Enhancing reproducibility of SALDI MS detection by concentrating analytes within laser spot

Surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI TOF MS) has become one of the most important analytical methods due to its less interference at low molecular weight range. However, it is still a challenge to obtain a good reproducibility of SALDI TOF MS because of the inhomogeneous distribution of analyte molecules induced by coffee ring effect. We propose a universal and reliable method to eliminate the coffee ring effect by concentrating all the analyte molecules within the laser spot. This method exhibits an excellent reproducibility of spot-to-spot and substrate-to-substrate, and the relative standard deviations (RSDs) for different concentrations are lower than 12.6%. It also performs good linear dependency (R² > 0.98) in the log-log plot with the concentration range of 1nM to 1μM, and the limit of detection for R6G is down to 1fmol.