Utilization of DNA and 2D metal oxide interaction for an optical biosensor.

The efficient monitoring and early detection of viruses may provide essential information about diseases. In this work, we have highlighted the interaction between DNA and a two-dimensional (2D) metal oxide for developing biosensors for further detection of viral infections. Spectroscopic measurements have been used to probe the efficient interactions between single-stranded DNA (ssDNA) and the 2D metal oxide and make them ideal candidates for detecting viral infections. We have also used fully atomistic molecular dynamics (MD) simulation to give a microscopic understanding of the experimentally observed ssDNA-metal oxide interaction. The adsorption of ssDNA on the inorganic surface was found to be driven by favourable enthalpy change, and 5'-guanine was identified as the interacting nucleotide base. Additionally, the in silico assessment of the conformational changes of the ssDNA chain during the adsorption process was also performed in a quantitative manner. Finally, we comment on the practical implications of these developments for sensing that could help design advanced systems for preventing virus-related pandemics.

FTIR microspectroscopy and multivariate analysis facilitate identification of dynamic changes in epithelial-to-mesenchymal transition induced by TGF-ß in prostate cancer cells.

The standard diagnosis of prostate cancer is accomplished by the identification of cytomorphological deviations in biopsied tissues while immunohistochemistry is used to resolve the equivocal cases. Accumulating evidence favors the concept that epithelial-to-mesenchymal transition (EMT) is a stochastic process composed of multiple intermediate states instead of a single binary switch. Despite its significant role in promoting cancer aggressiveness, the current tissue-based risk stratification tools do not include any of the EMT phenotypes as a metric. As a proof-of-concept, the present study analyzes the temporal progression of EMT in transforming growth factor-beta (TGF-ß) treated PC3 cells encompassing multifarious characteristics such as morphology, migration and invasion, gene expression, biochemical fingerprint, and metabolic activity. Our multimodal approach reinstates EMT plasticity in TGF-ß treated PC3 cells. Further, it highlights that mesenchymal transition is accompanied by discernible changes in cellular morphometry and molecular signatures particularly in the range of 1800-1600 cm-1 and 3100-2800 cm-1 of Fourier-transformed infrared (FTIR) spectra signifying Amide III and lipid, respectively. Investigation of attenuated total reflectance (ATR)-FTIR spectra of extracted lipids from PC3 cell populations undergoing EMT identifies changes in stretching vibration at FTIR peaks at 2852, 2870, 2920, 2931, 2954, and 3010 cm-1 characteristics of fatty acids and cholesterol. Chemometric analysis of these spectra indicates that the level of unsaturation and acyl chain length of fatty acid coregister with differential epithelial/mesenchymal states of TGF-ß treated PC3 cells. Observed changes in lipids also correlate with cellular nicotinamide adenine dinucleotide hydrogen (NADH) and flavin adenine dinucleotide dihydrogen (FADH2) levels and mitochondrial oxygen consumption rate. In summary, our study establishes that morphological and phenotypic traits of epithelial/mesenchymal variants of PC3 cells concur with their respective biochemical and metabolic properties. It also underscores that spectroscopic histopathology has a definitive potential to refine the diagnosis of prostate cancer reckoning its molecular and biochemical heterogeneities.

Synthesis and Characterization of Biotene: A New 2D Natural Oxide From Biotite.

In this work, the synthesis and characterization of ultrathin metal oxide, called biotene, using liquid-phase exfoliation from naturally abundant biotite are demonstrated. The atomically thin biotene is used for energy harvesting using its flexoelectric response under multiple bending. The effective flexoelectric response increases due to the presence of surface charges, and the voltage increases up to ≈8 V, with a high mechano-sensitivity of 0.79 V N-1 for normal force. This flexoelectric response is further validated by density functional theory (DFT) simulations. The atomically thin biotene shows an increased response in the magnetic field and thermal heating. The synthesis of two-dimensional (2D) metal-oxide biotene suggests a wealth of future 2D-oxide material for energy generation and energy harvesting applications.

