Researchers at the California Institute of Technology (Caltech) recently introduced DNA origami-based technology which may develop reusable affordable biosensors for medical diagnostic transformation. The researchers achieved detection of proteins together with nucleic acids in bodily fluids by means of nanoscale engineering which has developed a fast diagnosis system that could replace prolonged testing in conventional laboratories. The research can be found here:
Jeon, B., Guareschi, M. M., Stewart, J. M., Wu, E., Gopinath, A., Arroyo-Currás, N., Dauphin-Ducharme, P., Plaxco, K. W., Lukeman, P. S., & Rothemund, P. W. K. (2025). Modular DNA origami–based electrochemical detection of DNA and proteins. Proceedings of the National Academy of Sciences, 122(1). https://doi.org/10.1073/pnas.2311279121
The study, recently published in the Proceedings of the National Academy of Sciences, presents a single-step approach that enhances the sensitivity and versatility of biomarker detection. Led by Paul Rothemund, a visiting associate in computing and mathematical sciences at Caltech, the research builds on the foundation of DNA origami—a technique Rothemund first introduced in 2006. The lead authors of the paper are former Caltech postdoctoral scholar Byoung-jin Jeon and current graduate student Matteo M. Guareschi, who completed the work in Rothemund’s lab.
“Our work provides a proof-of-concept showing a path to a single-step method that could be used to identify and measure nucleic acids and proteins,” – Paul Rothemund
DNA origami enables scientists to fold long strands of DNA, by means of self assembly, into precise, nanoscale structures using short complementary DNA sequences that act as molecular “staples.” This self-assembly method allows for the creation of intricate shapes and devices at a scale 1,000 times thinner than a human hair. In earlier demonstrations, Rothemund crafted DNA into recognisable shapes, such as smiley faces.
In this latest work, the team applied DNA origami to fabricate a lilypad-like structure, roughly 100 nanometers in diameter, which serves as the core of their biosensing platform. This lilypad is tethered to a gold electrode through a DNA linker and is equipped with short DNA strands designed to capture specific analytes—molecules of interest like DNA fragments, proteins, or antibodies.
When an analyte binds to the lilypad’s DNA strands, it causes the structure to move closer to the gold electrode. This close proximity brings 70 redox-active reporter molecules into contact with the electrode surface, triggering an electrical current. The strength of this current correlates with the concentration of the target molecule, enabling precise detection.
“That means it can fit 70 reporters on a single molecule and keep them away from the surface before binding. Then when the analyte is bound and the lilypad reaches the electrode, there is a large signal gain, making the change easy to detect,”
Guareschi says.
Earlier biosensor models used single DNA strands. However, the DNA origami technique offers greater sensitivity and the ability to detect larger biomolecules. The lilypad’s larger surface area allows it to accomodate reporter molecules, amplifying the detection signal and making it easier to identify even low concentrations of target analytes.
The system can be quickly adapted to detect various biomolecules by simply adding different molecular adapters, such as aptamers or antibody fragments. In laboratory tests, the researchers demonstrated the sensor’s ability to switch between detecting DNA and proteins by incorporating specific adapters. For example, by adding vitamin biotin and a DNA aptamer, the system successfully detected the protein streptavidin and the disease-related protein PDGF-BB.
“We just add these simple molecules to the system, and it’s ready to sense something different,” Guareschi says. “It’s large enough to accommodate whatever you throw at it—that could be aptamers, nanobodies, fragments of antibodies—and it doesn’t need to be completely redesigned every time.”
Equally important is the biosensor’s reusability. The team found that the device could do multiple cycles of testing with only minor degradation in performance.
“You could have multiple sensors at the same time with different analytes, and then you could do a wash, switch the analytes, and remeasure. And you could do that several times,” Guareschi says. “Within a few hours, you could measure hundreds of proteins using a single system.”
Hassan graduated with a Master’s degree in Chemical Engineering from the University of Chester (UK). He currently works as a design engineering consultant for one of the largest engineering firms in the world along with being an associate member of the Institute of Chemical Engineers (IChemE).
