Conically channeled membranes designed for fast and efficient transport of macromolecules

Transport channels for the separation and sensing of biomacromolecules, especially therapeutic biodrugs, have attracted substantial interest. The growing attention underscores the critical need for appropriate control strategies over membrane channels characteristics including size, structure and shape. While homoporous membranes featuring conical nanopores have demonstrated excellent performance in facilitating the transport of small molecules and ions, the potential advantages of membranes with conical micropores for biomacromolecule transport remain inadequately explored. This gap primarily arises from the difficulty in scaling the cone tip to the micrometer range using traditional etching techniques. To address this challenge, we developed a shape-and-size sequential etching method with enhanced controllability, enabling the fabrication of microscale conical channels. A theoretical model of the etching period was proposed for etching scheme determination. Key experimental factors, including etching time, temperature, and adding ethanol as an additive, were investigated and shown to significantly influence etching performance. Notably, the as-prepared membrane with conical channels led to significantly increased fluxes (8.10 vs 3.84 μL/h at 0.08 MPa) and enhanced dynamic binding capacity (476.03 vs 382.88 pmol/cm 2 ), exhibiting remarkable advantages over the cylindrical-channel membrane. Overall, this sequential etching method allows customizable membrane fabrication with precise conical microchannels, offering a versatile membrane-based platform for a broad spectrum of challenging biopharmaceutical separation, biosensing, and drug delivery.