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Schematic representation of the surface-enhanced Raman scattering (SERS) from the electromagnetic (EM) effect.

Schematic representation of the surface-enhanced Raman scattering (SERS) from the electromagnetic (EM) effect.

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The diagnosis of respiratory viruses of zoonotic origin (RVsZO) such as influenza and coronaviruses in humans is crucial, because their spread and pandemic threat are the highest. Surface enhanced Raman spectroscopy (SERS) is an analytical technique with promising impact for the point-of-care diagnosis of viruses. It has been applied to a variety o...

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... phenomenon is known as surface plasmon resonance (SPR) [15]. Especially in some regions called hot spots, an intense local field enhancement is produced around the metal interface by the concentration of light, which creates an oscillating dipole on the molecules in close proximity with the nanoparticles; this results in an oscillating dipole that enhances the radiation efficiency ( Figure 1) [15,16]. In this situation, the magnitude of the electromagnetic field between the nanoparticle center and the analyte decays with distance. ...
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... that, the corresponding samples to be analyzed were put in contact with the surface of the experimental and control zones, followed by a staining with Cy3 dye, labeled RHA0385. The analytical signal in the experimental zone originated from the interaction of the reporter molecule (Cy3 dye) with the virus on the SERS substrate ( Figure 10). The analytical curve was constructed from the intensity variation of the band at 1587 cm −1 . ...
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... immunocomplex on the magnetic beads (IMC-MB) was prepared after mixing the MB with the sample (first step) and with the detection antibody (second step). The SERS tag-functionalized immunocomplex, on which the SERS signal is recorded, was produced after the successive interaction of the IMC-MB with streptavidin (third step) and SERS tag (fourth step), respectively ( Figure 11). The DMF-SERS method showed good performance when evaluating the H5N1 antigen concentration in the serum with a LOD of 74 pg/mL, which is lower than that from the standard Enzyme-Linked Immunosorbent Assay (ELISA) method (399 pg/mL). ...
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... the method showed good selectivity in the presence of the prostate-specific antigen (PSA), C-reactive protein (CRP), hepatitis B surface antigen (HBsAg), and cardiac troponin T (cTnT). Figure 11. Representation of the steps to obtain the SERS tag-functionalized immunocomplex on which the SERS signal was recorded for the detection of the H5N1 virus. ...
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... CoVs are known to be made up of a nucleocapsid and a positive single-stranded RNA (+ssRNA) as the genetic materials [145][146][147] that are surrounded by a lipid bilayer consisting of various proteins associated with the attachment to the cell that is invaded. The integral membrane proteins include spike (S), hemagglutinin esterase (HE), envelope (E), membrane (M), and nucleocapsid (N) (Figure 12). Among these integral proteins, the S glycoprotein spike is the one that plays an important role in the initial stage of CoV infection. ...
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... March 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic [146]. The number of confirmed cases and deaths reported globally is shown in Figure 13. The mortality rate of this disease has been estimated as 4.5% [171]. ...
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... literature suggests that mutations in different genomic regions of SARS-CoV-2 have a specific influence on viral adaptation and production. Thus, through a natural evolution mechanism, the virus must have acquired mutations for satisfactory binding with the human ACE-2 receptor, as seen in Figure 14 [158,159,185]. ...
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... et al. [194] explored the diagnosis of SARS-CoV-2 using SERS combined with a multivariate statistical analysis. In this analytical system (Figure 15), the human cellular receptor ACE-2 was physisorbed on aligned silver-nanorod SERS arrays deposited on silicon wafers (ACE-2@SN-SERS substrates). The ACE-2 enzyme is recognized as a functional receptor for the spike glycoprotein of the human coronavirus SARS-CoV-2, specifically in its S1 subunit [185]. ...

Citations

... These mechanisms work in tandem, enabling SERS to achieve highly sensitive molecular detection and analysis [22]. Examples of SERS enhancement include its successful application in biomedicine, such as the detection of tumor biomarkers or viral particles [23,24]. These examples underscore the significant potential of SERS technology in achieving high-sensitivity molecular detection. ...
