{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:09:32Z","timestamp":1773083372694,"version":"3.50.1"},"reference-count":47,"publisher":"IOP Publishing","issue":"46","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000183","name":"Army Research Office","doi-asserted-by":"crossref","award":["W911NF-18-1-0076"],"award-info":[{"award-number":["W911NF-18-1-0076"]}],"id":[{"id":"10.13039\/100000183","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["2153425"],"award-info":[{"award-number":["2153425"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Nanotechnology"],"published-print":{"date-parts":[[2023,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We describe the concept and roadmap of an engineered electronic nose with specificity towards analytes that differ by as little as one carbon atom, and sensitivity of being able to electrically register a single molecule of analyte. The analyte could be anything that natural noses can detect, e.g. trinitrotoluene (TNT), cocaine, aromatics, volatile organic compounds etc. The strategy envisioned is to genetically engineer a fused olfactory odorant receptor (odorant receptor (OR), a membrane-bound G-protein coupled receptor (GPCR) with high selectivity) to an ion channel protein, which opens in response to binding of the ligand to the OR. The lipid bilayer supporting the fused sensing protein would be intimately attached to a nanowire or nanotube network (either via a covalent tether or a non-covalent physisorption process), which would electrically detect the opening of the ion channel, and hence the binding of a single ligand to a single OR protein domain. Three man-made technological advances: (1) fused GPCR to ion channel protein, (2) nanowire sensing of single ion channel activity, and (3) lipid bilayer to nanotube\/nanowire tethering chemistry and on natural technology (sensitivity and selectivity of OR domains to specific analytes) each have been demonstrated and\/or studied independently. The combination of these three technological advances and the result of millions of years of evolution of OR proteins would enable the goal of single molecule sensing with specificity towards analytes that differ by as little as one carbon atom. This is both a review of the past and a vision of the future.<\/jats:p>","DOI":"10.1088\/1361-6528\/acebf3","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T22:21:31Z","timestamp":1690842091000},"page":"465502","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Nanowire biosensors with olfactory proteins: towards a genuine electronic nose with single molecule sensitivity and high selectivity"],"prefix":"10.1088","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-1812","authenticated-orcid":true,"given":"Sangjun","family":"Noh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9315-0352","authenticated-orcid":false,"given":"Francesco","family":"Tombola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-1014","authenticated-orcid":true,"given":"Peter","family":"Burke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2023,8,29]]},"reference":[{"key":"nanoacebf3bib1","doi-asserted-by":"publisher","DOI":"10.1063\/1.4867025","article-title":"Limit of detection of field effect transistor biosensors: effects of surface modification and size dependence","volume":"104","author":"Rajan","year":"2014","journal-title":"Appl. Phys. Lett."},{"key":"nanoacebf3bib2","doi-asserted-by":"publisher","first-page":"5315","DOI":"10.1021\/nl502366e","article-title":"Direct, rapid, and label-free detection of enzyme\u2014substrate interactions in physiological buffers using CMOS-compatible nanoribbon sensors","volume":"14","author":"Mu","year":"2014","journal-title":"Nano Lett."},{"key":"nanoacebf3bib3","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1038\/nnano.2009.353","article-title":"Label-free biomarker detection from whole blood","volume":"5","author":"Stern","year":"2010","journal-title":"Nat. Nanotechnol."},{"key":"nanoacebf3bib4","doi-asserted-by":"publisher","first-page":"4014","DOI":"10.1021\/nn306034f","article-title":"Regenerative electronic biosensors using supramolecular approaches","volume":"7","author":"Duan","year":"2013","journal-title":"ACS Nano"},{"key":"nanoacebf3bib5","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature05498","article-title":"Label-free immunodetection with CMOS-compatible semiconducting nanowires","volume":"445","author":"Stern","year":"2007","journal-title":"Nature"},{"key":"nanoacebf3bib6"},{"key":"nanoacebf3bib7","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1039\/c2an16205a","article-title":"Direct measurement of extracellular electrical signals from mammalian olfactory sensory neurons in planar triode devices","volume":"137","author":"Kim","year":"2012","journal-title":"Analyst"},{"key":"nanoacebf3bib8","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/nnano.2008.242","article-title":"Coupling ion channels to receptors for biomolecule sensing","volume":"3","author":"Moreau","year":"2008","journal-title":"Nat. Nanotechnol."},{"key":"nanoacebf3bib9","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/nrg2480","article-title":"The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity","volume":"9","author":"Nei","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"nanoacebf3bib10","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/0092-8674(91)90418-X","article-title":"A novel multigene family may encode odorant receptors: a molecular basis for odor recognition","volume":"65","author":"Buck","year":"1991","journal-title":"Cell"},{"key":"nanoacebf3bib11","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1101\/gr.169532.113","article-title":"Extreme expansion of the olfactory receptor gene repertoire in african elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals","volume":"24","author":"Niimura","year":"2014","journal-title":"Genome Res."