Size-selected silver nanoparticles for MALDI-TOF mass spectrometry of amyloid-beta peptides.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is one of the most efficient mass spectrometric techniques for the analysis of high-molecular-weight compounds with superior selectivity and sensitivity. Common MALDI matrices are low molecular weight (LMW) organics and will therefore produce a large amount of matrix-related ion peaks, which limits the use of MALDI-MS for the detection of LMW molecules. A major breakthrough of this limitation was made by the introduction of surface assisted desorption/ionization techniques, with graphite particles firstly as the matrix, followed by expansion into other types of nanoparticles or nanostructures. However, previous studies failed to address well the optimum size and concentration of Ag NPs to be used as the MALDI matrix. In this study, to explore and compare the efficiency of different sized silver nanoparticles (Ag NPs) as the MALDI matrix for the detection of LMW molecules, three different sized Ag NPs (2.8 ± 1.0, 12.8 ± 3.2 and 44.2 ± 5.0 nm) have been successfully developed as the MALDI time-of-flight MS (MALDI-TOF MS) matrix and amyloid-beta (Aβ) peptides, crucially involved in Alzheimer's disease and a variety of cancers, were chosen as an example of LMW molecules in our MALDI-TOF MS analysis with Ag NPs as matrices. The results showed size-selected MS signals with the smallest (2.8 ± 1.0 nm) Ag NP matrix producing the highest spectral intensities, when compared with other larger sized Ag NP matrices and conventional matrices such as SA and DHB. Furthermore, the optimal concentrations for different sized Ag NPs as matrices were determined as follows: 0.125 nM (2.8 ± 1.0 nm Ag NPs), 0.0625 nM (12.8 ± 3.2 nm Ag NPs), and 0.03125 nM (44.2 ± 5.0 nm Ag NPs), respectively. These results not only corroborated that Ag NPs could act as a very suitable matrix to assist in the desorption/ionization of LMW molecules but also revealed size-selected mass spectrometry signals with smaller Ag NPs as the MALDI matrix bearing more advantages than their larger counterparts. These novel findings paved the way for wider applications of MALDI-MS using Ag NPs as matrices for the analysis of LMW molecules.