Free-base amino acid-encoded microsystems for dual detection of narcotics and therapeutic antidote monitoring

In this proof-of-concept study, we demonstrate the simultaneous detection of narcotics and releasing of their respective antidote through real-time therapeutic drug monitoring (TDM). Our approach utilizes a free-base amino acid interface involving a two-step process. First, we create large surface area (4 × 4 mm) plasmonic gold nanostructures via a tryptophan (Trp) mediated supramolecular interface on pre-fabricated Si-nanopillars. Second, we protonate excess Trp (H⁺) to form a polymeric-Trp interface capable of entrapping drug particles like naloxone (OXN), an anti-opioid medication. This dual approach provides two distinct functionalities on a single Si-wafer substrate: (a) SERS-mediated detection of cocaine and heroin and (b) the evaluation of antidote drug (OXN) release kinetics using Raman spectroscopy. Combining supramolecular chemistry with microfabrication lays a strong foundation for developing highly ordered 3D nano/microstructures via a free-base amino acid chemistry towards next-generation theranostics.