39 research outputs found

    Single-atom-resolved probing of lattice gases in momentum space

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    Measuring the full distribution of individual particles is of fundamental importance to characterize many-body quantum systems through correlation functions at any order. Here we demonstrate the possibility to reconstruct the momentum-space distribution of three-dimensional interacting lattice gases atom-by-atom. This is achieved by detecting individual metastable Helium atoms in the far-field regime of expansion, when released from an optical lattice. We benchmark our technique with Quantum Monte-Carlo calculations, demonstrating the ability to resolve momentum distributions of superfluids occupying 10510^5 lattice sites. It permits a direct measure of the condensed fraction across phase transitions, as we illustrate on the superfluid-to-normal transition. Our single-atom-resolved approach opens a new route to investigate interacting lattice gases through momentum correlations.Comment: 7 pages, 5 figure

    Fast production of Bose-Einstein condensates of metastable Helium

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    We report on the Bose-Einstein condensation of metastable Helium-4 atoms using a hybrid approach, consisting of a magnetic quadrupole and a crossed optical dipole trap. In our setup we cross the phase transition with 2x10^6 atoms, and we obtain pure condensates of 5x10^5 atoms in the optical trap. This novel approach to cooling Helium-4 provides enhanced cycle stability, large optical access to the atoms and results in production of a condensate every 6 seconds - a factor 3 faster than the state-of-the-art. This speed-up will dramatically reduce the data acquisition time needed for the measurement of many particle correlations, made possible by the ability of metastable Helium to be detected individually

    Three-dimensional laser cooling at the Doppler limit

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    Many predictions of Doppler cooling theory of two-level atoms have never been verified in a three-dimensional geometry, including the celebrated minimum achievable temperature ℏΓ/2kB\hbar \Gamma/2 k_B, where Γ\Gamma is the transition linewidth. Here, we show that, despite their degenerate level structure, we can use Helium-4 atoms to achieve a situation in which these predictions can be verified. We make measurements of atomic temperatures, magneto-optical trap sizes, and the sensitivity of optical molasses to a power imbalance in the laser beams, finding excellent agreement with the Doppler theory. We show that the special properties of Helium, particularly its small mass and narrow transition linewidth, prevent effective sub-Doppler cooling with red-detuned optical molasses.Comment: 8 pages, 5 figure

    Mannosylated poly(ethylene imine) copolymers enhance saRNA uptake and expression in human skin explants

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    Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host–guest interaction between cyclodextrin and adamantane. We show that the host–guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery

    The In Vitro, Ex Vivo, and In Vivo Effect of Polymer Hydrophobicity on Charge-Reversible Vectors for Self-Amplifying RNA

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    RNA technology has the potential to revolutionize vaccination. However, the lack of clear structure-property relationships in relevant biological models mean there is no clear consensus on the chemical motifs necessary to improve RNA delivery. In this work, we describe the synthesis of a series of copolymers based on the self-hydrolyzing charge-reversible polycation poly(dimethylaminoethyl acrylate) (pDMAEA), varying the lipophilicity of the additional co-monomers. All copolymers formed stable polyplexes, showing efficient complexation with model nucleic acids from nitrogen/phosphate (N/P) ratios of N/P = 5, with more hydrophobic complexes exhibiting slower charge reversal and disassembly compared to hydrophilic analogues. The more hydrophobic copolymers outperformed hydrophilic versions, homopolymer controls and the reference standard polymer (polyethylenimine), in transfection assays on 2D cell monolayers, albeit with significantly higher toxicities. Similarly, hydrophobic derivatives displayed up to a 4-fold higher efficacy in terms of the numbers of cells expressing green fluorescent protein (GFP+) cells in ex vivo human skin (10%) compared to free RNA (2%), attributed to transfection enrichment in epithelial cells. In contrast, in a mouse model, we observed the reverse trend in terms of RNA transfection, with no observable protein production in more hydrophobic analogues, whereas hydrophilic copolymers induced the highest transfection in vivo. Overall, our results suggest an important relationship between the vector lipophilicity and RNA transfection in vaccine settings, with polymer biocompatibility potentially a key parameter in effective in vivo protein production

    Ornithine-derived oligomers and dendrimers forin vitrodelivery of DNA andex vivotransfection of skin cellsviasaRNA

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    © The Royal Society of Chemistry 2020. Gene therapies are undergoing a renaissance, primarily due to their potential for applications in vaccination for infectious diseases and cancers. Although the biology of these technologies is rapidly evolving, delivery strategies need to be improved to overcome the poor pharmacokinetics and cellular transport of nucleic acids whilst maintaining patient safety. In this work, we describe the divergent synthesis of biodegradable cationic dendrimers based on the amino acid ornithine as non-viral gene delivery vectors and evaluate their potential as delivery vectors for DNA and RNA. The dendrimers effectively complexed model nucleic acids at lower N/P ratios than polyethyleneimine and outperformed it in DNA transfection experiments with ratios above 5. Remarkably, all dendrimer polyplexes at N/P = 2 achieved up to 7-fold higher protein content over an optimized PEI formulation when used for transfections with self-amplifying RNA (saRNA). Finally, transfection studies utilizing human skin explants revealed an increase of cells producing protein from 2% with RNA alone to 12% with dendrimer polyplexes, attributed to expression enrichment predominantly in epithelial cells, fibroblasts and leukocytes, with minor enrichment in NK cells, T cells, monocytes, and B cells. Overall, this study indicates the clear potential of ornithine dendrimers as safe and effective delivery vectors for both DNA and RNA therapeutics
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