Energy Harvesting Using Cotton Fabric Embedded with 2D Hexagonal Boron Nitride.

Continuous health monitoring through sensitive physiological signals (using a wearable device) is crucial for the early detection of heart diseases and breathing problems. Here, we have developed a flexible hBN/cotton hybrid device that can detect minor signals such as heartbeat and breathed-out air pressure. Systematic observation of the real-time motion sensing showed a peak-to-peak voltage output of ∼1.5 V for each heart rate pulse. The as-fabricated device showed a high voltage output of up to ∼10 V upon applying a pressure of ∼3 MPa. The FTIR results and DFT calculation suggested a chemical interaction between hBN and cellulose, giving rise to flat band characteristics and partially filled σ-bonding (sp2) hybridization. The atomic-scale chemical interface between atomically thin hBN and surface functional groups present on cotton resulted in charge localization and enhanced output voltage. An hBN/cotton hybrid device can bring new insights and opportunities to develop a self-charging and health-monitoring energy-harvesting cloth.

Tunable phonon-plasmon hybridization in α-MoO3-graphene based van der Waals heterostructures.

The plasmon-phonon hybridization behavior between anisotropic phonon polaritons (APhP) of orthorhombic phase Molybdenum Trioxide (α - MoO3) and the plasmon-polaritons of Graphene layer - forming a van der Waals (vdW) heterostructure is investigated theoretically in this paper. It is found that in-plane APhP shows strong interaction with graphene plasmons lying in their close vicinity, leading to large Rabi splitting. Anisotropic behavior of biaxial MoO3 shows the polarization-dependent response with strong anti-crossing behavior at 0.55 eV and 0.3 eV of graphene's Fermi potential for [100] and [001] crystalline directions, respectively. Numerical results reveal unusual electric field confinement for the two arms of enhanced hybrid modes: the first being confined in the graphene layer representing plasmonic-like behavior. The second shows volume confined zigzag pattern in hyperbolic MoO3. It is also found that the various plasmon-phonon hybridized modes could be wavelength tuned, simply by varying the Fermi potential of the graphene layer. The coupling response of the hybrid structure is studied analytically using the coupled oscillator model. Furthermore, we also infer upon the coupling strength and frequency splitting between the two layers with respect to their structural parameters and interlayer spacing. Our work will provide an insight into the active tunable property of hybrid van der Waals (vdW) structure for their potential application in sensors, detectors, directional spontaneous emission, as well as for the tunable control of the propagating polaritons in fields of flat dispersion where strong localization of photons can be achieved, popularly known as the flatband optics.

Tunable Van der Waal's optical metasurfaces (VOMs) for biosensing of multiple analytes.

Van der Waal's heterostructure assembling low dimensional materials are the new paradigm in the field of nanophotonics. In this work, we theoretically investigate Van der Waal's optical metasurfaces consisting of graphene and hBN for the application of biosensing of multiple analytes in the mid-infrared (MIR) region. Phonon polaritons of hexagonal boron nitride (hBN) show an advantage over plasmon polaritons, as the phonon polaritons are lossless and possess high momentum and enhanced lifetime. The hybrid phonon mode produced at 6.78 µm in the mid-infrared (MIR) region with near-perfect absorption is used for surface-enhanced infrared absorption (SEIRA) based detection of organic analytes. Moreover, by adding the graphene layer, the device's overall resonance responses can be tuned, enabling it to identify multiple organic analytes-such as 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) and nitrobenzene (Nb) [C6H5NO2], just by changing graphene's fermi potential (Ef). Owing to large wave vector of phonon polariton, the device has the capability to detect small amount of number of molecules (390 for CBP and 1990 for nitrobenzene), thus creating a highly sensitive optical biosensor.

Comprehensive Evaluation of PAXgene Fixation on Oral Cancer Tissues Using Routine Histology, Immunohistochemistry, and FTIR Microspectroscopy.

