Modified linear ion trap-Orbitrap hybrid MS system for performing AI-NETD. (A) NETD, which involves oxidation of precursor peptide anions by a reagent cation, can now be performed in the mass-analyzing quadrupole linear ion trap (A-QLT) and multipurpose dissociation cell (MDC). (B) Modifying the MDC to perform NETD opens access to AI-NETD, in which anionic peptide precursors are concurrently irradiated with IR photons during the ion–ion reaction. This additional photoactivation disrupts peptide secondary gas-phase structure, increasing the efficiency of the NETD reaction. (C) Instrument schematic of the hybrid linear ion trap-Orbitrap mass spectrometer is modified with the MDC in place of the traditional HCD collision cell, in addition to an excavated beam path, ZnSe window, and affixed 10.6 μm CO2 laser for concentric irradiation of the MDC.