Bimetallic Ag–Cu Alloy SERS Substrates as Label-Free Biomedical Sensors: Femtomolar Detection of Anticancer Drug Mitoxantrone with Multiplexing

Surface-enhanced Raman spectroscopy (SERS) has been recognized as a promising label-free technology for clinical monitoring due to its high sensitivity and multiplexing ability, which should accelerate the screening of important drugs in the blood and plasma of cancer patients in a simpler, faster, and less-expensive manner. In this work, bimetallic Ag-Au and Ag-Cu alloy microflowers (MFs) with tunable surface compositions were fabricated on a glass cover slip by simple thermolysis of a metal alkyl ammonium halide precursor and used as SERS substrates for the sensitive detection of anticancer drug mitoxantrone (MTO). Two different laser excitation sources, 532 and 632.8 nm, were used to explore the possibility of surface-enhanced resonance Raman scattering. The Ag-Cu substrate showed superior detection capability over Ag-Au, whereby the sensor recorded a noteworthy "limit of detection" value of 1 fM for MTO. Theoretical electromagnetic field maps were simulated on appropriately chosen plasmonic systems to compare the electromagnetic field enhancements with the experimental SERS efficiencies of the substrates. Further, using a 10% Ag-Cu substrate, efficient multiplexing detection of MTO was demonstrated with another anticancer drug doxorubicin (DOX) in water and mouse blood plasma.