Gold nanoparticles-assisted laser desorption/ionization mass spectrometry : fundamental study and analytical application

Abstract

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is a direct sample analysis method. Upon ultraviolet (UV) laser irradiation, analytes are desorbed/ionized from the sample surface pre-coated with SALDI substrate, and subsequently analyzed by MS. SALDI substrates facilitate laser energy absorption and transfer, and assist desorption and ionization of analytes in the SALDI process. The SALDI performance of different substrates depends on their physicochemical properties, which are related to their size, morphology, and type. In this thesis, the effects of physicochemical properties on the ion desorption process of SALDI were investigated for four types of noble metal nanoparticles (NPs), including AuNPs, AgNPs, PdNPs, and PtNPs. AuNPs exhibited the best SALDI performance, and it was selected for further development of analytical applications. First, AuNPs-assisted SALDI-MS was bridged with Fourier transform infra-red (FT-IR) spectroscopy for pharmaceutical sample analysis. A solid state sample extraction method based on AuNPs-assisted laser ablation was then developed.

Ion-desorption efficiency and the extent of heat transfer during the noble metal NPs-assisted SALDI process were investigated using benzylpyridinium salt as chemical thermometer. The results were then correlated with the melting point, thermal conductivity, and laser-induced heating temperature of AuNPs, AgNPs, PdNPs, and PtNPs. It was found that ion-desorption efficiency increased with heat transfer and photo-absorption efficiency. These results suggested that the ion desorption process might follow the thermal desorption model. Moreover, it was found that metal NPs with a lower melting point could enhance ion-desorption efficiency via phase transition. In addition, a stronger binding between nanoparticles and analytes would hinder the desorption process. The results of this fundamental study indicated that high photo-absorption efficiency, low melting point, and weak binding interaction with analyte should constitute the essential criteria for selecting/developing efficient SALDI substrates.

FT-IR spectroscopy is a standard method for pharmaceutical analysis, but it lacks specificity. MS is a well-known specific detection method and capable of detecting multiple analytes in the presence of sample matrix interference. IR-transparent AuNPs can bridge FT-IR and SALDI-MS for the analysis of pharmaceutical products. Over-the-counter drugs and concentrated Chinese medicine (in the form of AuNP-coated KBr pellets) can be analyzed by FT-IR spectroscopy without additional interference due to the AuNPs. Major active ingredients (e.g., acetaminophen) in over-the-counter drugs can be clearly detected. In addition, minor ingredients which were not revealed by FT-IR could be detected by SALDI-MS from the same AuNP-coated KBr pellet.

Finally, a proof-of-concept solid state sample extraction method based on the interaction of UV laser with AuNPs was developed. Although conventional solvent-based extraction may have good recovery, the analyte spatial distribution in the original sample cannot be preserved. For biological tissues, the distribution of metabolites can reflect the biological/disease status of the tissue. Using the efficient laser-induced heating property of AuNPs, embedded metabolites from an AuNPs-coated biological tissue are vaporized upon laser irradiation. Our results showed that some metabolites (e.g., aspartic acid, hypoxanthine, glutamic acid and xanthine) have been successfully extracted and transferred from a mouse kidney tissue to a supporting glass. The spatial distributions of the biochemicals in the transferred sample were similar to those in the original tissue, as revealed by imaging MS analysis.