Laser-Based Sculpturing of Embedded Ultrathin Metal-Oxide Nanopores for Enhanced Biomolecular Sensing

Abstract

Nanopore sensors detect individual molecules by monitoring ionic current as analytes translocate through nanometer-scale pores. The resolution of molecular features depends on both the translocation speed and the dimensions of the pore. Here, a three-layer solid-state nanopore architecture engineered to optimize both parameters is presented. A 3 nm-thick hafnium dioxide (HfO2) layer is embedded between two supporting layers. Laser-assisted drilling reliably forms 3–5 nm pores in aqueous solution within the HfO2 layer, while simultaneously creating Gaussian-shaped cavities that enhance molecular translocation dynamics. High-resolution electron microscopy and cross-sectional analysis confirm the structural integrity and uniformity of the layered architecture. Compared to conventional single-layer silicon nitride (SiNx) nanopores, the three-layer pores slow DNA translocation by a factor of 12, enabling the detection of short 10 base pairs DNA. This enhanced spatial resolution also allows for label-free detection of 21-nucleotide microRNA (miRNA), with secondary current blockades revealing structural features. Protein detection is demonstrated by conjugating short oligonucleotides to cysteine residues, with secondary blockade signals corresponding to the number of cysteines within the protein. This robust nanopore platform combines the mechanical stability of a wide-bandgap metal oxide with a chemically etchable support structure, offering a versatile and high-resolution approach for single-molecule biomolecular analysis.