Laser post-ionisation combined with a high resolving power orbitrap mass spectrometer for enhanced MALDI-MS imaging of lipids

Abstract

Coupling laser post-ionisation with a high resolving power MALDI Orbitrap mass spectrometer has realised an up to ∼100-fold increase in the sensitivity and enhanced the chemical coverage for MALDI-MS imaging of lipids relative to conventional MALDI. This could constitute a major breakthrough for biomedical research.

Combining MALDI‐2 and transmission geometry laser optics to achieve high sensitivity for ultra‐high spatial resolution surface analysis

“…The MALDI‐2 laser beam was aligned with the MALDI‐1 spot and positioned ~1 mm above the surface. Longer delay time between MALDI‐1 and MALDI‐2 pulses as well as greater distance between the sample and MALDI‐2 focus were used as compared with front‐side geometry previously reported in literature . Adjustment of the stock MALDI laser optics was obviated by intercepting the beam as it left the laser head.…”

“…Longer delay time between MALDI-1 and MALDI-2 pulses as well as greater distance between the sample and MALDI-2 focus were used as compared with frontside geometry previously reported in literature. 14,15 Adjustment of the stock MALDI laser optics was obviated by intercepting the beam as it left the laser head. The beam was intercepted for the TG optics via a magnetically-mounted mirror, which simplifies switching between the two modes of operation (ie, front-side or TG operation).…”

“…Recently, a laser‐based post‐ionization approach, referred to as MALDI‐2, has been developed for improved sensitivity . Briefly, MALDI‐2 is performed by irradiating the plume of molecules and matrix generated by a primary MALDI ablation event with a second post‐ionization UV laser beam that is orthogonal to the primary ionization plume . MALDI‐2 has been shown to improve sensitivity up to 100‐fold for some lipid species by ionizing neutral molecules generated in the MALDI process .…”

“…14 Briefly, MALDI-2 is performed by irradiating the plume of molecules and matrix generated by a primary MALDI ablation event with a second post-ionization UV laser beam that is orthogonal to the primary ionization plume. 15 MALDI-2 has been shown to improve sensitivity up to 100-fold for some lipid species by ionizing neutral molecules generated in the MALDI process. 14 These initial studies focused on applications for front-side geometry optical path MALDI instruments with a beam diameter between 5 and 10 μm, Analysis to date has focused on lipid and glycan species -studies with peptide analytes have not produced significant signal enhancement.…”

DIUTHAME enables matrix‐free mass spectrometry imaging of frozen tissue sections

“…MSI is becoming a powerful analytical tool in biomedical and life sciences . The instrument technologies of MALDI mass spectrometers have greatly advanced in the past decade: for instance, implementing high‐repetition solid‐state lasers, continuous raster sampling, and galvanometer‐based optical scanners for improved throughput; spatially structured laser beam profiles and laser‐induced post‐ionization for improved sensitivity; laser beam shaping, fiber‐optic laser delivery systems, and transmission geometry vacuum MALDI source for improved spatial resolution; stigmatic imaging (microscope mode) instrumentation for both throughput and spatial resolution; and most recently, high‐performance elevated/atmospheric pressure MALDI . It could be argued that MALDI‐MSI applications have led this progress.…”