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A novel approach is proposed leveraging surface-enhanced Raman spectroscopy (SERS) combined with machine learning (ML) techniques, principal component analysis (PCA)-centroid displacement–based nearest neighbor (CDNN). This label-free approach can identify slight abnormalities between SERS spectra of gastric lesions at different stages, offering a promising avenue for detection and prevention of precancerous lesion of gastric cancer (PLGC). The agaric-shaped nanoarray substrate was prepared using gas–liquid interface self-assembly and reactive ion etching (RIE) technology to measure SERS spectra of serum from mice model with gastric lesions at different stages, and then a SERS spectral recognition model was trained and constructed using the PCA-CDNN algorithm. The results showed that the agaric-shaped nanoarray substrate has good uniformity, stability, cleanliness, and SERS enhancement effect. The trained PCA-CDNN model not only found the most important features of PLGC, but also achieved satisfactory classification results with accuracy, area under curve (AUC), sensitivity, and specificity up to 100%. This demonstrated the enormous potential of this analysis platform in the diagnosis of PLGC. Graphical Abstract
... A thermal cycler is used to measure the specimen's fluorescence emission. The computer, coupled with thermal cycler via appropriate software, records the information and generates an amplification graphic for each reaction cycle [2,37]. ...
... During qPCR, the number of copies of the target DNA sequence is exponentially amplified with each cycle, and the fluorescence emitted by the cleaved probe is continuously measured. This fluorescence data is then used to determine the quantity of targeted DNA present in the initial sample, allowing for accurate quantification (Figure 16) [37]. ...
... The spectra of SERS-based biosensors are simple but powerful results, in which every single component of the analytes can be recognized via characteristic vibrations of identical groups [1]. In particular, SERS is an ad-vantageous and practical choice for biosensors in clinical settings thanks to fast response [2], the ability of real-time measurements [3], extremely high sensitivity [4], remarkable selectivity [5], and tremendous versatility [4,6,7]. Many scholars have taken advantage of these properties in cancer diagnosis [8], detection of hazardous chemicals [9], tracing of microor- ganisms [7,10,11], and other analytical measurements regarding food, medical, and environmental issues [12][13][14]. ...
... In particular, SERS is an ad-vantageous and practical choice for biosensors in clinical settings thanks to fast response [2], the ability of real-time measurements [3], extremely high sensitivity [4], remarkable selectivity [5], and tremendous versatility [4,6,7]. Many scholars have taken advantage of these properties in cancer diagnosis [8], detection of hazardous chemicals [9], tracing of microor- ganisms [7,10,11], and other analytical measurements regarding food, medical, and environmental issues [12][13][14]. Undeniably, SERS is the future for sensor design. ...
Article
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Deep eutectic solvents (DESs) have recently emerged as an alternative solvent for nanoparticle synthesis. There have been numerous advancements in the fabrication of silver nanoparticles (Ag NPs), but the potential of DESs in Ag NP synthesis was neither considered nor studied carefully. In this study, we present a novel strategy to fabricate Ag NPs in a DES (Ag NPs-DES). The DES composed of ᴅ-glucose, urea, and glycerol does not contain any anions to precipitate with Ag ⁺ cations. Our Ag NPs-DES sample is used in a surface-enhanced Raman scattering (SERS) sensor. The two analytes for SERS quantitation are nitrofurantoin (NFT) and sulfadiazine (SDZ) whose residues can be traced down to 10 ⁻⁸ M. The highest enhancement factors (EFs) are competitive at 6.29 × 10 ⁷ and 1.69 × 10 ⁷ for NFT and SDZ, respectively. Besides, the linearity coefficients are extremely close to 1 in the range of 10 ⁻⁸ to 10 ⁻³ M of concentration, and the SERS substrate shows remarkable uniformity along with great selectivity. This powerful SERS performance indicates that DESs have tremendous potential in the synthesis of nanomaterials for biosensor substrate construction.
... Despite the greater difficulty in design and fabrication, devices based on organized nanostructures are of great interest for the fabrication of SERS substrates because they offer greater repeatability than colloidal systems and, in addition, are also more easily adaptable to different analysis needs by appropriately modifying their characteristic sizes. Although several platforms for the detection of SARS-CoV-2 virus based on the SERS technique have been developed in the literature, [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] only a few of these involve the use of organized engineered nanopatterns. Yang et al. realized a SERS biosensor to detect the SARS-CoV-2 virus in the contaminated water, based on a "virus-traps" composed of oblique gold nanoneedles. ...
