Low-resolution FAIMS for increased peptide coverage in low-load and single-cell proteomics

Field Asymmetric Ion Mobility Spectrometry (FAIMS) is an indispensable tool in single-cell and low-input proteomics. Here, we show that tuning FAIMS resolution via electrode temperature modulation improves sensitivity. We demonstrate that lowering FAIMS resolution broadens the compensation voltage window, thereby increasing ion transmission. This significantly improves ion counts, quantitative precision and peptide identifications by 25–34%. These results were mirrored when analyzing single cell samples.