},{"key":"nanoacebf3bib12","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/adma.200801435","article-title":"Single-carbon-atomic-resolution detection of odorant molecules using a human olfactory receptor-based bioelectronic nose","volume":"21","author":"Kim","year":"2009","journal-title":"Adv. Mater."},{"key":"nanoacebf3bib13","doi-asserted-by":"publisher","first-page":"5408","DOI":"10.1021\/nn200489j","article-title":"Biomimetic chemical sensors using nanoelectronic readout of olfactory receptor proteins","volume":"5","author":"Goldsmith","year":"2011","journal-title":"ACS Nano"},{"key":"nanoacebf3bib14","doi-asserted-by":"publisher","first-page":"4925","DOI":"10.1021\/nl403983u","article-title":"Single electron charge sensitivity of liquid-gated carbon nanotube transistors","volume":"14","author":"Sharf","year":"2014","journal-title":"Nano Lett."},{"key":"nanoacebf3bib15","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/bs.mie.2014.12.017","volume":"vol 556","author":"Moreau","year":"2015","edition":"1st edn"},{"key":"nanoacebf3bib16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0043766","article-title":"Engineering of an artificial light-modulated potassium channel","volume":"7","author":"Caro","year":"2012","journal-title":"PLoS One"},{"key":"nanoacebf3bib17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0018226","article-title":"B 2-adrenergic ion-channel coupled receptors as conformational motion detectors","volume":"6","author":"Caro","year":"2011","journal-title":"PLoS One"},{"key":"nanoacebf3bib18","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.str.2013.10.002","article-title":"Functional assay for T4 lysozyme-engineered G protein-coupled receptors with an ion channel reporter","volume":"22","author":"Niescierowicz","year":"2014","journal-title":"Struct.\/Folding Des."},{"key":"nanoacebf3bib19","doi-asserted-by":"publisher","DOI":"10.1038\/srep41154","article-title":"Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors","volume":"7","author":"Moreau","year":"2017","journal-title":"Sci. Rep."},{"key":"nanoacebf3bib20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2015.04.034","article-title":"Coupling of olfactory receptor and ion channel for rapid and sensitive visualization of odorant response","volume":"22","author":"Oh","year":"2015","journal-title":"Acta Biomater."},{"key":"nanoacebf3bib21","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.bios.2012.03.012","article-title":"Nanovesicle-based bioelectronic nose platform mimicking human olfactory signal transduction","volume":"35","author":"Jin","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"nanoacebf3bib22","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1021\/nn506494e","article-title":"Ion-channel-coupled receptor-based platform for a real-time measurement of g-protein-coupled receptor activities","volume":"9","author":"Lim","year":"2015","journal-title":"ACS Nano"},{"key":"nanoacebf3bib23","doi-asserted-by":"publisher","first-page":"9208","DOI":"10.1038\/srep09208","article-title":"Detection of single ion channel activity with carbon nanotubes","volume":"5","author":"Zhou","year":"2015","journal-title":"Sci. Rep."},{"key":"nanoacebf3bib24","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.1021\/nn501376z","article-title":"Charging the quantum capacitance of graphene with a single biological ion channel","volume":"8","author":"Wang","year":"2014","journal-title":"ACS Nano"},{"key":"nanoacebf3bib25","doi-asserted-by":"publisher","DOI":"10.1088\/2399-1984\/aac737","article-title":"Sensing the electrical activity of single ion channels with top-down silicon nanoribbons","volume":"2","author":"Zhou","year":"2018","journal-title":"Nano Furtures"},{"key":"nanoacebf3bib26","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S1389-0352(00)00012-X","article-title":"Functional tethered lipid bilayers","volume":"74","author":"Knoll","year":"2000","journal-title":"Rev. Mol. Biotechnol."},{"key":"nanoacebf3bib27","doi-asserted-by":"publisher","first-page":"13341","DOI":"10.1039\/c1cp20667b","article-title":"Tethered bilayer lipid micromembranes for single-channel recording: the role of adsorbed and partially fused lipid vesicles","volume":"13","author":"Becucci","year":"2011","journal-title":"Phys. Chem. Chem. Phys."},{"key":"nanoacebf3bib28","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.3390\/ma5122637","article-title":"Biotechnology applications of tethered lipid bilayer membranes","volume":"5","author":"Jackman","year":"2012","journal-title":"Materials"},{"key":"nanoacebf3bib29","volume":"vol 53","author":"Schmitt","year":"2012"},{"key":"nanoacebf3bib30","doi-asserted-by":"publisher","first-page":"14618","DOI":"10.1021\/acsami.7b00268","article-title":"Versatile bottom-up synthesis of tethered bilayer lipid membranes on nanoelectronic biosensor devices","volume":"9","author":"Zhou","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"nanoacebf3bib31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42003-021-01792-0","article-title":"Voltage-gated proton channels from fungi highlight role of peripheral regions in channel activation","volume":"4","author":"Zhao","year":"2021","journal-title":"Commun. Biol."