{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:22:20Z","timestamp":1788366140682,"version":"build-2803163510"},"reference-count":52,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T00:00:00Z","timestamp":1551052800000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["MOSS17GO"],"award-info":[{"award-number":["MOSS17GO"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/J01253X\/1"],"award-info":[{"award-number":["BB\/J01253X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ciliated lung epithelial cells and the airway surface liquid (ASL) comprise one of the body\u2019s most important protective systems. This system is finely tuned, and perturbations to ASL rheology, ASL depth, ASL pH, the transepithelial potential, and the cilia beat frequency are all associated with disease pathology. Further, these apparently distinct properties interact with each other in a complex manner. For example, changes in ASL rheology can result from altered mucin secretion, changes in ASL pH, or changes in ASL depth. Thus, one of the great challenges in trying to understand airway pathology is that the properties of the ASL\/epithelial cell system need to be assessed near-simultaneously and without perturbing the sample. Here, we show that nanosensor probes mounted on a scanning ion conductance microscope make this possible for the first time, without any need for labeling. We also demonstrate that ASL from senescence-retarded human bronchial epithelial cells retains its native properties. Our results demonstrate that by using a nanosensor approach, it is possible to pursue faster, more accurate, more coherent, and more informative studies of ASL and airway epithelia in health and disease.<\/jats:p>","DOI":"10.1021\/acsami.8b14122","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T11:02:36Z","timestamp":1547636556000},"page":"8731-8739","source":"Crossref","is-referenced-by-count":8,"title":["A\nNanosensor Toolbox for Rapid, Label-Free Measurement\nof Airway Surface Liquid and Epithelial Cell Function"],"prefix":"10.1021","volume":"11","author":[{"given":"Rositsa","family":"Ivanova","sequence":"first","affiliation":[{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C. H.","family":"Benton","sequence":"additional","affiliation":[{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa M.","family":"Munye","sequence":"additional","affiliation":[{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarinda","family":"Rangseesorranan","sequence":"additional","affiliation":[{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Hart","sequence":"additional","affiliation":[{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-6353","authenticated-orcid":true,"given":"Guy W. J.","family":"Moss","sequence":"additional","affiliation":[{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]},{"name":"University College London , , ,","place":["London, U.K., WC1E 6BT"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"2026090212112988600_cit1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1146\/annurev.med.58.071905.105316","article-title":"Airway\nSurface Dehydration in Cystic Fibrosis: Pathogenesis and Therapy","volume":"58","author":"Boucher","year":"2007","journal-title":"Annu. Rev. 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Biol."},{"key":"2026090212112988600_cit5","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1164\/rccm.200807-1056oc","article-title":"Ex Vivo Sputum Analysis Reveals Impairment\nof Protease-Dependent\nMucus Degradation by Plasma Proteins in Acute Asthma","volume":"180","author":"Innes","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026090212112988600_cit6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1378\/chest.129.1.118","article-title":"Mucus Properties In Children With\nPrimary Ciliary Dyskinesia","volume":"129","author":"Bush","year":"2006","journal-title":"Chest"},{"key":"2026090212112988600_cit7","doi-asserted-by":"publisher","first-page":"L109","DOI":"10.1152\/ajplung.00027.2015","article-title":"Automated Acquisition\nand Analysis\nof Airway Surface Liquid Height by Confocal Microscopy","volume":"309","author":"Choi","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"2026090212112988600_cit8","doi-asserted-by":"publisher","first-page":"11412","DOI":"10.1073\/pnas.0903609106","article-title":"SPLUNC1 Regulates\nAirway\nSurface Liquid Volume by Protecting ENaC from Proteolytic Cleavage","volume":"106","author":"Garcia-Caballero","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090212112988600_cit9","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1172\/jci83922","article-title":"Acidic PH Increases Airway Surface Liquid Viscosity\nin Cystic Fibrosis","volume":"126","author":"Tang","year":"2016","journal-title":"J. Clin. Invest."},{"key":"2026090212112988600_cit10","doi-asserted-by":"publisher","first-page":"ra46","DOI":"10.1126\/scisignal.2003755","article-title":"Mechanosensitive\nATP Release Maintains Proper Mucus Hydration of Airways","volume":"6","author":"Button","year":"2013","journal-title":"Sci. Signal."