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This work presents a new electrochemiluminescence (ECL) sensing device based on a bio\u2010inspired nanochannel membrane (NM) guarded with two differential gates. The recognition event at the aptamer gate is followed by the permitting of stimulator transport toward the metal\u2010organic framework (MOF) gate. Proof of concept application is evaluated using cytochrome C (Cytc) as the analyte, and glucose, a commonly existing nutriment as the stimulator. The oxidase\u2010mimic plasmonic nanoparticles induce an effective release of ECL luminophore from the MOF gate. This cascade\u2010gates guarded NM can effectively separate biological matrices from the detection cell. Consequently, the proposed system can achieve direct sensing of 1.0\u00a0n<jats:sc>m<\/jats:sc> Cytc in undiluted serum within the threshold concentrations of leukemia and lymphoma, making it attractive for point\u2010of\u2010care applications.<\/jats:p>","DOI":"10.1002\/smll.202205995","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T02:37:50Z","timestamp":1670812670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cascade\u2010Gates Guarded Asymmetrical Nanochannel Membrane: An Interference\u2010Free Device for Straightforward Detection of Trace Biomarker in Undiluted Serum"],"prefix":"10.1002","volume":"19","author":[{"given":"Xiaoxia","family":"Jian","sequence":"first","affiliation":[{"name":"Department of Chemistry College of Science Northeastern University  Shenyang 110819 P. R. 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