The heterogeneous reactivity of dinitrogen pentoxide (N 2 O 5 ) on ambient aerosols plays a key role in atmospheric fate of NO x and formation of secondary pollutants. To better understand the reactive uptake of N 2 O 5 on complex ambient aerosols, an in-situ experimental approach to direct measurement of N 2 O 5 uptake coefficient (γN 2 O 5 ) was developed for application in environments with high, variable ambient precursors. The method utilizes an aerosol flow-tube reactor coupled with an iterative chemical box model to derive γN 2 O 5 from the depletion of synthetically generated N 2 O 5 when mixed with ambient aerosols. Laboratory tests and model simulations were performed to characterize the system and the factors affecting γN 2 O 5 , including mean residence time, wall loss variability with RH, and N 2 O 5 formation and titration with high levels of NO/NO x /O 3 . The overall uncertainty was estimated to be 9 %–17 % at γN 2 O 5 of 0.03 for RH varying from 20 % to 70 %. The results indicate that this flow tube coupled with the iterative model method could be buffered to NO concentrations below 8 ppbv and against air mass fluctuations switching between aerosol and non-aerosol modes. The system was then deployed in the field to test its applicability under conditions of high ambient NO 2 /O 3 and fresh NO emission. The results demonstrate that the iterative model improved the accuracy of γN 2 O 5 calculations under polluted environments, and thus support the further field deployment of the system to study the impacts of heterogeneous N 2 O 5 reactivity on photochemistry and aerosol formation.