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      Single-particle mass spectrometry with arrays of frequency-addressed nanomechanical resonators

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          Abstract

          One of the main challenges to overcome to perform nanomechanical mass spectrometry analysis in a practical time frame stems from the size mismatch between the analyte beam and the small nanomechanical detector area. We report here the demonstration of mass spectrometry with arrays of 20 multiplexed nanomechanical resonators; each resonator is designed with a distinct resonance frequency which becomes its individual address. Mass spectra of metallic aggregates in the MDa range are acquired with more than one order of magnitude improvement in analysis time compared to individual resonators. A 20 NEMS array is probed in 150 ms with the same mass limit of detection as a single resonator. Spectra acquired with a conventional time-of-flight mass spectrometer in the same system show excellent agreement. We also demonstrate how mass spectrometry imaging at the single-particle level becomes possible by mapping a 4-cm-particle beam in the MDa range and above.

          Abstract

          Nano-electro-mechanical system-based mass spectrometry holds promise for detecting supramolecular assemblies at large molecular weights, but its efficiency is too poor to be practical. Sage et al. overcome this problem using a nanomechanical resonator array, which significantly decreases detection time.

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          Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data

          The occurrence and fate of pharmaceutically active compounds (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. In some investigations carried out in Austria, Brazil, Canada, Croatia, England, Germany, Greece, Italy, Spain, Switzerland, The Netherlands, and the U.S., more than 80 compounds, pharmaceuticals and several drug metabolites, have been detected in the aquatic environment. Several PhACs from various prescription classes have been found at concentrations up to the microg/l-level in sewage influent and effluent samples and also in several surface waters located downstream from municipal sewage treatment plants (STPs). The studies show that some PhACs originating from human therapy are not eliminated completely in the municipal STPs and are, thus, discharged as contaminants into the receiving waters. Under recharge conditions, polar PhACs such as clofibric acid, carbamazepine, primidone or iodinated contrast agents can leach through the subsoil and have also been detected in several groundwater samples in Germany. Positive findings of PhACs have, however, also been reported in groundwater contaminated by landfill leachates or manufacturing residues. To date, only in a few cases PhACs have also been detected at trace-levels in drinking water samples.
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            Single-protein nanomechanical mass spectrometry in real time

            Nanoelectromechanical systems (NEMS) resonators can detect mass with exceptional sensitivity. Previously, mass spectra from several hundred adsorption events were assembled in NEMS-based mass spectrometry using statistical analysis. Here, we report the first realization of single-molecule NEMS-based mass spectrometry in real time. As each molecule in the sample adsorbs upon the NEMS resonator, its mass and the position-of-adsorption are determined by continuously tracking two driven vibrational modes of the device. We demonstrate the potential of multimode NEMS-based mass spectrometry by analyzing IgM antibody complexes in real-time. NEMS-MS is a unique and promising new form of mass spectrometry: it can resolve neutral species, provides resolving power that increases markedly for very large masses, and allows acquisition of spectra, molecule-by-molecule, in real-time.
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              The molecular sociology of the cell.

              Proteomic studies have yielded detailed lists of the proteins present in a cell. Comparatively little is known, however, about how these proteins interact and are spatially arranged within the 'functional modules' of the cell: that is, the 'molecular sociology' of the cell. This gap is now being bridged by using emerging experimental techniques, such as mass spectrometry of complexes and single-particle cryo-electron microscopy, to complement traditional biochemical and biophysical methods. With the development of integrative computational methods to exploit the data obtained, such hybrid approaches will uncover the molecular architectures, and perhaps even atomic models, of many protein complexes. With these structures in hand, researchers will be poised to use cryo-electron tomography to view protein complexes in action within cells, providing unprecedented insights into protein-interaction networks.
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                Author and article information

                Contributors
                sebastien.hentz@cea.fr
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                16 August 2018
                16 August 2018
                2018
                : 9
                : 3283
                Affiliations
                [1 ]GRID grid.457348.9, Univ. Grenoble Alpes, CEA, LETI, ; 38000 Grenoble, France
                [2 ]ISNI 0000 0001 0482 5067, GRID grid.34980.36, Centre for Nano Science and Engineering, , Indian Institute of Science, ; Bangalore, 560012 India
                [3 ]Univ. Grenoble Alpes, CEA, CNRS, Grenoble INP, INAC-Spintec, 38000 Grenoble, France
                [4 ]ISNI 0000000107068890, GRID grid.20861.3d, Kavli Nanoscience Institute and Departments of Physics, Applied Physics, and Bioengineering, , California Institute of Technology, ; MC 149-33, Pasadena, CA 91125 USA
                [5 ]GRID grid.450307.5, Université Grenoble-Alpes, ; 38000 Grenoble, France
                [6 ]GRID grid.457348.9, CEA, BIG, Biologie à Grande Echelle, ; 38054 Grenoble, France
                [7 ]ISNI 0000000121866389, GRID grid.7429.8, Inserm, Unité 1038, ; 38054 Grenoble, France
                [8 ]Present Address: APIX Analytics, 7 parvis Louis Néel – CS20050, 38040 Grenoble, France
                Author information
                http://orcid.org/0000-0003-0479-9027
                Article
                5783
                10.1038/s41467-018-05783-4
                6095856
                30115919
                fcc4ec95-8563-4a6b-ad1c-c5dc53eab5f9
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 December 2017
                : 5 June 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000781, EC | European Research Council (ERC);
                Award ID: 616251
                Award Recipient :
                Funded by: Carnot LETI
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