The emergence of
a new strain of coronavirus in late 2019, SARS-CoV-2,
led to a global pandemic in 2020. This may have been preventable if
large scale, rapid diagnosis of active cases had been possible, and
this has highlighted the need for more effective and efficient ways
of detecting and managing viral infections. In this work, we investigate
three different optical techniques for quantifying the binding of
recombinant SARS-CoV-2 spike protein to surface-immobilized oligonucleotide
aptamers. Biolayer interferometry is a relatively cheap, robust, and
rapid method that only requires very small sample volumes. However,
its detection limit of 250 nM means that it is not sensitive enough
to detect antigen proteins at physiologically relevant levels (sub-pM).
Surface plasmon resonance is a more sensitive technique but requires
larger sample volumes, takes longer, requires more expensive instrumentation,
and only reduces the detection limit to 5 nM. Surface-enhanced Raman
spectroscopy is far more sensitive, enabling detection of spike protein
to sub-picomolar
concentrations. Control experiments performed using scrambled aptamers
and using bovine serum albumin as an analyte show that this apta-sensing
approach is both sensitive and selective, with no appreciable response
observed for any controls. Overall, these proof-of-principle results
demonstrate that SERS-based aptasensors hold great promise for development
into rapid, point-of-use antigen detection systems, enabling mass
testing without any need for reagents or laboratory expertise and
equipment.