The Seven S Criteria for Evaluating the Performance of a MALDI Mass Spectrometer for MSI.

Our goal in this work is to evaluate a new combination linear/reflector MALDI-TOF instrument toward satisfying all "7S criteria" for the ideal MSI mass spectrometer. The linear analyzer satisfies all of the 7 criteria except for Specificity. The new instrument described here adds a reflector to provide up to 50,000 mass resolving power with ppm mass accuracy and with no sacrifice in speed, spatial resolution, and sensitivity demonstrated earlier for the linear MALDI-TOF. This instrument employs new laser optics that produces a 5 kHz laser beam with 2.5-25 μm diameter under computer control. The most important advance is the patented combination of laser and ion optics that provides very high efficiency for production and detection of ions generated by laser desorption using small diameter laser beams. This provides spectra with a wide dynamic range summing a relatively small number of laser shots/pixels. Rat and mouse brain tissues have been used for these initial studies. Examples of negative ion images of lipids and positive ion images from tryptic digestion of proteins are presented. These results demonstrate a very high speed for MSI. This speed is derived from a combination of high laser rate (5 kHz), fast motion of sample relative to the laser beam (20 mm/s), very high ionization efficiency (up to 50%), and the ability to acquire, process, and save spectra at a very high rate (1000/s). As a result, the speed that is possible is imposed by other limits, including the mass range, concentration of samples on the surface, and the spatial resolution required.