Multi-labeling strategy to enhance direct aptamer sensor sensitivity for detecting MUC1 tumor marker

Aptamers hold great potential for point-of-care diagnostics (POC), but the complexity of sensor architectures and poor sensitivities in detecting small molecules remain challenging. In this study, we present a simple but effective approach to enhance the sensitivity of the electrochemical ap-tamer-based (E-AB) sensors. The proposed aptamer was labeled by double redox tags through a lysine linker and incorporated with an optimized length of passivation layer, which cooperatively led to gain enhancement and thus higher sensitivity. The analytical performance of this E-AB sen-sor was measured and compared with a conventional E-AB sensor towards the detection of MUC1 in buffer and serum. Our study revealed the double-tagged aptamer with a lysine linker's superior performance, yielding a low 2.4 nM limit of detection (LOD) for MUC1 in buffer, with a wide lin-ear dynamic range (LDR) from 5.0 × 101 to 4.0 × 102 nM. In contrast, the conventional counterpart exhibited a tenfold higher LOD (25.7 nM). This innovative synthetic strategy addresses the limita-tions of the signal-to-noise ratio (S/N) and the need for higher sensitivity towards the detection of the tumor markers, which may hold promise for rapid simple-to-answer technology for P.O·C testing.