Application of nanosecond mid-infrared lasers in mass spectrometry imaging of intact proteins

Picosecond mid-infrared lasers operating near 3 microns have been shown to extract fully intact biological molecules during ablation. However, the technical challenge of producing single-mode sub-ns lasers with high enough energy to drive the laser ablation process has limited their widespread use. In this study, we demonstrate a cost-effective solution, showing how a low-cost, commercially available 2.2 ns mid-infrared laser with a central wavelength of 2725 nm can drive the same extraction technique for the analysis of large intact proteins. We also show that the detection limit of this technique is comparable to the picosecond infrared laser techniques discussed previously and other state-of-the-art techniques like nano-desorption ionization mass spectrometry imaging. This work highlights the potential of using relatively low power (10 mW range) sub-10 ns lasers to enable mass spectrometry-based spatial biomolecular profiling on the micron scale, making the technology more accessible and affordable.