DNA origami enhances electrochemical biosensor performance

The new results provide a platform for more efficient, selective and sensitive DNA biosensors that can be used to detect various pathogens and diseases.

Electrochemical DNA biosensors hold significant promise for monitoring various diseases. Overall, the detection applications are vast, from DNA target analytes such as bacterial genes and tumor sequences to clinically relevant concentrations of SARS CoV-2 biomarkers, for example.

However, it is difficult to achieve appropriate sensitivity and selectivity of such systems and to enable their translation from the laboratory to a clinical setting, as these approaches often involve complex chemicals, electrochemical labeling, technically demanding materials or multi-step processing.

Now a team of researchers from Aalto University (Finland) and the University of Strathclyde (Glasgow, UK) have found a way to significantly enhance the sensitivity of electrochemical DNA sensors using modular DNA nanostructures as their new components. The researchers combined conventional DNA-based sensor techniques with programmable DNA origami structures to create a label-free sensor with significantly increased detection selectivity and sensitivity.

“In practice, our starting point is a rather simple and common type of DNA biosensor—we have an electrode system immersed in the analyte solution, where the sensing electrode is coated with single-stranded DNA probe strands that are complementary to the (single-stranded Once the strand target binds and hybridizes with the probe strand, the electrical charges near the electrode move a little, which means we can see a change in the electrochemical signal,” explains PhD student Petteri Piskunen from Aalto University, one of the authors of the research.

“This is where DNA origami nanostructures come into play. We equipped the tile-like DNA origami with target capture strands that can efficiently and selectively bind to one end of the target sequence while the other end of the target binds to the probe strands. Therefore, we create a sandwich-like complex where the target strand is trapped between the electrode and the DNA origami.Then, instead of recording a small signal change upon target binding, we see an enhanced effect due to the presence of the comparatively large origami DNA,” Piskunen continues.

“We demonstrated the feasibility of our system by detecting a gene fragment from antibiotic-resistant bacteria. We could selectively trap this target from a rather complex solution containing various types of single-stranded DNA, from short strands and unwanted fragments to long circular DNA. our sensor we could reliably detect 100-1000 times lower target concentrations than with conventional techniques,” says visiting scientist Veikko Linko (currently Associate Professor at the University of Tartu, Estonia).

“It is encouraging to believe that by combining flexible DNA origami with, for example, printable and disposable electrodes, we could create label-free detection platforms with such high sensitivity and specificity. This places our technology on a path towards mass manufacturing and widespread application as a point Currently, collaboration with the University of Strathclyde is underway to generalize the sensor setup for use with different kinds of biomarkers,” concludes Linko.

The findings are published in the journal ACS sensors.