Light sources and Beam delivery
The field of fiber optics was born in 1950s, and the Nobel Prize in Physics 2009 was awarded to Charles K. Kao for groundbreaking achievements concerning the transmission of light in fibers for optical communication. The field of nonlinear fiber optics emerged around early 1970s, but has attracted considerable interest since the discovery of fiber supercontinuum generation (i.e., ultra-broadband nonlinear frequency generation) by Ranka and co-workers in 2000. Today, fiber nonlinear frequency generation has found widespread applications in frequency metrology, spectroscopy, and microscopy. Noticeably, John L. Hall and Theodor W. Hänsch were awarded the Nobel Prize in Physics 2005 for developing optical frequency comb technology based on fiber supercontinuum generation from photonic crystal fibers (PCF). For a comprehensive understanding of this topic, we refer to a review article (J. M. Dudely et al. Rev. Mod. Phys. 78, 1135, 2006) and a textbook (G. P. Agrawal, Nonlinear Fiber Optics, 4th edition, Academic Press, 2007).
The PCF-based nonlinear frequency generation has been one of the most active research topics in optics over the past few years, and its application has profoundly influenced microscopy and biophotonic imaging (see Table below). To summarize, the multispectral excitation of supercontinuum has overcome the limitation of the discrete laser lines in conventional laser scanning confocal microscopy (LCSM) while the pulsed nature of the supercontinuum enabled the capability of fluorescence lifetime imaging microscopy, an excellent tool for studying biomolecule interaction. Also, it allows multi-photon microscopy (MPM) to be performed at the excitation wavelengths inaccessible from the source laser, and coherent anti-Stokes Raman microscopy (CARS) to be performed with a single ultrafast laser. Furthermore, the spectrally-broadened supercontinuum facilitates the high-resolution optical coherence tomography (OCT) imaging. The broader the bandwidth, the higher the resolution
The supercontinuum generation is a fascinating phenomenon that produces ultra-broadband output light from a narrowband input. It typically happens within highly nonlinear materials or structures with excellent optical confinement, such as optical fibers. In particular, the periodical structure of the photonic crystal fibers (PCFs) boasts the photon density within its core, greatly increase the efficiency of nonlinear frequency generation (Fig. 1). Furthermore, the zero-dispersion wavelength (ZDW) of the PCFs are engineered to be close to the input wavelengths, so that the different spectral components of the input light experience the slightest walk-off and constantly interact with each other throughout the propagation along the fiber (Fig. 1).
As the input light goes into the fiber through proper coupling, the wavelength components of the input start to interact with each other. These interactions are governed by several nonlinear optical processes, and the most dominated ones are self-phase modulation and Raman scattering. With our femtosecond laser sources, higher-order nonlinear optical processes like four-wave mixing also substantially contribute to the spectral broadening. As the light propagates in the fiber, the newly generated wavelengths further interact with the original input and continue to broaden the spectrum (Fig. 3).
An interesting effect in supercontinuum generation is the optical solution, which happens when the spectral broadening introduced by self-phase modulation and temporal broadening by the dispersion forms a unique balance. Under this condition, the optical pulses maintain its temporal shape within the fiber, displaying quantum effects.
Tu H,, et al. Coherent fiber supercontinuum for biophotonics. Laser Photonics Rev. 7(5) p. 628–645 (2013).
Liu Y., et al. Wave-breaking-extended fiber supercontinuum generation for high compression ratio transform-limited pulse compression. Optics Lett. 37(12) p. 2172-2174 (2012).
Tu H., et al. Stain-free histopathology by programmable supercontinuum pulses. 10(8) p. 534-540 (2016).
