Click-Reaction-Triggered SERS Signals for Specific Detection of Monoamine Oxidase B Activity

Human monoamine oxidases (MAOs) play important roles in maintaining the homeostasis of biogenic amines. One of its isoforms, monoamine oxidase B (MAOB), is thought to be involved in several neurodegenerative diseases, which make the selective detection of MAOB activity essential. In this work, a novel surface-enhanced Raman scattering (SERS) sensor was fabricated and the MAOB activity was specifically determined by detecting the SERS signals of an enzyme-catalyzed reaction product via an amine–aldehyde click reaction. This process was simply achieved by coating core–shell gold–silver nanoparticles (Au@Ag NPs) on 3-aminopropyl aminopropyl triethoxysilane (APTES)-modified glass, and then, a monolayer of cysteamine (CA) was attached to the nanoparticle surface as a linker through Ag–S bonds. Using phenethylamine (PA) as a specific substrate of MAOB, the enzyme product phenylacetaldehyde (PAA) will produce significant Raman signals via the amine–aldehyde click reaction with CA, while other molecules, such as MAOB and PA, have no signal output because they cannot form close interaction with nanoparticles due to the existence of a CA layer. This sensor was further used for the specific determination of MAOB activity in clinical blood samples and the MAOB inhibitor assessment successfully. Meanwhile, by changing the click reaction types and taking advantage of the SERS fingerprint peaks for the specific click reaction products, this strategy offers huge potential to detect multiple enzyme activities simultaneously and can be used for new click reaction screening, enzyme-related disease diagnosis, drug screening, and clinical diagnosis.