The choice of tissue fixation is critical for preserving the morphology and biochemical information of tissues. Fragile oral tissues with lower tensile strength are challenging to process for histological applications as they are prone to processing damage, such as tissue tear, wrinkling, and tissue fall-off from slides. This leads to loss of morphological information and unnecessary delay in experimentation. In this study, we have characterized the new PAXgene tissue fixation system on oral buccal mucosal tissue of cancerous and normal pathology for routine histological and immunohistochemical applications. We aimed to minimize the processing damage of tissues and improve the quality of histological experiments. We also examined the preservation of biomolecules by PAXgene fixation using FTIR microspectroscopy. Our results demonstrate that the PAXgene-fixed tissues showed significantly less tissue fall-off from slides. Hematoxylin and Eosin staining showed comparable morphology between formalin-fixed and PAXgene-fixed tissues. Good quality and slightly superior immunostaining for cancer-associated proteins p53 and CK5/6 were observed in PAXgene-fixed tissues without antigen retrieval than formalin-fixed tissues. Further, FTIR measurements revealed superior preservation of glycogen, fatty acids, and amide III protein secondary structures in PAXgene-fixed tissues. Overall, we present the first comprehensive evaluation of the PAXgene tissue fixation system in oral tissues. This study concludes that the PAXgene tissue fixation system can be applied to oral tissues to perform diagnostic molecular pathology experiments without compromising the quality of the morphology or biochemistry of biomolecules.

Road Map to Understanding SARS-CoV-2 Clinico-Immunopathology and COVID-19 Disease Severity.

SARS-CoV-2, a novel coronavirus, was first identified in Wuhan, China in December 2019. The rapid spread of the virus worldwide prompted the World Health Organization (WHO) to declare COVID-19 a pandemic in March 2020. COVID-19 discontinuing's a global health crisis. Approximately 80% of the patients infected with SARS-CoV-2 display undetectable to mild inflammation confined in the upper respiratory tract. In remaining patients, the disease turns into a severe form affecting almost all major organs predominantly due to an imbalance of innate and adaptive arms of host immunity. The purpose of the present review is to narrate the virus's invasion through the system and the host's reaction. A thorough discussion on disease severity is also presented regarding the behavior of the host's immune system, which gives rise to the cytokine storm particularly in elderly patients and those with comorbidities. A multifaceted yet concise description of molecular aspects of disease progression and its repercussion on biochemical and immunological features in infected patients is tabulated. The summary of pathological, clinical, immunological, and molecular accounts discussed in this review is of theranostic importance to clinicians for early diagnosis of COVID-19 and its management.

Engineering Near-Field SEIRA Enhancements in Plasmonic Resonators.

Engineering of the optical resonances in plasmonic resonators arrays is achieved by virtue of the intrinsic properties to the constituent structures such as composition, size and shape and by controlling the inter-resonator interactions by of virtue the array geometrical arrangement. The nanoscale confinement of the plasmonic field enhances light-matter interactions enabling, for instance, the surface enhanced infrared absorption (SEIRA) effect. However, the subwavelength confinement also poses an experimental challenge for discriminating the response stemming from the individual resonators and from the collective response in densely packed arrays. In this work, the photothermal induced resonance (PTIR) technique is leveraged to obtain nanoscale images and spectra of near-field SEIRA hot spots observed in isolated plasmonic resonators of different shapes and in selected resonators within closely packed plasmonic arrays informing on whether the interactions with neighboring resonators are beneficial or otherwise. Results are correlated with far-field spectra and theoretical calculations.

Metal-dielectric-metal resonators with deep subwavelength dielectric layers increase the near-field SEIRA enhancement.

