May 3 2021
Researchers from the University of Nottingham have designed a new ultrasonic imaging system that can be installed on the tip of a hair-thin optical fiber. The system can even be inserted into the human body to observe cell anomalies in 3D.
Conventional microscope pictures of model biological cells (top). The phonon probe reproduces 3D images of the objects (color is height). Simultaneously, the probe detected stiffness-related measurements which are mapped in green on the top left image (bottom). The white scale bars are 10 micrometers long. Image Credit: University of Nottingham.
The novel technology creates nanoscopic and microscopic resolution pictures that would someday enable clinicians to investigate cells that inhabit hard-to-reach parts of the body, like the gastrointestinal tract, and provide more effective diagnoses for various diseases spanning from bacterial meningitis to gastric cancer.
The technology delivers a high level of performance that is presently feasible only in sophisticated research laboratories that have huge, scientific instruments, and at the same time, the new, compact system has the ability to bring it into clinical settings to enhance patient care.
This breakthrough, funded by the Engineering and Physical Sciences Research Council (EPSRC), also minimizes the requirement for traditional fluorescent labels—chemicals applied to analyze cell biology under a microscope—which can be detrimental to human cells in bulk doses.
The results have been reported in a new paper titled “Phonon imaging in 3D with a fibre probe” published in Light: Science & Applications, the Nature journal.
We believe the system’s ability to measure the stiffness of a specimen, its bio-compatibility, and its endoscopic-potential, all while accessing the nanoscale, are what set it apart. These features set the technology up for future measurements inside the body; towards the ultimate goal of minimally invasive point-of-care diagnostics.
Dr Salvatore La Cavera III, Faculty of Engineering, University of Nottingham
La Cavera III also holds an EPSRC Doctoral Prize Fellowship at the University of Nottingham.
The non-invasive imaging tool, which is presently at the prototype phase, has been described by the research team as a “phonon probe,” and can be inserted into a traditional optical endoscope.
The optical endoscope is a thin tube with a strong light and camera fitted at the end and is navigated into the body to detect, examine, and operate on cancerous lesions, among various other disorders. Integrating phonon and optical technologies could be beneficial; for example, these technologies can accelerate the clinical workflow process and decrease the number of invasive test procedures meant for patients.
3D Mapping Capabilities
Just like how a doctor might perform a physical examination to feel for atypical “stiffness” in tissues under the skin that could denote tumors, the phonon probe takes this concept of “3D mapping” to a cellular level.
The phonon probe scans the ultrasonic probe in space and simulates a 3D map of stiffness and spatial characteristics of tiny structures both at and below the surface of the sample (for example, tissues). The probe does this with the power to capture tiny objects, such as a large-scale microscope, and the contrast to distinguish objects, for example, an ultrasonic probe.
Techniques capable of measuring if a tumour cell is stiff have been realised with laboratory microscopes, but these powerful tools are cumbersome, immobile, and unadaptable to patient-facing clinical settings. Nanoscale ultrasonic technology in an endoscopic capacity is poised to make that leap.
Dr Salvatore La Cavera III, Faculty of Engineering, University of Nottingham
How it Works
Two lasers are used by the novel ultrasonic imaging system and these produce brief pulses of energy to activate and identify vibrations in a sample. One laser pulse is absorbed by a layer of metal—that is, a nano-transducer (which operates by transforming energy from one form to another)—designed on the fiber tip; this process pumps high-frequency phonons, or sound particles, into the specimen.
A second laser pulse then bombards with the sound waves, a process called Brillouin scattering. If these “collided” laser pulses are detected, the shape of the traveling sound wave can be reproduced and shown visually.
The identified sound wave encodes data about material stiffness and even its geometry. The team from the University of Nottingham was the first to show this dual capability using optical fibers and pulsed lasers.
Generally, the power of an imaging device is quantified by the tiniest object that can be visualized by the system, that is, the resolution. In two dimensions, the new phonon probe can “resolve” objects on the order of 1 µm, analogous to a microscope; however, in the third dimension, or height, the same probe offers measurements on the scale of nanometers, which is unparalleled for a fiber-optic imaging system.
Future Applications
In the latest article, the team demonstrated that the novel technology can be used with a single optical fiber and also with the 10–20,000 fibers of an imaging bundle (measuring 1 mm in diameter), as utilized in traditional endoscopes.
As a result, wide fields of view and excellent spatial resolution could be routinely obtained by collecting spatial and stiffness data from many different points on a specimen without having to shift the device, thus bringing a new kind of phonon endoscope within reach.
Apart from clinical healthcare, fields like metrology and precision manufacturing could employ this high-resolution tool for material characterization and surface inspections—a replacement or complementary measurement for present-day scientific instruments.
Emerging technologies, like tissue engineering and 3D bio-printing, could also utilize the new phonon probe as an inline inspection instrument by directly combining it with the external diameter of the print needle.
The researchers have planned to develop a range of biological cell and tissue imaging applications, in association with the Nottingham Digestive Diseases Centre and the Institute of Biophysics, Imaging and Optical Science at the University of Nottingham, to develop a feasible clinical tool in the days to come.
Journal Reference:
La Cavera III, S., et al. (2021) Phonon imaging in 3D with a fibre probe. Light: Science & Applications. doi.org/10.1038/s41377-021-00532-7.