{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:11:12Z","timestamp":1782299472745,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000269","name":"Economic and Social Research Council","doi-asserted-by":"publisher","award":["ES\/S000208\/1"],"award-info":[{"award-number":["ES\/S000208\/1"]}],"id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/IN\/Indo-UK\/AMR\/03\/RKE"],"award-info":[{"award-number":["BT\/IN\/Indo-UK\/AMR\/03\/RKE"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>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 OD600 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.<\/jats:p>","DOI":"10.3390\/s21051872","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T04:01:25Z","timestamp":1615176085000},"page":"1872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Label-Free Electrochemical Sensor for Rapid Bacterial Pathogen Detection Using Vancomycin-Modified Highly Branched Polymers"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6446-2824","authenticated-orcid":false,"given":"Holger","family":"Schulze","sequence":"first","affiliation":[{"name":"Infection Medicine, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor\u2019s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Wilson","sequence":"additional","affiliation":[{"name":"Infection Medicine, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor\u2019s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Cara","sequence":"additional","affiliation":[{"name":"Infection Medicine, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor\u2019s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Carter","sequence":"additional","affiliation":[{"name":"Polymer and Biomaterials Chemistry Laboratories, School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward N.","family":"Dyson","sequence":"additional","affiliation":[{"name":"Polymer and Biomaterials Chemistry Laboratories, School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikrishnan","family":"Elangovan","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi 110016, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Rimmer","sequence":"additional","affiliation":[{"name":"Polymer and Biomaterials Chemistry Laboratories, School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6121-2021","authenticated-orcid":false,"given":"Till T.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Infection Medicine, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor\u2019s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1021\/ac302699x","article-title":"Bacteria screening, viability, and confirmation assays using bacteriophage-impedimetric\/loop-mediated isothermal amplification dual-response biosensors","volume":"85","author":"Tlili","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rentschler, S., Kaiser, L., and Deigner, H.P. (2021). Emerging options for the diagnosis of bacterial infections and the characterization of antimicrobial resistance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010456"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mib.2019.03.001","article-title":"Recent and emerging technologies for the rapid diagnosis of infection and antimicrobial resistance","volume":"51","author":"Trotter","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-27203-9","article-title":"Label-free detection of hypoxia-induced extracellular vesicle secretion from MCF-7 cells","volume":"8","author":"Kilic","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112949","DOI":"10.1016\/j.bios.2020.112949","article-title":"Faradaic electrochemical impedance spectroscopy for enhanced analyte detection in diagnostics","volume":"177","author":"Strong","year":"2021","journal-title":"Biosens. Bioelectron."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.bios.2019.02.017","article-title":"Development of an electrochemical impedimetric immunosensor for Corticotropin Releasing Hormone (CRH) using half-antibody fragments as elements of biorecognition","volume":"131","author":"Duran","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bios.2019.02.018","article-title":"Label-free electrochemical DNA biosensor for zika virus identification","volume":"131","author":"Faria","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bioelechem.2019.107447","article-title":"Electrochemical detection of specific interactions between apolipoprotein E isoforms and DNA sequences related to Alzheimer\u2019s disease","volume":"133","author":"Lima","year":"2020","journal-title":"Bioelectrochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Li, N., Chow, A.M., Ganesh, H.V.S., Ratnam, M., Brown, I.R., and Kerman, K. (2019). Diazonium-modified screen-printed electrodes for immunosensing growth hormone in blood samples. Biosensors, 9.","DOI":"10.3390\/bios9030088"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Su, H., Li, S., Terebiznik, M., Guyard, C., and Kerman, K. (2018). Biosensors for the detection of interaction between legionella pneumophila collagen-like protein and glycosaminoglycans. Sensors, 18.","DOI":"10.3390\/s18082668"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1146\/annurev-anchem-061318-115600","article-title":"Functional Molecular Interfaces for Impedance-Based Diagnostics","volume":"13","author":"Kanyong","year":"2020","journal-title":"Annu. Rev. Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112872","DOI":"10.1016\/j.bios.2020.112872","article-title":"Impedimetric aptamer-based glycan PSA score for discrimination of prostate cancer from other prostate diseases","volume":"175","author":"Estrela","year":"2021","journal-title":"Biosens. Bioelectron."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1021\/acssensors.0c01250","article-title":"Ultrasensitive and Label-Free Detection of the Measles Virus Using an N-Heterocyclic Carbene-Based Electrochemical Biosensor","volume":"5","author":"Mayall","year":"2020","journal-title":"ACS Sens."