A research team from Slovenia, China and the USA has created several types of biocompatible microlasers and demonstrated their lasing action when implanted into biological systems (Optica 4 1080).

"Lasers are widely employed in biomedical applications for diagnostics, imaging and therapies. The ability to implant micro-sized lasers into tissues brings new opportunities for these techniques," explained first author Matjaž Humar from the Jožef Stefan Institute. "Namely, the implanted lasers are closer to the target tissue and interact more closely with the biological system, enabling more accurate diagnostics and more targeted treatments."

Humar and co-workers demonstrated whispering-gallery-mode (WGM) lasing in transparent tissue, using green fluorescent polystyrene beads. They injected a dispersion of these beads into bovine cornea and pumped the microlasers with a pulsed optical parametric oscillator tuned to 475 nm. When a single bead was optically pumped, it exhibited lasing characteristics: a sharp intensity threshold and narrowband (less than 0.2  nm) emission.

Biodegradable options
While these beads are biocompatible, they are not biodegradable. To create biodegradable lasers, the researchers fabricated spheres of the transparent polymers PLGA (poly(lactic-co-glycolic acid)) and PLA (poly(lactic acid)), doped with the fluorescent dye Nile Red. These polymers are routinely used in clinics for medical implants, sutures and drug delivery, and degrade within days to months without any adverse effects.

"Typically, implantable lasers would only be used for a short time for diagnostics or treatments," Humar explained. "Afterwards, we would need to remove them. But we made them biodegradable, so they can be naturally absorbed by the body after a predetermined timeframe."

Pumping single PLA or PLGA beads with a 532 nm pulsed laser generated an emission spectrum with clear peaks, corresponding to WGM lasing. The team then tested the lasing operation of the beads mixed into whole human blood. Both PLA and PLGA lasers surrounded by red blood cells exhibited lasing with narrow lines in the emission spectrum. The researchers note that lasing in blood was as efficient as in water, showing that red blood cells and other blood constituents did not frustrate lasing.

The team also implanted PLA beads into porcine skin tissues using a tattoo machine. Illuminating a single bead, implanted about 100 μm below the skin surface, with a 532 nm pulsed laser generated a clear fluorescence emission. The emission spectrum also showed clear lasing peaks above a broad background fluorescence (largely skin autofluorescence).

Photonic crystal lasers
Finally, the researchers created photonic crystal lasers made from biocompatible cholesterol derivatives. They created a cholesteric mixture including Pyrromethene 580 fluorescent dye, and mixed this into glycerol to form liquid microdroplets.

The cholesterol droplets formed into an onion-like, radially resonant photonic crystal structure, with molecules oriented tangentially in each shell and creating a helical twist from the centre towards the surface. Illuminating a droplet with a 532 nm pulsed laser generated visible laser emission from the centre of the droplet. These lasers were also biodegradable - remaining stable in water solution for a few days then dissolving within a few weeks.

One advantage of a photonic crystal laser is that the lasing wavelength is independent of the droplet size, depending only on the periodicity. As such, the wavelength across different droplets only deviates by about 1  nm. This provides a more convenient platform than WGM lasers, where a reference spectrum must be measured for each bead, due to unknown diameter.

As the periodicity of cholesteric liquid crystals is temperature dependent, the lasing wavelength increases almost linearly with temperature, offering the potential for temperature sensing. The periodicity can also be made sensitive to a variety of analytes, for chemical and biomolecular sensing applications. Cholesterol droplets alone, however, cannot be used directly in tissues or blood and will need to be coated with a shell or embedded in a solid matrix before use in biological environments.

The researchers concluded that the availability of biocompatible and biodegradable microlasers made from materials approved for medical use or substances already present in the human body may open new opportunities for light-based diagnostics and therapies, as well as basic research.

"One of the first applications could be sensing and diagnostics," Humar told medicalphysicsweb. "For example, the biolasers could be functionalized to be sensitive to glucose. A person having these lasers implanted into the skin would simply measure their glucose level by reading the laser output with a small optical reader."