Femtosecond lasers for sub-surface tissue cutting

1. Femtosecond lasers for sub-surface tissue cutting Chris B. Schaffer http://www.bme.cornell.edu/schafferlab

2. Message • Using a tightly-focused femtosecond laser, it is possible to produce an micrometer-scale incision in the bulk of a tissue without affecting the overlying surface http://www.bme.cornell.edu/schafferlab

3. How sharp is our scalpel? • Minimum cut size is smaller than a single cell • Maximal depth is around 1 mm • Cut rates could be around 1 cm/s http://www.bme.cornell.edu/schafferlab

4. Nonlinear absorption Tight focusing of femtosecond pulses produces high intensity in the focal volume http://www.bme.cornell.edu/schafferlab

5. Nonlinear absorption High intensity leads to nonlinear absorption http://www.bme.cornell.edu/schafferlab

6. Nonlinear absorption Energy is deposited into a microscopic volume located in the bulk of the material http://www.bme.cornell.edu/schafferlab

7. Nonlinear absorption This energy deposition can lead to permanent structural changes in the bulk of the glass http://www.bme.cornell.edu/schafferlab

8. Can even cut inside a piece of glass Sub-surface damage in a glass sample C. B. Schaffer, et al., Appl. Phys. Lett84, 1441 (2004) http://www.bme.cornell.edu/schafferlab

9. In vivo cortical cutting • Urethane anesthetized rat with craniotomy for optical access to the brain • Intravenous injection of fluorescent dye with two-photon excited fluorescence microscopy to visualize vasculature • Translate animal at 10 µm/s while irradiating with • 1-kHz train of 0.5 to 7-µJ energy, 50-fs duration, 800-nm wavelength laser pulses • Focused at 0.95 NA at multiple depths between 100 and 700 µm beneath the brain surface. • Collaborative work with Ted Schwartz, Weill Cornell, Neurological Surgery http://www.bme.cornell.edu/schafferlab

10. In vivo fluorescent angiography during cut http://www.bme.cornell.edu/schafferlab

11. In vivo fluorescent angiography during cut http://www.bme.cornell.edu/schafferlab

12. Post-mortem of cut http://www.bme.cornell.edu/schafferlab

13. Post-mortem of cut http://www.bme.cornell.edu/schafferlab

14. Demonstrated capabilities and limits • Cuts up to 700 µm deep achievable in brain • We’ll likely reach the 1.1-mm theoretical limit (in brain) • Cuts size ranges from sub-micrometer to 10’s of micrometers, depending on laser energy • It is difficult to cut directly underneath large blood vessels http://www.bme.cornell.edu/schafferlab

15. Microvascular lesioning Can selectively target any vessel within the top 0.7 mm of cortex C. Schaffer, et al., PLoS Biology 4, e22 (2006) N. Nishimura, et al., Nature Methods 3, 99 (2006) http://www.bme.cornell.edu/schafferlab

16. Surface arteriole occlusion C. Schaffer, et al., PLoS Biology 4, e22 (2006) http://www.bme.cornell.edu/schafferlab

17. Flow change after surface arteriole occlusion C. Schaffer, et al., PLoS Biology 4, e22 (2006) http://www.bme.cornell.edu/schafferlab

18. Single-cell surgery Cutting the lateral dendrite in the Mauthner cell of a zebrafish Collaboration with Joe Fetcho, Cornell Neurobiology http://www.bme.cornell.edu/schafferlab

19. Acknowledgments Funding: Ellison Medical Foundation American Heart Association American Society of Laser Medicine and Surgery Photonics Technologies Assistantship Program Cornell Ithaca/Weill seed grant http://www.bme.cornell.edu/schafferlab

20. http://www.bme.cornell.edu/schafferlab