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 (∆λmax) 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. . Copyright 2012 Nature Publishing Group.