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

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 (10⁴ 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.