A Fiber-Based Femtosecond Laser Source for In Vivo Harmonic Generation Microscopy
Date Issued
2015
Date
2015
Author(s)
Huang, Jing-Yu
Abstract
Biopsy is an important tool for clinical diagnosis. Pathologist examined the tissue removed from patients to determine whether or not diseases are present and help doctors do a pre-operative assessment. The removed sample will go through the processes of chemical fixation (or frozen occlusion), being sliced and staining to help pathologist recognize the cell morphology and observe the development of diseases. The procedure of biopsy is complicated and takes lots of time. When removing the tissues from patients, it also makes patients suffer and the bleeding may have side effects such as infection and spread of disease cells. For these reasons, the noninvasive and label-free virtual optical biopsy has been developed. Virtual optical biopsy includes optical coherence tomography, confocal microscopy, multiphoton fluorescence microscopy, and harmonic generation microscopy. Compared with other techniques, harmonic generation microscopy such as second harmonic generation microscopy and third harmonic generation microscopy provides higher penetration depth and sub-micron resolution and it leaves negeligible energy in specimens due to its characteristic of virtual-state-transition. Instead of collecting fluorescence produced by photon absorption, harmonic generation microscopy obtains image by detecting nonlinear signal from light-matter interaction. Therefore, it is considered as a less photo damage and less photo toxicity tool for a in vivo imaging technique. In order to achieve deeper penetration depth, it usually employs femtosecond laser sources around 1200 nm in which light-tissue interaction like photon absorption and scattering is greatly reduced. Conventional solid state femtosecond laser source like Ti : sapphire laser cascaded with optical parametric oscillator or Cr : forsterite solid state laser can provide the laser source around 1200 nm. Unfortunately, the performance of solid state laser is easily affected by temperature and humidity and it''s not stable for medical use. In this thesis, we demonstrated a 7.5 MHz(&11.25MHz) repetition rate and 6.5 nJ pulse-energy fiber-based femtosecond laser source at 1160 nm. It was achieved by a soliton self-frequency shift in photonic crystal fiber and a second harmonic generation in a quasi-phase matching nonlinear crystal. We expect that such fiber-based laser system could replace the conventional solid state laser system to increase the stability of harmonic generation microscopy in clinical research.
Subjects
photonic crystal fiber
soliton
soliton self-frequency shift
quasi-phase matching
harmonic generation microscopy
Type
thesis
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