Inverse sensitivity sensing with enzyme-linked Au nanostars. (A) GOx generates hydrogen peroxide, which reduces silver ions to grow a silver coating around plasmonic nanosensors (Au nanostars); (i) at low concentrations of GOx the nucleation rate is slow, which favors the growth of a conformal silver coating that induces a large blueshift in the LSPR of the nanosensors; (ii) when GOx is present at high concentrations, the fast crystal growth conditions stimulate the nucleation of silver nanocrystals and less silver is deposited on the nanosensors, therefore generating a smaller variation of the LSPR. When the concentration of GOx is related to the concentration of a target molecule through immunoassay, this signal-generation step induces inverse sensitivity because condition (i) is fulfilled at low concentrations of analyte. (B, C) Blue shift of the LSPR absorbance band (Δλmax) as a function of the concentration of PSA (orange) and BSA (blue) in buffer (B) and of PSA (red) and BSA (green) spiked into whole serum (C). Reprinted with permission from ref. 121. Copyright 2012 Nature Publishing Group.