Strong histamine torsion Raman spectrum enables direct, rapid, and ultrasensitive detection of allergic diseases.

Allergic diseases are closely related to degranulation and release of histamine and difficult to diagnose because non-allergic diseases also exhibit the same clinical symptoms as allergy. Here, we report direct, rapid, and ultrasensitive detection of histamine using low-frequency molecular torsion Raman spectroscopy. We show that the low-frequency (<200 cm-1) Raman spectral intensities are stronger by one order of magnitude than those of the high-frequency Raman ones. Density functional theory calculation and nuclear magnetic resonance spectroscopy identify the strong spectral feature to be from torsions of carbon-carbon single bonds, which produce large variations of the polarizability densities in the imidazole ring and ethyl amino side chain. Using an omniphobic substrate and surface plasmonic effect of Au@SiO2 nanoparticles, the detection limit (signal-noise ratio >3) of histamine reaches 10-8 g/L in water and 10-6 g/L in serum. This scheme thus opens new lines of inquiry regarding the clinical diagnosis of allergic diseases.