RNA Resolution in an Electric Double Layer Generated by Metal–Organic Frameworks

The interaction between metal–organic frameworks (MOFs) and nucleic acids offers significant potential for smart biosensing platforms. However, the underlying mechanisms remain elusive, limiting their practical implementation. Herein, we unveil the critical role of the electric double layer (EDL) at the MOF–solution interface in mediating nucleic acid adsorption, recognition, and desorption with a particular focus on mRNA detection. We demonstrate that primers immobilized on the surface of MOFs (MIL-101, Zn 2 Ph 2 Da, and UiO-66) hybridize with target mRNAs within the EDL slipping plane and that EDL compression significantly modulates hybridization efficiency. This EDL-governed recognition enables direct qPCR without total RNA extraction, facilitating point-of-care testing (POCT) detection. Using this approach, we achieved ultrasensitive detection of highly malignant and drug-resistant liver cancer biomarkers (ABCB1 mRNA) in serum, with detection limits down to 10 –15 M. Furthermore, we developed a portable microfluidic device incorporating magnetic mRNA separation, providing a practical and integrated platform for clinical POCT applications.