Multiple Fano Resonances in Plasmonic Waveguide Based Cavity and Detection of Pathogenic Virus

A technique is implemented for the generation of multiple Fano-resonances in a plasmonic waveguide based rectangular cavity. A rectangular cavity provides four Fano peaks which can further be increased to nine by inserting the metallic bars in it. The trapped surface plasmon polaritons by metallic bars cause the generation of multiple Fano peaks over the wavelength range of 450 nm - 1300 nm. The obtained response is validated through Fano profile and Fano shape parameter is calculated for each resonance peak. The performance of the proposed device is numerically studied as refractive index sensor and method for analyzing the detection of pathogenic virus like SARS-Cov-2 is reported. Out of nine Fano peaks, the best values of sensing performance indices are obtained with full-width, half-maxima of 1.7 nm, quality factor of 405, sensitivity of 1145.71 nm/RIU and figure of merit of 393.25 RIU-1. IEEE

Plasmonic Scattering Imaging of Surface-Bonded Nanoparticles at the Solution-Solid Interface.

Imaging nanoscale objects at interfaces is essential for revealing surface-tuned mechanisms in chemistry, physics, and life science. Plasmonic-based imaging, a label-free and surface-sensitive technique, has been widely used for studying the chemical and biological behavior of nanoscale objects at interfaces. However, direct imaging of surface-bonded nanoscale objects remains challenging due to uneven image backgrounds. Here, we present a new surface-bonded nanoscale object detection microscopy that eliminates strong background interference by reconstructing accurate scattering patterns at different positions. Our method effectively functions at low signal-to-background ratios, allowing for optical scattering detection of surface-bonded polystyrene nanoparticles and severe acute respiratory syndrome coronavirus 2 pseudovirus. It is also compatible with other imaging configurations, such as bright-field imaging. This technique complements existing methods for dynamic scattering imaging and broadens the applications of plasmonic imaging techniques for high-throughput sensing of surface-bonded nanoscale objects, enhancing our understanding of the properties, composition, and morphology of nanoparticles and surfaces at the nanoscale.

A Sensitive Biosensor Based on Plasmonic-Graphene Configuration for Detection of COVID-19 Virus.

In this paper, four individual structures based on graphene-plasmonic nano combinations are proposed for detection of corona viruses and especially COVID-19. The structures are arranged based on arrays in the shapes of half-sphere and one-dimensional photonic crystal formats. The half-sphere and plate shaped layers are made of Al, Au, SiO2 and graphene. The one-dimensional photonic crystals lead the wavelength and peak corresponding to the absorption peak to lower and higher amounts, respectively. In order to improve the functionality of the proposed structures, effects of structural parameters and chemical potentials are considered. A defect layer of GZO is positioned in the middle of one-dimensional photonic crystal layers to shift the absorption's peak wavelength to the appropriate wavelength range for diagnosing corona viruses (~300 nm to 600 nm). The last proposed structure is considered as a refractive bio-sensor for detection of corona viruses. In the final proposed structure (based on different layers of Al, Au, SiO2, GZO and graphene), corona viruses are considered as the biomolecule layer and the results are obtained. The proposed bio-sensor can be a good and functional candidate for detection of corona viruses and especially COVID-19 in photonic integrated circuits with the satisfying sensitivity of ~664.8 nm/RIU (refractive index unit).

Sensitivity enhanced tunable plasmonic biosensor using two-dimensional twisted bilayer graphene superlattice

This study theoretically demonstrated an insight for designing a novel tunable plasmonic biosensor, which was created by simply stacking a twisted bilayer graphene (TBG) superlattice onto a plasmonic gold thin film. To achieve ultrasensitive biosensing, the plasmonic biosensor was modulated by Goos-Hänchen (GH) shift. Interestingly, our proposed biosensor exhibited tunable biosensing ability, largely depending on the twisted angle. When the relative twisted angle was optimized to be 55.3°, such a configuration: 44 nm Au film/1-TBG superlattice could produce an ultralow reflectivity of 2.2038 × 10-9and ultra-large GH shift of 4.4785 × 104μm. For a small refractive index (RI) increment of 0.0012 RIU (refractive index unit) in sensing interface, the optimal configuration could offer an ultra-high GH shift detection sensitivity of 3.9570 × 107μm/RIU. More importantly, the optimal plasmonic configuration demonstrated a theoretical possibility of quantitatively monitoring severe acute respiratory syndrome coronavirus (SARS-CoV-2) and human hemoglobin. Considering an extremely small RI change as little as 3 × 10-7RIU, a good linear response between detection concentration of SARS-CoV-2 and changes in differential GH shift was studied. For SARS-CoV-2, a linear detection interval was obtained from 0 to 2 nM. For human hemoglobin, a linear detection range was achieved from 0 to 0.002 g/L. Our work will be important to develop novel TBG-enhanced biosensors for quantitatively detecting microorganisms and biomolecules in biomedical application. © 2023 the author(s), published by De Gruyter, Berlin/Boston 2023.

