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

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. TiO 2 –ZrO 2 and ZrO 2 –TiO 2 , were used in the SPR–LMR sensing platforms. The responses to binding of the target protein HTR of both sensing configurations (TiO 2 –ZrO 2 –Au-nanoMIPs, ZrO 2 –TiO 2 –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 ZrO 2 –TiO 2 –Au-nanoMIPs configuration (sensitivity at low concentrations, S = 0.108 nm/fM) than for the TiO 2 –ZrO 2 –Au-nanoMIPs one (S = 0.061 nm/fM); while LMR was more efficient for TiO 2 –ZrO 2 –Au-nanoMIPs (S = 0.396 nm/fM) than for ZrO 2 –TiO 2 –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.