ABSTRACT
Significance In 2009, influenza A (H1N1) broke out in Mexico and the United States, influencing 214 countries and killing at least 14000 people. The novel coronavirus epidemic which broke out in 2020 has still been raging all over the world for two years as the results of the huge difficulty in the rapid and real-time epidemic prevention detection and the other reasons. In addition, the spread of other viruses including dengue virus (DENV) and human immunodeficiency virus (HIV) is also threatening human health significantly. Virus detection is the key to curb the spread of the viruses. At present, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), as the gold standard in the field of virus detection, can be used to detect and trace virus samples with a high sensitivity. But these samples need to be collected to the laboratory, and the viruses must be isolated and determined using the sophisticated lab equipment operated by professionals in order to get accurate results. Surface plasmon resonance (SPR)and local surface plasmon resonance (LSPR) biosensors may be an effective alternative, as their structures are simple and easy to be miniaturized. Especially, the LSPR-based device only needs a light source and some sensing elements. Once the sensing elements successfully capture the virus, the detection process will be quickly, sensitively, and selectively finished. These characteristics of the SPR and LSPR techniques show their great application potential in the field of virus detection, especially for the point-of-care testing with limited conditions. With the rapid development of SPR and LSPR-based virus detection researches, researchers have reviewed the progress of materials and structures of sensors, methods for plasmonic virus detection, and their characteristics of signal amplification, and so on. According to the four general virus detection methods and starting from the four kinds of target analytes captured by the sensor, this paper systematically outlines the latest researches of the SPR and LSPR techniques for detecting viruses, which are of great significance for their clinical application (Fig. 1). Progress First, according to the four methods for virus detection, the application progress of SPR and LSPR in the fields of antibody, antigen, nucleic acid, and virus particle detection is reviewed successively. For the SPR or LSPR sensors based on the binding principle of specific antigen-antibodies, the detection limit is further optimized by modifying the appropriate antigens or antibodies. More stable and inexpensive aptamers and molecularly imprinted polymers are expected to replace antibodies as sensor recognition elements to detect virus antigens or particles. Because the number of virus genomes in clinical samples is usually very small, the detection of nucleic acid by SPR or LSPR alone is limited. However, the detection of virus samples with the concentration at the femto scale can be realized by combining SPR or LSPR with DNA amplification and fluorescent substances. Second, the problems of biological medium contamination and repeatability encountered by biosensors as well as their solutions are introduced (Fig. 13). As for the contamination of biological media, self-assembled monolayers (SAM) can be synthesized on the surface of sensor elements to alleviate this problem. Riedel et al. further reduced or even completely inhibited the biological contamination of plasma and serum by synthesizing polymer brushes. In order to ensure the repeatability of sensing elements, Yoo et al. used magnetic beads replaced under the control of magnetic field as the sensing element, allowing that the sensor chip could still work stably after many repeated measurements. Third, the configurations and parameters of the SPR and LSPR sensors for virus detection in the past 15 years are listed (Table 1), and the advantages of the SPR and LSPR techniques are described. Finally, the optimization strategies of the SPR and LSPR techniques and the present existing problems are summarized. Moreover, e application prospect is also forecasted. Conclusion and Prospect According to the current research progress, the optimization strategy of the SPR sensor mainly focuses on film material sensitization and metal particle coupling sensitization. The former includes the application of 2D materials and molecular imprinting through the construction of surface films to enhance practicality and applicability. In contrast, the latter uses nanoparticles to form sandwich structures. The LSPR sensing strategies are concentrated on the design and optimization of nanoparticles or nanostructures, which are often combined with fluorescent substances such as quantum dots (QDs) to form sensing probes for virus detection by the light absorption peak shift or the fluorescence intensity change. The LSPR biosensors are normally easier to be miniaturized than the SPR counterparts. In a word, the SPR and LSPR sensors show great application prospects in the field of virus detection. Predictably, owing to the diversity of the SPR and LSPR virus sensor modifiers, it may be possible to detect specific viruses for multiple target analytes at the same time through the integration of sensor recognition elements, which enables the multi-dimensional evaluation of virus infection in a short time to avoid false negative and false positive cases. © 2022 Science Press. All rights reserved.
ABSTRACT
BACKGROUND: Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to µg mL-1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. RESULTS: In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL-1 within only a 15-min detection time and 500 µL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL-1 and a broad dynamic detection range of five orders of magnitude. CONCLUSION: Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs.