Near-infrared responsive gold nanorods for highly sensitive colorimetric and photothermal lateral flow immuno-detection of SARS-CoV-2.

The highly infectious characteristics of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the necessity of sensitive and rapid nucleocapsid (N) protein-based antigen testing for early triage and epidemic management. In this study, a colorimetric and photothermal dual-mode lateral flow immunoassay (LFIA) platform for the rapid and sensitive detection of the SARS-CoV-2 N protein was developed based on gold nanorods (GNRs), which possessed tunable local surface plasma resonance (LSPR) absorption peaks from UV-visible to near-infrared (NIR). The LSPR peak was adjusted to match the NIR emission laser 808 nm by controlling the length-to-diameter ratio, which could maximize the photothermal conversion efficiency and achieve photothermal detection signal amplification. Qualitative detection of SARS-CoV-2 N protein was achieved by observing the strip color, and the limit of detection was 2 ng mL-1, while that for photothermal detection was 0.096 ng mL-1. Artificial saliva samples spiked with the N protein were analyzed with the recoveries ranging from 84.38% to 107.72%. The intra-assay and inter-assay coefficients of variation were 6.76% and 10.39%, respectively. We further evaluated the reliability of this platform by detecting 40 clinical samples collected from nasal swabs, and the results matched well with that of nucleic acid detection (87.5%). This method shows great promise in early disease diagnosis and screening.

One-pot synthesized Au@Pt nanostars-based lateral flow immunoassay for colorimetric and photothermal dual-mode detection of SARS-CoV-2 nucleocapsid antibody.

In addition to confirming virus infection, quantitative identification of the antibodies to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) also evaluates persons immunity to guide personal protection. However, portable assays for fast and accurate quantification of SARS-CoV-2 antibodies remain challenging. In this work, we synthesized Au@Pt star-like nanoparticles (NPs) quickly and easily by a one-pot wet-chemical approach, allowing the stellate Au core to be partially decorated by Pt nanoshells. The nanoparticles were used as probe in a lateral flow immunoassay (LFIA) that operated in both colorimetric and photothermal dual modes, which could detect the antibodies to the SARS-CoV-2 nucleocapsid (N) protein with high sensitivity. Due to the sharp tips on the external region of nanostars and surface plasmon coupling effect between the Au core and Pt shell, the NIR absorption capacity and photothermal performance of these NPs were exceptional. Under optimal conditions, the colorimetric mode's detection limit for SARS-CoV-2 N protein antibody was 1 ng mL-1, which is significantly lower by 2-order of magnitude compared to commercially available colloidal gold strips. And the detection limit for the photothermal mode was as low as 24.91 pg mL-1, which was approximately 40-fold more sensitive than colorimetric detection. Moreover, the method demonstrated favorable specificity, reproducibility and stability. Finally, the approach was employed for the successful identification of actual serum samples. Therefore, the dual-mode LFIA can be applied for screening and tracking the early immunological reaction to SARS-CoV-2, and it has great promise for clinical application.

High-density Au nanoshells assembled onto Fe3O4 nanoclusters for integrated enrichment and photothermal/colorimetric dual-mode detection of SARS-CoV-2 nucleocapsid protein.

Traditional lateral flow immunoassays (LFIA) suffer from insufficient sensitivity, difficulty for quantitation, and susceptibility to complex substrates, limiting their practical application. Herein, we developed a polyethylenimine (PEI)-mediated approach for assembling high-density Au nanoshells onto Fe3O4 nanoclusters (MagAushell) as LFIA labels for integrated enrichment and photothermal/colorimetric dual-mode detection of SARS-CoV-2 nucleocapsid protein (N protein). PEI layer served not only as "binders" to Fe3O4 nanoclusters and Au nanoshells, but also "barriers" to ambient environment. Thus, MagAushell not only combined magnetic and photothermal properties, but also showed good stability. With MagAushell, N protein was first separated and enriched from complex samples, and then loaded to the strip for detection. By observation of the color stripes, qualitative detection was performed with naked eye, and by measuring the temperature change under laser irradiation, quantification was attained free of sophisticated instruments. The introduction of Fe3O4 nanoclusters facilitated target purification and enrichment before LFIA, which greatly improved the anti-interference ability and increased the detection sensitivity by 2 orders compared with those without enrichment. Moreover, the high loading density of Au nanoshells on one Fe3O4 nanocluster enhanced the photothermal signal of the nanoprobe significantly, which could further increase the detection sensitivity. The photothermal detection limit reached 43.64 pg/mL which was 1000 times lower than colloidal gold strips. Moreover, this method was successfully applied to real samples, showing great application potential in practice. We envision that this LFIA could serve not only for SARS-CoV-2 detection but also as a general test platform for other biotargets in clinical samples.

An achromatic colorimetric nanosensor for sensitive multiple pathogen detection by coupling plasmonic nanoparticles with magnetic separation.

