Miniature Microscopes Could Probe Hard-to-Reach Places in the Body

A technique from researchers at the University of Adelaide could enable microscopic imaging to be performed through a very thin optical fiber. This new technique could make it possible to image areas in the body that are difficult to reach using conventional methods.

The team from Adelaide worked with researchers from the University of Nottingham and the University of Cambridge to investigate how light propagates through a multimode optical fiber and how to control the light more effectively. The researchers developed a method that allowed them to achieve exceptional control over the amplitude, phase, and polarization of the light beam at the output of the fiber.

Experimental projection of Bessel, Airy, and Laguerre-Gauss beams through a 50 μm core multimode fiber. These beams underpin modern microscopy techniques. Courtesy of the University of Adelaide.

Most phase retrieval algorithms that are used for multimode fibers assume light propagation to be a unitary operation, but the transmission matrix of a multimode fiber is nonunitary. The researchers found that a method called the weighted Yang-Gu algorithm outperformed other phase retrieval algorithms in the nonunitary scenario. They leveraged the nonunitary property of the fiber’s transmission matrix to generate intricate intensity and phase patterns at the output of the fiber and shape specific output fields.

The new technique enables light that is traveling through an optical fiber to be pre-shaped into any desired optical pattern, even after the light is distorted.

“New approaches have begun to correct for this distortion, allowing ultrathin footprint devices to penetrate previously inaccessible parts of the body,” researcher Ralf Mouthaan said. “However, these approaches result in imperfect light beams, making them unsuitable for superresolution or wide-field microscopy.”

The researchers used their technique to shape light in the form of the Greek alpha. They also demonstrated the projection of exotic patterns of light, including Bessel beams, Airy beams, and Laguerre-Gaussian beams. These beams have special properties that support modern microscopy techniques.

Mouthaan believes that the new technique, which has a footprint smaller than any other fiber imaging device, will allow microscopic images to be collected from previously inaccessible parts of the human body, while minimizing associated tissue damage. The technique could be of particular benefit in light sheet microscopy, where a volumetric image of a sample is built by imaging one plane at a time, and in stimulated emission-depletion microscopy, which can image structures as small as 1 nm in diameter.

“While many advanced microscopes can occupy an entire lab, this approach is a major step for microscopes to be miniaturized to the point that microscope images can be taken inside the human body,” Mouthaan said. “Performing advanced microscopy in a hair-thin fiber will reveal a wealth of additional information.”

With the new technique, any pattern can be projected through an optical fiber. This example shows the projection of the Greek letter alpha. Courtesy of the University of Adelaide.

The next step for the researchers at the University of Adelaide will be to provide the first proof-of-concept demonstration of “endomicroscopes,” while the team at the University of Nottingham works to build an endoscope ready for clinical use.

“Recent advances in optics have made it possible to controllably deliver light through extremely thin optical fibers, but delivering more complicated light patterns that are needed to perform advanced microscopy has eluded researchers until now,” Mouthaan said.

The research was published in Advanced Optical Materials (www.doi.org/10.1002/adom.202401985).