High resolution mass spectrometry imaging using 3 micron laser ablation

We report a single-cell level resolution (≤10 µm), laser desorption-based mass spectrometry imaging platform. An optical parametric amplifier is used to generate ∼100 ps, 200 nJ pulses at around 3 µm with a maximum repetition rate of 500 kHz. The pulses are tightly focussed on to fresh frozen animal tissue samples with a thickness of 10 µm. Small volumes of tissue are readily ablated by the laser and are subsequently chemically analyzed using a Rapid Evaporative Ionization Mass Spectrometry (REIMS) source installed on a time of flight mass analyzer. Raster scanning the samples through the laser focus enables the acquisition of mass spectrometry data which can be processed into images with pixel size 10 µm without oversampling, corresponding to cellular level resolution.