WASHINGTON — Researchers have developed tiny flexible lasers that can be used to measure forces inside living cells. The new lasers could help illuminate various biological processes, including those involved in early development and tumor progression.
"Biological forces inside and between cells play an important role in many diseases," said research team leader Marcel Schubert from the University of Cologne . "For example, when cancer cells invade tissue, they have to squeeze through the other cells. Our tiny lasers make it possible to measure forces on the scale of individual cells, which has previously been very difficult to accomplish."
In the journal Optical Materials Express , the researchers describe their new spherical whispering gallery mode microbead lasers, which measure just 20 microns, about the width of a human hair. Whispering gallery mode lasers trap light in circular paths – in this case, inside a tiny elastomer bead doped with fluorescent dye – where the light circulates and amplifies until it emits coherent laser light.
The researchers showed that the spectral properties of the microlaser's emission change in direct proportion to applied external force, enabling force measurements up to 50 nanonewtons. This is comparable to the forces a cell can exert when pulling on another cell or its surrounding matrix.
"Our microbead lasers are extremely bright and very sensitive to deformations, making them ideally suited to measuring forces in developing tissue," said Schubert. "Adjusting the stiffness of the lasers could also make it possible to use them to measure stronger forces such as those involved in muscle or heart tissue contraction."
Creating a soft, but solid microlaser
Schubert's research team has been working for several years on building soft microlasers for measuring biological forces. Until now, these microlasers were all made from liquids, such as special oils, which makes them too soft for many types of biological force measurements.
In the new work, the researchers identified a commercially available elastomer that is soft but has a refractive index high enough for creating a laser. This was difficult because dense materials, which tend to be less flexible, are typically necessary to achieve a high refractive index.
The researchers used the material to form microlasers by incorporating a high concentration of fluorescent dye into the beads. When illuminated, the dye's emission becomes trapped along the bead's inner surface, creating whispering gallery mode lasers.
After verifying that the beads' chemical and mechanical properties remained stable with the added dye, the researchers found that the resulting microlasers exhibited mechanical stiffness similar to living cells.
"The stiffness is important because cells can 'feel' the mechanics of their environment and don't like to be in an environment that is too soft or too stiff," said Schubert. "Also, while it is very difficult for cells to take up oil-droplet lasers, they had no problems internalizing the soft beads."
Since force sensing is derived from shifts in the emitted laser spectrum, the beads allow researchers to measure forces in and around cells without direct imaging, which is difficult in dense tissue environments, Schubert noted.
Measuring force with light
To calibrate the beads and obtain quantitative force values, the researchers used an atomic force microscope to squeeze single microbeads while measuring the light emitted. When doped with the organic dye, the elastomer microbeads showed multimodal lasing with thresholds ranging from 2 to 11 nanoJoules.
The researchers also observed that the spectral properties of the laser emission — specifically, the width of the laser modes — changed proportionally to the applied external force. Tests of the microlasers in living cells showed that they remained stable under cell culture conditions for several days.
"Overall, our results suggest that elastomer-based microlasers offer low lasing thresholds along with mechanically compatible properties and stability in cell culture conditions," said Schubert. "These features make them useful for a range of biomechanical experiments, including force sensing and deep-tissue force measurements where imaging-based methods are not practical."
The researchers are now optimizing the microbead lasers to improve long-term stability and reduce variability between beads. They have shown that modifications to the fabrication method can produce a narrow size distribution and are now focused on making the process highly reproducible.
Paper: M. Bayrak, D. Ripp, J. S. Hill, M. Schubert. "Elastomer-based whispering gallery mode microlasers with low Young's modulus for biosensing applications," Opt. Mater. Express 16, 1440-1453 (2026).
DOI: 10.1364/OME.600106 .
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