Novel\nElectrochemical\nSensor Based on One-Step Encapsulation\nof Metal–Organic Framework (MOF) for Simultaneous Detection\nof SARS-CoV and SARS-CoV‑2

This study investigates three metal–organic\nframeworks\n(MOFs)\nwith distinct Brunauer–Emmett–Teller (BET) surface areas\nand pore sizes: MOF<sub>Zr</sub> (1274 m<sup>2</sup>/g, <0.7 nm),\nMOF<sub>Al</sub> (371 m<sup>2</sup>/g, 1.5 nm), and MOF<sub>Cr</sub> (1917 m<sup>2</sup>/g, 2 nm). Methylene blue (MB, 1.4 × 0.7\n× 0.2 nm<sup>3</sup>) and triferrocene (tri-FC, 1.2 × 0.9\n× 0.3 nm<sup>3</sup>) were adsorbed onto these MOFs. Specific\nDNA segments targeting SARS-CoV-2 (P<sub>R</sub> and P<sub>O</sub>) were employed to block the pores of the MOFs, leading to the formation\nof DNA-gated MOFs: MOF<sub><i>X</i></sub>/MB/<i>P</i><sub>R</sub> and MOF<sub><i>X</i></sub>/tri-FC/P<sub>O</sub>. These constructs were subsequently integrated with four-arm poly(ethylene\nglycol) amine (4-arm-PEG-NH<sub>2</sub>)-modified gold electrodes\nto create the corresponding sensors (MOF<sub><i>X</i></sub>/MB/P<sub>R</sub>+MOF<sub><i>X</i></sub>/tri-FC/P<sub>O</sub>@4-arm-PEG-NH<sub>2</sub>@Au NPs@GCE). The DNA-gated MOF<sub>Al</sub> system exhibited the highest loading capacity and a 3-fold increase\nin sensing efficiency following the introduction of SARS-CoV-2 target\nDNA, surpassing the performance of the other systems. This study highlights\nthe enhancement of the DNA-gated MOFs when the three-dimensional structures\nof the guest molecules closely align with the pore sizes of the MOFs.\nIt emphasizes a critical aspect of the traditional design approach\nfor electrochemical sensors based on MOF encapsulation, which often\nprioritizes BET surface areas while neglecting the compatibility between\nthe sizes of guest molecules and MOF pore diameters. Moreover, the\nsensor effectively discriminated between SARS-CoV-2 and SARS-CoV by\nprecisely aligning the SARS-CoV-2 target DNA with P<sub>R</sub> and\nP<sub>O</sub>. In contrast, the specific genetic targets (S<sub>R</sub>) from SARS-CoV showed complete mismatches with P<sub>O</sub> and\na three-base deviation with P<sub>R</sub>. This differentiation was\nachieved in a simple one-step assay, even in 5% serum, across a linear\nconcentration range of 10<sup>–9</sup> to 10<sup>–14</sup> M. This range signifies an expansion of 2 to 3 orders of magnitude\ncompared to sensors that inaccurately selected MOFs.