Rapid screening of multiple pathogens will greatly improve the efficiency of pandemic prevention and control. Colorimetric methods exhibit the advantages of convenience, portability, low cost, time efficiency, and free of sophisticated instruments, yet usually have difficulties in simultaneous detection and suffer from monotonous color changes with low visual resolution and sensitivity. Hence, coupled three kinds of plasmonic nanoparticles (NPs) with magnetic separation, we developed an achromatic colorimetric nanosensor with highly enhanced visual resolution for simultaneous detection of SARS-CoV-2, Staphylococcus aureus, and Salmonella typhimurium. The achromatic nanosensor was composed of SARS-CoV-2-targeting red gold NPs, S. aureus-targeting yellow silver NPs and S. typhimurium-targeting blue silver triangle NPs mixed as black color. In the detection, three corresponding magnetic probes were added into the above mixture. In the presence of a target pathogen, it would be recognized and combined with corresponding colored reporters and magnetic probes to form sandwich complexes, which were removed by magnetic separation, and the sensor changed from black to a chromatic color (the color of the reporters remained in supernatant). Consequently, different target pathogen induced different color. For example, SARS-CoV-2, S. aureus, and S. typhimurium respectively produced green, purple, and orange. While coexistence of S. aureus and S. typhimurium produced red, and coexistence of S. aureus and SARS-CoV-2 produced blue, etc. Therefore, by observing the color change or measuring the absorption spectra, multiple pathogen detection was achieved conveniently. Compared with most colorimetric sensors, this achromatic nanosensor involved rich color change, thus significantly enhancing visual resolution and inspection sensitivity. Therefore, this sensor opened a promising avenue for efficient monitoring and early warning of food safety and quality.

Colorimetric and Raman dual-mode lateral flow immunoassay detection of SARS-CoV-2 N protein antibody based on Ag nanoparticles with ultrathin Au shell assembled onto Fe3O4 nanoparticles.

Serological antibody tests are useful complements of nuclei acid detection for SARS-CoV-2 diagnosis, which can significantly improve diagnostic accuracy. However, antibody detection in serum or plasma remains challenging to do with high sensitivity. In this study, Ag nanoparticles with ultra-thin Au shells embedded with 4-mercaptobenzoic acid (MBA) (AgMBA@Au) were manufactured and then assembled onto Fe3O4 surface by electrostatic interaction to construct the Fe3O4-AgMBA@Au nanoparticles (NPs) with magnetic-Raman-colorimetric properties. Based on the composite nanoparticles, a colorimetric and Raman dual-mode lateral flow immunoassay (LFIA) for ultrasensitive identification of SARS-CoV-2 nucleocapsid (N) protein antibody was constructed. The magnetic nanoparticles (Fe3O4 NPs) were acted as the core and coated a layer of AgMBA@Au particles on the surface by electrostatic interaction to prepare Fe3O4-AgMBA@Au NPs, which can amplify the SERS signal due to multiple AgMBA@Au particles concentrated on a single magnetic nanoparticle. Moreover, the Fe3O4-AgMBA@Au NPs facilitated pre-purifying sample using magnetic separation, and complex matrix interference would be greatly decreased in the detection. The Fe3O4-AgMBA@Au NPs modified with N protein recognized and bound with N protein antibodies, which were trapped on the T-line, forming color band for observing detection. Under optimal conditions, the N protein antibodies could be qualitatively detected in colorimetric mode with the visual limit of 10-8 mg/mL and quantitatively detected by SERS signals between 10-6 and 10-10 mg /mL with 0.08 pg/mL detection limit. The coefficients variations (CV) of intra-assay was 8.0%, whereas of inter-assay was 11.7%, confirming of good reproducibility. Finally, this approach was able to discriminate between positive, negative, and weakly positive samples when detecting 107 clinical serum samples. The process enables highly sensitive quantitative assays that are valuable for evaluating disease processes and guiding treatment. Colorimetric and Raman dual-mode LFIA detection of SARS-CoV-2 N protein antibody based on Fe3O4-AgMBA@Au nanoparticles.

Fatigue Resistant Aerogel/Hydrogel Nanostructured Hybrid for Highly Sensitive and Ultrabroad Pressure Sensing.

Achieving high sensitivity over a broad pressure range remains a great challenge in designing piezoresistive pressure sensors due to the irreconcilable requirements in structural deformability against extremely high pressures and piezoresistive sensitivity to very low pressures. This work proposes a hybrid aerogel/hydrogel sensor by integrating a nanotube structured polypyrrole aerogel with a polyacrylamide (PAAm) hydrogel. The aerogel is composed of durable twined polypyrrole nanotubes fabricated through a sacrificial templating approach. Its electromechanical performance can be regulated by controlling the thickness of the tube shell. A thicker shell enhances the charge mobility between tube walls and thus expedites current responses, making it highly sensitive in detecting low pressure. Moreover, a nucleotide-doped PAAm hydrogel with a reversible noncovalent interaction network is harnessed as the flexible substrate to assemble the aerogel/hydrogel hybrid sensor and overcome sensing saturation under extreme pressures. This highly stretchable and self-healable hybrid polymer sensor exhibits linear response with high sensitivity (Smin  > 1.1 kPa-1 ), ultrabroad sensing range (0.12-≈400 kPa), and stable sensing performance over 10 000 cycles at the pressure of 150 kPa, making it an ideal sensing device to monitor pressures from human physiological signals to significant stress exerted by vehicles.