Nucleic acid biosensors: applications to cancer diagnostics and prenatal testing
Liquid biopsies have the potential to revolutionise the way patients are screened, treated and monitored and are key drivers of precision medicine. Although affordable full genome sequencing may help identify individuals at risk of developing specific pathologies, it will never replace snapshots provided by point-of-care testing through simple technologies that are both low-cost and highly automated. Circulating cell-free nucleic acids (cfNAs) in liquid biopsies have been reported as predictive, diagnostic and prognostic biomarkers for a broad range of conditions and technologies that can facilitate their detection in a point-of-care setting will impact the very broad population affected by these pathologies. However, they are particularly challenging to detect accurately due to their low concentration and high sequence homology. In our lab, we are developing and validating new sensing platforms for the automated and quantitative detection of cfNAs from whole blood. These technologies have great potential for (i) early diagnosis and improved prognosis of prostate cancer; (ii) improved diagnosis of Hepatitis B in developing countries; (iii) non-invasive early prediction of preterm birth. All these applications are currently being pursued through well-established collaborations with clinicians.
MicroRNA sensing via oligonucleotide-templated reactions. We have successfully designed and engineered Peptide Nucleic Acid (PNA) fluorogenic probes that can be detect endogenous concentrations of circulating miRNAs from patient blood. Compared to gold-standard, this technology requires no amplification step and is amenable to incorporation into low-cost portable devices (from immobilisation onto microtitre plates to embedding in engineered hydrogels).
Label-free, single molecule sensing and size-profiling of cell-free DNA using hydrogel-filled nanopipettes. We have successfully engineered an hydrogel-filled nanopore sensor that can detect, with single molecule resolution, small double-stranded DNA fragments the size of those found in body fluids (100-1000bp), while excluding larger fragments. This new platform is easily tuneable and is suitable for DNA size profiling.