A dual-modal approach using Raman spectroscopy and optical pH sensing was investigated to discriminate between normal and cancerous tissues. Raman spectroscopy has demonstrated the potential for in vivo cancer detection. However, Raman spectroscopy has suffered from strong fluorescence background of biological samples and subtle spectral differences between normal and disease tissues. To overcome those issues, pH sensing is adopted to Raman spectroscopy as a dual-modal approach. Based on the fact that the pH level in cancerous tissues is lower than that in normal tissues due to insufficient vasculature formation, the dual-modal approach combining the chemical information of Raman spectrum and the metabolic information of pH level can improve the specificity of cancer diagnosis. From human breast tissue samples, Raman spectra and pH levels are measured using fiber-optic-based Raman and pH probes, respectively. The pH sensing is based on the dependence of pH level on optical transmission spectrum. Multivariate statistical analysis is performed to evaluate the classification capability of the dual-modal method. The analytical results show that the dual-modal method based on Raman spectroscopy and optical pH sensing can improve the performance of cancer classification.
To discriminate between normal and cancerous tissue, a dual modal approach using Raman spectroscopy and pH sensor was designed and applied. Raman spectroscopy has demonstrated the possibility of using as diagnostic method for the early detection of precancerous and cancerous lesions in vivo. It also can be used in identifying markers associated with malignant change. However, Raman spectroscopy lacks sufficient sensitivity due to very weak Raman scattering signal or less distinctive spectral pattern. A dual modal approach could be one of the solutions to solve this issue. The level of extracellular pH in cancer tissue is lower than that in normal tissue due to increased lactic acid production, decreased interstitial fluid buffering and decreased perfusion. High sensitivity and specificity required for accurate cancer diagnosis could be achieved by combining the chemical information from Raman spectrum with metabolic information from pH level. Raman spectra were acquired by using a fiber optic Raman probe, a cooled CCD camera connected to a spectrograph and 785 nm laser source. Different transmission spectra depending on tissue pH were measured by a lossy-mode resonance sensor based on fiber optic. The discriminative capability of pH-Raman dual modal method was evaluated using principal component analysis (PCA). The obtained results showed that the pH-Raman dual modal approach can improve discriminative capability between normal and cancerous tissue, which can lead to very high sensitivity and specificity. The proposed method for cancer detection is expected to be used in endoscopic diagnosis later.
An optical method of measuring the number of layers in a graphene sample is formulated and compared with the conventional surface plasmon resonance (SPR) detection scheme, the latter being appropriate only for a very few graphene layers. Numerical results based on transfer-matrix method support that an alternative method, wherein the SPR substrate includes a dielectric overlayer, is feasible over a wide range of graphene layer numbers. While the multilayer graphene may lead to a broad and shallow SPR curve owing to the nonzero imaginary part in its relative permittivity, the dielectric overlayer makes the resonant surface plasmons less affected by graphene, resulting in a strong and deep absorption band at resonance. Linear regression analysis shows that the measurable graphene layer number can be as high as 50.
We investigated the effect of rough surface on the performance of extinction-based localized surface plasmon resonance
(LSPR) biosensors. The sensor measures resonance wavelength shifts in transmittance due to biomolecular interactions
amplified by periodic nanostructures. The numerical calculation was conducted using rigorous coupled-wave analysis
with Gaussian random profiles. The results suggest that, when a surface has a roughness smaller than 2 nm, the
sensitivity of an LSPR biosensor is not significantly affected regardless of correlation length (CL). However, we found
that extinction peak amplitude and curve width are affected substantially with a decrease in CL. At CL less than 100 nm,
surface roughness may induce interference between localized surface plasmons excited by the surface and nanowires,
which can lead to significant degradation of sensor performance.
