Nucleic acids, proteins, carbohydrates, and lipids are the four categories of molecules creating life. Nucleic acids, proteins, and carbohydrates are macromolecules with complex structures resulting from different subunits and sequence variations among these subunits. Despite well-established methods for sequencing nucleobases in nucleic acids and amino acids in proteins, the development of a robust analytical method to determine the primary structure of carbohydrates remains a challenge. The main difficulty in the primary structure determination of carbohydrates is caused by the large number of isomers and small differences between these isomers, owing to the diverse monosaccharide stereoisomers and numerous linkages between monosaccharides.
Dr. Ni has studied photodissociation of polyatomic molecules in molecular beam, molecular energy transfer in crossed molecular beam, and ionization mechanisms of matrix-assisted laser desorption ionization (MALDI) in the past 30 years. Based on these experiences, he investigated the dissociation mechanisms of monosaccharide and disaccharide in the gas phase using gas phase chemical kinetics and high level quantum chemistry calculations. Using the revealed dissociation mechanisms, Dr. Ni invented a new mass spectrometry method, namely logically derived sequence (LODES) tandem mass spectrometry (MSn), for oligosaccharide structural determination in 2017 (US patent US 10,796,788 B2, Oct. 6, 2020). This is the first and until now the only mass spectrometry method that can determine the compositions, sequences, linkage positions, anomericity, and monosaccharide stereoisomers in oligosaccharides. It has high sensitivity that the structures of small oligosaccharides eluted from HPLC can be determined online, and the entire LODES can be programmed into computer for automation. Dr. Ni’s group has used this method to discover many oligosaccharides which do not follow the rules and principles of current biosynthetic pathways.
The future research directions of Dr. Ni’s group include (1) applications of LODES/MSn to various biological samples, (2) development of LODES/MSn to an automatic procedure for comprehensive structural identification.