Metamaterial enhanced novel plasmonic biosensor for specific detection of SARS-CoV-2 spike protein

In this study, we theoretically propose a surface plasmon resonance (SPR) biosensor composed of a plasmonic gold film, double negative (DNG) metamaterial, graphene-MoS2-COOH Van der Waals heterostructures and gold nanoparticles (Au NPs). We use a novel scheme of Goos-Hanchen (GH) shift to study the biosensing performances of our proposed plasmonic biosensor. The calculation results show that, both an extreme low reflectivity of 8.52×10-10 and significantly enhanced GH sensitivity of 2.1530×107 μm/RIU can be obtained, corresponding to the optimal configuration: 32 nm Au film/120 nm metamaterial/4-layer graphene/4-layer MoS2-COOH. In addition, there is a theoretically excellent linear response between the concentration of target analytes (SARS-CoV-2 and S protein) and the change in differential GH shift. Our proposed biosensor promises to be a useful tool for performing the novel coronavirus detection. © 2023 SPIE.

The role of biosensors in coronavirus disease-2019 outbreak.

Herein, we have summarized and argued about biomarkers and indicators used for the detection of severe acute respiratory syndrome coronavirus 2. Antibody detection methods are not considered suitable to screen individuals at early stages and asymptomatic cases. The diagnosis of coronavirus disease 2019 using biomarkers and indicators at point-of-care level is much crucial. Therefore, it is urgently needed to develop rapid and sensitive detection methods which can target antigens. We have critically elaborated key role of biosensors to cope the outbreak situation. In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor, and surface plasmon resonance biosensors in the detection of severe acute respiratory syndrome coronavirus 2 has been underscored. Finally, we have outlined pros and cons of diagnostic approaches and future directions.

Ultrafast Plasmonic Nucleic Acid Amplification and Real-Time Quantification for Decentralized Molecular Diagnostics.

Point-of-care real-time reverse-transcription polymerase chain reaction (RT-PCR) facilitates the widespread use of rapid, accurate, and cost-effective near-patient testing that is available to the public. Here, we report ultrafast plasmonic nucleic acid amplification and real-time quantification for decentralized molecular diagnostics. The plasmonic real-time RT-PCR system features an ultrafast plasmonic thermocycler (PTC), a disposable plastic-on-metal (PoM) cartridge, and an ultrathin microlens array fluorescence (MAF) microscope. The PTC provides ultrafast photothermal cycling under white-light-emitting diode illumination and precise temperature monitoring with an integrated resistance temperature detector. The PoM thin film cartridge allows rapid heat transfer as well as complete light blocking from the photothermal excitation source, resulting in real-time and highly efficient PCR quantification. Besides, the MAF microscope exhibits close-up and high-contrast fluorescence microscopic imaging. All of the systems were fully packaged in a palm size for point-of-care testing. The real-time RT-PCR system demonstrates the rapid diagnosis of coronavirus disease-19 RNA virus within 10 min and yields 95.6% of amplification efficiency, 96.6% of classification accuracy for preoperational test, and 91% of total percent agreement for clinical diagnostic test. The ultrafast and compact PCR system can decentralize point-of-care molecular diagnostic testing in primary care and developing countries.

Overview of Optical Biosensors for Early Cancer Detection: Fundamentals, Applications and Future Perspectives.

