Gold-silver alloy hollow nanoshells-based lateral flow immunoassay for colorimetric, photothermal, and SERS tri-mode detection of SARS-CoV-2 neutralizing antibody

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)−temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of Ttype lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS−temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS−temperature synchronous dualmode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer onsite by simultaneous POC detection of t-PSA and f-PSA in blood.

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SERS–Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood

Fang,

Li,

Lin

et al. 2024

“…15 These emerging signal tags aim to achieve multisignal output and enable a multimodal complementary analysis approach. 16 For instance, Li et al constructed a composite nanomaterial MagAu shell NPs for colorimetric/photothermal dual-mode analysis that increased the sensitivity and accuracy of detection. 17 Yin et al proposed a cascade multimodal immunoassay using PtNiCo@ TA trimetallic nanoflowers as signal labels, which broadened the multisignal output capability of the nanoenzyme and achieved highly sensitive detection of the target.…”

Section: ■ Introductionmentioning

confidence: 99%

“…To overcome this inherent constraint, various composite nanoparticles have been designed with capabilities such as fluorescence, photothermal, magnetic, , electrochemical signal, , and catalysis signals . These emerging signal tags aim to achieve multisignal output and enable a multimodal complementary analysis approach . For instance, Li et al constructed a composite nanomaterial MagAu shell NPs for colorimetric/photothermal dual-mode analysis that increased the sensitivity and accuracy of detection .…”

Section: Introductionmentioning

confidence: 99%

“Three-in-One” Multifunctional Hollow Nanocages with Colorimetric Photothermal Catalytic Activity for Enhancing Sensitivity in Biosensing

Wu,

Bu,

Sun

et al. 2024

Immunochromatographic assays (ICAs) have been widely used in the field detection of mycotoxin contaminants. Nevertheless, the lack of multisignal readout capability and the ability of signaling tags to maintain their biological activity while efficiently loading antibodies remain a great challenge in satisfying diverse testing demands. Herein, we proposed a novel three-in-one multifunctional hollow vanadium nanomicrosphere (high brightness-catalytic-photothermal properties)-mediated triple-readout ICA (VHMS-ICA) for sensitive detection of T-2. As the key to this biosensing strategy, vanadium was used as the catalytic-photothermal characterization center, and natural polyphenols were utilized as the bridging ligands for coupling with the antibody while self-assembling with formaldehyde crosslinking into a hollow nanocage-like structure, which offers the possibility of realizing a three-signal readout strategy and improving the coupling efficiency to the antibody while preserving its biological activity. The constructed sensors showed a detection limit (LOD) of 2 pg/mL for T-2, which was about 345-fold higher than that of conventional gold nanoparticle-based ICA (0.596 ng/mL). As anticipated, the detection range of VHMS-ICA was extended about 8fold compared with the colorimetric signal alone. Ultimately, the proposed immunosensor performed well in maize and oat samples, with satisfactory recoveries. Owing to the synergistic and complementary interactions between distinct signaling modes, the establishment of multimodal immunosensors with multifunctional tags is an efficient strategy to satisfy diversified detection demands.

“…Due to their ease of use, low costs, and the ability to implement LFAs in areas where access to RT-qPCR is limited, these systems have become essential for point-of-care diagnostics . In fact, several studies have already reported the development of a LFA for the detection of neutralizing antibodies against SARS-CoV-2, employing functionalized gold nanoparticles (AuNPs) − or other labeling agents such as nanoshells, , latex microspheres, , quantum dots, europium nanoparticles, cellulose nanobeads, polydopamine nanoparticles, and aggregation-induced emission luminogen encapsulated polystyrene nanoparticles . However, these studies mainly rely on neutralizing the ACE2–RBD interaction but do not consider the full-length trimeric S protein, consisting of an S1 subunit with RBD and the S2 subunit (for each monomer).…”

mentioning

confidence: 99%

Application of a Biomimetic Nanoparticle-Based Mock Virus to Determine SARS-CoV-2 Neutralizing Antibody Levels in Blood Samples Using a Lateral Flow Assay

Schobesberger,

Thumfart,

Selinger

et al. 2024

The presence of neutralizing antibodies against SARS-CoV-2 in blood, acquired through previous infection or vaccination, is known to prevent the (re)occurrence of outbreaks unless the virus mutates. Therefore, the measurement of neutralizing antibodies constitutes an indispensable tool in assessing an individual’s and a population’s immunity against SARS-CoV-2. For this reason, we have developed an innovative lateral flow assay (LFA) capable of detecting blood-derived neutralizing antibodies using a biomimetic SARS-CoV-2 mock virus system. Here, functionalized gold nanoparticles (AuNPs) featuring the trimeric spike (S) protein at its surface imitate the virus’s structure and are applied to monitor the presence and efficacy of neutralizing antibodies in blood samples. The detection principle relies on the interaction between mock virus and the immobilized angiotensin-converting enzyme 2 (ACE2) receptor, which is inhibited when neutralizing antibodies are present. To further enhance the sensitivity of our competitive assay and identify low titers of neutralizing antibodies, an additional mixing pad is embedded into the device to increase the interaction time between mock virus and neutralizing antibodies. The developed LFA is benchmarked against the WHO International Standard (21/338) and demonstrated reliable quantification of neutralizing antibodies that inhibit ACE2 binding events down to a detection limit of an antibody titer of 59 IU/mL. Additional validation using whole blood and plasma samples showed reproducible results and good comparability to a laboratory-based reference test, thus highlighting its applicability for point-of-care testing.