In this study, we investigated the impact of surface roughness on the sensitivity of conventional and nanowire-based
surface plasmon resonance (SPR) biosensors. The theoretical research was conducted using rigorous coupled-wave
analysis with Gaussian surface profiles of gold films determined by atomic force microscopy. The results suggest that,
when surface roughness ranges 1 nm, the sensitivity of a conventional SPR system is not significantly affected regardless
of the correlation length. For a nanowire-based SPR biosensor, however, we found that the sensitivity degrades
substantially with a decreasing correlation length. Particularly, at a correlation length smaller than 100 nm, random
rough surface may induce destructive coupling between excited localized surface plasmons, which can lead to prominent
reduction of sensitivity enhancement.
In this study, we experimentally confirmed the sensitivity enhancement by the nanowire-based surface plasmon
resonance (SPR) sensor structure. Gold nanowire samples with a period of 500 nm were fabricated by interference
lithography on a gold-SF10 glass substrate. Sensitivity enhancement compared to a conventional SPR structure was
measured to be 31% when evaluated using a varied concentration of ethanol at a dielectric surrounding layer. This result
is consistent with numerical data of rigorous coupled-wave analysis. Rough surfaces of thin gold film and gold
nanowires are deemed to induce the sensitivity degradation by more than 10%. More significant sensitivity improvement
can be achieved by implementing finer nanowires.
In this study, we investigate the impact of the cross sectional profile of an array of metallic nanowires on the feasibility of a localized surface plasmons resonance (LSPR) biosensor. Calculations were performed using rigorous coupled wave analysis with an emphasis on the extinction properties of the LSPR structure. It was confirmed that the resonance spectrum strongly depends on the nanowire period and profile. Our numerical results indicate that the nanowire structure, particularly that of a T-profile, delivers extremely linear sensing performance over a wide range of target refractive index with much enhanced sensitivity. The extinction-based LSPR structure also involves relatively large dimension and thus is expected to provide a feasible biosensor using current semiconductor technology.
In this study, localized surface plasmon resonance (SPR) biosensors with gold nanowires regularly patterned on a gold film are considered for sensitivity enhancement. The theoretical investigation was conducted using rigorous coupled wave analysis (RCWA) in terms of various design metrics, such as the resonance angle shift, the SPR curve angular width (SPR CAW), and the minimum reflectance at resonance (MRR). Especially, when LSP modes couple resonantly, broad SPR CAW and shallow MRR as well as a large shift of the resonance angle can be observed due to absorptive damping and localized coupling. The results show that, in general, nanowires of a T-profile present more effective sensitivity enhancement than an inverse T-profile. The sensitivity enhancement mediated by the presence of nanowires has been clarified qualitatively based on the dispersion relation between metal film involving nanowires and surrounding dielectric medium. Moreover, optimal design parameters of nanowires are determined based on quantitative metrics that measure the sensor performance and the fabrication reliability.
It is well known that the use of noble metal nanoparticles can considerably enhance the sensitivity of conventional surface plasmon resonance (SPR) biosensors. In our study, we theoretically investigate this sensitivity enhancement effect using rigorous coupled-wave analysis. It is based on the assumption that the enhancement of localized plasmons can be demonstrated by the coupling phenomenon between the periodic noble metal structures and the incident light with an appropriate polarization. It is shown that the rigorous coupled-wave method can be applied to calculating a SPR structure that includes metallic nanoparticles of rectangular-like geometry, where the presence of nanoparticles induces significant changes in the position of reflectivity minimum. The influence of the nanoparticle period on the sensitivity enhancement is also confirmed. In the calculation, Au nanoparticles deposited on an Au film or adsorbed on a SAM layer are modified to regularly patterned one-dimensional nanowires. When the period is less than 300 nm, the calculated sensitivity enhancement of the nanoparticle-based SPR structure is more than ten-fold compared with that of a conventional SPR biosensors configuration.
When fabricating a large area holographic diffuser by cascading hologram of diffusion patterns with specified are, it was found that a fluctuation of diffraction intensity occurred at the boundaries of the two adjacent exposed areas. It was affirmed experimentally that this problem could be alleviated by controlling the intensity distribution of reference laser beam around the boundary of each exposure area. Using these method, the fluctuation was reduced considerably. For better compensation of the non- uniformity a theoretical analysis for the diffusion process of photopolymer is discussed and compared with the experimental result.
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