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Published January 2022 | public
Journal Article

Super-resolution mid-infrared spectro-microscopy of biological applications through tapping mode and peak force tapping mode atomic force microscope

Abstract

Small biomolecules at the subcellular level are building blocks for the manifestation of complex biological activities. However, non-intrusive in situ investigation of biological systems has been long daunted by the low spatial resolution and poor sensitivity of conventional light microscopies. Traditional infrared (IR) spectro-microscopy can enable label-free visualization of chemical bonds without extrinsic labeling but is still bound by Abbe's diffraction limit. This review article introduces a way to bypass the optical diffraction limit and improve the sensitivity for mid-IR methods – using tip-enhanced light nearfield in atomic force microscopy (AFM) operated in tapping and peak force tapping modes. Working principles of well-established scattering-type scanning near-field optical microscopy (s-SNOM) and two relatively new techniques, namely, photo-induced force microscopy (PiFM) and peak force infrared (PFIR) microscopy, will be briefly presented. With ∼ 10–20 nm spatial resolution and monolayer sensitivity, their recent applications in revealing nanoscale chemical heterogeneities in a wide range of biological systems, including biomolecules, cells, tissues, and biomaterials, will be reviewed and discussed. We also envision several future improvements of AFM-based tapping and peak force tapping mode nano-IR methods that permit them to better serve as a versatile platform for uncovering biological mechanisms at the fundamental level.

Additional Information

© 2021 Published by Elsevier. Received 24 August 2021, Revised 15 November 2021, Accepted 6 December 2021, Available online 11 December 2021. H. W. thanks Dr. Qingyun Guo for helpful discussions. X.G.X would like to thank the support from the National Science Foundation CHE 1847765 and the support of the Beckman Young Investigator award from the Arnold and Mabel Beckman Foundation. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional details

Created:
August 22, 2023
Modified:
October 23, 2023