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However, accurately monitoring the A\u03b2-42 level in serum is often thwarted by the challenges in sensitivity and specificity due to the multiplicated contaminations and intricated biofluid environments. Here, we develop a graphene field-effect transistor (G-FET) sensor modified with a type of rigid DNA framework aptamer\u2014tetrahedral DNA nanostructure (TDN) for A\u03b2-42 detection in serum. The A\u03b2-42 specific aptamer combined with the rigid tetrahedral nanostructure achieves higher binding affinity and better specificity and anti-fouling ability. The detectable concentration reaches 5 \u00d7 10\u221218 mol L\u22121 in serum, lower than most other assay approaches. Moreover, the sensor rapidly detects the A\u03b2-42 level in 6 supernatant samples from mice blood within 5 min and achieves high accuracy. This sensitive and specific method enabled by the DNA tetrahedron G-FET sensor has great potential in the monitoring of Alzheimer\u2019s disease and other diseases.<\/jats:p>","DOI":"10.3390\/s25113260","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T08:49:57Z","timestamp":1747903797000},"page":"3260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rigid DNA Frameworks Anchored Transistor Enabled Ultrasensitive Detection of A\u03b2-42 in Serum"],"prefix":"10.3390","volume":"25","author":[{"given":"Yungen","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"Shenzhen International Institute for Biomedical Research, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitao","family":"Lu","sequence":"additional","affiliation":[{"name":"Shenzhen International Institute for Biomedical Research, Shenzhen 518116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-9055","authenticated-orcid":false,"given":"Pei-Gen","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjian","family":"Xie","sequence":"additional","affiliation":[{"name":"Shenzhen Children\u2019s Hospital, Shantou University Medical College, Shenzhen 518038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 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