Technology for Fast Direct Detection of DNA and RNA has Clinical Potential

Technology for Fast Direct Detection of DNA and RNA has Clinical Potential
DNA blood cell on scientific background

A small sensor typically used in brain chemistry can detect RNA and DNA in less than a second, according to research from scientists at American University (AU). The device pairs a carbon fiber microelectrode (CFME) with fast-scan cyclic voltammetry (FSCV). It was able to detect these molecules first as free nucleosides, and with custom synthesized oligos, plasmid DNA, and RNA from the nematode Caenorhabditis elegans. They also demonstrated that this approach works in biologically complex serum samples.

“This is the first report demonstrating that FSCV, when used with CFMEs, is able to codetect nucleobases when polymerized into DNA or RNA and could potentially pave the way for future uses in clinical, diagnostic, or research applications,” the authors write.

The lead authors were Alexander Zestos, assistant professor of chemistry, and John Bracht, associate professor of biology. Both scientists are part of AU’s Center for Neuroscience and Behavior, which brings together researchers from a variety of fields to investigate the brain and its role in behavior.

Zestos and Bracht used a typical CFME with FSCV, the same kind of sensor used to detect neurotransmitters with subsecond temporal resolution. They modified the sensor with a specialized electrode and used it to detected the oxidative peaks of adenosine and guanosine. Their research methods were verified using both animal and synthetic RNA and DNA. A notable finding is that the sensor showed higher sensitivity toward shorter and single-stranded oligonucleotide samples than longer and double-stranded oligonucleotides, respectively.

The AU researchers believe the sensor is a useful tool for scientists engaged in clinical research to measure DNA metabolism, and that it could be a quick way for lab clinicians to distinguish ‘healthy’ from ‘sick’ samples and determine if a pathogen is fungal, bacterial, or viral, before conducting further analysis—a type of “pre-diagnostic.”

While there other tools for detecting and analyzing DNA and RNA, they have relatively long analysis times compared with this new sensor. The onset of disease or fungal infection can cause a quick rise in nucleic acids, which the sensor can measure, and possibly predict rapid infections. It can take up to a day or more for results from tests for coronavirus, for example.

Around the size of a strand of human hair, the sensor is small enough and sufficiently biocompatible to implant in cells, tissue, or in live organisms. The sensor can detect DNA or RNA in any fluid sample, including liquid droplets, saliva, blood or urine.

“Electrochemical sensors can be used for evaluating samples prior to sequence-based methods,” Bracht said. “We can envision several cases where clinically it’s useful to quickly measure DNA or RNA in a sample before further sequencing. For example, it might be used when there are a lot of samples to quickly check before doing more extensive testing.”

A next step in the research will be to modify the sensor further to see if it can detect a virus. Other potential applications for which further research will be needed include: within forensic science and other fields where sensors play a prominent role.

“We have also thought about whether we can measure DNA metabolism inside living brains and cells,” Bracht said. “We could possibly use one electrode to measure neurotransmitters like dopamine and also measure DNA and RNA and their building blocks in real-time in a brain.”