},{"key":"2026090212112988600_cit11","doi-asserted-by":"publisher","first-page":"15973","DOI":"10.1073\/pnas.1311999110","article-title":"Molecular\nBasis for PH-Dependent Mucosal Dehydration\nin Cystic Fibrosis Airways","volume":"110","author":"Garland","year":"2013","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"key":"2026090212112988600_cit12","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1126\/science.2464851","article-title":"The Scanning\nIon-Conductance Microscope","volume":"243","author":"Hansma","year":"1989","journal-title":"Science"},{"key":"2026090212112988600_cit13","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/s0006-3495(97)78100-1","article-title":"Scanning\nIon Conductance Microscopy of Living Cells","volume":"73","author":"Korchev","year":"1997","journal-title":"Biophys. 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Care Med."},{"key":"2026090212112988600_cit18","doi-asserted-by":"publisher","first-page":"094905","DOI":"10.1063\/1.3122007","article-title":"Image Formation, Resolution, and\nHeight Measurement\nin Scanning Ion Conductance Microscopy","volume":"105","author":"Rheinlaender","year":"2009","journal-title":"J. Appl.\nPhys."},{"key":"2026090212112988600_cit19","doi-asserted-by":"publisher","first-page":"2353","DOI":"10.1021\/ac402748j","article-title":"Contact-Free Scanning and Imaging\nwith the Scanning Ion Conductance Microscope","volume":"86","author":"Del Linz","year":"2014","journal-title":"Anal. Chem."},{"key":"2026090212112988600_cit20","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.1021\/ac303441n","article-title":"Scanning\nIon Conductance Microscopy Measurement of Paracellular Channel Conductance\nin Tight Junctions","volume":"85","author":"Chen","year":"2013","journal-title":"Anal. 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Chem."},{"key":"2026090212112988600_cit27","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/2046-2530-1-14","article-title":"CiliaFA: A Research Tool for Automated, High-Throughput\nMeasurement of Ciliary Beat Frequency Using Freely Available Software","volume":"1","author":"Smith","year":"2012","journal-title":"Cilia"},{"key":"2026090212112988600_cit28","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1177\/0194599816640219","article-title":"A Low-Cost Method\nof Ciliary Beat\nFrequency Measurement Using IPhone and MATLAB: Rabbit Study","volume":"155","author":"Chen","year":"2016","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"2026090212112988600_cit29","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1164\/ajrccm.157.3.9703059","volume":"157","author":"Feng","year":"1998","journal-title":"Am. J. Respir. Crit.\nCare\nMed."},{"key":"2026090212112988600_cit30","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nature11130","article-title":"Reduced\nAirway Surface\nPH Impairs Bacterial Killing in the Porcine Cystic Fibrosis Lung","volume":"487","author":"Pezzulo","year":"2012","journal-title":"Nature"},{"key":"2026090212112988600_cit31","doi-asserted-by":"publisher","first-page":"10260","DOI":"10.1073\/pnas.1106695108","article-title":"Human Cystic\nFibrosis Airway Epithelia Have Reduced Cl- Conductance but Not Increased\nNa+ Conductance","volume":"108","author":"Itani","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090212112988600_cit32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-017-00532-5","article-title":"Airway\nSurface Liquid PH Is Not Acidic in Children\nwith Cystic Fibrosis","volume":"8","author":"Schultz","year":"2017","journal-title":"Nat. Commun."},{"key":"2026090212112988600_cit33","doi-asserted-by":"publisher","first-page":"H430","DOI":"10.1149\/2.028308jes","article-title":"Local PH\nMeasurement\nwith Scanning Ion Conductance Microscopy","volume":"160","author":"Morris","year":"2013","journal-title":"J.\nElectrochem. Soc."},{"key":"2026090212112988600_cit34","doi-asserted-by":"publisher","first-page":"8070","DOI":"10.1021\/ac401883n","article-title":"Fabrication\nand Characterization of Dual Function Nanoscale PH-Scanning Ion Conductance\nMicroscopy (SICM) Probes for High Resolution PH Mapping","volume":"85","author":"Nadappuram","year":"2013","journal-title":"Anal. Chem."},{"key":"2026090212112988600_cit35","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.ultramic.2018.04.009","article-title":"A Continuous\nControl Mode with Improved Imaging Rate for Scanning Ion Conductance\nMicroscope (SICM)","volume":"190","author":"Zhuang","year":"2018","journal-title":"Ultramicroscopy"},{"key":"2026090212112988600_cit36","doi-asserted-by":"publisher","first-page":"e8157","DOI":"10.1371\/journal.pone.0008157","article-title":"Smoking\nIs Associated with Shortened Airway Cilia","volume":"4","author":"Leopold","year":"2009","journal-title":"PLoS\nOne"},{"key":"2026090212112988600_cit37","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.jaci.2014.07.038","article-title":"Impairment of Cilia\nArchitecture and Ciliogenesis in Hyperplastic\nNasal Epithelium from Nasal Polyps","volume":"134","author":"Li","year":"2014","journal-title":"J. Allergy\nClin. Immunol."},{"key":"2026090212112988600_cit38","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1073\/pnas.0712327105","article-title":"Loss\nof Bardet-Biedl\nSyndrome Proteins Alters the Morphology and Function of Motile Cilia\nin Airway Epithelia","volume":"105","author":"Shah","year":"2008","journal-title":"Proc. Natl. Acad. Sci.