Tiny lasers in cells could function as autonomous sensors
Despite remaining the gold standard for cellular study, fluorescent probes have several limitations. Their relatively broad emission spectrum makes it hard to distinguish individual probes when many work simultaneously (multiplexing). They are also prone to photobleaching, can be phototoxic to cells, and are sensitive to environmental factors such as pH levels or temperatures, making calibration difficult. The Cell-Lasers project, which was funded by the European Research Council(opens in new window), has pioneered ways of detecting stimulated laser emissions from novel ‘micro-lasers’ inserted within cells and tissues. “The extremely narrow emission linewidth, high coherence and intensity of these lasers, enable hundreds of cells to be tracked simultaneously. Additionally, as the laser lines move precisely with minute changes in the laser’s immediate surroundings, they can function as ultra-sensitive force and chemical sensors,” explains project coordinator Matjaž Humar from the Jožef Stefan Institute(opens in new window), the project host. The team had already demonstrated, for the first time, that a laser could be inserted into a cell. Cell-Lasers showed how such lasers could actually be used to study biological processes, work which earned Humar a Zois Prize for Outstanding Achievements(opens in new window) in Slovenia.
Introducing bead, bubble and edible lasers
Lasers are essentially the product of light being amplified within a medium. To induce this ‘lasing’(opens in new window) effect, Cell-Lasers introduced a fluorescent material inside a microscopic cavity (the media), which, when energised by an external light source, amplifies the light into a precise optical signal. To integrate these micro-lasers into cultured living cells and tissues, the team experimented with a range of laser media ranging from solid beads to soft oil droplets, before trying soap bubbles and even edible substances! Depending on the media under investigation, they were either naturally absorbed by the cells or injected with a tiny pipette. Analysis of the spectral shifts of the emitted light enabled cellular forces and lipid droplet dynamics to be measured. The team also developed a means to track cells deep inside tissues using diffuse spectral localisation imaging, expanding the range beyond standard microscopy. Extensive experiments were conducted, including injecting oil micro-droplets into hydrogels, brain tissue and fat cells to validate their use as force sensors. Computer simulations then helped correlate spectral shifts with specific droplet changes, ensuring the efficacy of the laser medium. “We monitored changes in the size of fat cell lipid droplets with nanometre precision, revealing metabolic dynamics previously invisible to standard microscopy. We also measured droplet deformations with one nanometre precision, detecting cellular forces as small as a few unit (piconewtons),” says Humar.
Pioneering new research directions in health and food safety
Cell-Lasers’ intracellular sensors offer new ways to study diseases such as cancer and diabetes at the single-cell level, potentially leading to better diagnostic devices such as ‘smart tattoo’ sensors for glucose monitoring. As an unexpected research direction, the project’s ‘edible laser’(opens in new window), could be used to tag valuable products such as olive oil or medicines. Made from materials such as gelatine and chlorophyll, which fluoresce and amplify the laser’s light, these could be integrated into food products, scannable by consumers to check freshness. A start-up company is being considered to commercialise the project’s sensor technologies. Meanwhile, the scientific research is progressing from cell cultures to patients’ cells, to better study diseases. Additionally, while searching for new ways to tag cells, quantum single-photon sources were used for the first time as barcodes within cells. This resulted in the first demonstration of entangled-photon generation in organic materials, opening new avenues in quantum optics currently being explored under the new SoftQuanta project.