Design of MXene-Based Multiporous Nanosheet Stacking Structures Integrating Multiple Synergistic SERS Enhancements for Ultrasensitive Detection of Chloramphenicol.

Motivated by the desire for more sensitivity and stable surface-enhanced Raman scattering (SERS) substrates to trace detect chloramphenicol due to its high toxicity and ubiquity, MXene has attracted increasing attention and is encountering the high-priority task of further observably improving detection sensitivity. Herein, a universal SERS optimization strategy that incorporates NH4VO3 to induce few-layer MXenes assembling into multiporous nanosheet stacking structures was innovatively proposed. The synthesized Nb2C-based multiporous nanosheet stacking structure can achieve a low limit of detection of 10-10 M and a high enhancement factor of 2.6 × 109 for MeB molecules, whose detection sensitivity is improved by 3 orders of magnitude relative to few-layer Nb2C MXenes. Such remarkably enhanced SERS sensitivity mainly originates from the multiple synergistic contributions of the developed physical adsorption, the chemical enhancement, and the conspicuously improved electromagnetic enhancement arising from the intersecting MXenes. Furthermore, the improved SERS sensitivity endows Nb2C-based multiporous structures with the capability to achieve ultrasensitive detection of chloramphenicol with a wide linear range from 100 µg/mL to 1 ng/mL. We believe it is of great significance in conspicuously developing the SERS sensitivity of other MXenes with surficial negative charges and has a great promising perspective for the trace detection of other antibiotics in microsystems.

Dual-Mode Lateral Flow Immunoassay Based on "Pompon Mum"-Like Fe3O4@MoS2@Pt Nanotags for Sensitive Detection of Viral Pathogens.

Lateral flow immunoassay (LFIA) has been widely used for the early diagnosis of diseases. However, conventional colorimetric LFIA possesses limited sensitivity, and the single-mode readout signal is easily affected by the external environment, leading to insufficient accuracy. Herein, multifunctional Fe3O4@MoS2@Pt nanotags with a unique "pompon mum"-like structure were triumphantly prepared, exhibiting excellent peroxidase (POD)-like activity, photothermal properties, and magnetic separation capability. Furthermore, the Fe3O4@MoS2@Pt nanotags were used to establish dual-mode LFIA (dLFIA) for the first time, enabling the catalytic colorimetric and photothermal dual-mode detection of severe acute respiratory syndrome coronavirus 2 nucleocapsid protein (SARS-CoV-2 NP) and influenza A (H1N1). The calculated limits of detection (cLODs) of SARS-CoV-2 NP and H1N1 were 80 and 20 ng/mL in catalytic colorimetric mode and 10 and 8 ng/mL in photothermal mode, respectively, demonstrating about 100 times more sensitive than the commercial colloidal Au-LFIA strips (1 ng/mL for SARS-CoV-2 NP; 1 µg/mL for H1N1). The recovery rates of dLFIA in simulated nose swab samples were 95.2-103.8% with a coefficient of variance of 2.3-10.1%. These results indicated that the proposed dLFIA platform showed great potential for the rapid diagnosis of respiratory viruses.

Next-Generation Rapid and Ultrasensitive Lateral Flow Immunoassay for Detection of SARS-CoV-2 Variants.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for rapid and accurate viral detection at the point-of-care testing (POCT). Compared with nucleic acid detection, lateral flow immunoassay (LFIA) is a rapid and flexible method for POCT detection. However, the sensitivity of LFIA limits its use for early identification of patients with COVID-19. Here, an innovative surface-enhanced Raman scattering (SERS)-LFIA platform based on two-dimensional black phosphorus decorated with Ag nanoparticles as important antigen-capturing and Raman-signal-amplification unit was developed for detection of SARS-CoV-2 variants within 5-20 min. The novel SERS-LFIA platform realized a limit of detection of 0.5 pg/mL and 100 copies/mL for N protein and SARS-CoV-2, demonstrating 1000 times more sensitivity than the commercial LFIA strips. It could reliably detect seven different SARS-CoV-2 variants with cycle threshold (Ct) < 38, with sensitivity and specificity of 97 and 100%, respectively, exhibiting the same sensitivity with q-PCR. Furthermore, the detection results for 48 SARS-CoV-2-positive nasopharyngeal swabs (Ct = 19.8-38.95) and 96 negative nasopharyngeal swabs proved the reliability of the strips in clinical application. The method also had good specificity in double-blind experiments involving several other coronaviruses, respiratory viruses, and respiratory medications. The results showed that the innovative SERS-LFIA platform is expected to be the next-generation antigen detection technology. The inexpensive amplification-free assay combines the advantages of rapid low-cost POCT and highly sensitive nucleic acid detection, and it is suitable for rapid detection of SARS-CoV-2 variants and other pathogens. Thus, it could replace existing antigens and nucleic acids to some extent.

