Low-dose intrapulmonary drug delivery device for studies on next-generation therapeutics in mice.

Although nebulizers have been developed for delivery of small molecules in human patients, no tunable device has been purpose-built for targeted delivery of modern large molecule and temperature-sensitive therapeutics to mice. Mice are used most of all species in biomedical research and have the highest number of induced models for human-relevant diseases and transgene models. Regulatory approval of large molecule therapeutics, including antibody therapies and modified RNA highlight the need for quantifiable dose delivery in mice to model human delivery, proof-of-concept studies, efficacy, and dose-response. To this end, we developed and characterized a tunable nebulization system composed of an ultrasonic transducer equipped with a mesh nebulizer fitted with a silicone restrictor plate modification to control the nebulization rate. We have identified the elements of design that influence the most critical factors to targeted delivery to the deep lungs of BALB/c mice. By comparing an in silico model of the mouse lung with experimental data, we were able to optimize and confirm the targeted delivery of over 99% of the initial volume to the deep portions of the mouse lung. The resulting nebulizer system provides targeted lung delivery efficiency far exceeding conventional nebulizers preventing waste of expensive biologics and large molecules during proof-of-concept and pre-clinical experiments involving mice. (Word Count =207).

Amplifying Lamb Wave Detection for Fiber Bragg Grating with a Phononic Crystal GRIN Lens Waveguide.

This paper demonstrates that a graded-index (GRIN) phononic lens, combined with a channel waveguide, can focus anti-symmetric Lamb waves for extraction by a detector with strong directional sensitivity. Guided ultrasonic wave inspection is commonly applied for structural health monitoring applications; however, obtaining sufficient signal amplitude is a challenge. In addition, fiber Bragg grating (FBG) sensors have strong directional sensitivity. We fabricate the GRIN structure, followed by a channel waveguide starting at the focal point, using a commercial 3D printer and mount it on a thin aluminum plate. We characterize the focusing of the A0 mode Lamb wave in the plate, traveling across the GRIN lens using 3D laser Doppler vibrometry. We also measure the extraction of focused energy using an FBG sensor, examining the optimal sensor bond location and bond length in the channel of the waveguide for maximum signal extraction. The measured amplification of the ultrasound signal is compared to theoretical predictions. The results demonstrate that significant amplification of the waveform is achieved and that selecting the location of the FBG sensor in the channel is critical to optimizing the amplification.

Demonstration of Coherent Interference between Acoustic Waves Using a Fiber Ring Resonator.

Optical fibers were previously demonstrated to propagate and detect acoustic modes that were converted from Lamb waves for structural health-monitoring applications; typically, a fiber Bragg grating sensor in the optical fiber is used to detect acoustic modes. Acoustic modes can transfer from one fiber to another through a simple adhesive bond coupler, preserving the waveform of the acoustic mode. This paper experimentally investigates the coherence of acoustic waves through the adhesive coupler, using a fiber ring resonator (FRR) configuration. This configuration was chosen because the wave coupled to the second fiber interferes with the original wave after it encircles the fiber ring. We performed this experiment using different geometries of optical fibers in the ring, including a standard single-mode optical fiber, a hollow silica capillary tube, and a large-diameter multi-mode fiber. The results demonstrate that the acoustic wave, when transferring through an adhesive coupler, interferes coherently even when the main and ring fibers are of different types. Finally, we demonstrate that the FRR can be applied for sensing applications by measuring the mode attenuations in the ring due to a changing external environment (water-level sensing) and measuring the optical-path length change in the ring (temperature sensing).

Optical Fiber Sensors for Ultrasonic Structural Health Monitoring: A Review.

Guided waves (GW) and acoustic emission (AE) -based structural health monitoring (SHM) have widespread applications in structures, as the monitoring of an entire structure is possible with a limited number of sensors. Optical fiber-based sensors offer several advantages, such as their low weight, small size, ability to be embedded, and immunity to electro-magnetic interference. Therefore, they have long been regarded as an ideal sensing solution for SHM. In this review, the different optical fiber technologies used for ultrasonic sensing are discussed in detail. Special attention has been given to the new developments in the use of FBG sensors for ultrasonic measurements, as they are the most promising and widely used of the sensors. The paper highlights the physics of the wave coupling to the optical fiber and explains the different phenomena such as directional sensitivity and directional coupling of the wave. Applications of the different sensors in real SHM applications have also been discussed. Finally, the review identifies the encouraging trends and future areas where the field is expected to develop.

Acoustic wave coupling between optical fibers of different geometries.

In this study, we investigate coupling of acoustic guided waves from different types of input fibers, through a bonded coupler, to an optical fiber. These acoustic waves can then be detected with conventional fiber Bragg gratings (FBGs). The input waves are measured using a high-resolution 3D laser Doppler vibrometer, and the output waves in the optical fiber are measured using an FBG. We demonstrate that the wave coupling between two waveguides varies with the cross-sectional area and the modulus of elasticity of the fibers.

Bi-directional ultrasonic wave coupling to FBGs in continuously bonded optical fiber sensing.

Fiber Bragg grating (FBG) sensors are typically spot-bonded onto the surface of a structure to detect ultrasonic waves in laboratory demonstrations. However, to protect the rest of the optical fiber from any environmental damage during real applications, bonding the entire length of fiber, called continuous bonding, is commonly done. In this paper, we investigate the impact of continuously bonding FBGs on the measured Lamb wave signal. In theory, the ultrasonic wave signal can bi-directionally transfer between the optical fiber and the plate at any adhered location, which could potentially produce output signal distortion for the continuous bonding case. Therefore, an experiment is performed to investigate the plate-to-fiber and fiber-to-plate signal transfer, from which the signal coupling coefficient of each case is theoretically estimated based on the experimental data. We demonstrate that the two coupling coefficients are comparable, with the plate-to-fiber case approximately 19% larger than the fiber-to-plate case. Finally, the signal waveform and arrival time of the output FBG responses are compared between the continuous and spot bonding cases. The results indicate that the resulting Lamb wave signal output is only that directly detected at the FBG location; however, a slight difference in signal waveform is observed between the two bonding configurations. This paper demonstrates the practicality of using continuously bonded FBGs for ultrasonic wave detection in structural health monitoring (SHM) applications.

Increasing signal amplitude in fiber Bragg grating detection of Lamb waves using remote bonding.

Networks of fiber Bragg grating (FBG) sensors can serve as structural health monitoring systems for large-scale structures based on the collection of ultrasonic waves. The demodulation of structural Lamb waves using FBG sensors requires a high signal-to-noise ratio because the Lamb waves are of low amplitudes. This paper compares the signal transfer amplitudes between two adhesive mounting configurations for an FBG to detect Lamb waves propagating in an aluminum plate: a directly bonded FBG and a remotely bonded FBG. In the directly bonded FBG case, the Lamb waves create in-plane and out-of-plane displacements, which are transferred through the adhesive bond and detected by the FBG sensor. In the remotely bonded FBG case, the Lamb waves are converted into longitudinal and flexural traveling waves in the optical fiber at the adhesive bond, which propagate through the optical fiber and are detected by the FBG sensor. A theoretical prediction of overall signal attenuation also is performed, which is the combination of material attenuation in the plate and optical fiber and attenuation due to wave spreading in the plate. The experimental results demonstrate that remote bonding of the FBG significantly increases the signal amplitude measured by the FBG.