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cebula, Z., Zo\u0142edowska, S., Dziabowska, K., Skwarecka, M., Malinowska, N., Bialobrzeska, W., Czaczyk, E., Siuzdak, K., Sawczak, M., and Bogdanwicz, R. (2019). Detection of the Plant Pathogen Pseudomonas Impedance Spectroscopy. Sensors, 19.","DOI":"10.3390\/s19245411"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Siller, I.G., Preuss, J., Urmann, K., Ho, M.R., Scheper, T., and Bahnemann, J. (2020). 3D-Printed Flow Cells for Aptamer-Based Impedimetric Detection of E. coli Crooks Strain. Sensors, 20.","DOI":"10.3390\/s20164421"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wu, C.C., Yen, H.Y., Lai, L.T., Perng, G.C., Lee, C.R., and Wu, S.J. (2020). A label-free impedimetric genosensor for the nucleic acid amplification-free detection of extracted RNA of dengue virus. Sensors, 20.","DOI":"10.3390\/s20133728"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kwasny, D., Tehrani, S.E., Almeida, C., Schj\u00f8dt, I., Dimaki, M., and Svendsen, W.E. (2018). Direct detection of candida albicans with a membrane based electrochemical impedance spectroscopy sensor. Sensors, 18.","DOI":"10.3390\/s18072214"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bios.2016.02.035","article-title":"Novel and simple electrochemical biosensor monitoring attomolar levels of miRNA-155 in breast cancer","volume":"80","author":"Cardoso","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7738","DOI":"10.1021\/acs.analchem.5b01270","article-title":"Rapid Electrochemical Detection of New Delhi Metallo-beta-lactamase Genes To Enable Point-of-Care Testing of Carbapenem-Resistant Enterobacteriaceae","volume":"87","author":"Huang","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.bios.2016.03.037","article-title":"Label- and amplification-free electrochemical detection of bacterial ribosomal RNA","volume":"81","author":"Henihan","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1039\/c3an01319g","article-title":"Development of a PCR-free electrochemical point of care test for clinical detection of methicillin resistant Staphylococcus aureus (MRSA)","volume":"138","author":"Corrigan","year":"2013","journal-title":"Analyst"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bios.2012.01.040","article-title":"Impedimetric detection of single-stranded PCR products derived from methicillin resistant Staphylococcus aureus (MRSA) isolates","volume":"34","author":"Corrigan","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/bm100922j","article-title":"Highly branched polymers with polymyxin end groups responsive to Pseudomonas aeruginosa","volume":"12","author":"Sarker","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5824","DOI":"10.1039\/C4SM00056K","article-title":"F\u00f6rster resonance energy transfer confirms the bacterial-induced conformational transition in highly-branched poly(N-isopropyl acrylamide with vancomycin end groups on binding to Staphylococcus aureus","volume":"10","author":"Sarker","year":"2014","journal-title":"Soft Matter"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1021\/ja907466y","article-title":"Binding bacteria to highly branched poly(N-isopropyl acrylamide) modified with vancomycin induces the coil-to-globule transition","volume":"132","author":"Shepherd","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1021\/acs.biomac.7b00800","article-title":"Binding of Bacteria to Poly(N-isopropylacrylamide) Modified with Vancomycin: Comparison of Behavior of Linear and Highly Branched Polymers","volume":"18","author":"Teratanatorn","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.chroma.2017.05.050","article-title":"Analysis using size exclusion chromatography of poly(N-isopropyl acrylamide) using methanol as an eluent","volume":"1508","author":"Swift","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21681","DOI":"10.1039\/C4RA16473C","article-title":"Surface modifications of gold nanorods for applications in nanomedicine","volume":"5","author":"Locatelli","year":"2015","journal-title":"RSC Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7328","DOI":"10.1021\/ja050432f","article-title":"Dithiocarbamate assembly on gold","volume":"127","author":"Zhao","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6024","DOI":"10.1021\/ja01000a006","article-title":"Slow Hydrogen-Deuterium Exchange in a Non-\u03b1-helical Polyamide","volume":"89","author":"Scarpa","year":"1967","journal-title":"J. Am. Chem. Soc."},{"key":"ref_31","first-page":"1","article-title":"Towards Detection Directly From Whole Blood: Current and Emerging Technologies for Rapid Diagnosis of Microbial Infections Without","volume":"31","author":"Sinha","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1136\/archdischild-2017-314189","article-title":"New technologies in microbiology and their potential impact on paediatric practice","volume":"104","author":"Narayanan","year":"2019","journal-title":"Arch. Dis. Child."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.actbio.2019.01.066","article-title":"Highly-branched poly(N-isopropyl acrylamide) functionalised with pendant Nile red and chain end vancomycin for the detection of Gram-positive bacteria","volume":"87","author":"Swift","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1473-3099(20)30477-1","article-title":"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","volume":"21","author":"Kadri","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_35","first-page":"214","article-title":"Empirical treatment of urinary tract infections: How rational are our guidelines?","volume":"74","author":"Barry","year":"2019","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/5\/1872\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:34:39Z","timestamp":1760160879000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/5\/1872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["s21051872"],"URL":"https:\/\/doi.org\/10.3390\/s21051872","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]}}}