Accurate In Vivo Bowman's Thickness Measurement Using Mirau Ultrahigh Axial Resolution Line Field Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the accuracy, repeatability, and performance limits of in vivo Mirau ultrahigh axial resolution (UHR) line field spectral domain (LF-SD) optical coherence tomography (OCT) for the measurement of Bowman's and epithelial thickness, and to provide a reference range of these values for healthy corneas. Methods: Volunteers with no history and evidence of corneal disease were included in this study. An in vivo graph search image segmentation of the central cornea was obtained at the normal interface vector orientation. The Mirau-UHR-LF-SD-OCT system used has an axial resolution down to 2.4 µm in air (1.7 µm in tissue), with an A-scan speed of 204.8 kHz and a signal to noise ratio (sensitivity) of 69 (83) dB. Results: Nine volunteers were included, one of whom wore contact lenses. The repeatability of mean Bowman's and epithelial thicknesses were 0.3 and 1.0 µm, respectively. The measured 95% population range for healthy in vivo thickness was 13.7 to 19.6 µm for the Bowman's layer, and 41.9 to 61.8 µm for the epithelial layer. Conclusions: The measured thicknesses of Bowman's layer and the corneal epithelium using the Mirau-UHR-LF-SD-OCT were both accurate, with the range for healthy in vivo thicknesses matching prior confocal and OCT systems of varying axial resolutions, and repeatable, equaling the best value prior reported. Translational Relevance: T1. Development of a commercially viable clinical UHR OCT technology, enabling accurate measurement and interpretation of Bowman's and epithelial layer thickness in clinical practice.

HR-Si prism coupled tightly confined spoof surface plasmon polaritons mode for terahertz sensing.

We report a high-resistivity silicon (HR-Si) prism coupled terahertz (THz) spoof surface plasmon polaritons (SSPPs) on flat subwavelength metasurface. Using a high refractive index prism as an external coupler, a more tightly confined SSPPs mode can be excited in a smaller resonant cavity, leading to strong light-matter interaction. Besides, theoretical analysis and experimental results have both indicated that the SSPPs resonance response to the filling patterns of analyte in the resonant cavity are quite different. In particular, we have found that the interaction between analyte and SSPPs wave can be maximized when the analyte filled with the whole resonant cavity and a higher sensitivity for THz sensing can be obtained. A high sensitivity varied from 0.31 THz/RIU to 0.85 THz/RIU is predicted. Furthermore, these SSPPs modes exhibit high Q-factor, and characteristic spectra of water caused by surface plasmon resonance (SPR) are observed, which is significant in promoting the THz-SPR sensing of polar liquids or aqueous analytes with THz metasurfaces.

Trapping waves with tunable prism-coupling terahertz metasurfaces absorber.

We experimentally demonstrated a corrugated metallic metasurface based tunable perfect absorber for terahertz (THz) frequencies in a total internal reflection geometry. The absorbance is strongly depend on the central layer of this three-layer absorber, which provides a feasible approach to tune the absorption. In particular, there exist an optimal gap that enables a perfect absorption at specific frequency. Due to the simple 1D geometric structure of metasurface, its absorption frequency can be easily tailored over a wide frequency range (0.625-1.499 THz). More importantly, the modulation of the effective refractive index and loss of medium environment can be accepted as an alternative approach for the absorption properties modulation. This prism coupling absorber provides a new route for modulation of the absorption characteristics with potential applications in biological sensing.

Optical manipulation of Rayleigh particles by metalenses-a numerical study.

Based on the focusing feature of a metalens, we numerically studied its application in optical manipulation of Rayleigh particles. Three types of metalenses-point focusing, line focusing, and line focusing with phase gradient-were designed. Simulation results using the finite-difference time-domain method showed that the incident optical beams could be focused into a spot or a line for stable particle trapping. Through engineering a gradient phase in the direction of the focal line, the proposed metalens can push the particles along the line. This provides a unique capability to move particles along a line without the need of any mechanical movement. Given its thin sheet structure and compactness, the proposed metalens can be easily integrated into microfluidic and optical tweezers systems, and it can find potential applications in optical sorting of biological cells.

