The issue of variability introduced into blood plasma and serum analysis by preanalytical procedures is the major obstacle to obtaining accurate and reproducible results. While the question of how to overcome this issue has been discussed in biochemical detection of analytes and omics technologies, its relevance to the field of optical spectroscopy remains mostly unexplored. In this work, we evaluated the freeze-thaw cycle (FTC)-induced alternations in blood serum optical properties by means of autofluorescence and Raman spectroscopy, including surface-enhanced Raman spectroscopy (SERS). In the case of regular Raman spectroscopy, FTC-specific spectral variability was estimated to be <1%, being significantly smaller than patient-specific variability, while the t-distributed stochastic neighbor embedding clustering of principal components yielded spectral grouping by patient ID independent of sample freezing. For SERS, FTC-specific and patient-specific spectral variabilities were 15% and >90%, respectively. Finally, parallel factor analysis of autofluorescence excitation-emission matrices revealed that patient-specific variability in the visible spectral range was 13%, whereas FTC-specific variability was 4%. We further evaluated disease-specific variability for two datasets, namely, for colorectal cancer diagnostics with autofluorescence and for chronic kidney disease diagnostics using SERS. Disease-associated variabilities were determined to be 8% and 49%, significantly exceeding the possible FTC-induced variability. Hence, the obtained results suggest that FTC blood serum samples can be used for disease diagnostics by Raman spectroscopy and SERS, as well as through autofluorescence spectroscopy, although the difference in FTC-induced and disease-induced variabilities was lowest in the latter case.
Antimicrobial resistance (AMR) is one of the top global health threats. In 2019, AMR was associated with 4.95 million deaths, of which 1.97 million were caused by drug-resistant infections directly. The main subset of AMR is antibiotic resistance, that is, the resistance of bacteria to antibiotic treatment. Traditional and most commonly used antibiotic susceptibility tests are based on the detection of bacterial growth and its inhibition in the presence of an antimicrobial. These tests typically take over 1-2 days to perform, so empirical therapy schemes are often administered before proper testing. Rapid tests for AMR are necessary to optimize the treatment of bacterial infection. Here, we combine the MTT test with Raman spectroscopy to provide a 1.5 h long test for minimal inhibitory concentration determination. Several Escherichia coli and Klebsiella pneumoniae strains were tested with three types of antibiotics, including ampicillin from penicillin family, kanamycin from aminoglycoside family and levofloxacin from fluoroquinolone family. The test provided the same minimal inhibitory concentrations as traditional Etest confirming its robustness.
The purpose of this study is to improve the efficiency of early diagnosis of endometrial cancer using the analysis of surface-enhanced Raman scattering (SERS) of blood plasma. Blood plasma of patients aged 22 to 79 years was investigated. The study included 95 women. All patients were divided into 3 groups: group 1 consists of 29 women with endometrial adenocarcinoma, group 2 − 31 patients with endometrial polyp, group 3 – 10 women with endometrial hyperplasia. A control group consisted of 25 healthy women. The SERS spectra of dried samples were studied on an experimental stand consisting of a Photon-Bio RL785 spectrometric system based on a charge-coupled device (CCD) detector and a laser radiation source with a wavelength of 785 nm and an ADF U300 microscope. In order to realize the effect of surface enhancement of the Raman signal from blood plasma, we used a silver substrate based on a dried silver colloid. In the result of the study, the spectral features and specific features which characteristic of adenocarcinoma, polyps and endometrial hyperplasia were determined. With the use of discriminant analysis by projection onto latent structures (PLS-DA) method, the accuracy of optical diagnostics of endometrial adenocarcinoma relative to the control group and endometrial hyperplasia for the calibration and verification sets of spectra was 87% and 85%, respectively. Class discrimination accuracy of the control group with respect to endometrial hyperplasia and adenocarcinoma was 85%, and endometrial hyperplasia relative to the control group and endometrial adenocarcinoma was 81% for the verification set of spectra. The study shows the possibility of using SERS for differential express diagnostics of endometrial cancer and its benign pathological conditions.
