The
lipids with a rich diversity of isomers face a formidable challenge
in comprehensive structural analysis. The commonly used mass spectrometry-based
techniques usually require a considerable number of molecules with
sophisticated chemical derivatization or ion mobility separation,
but the co-existing of structurally similar isomers often makes the
distinction impossible. Here, we develop an alternative powerful liquid/liquid
interfacial surface-enhanced Raman spectroscopy (SERS) strategy at
normal temperature and pressure without any sources of ionization
or radiation. This strategy generates high-resolution fingerprints
in molecular chain length, CC position, saturation, and regio-
and stereoisomers of both glycerides and fatty acids and requires
only trace amounts of molecules down to 1 ppb to achieve discrimination
and exhibits great potentials to push the identification capability
to trace levels or even the single-molecule level. According to experimental
data and theoretical simulations, these targets have the amphiphilic
and emulsifying properties, exhibit ordered molecular orientation
and adsorption patterns, promote the co-assembly with plasmonic nanoarrays
at the immiscible liquid/liquid interface, and consequently amplify
the detection sensitivity. As a contrast, the typical SERS based on
solid/air interfacial plasmonic nanoarrays faces the intrinsic bottleneck
of extremely weak intensity and indistinguishable spectral fingerprints
of lipid molecules. The vibrational fingerprints exhibit a rich range
of well-resolved absorption features that are clearly diagnostic for
fine structural changes and pave a new way for straightforward measurement
without laborsome sample purification, enrichment, or complex derivatization.
Although challenging, its unprecedented resolving power expands the
potentials of SERS, serving as an ultimate analytical method to provide
insights into the detailed structural features of other lipids under
facile conditions in the future.