A Review of THz Technologies for Rapid Sensing and Detection of Viruses including SARS-CoV-2

Abstract

Virus epidemics such as Ebola virus, Zika virus, MERS-coronavirus, and others have wreaked havoc on humanity in the last decade. In addition, a coronavirus (SARS-CoV-2) pandemic and its continuously evolving mutants have become so deadly that they have forced the entire technical advancement of healthcare into peril. Traditional ways of detecting these viruses have been successful to some extent, but they are costly, time-consuming, and require specialized human resources. Terahertz-based biosensors have the potential to lead the way for low-cost, non-invasive, and rapid virus detection. This review explores the latest progresses in terahertz technology-based biosensors for the virus, viral particle, and antigen detection, as well as upcoming research directions in the field.

Keywords: SARS-CoV-2; biosensing; immunobiosensing; metasenors; plasmonics; terahertz.

Figure 1

Schematic presentation of spherical genome structure of the SARS-CoV-2. Reprinted with permission from [29]. Copyright 2020 Springer.

Figure 2

A visual summary of the currently available SARS-CoV-2 detection process. Reprinted with permission from [39]. Copyright 2020 American Chemical Society.

Figure 3

(a) Schematic of a standard THz-TDS setup, (b) time domain THz pulse, and (c) frequency domain THz pulse. Reprinted with permission from [48]. Copyright 2019 Wiley.

Figure 4

(a) Diagram of virus detection with THz nano-gap metamaterial. (b) Image (SEM) of viruses (width of gap 200 nm) and THz transmission amplitudes (normalized) of THz metamaterials with deposited PRD1 of different surface densities for gap width of (c) w = 3 µm (d) w = 200 nm. Reprinted with permission from [42]. Copyright 2019 The Optical Society.

Figure 5

(a) Absorption spectra for pallet types of viruses included a protein sample (H9N2) and a control sample (without virus). (b) A conceptual schematic of THz detection of virus samples. (c) Optical images of dropped virus solutions onto the multi-resonance nano-antenna array before (top) and after (down) THz excitation. (d–g) Normalized THz spectra for various concentrations (0, 1, 0.14, 0.28 mg/mL) of H9N2 virus in buffer solution. Reprinted with permission from [49]. Copyright 2017 Springer.

Figure 6

(a) 3D schematic diagram of the THz biosensing metamaterial absorber (b) geometrical parameters, (c) FDTD simulation results of absorption spectroscopy for three equivalent AI virus model samples: n + iκ (H5N2), n + 1.4iκ (H1N1), 1.2n + 1.4iκ (H9N2), (d) ΔA and ΔF of three different AI virus model samples: n + iκ (H5N2), n + 1.4iκ (H1N1), 1.2n + 1.4iκ (H9N2), (e) FDTD simulation results of absorption spectroscopy with analyte thickness for H9N2, (f) ΔFth versus different virus thickness of H9N2. Reprinted with permission from [52]. Copyright 2018 Wiley.

Figure 7

(a) Artistic perspective of compositional plasmonic resonators, (b) schematic demonstration of ZIKV envelope protein binding with respective antibody and transmission spectra for the toroidal resonant mode behavior for presence of different concentration of ZIKV envelope protein from (c) antibody to 50 pg/mL and (d) 100 pg/mL to 104 pg/mL. Reprinted with permission from [59]. Copyright 2017 American Chemical Society.

Figure 8

(a) Schematic flowchart of functionalized gold nanoparticle conjugation with ZIKV-AB and ZIKV-EPs NS1 with an explanation of the different parts. (b) Schematic representation of gold-nanoparticle-integrated toroidal unit cells. SEM images of a plasmonic metamolecule in the presence of (c) GNPs with AB and (d) ZIKV-Eps. (e) Transmission amplitude spectra for W/and W/O GNPs regimes in the presence of ZIKV-AB and ZIKV-EPs with different concentrations. (f) The toroidal resonance shift as a function of ZIKV-EPs concentration W/and W/O GNPs, and (g) the magnified transmission spectra as a function of frequency. Reprinted with permission from [63].

Figure 9

(a) Schematic illustration of the unit cell, (b) simulated reflection spectrum of biosensor in different mediums metamaterial reflector and (c) simulated results of reflectance spectra for different AI virus vs. frequency. Reprinted with permission from [65]. Copyright 2019 IEEE.

Figure 10

(a) Changes in orientation angle as κ is increased from 0 to 0.4 calculated at the frequencies where dominant power is reflected as cross-polarized fields. (b) contour path traversed by locus tip of electric field vector in time at fixed frequency of 1.7 THz for κ = 0 0 and κ = 0.4. (b) Magnitude response of (i) co-polarized (ii) cross-polarized reflection coefficients of the sensor for three different strains of Influenza viruses H1N1, H5N2 and H9N2. (c) PER and (d) Orientation angle spectrum for three different strains of influenza viruses H1N1, H5N2 and H9N2. The contour path traversed by locus tip of electric field vector in time at fixed frequency of (e) 1.364 THz and (f) 1.717 THz for all three strains of viruses. Reprinted with permission from [66]. Copyright 2021 Elsevier.

Figure 11

(a) Schematic of the THz hybrid slot antenna with protruding AgNWs. (b) fabrication processes for the THz hybrid slot antenna, (c) FDTD simulation transmission spectra through the bare slot antenna with (red) and without (black) PMMA [L = 200 μm and wgap = 15 μm]. (d) Transmission spectra through the hybrid slot antenna with (red) and without (black) PMMA for lNW = 5 μm. (e) Resonant-frequency shift as a function of the total number of AgNWs (NNW). (f) Enhancement factor as a function of wgap for fixed NNW = 80 and lNW/wgap = 1/3. Reprinted with permission from [67]. Copyright 2018 Springer.

Figure 12

(a) Plot of tan δ versus ratio of binding sites of H9 HA and F10 and negative control, and H9 HA solutions. (b) Specificity and sensitivity measurements by ELISA. Reprinted with permission from [68]. Copyright 2015 SPIE.

Figure 13

(a) Terahertz reflection (S11) properties of aptamer, aptamer/Zika, and Zika on polyester substrate. (b) Reflection spectra minima of different materials on polyester substrate. (c) Terahertz reflection coefficient of different aptamer and Zika on graphene. (d) Terahertz reflection minima for different analytes on graphene. Reprinted with permission from [69].

Figure 14

(a) Schematic workflow of the developed functionalized gold NPs conjugated with the respective SARS-CoV-2 antibody and spike proteins. (b) Measured transmission spectra of the THz metasensor device for different concentrations (4 fmol to 12 fmol) of SARS-CoV-2 spike protein. (c,d) Measured transmission spectra of the THz metasensor device for different concentrations (from 4 fmol to 30 fmol) of BSA and SARS-CoV-2 spike protein + BSA, respectively. Reprinted with permission from [70]. Copyright 2021 Elsevier.