Dual-Modal Colorimetric and Surface-Enhanced Raman Scattering (SERS)-Based Lateral Flow Immunoassay for Ultrasensitive Detection of SARS-CoV-2 Using a Plasmonic Gold Nanocrown.

The 2019 coronavirus disease (COVID-19) outbreak created an unprecedented need for rapid, sensitive, and cost-effective point-of-care diagnostic tests to prevent and mitigate the spread of the SARS-CoV-2 virus. Herein, we demonstrated an advanced lateral flow immunoassay (LFIA) platform with dual-functional [colorimetric and surface-enhanced Raman scattering (SERS)] detection of the spike 1 (S1) protein of SARS-CoV-2. The nanosensor was integrated with a specially designed core-gap-shell morphology consisting of a gold shell decorated with external nanospheres, a structure referred to as gold nanocrown (GNC), labeled with a Raman reporter molecule 1,3,3,1',3',3'-hexamethyl-2,2'-indotricarbocyanine iodide (HITC) to produce a strong colorimetric signal as well as an enhanced SERS signal. Among the different plasmonics-active GNC nanostructures, the GNC-2 morphology, which has a shell decorated with an optimum number and size of nanospheres, produces an intense dark-blue colorimetric signal and ultrahigh SERS signal. The limit of detection (LOD) of the S1 protein via colorimetric detection LFIA was determined to be 91.24 pg/mL. On the other hand, the LOD for the SERS LFIA method was more than three orders of magnitude lower at 57.21 fg/mL. Furthermore, we analyzed the performance of the GNC-2 nanosensor for directly analyzing the S1 protein spiked in saliva samples without any sample pretreatment and achieving the LOD as low as 39.65 fg/mL using SERS-based plasmonics-enhanced LFIA, indicating ultrahigh detection sensitivity. Overall, our GNC nanosensor showed excellent sensitivity, reproducibility, and rapid detection of the SARS-CoV-2 S1 protein, demonstrating excellent potential as a promising point-of-care platform for the early detection of respiratory virus infections.

A simple low-cost flexible plasmonic patch based on spiky gold nanostars for ultra-sensitive SERS sensing.

Recently, transparent and flexible surface-enhanced Raman scattering (SERS) substrates have received great interest for direct point-of-care detection of analytes on irregular nonplanar surfaces. In this study, we proposed a simple cost-effective strategy to develop a flexible SERS patch utilizing multibranched sharp spiked gold nanostars (GNS) decorated on a commercially available adhesive Scotch Tape for achieving ultra-high SERS sensitivity. The experimental SERS measurements were correlated with theoretical finite element modeling (FEM), which indicates that the GNS having a 2.5 nm branch tip diameter (GNS-4) exhibits the strongest SERS enhancement. Using rhodamine 6G (R6G) as a model analyte, the SERS performance of the flexible SERS patch exhibited a minimum detection limit of R6G as low as 1 pM. The enhancement factor of the SERS patch with GNS-4 was calculated as 6.2 × 108, which indicates that our flexible SERS substrate has the potential to achieve ultra-high sensitivity. The reproducibility was tested with 30 different spots showing a relative standard deviation (RSD) of SERS intensity of about 5.4%, indicating good reproducibility of the SERS platform. To illustrate the usefulness of the flexible SERS sensor patch, we investigated the detection of a carcinogenic compound crystal violet (CV) on fish scales, which is often used as an effective antifungal agent in the aquaculture industry. The results realized the trace detection of CV with the minimum detection limit as low as 1 pM. We believe that our transparent, and flexible SERS patch based on GNS-4 has potential as a versatile, low-cost platform for real-world SERS sensing applications on nonplanar surfaces.

Rapid SERS assay for determination of the opioid fentanyl using silver-coated sharply branched gold nanostars.

A high-throughput surface-enhanced Raman scattering (SERS)-sensing platform is presented for FNT detection in human urine without any sample preparation. The sensing platform is based on plasmonics-active silver-coated sharply branched gold nanostars (SGNS). The effect of silver thickness was investigated experimentally and theoretically, and the results indicated that SERS enhancement was maximum at an optimum silver thickness of 45 nm on the sharply spiked SGNS. The proposed high-throughput SERS platform exhibited ultrahigh sensitivity and excellent enhancement uniformity for a model analyte, i.e., crystal violet. Moreover, the SERS-sensing platform demonstrated good sensitivity of FNT spiked in human urine samples with two differential linear response ranges of 2 to 0.2 µg/mL and 0.1 µg/mL to 100 pg/mL, respectively,  with a detection limit as low as 10.02 pg/mL. The spiked human urine samples show satisfactory recovery values from 92.5 to 102% with relative standard deviations (RSD) of less than 10%. In summary, the high-throughput performance of the proposed microplate-based SERS platform demonstrated great potential for rapid low-cost SERS-based sensing applications.

Improved solution-based SERS detection of creatinine by inducing hydrogen-bonding interaction for effective analyte capture.

Recently, solution-based surface-enhanced Raman scattering (SERS) detection technique has been widely recognized due to its cost-effectiveness, simplicity, and ease of use. However, solution-based SERS is limited for practical applications mainly because of the weak adsorption affinity of the target biomolecules to the surface of plasmonic nanoparticles. Herein, we developed a highly sensitive solution-based SERS sensing platform based on mercaptopropionic acid (MPA)-capped silver-coated gold nanostars (SGNS@MPA), which allows efficient enrichment on the nanostars surface for improved detection of an analyte: creatinine, a potential biomarker of chronic kidney disease (CKD). The SGNS@MPA exhibited high enrichment ability towards creatinine molecules in alkaline medium (pH-9) through multiple hydrogen bonding interaction, which causes aggregation of the nanoparticles and enhances the SERS signal of creatinine. The detection limit for creatinine was achieved at 0.1 nM, with a limit of detection (LOD) value of 14.6 pM. As a proof-of-concept demonstration, we conducted the first quantitative detection of creatinine in noninvasive human fluids, such as saliva and sweat, under separation-free conditions. We achieved a detection limit of up to 1 nM for both saliva and sweat, with LOD values as low as 0.136 nM for saliva and 0.266 nM for sweat. Overall, our molecular enrichment strategy offers a new way to improve the solution-based SERS detection technique for real-world practical applications in point-of-care settings and low-resource settings.