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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has become a dangerous human pathogen and caused severe illness that can lead to death. Yet, the standard practical diagnostic tools for detecting the SARS-CoV-2 virus require multi-step assay, including extraction and labeling steps. Thus, a simple and accurate detection tool is incredibly desirable to support on-site screening, preventing its spread. In this work, we developed a portable surface plasmon resonance (SPR) sensor chip modified with metal–organic frameworks (MOF) UiO-66 that serves as an immobilization matrix of single-chain variable fragment (scFv) receptors. Large surface area and good adsorption of UiO-66/scFv-modified surface lead to an improvement of binding capacity towards the protein target of the SARS-CoV-2 receptor binding domain (RBD). We further successfully demonstrated the use of this portable SPR …