**4. Application of quantum dots in LFA to detect communicable (infectious) diseases**

Quantum dots have superior fluorescent properties that render them ideal labels. Their application in LFA has improved the detection sensitivity of LFA as a result of their chemical-physical properties (i.e. high signal-to-noise ratio, narrow emission, high fluorescent quantum yields, and broad excitation) [30]. The bright luminescence and stability of QDs qualify their use in LFA for the sensitive detection of communicable (infectious diseases) and non-communicable (chronic) diseases.

#### **4.1 Severe acute respiration syndrome coronavirus 2 (SARS-CoV-2)**

Severe acute respiration syndrome coronavirus 2 (SARS-CoV-2) originated in 2019 as the source of the coronavirus disease 2019 (COVID-19). Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) has been the primary test used for the molecular detection of SARS-CoV-2. Its application requires a certified laboratory infrastructure and trained personnel [31]. Nonetheless, for large-scale testing, quick results and contact tracing, RT-PCR is not a suitable diagnosis technique. COVID-19 diagnostic LFIA tests have provided fast, low-cost, and are a widely available tool for COVID-19 testing. Generally, these essential requirements are performed by serological tests based on lateral flow immunoassay (LFIA) [32]. The mechanism of COVID-19 detection/sensing using QDs is based on various paths that include; (i) inhibition of the binding of S protein receptors of the virus to the host cells, (ii) the generation of antiviral radicals upon exposure to light, (iii) reducing of viral RNA genome amplification and (iv) application of QDs as bright labels for COVID-19 [33, 34]. The unique properties (i.e. water solubility, small size ~10 nm, high sustainability, alluring photoluminescence) of carbon QDs (CQDs) have seen their application in the detection, inhibition, and treatment of viral infections [35]. Research on the interaction of QDs with genetic material (i.e. RNA and DNA), and cellular receptors to inhibit biological processes is still at its infancy. Nonetheless, their small sizes, ability to interact with cellular material, biocompatible nature and tuneable optical properties has seen growing reports on their importance in disease/virus inhibition processes. Loczechin et al., 2019 [33] reported on synthesizing carbon dots and their concentration-dependent interference with HCoV-229E-Luc infection. The mechanism of inhibition was said to be based on the CQD's ability to act in the early stages of virus infection by inhibiting the protein S-receptors with the host cell membrane. The group reported that the CQDs inhibited the HCoV-229E from entering the host cells infection as the functional groups of the CQDs interacted with the HCoV-229E entry receptors [36]. Another study by [19] reported on viral inhibition properties of CQDs via type 1 interferon responses. The study reported that the CQDs functioned by expressing IFN-stimulating genes (ISGs) and inducing interferon-α (IFN-α) production, which are responsible for inhibiting virus replication. Recently, Li et al., 2022 [36] reported on a smartphone-based QD-LFIA to detect IgG and Nab specific to SARS-CoV-2 in biological samples. The QDs were conjugated to anti-His mAb via covalent attachment (i.e. EDC/NHS). To enhance the performance of the LFIA, parameters such as the quantity of anti-His mAb-labeled QDs, the type of sample pads, the sample and the treatment buffer to reduce non-specific interactions within the QDs-LFIA were optimized. The developed QD-LFIA quantitatively detected IgG and Nab. The accurate and sensitive detection of the immune status of the clinical samples compared well with other methods. This highlights the progression in QD-LFIA application for the clinical detection of COVID-19.

#### **4.2 Human immunodeficiency virus (HIV)**

Human Immunodeficiency Virus (HIV) is an immunodeficiency disease that progresses into acquired immune deficiency syndrome (AIDS) at low CD4 levels (<200 cells/uL) [37, 38]. Currently, the most used approach to detect HIV is a dip-stick test which detects the virus antibodies [39]. The growing interest in the application of QDs for the detection of HIV is a result of QDs (i) small size that permits ease of flow over the strip, (ii) fluorescence lifetime and photostability, which enables QDs to be

#### *Application of Quantum Dots in Lateral Flow Immunoassays: Non-Communicable… DOI: http://dx.doi.org/10.5772/intechopen.107947*

signifiers for detection, (iii) a surface area-to-volume ratio that enables increasing binding sites and (iv) ability to combine with bio-molecules with ease as a result of their compatibility and stability [40, 41]. Deng et al., 2018 [41] used a fluorescent LFA strip to detect HIV-DNA quantitatively. The group used a one-step synthetic method to assemble the CdTe QDs with hairpin DNA as the reporter probe. At the same time, strand displacement amplification (SDA) worked as an amplification tool. The LFA consisted of a test and control zone on a nitrocellulose membrane immobilized with streptavidin in biotinylated t-DNA and cDNA, respectively. The developed LFA strip reproducibly detected HIV-DNA using CdTe-dsDNA (double-strand DNA) at a LOD of 0.76 pm.

#### **4.3 Influenza**

Influenza is seasonal endemic viruses that circulate yearly, causing mild to severe illnesses. Type A viruses such as (H1N1) and A (H3N2) are seasonal influenza caused by human infection. While Avian influenza viruses, A (H5N1) A(H5N6), A(H7N9), and A(H9N2), usually passed to domiciliary poultry leading to high disease surges resulting in life-threatening infections among humans [42]. Therefore, the accurate and fast diagnosis of influenza viruses is essential for early detection, hospital care and prevention of influenza infection outbreaks. The brightly fluorescent nature of QDs and bio-labelling properties have enabled the specific, accurate, quick, and simultaneous detection of *influenza* viruses. The sensitive, reproducible, and simultaneous detection of influenza A virus subtypes H5 and H9 using water-soluble COOH- functionalized QDs has been reported [43]. The QDs were covalently bounded to the influenza A virus antibodies and used as fluorescent tags in the LFA. The study harnessed the fluorescent signal produced by the QDs on the LFA strips to quantify the influenza A viruses (at LOD =0.016 HAU and 0.25 HAU for influenza virus H5 and H9 subtypes, respectively). In another study, Nguyen and co-workers [42] produced a CdSe/CdS/ ZnS QDs LFA for sensitive and quick analysis of two influenza subtypes (H1N1 and H3N2). The test and control lines were coated with anti-influenza monoclonal and goat anti-mouse IgG antibodies. Although the number of positive samples was limited, the study could detect A/H1N1 64-folds higher than rapid diagnostic test (RDT; Standard Diagnostics BIOLINE Influenza A/B). These works highlight the potential of fluorescent QDs-based LFAs for clinical use in detecting influenza strains.
