Improving the signal intensity and sensitivity of MALDI mass spectrometry by using nanoliter spots deposited by induction-based fluidics

A new contact-free, small droplet deposition method using an induction-based fluidics (IBF) technique to dispense nanoliter drops is described and evaluated for sample preparation in matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The signal intensities available when using nanoliter spots are greater than those obtained with normal, microliter spots when the same amount of analyte is used. When using an ionic-liquid matrix, the improvement in sensitivity is equal to the concentration enhancement that was achieved by using smaller quantities of matrix. When using a conventional solid matrix, however, the increase in signal intensity shows a more complicated relationship to concentration. The approach of nanoliter deposition also supports multiple spotting to increase sample concentration and, thus, sample signal intensity. Nanoliter spotting not only improves the signal intensity and sensitivity achieved by MALDI-MS but also allows a major fraction of trace samples to be saved for other experiments, thus expanding the application of MALDI-MS to biological studies where sample quantity is limited.