  Terahertz time-domain spectroscopy (THz-TDS) is a non-invasive, non-contact
and label-free technique for biological and chemical sensing as THz-spectra is
less energetic and lies in the characteristic vibration frequency regime of
proteins and DNA molecules. However, THz-TDS is less sensitive for detection of
micro-organisms of size equal to or less than $ \lambda/100 $ (where, $ \lambda
$ is wavelength of incident THz wave) and, molecules in extremely low
concentrated solutions (like, a few femtomolar). After successful
high-throughput fabrication of nanostructures, nanoantennas and metamaterials
were found to be indispensable in enhancing the sensitivity of conventional
THz-TDS. These nanostructures lead to strong THz field enhancement which when
in resonance with absorption spectrum of absorptive molecules, causing
significant changes in the magnitude of the transmission spectrum, therefore,
enhancing the sensitivity and allowing detection of molecules and biomaterials
in extremely low concentrated solutions. Hereby, we review the recent
developments in ultra-sensitive and selective nanogap biosensors. We have also
provided an in-depth review of various high-throughput nanofabrication
techniques. We also discussed the physics behind the field enhancements in
sub-skin depth as well as sub-nanometer sized nanogaps. We introduce
finite-difference time-domain (FDTD) and molecular dynamics (MD) simulations
tools to study THz biomolecular interactions. Finally, we provide a
comprehensive account of nanoantenna enhanced sensing of viruses (like, H1N1)
and biomolecules such as artificial sweeteners which are addictive and
carcinogenic.
