Nanoscale investigations of biomaterials using atomic force microscopy and enhanced raman spectroscopy

In this thesis, AFM and enhanced Raman spectroscopy were applied for investigating the mode of action of CaL and the detection of SARS-CoV-2. Last but not least, a simple method for suppressing sample degradation in enhanced Raman spectroscopy will be introduced. Chapter 1 introduces some representative super-resolution techniques, including near-field scanning optical microscopy, far-field super-resolution fluorescent microscopy, and non-optical microscopy. Among these techniques, atomic force microscopy and Raman spectroscopy are highlighted. The principle of atomic force microscopy in topographical and mechanical research is explained in Chapter 1.2. Raman spectroscopy, including conventional Raman, SERS, and TERS are specified in Chapter 1.3. A short outline of this thesis is listed in Chapter 1.4. All instruments and experimental materials used in the experiments are discussed in Chapter 2. Investigations of water-resistant silver (Ag) SERS substrates are presented in Chapter 3. More importantly, a simple and very promising method, which suppresses sample degradation in enhanced Raman spectroscopy, will be firstly introduced in this chapter. This method furthermore improves the reliability and reproducibility of measurements using enhanced Raman spectroscopy. Chapter 4 is concerned with the applications of AFM and enhanced Raman spectroscopy in the investigations of the fungal peptide CaL. The mode of action of CaL, especially its pore formation, is investigated and discussed using AFM and Raman spectroscopy for the first time. The same AFM-TERS setup was also used to investigate SARS-CoV-2. Topographical, mechanical, and chemical information of SARS-CoV-2 virions are presented in Chapter 5. It is found that with the combination of topographical and mechanical information, AFM was able to recognize virions. TERS was preliminary applied to the analysis of the surface chemical compositions of virus-like particles.