Nanopore sensor paves the way for fast, low-cost DNA sequencing

Researchers from the Grainger College of Engineering at the University of Illinois Urbana-Champaign have created a new nanopore sensor for single-biomolecule detection. Their findings were published in the journal PNAS

The new nanopore sensor was created using 2D materials. Image from University of Illinois Urbana-Champaign

Nanopore sensors detect and analyze individual molecules by measuring ionic changes as the molecules pass through openings in the device. Nanopore sensors can be made from biological materials or inorganic solid-state materials. Biological nanopores are commercially available, but solid-state nanopores “offer a significant advantage over biological nanopores for massively parallelized, low-cost sequencing,” said Sihan Chen, an Illinois Grainger postdoctoral researcher and the lead author of the paper.

However, the sensor has to be small enough to have base-by-base resolution as single molecules pass through and to electrically read out the translocation of the molecules. This poses significant challenges in fabricating ultra-thin metal films encapsulated in dielectric layers. 

An innovative 2D design

This team brought together a nanopore sensor expert, Rashid Bashir, and a 2D materials expert, Arend van der Zande, to overcome the barriers presented by using ultra-thin 3D materials. 

The team integrated a 2D heterostructure into the nanopore membrane, creating a nanometer-thick out-of-plane diode for the molecules to pass through. This diode allows them to simultaneously measure the changes in electrical current during DNA translocation and apply out-of-plane biases across the diode to control the speed of the DNA translocation. 

Looking forward: important applications 

This device has potential applications in the future of precision medicine, a concept that dates back to the early 2000s but whose applications have lagged behind the initial enthusiasm. Also called personalized medicine, this approach to disease prevention and treatment is based on an individual patient’s genes, environment, and lifestyle. Creating tailored medicine and therapy regimens will require fast and affordable sequencing techniques such as this nanopore sensor. 

“In the future, we envision arrays of millions of 2D diodes with nanopores inside that could read out the sequences of DNA in parallel, reducing sequencing time from two weeks to as little as one hour,” said Rashid Bashir, Dean of The Grainger College of Engineering and an author of the paper. This could have important implications for precision medicine, making it easier and less expensive to create treatments tailored to a patient’s genetic makeup. 

The researchers anticipate further studies to improve on their design, particularly its single p-n junction, which limits the quality of control of DNA translocation. One possibility for future investigation is to use a three-layer structure to enable opposing electric fields to stretch the DNA and achieve base-by-base translocation control. 

“This work represents an important step towards base-by-base molecular control and opens doors to more advanced DNA sequencing technologies,” said Arend van der Zande, a professor of mechanical science and engineering and materials science and engineering. 

Precision medicine: a growing market 

According to Global Market Insights, the global precision medicine market is estimated at $79.9 billion in 2023, and is projected to reach $157.1 billion by 2032. 

Innovations in technology, like the new nanopore sensor, as well as the rising prevalence of cancer, are both factors that are expected to contribute to this growing market. Rising investments in human genome research will also contribute to market growth. The National Institute of Health provided $5.2 billion in funding for genome research in 2024. 

Personalized medicines accounted for 25% of the new drugs approved by the FDA in 2019, an increase from 5% in 2005, according to Global Market Insights. The number of personalized medicines on the market grew from 132 in 2016 to 286 in 2020.

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