tissues. We studied by immunohistochemistry (IHC) on tissue-microarrays the expression in the same tumors, of the protein product of three potential tumor genes lying close to or within the subregions of LOH. In most samples, the TACC1 gene product was downregulated in tumor cells as compared to normal cells. Our results show that the centromeric portion of chromosome arm 8p is frequently altered in breast tumor cells.

Self-assembly of diblock copolymer-maghemite nanoparticle hybrid thin films.

The arrangement of maghemite (γ-Fe2O3) nanoparticles (NPs) in poly(styrene-d8-block-n-butyl methacrylate) P(Sd-b-BMA) diblock copolymer (DBC) films via a self-assembly process was investigated toward the fabrication of highly ordered maghemite-polymer hybrid thin films. The resulting thin films exhibited a perforated lamella with an enrichment layer containing NPs as investigated with X-ray reflectometry, scanning electron microscopy, atomic force microscopy, and time-of-flight grazing incidence small angle neutron scattering as a function of the NP concentrations. The NPs were selectively deposited in the PSd domains of the DBC during the microphase separation process. At low NP concentrations, the incorporation of the NPs within the DBC thin films resulted in an enhanced microphase separation process and formation of highly oriented and ordered nanostructured hybrid films. At higher NP concentrations, the aggregation of the NPs was dominating and large sized metal oxide clusters were observed. The superparamagnetic properties of the metal oxide-polymer hybrid films at various NP concentrations were probed by a superconducting quantum interference device magnetometer, which shows that the hybrid films are highly attractive for optical devices, magnetic sensors, and magnetic recording devices.

Probing opto-mechanical stresses within azobenzene-containing photosensitive polymer films by a thin metal film placed above.

Azo-modified photosensitive polymers offer the interesting possibility to reshape bulk polymers and thin films by UV-irradiation while being in the solid glassy state. The polymer undergoes considerable mass transport under irradiation with a light interference pattern resulting in the formation of surface relief grating (SRG). The forces inscribing this SRG pattern into a thin film are hard to assess experimentally directly. In the current study, we are proposing a method to probe opto-mechanical stresses within polymer films by characterizing the mechanical response of thin metal films (10 nm) deposited on the photosensitive polymer. During irradiation, the metal film not only deforms along with the SRG formation but ruptures in a regular and complex manner. The morphology of the cracks differs strongly depending on the electrical field distribution in the interference pattern, even when the magnitude and the kinetics of the strain are kept constant. This implies a complex local distribution of the opto-mechanical stress along the topography grating. In addition, the neutron reflectivity measurements of the metal/polymer interface indicate the penetration of a metal layer within the polymer, resulting in a formation of a bonding layer that confirms the transduction of light-induced stresses in the polymer layer to a metal film.

Cell motility on polyethylene glycol block copolymers correlates to fibronectin surface adsorption.

Adhesion and motility of cells on polyethylene glycol (PEG) engineered surfaces are of fundamental interest for the development of biotechnological devices. Here, the structure of PEG block copolymers physisorbed to surfaces by polyLlysine (PLL) or polypropylene oxide (PPO) is studied. Cell behavior on such surfaces incubated with fibronectin (FN) is analyzed via time-lapse microscopy, the amount and the location of FN is determined via neutron reflectivity. While FN does not adsorb onto PPOPEG, 0.4-0.7 mg m(-2) of FN is found in the vicinity of the PLL moiety of PLLPEG. Cells exhibit 21% increased motility on PLLPEG (5 kDa PEG chains) compared to pure FN layers, and 12% decreased motility for PLLPEG (2 kDa PEG chains). These findings suggest that by design of PEGylated surfaces cell migration can be controlled.