Rational design of thiolated polyenes as trifunctional Raman reporter molecules in surface-enhanced Raman scattering nanotags for cytokine detection in a lateral flow assay.

The characteristic vibrational spectroscopic fingerprint of Raman reporter molecules adsorbed on noble metal nanoparticles is employed for the identification of target proteins by the corresponding surface-enhanced Raman scattering (SERS) nanotag-labeled antibodies. Here, we present the modular synthesis of thiolated polyenes with two to five C═C double bonds introduced via stepwise Wittig reactions. The experimental characterization of their electronic and vibrational properties is complemented by density functional theory calculations. Highly SERS-active nanotags are generated by using the thiolated polyenes as Raman reporter molecules in Au/Au core/satellite supraparticles with multiple hot spots. The cytokines IL-1β and IFN-γ are detected in a duplex SERS-based lateral flow assay on a nitrocellulose test strip by Raman microscopy. The thiolated polyenes are suitable for use in immuno-SERS applications such as point-of-care testing as well as cellular and tissue imaging.