Atomic force microscopy-infrared microscopy (AFM-IR) provides a route to bypass Abbe's diffraction limit through photothermal detections of infrared absorption. With the combination of total internal reflection, AFM-IR can operate in the aqueous phase. However, AFM-IR in contact mode suffers from surface damage from the lateral shear force between the tip and sample, and can only achieve 20~25-nm spatial resolution. Here, we develop the liquid-phase peak force infrared (LiPFIR) microscopy that

more »

... voids the detrimental shear force and delivers an 8-nm spatial resolution. The non-destructiveness of the LiPFIR microscopy enables <i>in situ</i> chemical measurement of heterogeneous materials and investigations on a range of chemical and physical transformations, including polymer surface reorganization, hydrogen-deuterium isotope exchange, and ethanol-induced denaturation of proteins. We also perform LiPFIR imaging of the budding site of yeast cell wall in the fluid as a demonstration of biological applications. LiPFIR unleashes the potential of in liquid AFM-IR for chemical nanoscopy.