Researchers from The Grainger College of Engineering at the University of Illinois Urbana-Champaign have developed a groundbreaking nanopore sensing platform capable of detecting single biomolecules. Their work, recently published in Proceedings of the National Academy of Sciences, offers promising advancements for solid-state, label-free DNA sequencing, with far-reaching implications for precision medicine.

Nanopore sensors operate by detecting changes in ionic current as individual molecules pass through nanoscale openings. These devices come in two primary forms: biological nanopores and solid-state nanopores. While biological nanopore sequencing has already reached commercial use, engineers at Illinois Grainger aimed to develop a solid-state alternative that is more compatible with scalable manufacturing.

Solid-state nanopores have the potential to support mass production through wafer-scale processes, which could drastically reduce the cost and increase the accessibility of DNA sequencing. However, building a sensor capable of resolving DNA sequences base by base has long been a technical challenge. Previous attempts, such as IBM’s concept of DNA transistors in the 2000s, were stymied by the difficulty of fabricating ultra-thin metal-dielectric layers using 3D materials.

A revival of interest came when researchers revisited this idea using two-dimensional (2D) materials. The new effort emerged from a collaboration between experts in nanopore sensors and 2D materials—uniting fields of bioengineering, materials science, and mechanical engineering. Their combined expertise led to a reimagined approach that addressed the limitations of 3D materials, such as rough surfaces and dangling bonds that interfere with electrical performance.

The team chose atomically thin 2D materials like molybdenum disulfide and tungsten diselenide, which naturally exist as monolayers without dangling bonds. These materials were stacked to create a 2D heterostructure, forming the core of the new nanopore membrane. The design includes a nanometer-thick out-of-plane diode through which DNA molecules can pass. This configuration enables simultaneous measurement of electrical signals and control over the DNA’s translocation speed via applied biases.

This dual capability is significant because it allows for real-time tracking and modulation of molecular movement—a long-standing goal in nanopore research. By precisely measuring changes in current as DNA moves through the pore, and slowing the movement enough to detect each base, the team has achieved a technical milestone previously considered out of reach.

The researchers believe this platform could ultimately lead to rapid and cost-effective genome sequencing. Instead of weeks, sequencing could be completed in an hour using arrays of millions of nanopores. The affordability of the process could also improve significantly, with projections estimating costs up to ten times lower than current methods.

Looking ahead, the team plans to explore a more advanced configuration using alternating stacks of p-type and n-type 2D monolayers. This tri-layer design would enhance electrical control, allowing DNA strands to be stretched and sequenced one base at a time—further refining the accuracy and efficiency of the system.

This innovation not only marks a pivotal advancement in 2D electronics and nanopore sensing but also lays the foundation for transformative applications in genomics and personalized healthcare. As the demand for fast, scalable DNA sequencing grows, the Illinois Grainger team’s contribution could redefine the future of biomedical diagnostics and treatment.

By Impact Lab