Haohua Tu

Optical frequency up-conversion by supercontinuum-free widely- tunable fiber-optic Cherenkov radiation

Spectrally-isolated narrowband Cherenkov radiation from commercial nonlinear photonic crystal fibers is demonstrated as an ultrafast optical source with a visible tuning range of 485-690 nm, which complementarily extends the near-infrared tuning range of 690-1020 nm from the corresponding femtosecond Ti:sapphire pump laser. Pump-tosignal conversion efficiency routinely surpasses 10%, enabling multimilliwatt visible output across the entire tuning range. Appropriate selection of fiber parameters and pumping conditions efficiently suppresses the supercontinuum generation typically associated with Cherenkov radiation.

Characterization and Analysis of Relative Intensity Noise in Broadband Optical Sources for Optical Coherence Tomography

Relative intensity noise (RIN) is one of the most significant factors limiting the sensitivity of an optical coherence tomography (OCT) system. The existing and prevalent theory being used for estimating RIN for various light sources in OCT is questionable, and cannot be applied uniformly for different types of sources. The origin of noise in various sources differs significantly, owing to the different physical nature of photon generation. In this study, we characterize and compare RIN of several OCT light sources including superluminescent diodes (SLDs), an erbium-doped fiber amplifier, multiplexed SLDs, and a continuous-wave laser. We also report a method for reduction of RIN by amplifying the SLD light output by using a gain-saturated semiconductor optical amplifier.

Coherent fiber supercontinuum for biophotonics

Biophotonics and nonlinear fiber optics have traditionally been two independent fields. Since the discovery of fiber-based supercontinuum generation in 1999, biophotonics applications employing incoherent light have experienced a large impact from nonlinear fiber optics, primarily because of the access to a wide range of wavelengths and a uniform spatial profile afforded by fiber supercontinuum. However, biophotonics applications employing coherent light have not benefited from the most well-known techniques of supercontinuum generation for reasons such as poor coherence (or high noise), insufficient controllability, and inadequate portability. Fortunately, a few key techniques involving nonlinear fiber optics and femtosecond laser development have emerged to overcome these critical limitations. Despite their relative independence, these techniques are the focus of this review, because they can be integrated into a low-cost portable biophotonics source platform. This platform can be shared across many different areas of research in biophotonics, enabling new applications such as point-of-care coherent optical biomedical imaging.

Non-invasive optical interferometry for the assessment of biofilm growth in the middle ear

Otitis media (OM) is the most common illness in children in the United States. Three-fourths of children under the age of three have OM at least once. Children with chronic OM, including OM with effusion and recurrent OM, will often have conductive hearing loss and communication difficulties, and need surgical treatment. Recent clinical studies provide evidence that almost all chronic OM cases are accompanied by a bacterial biofilm behind the tympanic membrane (eardrum) and within the middle ear. Biofilms are typically very thin, and cannot be recognized using a regular otoscope. Here we demonstrate how optical low coherence interferometry (LCI) noninvasively depth-ranges into the middle ear to detect and quantify biofilm microstructure. A portable diagnostic system integrating LCI with a standard video otoscope was constructed and used to detect and quantify the presence of biofilms in a newly-developed pre-clinical animal model for this condition. Using a novel classification algorithm for acquired LCI data, the system identified the presence of a biofilm with 86% sensitivity and 90% specificity, compared to histological findings. This new information on the presence of a biofilm, its structure, and its response to antibiotic treatment, will not only provide better understanding of fundamental principles that govern biofilm formation, growth, and eradication, but may also provide much needed clinical data to direct and monitor protocols for the successful management of otitis media.

Wave-breaking-extended fiber supercontinuum generation for high compression ratio transform-limited pulse compression

Wave-breaking often occurs when a short intense optical pulse propagates in a long normally dispersive optical fiber. This effect has conventionally been avoided in fiber (super-)continuum-based pulse compression because the accumulated frequency chirp of the output pulse cannot be fully compensated by a standard prism (or grating) pair. Thus, the spectral extending capability of the wave-breaking has not been utilized to shorten the compressed pulse. We demonstrate that wave-breaking-free operation is not necessary if a 4f pulse shaper-based compressor is employed to remove both the linear and nonlinear chirp of the output pulse. By propagating a 180 fs (FWHM) input pulse in a nonlinear photonic crystal fiber beyond the wave-breaking limit, we compress the wave-breaking-extended supercontinuum output pulse to the bandwidth-limited duration of 6.4 fs (FWHM). The combination of high compression ratio (28×) and short pulse width represents a significant improvement over that attained in the wave-breaking-free regime.

All-fiber femtosecond Cherenkov radiation source

An all-fiber femtosecond source of spectrally isolated Cherenkov radiation is reported, to the best of our knowledge, for the first time. Using a monolithic, self-starting femtosecond Yb-doped fiber laser as the pump source and the combination of photonic crystal fibers as the wave-conversion medium, we demonstrate milliwatt-level, stable, and tunable Cherenkov radiation at visible wavelengths 580-630 nm, with pulse duration of sub-160-fs, and the 3 dB spectral bandwidth not exceeding 36 nm. Such an all-fiber Cherenkov radiation source is promising for practical applications in biophotonics such as bioimaging and microscopy.

Numerical analysis of gradient index lens-based optical coherence tomography imaging probes

We report the numerical analysis of gradient index (GRIN) lens-based optical coherence tomography imaging probes to derive optimal design parameters. Long and short working distance probes with a small focal spot are considered. In each model, the working distance and beam waist are characterized and compared for different values of length and refractive index of the probe components. We also explore the influence of the outer tubing and refractive index of the sample media. Numerical results show that the adjustment of the maximum beam diameter and focusing angle at the end of the GRIN lens surface is very important for determining the optical performance parameters of the probe.

Nonlinear polarization dynamics in a weakly birefringent all-normal dispersion photonic crystal fiber: toward a practical coherent fiber supercontinuum laser.

Dispersion-flattened dispersion-decreased all-normal dispersion (DFDD-ANDi) photonic crystal fibers have been identified as promising candidates for high-spectral-power coherent supercontinuum (SC) generation. However, the effects of the unintentional birefringence of the fibers on the SC generation have been ignored. This birefringence is widely present in nonlinear non-polarization maintaining fibers with a typical core size of 2 µm, presumably due to the structural symmetry breaks introduced in the fiber drawing process. We find that an intrinsic form-birefringence on the order of 10−5 profoundly affects the SC generation in a DFDD-ANDi photonic crystal fiber. Conventional simulations based on the scalar generalized nonlinear Schrödinger equation (GNLSE) fail to reproduce the prominent observed features of the SC generation in a short piece (9-cm) of this fiber. However, these features can be qualitatively or semi-quantitatively understood by the coupled GNLSE that takes into account the form-birefringence. The nonlinear polarization effects induced by the birefringence significantly distort the otherwise simple spectrotemporal field of the SC pulses. We therefore propose the fabrication of polarization-maintaining DFDD-ANDi fibers to avoid these adverse effects in pursuing a practical coherent fiber SC laser.

Stain-free histopathology by programmable supercontinuum pulses

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.

Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation.

Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring.