Nano-chemical Imaging and Spectroscopy towards the Single-molecule Level

Here, we show the latest years development and application of infrared absorption nano-imaging and spectroscopy (AFM-IR) as a real breakthrough for the analysis of heterogeneous (bio-)organic molecules and materials from the single molecule scale to several multiple length scales in air and liquid environment. As a major advance in the field, we demonstrate the achievement of single protein molecule detection of infrared absorption spectra and maps by introducing off-resonance, low power and short pulse ORS-nanoIR.[1] The technique enables the accurate determination of the secondary structure elements of single proteins in the amide band I region, such as alpha-helices and beta-sheets. Then, we show the application of this single molecule sensitivity to unravel the molecular interaction fingerprint between a small molecule and its target [2]. Similarly, we demonstrate the application of the technique to probe the surface and structural properties of functional materials, such as artificial model membranes [3], functional protein self-assemblies [4-6], and perovskites [7]. Overall, our aim is to expand the capabilities of analytical nanoscience to shed light on the structure-activity relationship of biomolecules and functional materials design. [1] Ruggeri, Nature Comm., 2020. [2] Ruggeri, Nature Comm., 2021. [3] Marchesi, Advanced Functional Materials, 2020. [4] Ramer*, Ruggeri*, ACS Nano, 2018. [5] Shen, Ruggeri, Nature Nanotechnology, 2020. [6] Otzen,…, Ruggeri, Small Methods, 2021. [7] Doherty, Science, 2021.