Terahertz phase jumps for ultra-sensitive graphene plasmon sensing.

Phase behavior of the reflected terahertz radiation (THz) under surface plasmon resonance (SPR) supported by doped graphene has been comprehensively investigated via theoretical analysis with simulation verifications. For a TM-polarized wave, the dependence of the phase on the angle of incidence has a region with an abrupt jump-like change. We found in particular that the resonance phase dependence would change from step-like contour to Fano lineshape when the system passed through the optimum SPR conditions (i.e., R = 0) in terahertz regime. Monitoring the transformation could provide ultrahigh-sensitive label-free detection of biomolecules. Importantly, the characteristic of phase jumps as a readout response to achieve refractive index sensing that outperforms traditional terahertz-amplitude-based attenuated total reflection (ATR) spectroscopy is valuable. The results demonstrated a high figure of merit (FOM) of up to 171, based on the terahertz phase information. Moreover, the sensing range could be tuned by changing the surface conductivity of graphene via high doping levels or with few-layer graphene. These terahertz phase response characteristics of graphene plasmon are promising for tunable ultra-sensitivity (bio)chemical sensing applications.

Deformation velocity imaging using optical coherence tomography and its applications to the cornea.

Optical coherence tomography (OCT) can monitor human donor corneas non-invasively during the de-swelling process following storage for corneal transplantation, but currently only resultant thickness as a function of time is extracted. To visualize and quantify the mechanism of de-swelling, we present a method exploiting the nanometer sensitivity of the Fourier phase in OCT data to image deformation velocities. The technique was demonstrated by non-invasively showing during de-swelling that osmotic flow through an intact epithelium is negligible and removing the endothelium approximately doubled the initial flow at that interface. The increased functional data further enabled the validation of a mathematical model of the cornea. Included is an efficient method of measuring high temporal resolution (1 minute demonstrated) corneal thickness, using automated collection and semi-automated graph search segmentation. These methods expand OCT capabilities to measure volume change processes for tissues and materials.

Investigating Intra-Tablet Coating Uniformity With Spectral-Domain Optical Coherence Tomography.

Spectral domain optical coherence tomography (SD-OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for direct quantification of thin film coatings that cannot easily be resolved with other techniques. While previous studies with SD-OCT have estimated the intra-tablet coating uniformity, the estimates were based on limited number of B-scans. In order to obtain a more accurate estimate, a greater number of B-scans are required that can quickly lead to an overwhelming amount of data. To better manage the data so as to generate a more accurate representation of the intra-tablet coating uniformity without compromising on the achievable axial resolution and imaging depth, we comprehensively examine an algebraic reconstruction technique with OCT to significantly reduce the data required. Specifically, a set of coated pharmaceutical tablets with film coating thickness in the range of 60-100 µm is investigated. Results obtained from performing the reconstruction reveal that only 30% of the acquired data are actually required leading to a faster convergence time and a generally good agreement with benchmark data against the intra-tablet coating uniformity measured with terahertz pulsed imaging technology.

High resolution corneal and single pulse imaging with line field spectral domain optical coherence tomography.

We report the development of a Spectral Domain Line Field Optical Coherence Tomography (LF-OCT) system, using a broad bandwidth and spatial coherent Super-Continuum (SC) source. With conventional quasi-Continuous Wave (CW) setup we achieve axial resolutions up to 2.1 µm in air and 3D volume imaging speeds up to 213 kA-Scan/s. Furthermore, we report the use of a single SC pulse, of 2 ns duration, to temporally gate an OCT B-Scan image of 70 A-Scans. This is the equivalent of 35 GA-Scans/s. We apply the CW setup for high resolution imaging of the fine structures of a human cornea sample ex-vivo. The single pulse setup is applied to imaging of a coated pharmaceutical tablet. The fixed pattern noise due to spectral noise is removed by subtracting the median magnitude A-Scan. We also demonstrate that the Fourier phase can be used to remove aberration caused artefacts.

