Cilia, small, slender, hair-like structures present on the surface of all mammalian cells, play a major role in locomotion and are involved in mechanoreception. Ciliary motion in the upper airway is the primary mechanism by which the body transports foreign particulates out of the respiratory system to maintain proper respiratory function.

Ciliary motion plays a critical role in the overall respiratory health of the upper airway. Cilia beat at a native frequency, and in a synchronized pattern, to continuously transport foreign particulate trapped in a layer of mucous out of the upper airway.

The ciliary beating frequency (CBF) is often disrupted with the onset of disease as well as other conditions, such as changes in temperature or in response to drug administration. Disruption of ciliary motion can lead to severe respiratory diseases and compromised respiratory function.

Measuring CBF is a technical challenge and difficult to perform in vivo. Current imaging of cilia motion relies on microscopy and high-speed cameras which cannot be easily adapted to in vivo imaging.

Phase-contrast microscopy (PCM) is the standard for measuring CBF but has limitations. PCM does not permit appreciation of how CBF varies across the complex landscape of the nasal vault and sinus tissues. Additionally, optical coherence tomography (OCT) has proven to be a powerful imaging modality capable of visualization of ciliary activity, but its field of view is limited.

Spectrally encoded interferometric microscopy
A team of scientists and engineers at the Chen F-OCT Group, part of the Beckman Laser Institute of the Department of Biomedical Engineering at the University of California, Irvine (UCI), have designed a system capable of overcoming these limitations.
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Previously, the group developed a phase resolved Doppler optical coherence tomography (PR-D-OCT) system that was able to obtain lateral cross-sectional images of cilia and cilia movement in real-time. The inventors realized the need to observe the surface dynamics of cilia over time and spatially, so they developed a spectrally encoded interferometric microscopy (SEIM) system with PR-D technology. As a result, fast, high-resolution en face images of human CBF can be captured and processed in real-time. Additionally, the integration of PR-D-OCT with PR-D-SEIM provides a multidimensional view of cilia.
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SEIM has emerged as a high-speed, high-resolution methodology, allowing for visualization of both temporal and spatial ciliary motion patterns across the surface of upper airway tissues, as well as propagation of metachronal wave, says Zhikai Zhu, Ph.D. candidate with the Chen F-OCT Group. SEIM can detect displacement on the nanometer scale at a kilohertz frame rate..
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When coupled with a wavelength-swept laser and a spectral disperser, SEIM can image tissue en face, Zhu explains. SEIM uses a phase-resolved Doppler (PR-D) algorithm to measure and map the CBF within an en face region, providing insight into the changes in CBF across tissue surfaces.

Need for vibration isolation
Since we are imaging cilia tissue that is in motion, we need a stable environment to produce reliable images, Zhu continues. Without vibration isolation, reliable imaging from our SEIM system is sporadic. Our lab is adjacent to a heavy foot traffic area, creating vibrations that affect our signals, Zhu adds. Our need to isolate these ambient vibrations is critical.
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The F-OCT Laboratory selected Negative-Stiffness vibration isolation for its SEIM system. Introduced in the mid-1990s by Minus K Technology, Negative-Stiffness vibration isolation has been widely accepted for vibration-critical applications, largely because of its ability to effectively isolate lower frequencies, both vertically and horizontally.

Advancements in nanofabrication, pharmaceuticals, energy and aerospace follow breakthroughs in the understanding of materials. These breakthroughs unlock unique functionalities that create new pathways to design future devices.

The Center for Nanophase Materials Sciences (CNMS) at Oak Ridge National Laboratory (ORNL) is at the forefront of one of the most powerful capabilities for exploring the nature of materials and energy. CNMS emphasizes discovery of new materials, and the understanding of underlying physical and chemical interactions that enable the creation of nanomaterials.

The center is unique in that it provides a platform for a vibrant national and international research community that brings together ORNL research staff, technical support staff, students, postdoctoral fellows and collaborating guest scientists, accommodating both short-term and long-term collaborative research projects.

To support this impressive research capability, CNMS researchers have access to state-of-the-art microscopy instruments in its Advanced Microscopy Laboratory (AML) for a broad range of nanoscience research, including nanomaterials synthesis, nanofabrication, imaging/microscopy/characterization, and theory/modeling/simulation.
Amongst the instruments used for materials research in the ALM are some of the most advanced Transmission Electron Microscopes (TEM) and Scanning Transmission Electron Microscopes (STEM)..

Transmission Electron Microscopy
TEMs utilize a technique in which a beam of electrons is transmitted through an ultra-thin specimen, interacting with the specimen as it passes through. An image is formed from the interaction of the electrons transmitted through the specimen. The image is magnified and focused onto an imaging device, such as a fluorescent screen, a layer of photographic film, or to be detected by a sensor such as a CCD camera. TEMs use phase-contrast, and therefore, produce results which need interpretation by simulation.

The ability of electron microscopes to analyze atoms in individual nanostructures has been limited by lens aberrations, but advances in aberration-correcting optics have led to greatly enhanced instrument performance and enabled new techniques in electron microscopy.

Correction of spherical aberration in the Transmission Electron Microscope, for example, has allowed routine sub-angstrom resolution imaging. Higher resolution greatly improves sensitivity to single atoms either lying on a materials surface or inside the bulk permitting the atomic structure of materials to be seen more clearly, and allowing light elements to be seen in the presence of heavy atoms. Aberration correctors have enabled electron probes with sub-angstrom diameters to be used, making it possible to identify individual atom columns with unprecedented clarity.