The sensitivity of surface enhanced Raman spectroscopy to silver nano-particle/peptide aggregates is increased by prior treatment of the peptides. According to a first type of embodiment, an enzyme such as Glu-C is used for protein(s) digestion based on the enzyme's ability to cleave proteins at a selected location having a negative charge, such as at aspartic acid and glutamic acid. This type of digestion is used to derive a higher proportion of positively charged component peptides sequences as compared to the component peptides sequences obtained by standard tryptic digestion of protein(s). According to a second type of embodiment, methyl-esterification of peptides suppresses the negative charge contributions of portions of the peptides such as aspartic acid, glutamic acid, and the C-terminus. Both types of embodiments result in increased binding affinity of the resulting component sequence peptides with negatively charged nano-particles such as silver nano-particles. According to yet other embodiments, the first and second types of embodiments can be combined for further sensitivity increase.