Fast and Deterministic Fabrication of Sub-5 Nanometer Solid-State Pores by Feedback-Controlled Laser Processing

[Image: see text] Nanopores are single-molecule sensors capable of detecting and quantifying a broad range of unlabeled biomolecules including DNA and proteins. Nanopores’ generic sensing principle has permitted the development of a vast range of biomolecular applications in genomics and proteomics, including single-molecule DNA sequencing and protein fingerprinting. Owing to their superior mechanical and electrical stability, many of the recent studies involved synthetic nanopores fabricated in thin solid-state membranes such as freestanding silicon nitride. However, to date, one of the bottlenecks in this field is the availability of a fast, reliable, and deterministic fabrication method capable of repeatedly forming small nanopores (i.e., sub 5 nm) in situ. Recently, it was demonstrated that a tightly focused laser beam can induce controlled etching of silicon nitride membranes suspended in buffered aqueous solutions. Herein, we demonstrate that nanopore laser drilling (LD) can produce nanopores deterministically to a prespecified size without user intervention. By optimizing the optical apparatus, and by designing a multistep control algorithm for the LD process, we demonstrate a fully automatic fabrication method for any user-defined nanopore size within minutes. The LD process results in a double bowl-shaped structure having a typical size of the laser point-spread function (PSF) at its openings. Numerical simulations of the characteristic LD nanopore shape provide conductance curves that fit the experimental result and support the idea that the pore is produced at the thinnest area formed by the back-to-back facings bowls. The presented LD fabrication method significantly enhances nanopore fabrication throughput and accuracy and hence can be adopted for a large range of biomolecular sensing applications.