\nU.S.A."},{"key":"2026090212112988600_cit39","first-page":"551","article-title":"Length\nand Distribution of Cilia in Human and Canine\nAirways","volume":"13","author":"Serafini","year":"1977","journal-title":"Bull Eur Physiopathol Respir"},{"key":"2026090212112988600_cit40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1085\/jgp.201611696","article-title":"Progress\nin Ciliary Ion Channel Physiology","volume":"149","author":"Pablo","year":"2016","journal-title":"J. Gen. Physiol."},{"key":"2026090212112988600_cit41","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.semcdb.2017.09.024","article-title":"Scanning Ion\nConductance\nMicroscopy for Visualizing the Three-Dimensional Surface Topography\nof Cells and Tissues","volume":"73","author":"Nakajima","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"2026090212112988600_cit42","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1021\/acs.analchem.7b05112","article-title":"Nanoscale\nImaging of Primary Cilia with Scanning Ion Conductance Microscopy","volume":"90","author":"Zhou","year":"2018","journal-title":"Anal. Chem."},{"key":"2026090212112988600_cit43","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1152\/jappl.1995.78.6.2020","article-title":"State of Airway\nSurface Liquid on Guinea Pig Trachea","volume":"78","author":"Rahmoune","year":"1995","journal-title":"J. Appl.\nPhysiol."},{"key":"2026090212112988600_cit44","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1165\/rcmb.2010-0484oc","article-title":"Measurement of the\nAirway Surface Liquid Volume with Simple Light Refraction Microscopy","volume":"45","author":"Harvey","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026090212112988600_cit45","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1085\/jgp.201010490","article-title":"Airway\nSurface Liquid\nDepth Imaged by Surface Laser Reflectance Microscopy","volume":"136","author":"Thiagarajah","year":"2010","journal-title":"J. Gen. Physiol."},{"key":"2026090212112988600_cit46","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.1021\/ac4002723","article-title":"Deuterium\nOxide Dilution: A Novel Method to Study Apical Water Layers and Transepithelial\nWater Transport","volume":"85","author":"Neubauer","year":"2013","journal-title":"Anal. Chem."},{"key":"2026090212112988600_cit47","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1172\/jci11154","article-title":"Noninvasive\nin Vivo Fluorescence Measurement of Airway Surface Liquid Depth, Salt\nConcentration, and PH","volume":"107","author":"Jayaraman","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2026090212112988600_cit48","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1164\/rccm.201404-0670oc","article-title":"A Functional Anatomic Defect of the Cystic Fibrosis\nAirway","volume":"190","author":"Birket","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026090212112988600_cit49","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1016\/s0006-3495(01)75826-2","article-title":"Simultaneous Measurement\nof Ca2+ and Cellular Dynamics:\nCombined Scanning Ion Conductance and Optical Microscopy to Study\nContracting Cardiac Myocytes","volume":"81","author":"Shevchuk","year":"2001","journal-title":"Biophys. J."},{"key":"2026090212112988600_cit50","doi-asserted-by":"publisher","first-page":"10118","DOI":"10.1021\/ja1029478","article-title":"Simultaneous\nNoncontact Topography\nand Electrochemical Imaging by SECM\/SICM Featuring Ion Current Feedback\nRegulation","volume":"132","author":"Takahashi","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"2026090212112988600_cit51","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1021\/ac902224q","article-title":"Integrated\nUltramicroelectrode-Nanopipet Probe for Concurrent Scanning Electrochemical\nMicroscopy and Scanning Ion Conductance","volume":"82","author":"Elam","year":"2010"},{"key":"2026090212112988600_cit52","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1021\/acs.analchem.6b04629","article-title":"Quantitative\nVisualization of Molecular Delivery and Uptake at Living Cells with\nSelf-Referencing Scanning Ion Conductance Microscopy (SICM) \u2013\nScanning Electrochemical Microscopy (SECM)","volume":"89","author":"Page","year":"2017","journal-title":"Anal. Chem."}],"container-title":["ACS Applied Materials &amp; Interfaces"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsami.8b14122","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/11\/9\/8731\/66927182\/acsami.8b14122.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/11\/9\/8731\/66927182\/acsami.8b14122.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:11:33Z","timestamp":1788365493000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aamick\/article\/11\/9\/8731\/1725238\/A-Nanosensor-Toolbox-for-Rapid-Label-Free"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,16]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,1,16]]},"published-print":{"date-parts":[[2019,3,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acsami.8b14122","relation":{},"ISSN":["1944-8244","1944-8252"],"issn-type":[{"value":"1944-8244","type":"print"},{"value":"1944-8252","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,16]]}}}