Abstract

Hydrogel-based Optical and Electrical Sensors for Ultrasensitive Detection of Circulating Nucleic Acids in Liquid Biopsies

Dana Al Sulaiman, Postgraduate Researcher, Imperial College London

Nucleic acid sensing has recently emerged as a highly promising strategy for the detection of many human diseases, including cancer. Circulating cell-free Nucleic Acids (cfNAs) found in biofluids have received significant attention; however, their naturally low abundance, short length and high sequence homology represent a major challenge for quantitative and specific detection. Herein, we demonstrate how chemical and physical hydrogels can be engineered and used as low-cost and easily tuneable matrices for the development of the next generation of optical and electrical nucleic acid sensors, compatible with cfNAs. Low-cost nucleic acid biosensors commonly rely on optical readout; however, sensitivity is often compromised by high levels of background noise. [1] We will report how embedding optical probes within hydrogels can improve the limit of detection by up to three orders of magnitude through significant reduction in background noise. [2] Alternatively, we also show that engineered hydrogels can be used to improve sensitivity in label-free methods such nanopore sensing. [3] Whilst this technique already allows for single-molecule sensitivity, it is typically only suitable for the detection of large nucleic acid fragments. Herein, we will report how combining nanopore technology with hydrogels can drastically lower the minimum DNA size detectable without compromising sensitivity.