},{"key":"nanoacebf3bib32","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nsmb.1738","article-title":"The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity","volume":"17","author":"Tombola","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"nanoacebf3bib33","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: a unified platform for automated protein structure and function prediction","volume":"5","author":"Roy","year":"2010","journal-title":"Nat. Protoc."},{"key":"nanoacebf3bib34","doi-asserted-by":"publisher","first-page":"W429","DOI":"10.1093\/nar\/gkz384","article-title":"LOMETS2: improved meta-threading server for fold-recognition and structure-based function annotation for distant-homology proteins","volume":"47","author":"Zheng","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"nanoacebf3bib35","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/S0169-328X(97)00099-5","article-title":"Functional expression of olfactory-adrenergic receptor chimeras and intracellular retention of heterologously expressed olfactory receptors","volume":"48","author":"McClintock","year":"1997","journal-title":"Mol. Brain. Res."},{"key":"nanoacebf3bib36","doi-asserted-by":"publisher","first-page":"7285","DOI":"10.1074\/jbc.M005433200","article-title":"Olfactory receptor trafficking involves conserved regulatory steps","volume":"276","author":"Gimelbrant","year":"2001","journal-title":"J. Biol. Chem."},{"key":"nanoacebf3bib37","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1093\/chemse\/bjj049","article-title":"A specific heat shock protein enhances the expression of mammalian olfactory receptor proteins","volume":"31","author":"Neuhaus","year":"2006","journal-title":"Chem. Senses"},{"key":"nanoacebf3bib38","doi-asserted-by":"publisher","first-page":"16148","DOI":"10.1073\/pnas.1409802111","article-title":"Stretch-activated ion channel piezo1 directs lineage choice in human neural stem cells","volume":"111","author":"Pathak","year":"2014","journal-title":"PNAS"},{"key":"nanoacebf3bib39","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/nature05396","article-title":"The twisted ion-permeation pathway of a resting voltage-sensing domain","volume":"445","author":"Tombola","year":"2007","journal-title":"Nature"},{"key":"nanoacebf3bib40","doi-asserted-by":"publisher","first-page":"9971","DOI":"10.1073\/pnas.1324012111","article-title":"Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives","volume":"111","author":"Hong","year":"2014","journal-title":"PNAS"},{"key":"nanoacebf3bib41","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1085\/jgp.202012832","article-title":"HIFs: new arginine mimic inhibitors of the Hv1 channel with improved VSD\u2013ligand interactions","volume":"153","author":"Zhao","year":"2021","journal-title":"J. Gen. Physiol."},{"key":"nanoacebf3bib42","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1038\/nprot.2008.120","article-title":"Evaluating cell-surface expression and measuring activation of mammalian odorant receptors in heterologous cells","volume":"3","author":"Zhuang","year":"2008","journal-title":"Nat. Protoc."},{"key":"nanoacebf3bib43","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/j.jhazmat.2009.10.054","article-title":"Detection of explosives by olfactory sensory neurons","volume":"175","author":"Corcelli","year":"2010","journal-title":"J. Hazard. Mater."},{"key":"nanoacebf3bib44","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.1021\/nn103324p","article-title":"Selective and sensitive TNT sensors using biomimetic polydiacetylene- coated CNT-FETs","volume":"5","author":"Kim","year":"2011","journal-title":"ACS Nano"},{"key":"nanoacebf3bib45","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.bios.2016.09.040","article-title":"A portable and multiplexed bioelectronic sensor using human olfactory and taste receptors","volume":"87","author":"Son","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"nanoacebf3bib46","doi-asserted-by":"publisher","first-page":"11283","DOI":"10.1021\/acs.analchem.6b03284","article-title":"Bioelectronic nose using odorant binding protein-derived peptide and carbon nanotube field-effect transistor for the assessment of salmonella contamination in food","volume":"88","author":"Son","year":"2016","journal-title":"Anal. Chem."},{"key":"nanoacebf3bib47","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.tibtech.2016.12.007","article-title":"Bioelectronic nose: an emerging tool for odor standardization","volume":"35","author":"Son","year":"2017","journal-title":"Trends Biotechnol."}],"container-title":["Nanotechnology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T07:24:31Z","timestamp":1693293871000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/acebf3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,29]]},"references-count":47,"journal-issue":{"issue":"46","published-online":{"date-parts":[[2023,8,29]]},"published-print":{"date-parts":[[2023,11,12]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6528\/acebf3","relation":{},"ISSN":["0957-4484","1361-6528"],"issn-type":[{"value":"0957-4484","type":"print"},{"value":"1361-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,29]]},"assertion":[{"value":"Nanowire biosensors with olfactory proteins: towards a genuine electronic nose with single molecule sensitivity and high selectivity","name":"article_title","label":"Article Title"},{"value":"Nanotechnology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2023 The Author(s). Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2023-01-20","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2023-07-31","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2023-08-29","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}