Nanomaterials as signal amplifiers in CRISPR/Cas biosensors: A path toward multiplex point-of-care diagnostics

With the recent shift in perspective in compacting diagnostic laboratories to recreate miniaturised and portable diagnostic tools that can perform rapid, on-site detection, novel nanomaterials have been explored for their application in developing unique point-of-care systems. Upon integration with CRISPR/Cas, it can perform large-scale screening and potentially be applied even under remote conditions, especially in sudden outbreaks and pandemics. Despite the high trans-cleavage activity of the CRISPR/Cas system to give a rapid fluorometric response, their application towards detecting target analytes from complex samples suffers from limited stability and sensitivity. On the contrary, nanomaterials demonstrate robust activity and versatile properties, including rapid optical and electrocatalytic activity, which places them in an ideal position to be applied as signal amplifier systems along with CRISPR/Cas. With the integration of trans-cleavage activity of CRISPR/Cas and nanomaterials, it is possible to develop the next generation of diagnostics that can detect various kinds of biomarkers using different optical and electrochemical transduction methods, which play a crucial role in personalised medicine and precision agriculture. Through this review, we aim to explore the recent advances in the field of CRISPR/Cas – nanomaterial-based biosensors that offer the promising potential to be applied in the highly sensitive and selective detection of multiple target analytes. The potential of applying such biosensors towards developing multiplex biosensors will also be explored, followed by the outlook of this promising diagnostic technology.