Though it is difficult to directly probe the protein and sugar interaction, vibrational spectroscopic tools, such as FTIR and Raman spectroscopy, were still often utilized to correlate the secondary structural changes with protein stability and assess the sugar stabilization effect in preserving the protein's native state in the dried state. For example, Chang et al. have examined the effect of different sugars on the secondary structure of IgG1 antibody. Both trehalose and sucrose can retain a more "native-like" structure compared to sorbitol. Generally, the spectral correlation coefficient, 𝑟, represents the degree of similarity of protein secondary structures and a large 𝑟 value (≤1) denotes less structural changes during drying. A number of studies have utilized 𝑟 to quantitatively assess the stabilization effect of sugars on the protein formulations. High 𝑟 values were often obtained for the dehydrated proteins with the presence of stabilizers. Meanwhile, more stable protein formulations are accompanied by larger 𝑟 values, indicating a more "native" protein structure in the dry state. Such a correlation between stability and protein structure similarity provides evidence for the water replacement hypothesis as an indirect measurement.