Revolutionizing Molecular Detection with Tiny Electric Tunnels

Solid-state nanopores have emerged as transformative tools for single-molecule detection and analysis of DNA, RNA, and proteins in the field of biotechnology. This review focuses on controlled dielectric breakdown (CBD), an in-situ fabrication technique that utilizes electric fields to induce membrane dielectric breakdown, offering low-cost, scalable nanopore fabrication in insulating materials. The principles of dielectric breakdown mechanisms, integrating thermal, electrical, and chemical mechanisms, are analyzed, highlighting the critical role of parameters such as electric field intensity, material dielectric properties, and solid-liquid interface dynamics in enabling precise control over nanopore fabrication. Unlike expensive lithography methods, CBD avoids complex ex situ processes, enabling real-time monitoring via leakage currents. Key advancements in strategies for localized area thinning and laser-assisted pre-damage, micropipette-based localized confined electrolyte, and atomic force microscope tip-induced localized electric field have addressed the traditional CBD's stochasticity. These strategies enable deterministic sub-2 nm nanopore formation with tunable morphology. Advanced CBD techniques have evolved from a probabilistic method to a versatile platform for scalable and rapid nanopore fabrication. Future directions emphasize microfluidic integration with novel dielectric materials, positioning CBD as a versatile platform for next-generation single-molecule biosensing and sequencing applications.