... However, in the context of biological-based SERS detection [5][6][7] or some other detections (such as microplastics), 8,9 certain target analytes possess physical dimensions comparable to or even greater than the dimensions of hot-spots. For instance, proteins like BSA typically have a nominal size of 7.1 nm, 10 viruses span diameters ranging from 20 nm to 250-400 nm (with the SARS-CoV-2 virus being approximately 100 nm in diameter), 11 bacteria exhibit considerable size of around or larger than 1 μm, 12 while microplastics shows particle size varying from tens of nanometers to a few micrometers. ...
Article
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The study systematically explores the connection between analyte particle size and the hot-spot in Au nanoparticle (NP) dimer systems. Contrary to the conventional understanding tied to localized surface plasmon resonance (LSPR), we show that depending on the analyte particle's size, the location to produce surface-enhanced Raman scattering (SERS), defined as effective hot-spot, is different from the gap based hot-spot, where the electric field reaches maximum intensity, and the corresponding resonant wavelength is also shifted significantly from LSPR wavelength. This effective hot-spot occurs primarily at the point where the Au NP contacts the analyte particle, covering a larger area than the traditional hot-spot and having a significantly smaller enhancement factor. Moreover, different effective hot-spots can be activated under various polarizations. The local electric field versus distance relationship decays significantly slower, complicating the interpretation of SERS spectra of large analyte particles. This complexity offers tunability, allowing for a more precise representation of unique molecular features of the analyte. Consequently, our findings demonstrate the necessity for SERS substrate design rules to be contingent on analyte particle size. Although interpreting SERS spectra is intricate, it can be refined to effectively capture distinctive molecular characteristics. These insights pave a new way to tailor SERS substrate design specifically catering to large analyte particles.
... A thermal cycler is used to measure the specimen's fluorescence emission. The computer, coupled with thermal cycler via appropriate software, records the information and generates an amplification graphic for each reaction cycle [2,37]. ...
... During qPCR, the number of copies of the target DNA sequence is exponentially amplified with each cycle, and the fluorescence emitted by the cleaved probe is continuously measured. This fluorescence data is then used to determine the quantity of targeted DNA present in the initial sample, allowing for accurate quantification (Figure 16) [37]. ...
Chapter
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The global health field is significantly affected by viral infections, and sero-diagnosis is crucial in diagnostic virology. Various laboratory techniques such as nucleic acid detection, viral culture, and antigen detection are essential for diagnosing viral infections. Advances in science have led to the development of new immunologic and molecular techniques, enabling rapid and simplified diagnosis of different viruses. Timely and accurate identification of viral infections is vital for effective outbreak management. Immunological techniques, detecting viral antigens or antibodies, are widely used in diagnostic and epidemiological research, aiding in epidemic identification, appropriate diagnostic tests, vaccination programs, and detecting common and emerging viruses. However, traditional viral identification methods demand extensive technical expertise, time, and financial resources. Consequently, scientists worldwide are dedicated to developing precise diagnostic methods for viral diseases. Various innovative approaches are being explored, aiming to create more accessible, time-efficient, and cost-effective viral disease diagnosis methods, thereby benefiting low-income countries.
... The main direction in the development of these techniques was the creation of biosensors based on nanostructures [8,9], including optical biosensors operating on the surface-enhanced Raman scattering (SERS) effect [10][11][12]. Optical biosensors, the operation of which is based on the electromagnetic SERS mechanism, are one of the most promising areas. Due to the interaction of light with free electrons located near the surface of a specially created metal nanoparticle/array, a localized surface plasmon resonance (LSPR) is formed, depending on the electronic properties of the nanoparticle material [13,14], its size and geometry [15][16][17][18][19][20], as well as on the properties of the surrounding permittivity medium [21][22][23][24]. ...
... The SERS method provides highly sensitive and selective detection of pathogens without specific labels [25][26][27]. It allows us to enhance the signal from the analyte, even at its concentration down to one molecule [6,28] and to obtain a signal enhancement factor from the desired analyte of the order of 10 3 -10 12 [29,30]. ...
