Novel Electrochemical Sensor Based on One-Step Encapsulation of Metal–Organic Framework (MOF) for Simultaneous Detection of SARS-CoV and SARS-CoV-2

This study investigates three metal-organic frameworks (MOFs) with distinct Brunauer-Emmett-Teller (BET) surface areas and pore sizes: MOF_Zr (1274 m²/g, <0.7 nm), MOF_Al (371 m²/g, 1.5 nm), and MOF_Cr (1917 m²/g, 2 nm). Methylene blue (MB, 1.4 × 0.7 × 0.2 nm³) and triferrocene (tri-FC, 1.2 × 0.9 × 0.3 nm³) were adsorbed onto these MOFs. Specific DNA segments targeting SARS-CoV-2 (P_R and P_O) were employed to block the pores of the MOFs, leading to the formation of DNA-gated MOFs: MOF_X/MB/P_R and MOF_X/tri-FC/P_O. These constructs were subsequently integrated with four-arm poly(ethylene glycol) amine (4-arm-PEG-NH₂)-modified gold electrodes to create the corresponding sensors (MOF_X/MB/P_R+MOF_X/tri-FC/P_O@4-arm-PEG-NH₂@Au NPs@GCE). The DNA-gated MOF_Al system exhibited the highest loading capacity and a 3-fold increase in sensing efficiency following the introduction of SARS-CoV-2 target DNA, surpassing the performance of the other systems. This study highlights the enhancement of the DNA-gated MOFs when the three-dimensional structures of the guest molecules closely align with the pore sizes of the MOFs. It emphasizes a critical aspect of the traditional design approach for electrochemical sensors based on MOF encapsulation, which often prioritizes BET surface areas while neglecting the compatibility between the sizes of guest molecules and MOF pore diameters. Moreover, the sensor effectively discriminated between SARS-CoV-2 and SARS-CoV by precisely aligning the SARS-CoV-2 target DNA with P_R and P_O. In contrast, the specific genetic targets (S_R) from SARS-CoV showed complete mismatches with P_O and a three-base deviation with P_R. This differentiation was achieved in a simple one-step assay, even in 5% serum, across a linear concentration range of 10^-9 to 10^-14 M. This range signifies an expansion of 2 to 3 orders of magnitude compared to sensors that inaccurately selected MOFs.