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Herein, a novel sandwich-type biosensor was fabricated for highly sensitive detection of exosomes. Amino-functionalized Fe3O4 nanoparticles were synthesized as a sensing interface with a large surface area and rapid enrichment capacity, while two-dimensional MXene nanosheets were used as signal amplifiers with excellent electrical properties. Specifically, CD63 aptamer attached Fe3O4 nanoprobes capture the target exosomes. MXene nanosheets modified with epithelial cell adhesion molecule (EpCAM) aptamer were tethered on the electrode surface to enhance the quantification of exosomes captured with the detection of remaining protein sites. With such a design, the proposed biosensor showed a wide linear range from 102 particles \u03bcL\u22121 to 107 particles \u03bcL\u22121 for sensing 4T1 exosomes, with a low detection limit of 43 particles \u03bcL\u22121. In addition, this sensing platform can determine four different tumor cell types (4T1, Hela, HepG2, and A549) using surface proteins corresponding to aptamers 1 and 2 (CD63 and EpCAM) and showcases good specificity in serum samples. These preliminary results demonstrate the feasibility of establishing a sensitive, accurate, and inexpensive electrochemical sensor for detecting exosome concentrations and species. Moreover, they provide a significant reference for exosome applications in clinical settings, such as liquid biopsy and early cancer diagnosis.<\/jats:p>","DOI":"10.3390\/s23073508","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T01:41:34Z","timestamp":1679967694000},"page":"3508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["High-Performance Detection of Exosomes Based on Synergistic Amplification of Amino-Functionalized Fe3O4 Nanoparticles and Two-Dimensional MXene Nanosheets"],"prefix":"10.3390","volume":"23","author":[{"given":"Linlin","family":"Zhuang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China"},{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiannan","family":"You","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China"},{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Su","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China"},{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfeng","family":"Ge","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Mei","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1319-3166","authenticated-orcid":false,"given":"Wenfei","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China"},{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0141-2798","authenticated-orcid":false,"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China"},{"name":"Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0092-8674(83)90040-5","article-title":"Fate of the transferrin receptor during maturation of sheep reticulocytes invitro\u2014selective externalization of the receptor","volume":"33","author":"Pan","year":"1983","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1084\/jem.183.3.1161","article-title":"B lymphocytes secrete antigen-presenting vesicles","volume":"183","author":"Raposo","year":"1996","journal-title":"J. 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