Gas-aggregated Ag nanoparticles for detection of small molecules using LDI MS

Several reports demonstrate that silver nanomaterials can serve as surface-assisted laser desorption ionization mass spectrometry (SALDI MS) substrates for low molecular weight analytes. Substrate with tailored silver nanostructures, primarily representing the upmost layer of the bulk, i.e., occurring beneath the analyzed medium, limits the use of silver only for desorption enhancement; the charge transfer progresses through atoms from the absorbing analyte or an additional matrix (resulting in the formation of analyte/hydrogen, sodium, or potassium adducts in the most cases). In the presented approach, we utilize a homogeneous layer of silver nanoparticles, prepared under low-pressure conditions, deposited onto a dried analyte. We demonstrate that the nanoparticle layer can fully replace a matrix typically used for the detection of small molecules by laser desorption/ionization mass spectrometry-based technique (LDI MS) and can be applied to the already prepared samples. Various chemical species were detected as [M + Ag]⁺ adduct ions employing the proposed technique. The normalized signal of the analyte/silver adduct can be utilized to characterize a quantitative presence of analytes on the surface similar to signal-to-noise value, here demonstrated by the detection of trimethoprim molecule. This study also includes a detailed description of additional features one needs to take into account, such as a formation of [M_x + Ag_y]⁺ adducts, presence of silver ions (can be used for m/z calibration), analyte fragmentation, and influence of deposited nanoparticles quantity on the signal intensity. Graphical abstract.