AFM-based force spectroscopy for bioimaging and biosensing

The interactions between biomolecules and material interfaces at the molecular level are complicated but very important for the development of materials science, nanotechnology, biophysics, biomedicine, and analytical science. Atomic force microscopy-based force spectroscopy (AFM-FS) is a useful technique for directly measuring the interactions between biomolecules and different material interfaces from the hard inorganic surfaces to the soft bio-substrates. In this review, we summarize recent studies on how to utilize AFM-FS to investigate the interactions between biomolecules and materials interfaces at the single-molecule level. Furthermore, we highlight the typical cases on applying AFM-FS for imaging DNA, proteins, antibodies, bacteria, and cells on one side, and for label-free sensing of DNA, RNA, proteins, enzymes, small molecules, and metallic ions on the other side. The key aspects of the modification of probes, the preparation of material interfaces, and the construction of the AFM-FS measurement system are introduced and discussed in detail. We expect that this work will be helpful for researchers to understand fundamental molecular interactions and to gain insights into the biological functions of various bio-hybrid materials.