Cascade‐Gates Guarded Asymmetrical Nanochannel Membrane: An Interference‐Free Device for Straightforward Detection of Trace Biomarker in Undiluted Serum

Accurate detection of trace biomarkers in biological samples is a key task in diagnostic testing, but it remains challenging due to the high concentration of other physiologically relevant interferences. This work presents a new electrochemiluminescence (ECL) sensing device based on a bio‐inspired 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‐organic 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‐mimic plasmonic nanoparticles induce an effective release of ECL luminophore from the MOF gate. This cascade‐gates guarded NM can effectively separate biological matrices from the detection cell. Consequently, the proposed system can achieve direct sensing of 1.0 nm Cytc in undiluted serum within the threshold concentrations of leukemia and lymphoma, making it attractive for point‐of‐care applications. An electrochemiluminescence biosensing strategy using a cascade‐gates guarded membrane is developed for eliminating matrix interference and regulating the delivery of signal reporters from two separate but correlated binding events. Using cytochrome C as the model analyte, the membrane demonstrates outstanding performance for direct analysis of trace biomarker in undiluted serum.