Paper spray ionization devices for direct, biomedical analysis using mass spectrometry.

Paper spray ionization has been developed as a direct, fast and low-cost sampling and ionization method for qualitative and quantitative mass spectrometric (MS) analysis of complex mixtures. Analyte ions are generated by applying a high voltage and a small volume (~10 μL) of spray solvent onto a porous substrate. The sample can be preloaded onto the paper or mixed into the spray solution. The geometry of the paper and the method of supplying the necessary internal standard are important factors that affect the ionization efficiency and subsequently the sensitivity and quantitation accuracy of the analytical data. As the cut angle of the paper tip is changed, the spray plume, the total spray current and the electric field intensity at the tip all vary correspondingly, with resulting differences in signal intensity. Sample load is another important factor for obtaining a stable MS signal and accurate quantitative results. The optimal sample load was found to be dependent on the paper size. The dissolution and spray process was also investigated and analyte transfer on paper was shown to be largely associated with bulk solution flow towards the spray tip. The information gathered from these systematic studies provides guidance for the design and optimization of a disposable sample cartridge for paper spray MS, a device which potentially is suitable for fast clinical analysis, especially for point-of-care diagnostics.