Nicolas Lequeux

Cadmium-Free CuInS2/ZnS Quantum Dots for Sentinel Lymph Node Imaging with Reduced Toxicity

Semiconductor quantum dots (QDs) could significantly impact the performance of biomedical near-infrared (NIR) imaging by providing fluorescent probes that are brighter and more photostable than conventional organic dyes. However, the toxicity of the components of NIR emitting II-VI and IV-VI QDs that have been made so far (Cd, Hg, Te, Pb, etc.) has remained a major obstacle to the clinical use of QDs. Here, we present the synthesis of CuInS(2)/ZnS core/shell QDs emitting in the NIR ( approximately 800 nm) with good quantum yield and stability even after transfer into water. We demonstrate the potential of these QDs by imaging two regional lymph nodes (LNs) in vivo in mice. We then compare the inflammatory response of the axillary LN induced by different doses of CuInS(2)/ZnS and CdTeSe/CdZnS QDs and show a clear difference in acute local toxicity, the onset of inflammation only occurring at a 10 times more concentrated dose for CuInS(2)/ZnS QDs than for their Cd-containing counterparts.

Small and Stable Sulfobetaine Zwitterionic Quantum Dots for Functional Live-Cell Imaging

We have developed a novel surface coating for semiconductor quantum dots (QDs) based on a heterobifunctional ligand that overcomes most of the previous limits of these fluorescent probes in bioimaging applications. Here we show that QDs capped with bidentate zwitterionic dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands are a favorable alternative to polyethylene glycol-coated nanoparticles since they combine small sizes, low nonspecific adsorption, preserved optical properties, and excellent stability over time and a wide range of pH and salinity. Additionally, these QDs can easily be functionalized with biomolecules such as streptavidin (SA) and biotin. We applied streptavidin-functionalized DHLA-SB QDs to track the intracellular recycling of cannabinoid receptor 1 (CB1R) in live cells. These QDs selectively recognized the pool of receptors at the cell surface via SA-biotin interactions with negligible nonspecific adsorption. The QDs retained their optical properties, allowing the internalization of CB1R into endosomes to be followed. Moreover, the cellular activity was apparently unaffected by the probe.

Non-blinking quantum dot with a plasmonic nanoshell resonator

Colloidal semiconductor quantum dots are fluorescent nanocrystals exhibiting exceptional optical properties, but their emission intensity strongly depends on their charging state and local environment. This leads to blinking at the single-particle level or even complete fluorescence quenching, and limits the applications of quantum dots as fluorescent particles. Here, we show that a single quantum dot encapsulated in a silica shell coated with a continuous gold nanoshell provides a system with a stable and Poissonian emission at room temperature that is preserved regardless of drastic changes in the local environment. This novel hybrid quantum dot/silica/gold structure behaves as a plasmonic resonator with a strong Purcell factor, in very good agreement with simulations. The gold nanoshell also acts as a shield that protects the quantum dot fluorescence and enhances its resistance to high-power photoexcitation or high-energy electron beams. This plasmonic fluorescent resonator opens the way to a new family of plasmonic nanoemitters with robust optical properties.

Relationship between short-range order and ease of nucleation in Na2Ca2Si3O9, CaSiO3 and PbSiO3 glasses

Abstract A relationship between the short-range order around the modifier cations and the crystal nucleation tendency in silicate glasses is demonstrated. New extended X-ray absorption fine spectroscopy (EXAFS) results on the local structure around calcium and lead atoms were obtained and analyzed for both vitreous and crystalline samples. Three different silicate systems were studied: wollastonite (CaSiO3) and soda-lime–silica (Na2Ca2Si3O9), for which volume nucleation is easily observed and lead metasilicate (PbSiO3) for which nucleation occurs only on the sample surfaces in typical laboratory conditions. In the glasses that have a high nucleation tendency (Na2Ca2Si3O9 and CaSiO3), the local structures of these modifier cations are similar to their short-range order in the isochemical crystalline phases, whereas the local structure in the glass that presents a low nucleation tendency (PbSiO3) is quite different from that of its isochemical crystal phase.

