Many of the quantitative descriptions of secondary organic aerosol (SOA) formation in regional and global models are derived from environmental chamber experiments, an experimental approach commonly used to assess multi-phase product distributions from atmospheric oxidation pathways.  As such, model accuracy for predicting aerosol abundance hinges on our ability to represent atmospheric conditions in chambers.  Here, we develop a new experimental approach that leverages both global modeling and detailed mechanisms to design chamber SOA experiments that capture atmospheric chemical environments for two key branching points in VOC oxidation: atmospheric oxidant balances and atmospheric RO₂ chemistry. Using isoprene as a model system for multi-generation SOA production, we focus first on competition between oxidation by OH and Cl.  Global modeling indicates that multi-oxidant, multi-generation oxidation outcompetes single-oxidant, multi-generation oxidation in this system; we design and perform a series of chamber experiments to measure multi-phase product distributions from multi-oxidant, multi-generation isoprene oxidation.  Second, we develop a framework for quantitatively describing atmospheric RO₂ chemistry and show that no previous experimental approaches to studying SOA formation have accessed the relevant atmospheric RO₂ chemistry.  Leveraging multi-scale modeling, we design and perform a series of chamber experiments to measure isoprene SOA production under a range of atmospheric RO₂ fate distributions.