A phase transition accompanied by the appearance of a spike in the longitudinal resistance of a two-dimensional electron system has been studied using the electron spin resonance near the filling factor ν = 3 in the ZnO/MgZnO heterojunction. This transition occurs when the tilt angle θ of the magnetic field is increased to some critical value θc. An analysis of the spin resonance amplitude has made it possible to demonstrate the spin nature of this phenomenon. For example, the ground state of the system on both sides of the transition has a nonzero spin polarization, which changes by several times when the phase of the system is changed. Strong spin resonance is observed both at θ < θc and at θ > θc. Surprisingly, the spin resonance at the critical angle θc has been detected in only one phase, which lies in the region of magnetic fields below the critical field Bc corresponding to the spike position in the longitudinal resistance. An increase in the magnetic field to this value leads to a decrease in the resonance amplitude and an increase in the resonance width. In the field region above Bc, the spin resonance disappears completely. Such behavior of the spin resonance is most likely due to the formation of domains with different spin polarizations in the electron system.
The optical properties of silver and gold sols with different sizes of nanoparticles and the method of their chemical deposition on the surface of silicon, silicon oxide, glass and aluminum foil were studied in order to obtain SERS substrates – promising platforms for the development of aptamer sensors and immunochemical analysis of various pathogens. It has been established that for operation on lasers with exciting radiation wavelengths of 532, 638 and 785 nm, it is possible to create universal SERS substrates based on colloidal solutions obtained by the liquid-phase chemical method with an average silver particle size of 40 nm and by the Leopold-Lendl method with an average size of 20 nm.
The transmission of electromagnetic radiation through a silicon substrate with a square metallic grid deposited on one side has been studied experimentally. It has been established that the electrodynamic response of the structure is equivalent to the excitation of a transverse electromagnetic plasma mode in it with the plasma frequency determined by the geometric parameters of the grating, as well as by the thickness and relative permittivity of the substrate. A theoretical model has been developed to qualitatively describe the experimental results obtained.
We study the effect of the pseudospin ferromagnetism with the aid of an electrically detected electron spin resonance in a wide AlAs quantum well containing a high quality two-dimensional electron system. Here, pseudospin emerges as a two-component degree of freedom, that labels degenerate energy minima in momentum space populated by electrons. The built-in mechanical strain in the sample studied imposes a finite "Zeeman" splitting between the pseudospin "up" and "down" states. Because of the anisotropy of the electron spin splitting we were able to independently measure the electron spin resonances originating from the two in-plane valleys. By analyzing the relative resonance amplitudes, we were able to investigate the ferromagnetic phase transitions taking place at integer filling factors of the quantum Hall effect when the magnetic field is tilted. The pseudospin nature of these transitions is demonstrated.
The efficiency η of sub-THz-to-DC energy conversion of a silicon-based plasmonic detector was studied. The dependence of the detector output signal on the incident radiation power was measured. It was shown that, in the linear-power region, the efficiency η increases with increasing power and saturates sublinearly. The maximum achieved values of η were 0.4
The long-term relaxation dynamics of neutral excitations with spin 1 in the Laughlin liquid at an electron filling factor of 1/3 has been studied. It has been found that there are two types of excitations with the same energies, the relaxation times of which to the ground state differ by at least two orders of magnitude. Assumptions are made about the nature of these excitations.
An unconventional behavior of the spin order in strongly correlated two-dimensional electron systems based on MgZnO/ZnO heterostructures has been detected in the quantum limit at the filling factors 1 ≤ ν ≤ 2. Under the variation of the filling factor and the orientation of a magnetic field, inelastic light scattering spectra exhibit characteristic transformations of collective spin excitations, which indicate qualitatively different rearrangements of the spin configuration in the system: smooth depolarization at 1 < ν < 3/2 with the formation of spin textures and sharp ferromagnetic instability at a certain filling factor in the range 3/2 < ν ≤ 2. Comparison with the magnetotransport experiments reported in [J. Falson, D. Maryenko, B. Friess, et al., Nature Phys. 11, 347 (2015)] shows that the disappearance of spin textures under the variation of the field tilt angle correlates with the appearance of an incompressible state at ν = 3/2.
