Direct Laser Writing for Deterministic Lateral Displacement of Submicron Particles

Emerging additive manufacturing (or “three-dimensional (3D) printing”) strategies offer the potential to vastly extend the capabilities of established microfluidic technologies. For example, the operational performance of “deterministic lateral displacement (DLD)” - a technique in which micro/nanoposts arrayed inside of a microfluidic channel enable passive transport of target suspended particles away from their initial flow streams - is based on geometric design variables, such as the gap spacing between the arrayed posts (G). For applications that involve DLD processing of submicron-scale particles (e.g., extracellular vesicles), however, achieving the requisite geometric control via conventional microfabrication protocols represents a technically challenging manufacturing hurdle. To bypass such barriers, here we explore the use of two-photon “direct laser writing (DLW)” for additively manufacturing DLD arrays capable of submicron particle handling. Studies of DLW fabrication conditions revealed that increasing the laser power from 22.5 mW to 27.5 mW significantly decreased G from 1.51±0.04 μm to 1.02±0.05 μm, respectively. Experimental microfluidic testing of 860 nm-in-diameter fluorescent particles within the DLW-printed DLD system revealed effective hydrodynamic railing of particles along the angled arrayed microposts, with a lateral displacement of 15.3±8.6 μm over a channel length of 500 μm. These results represent, to our knowledge, the first report of a 3D printed DLD system capable of processing submicron particles, thereby offering a promising foundation for DLW-enabled DLD-based biomedical applications.