Second, appropriate sample collection method, including coughing out, saliva swabs, and direct collection from the salivary gland duct, ought to be pre-determined depending on the targeted biomarkers, since it may also affect the accuracy of final detection results. Biomedical Corporation), detecting the presence of morphine, methamphetamine (Chemtrue, Shanghai Kaichuang Biological Technology Co., Ltd), and helicobacter pylori (Helicobacter pylori Rapid detection test, Guangzhou BEISIQI Reagent CO., Ltd), as well as large-scale screening of coronavirus disease 2019 (COVID-19) (Bellagambi et?al., 2020) (Fig.?1). This perspective article mainly focuses on the potential value of saliva-based POCT for COVID-19 detection. Open in a separate window Fig.?1 Saliva-based applications. SPR, surface plasmon resonance; FET, field-effect transistor; QCM, quartz crystal microbalance; HIV, human immunodeficiency virus; COVID-19, coronavirus disease 2019. The COVID-19 pandemic has led to more than 446 million confirmed cases and over 6 million deaths worldwide ( Thus, efficient POCT techniques for mass screening to control COVID-19 are urgently needed. Currently, the most commonly adopted methods to detect COVID-19 involve serological testing or nasopharyngeal/oropharyngeal swabs, wherein samples are collected invasively and often require trained professionals for taking blood or nasopharyngeal and SirReal2 throat swabs, which not only cause discomfort to the testers but also put the trained personnel at risk. By contrast, saliva-based detection exhibits distinct merits since the noninvasive sample collection can be self-conducted, which induces minimal discomfort and the lowest cross-infection possibilities. Recent studies have reported the feasibility to detect either viral nucleic acid or related antibodies against COVID-19. The viral load in saliva is reported to be the highest during the first week after infection onset (To et?al., 2020). Besides, viral nucleic acid detection in saliva shows a higher sensitivity (84.2%) and specificity (98.9%) than that of nasopharyngeal/oropharyngeal swabs (Pasomsub et?al., 2021). Therefore, the direct monitoring of viral nucleic acid in saliva can act as an effective way to diagnose COVID-19, which is safe, timely and highly sensitive. However, nucleic acid detection alone is often inadequate to diagnose a specific disease, since it is influenced by the quality of the test techniques, thermal inactivation, and the cellular material content in the samples (Zhang et?al., 2020). In this regard, immunological diagnostic methods can overcome the shortcomings of nucleic-acid-based COVID-19 detection. As the unique evidence of a COVID-19 infection, the detection of related antibodies or antigens in saliva can help to confirm the infection status. Isho et?al. observed a significant positive correlation of various SARS-CoV-2-related antibodies in saliva and serum (Isho et?al., 2020). In our recent study, the correlation between IgG antibody levels in both saliva and serum was SirReal2 tested using an enzyme-linked immunosorbent assay (ELISA) kit. One hundred patients infected with COVID-19 were enrolled from Wuhan Jinyintan hospital. Among them, 94% of the serum samples tested positive for IgG antibodies, while 83% of the saliva samples were positive. The sensitivity and specificity of IgG antibody detection in saliva were 87.23% and 83.33%, respectively. Notably, the IgG antibody titers in SirReal2 saliva were positively correlated with DFNA13 those in serum (geneThe designed CRISPR-based LFA assay provides a visual and faster alternative to RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.LFA (Xiang et?al., 2020)SerumIgG, IgMThe LFA has demonstrated a clinical sensitivity, specificity, and accuracy of 57%, 100%, and 69% for IgM and 81%, 100%, and 86% for IgG, respectively.LFSM assay (Yu et?al., 2020)Nasopharyngeal swabs and sputumgene, gene, and geneThe percent positive agreement, percent negative agreement, and overall percent agreement of the LFSM assay with the commercial assay were 100% (94.2%C100%), 99.0% (94.6%C100%), SirReal2 and 99.4% (96.6%C100%), respectively.Nanozyme chemiluminescence paper (Liu et?al., 2020)Buffer solutionSARS-CoV-2 antigenThis testing can be completed within 16??min. The detection limit for recombinant spike antigen of SARS-CoV-2 was 0.1??ng/mL, with a linear range of 0.2C100??ng/mL.Electrochemical sensor (Raziq et?al., 2021)Nasopharyngeal swabSARS-CoV-2 nucleoprotein (ncovNP)The sensor showed a linear response to ncovNP in the lysis buffer up to 111??fmol/L with a detection and quantification limit of 15??fmol/L and 50??fmol/L, respectively, which was capable of signaling ncovNP presence in nasopharyngeal swab samples of COVID-19 positive patients.FET (Seo et?al., 2020)Nasopharyngeal swabSARS-CoV-2 spike proteinThe sensor detects target SARS-CoV-2 antigen protein with a limit of detection (LOD) of 1 1??fg/mL, which is able to detect SARS-CoV-2 virus in clinical samples.Colorimetric sensor (Moitra et?al., 2020)Nasopharyngeal swabgeneThe sensor exhibits a linear range of 0.2C3??ng/L, with a detection limit of 0.18??ng/L for SARS-CoV-2 RNA within 20??min.Colorimetric biosensor (COLOR) (Ferreira et?al., 2021)Nasopharyngeal/oropharyngealSARS-CoV-2 spike proteinThe sensor generates a result within 5??min, and it is highly sensitive (e.g., LOD of 154??fg/mL for SP), and demonstrates 90% accuracy in a study using 100 clinical samples.RAPID 1.0 (Torres et?al.,.