A Self-Immolative Fluorescent Probe for Selective Detection of SARS-CoV-2 Main Protease.

Existing tools to detect and visualize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suffer from low selectivity, poor cell permeability, and high cytotoxicity. Here we report a novel self-immolative fluorescent probe (MP590) for the highly selective and sensitive detection of the SARS-CoV-2 main protease (Mpro). This fluorescent probe was prepared by connecting a Mpro-cleavable peptide (N-acetyl-Abu-Tle-Leu-Gln) with a fluorophore (i.e., resorufin) via a self-immolative aromatic linker. Fluorescent titration results show that MP590 can detect Mpro with a limit of detection (LoD) of 35 nM and is selective over interferents such as hemoglobin, bovine serum albumin (BSA), thrombin, amylase, SARS-CoV-2 papain-like protease (PLpro), and trypsin. The cell imaging data indicate that this probe can report Mpro in HEK 293T cells transfected with a Mpro expression plasmid as well as in TMPRSS2-VeroE6 cells infected with SARS-CoV-2. Our results suggest that MP590 can both measure and monitor Mpro activity and quantitatively evaluate Mpro inhibition in infected cells, making it an important tool for diagnostic and therapeutic research on SARS-CoV-2.

Noncontact Strain Monitoring of Osseointegrated Prostheses.

The objective of this study was to develop a noncontact, noninvasive, imaging system for monitoring the strain and deformation states of osseointegrated prostheses. The proposed sensing methodology comprised of two parts. First, a passive thin film was designed such that its electrical permittivity increases in tandem with applied tensile loading and decreases while unloading. It was found that patterning the thin films could enhance their dielectric property's sensitivity to strain. The film can be deposited onto prosthesis surfaces as an external coating prior to implant. Second, an electrical capacitance tomography (ECT) measurement technique and reconstruction algorithm were implemented to capture strain-induced changes in the dielectric property of nanocomposite-coated prosthesis phantoms when subjected to different loading scenarios. The preliminary results showed that ECT, when coupled with strain-sensitive nanocomposites, could quantify the strain-induced changes in the dielectric property of thin film-coated prosthesis phantoms. The results suggested that ECT coupled with embedded thin films could serve as a new noncontact strain sensing method for scenarios when tethered strain sensors cannot be used or instrumented, especially in the case of osseointegrated prostheses.

Understanding the effects of Doppler phenomena in white light Fabry-Perot interferometers for simultaneous position and velocity measurement.

In static tests, low-power (<5 mW) white light extrinsic Fabry-Perot interferometric position sensors offer high-accuracy (µm) absolute measurements of a target's position over large (cm) axial-position ranges, and since position is demodulated directly from phase in the interferogram, these sensors are robust to fluctuations in measured power levels. However, target surface dynamics distort the interferogram via Doppler shifting, introducing a bias in the demodulation process. With typical commercial off-the-shelf hardware, a broadband source centered near 1550 nm, and an otherwise typical setup, the bias may be as large as 50-100 µm for target surface velocities as low as 0.1 mm/s. In this paper, the authors derive a model for this Doppler-induced position bias, relating its magnitude to three swept-filter tuning parameters. Target velocity (magnitude and direction) is calculated using this relationship in conjunction with a phase-diversity approach, and knowledge of the target's velocity is then used to compensate exactly for the position bias. The phase-diversity approach exploits side-by-side measurement signals, transmitted through separate swept filters with distinct tuning parameters, and permits simultaneous measurement of target velocity and target position, thereby mitigating the most fundamental performance limitation that exists on dynamic white light interferometric position sensors.

Dynamics of a noncontacting, white light Fabry-Perot interferometric displacement sensor.

A white light extrinsic Fabry-Perot interferometer is implemented as a noncontacting displacement sensor, providing robust, absolute displacement measurements with micrometer accuracy at a sampling rate of 10 Hz. This paper presents a dynamic model of the sensing cavity between the sensor probe and the nearby target surface using a Fabry-Perot etalon approach obtained from straightforward electromagnetic field formulations. Such a model is important for system characterization, as the dynamically changing cavity length imparts a Doppler shift on any signals circulating within the sensing cavity. Contrary to previously published results, Doppler-induced shifting within the low-finesse sensing cavity is shown to significantly distort the measurement signal as recorded by the sensor. Experimental and simulation results are compared, and the direct effects of cavity dynamics on the measurement signal are analyzed along with their indirect impact on sensor performance. This document has been approved by Los Alamos National Laboratory for unlimited public release (LA-UR 12-00301).

A probabilistic computational framework for the prediction of corrosion-induced cracking in large structures.

Corrosion can initiate cracking that leads to structural integrity reduction. Quantitative corrosion assessment is challenging, and the modeling of corrosion-induced crack initiation is essential for model-based corrosion reliability analysis of various structures. This paper proposes a probabilistic computational analysis framework for corrosion-to-crack transitions by integrating a phase-field model with machine learning and uncertainty quantification. An electro-chemo-mechanical phase-field model is modified to predict pitting corrosion evolution, in which stress is properly coupled into the electrode chemical potential. A crack initiation criterion based on morphology is proposed to quantify the pit-to-cracking transition. A spatiotemporal surrogate modeling method is developed to facilitate this, consisting of a Convolution Neural Network (CNN) to map corrosion morphology to latent spaces, and a Gaussian Process regression model with a nonlinear autoregressive exogenous model (NARX) architecture for prediction of corrosion dynamics in the latent space over time. It enables the real-time prediction of corrosion morphology and crack initiation behaviors (whether, when, and where the corrosion damage triggers the crack initiation), and thus makes it possible for probabilistic analysis, with uncertainty quantified. Examples at various stress and corrosion conditions are presented to demonstrate the proposed computational framework.

