NIST Scientists Use DNA Origami on a Chip to Detect Biomolecules

Using strands of DNA to create miniature hinges that pop open or shut when binding to specific molecules, researchers at the National Institute of Standards and Technology (NIST) have developed a chip-scale device that has the potential to measure with high accuracy the presence and concentration of trace amounts of compounds important for human health and the environment.

Folding long strands of DNA into a variety of shapes, a technique known as DNA origami was developed nearly 20 years ago. The folded DNA can be tailored to bind to an assortment of different molecules. Jacob Majikes, Arvind Balijepalli, and their NIST colleagues adapted the origami method to create DNA structures that changed their shape upon electrochemically binding to a specific molecule. In particular, they constructed DNA “hinges” that opened or closed when they attached to the molecule they were designed to detect.

Droplets of liquid containing as few as 12,000 molecules were fed by a micro vessel onto a chip containing as many as a million of the DNA hinges. Each hinge contained about 8,000 base pairs—the rungs on the ladder that support the DNA helix.

For their initial experiment, the team tested the ability of the hinges to detect short strands of DNA, about 20 to 30 base pairs long. Over the next year, the researchers plan to reach their ultimate goal: Binding the origami shapes to molecules that have a direct impact on the environment, such as toxins or pollutants, and to human health, such as markers for cancer or other human diseases.

To determine how well their system recognized the short DNA strands, the researchers measured the change in capacitance—the ability to store electrical charge—of the hinges before and after they bound to the strands. The scientists then compared those measurements to the change in capacitance recorded when chains of DNA strands without hinges bound to the same short DNA strands. The scientists found that the hinges amplified the electrical signal about 20,000 times, dramatically enhancing the ability to detect molecule of interest.

The team not only detected the presence of the short strands through their electro-chemical interaction with the hinges, but also determined the concentration of the strands. The scientists accomplished this by assessing how many closed hinges popped open and how many opened hinges snapped closed. The greater the concentration of the short strands, the greater the number of hinges that changed their configuration and the larger the measured signal.

The researchers, which also include Seulki Cho, Thomas Cleveland and J. Alexander Liddle, reported their study online Oct. 16 in RSC Nanoscale.

Paper: Jacob M. Majikes, Seulki Cho, Thomas E. Cleveland IV, J. Alexander Liddle, Arvind Balijepalli. Variable Gain DNA Nanostructure Charge Amplifiers for Biosensing. RSC Nanoscale, 2024. DOI: https://doi.org/10.1039/D4NR02959C