Plasmonic nanostructures presenting either structural asymmetry or metal-dielectric-metal (M-D-M) architecture are commonly used structures to increase the quality factor and the near-field confinement in plasmonic materials. This characteristic can be leveraged for example to increase the sensitivity of IR spectroscopy, via the surface enhanced IR absorption (SEIRA) effect. In this work, we combine structural asymmetry with the M-D-M architecture to realize Ag-Ag(2)O-Ag asymmetric ring resonators where two Ag layers sandwich a native silver oxide (Ag(2)O) layer. Their IR response is compared with the one of fully metallic (Ag) resonators of the same size and shape. The photothermal induced resonance technique (PTIR) is used to obtain near-field SEIRA absorption maps and spectra with nanoscale resolution. Although the native Ag(2)O layer is only 1 nm to 2 nm thick, it increases the quality factor of the resonators' dark-mode by ≈27% and the SEIRA enhancement by ≈44% with respect to entirely Ag structures.

Near-field asymmetries in plasmonic resonators.

Surface-enhanced infrared absorption (SEIRA) spectroscopy exploits the locally enhanced field surrounding plasmonic metamaterials to increase the sensitivity of infrared spectroscopy. The light polarization and incidence angle are important factors for exciting plasmonic nanostructures; however, such angle dependence is often ignored in SEIRA experiments, typically carried out with Cassegrain objectives. Here, the photothermal induced resonance technique and numerical simulations are used to map the distribution and intensity of SEIRA hot-spots surrounding gold asymmetric split ring resonators (ASRRs) as a function of light polarization and incidence angle. The results show asymmetric near-field SEIRA enhancements as a function of the incident illumination direction which, in analogy with the symmetry-breaking occurring in asymmetric transmission, we refer to as symmetry-breaking absorption. Numerical calculations reveal that the symmetry-breaking absorption in ASRRs originates in the angle-dependent interference between the electric and magnetic excitation channels of the resonators' dark-mode. Consequently, to maximize the SEIRA intensity, ASRRs should be illuminated from the dielectric side at an angle that maximizes the constructive interference of the two excitation channels, (35° for the structures studied here), in place of the Cassegrain objectives. These results can be generalized to all structures characterized by plasmonic excitations that give rise to a surface-normal magnetic moment and that possess an electric dipole.

Nanoscale imaging of plasmonic hot spots and dark modes with the photothermal-induced resonance technique.

The collective oscillation of conduction electrons, responsible for the localized surface plasmon resonances, enables engineering nanomaterials by tuning their optical response from the visible to terahertz as a function of nanostructure size, shape, and environment. While theoretical calculations helped tremendously in understanding plasmonic nanomaterials and optimizing their light matter interaction, only a few experimental techniques are available to study these materials with high spatial resolution. In this work, the photothermal-induced resonance (PTIR) technique is applied for the first time to image the dark plasmonic resonance of gold asymmetric split ring resonators (A-SRRs) in the mid-infrared (IR) spectral region with nanoscale resolution. Additionally, the chemically specific PTIR signal is used to map the local absorption enhancement of poly(methyl methacrylate) coated on A-SRRs, revealing hot spots with local enhancement factors up to ≈30 at 100 nm lateral resolution. We argue that PTIR nanoscale characterization will facilitate the engineering and application of plasmonic nanomaterials for mid-IR applications.

Enhanced Fano resonance of organic material films deposited on arrays of asymmetric split-ring resonators (A-SRRs).

Depositing very thin organic films on the surface of arrays of asymmetric split-ring resonators (A-SRRs) produces a shift in their resonance spectra that can be utilized for sensitive analyte detection. Here we show that when poly-methyl-methacrylate (PMMA) is used as an organic probe (analyte) on top of the A-SRR array, the phase and amplitude of a characteristic molecular Fano resonance associated with a carbonyl bond changes according to the spectral positions of the trapped mode resonance of the A-SRRs and their plasmonic reflection peaks. Furthermore, we localize blocks of PMMA at different locations on the A-SRR array to determine the effectiveness of detection of very small amounts of non-uniformly distributed analyte.

Chemical imaging beyond the diffraction limit: experimental validation of the PTIR technique.

