Novel Nanopore Sensing Platform Paves Way for Solid-State, Label-Free DNA Sequencing Technologies

Nanopore sensors are extremely small devices designed to detect and examine individual molecules by monitoring ionic changes as these molecules move through nanoscale pores. These sensors fall into two categories: those constructed from biological substances and those made from inorganic solid-state materials. DNA sequencing that uses biological nanopores is already available in the market. However, solid-state nanopores, which are compatible with wafer-scale manufacturing, present a major advantage for large-scale, cost-effective sequencing due to their ability to be mass-produced. The key hurdle in achieving solid-state nanopore sequencing lies in developing a sensor with the precision to detect each DNA base as it passes through the pore and to accurately capture the electrical signal associated with this movement. Back in the late 2000s, IBM introduced the concept of DNA transistors. These devices were envisioned as metal-dielectric layered structures with electrostatic traps that would allow for both controlled DNA movement and detection. However, this idea was never implemented in practice because of the technical difficulties in fabricating ultra-thin metal layers encapsulated within dielectric materials using 3D structures.

Now, researchers from The Grainger College of Engineering at the University of Illinois Urbana-Champaign (Urbana, IL, USA) have developed a breakthrough nanopore sensing platform that enables the detection of single biomolecules. Their work, published in PNAS, brings solid-state, label-free DNA sequencing technologies closer to practical use, which could transform precision medicine. In developing the technology, the team addressed the barriers associated with 3D biosensors. Conventional ultra-thin 3D materials often have uneven surfaces and dangling bonds that degrade electrical performance and sensitivity. The team determined that these problems could be avoided by turning to 2D materials such as molybdenum disulfide and tungsten diselenide, which naturally exist in single-layer forms free of dangling bonds. By incorporating a 2D heterostructure into the nanopore membrane, the researchers created a nanometer-scale out-of-plane diode that allows DNA molecules to pass through it. This innovative architecture enabled real-time measurement of current changes through the diode during DNA passage while also applying an out-of-plane voltage to regulate the DNA’s speed as it translocates.

Though the development of this new sensing platform took years, it holds promise for advancing precision medicine. Gathering genomic information from billions of individuals to create customized treatment strategies will demand high-speed, dependable, and low-cost sequencing solutions—capabilities demonstrated by this study. The approach developed by the team could also reduce sequencing costs by a factor of ten compared to existing methods. Looking ahead, the researchers aim to create arrays with millions of these 2D diode-nanopore units to enable parallel sequencing of DNA, potentially cutting sequencing time from two weeks to just one hour. The team also plans to further refine their design in upcoming studies by introducing alternating layers of p-type and n-type 2D monolayers to go beyond the single p-n junction used in the current version. By implementing a three-layer stack that sandwiches an n-type layer between two p-type layers, they aim to generate opposing electric fields that can stretch the DNA strand. This advancement would mark a crucial step toward achieving base-by-base control over DNA translocation.

“We have used these new materials to finally realize a decades-old dream of the nanopore community that was previously impossible,” said Arend van der Zande, a professor of mechanical science and engineering and materials science and engineering. “This work represents an important step towards base-by-base molecular control and opens doors to more advanced DNA sequencing technologies.”

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The Grainger College of Engineering