The tandem differential mobility spectrometer (DMS)-ion modulator instrument provides improved resolution relative to traditional DMS for molecules with larger masses. The instrument includes multiple ion-bunching electrodes, each with an AC field synchronized to the transit time of the ion flow which is positioned downstream of a DMS. The ion bunching electrodes produce each a mobility-dependent modulation of the ion current. The ratio of AC to DC current provides a measure of the mobility of a large ion, even if it has little differential mobility, thereby extending the useful range of mobility characterization of a DMS system. The instrument does not require high voltages or high frequencies. Modulation before DMS separation or between tandem DMS separations produces a variable range of analyte and reactant ion densities as well as spatially separating negative and positive ions to reduce ion recombination.