Conventional cancer detection and treatment methodologies are based on surgical, chemical and radiational processes, which are expensive, time consuming and painful. Therefore, great interest has been directed toward developing sensitive, inexpensive and rapid techniques for early cancer detection. Optical biosensors have advantages in terms of high sensitivity and being label free with a compact size. In this review paper, the state of the art of optical biosensors for early cancer detection is presented in detail. The basic idea, sensitivity analysis, advantages and limitations of the optical biosensors are discussed. This includes optical biosensors based on plasmonic waveguides, photonic crystal fibers, slot waveguides and metamaterials. Further, the traditional optical methods, such as the colorimetric technique, optical coherence tomography, surface-enhanced Raman spectroscopy and reflectometric interference spectroscopy, are addressed.

Label-free detection and discrimination of respiratory pathogens based on electrochemical synthesis of biomaterials-mediated plasmonic composites and machine learning analysis.

Seasonal outbreaks of respiratory viral infections remain a global concern, with increasing morbidity and mortality rates recorded annually. Timely and false responses contribute to the widespread of respiratory pathogenic diseases owing to similar symptoms at an early stage and subclinical infection. The prevention of emerging novel viruses and variants is also a big challenge. Reliable point-of-care diagnostic assays for early infection diagnosis play a critical role in the response to threats of epidemics or pandemics. We developed a facile method for specifically identifying different viruses based on surface-enhanced Raman spectroscopy (SERS) with pathogen-mediated composite materials on Au nanodimple electrodes and machine learning (ML) analyses. Virus particles were trapped in three-dimensional plasmonic concave spaces of the electrode via electrokinetic preconcentration, and Au films were simultaneously electrodeposited, leading to the acquisition of intense and in-situ SERS signals from the Au-virus composites for ultrasensitive SERS detection. The method was useful for rapid detection analysis (<15 min), and the ML analysis for specific identification of eight virus species, including human influenza A viruses (i.e., H1N1 and H3N2 strains), human rhinovirus, and human coronavirus, was conducted. The highly accurate classification was achieved using the principal component analysis-support vector machine (98.9%) and convolutional neural network (93.5%) models. This ML-associated SERS technique demonstrated high feasibility for direct multiplex detection of different virus species for on-site applications.

Thermal-annealing-regulated plasmonic enhanced fluorescence platform enables accurate detection of antigen/antibody against infectious diseases.

Plasmonic enhanced fluorescence (PEF) technology is a powerful strategy to improve the sensitivity of immunofluorescence microarrays (IFMA), however, current approaches to constructing PEF platforms are either expensive/time-consuming or reliant on specialized instruments. Here, we develop a completely alternative approach relying on a two-step protocol that includes the self-assembly of gold nanoparticles (GNPs) at the water-oil interface and subsequent annealing-assisted regulation of gold nanogap. Our optimized thermal-annealing GNPs (TA-GNP) platform generates adequate hot spots, and thus produces high-density electromagnetic coupling, eventually enabling 240-fold fluorescence enhancement of probed dyes in the near-infrared region. For clinical detection of human samples, TA-GNP provides super-high sensitivity and low detection limits for both hepatitis B surface antigen and SARS-CoV-2 binding antibody, coupled with a much-improved detection dynamic range up to six orders of magnitude. With fast detection, high sensitivity, and low detection limit, TA-GNP could not only substantially improve the outcomes of IFMA-based precision medicine but also find applications in fields of proteomic research and clinical pathology. Electronic Supplementary Material: Supplementary material (UV-Vis absorption and transmission spectra of GNPs, SEM, microscopy and digital images of PEF platforms, and fluorescence images of IFMA on PEF platforms) is available in the online version of this article at 10.1007/s12274-022-5035-6.

Plasmonic Biosensors with Nanostructure for Healthcare Monitoring and Diseases Diagnosis.

Nanophotonics has been widely utilized in enhanced molecularspectroscopy or mediated chemical reaction, which has major applications in the field of enhancing sensing and enables opportunities in developing healthcare monitoring. This review presents an updated overview of the recent exciting advances of plasmonic biosensors in the healthcare area. Manufacturing, enhancements and applications of plasmonic biosensors are discussed, with particular focus on nanolisted main preparation methods of various nanostructures, such as chemical synthesis, lithography, nanosphere lithography, nanoimprint lithography, etc., and describing their respective advances and challenges from practical applications of plasmon biosensors. Based on these sensing structures, different types of plasmonic biosensors are summarized regarding detecting cancer biomarkers, body fluid, temperature, gas and COVID-19. Last, the existing challenges and prospects of plasmonic biosensors combined with machine learning, mega data analysis and prediction are surveyed.

