Tissue-Integrated Microlasers Measure Beating Heart of Zebra Fish

An imaging method developed by researchers at the University of St. Andrews aims to overcome difficulties in analyzing and imaging the beating heart. Researchers integrated tiny lasers into heart muscle cells of live zebra fish to acquire high-resolution measurements of their contractility. The method allowed them to perform the measurements at locations several times deeper than with other light-based techniques.

Obtaining images and analyses of the beating heart is difficult due to the constant motion of living tissue. The dense muscle fibers of the heart tend to strongly scatter and absorb light. While advanced microscopy methods such as multiphoton imaging are able to see up to 1 mm into the brain, the challenging environment of the heart limits functional imaging to about 100 µm.

“In the future, this technique could help to overcome the increasing burden of cardiovascular diseases by guiding the development of artificial cardiac tissue and regenerative cardiac therapies,” said Marcel Schubert, a researcher at the Centre for Biophotonics at the University of St. Andrews.

The new work employs spherical microlasers that are just 15 µm in diameter. Due to their unique emission characteristics, they are well suited to applications requiring high signal strength and short acquisition times, the researchers said. The lasers are specifically able to be internalized by neonatal mouse heart muscle cells.

Once inside the cell, the laser remains in direct contact with myofibrils, the contractile filaments forming the muscle fiber. The cell’s contraction changes the refractive index of the myofibrils touching the laser, creating detectable pulse-shaped perturbations to the lasing wavelength. The changes in refractive index correlate directly with contractility.

The team also injected the microlasers into the outer wall of a zebra fish embryo, and results based on the concentration profiles it obtained showed that the technique isn’t affected by the rapid motion of the heart. The approach also worked, researchers found, in thick sections of heart tissues, which could be used for drug screening or testing regenerative cardiac therapies. In these thicker tissue sections, the microlaser signals and heart contraction could be measured through tissue that was up to 400 µm thick.

“In the future, this approach could be used to study transplanted cells and engineered cardiac tissue,” Schubert said.

The next step will be to reduce the size of the microlasers and to improve their biocompatibility. The researchers intend to switch to multiphoton excitation or infrared-emitting lasers, which could drastically increase light penetration, thereby allowing the sensing of contractions deep inside the beating heart.

The work will be presented at the 2021 Biophotonics Congress: Optics in the Life Sciences on April 14.