These instruments contain an integrated travelling wave ion mobility (TWIM) cell with linear geometry which permits contiguous IM separations throughout bottom-up LC-MS experiments . For peptide identification and sequence mapping, SYNAPT instruments can perform MS E data acquisition, whereby the instrument collision energy is periodically switched between low-energy (LE) and high-energy (HE) states to provide alternate scans of intact precursor ions and their corresponding fragment (product) ions . Thus, peptide precursors are identified via retention time (RT) assisted alignment with their associated products. When the TWIM device is activated, high definition MS E (HDMS E ) can be performed, whereby the above process is conducted but with the addition of contiguous IM-based separation of precursor ions prior to fragmentation. Thus, for HDMS E , drift time assisted alignment can be performed in addition to RT assisted alignment, thereby providing higher accuracy precursor-product matching. Consequently, HDMS E has previously been shown to improve data quality in HDX-MS and other bottom-up "omics" applications . In addition to drift time alignment, HDMS E also allows ions with the same retention time to be separated based on drift time. Thus, processed spectra can be generated with reduced complexity based on their drift time extraction, which can, in turn, facilitate identification of the isotopic distribution for a peptide of interest . This is particularly beneficial for HDX-MS analyses, where short chromatographic gradients often result in co-eluting peptides with overlapping spectra which hinders peptide identification and/or spectral deconvolution (which can be challenging under deuterated conditions owing to the increased complexity of deuterated peptide isotopic distributions). Despite these improvements, the increasing complexity of samples being investigated by HDX-MS, such as mimetic reconstituted and in vivo IMPs, has generated need for instrumentation with greater resolving power .