Plasmonic/magnetic nanoarchitectures: From controllable design to biosensing and bioelectronic interfaces.

Controllable design of the nanocrystal-assembled plasmonic/magnetic nanoarchitectures (P/MNAs) inspires abundant methodologies to enhance light-matter interactions and control magnetic-induced effects by means of fine-tuning the morphology and ordered packing of noble metallic or magnetic building blocks. The burgeoning development of multifunctional nanoarchitectures has opened up broad range of interdisciplinary applications including biosensing, in vitro diagnostic devices, point-of-care (POC) platforms, and soft bioelectronics. By taking advantage of their customizability and efficient conjugation with capping biomolecules, various nanoarchitectures have been integrated into high-performance biosensors with remarkable sensitivity and versatility, enabling key features that combined multiplexed detection, ease-of-use and miniaturization. In this review, we provide an overview of the representative developments of nanoarchitectures that being built by plasmonic and magnetic nanoparticles over recent decades. The design principles and key mechanisms for signal amplification and quantitative sensitivity have been explored. We highlight the structure-function programmability and prospects of addressing the main limitations for conventional biosensing strategies in terms of accurate selectivity, sensitivity, throughput, and optoelectronic integration. State-of-the-art strategies to achieve affordable and field-deployable POC devices for early multiplexed detection of infectious diseases such as COVID-19 has been covered in this review. Finally, we discuss the urgent yet challenging issues in nanoarchitectures design and related biosensing application, such as large-scale fabrication and integration with portable devices, and provide perspectives and suggestions on developing smart biosensors that connecting the materials science and biomedical engineering for personal health monitoring.

Phase-based plasmonic biosensor for SARS-COV-2 virus detection

The detection scheme based on phase detection of SPR response was developed. We show that the proposed biosensing scheme can detect SARS-CoV-2 genetic material with high specificity, low detection limit and short detection time. © Optica Publishing Group 2022 The Authors.

Phase-based plasmonic biosensor for SARS-COV-2 virus detection

The detection scheme based on phase detection of SPR response was developed. We show that the proposed biosensing scheme can detect SARS-CoV-2 genetic material with high specificity, low detection limit and short detection time. © Optica Publishing Group 2022 The Authors.

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting.

Plasmonic metasurfaces (PMs) functionalized with the monoclonal antibody (mAb) are promising biophotonic sensors for biomolecular interaction analysis and convenient immunoassay of various biomarkers, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Previous PM biosensing suffers from the slow affinity detection rate and lack of sufficient immunoassay studies on various SARS-CoV-2 variants. Here, we develop a high-efficiency affinity testing method based on label-free PM sensors with mAbs and demonstrate their binding characteristics to 12 spike receptor binding domain (RBD) variants of SARS-CoV-2. In addition to the research of plasmonic near-field influence on surface biomolecule sensing, we provide a comprehensive report about the Langmuir binding equilibrium of molecular kinetics between 12 SARS-CoV-2 RBD variants and mAb-functionalized PMs, which plays a crucial role in label-free immunosensing. A high-affinity mAb can be combined with the highly sensitive propagating plasmonic mode to boost the detection of SARS-CoV-2 variants. Owing to a better understanding of molecular dynamics on PMs, we develop an ultrasensitive biosensor of the SARS-CoV-2 Omicron variant. The experiments show great distinguishment of P < 0.0001 from respiratory diseases induced by other viruses, and the limit of detection is 2 orders smaller than the commercial colloidal gold immunoassay. Our study shows the label-free biosensing by low-cost wafer-scale PMs, which will provide essential information on biomolecular interaction and facilitate high-precision point-of-care testing for emerging SARS-CoV-2 variants in the future.

Bioinspired Plasmo-virus for Point-of-Care SARS-CoV-2 Detection.

Directly identifying the presence of the virus in infected hosts with an appropriate speed and sensitivity permits early epidemic management even during the presymptomatic incubation period of infection. Here, we synthesize a bioinspired plasmo-virus (BPV) particle for rapid and sensitive point-of-care (POC) detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via a self-assembled plasmonic nanoprobe array on spike proteins. The BPV enables strong near-infrared (NIR) extinction peaks caused by plasmonic nanogaps. We quantify SARS-CoV-2 in viral transport medium (VTM) at low titers within 10 min with a limit of detection (LOD) of 1.4 × 101 pfu/mL, which is 103 times more sensitive than the current gold-standard method. The high-sensitivity and high-speed POC detection may be widely used for the timely, individualized diagnosis of infectious agents in low-resource settings.

