Imaging
biological systems with simultaneous intrinsic chemical
specificity and nanometer spatial resolution in their typical native
liquid environment has remained a long-standing challenge. Here, we
demonstrate a general approach of chemical nanoimaging in liquid based
on infrared scattering scanning near-field optical microscopy (IR s-SNOM). It is enabled by combining AFM operation in a fluid
cell with evanescent IR illumination via total internal reflection,
which provides spatially confined excitation for minimized IR water
absorption, reduced far-field background, and enhanced directional
signal emission and sensitivity. We demonstrate in-liquid IR s-SNOM vibrational nanoimaging and conformational identification
of catalase nanocrystals and spatio-spectral analysis of biomimetic
peptoid sheets with monolayer sensitivity and chemical specificity
at the few zeptomole level. This work establishes the principles of
in-liquid and in situ IR s-SNOM
spectroscopic chemical nanoimaging and its general applicability to
biomolecular, cellular, catalytic, electrochemical, or other interfaces
and nanosystems in liquids or solutions.