Article
The combination of Surface-enhanced Raman Scattering (SERS) method and machine learning algorithms has been successfully demonstrated for the detection and differentiation of influenza A virus in buffer medium. Dendritic Ag nanostructures on single-crystal Si wafer have been proposed as SERS-active substrates, which are fabricated using a low-cost and reproducible AgNO 3 reduction method. Depending on the time of Ag deposition, structures of different morphologies were obtained. These structures were studied by spectroscopic ellipsometry (SE). To analyze the spectra obtained by SE, we used the Bruggeman effective medium approximation to determine the volume fraction and height of the metal, the Drude model to describe free electrons, the Tauc-Lorentz model to describe the influence of interband transitions, as well as Lorentz model and Gauss model to describe localized surface plasmon resonance (LSPR). SERS was achieved through LSPR excitation and the presence of "hot spots" in the regions around the tips and in the spaces between close-packed dendritic Ag nanostructures. The sample with the most developed surface is the most promising for SERS, since the spectral position of the LSPR is at 658 nm, which is close to the excitation wavelength of the He-Ne laser. The SERS spectra of influenza A virus in buffer medium are difficult to distinguish, so a machine learning algorithms (principal component analysis and support vector machine) were used to directly classify them. For the sample with the most developed morphology, the detection accuracy of influenza A virus was 76.6 ± 4.2 % at a total protein concentration in the test analyte of 300 μg/ml (according to the Lowry method).
... In recent years, spectroscopic techniques such as surface-enhanced Raman spectroscopy (SERS) are increasingly being used for the detection of viruses using indirect and direct methods [14][15][16][17]. Indirect detection uses an SERS tag: Raman reporter molecule (e.g., p-MBA) with the recognition element (specific antibody) and capture substrate, which is functionalized with a capture antibody. ...
Article
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The rapid, low cost, and efficient detection of SARS-CoV-2 virus infection, especially in clinical samples, remains a major challenge. A promising solution to this problem is the combination of a spectroscopic technique: surface-enhanced Raman spectroscopy (SERS) with advanced chemometrics based on machine learning (ML) algorithms. In the present study, we conducted SERS investigations of saliva and nasopharyngeal swabs taken from a cohort of patients (saliva: 175; nasopharyngeal swabs: 114). Obtained SERS spectra were analyzed using a range of classifiers in which random forest (RF) achieved the best results, e.g., for saliva, the precision and recall equals 94.0% and 88.9%, respectively. The results demonstrate that even with a relatively small number of clinical samples, the combination of SERS and shallow machine learning can be used to identify SARS-CoV-2 virus in clinical practice.
... The primary challenge impeding the progress of SERS-based DNA nanobiosensors is attributed to the requirement for close contact between the analyte and the surface, as prolonged usage may lead to a partial loosening of this contact, consequently diminishing the signal intensity [146]. To meet the escalating need for precise and expeditious virus detection, SERS-sensing technologies have demonstrated great potential for multiple immunoassays [147]. ...
Article
Full-text available
Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from low sensitivity and specificity, are time-consuming, have a high cost, etc. Recently, DNA biosensors based on DNA nanotechnology have shown great potential in virus detection. DNA nanotechnology, specifically DNA tiles and DNA aptamers, has achieved atomic precision in nanostructure construction. Exploiting the programmable nature of DNA nanostructures, researchers have developed DNA nanobiosensors that outperform traditional virus-detection methods. This paper reviews the history of DNA tiles and DNA aptamers, and it briefly describes the Baltimore classification of virology. Moreover, the advance of virus detection by using DNA nanobiosensors is discussed in detail and compared with traditional virus-detection methods. Finally, challenges faced by DNA nanobiosensors in virus detection are summarized, and a perspective on the future development of DNA nanobiosensors in virus detection is also provided.
... Ever since the discovery, in the 1970s, of the Raman enhancement effect [9], Surface Enhanced Raman Spectroscopy (SERS) has become a powerful, nondestructive analytical tool, with high selectivity and sensitivity [10], being able to detect different chemical species through the vibrational fingerprints. During last years, this was extensively used to identify a wide range of molecules, which are affecting various fields, such as human health [11], environmental pollutants [12][13][14], pesticides [15,16], food safety [17] and even explosives [18,19]. As stated before, the electromagnetic enhancement is playing the leading role, due to the localized surface plasmon resonance (LSPR) excitation of the metallic nanostructures, when the so-called 'hot spots' are forming [20][21][22]. ...