Wafer-Scale Laser-Writing of Nanoporous Membranes with Monodisperse Pores for Robust Immunoisolation.

Abstract

Membranes that prevent cellular infiltration are essential components of immune-isolation devices. Stringent pore size control is critical to robustly exclude immune cells while preserving the efficient transport of nutrients and therapeutic molecules. Conventional membrane fabrication methods, however, struggle to balance these two properties. For instance, phase separation and fiber spinning generate highly tortuous pores that restrict diffusion, while random pore overlaps due to ion track etching result in oversized defects that compromise immune isolation. Here, we leverage scalable laser-writing tools to achieve spatially controlled open-through and dense pores with uniformly distributed submicrometer sizes for rapid transport and robust immune cell exclusion. Given the optical limits of laser aligners when fabricating submicrometer features, we tuned substrate reflectivity and exposure parameters to overcome these resolution limits. Self-standing and flexible membranes were achieved via thickness-tunable grid layers supporting membrane mechanical integrity. We report pore sizes as small as <i>ca</i>. 600 nm (below the resolution limits of the laser exposure systems) and over 20% open area at the exposure times of ∼3 min/cm². Compared with conventional methods, this approach minimizes pore tortuosity, narrows the pore distribution, and improves the open pore density. Enhanced pore control is highlighted by macrophage infiltration studies, which indicate that these membranes reliably exclude macrophages at nominal pore sizes greater than those previously achievable. This approach thus provides a scalable pathway toward next-generation immunoisolation membranes for enhanced implantable therapeutic devices.