Cologne University uses microscale lasers to measure subtle forces inside cells

Researchers at the University of Cologne have developed an optical method that can sense the internal mechanical forces generated by living cells during development or pathology. The core of this method lies in a micro flexible laser material that can be placed inside cells, and its output beam will be modulated according to changes in the surrounding environment of the cells. According to Optical Materials Express, this new type of laser has the potential to reveal various biological processes, including early cell development and tumor progression.

"Biological forces inside and between cells play an important role in many diseases," said Marcel Schubert from the University of Cologne.


Researchers developed tiny flexible lasers that change emission properties in response to external force, allowing them to be used inside living cells to measure forces in and between cells.

"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."

Revealing those forces with micro-scale lasing materials is an emerging technique that offers significant advantages over conventional fluorescent probes and imaging, noted the team in its paper. However, the limited availability of suitable deformable or elastic microlaser materials has restricted the scale of forces that can be detected, and narrowed their overall applicability.

Marcel Schubert's research team has been working for several years on building this kind of soft microlaser for measuring biological forces, but until now those microlasers were all made from liquids, such as special oils, which made them too soft for many types of biological force measurements.

The Cologne project fabricated its new flexible microlasers using a commercial two-component silicone gel and a co-focusing microfluidic chip, to produce fluorescently-doped microbeads with adjustable diameters ranging from 8 to 30 microns. When optically pumped, these emit light via whispering gallery modes in which emission becomes trapped along the bead's inner surface, greatly reducing the loss experienced by the system.

Forces acting on the beads then cause shifts in the emitted laser spectrum. This lets researchers assess those forces in and around cells without direct imaging, a difficult task in dense tissue environments.

Deep-tissue force measurements

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. Tests of the microlasers in living cells also showed that they remained stable under cell culture conditions for several days.

"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 Marcel Schubert. "Also, while it is very difficult for cells to take up oil-droplet lasers, they had no problems internalizing the soft beads."

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.

"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."

Source: optics.org