Infrared Photodetection Based on Colloidal Quantum-Dot Films with High Mobility and Optical Absorption up to THz

Infrared thermal imaging devices rely on narrow band gap semiconductors grown by physical methods such as molecular beam epitaxy and chemical vapor deposition. These technologies are expensive, and infrared detectors remain limited to defense and scientific applications. Colloidal quantum dots (QDs) offer a low cost alternative to infrared detector by combining inexpensive synthesis and an ease of processing, but their performances are so far limited, in terms of both wavelength and sensitivity. Herein we propose a new generation of colloidal QD-based photodetectors, which demonstrate detectivity improved by 2 orders of magnitude, and optical absorption that can be continuously tuned between 3 and 20 μm. These photodetectors are based on the novel synthesis of n-doped HgSe colloidal QDs whose size can be tuned continuously between 5 and 40 nm, and on their assembly into solid nanocrystal films with mobilities that can reach up to 100 cm(2) V(-1) s(-1). These devices can be operated at room temperature with the same level of performance as the previous generation of devices when operated at liquid nitrogen temperature. HgSe QDs can be synthesized in large scale (>10 g per batch), and we show that HgSe films can be processed to form a large scale array of pixels. Taken together, these results pave the way for the development of the next generation mid- and far-infrared low-cost detectors and camera.

Influence of Luminescence Quantum Yield, Surface Coating, and Functionalization of Quantum Dots on the Sensitivity of Time-Resolved FRET Bioassays

In clinical diagnostics, homogeneous time-resolved (TR) FRET immunoassays are used for fast and highly sensitive detection of biomarkers in serum samples. The most common immunoassay format is based on europium chelate or cryptate donors and allophycocyanin acceptors. Replacing europium donors with terbium complexes and the acceptors with QDs offers large photophysical advantages for multiplexed diagnostics, because the Tb-complex can be used as FRET donor for QD acceptors of different colors. Water-soluble and biocompatible QDs are commercially available or can be synthesized in the laboratory using many available recipes from the literature. Apart from the semiconductor material composition, an important aspect of choosing the right QD for TR-FRET assays is the thickness of the QD coating, which will influence the photophysical properties and long-term stability as well as the donor-acceptor distance and FRET efficiency. Here we present a detailed time-resolved spectroscopic study of three different QDs with an emission maximum around 605 nm for their application as FRET acceptors (using a common Tb donor) in TR-bioassays: (i) Invitrogen/Life Technologies Qdot605, (ii) eBioscience eFluorNC605 and iii) ter-polymer stabilized CdSe/CdS/ZnS QDs synthesized in our laboratories. All FRET systems are very stable and possess large Förster distances (7.4-9.1 nm), high FRET efficiencies (0.63-0.80) and low detection limits (0.06-2.0 pM) within the FRET-bioassays. Shapes, sizes and the biotin/QD ratio of the biocompatible QDs could be determined directly in the solution phase bioassays at subnanomolar concentrations. Both commercial amphiphilic polymer/lipid encapsulated QDs and self-made ligand-exchanged QDs provide extremely low detection limits for highly sensitive TR-FRET bioassays.

Organic calcium silicate hydrate hybrids: a new approach to cement based nanocomposites

Novel hybrid organic–inorganic calcium silicate hydrate (C–S–H) materials have been synthesized via a sol–gel process. The materials are obtained by precipitation in alkali media of a mixture of trialkoxysilane (ethyltriethoxysilane, n-butyltrimethoxysilane or 3-aminopropyltriethoxysilane) and tetraethoxysilane diluted in CaCl2 ethanol–water solution. XRD experiments show an increase of the basal distance of C–S–H with the content of trialkoxysilane suggesting the incorporation of organic moieties in the interlayer. 29Si NMR data show that the organic species do not disrupt the inorganic framework of C–S–H. 2D 1H–29Si HETCOR NMR experiments confirm that trialkoxysilanes such as ethyl- or aminopropyl-silane are incorporated in the silicate chains of the C–S–H structure. In the case of highly hydrophobic trialkoxysilanes such as n-butyltrimethoxysilane, the results suggest that a separation occurs between silicates and trialkoxysilanes, leading to a mixture of inorganic C–S–H on one hand and 100% organosilane calcium hybrid phase on the other hand.

