Soft molecularly imprinted nanoparticles with simultaneous lossy mode and surface plasmon multi-resonances for femtomolar sensing of serum transferrin protein

Abstract

The simultaneous interrogation of both lossy mode (LMR) and surface plasmon (SPR) resonances was herein exploited for the first time to devise a sensor in combination with soft molecularly imprinting of nanoparticles (nanoMIPs), specifically entailed of the selectivity towards the protein biomarker human serum transferrin (HTR). Two distinct metal-oxide bilayers, i.e. TiO₂-ZrO₂ and ZrO₂-TiO₂, were used in the SPR-LMR sensing platforms. The responses to binding of the target protein HTR of both sensing configurations (TiO₂-ZrO₂-Au-nanoMIPs, ZrO₂-TiO₂-Au-nanoMIPs) showed femtomolar HTR detection, LODs of tens of fM and K_Dapp ~ 30 fM. Selectivity for HTR was demonstrated. The SPR interrogation was more efficient for the ZrO₂-TiO₂-Au-nanoMIPs configuration (sensitivity at low concentrations, S = 0.108 nm/fM) than for the TiO₂-ZrO₂-Au-nanoMIPs one (S = 0.061 nm/fM); while LMR was more efficient for TiO₂-ZrO₂-Au-nanoMIPs (S = 0.396 nm/fM) than for ZrO₂-TiO₂-Au-nanoMIPs (S = 0.177 nm/fM). The simultaneous resonance monitoring is advantageous for point of care determinations, both in terms of measurement's redundancy, that enables the cross-control of the measure and the optimization of the detection, by exploiting the individual characteristics of each resonance.