Computationally Guided Liquid Crystal‐Based Competitive Binding Sensing Platform for Optical Detection of Spike Protein

Abstract A liquid crystal (LC)‐based sensing platform for the rapid optical detection of SARS‐CoV‐2′s spike protein's receptor binding domain (RBD) domain is introduced. This platform utilizes a thermotropic LC, hosted on metal‐cation decorated substrates, onto which the spike protein can competitively bind. Density functional theory (DFT) calculations guide the experiments that reveal a homeotropic‐to‐planar transition in the LCs upon exposure to SARS‐CoV‐2 spike‐decorated yeast, providing a basis for sensitive virus detection. The sensor's reversibility/specificity is confirmed through antibody‐induced orientation recovery of the LCs initial orientation. Strikingly, the sensor can detect ≈2000 copies of the spike protein per mL, which is well below the typical concentration of the virus in the saliva of an infected human (10 4 copies per mL)‐ revealing the practical applicability of the sensor. More broadly, it describes the design principles of the DFT‐guided LC‐based competitive binding platform for the detection of previously unknown pathogens for which antibody‐based detection mechanisms may not be readily available.