Recent development of surface-enhanced Raman scattering for biosensing.

Surface-Enhanced Raman Scattering (SERS) technology, as a powerful tool to identify molecular species by collecting molecular spectral signals at the single-molecule level, has achieved substantial progresses in the fields of environmental science, medical diagnosis, food safety, and biological analysis. As deepening research is delved into SERS sensing, more and more high-performance or multifunctional SERS substrate materials emerge, which are expected to push Raman sensing into more application fields. Especially in the field of biological analysis, intrinsic and extrinsic SERS sensing schemes have been widely used and explored due to their fast, sensitive and reliable advantages. Herein, recent developments of SERS substrates and their applications in biomolecular detection (SARS-CoV-2 virus, tumor etc.), biological imaging and pesticide detection are summarized. The SERS concepts (including its basic theory and sensing mechanism) and the important strategies (extending from nanomaterials with tunable shapes and nanostructures to surface bio-functionalization by modifying affinity groups or specific biomolecules) for improving SERS biosensing performance are comprehensively discussed. For data analysis and identification, the applications of machine learning methods and software acquisition sources in SERS biosensing and diagnosing are discussed in detail. In conclusion, the challenges and perspectives of SERS biosensing in the future are presented.

Recent Advances of Representative Optical Biosensors for Rapid and Sensitive Diagnostics of SARS-CoV-2.

The outbreak of Corona Virus Disease 2019 (COVID-19) has again emphasized the significance of developing rapid and highly sensitive testing tools for quickly identifying infected patients. Although the current reverse transcription polymerase chain reaction (RT-PCR) diagnostic techniques can satisfy the required sensitivity and specificity, the inherent disadvantages with time-consuming, sophisticated equipment and professional operators limit its application scopes. Compared with traditional detection techniques, optical biosensors based on nanomaterials/nanostructures have received much interest in the detection of SARS-CoV-2 due to the high sensitivity, high accuracy, and fast response. In this review, the research progress on optical biosensors in SARS-CoV-2 diagnosis, including fluorescence biosensors, colorimetric biosensors, Surface Enhancement Raman Scattering (SERS) biosensors, and Surface Plasmon Resonance (SPR) biosensors, was comprehensively summarized. Further, promising strategies to improve optical biosensors are also explained. Optical biosensors can not only realize the rapid detection of SARS-CoV-2 but also be applied to judge the infectiousness of the virus and guide the choice of SARS-CoV-2 vaccines, showing enormous potential to become point-of-care detection tools for the timely control of the pandemic.

Localized plasmonic sensor for direct identifying lung and colon cancer from the blood.

The tissue inhibitor of metalloproteinases-1 (TIMP-1) protein can regulate the expression of certain proteases and microRNAs in cancer cells, and it is highly possible to diagnose cancers through analyzing the expression of TIMP-1 on exosomes. However, it is still a great challenge to obtain reliable physiological information on TIMP-1 by label-free method from exosomes in plasma. Here, we designed a porous-plasmonic SERS chip functionalized with synthesized CP05 polypeptide, which can specifically capture and distinguish exosomes from diverse origins. The SERS chip can accurately locate the plasmon in TIMP-1 protein to analyze the discrepancy of related fingerprint peaks of different exosomes. Based on the designed SERS chip, we successfully distinguished the lung and colon cancer cell-derived exosomes from normal exosomes at the single vesicle level by unique Raman spectroscopy and machine learning methods. This work not only provides a practical SERS chip for the application of Raman technology in human tumor monitoring and prognosis, but also provides a new idea for analyzing the feature of exosomes at the spectral level.

High-sensitivity and point-of-care detection of SARS-CoV-2 from nasal and throat swabs by magnetic SERS biosensor.