Cement-polymer and clay-polymer nano- and meso-composites: spotting the difference

Calcium silicate hydrate (C-S-H), the most important reaction product of Portland cement with water, is a layered lattice silicate which has much in common with smectite clays. Both materials may be synthesised (C-S-H) or found in nature (smectites) in the form of particles which are stacks of negatively charged nanometre-thick platelets separated by water molecules and charge-compensating cations. Smectite clays are well known for their ability to intercalate molecular species including polymers, to “swell” in a remarkable variety of solvents and to form nano-composites with polymers in which total delamination may eventually be obtained. In this work, we explore the possibility of intercalating cationic, anionic and neutral water-soluble polymers in C-S-H. Contrary to recent reports, no clear signs for intercalation of the macromolecules were observed. Nevertheless, the significant amount of polymer retained by the silicate suggests that the composite materials formed may be considered as meso-composites in which the individual solid units are not the individual C-S-H sheets but crystallites thereof. The localisation of electric charges and the strong Coulombic forces acting in cement hydrates are thought to be responsible for this difference.

New covalent bonded polymer–calcium silicate hydrate composites

New covalent bonded polymer–calcium silicate hydrate (C–S–H) composites were prepared. For this purpose, two sets of hydrosoluble copolymers, both containing trialkoxysilane (T-silane) and/or methyldialkoxysilane (D-silane) functions, were synthesized. The addition of these polymers during the synthesis of C–S–H by the sol–gel method allowed us to obtain hybrid materials. The influence of different synthesis parameters, such as the silane content and the nature of the silane functions grafted to the polymer backbone, was studied. Characterisation of the composite materials by thermogravimetry and elemental analysis showed that chemical interaction of polymers and C–S–H is due only to the presence of T-silane functions. 29Si CP MAS NMR analysis confirmed the existence of covalent linkages between the inorganic silicate chains of the C–S–H crystallites and the T-silane functions. The specific incorporation of these new classes of silane-modified polymers in C–S–H structure may be successfully used in the preparation of new polymer–cement composites with reinforced mechanical properties.

Comparing Intracellular Stability and Targeting of Sulfobetaine Quantum Dots with Other Surface Chemistries in Live Cells

The in vivo labeling of intracellular components with quantum dots (QDs) is very limited because of QD aggregation in the cell cytoplasm and/or QD confinement into lysosomal compartments. In order to improve intracellular targeting with QDs, various surface chemistries and delivery methods have been explored, but they have not yet been compared systematically with respect to the QD intracellular stability. In this work, the intracellular aggregation kinetics of QDs for three different surface chemistries based on ligand exchange or encapsulation with amphiphilic polymers are compared. For each surface chemistry, three delivery methods for bringing the nanoparticles into the cells are compared: electroporation, microinjection, and pinocytosis. It is concluded that the QD intracellular aggregation behavior is strongly dependent on the surface chemistry. QDs coated with dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands diffuse freely in cells for longer periods of time than for QDs in the other chemistries tested, and they can access all cytoplasmic compartments. Even when conjugated to streptavidin, these DHLA-SB QDs remain freely diffusing inside the cytoplasm and unaggregated, and they are able to reach a biotinylated target inside HeLa cells. Such labeling was more efficient when compared to commercial streptavidin-conjugated QDs, which may be due to the smaller size of DHLA-SB QDs and/or to their superior intracellular stability.