The electronic biosensor uses DNA aptamers to detect biomarkers in whole blood samples

A team of researchers has developed an electronic biosensor based on DNA aptamers that can detect biomarkers in whole blood samples without adding reagents. As the team explains in the journal Angewandte Chemie International EditionDNA aptamers recognize marker proteins as efficiently as antibodies do, but are easier to prepare and more adaptable. The biosensor was able to detect clinically relevant levels of a protein that markers cardiovascular disease without any additional sample preparation.

The researchers aim to develop diagnostic tools that can detect disease biomarkers directly and reliably in the field, without the need to send samples to specialized laboratories for analysis. Kelly from the University of Toronto, Canada, and Northwestern University in Evanston, Illinois, US, and her team developed a simple chip-based device for detecting marker proteins in complex samples using chronometer measurements.

Their nanosensing system acts like a molecular “pendulum”: it measures the extra load that a protein places on the pendulum, which consists of a strand of DNA attached to an electrode. The approach does not require any external reagents.

Antibodies are commonly used to search for and bind marker proteins in complex mixtures. However, antibodies are themselves proteins, and thus are very complex to design and produce. Kelly and colleagues have now found that smaller, simpler DNA aptamers can be used in place of antibodies. DNA aptamers are short synthetic fragments with specific shapes and structures. They are relatively easy to make, and with their customizable formulations, are cheaper to produce than antibodies.

Like antibodies, DNA aptamers can bind marker proteins through molecular and structural interactions, but are easier to design. “DNA has the most predictable and programmable interactions of any natural or synthetic molecule,” Kelly and her team explain. To develop an aptamer-based sensor, they created a DNA aptamer that specifically detects type B natriuretic peptide (BNP), a biomarker of cardiovascular disease, and coupled this aptamer with a DNA pendulum tethered to a gold electrode to create the sensor molecular pendulum.

The completed biosensor successfully detected BNP, even in complex mixtures such as untreated whole blood from cardiac patients. Since Kelly and colleagues found that the sensitivity of the aptamer-based system was as high as that of antibody-based detection, they suggested further investigation and the use of DNA aptamers for laboratory-independent diagnosis.