Nucleic acid amplification-free detection of DNA and RNA at ultralow concentration

The broad spectrum of approaches for nucleic acid amplification-free detection of DNA and RNA at single-digit attomolar (10^-18 M) concentration and lower is reviewed. These low concentrations correspond roughly to the most clinically desirable detection range for pathogen-specific nucleic acid as well as the detection limits of commercially available, nucleic acid amplification tests based primarily on polymerase chain reaction (PCR). The need for more rapid and inexpensive, yet still highly accurate tests, has become evident during the pandemic. It is expected that publication of reports describing improved tests will accelerate soon, and this review covers the wide variety of detection methods based on both optical and electrical measurements that have been conceived over recent years, enabled generally by the advent of nanotechnology.