The optical properties of silver and gold sols with different sizes of nanoparticles and the method of their chemical deposition on the surface of silicon, silica, glass, and aluminum foil were studied in order to obtain SERS substrates, promising platforms for the development of aptamer sensors and immunoassay of various pathogens. It was determined that, for operation of lasers with exciting radiation wavelengths of 532, 638, and 785 nm, it is possible to create universal SERS substrates based on colloidal solutions obtained by the liquid-phase chemical method with an average silver particle size of 40 nm and by the Leopold–Lendl method with an average size of 20 nm.
We realize a simple technology to assemble a three-dimensional metamaterial consisting of stacked planar silicon chips with a metallic mesh lithographically fabricated on the chip surface. We use FabryPerot resonance spectroscopy to accurately measure the metamaterial dispersion in the terahertz frequency range. For large mesh periods, the dispersion closely follows the plasmonic dependence, with the plasma frequency determined by the geometric parameters of the metamaterial. For small mesh periods, the dispersion gains extreme sensitivity to the radiation frequency. Such a superdispersive property may have implications in the field of spectroscopy and multiplexing.
A W-band (75–110-GHz) phase shifter was designed and numerically modeled. The phase shifter is a periodic array of rectangular patch antennas on a dielectric substrate with built-in PIN diodes. It was numerically demonstrated that one can achieve a phase shift of the transmitted wave up to 87° at a frequency of 96 GHz with transmittance losses of no more than –7 dB.
We studied the absorption of microwave electromagnetic radiation incident normal to a two-dimensional electron system on a dielectric substrate with a metallic back reflector. We have shown that the presence of a back gate strongly modifies the spectrum of plasmon polaritons in such a structure. We observe a transverse plasmon mode which starts from zero frequency at zero magnetic field and follows renormalized cyclotron resonance. This renormalization occurs from the hybridization of plasma modes with Fabry-P & eacute;rot photonic resonances in the substrate, which indicates their transverse nature. Finally, we speculate that the observed modes resemble helicon waves in three-dimensional metals.
Background. This study aimed to enhance early detection of endometrial cancer in women and distinguish benign conditions from endometrial cancer using surface-enhanced Raman scattering (SERS) analysis of blood plasma, thus increasing diagnostic efficacy. Materials and methods. The study of blood plasma from 95 female patients aged 22–79 years was performed. The patients were divided into four groups: group 1 included 29 women with endometrial adenocarcinoma, group 2 included 31 patients with endometrial polyp, group 3 included 10 women with endometrial hyperplasia, and the comparison group consisted of 25 healthy women. Blood plasma was analyzed via SERS, with three Raman spectra recorded per sample. Spectral measurements of the SERS substrate were assessed using dried samples on an experimental bench equipped with the spectrometric system RL785 (LLC “Foton-Bio”, Russia), incorporating a CCD detector, laser radiation source with a wavelength of 785 nm, and ADF U300 microscope (ADF, China). A silver substrate composed of dried silver colloid was used to demonstrate the enhancement effect on the Raman signal from the surface of the blood plasma. Results. Spectral and specific features that distinguish adenocarcinoma, polyps, and endometrial hyperplasia were identified and evaluated. Spectral and quantitative differences specific to each condition, which are crucial for the differential diagnosis of pathologic tissues, were also identified. The accuracy rates of the optical diagnostics in distinguishing endometrial adenocarcinoma from the control group and endometrial hyperplasia were 87% and 85%, respectively, for the calibration and verification spectral sets (where the sensitivity and specificity were 66% and 92% for the spectral verification set, respectively). The accuracy rates of distinguishing control from endometrial hyperplasia and endometrial adenocarcinoma were 86% and 85%, respectively, and the accuracy of distinguishing endometrial hyperplasia from control and endometrial adenocarcinoma was 81% for the calibration and verification sets of spectra. In addition, the study demonstrated improved accuracy in differentiating adenocarcinoma from hyperplasia, including polyps. The accuracy rate was 93% in the calibration set of spectra, with sensitivity and specificity of 96% and 90%, whereas in the validation set, it was 91%, with sensitivity and specificity of 93% and 88%, respectively. Conclusions. The study demonstrated the potential use of SERS for differentiating expression patterns in endometrial cancer from those in benign conditions.