Photothermal induced resonance (PTIR) has recently attracted great interest for enabling chemical identification and imaging with nanoscale resolution. In this work, electron beam nanopatterned polymer samples are fabricated directly on 3D zinc selenide prisms and used to experimentally evaluate the PTIR lateral resolution, sensitivity and linearity. It is shown that PTIR lateral resolution for chemical imaging is comparable to the lateral resolution obtained in the atomic force microscopy height images, up to the smallest feature measured (100 nm). Spectra and chemical maps are produced from the thinnest sample analyzed (40 nm). More importantly, experiments show for the first time that the PTIR signal increases linearly with thickness for samples up to ≈ 1 µm (linearity limit); a necessary requirement towards the use of the PTIR technique for quantitative chemical analysis at the nanoscale. Finally, the analysis of thicker samples provides the first evidence that the previously developed PTIR signal generation theory is correct. It is believed that the findings of this work will foster nanotechnology development in disparate applications by proving the basis for quantitative chemical analysis with nanoscale resolution.

Impact of titanium adhesion layers on the response of arrays of metallic split-ring resonators (SRRs).

At higher frequencies (visible and infrared) both the dimensions and the individual metal properties play an important role in determining the resonant response of arrays of SRRs. As a result, a substantial difference between the responses of gold- and Al-based SRR arrays has been observed. Additionally, deposition of gold SRRs onto a substrate typically involves the use of an additional adhesion layer. Titanium (Ti) is the most common adhesive thin-film material used to attach gold onto dielectric/semiconductor substrates. In this paper we investigate the impact of the Ti adhesion layer on the overall response of Au-based nano-scale SRRs. The results quantify the extent to which the overall difference in the resonance frequencies between Au- and Al-based SRRs is due to the presence of the Ti. We show that even a 2-nm-thick Ti layer can red-shift the position of SRR resonance by 20 nm. Finally, we demonstrate that by intentional addition of titanium in the Au-based SRRs, their overall resonant response can be tuned widely in frequency, but at the expense of resonance magnitude.

Magnetic response of split ring resonators (SRRs) at visible frequencies.

In this paper, we report on a substantial shift in the response of arrays of similarly sized Split Ring Resonators (SRRs), having a rectangular U-shaped form--and made respectively of aluminium and of gold. We also demonstrate that it is possible to obtain the polarization dependent LC peak in the visible spectrum--by using SRRs based on aluminium, rather than gold. The response of metallic SRRs scales linearly with size. At optical frequencies, metals stop behaving like nearly perfect conductors and begin displaying characteristically different behaviour, in accord with the Drude model. The response at higher frequencies, such as those in the visible and near infra-red, depends both on their size and on the individual properties of the metals used. A higher frequency limit has been observed in the polarization dependent response (in particular the LC resonance peak) of gold based SRRs in the near infrared region. By using aluminium based SRRs instead of gold, the higher frequency limit of the LC resonance can be further shifted into the visible spectrum.

Asymmetric split ring resonators for optical sensing of organic materials.

Asymmetric Split Ring Resonators are known to exhibit resonant modes where the optical electric field is strongest near the ends of the arms, thereby increasing the sensitivity of spectral techniques such as surface enhanced Raman scattering (SERS). By producing asymmetry in the structures, the two arms of the ring produce distinct plasmonic resonances related to their lengths - but are also affected by the presence of the other arm. This combination leads to a steepening of the slope of the reflection spectrum between the resonances that increases the sensitivity of the resonant behavior to the addition of different molecular species. We describe experimental results, supported by simulation, on the resonances of a series of circular split ring resonators with different gap and section lengths--at wavelengths in the mid-infra red regions of the spectrum--and their utilization for highly sensitive detection of organic compounds. We have used thin films of PMMA with different thicknesses, resulting in characteristic shifts from the original resonance. We also demonstrate matching of asymmetric split ring resonators to a molecular resonance of PMMA.