{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:27:11Z","timestamp":1780374431476,"version":"3.54.1"},"reference-count":60,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2033 \u2010 390677874 \u2010 RESOLV"],"award-info":[{"award-number":["EXC 2033 \u2010 390677874 \u2010 RESOLV"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010571","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft, Forschung und Technologie","doi-asserted-by":"publisher","award":["03VP11340"],"award-info":[{"award-number":["03VP11340"]}],"id":[{"id":"10.13039\/501100010571","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biosensors based on DNA aptamer receptors are increasingly used in diagnostic applications. To improve the sensitivity and specificity of aptasensors, parameters affecting the stability and binding efficiency of the receptor layer need to be identified and studied. For example, the blocking step, i.e., the addition of inert molecules to the receptor layer, can improve sensor performance, but can also cause phase separation into nanodomains of unknown composition and structure. Here, nano\u2010IR spectroscopy is used together with complementary macroscopic spectroscopic methods to study the nano\u2010structural variations during the fabrication of a recently developed SARS\u2010CoV\u20102 aptasensor. The blocking step by polyethylene glycol (PEG) causes a significant thickening of the receptor layer and a phase separation into nanodomains consisting of an aptamer\u2010rich and a slightly thicker PEG\u2010rich phase. The unambiguous chemical identification of the nanodomains is achieved by analysis of nano\u2010IR images. Furthermore, bound analyte (spike protein of SARS\u2010CoV\u20102) is detected at the single molecule level. Detailed analysis of the local nano\u2010IR spectra revealed structural properties such as the amorphous state of the PEG molecules within the nanodomains and a strong change in the secondary structure of the analyte. This study significantly advances the understanding of nanoscale chemical processes in the receptor layer of\u00a0aptasensors.<\/jats:p>","DOI":"10.1002\/smll.202409369","type":"journal-article","created":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T22:49:23Z","timestamp":1737326963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nano\u2010Phase Separation and Analyte Binding in Aptasensors Investigated by Nano\u2010IR Spectroscopy"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6532-4603","authenticated-orcid":false,"given":"Nafiseh","family":"Samiseresht","sequence":"first","affiliation":[{"name":"Department of Interface Chemistry and Surface Engineering Max Planck Institute for Sustainable Materials 40237 D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-5547","authenticated-orcid":false,"given":"Gabriela","family":"Figueroa Miranda","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing Bioelectronics (IBI\u20103) Forschungszentrum J\u00fclich GmbH 52428 J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Interface Chemistry and Surface Engineering Max Planck Institute for Sustainable Materials 40237 D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Graef","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing Bioelectronics (IBI\u20103) Forschungszentrum J\u00fclich GmbH 52428 J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-8265","authenticated-orcid":false,"given":"Dirk","family":"Mayer","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing Bioelectronics (IBI\u20103) Forschungszentrum J\u00fclich GmbH 52428 J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-5355","authenticated-orcid":false,"given":"Martin","family":"Rabe","sequence":"additional","affiliation":[{"name":"Department of Interface Chemistry and Surface Engineering Max Planck Institute for Sustainable Materials 40237 D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,19]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/bios10050045"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c14788"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c04498"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/346818a0"},{"key":"e_1_2_8_5_1","first-page":"223","volume":"3","author":"Cai R.","year":"2022","journal-title":"J. SMAB"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/521274a"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac060830g"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/45.9.1628"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2011.0313"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2014.10.057"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA08243E"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2022.114633"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/bios15010024"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2116\/analsci.19P240"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9719586"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja029450c"},{"key":"e_1_2_8_17_1","author":"Figueroa\u2010Miranda G.","year":"2020","journal-title":"Bioelectrochemistry"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1116\/1.2219110"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac052137j"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/la060222w"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00076a032"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-0286(99)00018-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp972635z"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2004.01.034"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1116\/1.3647506"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55248-x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/la034944o"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja981897r"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac0346003"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8SM02589D"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/admi.202200364"},{"key":"e_1_2_8_32_1","first-page":"675","volume-title":"Aptamers: Versatile Tools for Reagentless Aptasensing","author":"Baldrich E.","year":"2009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/la010989i"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0063902"},{"key":"e_1_2_8_35_1","volume":"8","author":"Lu F.","year":"2014","journal-title":"Nat. Photonics"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2019.02.016"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16728-1"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-23637-4"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2010.08.029"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76351-X"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physa.2012.09.022"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1088\/1367-2630\/1\/1\/006"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00511F"},{"key":"e_1_2_8_44_1","author":"Banyay M.","year":"2003","journal-title":"Biophys. Chem."},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200905693"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006350920060159"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1726462"},{"key":"e_1_2_8_48_1","author":"Zucchiatti P.","year":"2016","journal-title":"Anal. Chem."},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/la991590l"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100082a040"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/la950630s"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1209\/0295-5075\/119\/66001"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn7760"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2010.12.007"},{"key":"e_1_2_8_55_1","first-page":"1","volume":"2012","author":"Bergeron C.","year":"2012","journal-title":"J. Spectrosc."},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1726373"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/pol.1969.160071009"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-1425(98)00062-6"},{"key":"e_1_2_8_59_1","author":"Barth A.","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA) \u2010 Bioenergetics"},{"key":"e_1_2_8_60_1","doi-asserted-by":"crossref","unstructured":"B. H.Stuart Infrared Spectroscopy: Fundamentals and Applications Wiley 2004.","DOI":"10.1002\/0470011149"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202409369","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:13:48Z","timestamp":1753089228000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202409369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,19]]},"references-count":60,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/smll.202409369"],"URL":"https:\/\/doi.org\/10.1002\/smll.202409369","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,19]]},"assertion":[{"value":"2024-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2409369"}}