LASE With Nano-Lasers

Robert L. Stevenson, Ph.D.

Want to improve contrast and definition in super-resolution imaging, especially in the z-axis? A report by Sangyeon Cho and colleagues at Harvard Medical School shows that nano-lasers are a clever new technology for labeling and imaging.¹

Laser-imaging action is the key to improving the signal-to-noise, as shown in Figure 1. A strongly focused pump beam illuminates the small sample area. In this case, the sampling area includes a nano-laser. Laser light is emitted only when the pump beam’s intensity (photon flux) exceeds the laser threshold (P_th). This only occurs in the narrow neck of the focus of the pump beam.

 Figure 1 – LASE Microscopy explained: a) Laser nano-particles are present in the sample, but the light flux is sufficient for triggering laser light only when the flux is very high, which is in the narrow throat of the pump beam. b) Particles that are not in the intense part of the pump beam will not emit laser light. Laser light is emitted after reaching the laser threshold (P_th). c) The laser light is up to five times more narrow in the x, y and z directions than predicted for images collected with conventional light illumination, called the diffraction limit (Diff. limit). (Figure reproduced with permission from Ref. 1 [Phys. Rev. Letts.] and from Seok-Hyun Andy Yun, Ph.D., Associate Professor, MGH Research Scholar, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Cambridge, Mass.)

The focused pump light improves the signal-to-background contrast signal while also improving spatial resolution, particularly in depth (z) by about a factor of 5 compared to traditional fluorescence imaging. Nano-laser particles outside the sample volume lack high intensity light required for lasing. These particles slough off the energy through non-lasing processes.

The authors expect that LASE microscopy will be useful because:

1. The optical system does not need a pinhole or more complex optical systems for imaging even in the super resolution space. Pinholes significantly reduce light signal.
2. LASE is expected to be useful for deep tissue imaging, especially since the technique provides super resolution in the x, y and z directions.
3. LASE technology may be similar to quantum dots in application but superior in light-to-background ratio. This includes the possibility of using nano-lasers to simultaneously label (label or detect) samples with different emission wavelengths for multiplexing and co-localization studies.

Cho’s report appears to be a work in progress. It contains enough information to show proof-of-principle, but the particular example uses lead iodide perovskite, which is not compatible with water or oxygen. More robust nano-lasers will need to be developed. Indeed, the report seems to be a research progress report.

Reference

1. Cho, S.; Humar, M. et al. Laser particle stimulated emission microscopy. Phys. Rev. Letts. 2016, 117, 193902.

Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected].