Terahertz time-domain spectroscopy (THz-TDS) is a non-invasive, non-contact and label-free technique for biological and chemical sensing as THz-spectra are less energetic and lie in the characteristic vibration frequency regime of proteins and DNA molecules. However, THz-TDS is less sensitive for the detection of micro-organisms of size equal to or less than λ/100 (where, λ is the wavelength of the incident THz wave), and molecules in extremely low concentration solutions (like, a few femtomolar). After successful high-throughput fabrication of nanostructures, nanoantennas were found to be indispensable in enhancing the sensitivity of conventional THz-TDS. These nanostructures lead to strong THz field enhancement when in resonance with the absorption spectrum of absorptive molecules, causing significant changes in the magnitude of the transmission spectrum, therefore, enhancing the sensitivity and allowing the detection of molecules and biomaterials in extremely low concentration solutions. Herein, 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 the sub-skin depth as well as sub-nanometer sized nanogaps. We introduce finite-difference time-domain (FDTD) and molecular dynamics (MD) simulation 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.
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