Aptasensors based on surface-enhanced Raman spectroscopy (SERS) are of high interest due to the superior specificity and low limit of detection. It is possible to produce stable and cheap SERS-active substrates and portable equipment meeting the requirements of point-of-care devices. Here we combine the membrane filtration and SERS-active substrate in the one pot. This approach allows efficient adsorption of the viruses from the solution onto aptamer-covered silver nanoparticles. Specific determination of the viruses was provided by the aptamer to influenza A virus labeled with the Raman-active label. The SERS-signal from the label was decreased with a descending concentration of the target virus. Even several virus particles in the sample provided an increase in SERS-spectra intensity, requiring only a few minutes for the interaction between the aptamer and the virus. The limit of detection of the aptasensor was as low as 10 viral particles per mL (VP/mL) of influenza A virus or 2 VP/mL per probe. This value overcomes the limit of detection of PCR techniques (∼103 VP/mL). The proposed biosensor is very convenient for point-of-care applications.
The behavior of magnetoplasmon modes in high-quality two-dimensional electron systems based on AlGaAs/GaAs heterostructures with a disk mesa is studied by the optical detection method for resonant microwave absorption. A magnetic field at which a two-dimensional skin layer is formed along the edge of a two-dimensional electron system and, as a result, the magnetoplasma mode becomes an edge mode has been determined by analyzing the magnetodispersion dependence. The dependence of this magnetic field on the two-dimensional electron density is studied. A model has been developed to describe the reported experimental results.
An ensemble of neutral excitations is constructed experimentally in the Laughlin liquid at the electron filling factor 1/3. The excitations are found to induce a nonlinear optical response, manifested as a quadratic dependence of the reflection signal on the excitation power. The reported experimental results indicate that the observed effect is due to the anti-Stokes–Stokes scattering of light from the excited Laughlin liquid.
Surface-enhanced Raman scattering (SERS) is a powerful technique for decoding of 2-5-component mixes of analytes. Low concentrations of analytes and complex biological media are usually non-decodable with SERS. Recognition molecules, such as antibodies and aptamers, provide an opportunity for a specific binding of ultra-low contents of analyte dissolved in complex biological media. Different approaches have been proposed to provide changes in SERS intensity of an external label upon binding of ultra-low contents of the analytes. In this paper, we propose a SERS-based sensor for the rapid and sensitive detection of botulinum toxin type A. The silver nanoisland SERS substrate was functionalized using an aptamer conjugated with a Raman label. The binding of the target affects the orientation of the label, providing changes in an analytical signal. This trick allowed detecting botulinum toxin type A in a one-stage manner without additional staining with a monotonous dose dependence and a limit of detection of 2.4 ng/mL. The proposed sensor architecture is consistent with the multiarray detection systems for multiplex analyses.
— Colloidal solutions of silver nanoparticles have been prepared by the electric discharge method using three distinct modifiers: carbonate and citrate ions and polyethylenimine. According to optical absorption spectroscopy data and their zeta potential, the solutions were highly stable. The geometric parameters of the nanoparticles have been determined by transmission electron microscopy. The nanoparticles have been immobilized on the surface of polyethylene terephthalate track-etched membranes. The resultant surface nanostructures have been examined by scanning electron microscopy and Raman spectroscopy. The materials thus obtained have been shown to exhibit surface-enhanced Raman scattering using 4-aminothiophenol as test molecule. Relative Raman gain coefficients have been calculated.