{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:48:46Z","timestamp":1791650926422,"version":"4.3.4"},"reference-count":96,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,10,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Three\u2010dimensional (3D) cell culture systems called spheroids have emerged as a valuable alternative to traditional two\u2010dimensional cell cultures due to their ability to closely mimic the complexity of in vivo environments. In this study we propose a hybrid \u201cconfocal\u201d electrochemiluminescence (ECL) approach that harnesses the optical sectioning ability of confocal microscopy and the high spatial resolution of ECL, overcoming the surface\u2010confinement barrier of conventional ECL and enabling depth\u2010resolved mapping of living spheroids up to 150 \u00b5m from the electrode while resolving the temporal evolution of ECL. By exploiting the sluggish heterogeneous electron\u2010transfer kinetics of the 2\u2010(dibutylamino)ethanol coreactant at ITO electrodes, homogeneous redox events driven by the sequential oxidation of [Ru(bpy)\n                    <jats:sub>3<\/jats:sub>\n                    ]\n                    <jats:sup>2+<\/jats:sup>\n                    propagate deep into the cellular architecture. Spatiotemporal mapping reveals the evolution of these processes across the spheroid volume, establishing time as an additional dimension for visualizing ECL reaction\u2010diffusion behavior within living 3D systems over time. We demonstrate that the 3D microenvironment acts as a reaction\u2010diffusion chamber that confines reactive intermediates, enhancing the signal in internal regions. This method achieves single\u2010cell resolution and provides a non\u2010invasive tool to probe internal permeability and redox metabolic states, transitioning ECL from a surface technique to a powerful volumetric imaging modality for tissue\u2010engineered models.\n                  <\/jats:p>","DOI":"10.1002\/anie.5240036","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:30:46Z","timestamp":1787736646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Four\u2010Dimensional Electrochemiluminescence Microscopy Enables Depth\u2010Resolved Imaging of Single, Living Spheroids"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5960-2472","authenticated-orcid":false,"given":"Elisa","family":"D'Arrigo","sequence":"first","affiliation":[{"name":"Univ. Bordeaux Bordeaux INP ISM UMR CNRS 5255  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-2488","authenticated-orcid":false,"given":"Vanshika","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry Purdue University  West Lafayette USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1882-1734","authenticated-orcid":false,"given":"Bertrand","family":"Goudeau","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux Bordeaux INP ISM UMR CNRS 5255  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-9705","authenticated-orcid":false,"given":"Jeffrey E.","family":"Dick","sequence":"additional","affiliation":[{"name":"Department of Chemistry Purdue University  West Lafayette USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5144-1015","authenticated-orcid":false,"given":"Neso","family":"Sojic","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux Bordeaux INP ISM UMR CNRS 5255  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010018\u20100005\u2010x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2017.09.003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176225"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc800233a"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460440902821657"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12263\u2010008\u20100107\u20100"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164\u2010017\u20100084\u20103"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202200434"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758\u20105090\/ac1ea8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.10.031"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15194846"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.4c00088"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472630318756058"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041327"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758\u20105090\/ac6d11"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346\u2010025\u201001927\u20104"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp500002y"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.5c00021"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1179\/2046023614Y.0000000047"},{"key":"e_1_2_8_21_1","article-title":"Confocal Microscopy: Principles and Modern Practices","volume":"92","author":"Elliott A. D.","year":"2020","journal-title":"Currents Protocol"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106463\/accc3d"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep15348"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201071443\u2010x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2014.11.036"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313369110"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00086F"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8SC03209B"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.asems.2022.100028"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.2c00007"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010019\u201001761\u2010x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.5c06606"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202420184"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c03139"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2021.339346"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2SD00232A"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphc.200500626"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b09260"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c05735"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202101467"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010anchem\u2010061318\u2010115226"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.5c00105"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coelec.2022.101096"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.5c00252"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b08080"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.electacta.2024.144291"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2021.113123"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.4c00105"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2025.137944"},{"key":"e_1_2_8_50_1","doi-asserted-by":"crossref","unstructured":"K.Hiramoto K.Ino K.Komatsu Y.Nashimoto andH.Shiku \u201cElectrochemiluminescence Imaging for High Throughput Analysis of Spheroids \u201d inECS Meeting Abstracts MA2021\u201001(IOP Science 2021) 1621.","DOI":"10.1149\/MA2021-01611621mtgabs"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.electacta.2023.142507"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202503594"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010023\u201004876\u20104"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c10211"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.5c00143"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202407588"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202510193"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.5c00269"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201911190"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.3c00066"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c02479"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202218574"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202506610"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b09020"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/anse.202500063"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA09371A"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202500007"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202012171"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.electacta.2024.143957"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c05663"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acselectrochem.5c00086"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202012340"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.630246"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200603491"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5AN01216C"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1932"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.8508105"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521\u20104109(200109)13:13<1083::AID\u2010ELAN1083>3.0.CO;2\u2010D"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja027532v"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6c00742"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202216525"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4SC00312H"},{"key":"e_1_2_8_83_1","unstructured":"P. C. Bethesda (MD): National Library of Medicine (US) National Center for Biotechnology Information; 2004\u2010. PubChem Compound Summary for CID 7621 2\u2010(Dibutylamino)ethanol https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/2\u2010_Dibutylamino_ethanol."},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c07566"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c10505"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.5c00135"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202521454"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c16512"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c04250"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fmre.2021.11.018"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016476\u20102"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b12833"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2012.708334"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0296529"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00801a073"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1039\/b718505g"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00633.2023"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5240036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.5240036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5240036","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5240036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:49:23Z","timestamp":1791647363000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.5240036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":96,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2026,10,12]]}},"alternative-id":["10.1002\/anie.5240036"],"URL":"https:\/\/doi.org\/10.1002\/anie.5240036","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"2026-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5240036"}}