Thermoplastic polyurethanes
(TPUs) are designed using a large variety
of basic building blocks but are only synthesized in a limited number
of solvent systems. Understanding the behavior of the copolymers in
a selected solvent system is of particular interest to tune the intricate
balance of microphase separation/mixing, which is the key mechanism
behind the structure formation in TPUs. Here, we present a computationally
efficient approach for selecting TPU building blocks and solvents
based on their Flory–Huggins interaction parameters for a precise
control over the microphase separation/mixing. We first cluster eight
soft segments (PEO, PPO, PTMO, PBA, PCL, PDMS, PIB, or PEB) used frequently
in TPUs into three categories according to the strength of their interactions
with the binary solvent THF/DMF. We then perform a comprehensive set
of dissipative particle dynamics simulations of the TPUs in a range
of solvent ratios. This enables us to demonstrate the emergence of
the unusual channel-like structures in a narrow range of parameters
and to determine the critical interactions operative for obtaining
either microphase separated or mixed structures. The findings are
supported by thermodynamic arguments. The approach developed here
is useful for designing novel TPUs with well-defined conformational
characteristics, controlled morphologies, and advanced functional
properties.