Femtosecond Laser Sources & Multiphoton Microscopy Patent

Awarded in December 2020 our Femtosecond Laser Sources & Multiphoton Microscopy (U.S. Patent No. 10,862,263) introduces a novel femtosecond fiber laser source designed for multiphoton microscopy (MPM). MPM is a powerful imaging technique that enables high-resolution, three-dimensional visualization of biological tissues with minimal damage by using high-peak-power, ultrashort laser pulses.

Advantages Over Traditional Lasers

Traditional femtosecond sources like Ti:sapphire lasers offer broad tunability but are costly and complex. Fiber lasers, particularly ytterbium-based systems, are compact and easier to integrate but lack tunability. Raman shifting in fibers extends their output into the near-infrared (1100–1300 nm) range, but these systems often produce only one wavelength at a time and require narrow linewidths for efficient second harmonic generation (SHG).

Because protein fluorescence scales with pulse peak power, femtosecond lasers are preferred over picosecond lasers. They achieve high peak powers at lower average power and higher repetition rates, reducing the risk of tissue damage while enabling efficient multiphoton imaging.

Technical Highlights and Benefits

This patented system uses a two-step process to generate femtosecond pulses:

• ‍Raman-shifted pulse generation: A picosecond pulse is shifted to a new wavelength via Raman scattering, and its spectrum is broadened by self-phase modulation (SPM).‍
• Pulse compression: The broadened pulse is compressed using a dispersive element to produce an ultrashort, high-peak-power femtosecond pulse.

Key benefits include:

• ‍Compact and robust design: The fiber-based architecture makes the laser source more compact and easier to integrate compared to traditional solid-state systems.
• High peak power: Essential for exciting nonlinear optical processes in biological samples, enabling deep tissue imaging with reduced photodamage.‍
• Spectral and temporal tunability: The system’s use of Raman shifting and SPM allows flexibility in adjusting the wavelength and pulse duration, making it adaptable for various microscopy techniques.‍
• Raman shifting allows wavelength tuning and improved excitation at specific Fluorophore absorption bands.‍
• Self-phase modulation (SPM) broadens the pulse spectrum, which is then compressed to achieve the desired femtosecond duration.‍
• Access to unique wavelengths: enhancing imaging capabilities by enabling greater scanning depth in biological tissues, thanks to the system’s ability to produce pulses in critical near-infrared regions.

This patented technology represents a significant step forward in multiphoton microscopy, combining the advantages of fiber lasers with the demanding requirements of ultrafast pulse generation, and enhancing performance, accessibility, and flexibility in biomedical imaging and other multiphoton applications.