Fabrication of solid-state nanopores via tip-controlled local breakdown

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A nanopore device consists of a nanoscale pore in a thin membrane. Under the influence of an electric field, single molecules transit through the pore. Chemical information, like DNA sequence, can be determined from monitoring electric current through the pore, which dynamically fluctuates as the pore is locally blocked by the transiting molecule. Nanopore sequencing devices are currently based on protein pores embedded in fragile lipid bilayer membranes. There is great interested in replacing these biological pores with solid-state pores based on standard semiconductor materials such as silicon nitride. Solid-state pores would be more robust, cheaper to mass-produce and might potentially have a higher resolution, decreasing sequencing error-rates. Yet, despite the great interest in solid-state pore devices, approaches for fabricating solid-state pores are limited. The main challenge is the lack of industrially scalable processes for fabricating solid-state pores that permit integration of the pores with other nanoscale elements required for solid-sate sequencing schemes. Recently, we have developed a new approach for fabrication of sub 5 nm pores. In our approach, which we call Tip-Controlled Local Breakdown (TCLB), a conductive tip controlled by an atomic force microscope (AFM) is brought into contact with a nitride membrane. Application of a voltage pulse leads within several hundred milliseconds to formation of a nanoscale pore that can be detected by a subsequent AFM scan. This approach is powerful because it is (1) inexpensive, (2) potentially easy to scale to industry and (3) can make sub 5nm pores that can be positioned with nm precision via AFM. In this proposal we will go beyond our initial proof-of-principle and demonstrate that TCLB has potential to be an industrially competitive pore fabrication approach that could drive emerging solid-state nanopore sequencing schemes.****