Chemical patterning for the highly specific and programmed assembly of nanostructures

We have developed a new chemical patterning technique based on standard lithography-based processes to assemble nanostructures on surfaces with extraordinarily high selectivity. This patterning process is used to create patterns of aminosilane molecular layers surrounded by highly inert poly (ethylene glycol) (PEG) molecules. While the aminosilane regions facilitate nanostructure assembly, the PEG coating prevents adsorption of molecules and nanostructures, thereby priming the semiconductor substrate for the highly localized and programmed assembly of nanostructures. We demonstrate the power and versatility of this manufacturing process by building multilayered structures of gold nanoparticles attached to molecules of DNA onto the aminosilane patterns, with zero nanocrystal adsorption onto the surrounding PEG regions. The highly specific surface chemistry developed here can be used in conjunction with standard microfabrication and emerging nanofabrication technology to seamlessly integrate various nanostructures with semiconductor electronics

Effects of climate change on high Alpine mountain environments: Evolution of mountaineering routes in the Mont Blanc massif (Western Alps) over half a century

International audienceIn high alpine environments, glacial shrinkage and permafrost warming due to climate change have significant consequences on mountaineering routes. Few research projects have studied the relationship between climate change and mountaineering; this study attempts to characterize and explain the evolution over the past 40 years of the routes described in The Mont Blanc Massif: The 100 Finest Routes, Gaston Rébuffat's emblematic guidebook, published in 1973.The main elements studied were the geomorphic and cryospheric changes at work and their impacts on the itinerary's climbing parameters, determining the manner and possibility for an itinerary to be climbed. Thirty-one interviews, and comparison with other guidebooks, led to the identification of 25 geomorphic and cryospheric changes related to climate change that are affecting mountaineering itineraries. On average, an itinerary has been affected by nine changes. Among the 95 itineraries studied, 93 have been affected by the effects of climate change-26 of them have been greatly affected; and three no longer exist. Moreover, periods during which these itineraries can be climbed in good conditions in summer have tended to become less predictable and periods of optimal conditions have shifted toward spring and fall, because the itineraries have become more dangerous and technically more challenging

Molecular Microfluidic Bioanalysis: Recent Progress in Preconcentration, Separation, and Detection

This chapter reviews the state-of-art of microfluidic devices for molecular bioanalysis with a focus on the key functionalities that have to be successfully integrated, such as preconcentration, separation, signal amplification, and detection. The first part focuses on both passive and electrophoretic separation/sorting methods, whereas the second part is devoted to miniaturized biosensors that are integrated in the last stage of the fluidic device

Overview of Materials for Microfluidic Applications

For each material dedicated to microfluidic applications, inherent microfabrication and specific physico‐chemical properties are key concerns and play a dominating role in further microfluidic operability. From the first generation of inorganic glass, silicon and ceramics microfluidic devices materials, to diversely competitive polymers alternatives such as soft and rigid thermoset and thermoplastics materials, to finally various paper, biodegradable and hydrogel materials; this chapter will review their advantages and drawbacks regarding their microfabrication perspectives at both research and industrial scale. The chapter will also address, the evolution of the materials used for fabricating microfluidic chips, and will discuss the application‐oriented pros and cons regarding especially their critical strategies and properties for devices assembly and biocompatibility, as well their potential for downstream biochemical surface modification are presented

Nano-scale superhydrophobicity: suppression of protein adsorption and promotion of flow-induced detachment

