Ultra-sensitive Detection Of Small Molecules By Composite Nanomaterial Matrix-assisted LDI Mass Spectrometry And Mechanistic Studies

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)emerges as a MS technology featured withsoft ionization,which has been widely used in life science and other fields.Due toits unique advantages such as fast detection speed,high sensitivity,simple sample preparation,and high salt tolerance,it has been widely applied foridentification of biomacromolecules such as proteins,peptides and nucleic acids.However,the conventional organic matrices commonly used in MALDI-TOF MS suffer fromintensive background noise in the small molecular range due to matrix fragmentation,which limits the detection of the true signals of small molecule analytes.This thesis describes my research efforts on the performance and mechanistic studies of two types of composite nanomaterials as novel MALDI matrices for detection of small molecules,including two parts sequentially:First,we has prepared a composite nanomaterial(CuCoO-GO)for small molecule analysis by MALDI TOF MS.The new matrix is a graphene-based nanomaterial,composed of few-layered GO nanosheets with decorationof CuCoO nanoparticles(10 nm in the averaged size),exhibiting excellent aqueous suspensibility.By the combination of CuCoO-GO matrix and MALDI TOF MS,we have successfully achieved sensitive detection of various antibiotics.Compared with the literature reports,our method has improved the limit of detection value(LOD)by several hundred foldsfor the detection of a panel of representative antibiotics.We have demonstrated accurate quantification of sulfonamides in milk samples,but alsointrabacterial and extrabacterial residual concentration of the antibiotic.For the first time,this thesis has attempted toreveal the molecular mechanism of the enhanced desorption/ionization efficiency by CuCoO-GO matrixwith the synchrotron radiation techniques.Secondly,we have developed Ir/SiNW composite nanomaterial as the MALDI matrix featuring good optoelectronic properties and UV absorption,and successfully achieved the high sensitivity detection of Clenbuterol.We have demonstratedthat Ir/SiNWmatrix exhibits low background noise in the small molecular range,bypassing the background noise interference of traditional matrices,but also high reproducibility in the detection.Assisted by the stable isotope labeling technique,accurate quantification of Clenbuterol in blood samples has been demonstratedwith our new nano-matrix.Furthermore,it can be used for the detection of various biological small molecules including amino acids,sugars,lipids,peptides,etc.The experimental results support that Ir/SiNW serves as an excellent MALDI matrix for small molecule detectionin a broad range of applications.In summary,the composite nanomaterials CuCoO-GO and Ir/SiNW matrix have been successfully prepared in this thesis.They have been demonstrated in a variety of applications by solvinglimitations of traditional organic matrices in MALDI-MS,and achieved the highly sensitive detection of various small molecule compounds.We have investigated the interactions between the molecule ofSDZ and CuCoO-GO matrix for the ionization mechanism,providinga new understandingfor matrix development and ultrasensitive detection of small molecules.