<div>Amongst the various classes of mass analyzers, the quadrupole ion trap (QIT) is by far the most versatile. Although it can achieve only modest resolution (unit) and mass accuracy (101-102 ppm), it has high sensitivity and selectivity, can operate at pressures exceeding 10-3 torr, is tolerant to various electrode imperfections, and has single analyzer tandem mass spectrometry (MS/MS) capabilities in the form of product ion scans. These characteristics make the QIT ideal for mass spectrometer miniaturization, as most of the fundamental performance metrics of the QIT do not depend on device size. As such, the current drive in miniature systems is to adopt miniature ion traps in various forms – 3D, linear, toroidal, rectilinear, cylindrical, arrays, etc.</div><div><br></div><div>Despite being one of the two common mass analyzers with inherent MS/MS capabilities (the other being the Fourier transform ion cyclotron resonance mass spectrometer), it is commonly accepted that the QIT cannot perform one-dimensional precursor ion scans and neutral loss scans - the other two main MS/MS scan modes - or two-dimensional MS/MS scans. The former two are usually conducted in triple quadrupole instruments in which a first and third quadrupole are used to mass select precursor and product ions while fragmentation occurs in an intermediate collision cell. The third scan can be accomplished by acquiring a product ion scan of every precursor ion, thus revealing the entire 2D MS/MS data domain (precursor ion m/z vs. product ion m/z). This, however, is not one scan but a set of scans. Because the ion trap is a tandem-in-time instrument rather than a tandem-in-space analyzer, precursor ion scans, neutral loss scans, and 2D MS/MS are, at best, difficult.</div><div><br></div><div>Yet miniature mass spectrometers utilizing quadrupole ion traps for mass analysis would perhaps benefit the most from precursor scans, neutral loss scans, and 2D MS/MS because they generally have acquisition rates (# scans/s) an order of magnitude lower than their benchtop counterparts. This is because they usually use a discontinuous atmospheric pressure interface (DAPI) to reduce the gas load on the backing pumps, resulting in a ~1 scan/s acquisition rate and making the commonly-used data-dependent acquisition method (i.e. obtaining a product ion scan for every abundant precursor ion) inefficient in terms of sample consumption, time, and instrument power. Precursor and neutral loss scans targeting specific molecular functionality of interest - as well as 2D MS/MS – are more efficient ways of moving through the MS/MS data domain and thus pair quite readily with miniature ion traps.</div><div><br></div><div>Herein we demonstrate that precursor ion scans, neutral loss scans, and 2D MS/MS are all possible in a linear quadrupole ion trap operated in the orthogonal double resonance mode on both benchtop and portable mass spectrometers. Through application of multiple resonance frequencies matching the secular frequencies of precursor and/or product ions of interest, we show that precursor ions can be fragmented mass-selectively and product ions ejected simultaneously, preserving their relationship, precursor ion -> product ion + neutral, in the time domain and hence allowing the correlation between precursor and product ions without prior isolation. By fixing or scanning the resonance frequencies corresponding to the targeted precursor and product ions, a precursor ion scan or neutral loss scan can be conducted in a single mass analyzer. We further show that 2D MS/MS - acquisition of all precursor ion m/z values and a product ion mass spectrum for every precursor ion, all in a single scan - is possible using similar methodology. These scan modes are particularly valuable for origin-of-life and forensic applications for which the value of miniature mass spectrometers is readily evident.</div>