Wall adsorption is a common problem in microfluidic devices, particularly when proteins are used. Here we show how superhydrophobic surfaces can be used to reduce protein adsorption and to promote desorption. Hydrophobic surfaces, both smooth and having high surface roughness of varying length scales (to generate superhydrophobicity), were incubated in protein solution. The samples were then exposed to flow shear in a device designed to simulate a microfluidic environment. Results show that a similar amount of protein adsorbed onto smooth and nanometer-scale rough surfaces, although a greater amount was found to adsorb onto superhydrophobic surfaces with micrometer scale roughness. Exposure to flow shear removed a considerably larger proportion of adsorbed protein from the superhydrophobic surfaces than from the smooth ones, with almost all of the protein being removed from some nanoscale surfaces. This type of surface may therefore be useful in environments, such as microfluidics, where protein sticking is a problem and fluid flow is present. Possible mechanisms that explain the behaviour are discussed, including decreased contact between protein and surface and greater shear stress due to interfacial slip between the superhydrophobic surface and the liquid

Neuropilin-2 Expression Promotes TGF-β1-Mediated Epithelial to Mesenchymal Transition in Colorectal Cancer Cells

Neuropilins, initially characterized as neuronal receptors, act as co-receptors for cancer related growth factors and were recently involved in several signaling pathways leading to cytoskeletal organization, angiogenesis and cancer progression. Then, we sought to investigate the ability of neuropilin-2 to orchestrate epithelial-mesenchymal transition in colorectal cancer cells. Using specific siRNA to target neuropilin-2 expression, or gene transfer, we first observed that neuropilin-2 expression endows HT29 and Colo320 for xenograft formation. Moreover, neuropilin-2 conferred a fibroblastic-like shape to cancer cells, suggesting an involvement of neuropilin-2 in epithelial-mesenchymal transition. Indeed, the presence of neuropilin-2 in colorectal carcinoma cell lines was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed by surface plasmon resonance experiments that neuropilin-2 is a receptor for transforming-growth factor-β1. The expression of neuropilin-2 on colon cancer cell lines was indeed shown to promote transforming-growth factor-β1 signaling, leading to a constitutive phosphorylation of the Smad2/3 complex. Treatment with specific TGFβ-type1 receptor kinase inhibitors restored E-cadherin levels and inhibited in part neuropilin-2-induced vimentin expression, suggesting that neuropilin-2 cooperates with TGFβ-type1 receptor to promote epithelial-mesenchymal transition in colorectal cancer cells. Our results suggest a direct role of NRP2 in epithelial-mesenchymal transition and highlight a cross-talk between neuropilin-2 and TGF-β1 signaling to promote cancer progression. These results suggest that neuropilin-2 fulfills all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

PurposeCancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity.MethodsWe performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity.ResultsEighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients.ConclusionsElderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response

Modification of Hydrophilic and Hydrophobic Surfaces Using an Ionic-Complementary Peptide

Ionic-complementary peptides are novel nano-biomaterials with a variety of biomedical applications including potential biosurface engineering. This study presents evidence that a model ionic-complementary peptide EAK16-II is capable of assembling/coating on hydrophilic mica as well as hydrophobic highly ordered pyrolytic graphite (HOPG) surfaces with different nano-patterns. EAK16-II forms randomly oriented nanofibers or nanofiber networks on mica, while ordered nanofibers parallel or oriented 60° or 120° to each other on HOPG, reflecting the crystallographic symmetry of graphite (0001). The density of coated nanofibers on both surfaces can be controlled by adjusting the peptide concentration and the contact time of the peptide solution with the surface. The coated EAK16-II nanofibers alter the wettability of the two surfaces differently: the water contact angle of bare mica surface is measured to be <10°, while it increases to 20.3±2.9° upon 2 h modification of the surface using a 29 µM EAK16-II solution. In contrast, the water contact angle decreases significantly from 71.2±11.1° to 39.4±4.3° after the HOPG surface is coated with a 29 µM peptide solution for 2 h. The stability of the EAK16-II nanofibers on both surfaces is further evaluated by immersing the surface into acidic and basic solutions and analyzing the changes in the nanofiber surface coverage. The EAK16-II nanofibers on mica remain stable in acidic solution but not in alkaline solution, while they are stable on the HOPG surface regardless of the solution pH. This work demonstrates the possibility of using self-assembling peptides for surface modification applications