Using a validated transmission model for the optimization of bundled fiber optic displacement sensors.

A variety of intensity-modulated optical displacement sensor architectures have been proposed for use in noncontacting sensing applications, with one of the most widely implemented architectures being the bundled displacement sensor. To the best of the authors' knowledge, the arrangement of measurement fibers in previously reported bundled displacement sensors has not been configured with the use of a validated optical transmission model. Such a model has utility in accurately describing the sensor's performance a priori and thereby guides the arrangement of the fibers within the bundle to meet application-specific performance needs. In this paper, a recently validated transmission model is used for these purposes, and an optimization approach that employs a genetic algorithm efficiently explores the design space of the proposed bundle sensor architecture. From the converged output of the optimization routine, a bundled displacement sensor configuration is designed and experimentally tested, offering linear performance with a sensitivity of -0.066 µm(-1) and displacement measurement error of 223 µm over the axial displacement range of 6-8 mm. It is shown that this optimization approach may be generalized to determine optimized bundle configurations that offer high-sensitivity performance, with an acceptable error level, over a variety of axial displacement ranges. This document has been approved by Los Alamos National Laboratory for unlimited public release (LA-UR 11-03413).

Spatial ultrasonic wavefront characterization using a laser parametric curve scanning method.

Ultrasonic wavefield imaging (UWI) provides insightful spatial information about ultrasonic wave propagation in planar (2-D) space for nondestructive evaluation and structural health monitoring (NDE-SHM) applications. In all materials, the wavefronts of the incident and reflected waves propagate with unique patterns that may be represented by parametrized polar curves in 2-D geometric space. In this paper, a spatial ultrasonic wavefront characterization method based on a parametric curve laser scan is proposed to characterize the spatial ultrasonic wavefront for both isotropic and anisotropic materials. Three parametric curves (circular, hyperbolic, and cyclic-harmonic curves) were considered. Two wavefront characterization process were carried out, namely (i) deciding the parametric equation of the closed-form geometric plane curve via UWI, and (ii) measuring and updating the ultrasound via laser ultrasonic interrogation system (LUIS) and quantifying the values(s) of the predicted parametric curve equation using a temporal cross-correlation technique. The proposed method was tested on pristine aluminum and cross-ply CFRP plates to characterize the spatial incident and reflected wavefronts of the plates. The non-fiber direction region (105°â©½Ï•S⩽165°) and the fiber direction region (165°â©½Ï•S⩽195°) of the cross-ply CFRP plate were considered in the test. The laser circle scan and the laser cyclic-harmonic curve scan showed the ability to characterize the incident wavefronts of the S0 and A0 modes in the aluminum plate and the CFRP plate, respectively, followed by the laser hyperbolic curve scan. With the promising results obtained in the proposed method, the integration of the parametric curve scanning method into LUIS may provide a new approach to damage detection and useful information for ultrasonic algorithm design in NDE-SHM applications.

Scattering of plane guided waves obliquely incident on a straight feature with uniform cross-section.

A frequency-domain finite element (FE) method is presented for modeling the scattering of plane guided waves incident on an infinitely-long, straight feature with uniform cross-section in a planar host waveguide. The method utilizes a mesh of 2-dimensional finite elements with harmonic shape functions in the perpendicular direction. The model domain comprises a cross-section through the feature and short lengths of the adjoining host waveguide. A spatial frequency equal to the wavenumber of the desired incident mode multiplied by the sine of the desired incidence angle is prescribed for the element shape functions. An integral representation of the incident mode is used to determine a suitable system of harmonic forces to uniquely excite that mode. These are applied at nodes through the thickness of the host waveguide on one side of the feature. The displacement field is measured at nodes through the thickness of the host waveguide on either side of the feature and decomposed into reflected and transmitted modes. The cases of guided wave transmission in a featureless waveguide and the reflection of guided waves from a free-edge are examined as validation cases. Finally, the results for transmission at an adhesively-bonded stiffener are presented and compared with experimental measurements.

Dispersion curve estimation via a spatial covariance method with ultrasonic wavefield imaging.

Numerous Lamb wave dispersion curve estimation methods have been developed to support damage detection and localization strategies in non-destructive evaluation/structural health monitoring (NDE/SHM) applications. In this paper, the covariance matrix is used to extract features from an ultrasonic wavefield imaging (UWI) scan in order to estimate the phase and group velocities of S0 and A0 modes. A laser ultrasonic interrogation method based on a Q-switched laser scanning system was used to interrogate full-field ultrasonic signals in a 2-mm aluminum plate at five different frequencies. These full-field ultrasonic signals were processed in three-dimensional space-time domain. Then, the time-dependent covariance matrices of the UWI were obtained based on the vector variables in Cartesian and polar coordinate spaces for all time samples. A spatial covariance map was constructed to show spatial correlations within the full wavefield. It was observed that the variances may be used as a feature for S0 and A0 mode properties. The phase velocity and the group velocity were found using a variance map and an enveloped variance map, respectively, at five different frequencies. This facilitated the estimation of Lamb wave dispersion curves. The estimated dispersion curves of the S0 and A0 modes showed good agreement with the theoretical dispersion curves.

Bragg grating-based fibre optic sensors in structural health monitoring.

This work first considers a review of the dominant current methods for fibre Bragg grating wavelength interrogation. These methods include WDM interferometry, tunable filter (both Fabry-Perot and acousto-optic) demultiplexing, CCD/prism technique and a newer hybrid method utilizing Fabry-Perot and interferometric techniques. Two applications using these techniques are described: hull loads monitoring on an all-composite fast patrol boat and bolt pre-load loss monitoring in a composite beam in conjunction with a state-space modelling data analysis technique.