Flow-programmable and reversible surface-induced LLPS in nanofluidic channels

Liquid-liquid phase separation (LLPS) functions as a high-performance reactor strategy in cells, creating dynamic "membrane-less organelles" that selectively concentrate biomolecules. Mimicking this volumetric strategy on a chip offers a route to transcend the capacity and kinetic limits of conventional static surface functionalization; however, engineering applications have been hindered by the stochastic nature of condensate nucleation in bulk mixing. Here, we present "flow-programmable nanofluidic surface LLPS," a method for deterministically and instantaneously inducing and manipulating surface-mediated LLPS condensates by utilizing the high surface area-to-volume ratio of nanochannels. Unlike random bulk formation, the high surface-to-volume ratio in nanochannels ensures exhaustive molecular recruitment, enabling millisecond-scale equilibration and precise thickness programming governed by diffusion-limited transport physics (δ ∝ Q^0.3). Furthermore, the formed condensates exhibit viscous dewetting dynamics, allowing for flow-tunable manipulation including nm-scale thickness control and reversible hydrodynamic peel-off. The unique properties of these surface LLPS reactors hold the potential to overcome limitations of conventional approaches for functional molecule immobilization on 2D surfaces. Examples include the high-capacity accommodation of functional molecules within 3D condensed phases, the dynamic operation of the reactors themselves, and the implementation of complex interactions such as substrate channeling.