The Future of Proteomics is Up in the Air: Can Ion Mobility Replace Liquid Chromatography for High Throughput Proteomics?

Abstract

The coevolution of liquid chromatography (LC) with mass spectrometry (MS) has shaped contemporary proteomics. LC hyphenated to MS now enables quantification of more than 10,000 proteins in a single injection, a number that likely represents most proteins in specific human cells or tissues. Separations by ion mobility spectrometry (IMS) have recently emerged to complement LC and further improve the depth of proteomics. Given the theoretical advantages in speed and robustness of IMS in comparison to LC, we envision that ongoing improvements to IMS paired with MS may eventually make LC obsolete, especially when combined with targeted or simplified analyses, such as rapid clinical proteomics analysis of defined biomarker panels. In this perspective, we describe the need for faster analysis that might drive this transition, the current state of direct infusion proteomics, and discuss some technical challenges that must be overcome to fully complete the transition to entirely gas phase proteomics.

Rapid Plasma Proteome Profiling via Nanoparticle Protein Corona and Direct Infusion Mass Spectrometry

“…Nevertheless, opportunities exist to refine DISPA to enable faster and deeper analysis of low-abundance biomarkers in plasma and other fluids, including cerebrospinal fluid (CSF), urine, and serum. This enhancement can be achieved through advances in the following dimensions, as we discussed more extensively in our recent perspective article Instrumentation.…”

“…Second, currently, DISPA only uses Orbitrap mass analyzers. Faster mass spectrometers, such as the newly launched Astral, could allow us to significantly increase the scanning speed (up to ∼200 Hz), enabling us to target more biomarkers. , One challenge with new equipment is the need to develop software to manage new types of data. A third route to improving our approach with hardware advances is through increasing ionization efficiency, which can also enhance the depth of DISPA analysis.…”