Trends in ultrasensitive proteomics

Here we review recent developments and trends in sample preparation, pre-fractionation, chromatography and mass spectrometry contributing towards the ultra-sensitive global analysis of proteins. Highly sensitive MS-based proteomics is not only beneficiary for the proteome analysis of single cells, an aim which is getting into reach, but also clearly relevant for the analysis of (a) subcellular organelles, (b) specific low-abundant cell-types such as adult stem cells, and (c) smaller but more homogeneous cell populations sorted or dissected from (diseased) tissue.

► Proteomics provides a tool to understand molecular regulatory mechanisms.
► Several biological questions require improved dynamic range and sensitivity.
► Better sample handling and LC–MS performance enables small sample volume analysis.
► Proteomics of about a 1000 cells is becoming feasible, permitting FACS LC–MS.
► Encouraging single cell results have been obtained with chips and mass cytometry.