The preparation, staining, visualization, and interpretation of histological images of tissue is well-accepted as the gold standard process for the diagnosis of disease. These methods were developed historically, and are used ubiquitously in pathology, despite being highly time and labor intensive. Here we introduce a unique optical imaging platform and methodology for label-free multimodal multiphoton microscopy that uses a novel photonic crystal fiber source to generate tailored chemical contrast based on programmable supercontinuum pulses. We demonstrate collection of optical signatures of the tumor microenvironment, including evidence of mesoscopic biological organization, tumor cell migration, and (lymph-)angiogenesis collected directly from fresh ex vivo mammary tissue. Acquisition of these optical signatures and other cellular or extracellular features, which are largely absent from histologically processed and stained tissue, combined with an adaptable platform for optical alignment-free programmable-contrast imaging, offers the potential to translate stain-free molecular histopathology into routine clinical use.

Abstract:We investigate hollow-core fibers for fiber delivery of high power ultrashort laser pulses. We use numerical techniques to design an anti-resonant hollow-core fiber having one layer of non-touching tubes to determine which structures offer the best optical properties for the delivery of high power picosecond pulses. A novel fiber with 7 tubes and a core of 30µm was fabricated and it is here described and characterized, showing remarkable low loss, low bend loss, and good mode quality. Its optical properties are compared to both a 10µm and a 18µm core diameter photonic band gap hollow-core fiber. The three fibers are characterized experimentally for the delivery of 22 picosecond pulses at 1032nm. We demonstrate flexible, diffraction limited beam delivery with output average powers in excess of 70W. "Efficient spectral broadening in the 100-W average power regime using gas-filled kagome HC-PCF and pulse compression," Opt. Lett. 39, 6843-6846 (2014). 8. D. C. Jones, C. R. Bennett, M. a. Smith, and a. M. Scott, "High-power beam transport through a hollow-core photonic bandgap fiber," Opt. Lett. 39, 3122-3125 (2014). 9. T. P. Hansen, J. Broeng, C. Jakobsen, G. Vienne, H. R. Simonsen, M. D. Nielsen, P. M. W. Skovgaard, J. R.Folkenberg, and A. Bjarklev, "Air-guiding photonic bandgap fibers: spectral properties, macrobending loss, and practical handling," J. Light.

We present a detailed comparison between modeling and experiments on supercontinuum (SC) generation in a commercial ZBLAN step-index fiber. Special emphasis is put on identifying accurate material parameters by incorporating measurements of the ZBLAN Raman gain, fiber dispersion, and loss. This identification of accurate parameters is of great importance to substantiate numerical simulations of SC generation in soft-glass fibers. Good agreement between measurement and simulation is obtained when pumping both in the normal and anomalous dispersion regimes.

Ytterbium-doped solid-core photonic bandgap fiber amplifiers operating at the long-wavelength edge of the ytterbium gain band are reported. The low-loss bandgap transmission window is formed in the very low gain region, whilst outside the bandgap, large attenuation inhibits the exponential growth of amplified spontaneous emission in the huge-gain 1030-1100 nm region. Hence parasitic-lasing-free, high-power amplification with a marked efficiency is enabled. A 32 W output at 1156 nm with a 66% slope efficiency and 30 W output at 1178 nm with a 58% slope efficiency were successfully obtained. To our knowledge, these are the highest output powers generating from active photonic bandgap fibers, as well as from ytterbium-doped fiber lasers at these wavelengths.

The supercontinuum generated exclusively in the normal dispersion regime of a nonlinear fiber is widely believed to possess low optical noise and high spectral coherence. The recent development of flattened all-normal dispersion fibers has been motivated by this belief to construct a general-purpose broadband coherent optical source. Somewhat surprisingly, we identify a large short-term polarization noise in this type of supercontinuum generation that has been masked by the total-intensity measurement in the past, but can be easily detected by filtering the supercontinuum with a linear polarizer. Fortunately, this hidden intrinsic noise and the accompanied spectral decoherence can be effectively suppressed by using a polarization-maintaining all-normal dispersion fiber. A polarization-maintaining coherent supercontinuum laser is thus built with a broad bandwidth (780–1300 nm) and high spectral power (~1 mW/nm).