Sub‐Femtomolar, Label‐Free Small‐Molecule Sensing with Nanoarchitectonic Metal‐Organic Frameworks

Abstract This work presents a broadly applicable strategy for integrating highly conductive 2D conjugated metal‐organic frameworks (2D c‐MOFs) into electronic biosensors, demonstrated through the ultrasensitive detection of cortisol. For the first time, we report the solid‐phase conversion of a pre‐patterned Cu(OH) ₂ nanoarray into vertically aligned CuHITP (HITP = 2,3,6,7,10,11‐hexaiminotriphenylene). The Cu(OH) ₂ nanoarray with tubular architecture provides uniform nucleation sites, resulting in a continuous, well‐adhered, and 3D c‐MOF film directly grown on the working electrodes. Long‐standing challenges in the fabrication of conductive MOFs (c‐MOFs) are overcome by enhancing the mass transport within the MOF layer. The resulting CuHITP film is integrated into an extended‐gate field‐effect transistor (EG‐FET) biosensing platform functionalized via amine groups inherent to the c‐MOF structure, enabling the optimal covalent attachment of cortisol‐specific aptamers. The sensors achieve an impressive limit of detection down to 0.1 f M , with a broad dynamic range spanning 11 orders of magnitude. Additionally, the devices exhibit a high pH sensitivity (23 mV/pH), indicating the potential of a multi‐purpose assay. These findings not only demonstrate the successful preservation of c‐MOF structural integrity during fabrication but also establish 2D c‐MOFs as a promising material for high‐performance, ultrasensitive biosensors targeting small biomolecules.