Recent advances in single-cell MALDI mass spectrometry imaging and potential clinical impact

Abstract

Single-cell analysis is gaining popularity in the field of mass spectrometry as a method for analyzing protein and peptide content in cells. The spatial resolution of MALDI mass spectrometry (MS) imaging is by a large extent limited by the laser focal diameter and the displacement of analytes during matrix deposition. Owing to recent advancements in both laser optics and matrix deposition methods, spatial resolution on the order of a single eukaryotic cell is now achievable by MALDI MS imaging. Provided adequate instrument sensitivity, a lateral resolution of ~10 µm is currently attainable with commercial instruments. As a result of these advances, MALDI MS imaging is poised to become a transformative clinical technology. In this article, the crucial steps needed to obtain single-cell resolution are discussed, as well as potential applications to disease research.

Nanomanipulation-Coupled Matrix-Assisted Laser Desorption/ Ionization-Direct Organelle Mass Spectrometry: A Technique for the Detailed Analysis of Single Organelles

“…MALDI mass spectrometry imaging (MALDI-MSI) has become revolutionary in mapping lipids [19], proteins [20], and other small molecules [21] in tissues, and additionally in combination with liquid chromatography [22]. However, its spatial resolution for single cell and organelle imaging has been limited by dispersement of analytes during spotting of matrix and laser spot size [23]. Here, we introduce a novel technique to provide an alternative solution to the problem, by coupling the microextraction capabilities of the nanomanipulation workstation with a co-deposition method for use in MALDI MS analysis using a high-resolution, accurate mass (<3 ppm [24]) hybrid MALDI-LTQ-XL-Orbitrap mass spectrometer.…”

Surface-enhanced laser desorption ionization time-of-flight mass spectrometry used to screen serum diagnostic markers of colon cancer recurrence in situ following surgery

“…In order to conduct SELDI-TOF-MS, only a blood sample is required; therefore, it is a relatively simple technique compared with other clinical examinations (16). Furthermore, SELDI-TOF-MS is able to detect highly-specific serum proteins in patients with colon cancer recurrence in situ following surgery.…”

Nanoscience, nanotechnology and spectrometry

“…Techniques include, amongst others, Matrix-Assisted Laser Desorption Ionization (MALDI) [30]. Lateral resolution in MALDI has been reported to be as good as 0.6-0.7 μm, but it is more common to consider a lateral resolution on the order of a few μm, unsuitable for localized analysis on the sub-micrometer scale) [31]. Imaging mass spectroscopic methods that are able to reach sub-micrometer lateral resolution include static or dynamic Secondary Ion Mass Spectrometry (S-SIMS, D-SIMS), which can attain sub-micrometer imaging resolution [32].…”