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In this work, we developed a practical supramolecular Ab conjugation strategy based on resorc[4]arene modifiers. To improve the Ab orientation on the CNTs surface and optimizing the Ab\/Ag interaction, we exploited the host\u2010guest approach by synthesizing two newly resorc[4]arene linkers <jats:bold>R1<\/jats:bold> and <jats:bold>R2<\/jats:bold> <jats:italic>via<\/jats:italic> well\u2010established procedures. The upper rim was decorated with eight methoxyl groups to promote selective recognition of the fragment crystallizable (F<jats:sub>c<\/jats:sub>) region of the Ab. Moreover, the lower rim was functionalized with 3\u2010bromopropyloxy or 3\u2010azidopropiloxy substituents to bind the macrocycles on the multi\u2010walled carbon nanotubes (MWCNTs) surface. Accordingly, several chemical modifications of MWCNTs were evaluated. After the morphological and electrochemical characterization of nanomaterials, the resorc[4]arene\u2010modified MWCNTs were deposited onto a glassy carbon electrode surface to evaluate their potential applicability for label\u2010free immunosensor development. The most promising system showed an improved electrode active area (A<jats:sub>EL<\/jats:sub>) of almost 20\u2009% and a site\u2010oriented immobilization of the SARS\u2010CoV\u20102 spike protein S1 antibody (Ab\u2010SPS1). The developed immunosensor revealed a good sensitivity (23.64\u2005\u03bcA\u2009mL\u2009ng<jats:sup>\u22121<\/jats:sup>\u2009cm<jats:sup>\u22122<\/jats:sup>) towards the SPS1 antigen and a limit of detection (LOD) of 1.01\u2009ng\u2009mL<jats:sup>\u22121<\/jats:sup>.<\/jats:p>","DOI":"10.1002\/cbic.202300030","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T14:39:07Z","timestamp":1677854347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resorc[4]arene Modifiers for Supramolecular Site\u2010Directed Immobilization of Antibodies on Multi\u2010Walled Carbon Nanotubes"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-6091","authenticated-orcid":false,"given":"Francesca","family":"Polli","sequence":"first","affiliation":[{"name":"Department of Chemistry and Technology of Drugs Department of Excellence 2018\u20132022 Sapienza-University of Rome, P.le Aldo  Moro 5 00185 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6969-2071","authenticated-orcid":false,"given":"Gabriele","family":"Cianfoni","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs Department of Excellence 2018\u20132022 Sapienza-University of Rome, P.le Aldo  Moro 5 00185 Rome Italy"},{"name":"Center for Life Nano- and Neuro-Science@Sapienza Italian Institute of Technology  Viale Regina Elena 291 00161 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4072-0457","authenticated-orcid":false,"given":"Rem","family":"Elnahas","sequence":"additional","affiliation":[{"name":"Department of Chemistry Sapienza-University of Rome P.le Aldo  Moro 5 00185 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Mangiardi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs Department of Excellence 2018\u20132022 Sapienza-University of Rome, P.le Aldo  Moro 5 00185 Rome Italy"},{"name":"Center for Life Nano- and Neuro-Science@Sapienza Italian Institute of Technology  Viale Regina Elena 291 00161 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-5252","authenticated-orcid":false,"given":"Francesca A.","family":"Scaramuzzo","sequence":"additional","affiliation":[{"name":"Department of Basic and Applied Sciences for Engineering Sapienza - 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