Near‐Field Nanoscopic Terahertz Imaging of Single Proteins

Terahertz (THz) biological imaging has attracted intense attention due to its capability of acquiring physicochemical information in a label‐free, noninvasive, and nonionizing manner. However, extending THz imaging to the single‐molecule level remains a challenge, partly due to the weak THz reflectivity of biomolecules with low dielectric constants. Here, the development of graphene‐mediated THz scattering‐type scanning near‐field optical microscope for direct imaging of single proteins is reported. Importantly, it is found that a graphene substrate with high THz reflectivity and atomic flatness can provide high THz contrast against the protein molecules. In addition, a platinum probe with an optimized shaft length is found enabling the enhancement of the amplitude of the scattered THz near‐field signals. By coupling these effects, the topographical and THz scattering images of individual immunoglobulin G (IgG) and ferritin molecules with the size of a few nanometers are obtained, simultaneously. The demonstrated strategy thus opens new routes to imaging single biomolecules with THz. Terahertz (THz) imaging has promising biomedical applications, but its application in single biomolecule detection remains challenging. Herein, by taking the advantages of high THz reflectivity and atomic smoothness of graphene and the high scattering cross‐section of long Pt probe, single IgG protein molecules are unambiguously imaged with a state‐of‐the‐art THz scattering‐type scanning near‐field optical microscope.