Investigation of phase SPR biosensor for efficient targeted drug screening with high sensitivity and stability

We investigate an application case study of a phase sensitive surface plasmon resonance (SPR) biosensor based on Mach-Zehnder configuration for efficient targeted drug screening, where calculating reaction kinetic constants, inhibition effect and cytotoxicity analysis are three key factors in the evaluation. As a typical targeted drug, cetuximab is selected in the measurements assisted by the phase SPR biosensor with a sensitivity of 10−6 in terms of refractive index unit (RIU) and stability of 6 × 10−7 RIU in 80 min. The reaction kinetic constants of cetuximab binding to epidermal growth factor receptor (EGFR) are found as: kd (dissociation constant) = 1.75 ± 0.29 × 10−3 S−1, kD (equilibrium dissociation constant) = 4.19 ± 0.58 nM. The results of inhibition effect analysis show that cetuximab can block EGFR binding to its two ligands, epidermal growth factor (EGF) and EGFR-transforming growth factor α (TGF-α). This effect has been tested in three cell lines of lung adenocarcinoma, colon cancer and breast cancer. Comparing to other conventional methods, we find that the phase SPR biosensor can determine the cell sensitivity to cetuximab in just 4 h. As a label-free, real-time, high sensitivity and stability biosensor, the phase SPR biosensor is a potential optical technique for targeted drug screening and analysis of cell resistance to drugs with comparative advantages.