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      Label-Free Electrochemical Sensor for Rapid Bacterial Pathogen Detection Using Vancomycin-Modified Highly Branched Polymers

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          Abstract

          Rapid point of care tests for bacterial infection diagnosis are of great importance to reduce the misuse of antibiotics and burden of antimicrobial resistance. Here, we have successfully combined a new class of non-biological binder molecules with electrochemical impedance spectroscopy (EIS)-based sensor detection for direct, label-free detection of Gram-positive bacteria making use of the specific coil-to-globule conformation change of the vancomycin-modified highly branched polymers immobilized on the surface of gold screen-printed electrodes upon binding to Gram-positive bacteria. Staphylococcus carnosus was detected after just 20 min incubation of the sample solution with the polymer-functionalized electrodes. The polymer conformation change was quantified with two simple 1 min EIS tests before and after incubation with the sample. Tests revealed a concentration dependent signal change within an OD 600 range of Staphylococcus carnosus from 0.002 to 0.1 and a clear discrimination between Gram-positive Staphylococcus carnosus and Gram-negative Escherichia coli bacteria. This exhibits a clear advancement in terms of simplified test complexity compared to existing bacteria detection tests. In addition, the polymer-functionalized electrodes showed good storage and operational stability.

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          Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals

          The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections.
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            Label-free electrochemical DNA biosensor for zika virus identification

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              Novel and simple electrochemical biosensor monitoring attomolar levels of miRNA-155 in breast cancer.

              This work, describes for the first time, a simple biosensing design to yield an ultrasensitive electrochemical biosensor for a cancer biomarker detection, miRNA-155, with linear response down to the attomolar range. MiRNA-155 was selected for being overexpressed in breast cancer. The biosensor was assembled in two stages: (1) the immobilization of the anti-miRNA-155 that was thiol modified on an Au-screen printed electrode (Au-SPE), followed by (2) blocking the areas of non-specific binding with mercaptosuccinic acid. Atomic force microscopy (AFM) and electrochemical techniques including cyclic voltammetry (CV), impedance spectroscopy (EIS) and square wave voltammetry (SWV) confirmed the surface modification of these devices and their ability to hybridize successfully and stably with miRNA-155. The final biosensor provided a sensitive detection of miRNA-155 from 10 aM to 1.0 nM with a low detection limit (LOD) of 5.7 aM in real human serum samples. Good results were obtained in terms of selectivity towards breast cancer antigen CA-15.3 and bovine serum albumin (BSA). Raw fluid extracts from cell-lines of melanoma did not affect the biosensor response (no significant change of the blank), while raw extracts from breast cancer yielded a positive signal against miRNA-155. This simple and sensitive strategy is a promising alternative for simultaneous quantitative analysis of multiple miRNA in physiological fluids for biomedical research and point-of-care (POC) diagnosis.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                08 March 2021
                March 2021
                : 21
                : 5
                : 1872
                Affiliations
                [1 ]Infection Medicine, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK; holger.schulze@ 123456ed.ac.uk (H.S.); harrywilson412@ 123456gmail.com (H.W.); ines.cara@ 123456grenoble-inp.org (I.C.)
                [2 ]Polymer and Biomaterials Chemistry Laboratories, School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK; S.R.Carter@ 123456bradford.ac.uk (S.C.); E.N.Dyson@ 123456bradford.ac.uk (E.N.D.); S.Rimmer@ 123456bradford.ac.uk (S.R.)
                [3 ]Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi 110016, India; elangovan@ 123456iitd.ac.in
                Author notes
                [* ]Correspondence: till.bachmann@ 123456ed.ac.uk ; Tel.: +44-131-242-9437
                Author information
                https://orcid.org/0000-0002-6446-2824
                https://orcid.org/0000-0001-6121-2021
                Article
                sensors-21-01872
                10.3390/s21051872
                7962439
                33800145
                328b83bf-daf4-47b5-955a-eda7dc2c67c1
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 February 2021
                : 05 March 2021
                Categories
                Article

                Biomedical engineering
                electrochemical impedance spectroscopy (eis),highly branched polymers,bacteria pathogen detection,label-free,point of care diagnostics,amr

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