Alkyne-tag SERS imaging for visualizing small molecule drugs in live cells

Raman microscopy is a powerful tool to observe molecular distribution in live cells. Here, we propose a technique to detect small molecule drugs using alkyne-tag surface-enhanced Raman scattering (SERS) imaging. To obtain SERS effect, we use gold nanoparticles as SERS probes so that we can enhance Raman scattering of small molecule drugs at low concentration with several orders of magnitude. We use alkyne tag to selectively detect the drug molecules by using the Raman peak of alkyne in the spectral silent region. Home-built slit-scanning Raman microscopy enables us to perform rapid SERS imaging. We successfully detect SERS signal from an alkyne-tagged inhibitor of a lysosomal enzyme with gold nanoparticle modified glass substrate.