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.

Advanced Plasmonic Nanoparticle-Based Techniques for the Prevention, Detection, and Treatment of Current COVID-19.

Coronavirus is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2. Coronavirus disease 2019 known as COVID-19 is the worst pandemic since World War II. The outbreak of COVID-19 had a significant repercussion on the health, economy, politics, and environment, making coronavirus-related issues more complicated and becoming one of the most challenging pandemics of the last century with deadly outcomes and a high rate of the reproduction number. There are thousands of different types - or variants - of COVID circulating across the world. Viruses mutate all the time; it emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis, and effective antiviral and protective therapeutics. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis, and treatment of COVID-19. This review presents an outline of the platforms developed using plasmonic nanoparticles in the detection, treatment, and prevention of SARS-CoV-2. We select the best strategies in each of these approaches. The properties of metallic plasmon NPs and their relevance in the development of novel point-of-care diagnosis approaches for COVID-19 are highlighted. Also, we discuss the current challenges and the future perspectives looking towards the clinical translation and the commercial aspects of nanotechnology and plasmonic NP-based diagnostic tools and therapy to fight COVID-19 pandemic. The article could be of significance for researchers dedicated to developing suitable plasmonic detection tools and therapy approaches for COVID-19 viruses and future pandemics.

Development of a Single-Chain Variable Fragment of CR3022 for a Plasmonic-Based Biosensor Targeting the SARS-CoV-2 Spike Protein.

Two years after SARS-CoV-2 caused the first case of COVID-19, we are now in the "new normal" period, where people's activity has bounced back, followed by the easing of travel policy restrictions. The lesson learned is that the wide availability of accurate and rapid testing procedures is crucial to overcome possible outbreaks in the future. Therefore, many laboratories worldwide have been racing to develop a new point-of-care diagnostic test. To aid continuous innovation, we developed a plasmonic-based biosensor designed explicitly for portable Surface Plasmon Resonance (SPR). In this study, we designed a single chain variable fragment (scFv) from the CR3022 antibody with a particular linker that inserted a cysteine residue at the second position. It caused the linker to have a strong affinity to the gold surface through thiol-coupling and possibly become a ready-to-use bioreceptor toward a portable SPR gold chip without purification steps. The theoretical affinity of this scFv on spike protein was -64.7 kcal/mol, computed using the Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method from the 100 ns molecular dynamics trajectory. Furthermore, the scFv was produced in Escherichia coli BL21 (DE3) as a soluble protein. The binding activity toward Spike Receptor Binding Domain (RBD) SARS-CoV-2 was confirmed with a spot-test, and the experimental binding free energy of -10.82 kcal/mol was determined using portable SPR spectroscopy. We hope this study will be useful in designing specific and low-cost bioreceptors, particularly early in an outbreak when the information on antibody capture is still limited.

Colorimetric Detection of SARS-CoV-2 Using Plasmonic Biosensors and Smartphones.

Low-cost, instrument-free colorimetric tests were developed to detect SARS-CoV-2 using plasmonic biosensors with Au nanoparticles functionalized with polyclonal antibodies (f-AuNPs). Intense color changes were noted with the naked eye owing to plasmon coupling when f-AuNPs form clusters on the virus, with high sensitivity and a detection limit of 0.28 PFU mL-1 (PFU stands for plaque-forming units) in human saliva. Plasmon coupling was corroborated with computer simulations using the finite-difference time-domain (FDTD) method. The strategies based on preparing plasmonic biosensors with f-AuNPs are robust to permit SARS-CoV-2 detection via dynamic light scattering and UV-vis spectroscopy without interference from other viruses, such as influenza and dengue viruses. The diagnosis was made with a smartphone app after processing the images collected from the smartphone camera, measuring the concentration of SARS-CoV-2. Both image processing and machine learning algorithms were found to provide COVID-19 diagnosis with 100% accuracy for saliva samples. In subsidiary experiments, we observed that the biosensor could be used to detect the virus in river waters without pretreatment. With fast responses and requiring small sample amounts (only 20 µL), these colorimetric tests can be deployed in any location within the point-of-care diagnosis paradigm for epidemiological control.