A recent breakthrough in the field of molecular detection has emerged from a collaboration between researchers at The Grainger College of Engineering at the University of Illinois Urbana-Champaign. Their innovative work on a novel nanopore sensing platform has been documented in the Proceedings of the National Academy of Sciences. This technology promises to revolutionize solid-state, label-free DNA sequencing with important implications for precision medicine.

Understanding Nanopore Sensing

Nanopore sensors are specialized devices designed to detect and analyze individual biomolecules by measuring the ionic changes that occur as these molecules pass through nanometer-scale openings. The current available technology encompasses two primary types of nanopores:

  • Biological Nanopores: These are derived from natural sources and have been commercially utilized for DNA sequencing.
  • Solid-State Nanopores: These use inorganic materials, offering distinct advantages for scalability and cost-effectiveness.

The research team at Illinois aimed to develop solid-state nanopores that could improve upon the limitations of biological nanopores, particularly in terms of scalability and manufacturing costs. As highlighted by Sihan Chen, a postdoctoral researcher and lead author, “Solid-state nanopores are compatible with wafer-scale manufacturing processes and therefore offer a significant advantage over biological nanopores for massively parallelized, low-cost sequencing.”

The Challenge of Base-by-Base Resolution

A principal challenge in achieving effective solid-state nanopore sequencing lies in the requirement for devices that can deliver base-by-base resolution as individual molecules traverse the nanopore. The previous attempts, notably the concept of DNA transistors proposed by IBM, faced significant hurdles in implementing the necessary ultra-thin metal films. Chen noted that a pause in solid-state DNA transistor development existed until their team began exploring approaches using 2D materials.

Through collaboration with Arend van der Zande from the Department of Mechanical Science and Engineering and Rashid Bashir from Bioengineering, the research team emphasized the potential of 2D materials. By addressing the challenges tied to 3D materials, which often possess rough surfaces detrimental to electrical performance, they found that 2D materials such as molybdenum disulfide (MoS2) and tungsten diselenide (WSe2) present a solution. These materials naturally exist as monolayers and do not have the dangling bonds that negatively impact performance.

Technical Innovations and Findings

The research culminated in the integration of a 2D heterostructure into the nanopore membrane, facilitating the creation of a nanometer-thick out-of-plane diode. This configuration allowed the team to:

  • Measure electrical current changes during DNA translocation.
  • Control the speed of DNA translocation by applying out-of-plane biases across the diode.

“By using these new materials, we have finally realized a decades-old dream of the nanopore community,” van der Zande stated. “This work represents an important step towards base-by-base molecular control and opens doors to more advanced DNA sequencing technologies.”

Implications for Precision Medicine

The practical applications of this novel nanopore sensing platform are substantial. As precision medicine continues to gain traction, there is a critical need for fast, reliable, and cost-effective sequencing techniques. The Illinois team estimates that this new technology could:

Current Method (Estimated) New Method (Projected)
Sequencing Time: 2 weeks Sequencing Time: 1 hour
Cost: High Cost: Tenfold reduction

Researchers anticipate that their platform could lead to sequencing arrays of millions of 2D diodes, enhancing the throughput and efficiency in DNA sequencing. The ongoing development aims to utilize alternating stacks of p-type and n-type 2D monolayers for improved control, potentially achieving base-by-base translocation control.

Looking Ahead

The Illinois Grainger team plans to continue their pioneering work in this arena, striving towards enhanced molecular control. Rashid Bashir remarked, “We are at the frontier of 2D electronics, which we are bridging with the frontier of 3D sensing. This intersection makes our project uniquely challenging and incredibly rewarding.”

“This work represents an important step towards base-by-base molecular control and opens doors to more advanced DNA sequencing technologies.” – Arend van der Zande

As this nascent technology evolves, it holds the promise to significantly impact how genomics can shape personalized medicine, representing a future where medical therapies are tailored to individual genetic profiles, ultimately leading to better patient outcomes.

For more detailed information, refer to the original research published by Sihan Chen et al. in the Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2422135122.

References

[1] Chen, S., et al. Detecting DNA translocation through a nanopore using a van der Waals heterojunction diode, Proceedings of the National Academy of Sciences (2025).

[2] Illinois Grainger College of Engineering.

[3] Additional references and resources related to nanopore technology and precision medicine.