The outbreak of COVID-19 caused by SARS-CoV-2 urges the development of rapidly and accurately diagnostic methods. Here, one high-sensitivity and point-of-care detection method based on magnetic SERS biosensor composed of Fe3O4-Au nanocomposite and Au nanoneedles array was developed to detect SARS-CoV-2 directly. Among, the magnetic Fe3O4-Au nanocomposite is applied to capture and separate virus from nasal and throat swabs and enhance the Raman signals of SARS-CoV-2. The magnetic SERS biosensor possessed high sensitivity by optimizing the Fe3O4-Au nanocomposite. More significantly, the on-site detection of inactivated SARS-CoV-2 virus was achieved based on the magnetic SERS biosensor with ultra-low limit of detection of 100 copies/mL during 15 mins. Furthermore, the contaminated nasal and throat swabs samples were identified by support vector machine, and the diagnostic accuracy of 100% was obtained. The magnetic SERS biosensor combined with support vector machine provides giant potential as the point-of-care detection tool for SARS-CoV-2.

Identifying infectiousness of SARS-CoV-2 by ultra-sensitive SnS2 SERS biosensors with capillary effect.

The current COVID-19 pandemic urges us to develop ultra-sensitive surface-enhanced Raman scattering (SERS) substrates to identify the infectiousness of SARS-CoV-2 virions in actual environments. Here, a micrometer-sized spherical SnS2 structure with the hierarchical nanostructure of "nano-canyon" morphology was developed as semiconductor-based SERS substrate, and it exhibited an extremely low limit of detection of 10-13 M for methylene blue, which is one of the highest sensitivities among the reported pure semiconductor-based SERS substrates. Such ultra-high SERS sensitivity originated from the synergistic enhancements of the molecular enrichment caused by capillary effect and the charge transfer chemical enhancement boosted by the lattice strain and sulfur vacancies. The novel two-step SERS diagnostic route based on the ultra-sensitive SnS2 substrate was presented to diagnose the infectiousness of SARS-CoV-2 through the identification standard of SERS signals for SARS-CoV-2 S protein and RNA, which could accurately identify non-infectious lysed SARS-CoV-2 virions in actual environments, whereas the current PCR methods cannot.

Human ACE2-Functionalized Gold "Virus-Trap" Nanostructures for Accurate Capture of SARS-CoV-2 and Single-Virus SERS Detection.

The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold "virus traps" nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106-fold virus enrichment originating from high-affinity of ACE2 with S protein as well as "virus-traps" composed of oblique gold nanoneedles, and 109-fold enhancement of Raman signals originating from multi-component SERS effects. Furthermore, the identification standard of virus signals is established by machine-learning and identification techniques, resulting in an especially low detection limit of 80 copies mL-1 for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min, which is of great significance for achieving real-time monitoring and early warning of coronavirus. Moreover, here-developed method can be used to establish the identification standard for future unknown coronavirus, and immediately enable extremely sensitive and rapid detection of novel virus. Supplementary Information: The online version contains supplementary material available at 10.1007/s40820-021-00620-8.

Charge-Transfer Resonance and Electromagnetic Enhancement Synergistically Enabling MXenes with Excellent SERS Sensitivity for SARS-CoV-2 S Protein Detection.

The outbreak of coronavirus disease 2019 has seriously threatened human health. Rapidly and sensitively detecting SARS-CoV-2 viruses can help control the spread of viruses. However, it is an arduous challenge to apply semiconductor-based substrates for virus SERS detection due to their poor sensitivity. Therefore, it is worthwhile to search novel semiconductor-based substrates with excellent SERS sensitivity. Herein we report, for the first time, Nb2C and Ta2C MXenes exhibit a remarkable SERS enhancement, which is synergistically enabled by the charge transfer resonance enhancement and electromagnetic enhancement. Their SERS sensitivity is optimized to 3.0 × 106 and 1.4 × 106 under the optimal resonance excitation wavelength of 532 nm. Additionally, remarkable SERS sensitivity endows Ta2C MXenes with capability to sensitively detect and accurately identify the SARS-CoV-2 spike protein. Moreover, its detection limit is as low as 5 × 10-9 M, which is beneficial to achieve real-time monitoring and early warning of novel coronavirus. This research not only provides helpful theoretical guidance for exploring other novel SERS-active semiconductor-based materials but also provides a potential candidate for the practical applications of SERS technology.

Theoretical and Experimental Studies of Ti3C2 MXene for Surface-Enhanced Raman Spectroscopy-Based Sensing.