Vertically-oriented nanoparticle dimer based on focused plasmonic trapping.

We proposed a vertically-oriented dimer structure based on focused plasmonic trapping of metallic nanoparticle. Quantitative FDTD calculations and qualitative analysis by simplified dipole approximation revealed that localized surface plasmon coupling dominates in the plasmon hybridization, and the vertically-oriented dimer can effectively make use of the dominant longitudinal component of the surface plasmon virtual probe thus providing much stronger electric field in the gap. Furthermore, for practical application the top nanoparticle of the dimer can be replaced with an atomic force microscope tip which enables the precise control of the gap distance of the dimer. Therefore the proposed vertically-oriented dimer structure provides both the scanning capability and the extremely-high electrical field necessary for the high sensitivity Raman imaging.

Nondestructive analysis of automotive paints with spectral domain optical coherence tomography.

We have demonstrated for the first time, to our knowledge, the use of optical coherence tomography (OCT) as an analytical tool for nondestructively characterizing the individual paint layer thickness of multiple layered automotive paints. A graph-based segmentation method was used for automatic analysis of the thickness distribution for the top layers of solid color paints. The thicknesses measured with OCT were in good agreement with the optical microscope and ultrasonic techniques that are the current standard in the automobile industry. Because of its high axial resolution (5.5 µm), the OCT technique was shown to be able to resolve the thickness of individual paint layers down to 11 µm. With its high lateral resolution (12.4 µm), the OCT system was also able to measure the cross-sectional area of the aluminum flakes in a metallic automotive paint. The range of values measured was 300-1850 µm2. In summary, the proposed OCT is a noncontact, high-resolution technique that has the potential for inclusion as part of the quality assurance process in automobile coating.

Non-destructive evaluation of polymer coating structures on pharmaceutical pellets using full-field optical coherence tomography.

Full-field optical coherence tomography (FF-OCT) using a conventional light-emitting diode and a complementary metal-oxide semiconductor camera has been developed for characterising coatings on small pellet samples. A set of en-face images covering an area of 700 × 700 µm(2) was taken over a depth range of 166 µm. The three-dimensional structural information, such as the coating thickness and uniformity, was subsequently obtained by analysis of the recorded en-face images. Drug-loaded pharmaceutical sustained-release pellets with two coating layers and of a sub-millimetre diameter were studied to demonstrate the usefulness of the developed system. We have shown that both coatings can be clearly resolved and the thickness was determined to be 40 and 50 µm for the outer and inner coating layers, respectively. It was also found that the outer coating layer is relatively uniform, whereas the inner coating layer has many particle-like features. X-ray computed microtomography measurements carried out on the same pellet sample confirmed all these findings. The presented FF-OCT approach is inexpensive and has better spatial resolution compared with other non-destructive analysis techniques such as terahertz pulsed imaging, and is thus considered advantageous for the quantitative analysis of thin coatings on small pellet samples.

Terahertz pulsed spectroscopy and imaging for pharmaceutical applications: a review.

The terahertz region of the electromagnetic spectrum spans the frequency range between the infrared and the microwave. Traditionally the exploitation of this spectral region has been difficult owing to the lack of suitable source and detector. Over the last ten years or so, terahertz technology has advanced considerably with both terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) instruments now commercially available. This review outlines some of the recent pharmaceutical applications of terahertz pulsed spectroscopy and imaging. The following application areas are highlighted: (1) discrimination and quantification of polymorphs/hydrates, (2) analysis of solid form transformation dynamics, (3) quantitative characterisation of tablet coatings: off-line and on-line, (4) tablet coating and dissolution, (5) spectroscopic imaging and chemical mapping. This review does not attempt to offer an exhaustive assessment of all anticipated pharmaceutical applications; rather it is an attempt to raise the awareness of the emerging opportunities and usefulness offered by this exciting technology.