Supramolecular Recognition‐Mediated Layer‐by‐Layer Self‐Assembled Gold Nanoparticles for Customized Sensitivity in Paper‐Based Strip Nanobiosensors

Abstract Herein, a smart supramolecular self‐assembly‐mediated signal amplification strategy is developed on a paper‐based nanobiosensor to achieve the sensitive and customized detection of biomarkers. The host–guest recognition between β‐cyclodextrin‐coated gold nanoparticles (AuNPs) and 1‐adamantane acetic acid or tetrakis(4‐carboxyphenyl)porphyrin is designed and applied to the layer‐by‐layer self‐assembly of AuNPs at the test area of the strip. Thus, the amplified platform exhibits a high sensitivity with a detection limit at subattogram levels (approximately dozens of molecules per strip) and a wide dynamic range of concentration over seven orders of magnitude. The applicability and universality of this sensitive platform are demonstrated in clinically significant ranges to measure carcinoembryonic antigen and HIV‐1 capsid p24 antigen in spiked serum and clinical samples. The customized biomarker detection ability for the on‐demand needs of clinicians is further verified through cycle incubation‐mediated controllable self‐assembly. Collectively, the supramolecular self‐assembly amplification method is suitable as a universal point‐of‐care diagnostic tool and can be readily adapted as a platform technology for the sensitive assay of many different target analytes.