Recent advances in MXenes with high carrier mobility show great application prospects in the surface-enhanced Raman scattering (SERS) field. However, challenges remain regarding the improvement of the SERS sensitivity. Herein, an effective strategy considering charge-transfer resonance for semiconductor-based substrates is presented to optimize the SERS sensitivity with the guidance of the density functional theory calculation. The theoretical calculation predicted that the excellent SERS enhancement for methylene blue (MeB) on Ti3C2 MXene can be excited by both 633 and 785 nm lasers, and the Raman enhanced effect is mainly originated from the charge-transfer resonance enhancement. In this work, the Ti3C2 MXenes exhibit an excellent SERS sensitivity with an enhancement factor of 2.9 × 106 and a low detection limit of 10-7 M for MeB molecules. Furthermore, the SERS enhancement of Ti3C2 and Au-Ti3C2 substrates exhibit higher selectivity on different molecules, which contributes to the detection of target molecules in complex solution environments. This work can provide some theoretical and experimental basis for the research on SERS activity of other MXene materials.

Pt Nanoparticles with High Oxidase-Like Activity and Reusability for Detection of Ascorbic Acid.

Noble metal nanoenzymes such as Pt, Au, Pd, etc. exhibit magnificent activity. However, due to the scarce reserves and expensive prices of precious metals, it is essential to investigate their enzyme-like activity and explore the possibility of their reuse. In this work, the oxidase-like activity and reusability of several Pt nanoparticles with different morphologies were detected. We compared the Pt nanoparticles (NPs) with a size of about 30 nm self-assembled by 5 nm Pt nanoparticles and Pt nanoparticles (Pt-0 HCl) with a diameter of about 5 nm, and found that their Michaelis-Menten constants (Km) were close and their initial performance similar, but the Pt NPs had better reusability. This was probably attributed to the stacked structure of Pt NPs, which was conducive to the substance transport and sufficient contact. At the same time, it was found that the size, dispersion, and organic substances adsorbed on the surface of Pt nanoparticles would have a significant impact on their reusability. A colorimetric detection method was designed using the oxidase-like activity of Pt NPs to detect ascorbic acid in triplicate. The limits of detection were 131 ± 15, 144 ± 14, and 152 ± 9 nM, with little difference. This research not only showed that the morphology of the catalyst could be changed and its catalytic performance could be controlled by a simple liquid phase synthesis method, but also that it had great significance for the reuse of Pt nanoenzymes in the field of bioanalysis.

A Novel Ultra-Sensitive Semiconductor SERS Substrate Boosted by the Coupled Resonance Effect.

Recent achievements in semiconductor surface-enhanced Raman scattering (SERS) substrates have greatly expanded the application of SERS technique in various fields. However, exploring novel ultra-sensitive semiconductor SERS materials is a high-priority task. Here, a new semiconductor SERS-active substrate, Ta2O5, is developed and an important strategy, the "coupled resonance" effect, is presented, to optimize the SERS performance of semiconductor materials by energy band engineering. The optimized Mo-doped Ta2O5 substrate exhibits a remarkable SERS sensitivity with an enhancement factor of 2.2 × 107 and a very low detection limit of 9 × 10-9 m for methyl violet (MV) molecules, demonstrating one of the highest sensitivities among those reported for semiconductor SERS substrates. This remarkable enhancement can be attributed to the synergistic resonance enhancement of three components under 532 nm laser excitation: i) MV molecular resonance, ii) photoinduced charge transfer resonance between MV molecules and Ta2O5 nanorods, and iii) electromagnetic enhancement around the "gap" and "tip" of anisotropic Ta2O5 nanorods. Furthermore, it is discovered that the concomitant photoinduced degradation of the probed molecules in the time-scale of SERS detection is a non-negligible factor that limits the SERS performance of semiconductors with photocatalytic activity.

Multifunctional Ag-decorated g-C3N4 nanosheets as recyclable SERS substrates for CV and RhB detection.

In this study, g-C3N4/Ag hybrid nanostructures were fabricated by facilely decorating silver nanoparticles on atmosphere-treated g-C3N4 and served as efficient SERS-active substrates. The observed significant SERS enhancement of crystal violet (CV) molecules on g-C3N4/Ag could be attributed to the high ability to concentrate target molecules through π-π stacking interactions and the near-field enhancement caused by the boosting SPR effect of the Ag NPs. The atmosphere and calcination time have a considerable impact on the SERS enhancement effect of the g-C3N4/Ag substrate. Furthermore, it took only 10 min to degrade dye molecules under visible light, and after 6 cycles the g-C3N4/Ag substrates still maintained sensitive SERS activity. This research indicates that g-C3N4/Ag hybrids can be applied as reusable SERS substrates.