Selecting Surface-Enhanced Raman Spectroscopy Flavors for Multiplexed Imaging Applications: Beyond the Experiment

Multiplexing capabilities and sensitivity
of surface-enhanced Raman
spectroscopy (SERS) nanoparticles (NPs) are strongly dependent on
the selected Raman reporter. These Raman-active molecules are responsible
for giving each batch of SERS NPs its unique spectral fingerprint.
Herein, we studied four types of SERS NPs, namely, AuNPs labeled with trans-1,2-bis­(4-pyridyl)­ethylene (BPE), 4,4′-bis­(mercaptomethyl)­biphenyl
(BMMBP), 5-(4-pyridyl)-1,3,4-oxadiazole-2-thiol (PODT), and 5-(4-pyridyl)-1H-1,2,4-triazole-3-thiol
(PTT), and demonstrated that the best level of theory could be chosen
based on inner products of DFT-calculated and experimental Raman spectra.
We also calculated the theoretical spectra of these Raman reporters
bound to Au20 clusters to interrogate how SERS enhancement
would affect their spectral fingerprint. Importantly, we found a correlation
between B3LYP-D3 calculated and experimental enhancement factors,
which opens up an avenue toward predicting which Raman reporters could
offer improved sensitivity. We observed 0.5 and 3 fM limits of detection
for BMMBP- and PTT-labeled 60 nm AuNPs, respectively.