Much of the clinical research performed in our group would not be possible without the construction of portable versions of our many systems and handheld probes. In the process of taking large benchtop optical systems in our labs and squeezing their functionality into handheld probes and portable carts, there are many tradeoffs and engineering challenges that have to be managed. To miniaturize a system, the original functionality of the system (not to mention the appropriate signal quality and optical safety limits) have to be adapted to a clinical environment. Space is also much more of a concern –while benchtop systems can accommodate modifications and upgrades over time, miniaturized systems often are not so flexible. Being realistic about what the design absolutely needs to function is paramount. To design the system, often the benchtop system is used asa guide to miniaturize the system along with optical design tools. These speed up optical system design by digitizing and streamlining the underlying laws of physics: geometrical optics and ray tracing. Often multiple optical paths must be combined to integrate a color CCD camera to visualize the tissue and where the optical beam will be scanned, which adds significant complexity. It is also usually helpful to avoid creating customized components, as these rapidly increase the price of a system. Thankfully many optical components are available commercially. Often, a design goes through 2-3 iterations and prototypes before a finalized design is physically constructed. Design software and 3D printing are extremely helpful to rapidly prototype the various iterations. In terms of the portable cart, it must accommodate all this hardware and maintain optical stability during shipping to and from clinical sites or even just at the imaging site. Every seam or crack in the floor becomes more perilous than at first realized. Because of this –ruggedized commercial equipment that can tolerate shock and shipping are extremely helpful to improve the reliability of a system. If pre-scan calibration or any repairs need to be made, the entire system should be able to be slightly adjusted or completely dismantled and reassembled without issue. Perhaps just as important -the cart needs to look like it fits into a clinical environment in all senses of the word –in appearance, safety, and ease of use. When invited into a clinical space, any time shared with researchers is extremely precious!
Gail McConnell, "Confocal laser scanning fluorescence microscopy with a visible continuum source," Opt. Express 12, 2844-2850 (2004).
C. Dunsby et. al., "An electronically tunable ultrafast laser source applied to fluorescence imaging and fluorescence lifetime imaging microscopy," J. Phys. D 37, 3296 (2004).
J. H. Frank, A. D. Elder, J. Swartling, A. R. Venkitaraman, A. D. Jeyasekharan, and C. F. Kaminski, "A white light confocal microscope for spectrally resolved multidimensional imaging," J. Microsc. 227, 203-215 (2007).
G. McConnell and E. Riis, "Photonic crystal fibre enables short-wavelength two-photon laser scanning fluorescence microscopy with fura-2," Phys. Med. Biol. 49, 4757-4763 (2004).
J. Palero, V. Boer, J. Vijverberg, H. Gerritsen, and H. J. C. M. Sterenborg, "Short-wavelength two-photon excitation fluorescence microscopy of tryptophan with a photonic crystal fiber based light source," Opt. Express 13, 5363-5368 (2005).
Henrik Nrgaard Paulsen, et. al., "Coherent anti-Stokes Raman scattering microscopy with a photonic crystal fiber based light source," Opt. Lett. 28, 1123-1125 (2003).
Tak W. Kee and M. T. Cicerone, "Simple approach to one-laser, broadband coherent anti-Stokes Raman scattering microscopy," Opt. Lett. 29, 2701-2703 (2004).
V. P. Mitrokhin, et. al., "Coherent anti-Stokes Raman scattering microspectroscopy of silicon components with a photonic-crystal fiber frequency shifter," Opt. Lett. 32, 3471-3473 (2007).
I. Hartl, et. al., "Ultrahigh-resolution optical coherence tomography using continuum generation in an air–silica microstructure optical fiber," Opt. Lett. 26, 608-610 (2001).
Hyungsik Lim, Yi Jiang, Yimin Wang, Yu-Chih Huang, Zhongping Chen, and Frank W. Wise, "Ultrahigh-resolution optical coherence tomography with a fiber laser source at 1 µm," Opt. Lett. 30, 1171-1173 (2005).
Hui Wang, Christine P. Fleming, and Andrew M. Rollins, "Ultrahigh-resolution optical coherence tomography at 1.15 μm using photonic crystal fiber with no zero-dispersion wavelengths," Opt. Express 15, 3085-3092 (2007).
G. Mcconnell, "Sequential confocal and multiphoton laser scanning microscopy using a single photonic crystal fibre based light source," Appl. Phys. B 81, 783-786 (2005).
D. Träutlein, F. Adler, K. Moutzouris, A. Jeromin, A. Leitenstorfer, E. Ferrando-May, "Highly versatile confocal microscopy system based on a tunable femtosecond Er:fiber source," J. Biophoton. 1, 53-61 (2008).