Functional Magnetic Nanoparticles For MALDI-TOF MS Analysis

Magnetic nanoparticles?MNPs?have the features of small dimension,magnetic responsivity and easily surface modification,which make them widely applied in many fields of separation science,such as adsorption and sample pretreatment.However,the reported MNPs showed nonspecific enrichment of analyte,surface functionalization is necessary.Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry?MALDI-TOF MS?is one of the major tools for protein identification,but the signal of the target protein in protein mixture and biological samples often suffers strong interference from highly abundant proteins and salts.In addition,conventional organic matrices often lead to background interference and poor reproducibility when testing small molecules?m/z<500 Da?.This work aims to analyze target proteins and small molecules,and improve their signals by combining functional MNPs with MALDI-TOF MS.The main contents are summarized as follows:?1?Molecularly imprinted polymers?MIPs?were applied to selective enrichment of target protein in MALDI-TOF MS analysis for the first time.Lysozyme-imprinted polymers?Lyz-MIPs?were successfully prepared by immobilization of template Lyz and self-polymerization of dopamine on silica Fe₃O₄,and showed good selectivity toward Lyz.Excellent enhancement in MALDI-TOF MS signal to noise?S/N?was achieved for Lyz from spiked protein mixture and chicken egg white without the interference of other proteins and salts.?2?Magnetic metal-organic frameworks?MOFs?were adopted for the pretreatment of biosamples for MALDI-TOF MS analysis.Fe₃O₄@MIL-100?Fe?nanoparticles were synthesized based on step-by-step assembly over poly?acrylic acid??PAA?modified Fe₃O₄?Fe₃O₄-PAA?.Fe₃O₄@MIL-100?Fe?showed intriguing ability for selective enrichment of Lyz and RNA and the exclusion of other undesired proteins.Size selectivity,electrostatic interactions,metal coordination and hydrophobic interactions played important roles in the absorption process.MS signals were significantly enhanced for Lyz and RNA in protein mixture,egg white and human serum.?3?Fe₃O₄@MIL-100?Fe?nanoparticles were acted as novel matrices for MALDI-TOF MS analysis instead of conventional organic matrices.The as-prepared materials exhibited?-conjugated networks,large specific surface area and high absorption capability in the UV-visible range,and could transfer energy to analytes for the desorption/ionization process.Strong MS signals and little matrix ion background were obtained successfully when purine and pyrimidine,nucleoside,amino acid and polyamines were analyzed using Fe₃O₄@MIL-100?Fe?as matrices.This study broadened the applications of biological small molecules for employing MOFs for MALDI-TOF MS analysis.