title: Fiber-based 1150-nm femtosecond laser source for the minimally invasive harmonic generation microscopy.
abstract: Harmonic generation microscopy (HGM) has become one unique tool of optical virtual biopsy for the diagnosis of cancer and the in vivo cytometry of leukocytes. Without labeling, HGM can reveal the submicron features of tissues and cells in vivo. For deep imaging depth and minimal invasiveness, people commonly adopt 1100- to 1300-nm femtosecond laser sources. However, those lasers are typically based on bulky oscillators whose performances are sensitive to environmental conditions. We demonstrate a fiber-based 1150-nm femtosecond laser source, with 6.5-nJ pulse energy, 86-fs pulse width, and 11.25-MHz pulse repetition rate. It was obtained by a bismuth borate or magnesium-doped periodically poled lithium niobate (MgO:PPLN) mediated frequency doubling of the 2300-nm solitons, generated from an excitation of 1550-nm femtosecond pulses on a large mode area photonic crystal fiber. Combined with a home-built laser scanned microscope and a tailor-made frame grabber, we achieve a pulse-per-pixel HGM imaging in vivo at a 30-Hz frame rate. This integrated solution has the potential to be developed as a stable HGM system for routine clinical use.
authors.affiliation: National Taiwan University, Institute of Biomedical Engineering, Taipei, Taiwan.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Huang
authors.affiliation: National Taiwan University, Institute of Biomedical Engineering, Taipei, Taiwan.
authors.forename: Lun-Zhang
authors.initials: LZ
authors.lastname: Guo
authors.affiliation: National Taiwan University, Institute of Biomedical Engineering, Taipei, Taiwan.
authors.forename: Jing-Zun
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: National Taiwan University, Institute of Biomedical Engineering, Taipei, Taiwan.
authors.forename: Tse-Chung
authors.initials: TC
authors.lastname: Li
authors.affiliation: National Taiwan University, Graduate Institute of Photonics and Optoelectronics, Taipei, Taiwan.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Instrument Technology Research Center, National Applied Research Laboratories, Hsinchu, Taiwan.
authors.forename: Po-Kai
authors.initials: PK
authors.lastname: Chiu
authors.affiliation: National Taiwan University, Graduate Institute of Photonics and Optoelectronics, Taipei, Taiwan.
authors.forename: Lung-Han
authors.initials: LH
authors.lastname: Peng
authors.affiliation: National Taiwan University, Institute of Biomedical Engineering, Taipei, TaiwandUniversity of Macau, Faculty of Health Sciences, Taipa, Macao SAR, ChinaeNational Taiwan University, Molecular Imaging Center, Taipei, Taiwan.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Liu
mesh_terms: D003952:Diagnostic Imaging / Q000295:instrumentation*; D007834:Lasers; D008027:Light; D008853:Microscopy / Q000295:instrumentation*; D017785:Photons