Microfluidic-assisted self-assembly of information-bearing oligomers

Increasing the complexity of self-assembled supramolecular nanostructures necessitates considered design and synthesis of the precursor molecular components as well as precise control over the reaction microenvironment. Conventional batch techniques are susceptible to kinetic trapping of intermediate species, resulting in reduced target yields for progressively complex assemblies. In contrast, the microenvironmental control offered by microfluidics enables local thermodynamic minima to be circumvented, enabling self-assembly processes to proceed to completion. Here, the dynamic covalent assembly of imine-based molecular ladders and branched nanostructures is achieved through droplet microfluidics. Droplets of an organic solution composed of a solvent (chloroform), a multi-role Lewis acidic reagent (scandium triflate), and complementary oligo(peptoid) precursor strands bearing amine and aldehyde pendant groups are generated in an aqueous solution. Downstream hydrodynamic microtraps immobilized the droplets in the flowing aqueous phase, hence the media around the droplet is constantly replaced, thereby avoiding coevolution of the two phases and enabling continuous extraction of reagent from the entrapped droplet into the surrounding microflow via interfacial diffusion. As the reagent concentration is altered, so are the equilibrium conditions. At high reagent concentration, the amine and aldehyde condensation reaction product between the reactive pendant groups affixed to the oligomeric precursor species is supported. As the concentration drops, Sc³⁺-catalyzed imine bond rearrangement occurs, providing an error correction mechanism, enabling the generated ladder constructs to come into registry which were confirmed by off-chip analysis of the collected droplets using MALDI-MS. Furthermore, the assembly of three complementary oligo(peptoid) precursor strands into three-way, imine-based nanostructures was achieved.