A tandem collision/reaction cell (110, 410), comprising: a housing (187, 487) comprising a cell entrance, a cell exit spaced from the cell entrance along a longitudinal axis of the collision/reaction cell (110, 410), and a gas supply port communicating with an interior of the housing (187, 487); a first ion guide (174, 274) positioned in the housing (187, 487) and comprising a first ion guide entrance and a first ion guide exit, the first ion guide (174, 274) configured to generate a first RF confining field effective to confine ions in a radial direction orthogonal to the longitudinal axis; a second ion guide (178, 278) positioned in the housing (187, 487) and comprising a second ion guide entrance and a second ion guide exit, wherein the second ion guide entrance is spaced from the first ion guide exit by an axial gap, the second ion guide (178, 278) configured to generate a second RF confining field effective to confine ions in a radial direction orthogonal to the longitudinal axis; an intermediate electrode (182, 282, 382, 482) configured to generate an on-axis DC potential barrier in a vicinity of the first ion guide exit, wherein the on-axis DC potential barrier is effective to prevent at least some interfering ions from exiting the first ion guide (174, 274) and low enough to allow analyte ions of smaller cross-section than the interfering ions to exit the first ion guide (174, 274); and an ion optics component (124, 224, 158, 458) positioned downstream from the second ion guide exit and configured to generate a second DC potential barrier effective to prevent at least some interfering ions from passing through a mass analyzer downstream from the cell exit, and low enough to allow analyte ions to pass through the mass analyzer, a voltage source or voltage sources configured to apply a first RF potential superimposed on a first DC bias potential to electrodes of the first ion guide (174, 274) to generate the first RF confining field, apply a second RF potential superimposed on a second DC bias potential to electrodes of the second ion guide (178, 278) to generate the second RF confining field, to apply a third DC potential to the intermediate electrode (182, 282, 382, 482) to generate the on-axis DC potential barrier, and to apply a forth DC voltage to the ion optics component (124, 224, 158, 458) to generate the second DC potential barrier, wherein the second DC bias potential is more negative than the first DC bias potential. a housing (187, 487) comprising a cell entrance, a cell exit spaced from the cell entrance along a longitudinal axis of the collision/reaction cell (110, 410), and a gas supply port communicating with an interior of the housing (187, 487); a first ion guide (174, 274) positioned in the housing (187, 487) and comprising a first ion guide entrance and a first ion guide exit, the first ion guide (174, 274) configured to generate a first RF confining field effective to confine ions in a radial direction orthogonal to the longitudinal axis; a second ion guide (178, 278) positioned in the housing (187, 487) and comprising a second ion guide entrance and a second ion guide exit, wherein the second ion guide entrance is spaced from the first ion guide exit by an axial gap, the second ion guide (178, 278) configured to generate a second RF confining field effective to confine ions in a radial direction orthogonal to the longitudinal axis; an intermediate electrode (182, 282, 382, 482) configured to generate an on-axis DC potential barrier in a vicinity of the first ion guide exit, wherein the on-axis DC potential barrier is effective to prevent at least some interfering ions from exiting the first ion guide (174, 274) and low enough to allow analyte ions of smaller cross-section than the interfering ions to exit the first ion guide (174, 274); and an ion optics component (124, 224, 158, 458) positioned downstream from the second ion guide exit and configured to generate a second DC potential barrier effective to prevent at least some interfering ions from passing through a mass analyzer downstream from the cell exit, and low enough to allow analyte ions to pass through the mass analyzer, a voltage source or voltage sources configured to apply a first RF potential superimposed on a first DC bias potential to electrodes of the first ion guide (174, 274) to generate the first RF confining field, apply a second RF potential superimposed on a second DC bias potential to electrodes of the second ion guide (178, 278) to generate the second RF confining field, to apply a third DC potential to the intermediate electrode (182, 282, 382, 482) to generate the on-axis DC potential barrier, and to apply a forth DC voltage to the ion optics component (124, 224, 158, 458) to generate the second DC potential barrier, wherein the second DC bias potential is more negative than the first DC bias potential.