Yu Chung Chang

High-energy and high-peak-power nanosecond pulse generation with beam quality control in 200-μm core highly multimode Yb-doped fiber amplifiers

We explored high-energy and high-peak-power pulse generation in large-core multimode fiber amplifiers, achieving what is to our knowledge the highest reported energies, up to 82 mJ for 500-ns pulses, 27 mJ for 50-ns pulses, and 2.4-MW peak power for 4-ns pulses at 1064 nm, using 200-microm-diameter and 0.062-N.A. core Yb-doped double-clad fiber amplifiers. The highly multimode nature of the fiber core was mitigated by use of a coiling-induced mode-filtering effect to yield a significant improvement in output-beam quality from M2 = 25 from an uncoiled fiber to M2 = 6.5 from a properly coiled fiber, with the corresponding reduction in number of propagating transverse modes from > or = 200 to < or = 20.

Investigation of tumor cell targeting of a dendrimer nanoparticle using a double-clad optical fiber probe

Fluorescence quantification in tissues using conventional techniques can be difficult due to the absorption and scattering of light in tissues. Our previous studies have shown that a single-mode optical fiber (SMF)-based, two-photon optical fiber fluorescence (TPOFF) probe could be effective as a minimally invasive, real-time technique for quantifying fluorescence in solid tumors. We report improved results with this technique using a solid, double-clad optical fiber (DCF). The DCF can maintain a high excitation rate by propagating ultrashort laser pulses down an inner single-mode core, while demonstrating improved collection efficiency by using a high-numerical aperture multimode outer core confined with a second clad. We have compared the TPOFF detection efficiency of the DCF versus the SMF with standard solutions of the generation 5 poly(amidoamine) dendrimer (G5) nanoparticles G5-6TAMRA (G5-6T) and G5-6TAMRA-folic acid (G5-6T-FA). The DCF probe showed three- to five-fold increases in the detection efficiency of these conjugates, in comparison to the SMF. We also demonstrate the applicability of the DCF to quantify the targeted uptake of G5-6T-FA in mouse tumors expressing the FA receptor. These results indicate that the TPOFF technique using the DCF probe is an appropriate tool to quantify low nanomolar concentrations of targeted fluorescent probes from deep tissue.

Demonstration of fiber-laser-produced plasma source and application to efficient extreme UV light generation.

Efficient generation of extreme UV (EUV) light at lambda = 13.5 nm from a bulk Sn target has been demonstrated by using a fiber laser. The conversion efficiency from the 1064 nm IR to the EUV was measured to be around 0.9% into 2pi steradians within a 2% bandwidth. To the best of our knowledge, this is the first time an all-fiber system was used to generate EUV or soft x rays.

Optical Asymmetry and Nonlinear Light Scattering from Colloidal Gold Nanorods

A systematic study is presented of the intensity-dependent nonlinear light scattering spectra of gold nanorods under resonant excitation of the longitudinal surface plasmon resonance (SPR). The spectra exhibit features due to coherent second and third harmonic generation as well as a broadband feature that has been previously attributed to multiphoton photoluminescence arising primarily from interband optical transitions in the gold. A detailed study of the spectral dependence of the scaling of the scattered light with excitation intensity shows unexpected scaling behavior of the coherent signals, which is quantitatively accounted for by optically induced damping of the SPR mode through a Fermi liquid model of the electronic scattering. The broadband feature is shown to arise not from luminescence, but from scattering of the second-order longitudinal SPR mode with the electron gas, where efficient excitation of the second order mode arises from an optical asymmetry of the nanorod. The electronic-temperature-dependent plasmon damping and the Fermi-Dirac distribution together determine the intensity dependence of the broadband emission, and the structure-dependent absorption spectrum determines the spectral shape through the fluctuation-dissipation theorem. Hence a complete self-consistent picture of both coherent and incoherent light scattering is obtained with a single set of physical parameters.

Optical fiber-based in vivo quantification of growth factor receptors†

Growth factor receptors such as epidermal growth factor receptor 1 and human epidermal growth receptor 2 (HER2) are overexpressed in certain cancer cells. Antibodies against these receptors (eg. cetuximab and transtuzumab [Herceptin]) have shown therapeutic value in cancer treatment. The existing methods for the quantification of these receptors in tumors involve immunohistochemistry or DNA quantification, both in extracted tissue samples. The goal of the study was to evaluate whether an optical fiber‐based technique can be used to quantify the expression of multiple growth factor receptors simultaneously.

Two-photon in vivo flow cytometry using a fiber probe

We have demonstrated the use of a double-clad fiber probe to conduct two-photon excited flow cytometry in vitro and in vivo. We conducted two-channel detection to measure fluorescence at two distinct wavelengths simultaneously. Because the scattering and absorption problems from whole blood were circumvented by the fiber probe, the detected signal strength from the cells were found to be similar in PBS and in whole blood. We achieved the same detection efficiency of the membrane-binding lipophilic dye DiD labeled cells in PBS and in whole blood. High detection efficiency of green fluorescent protein (GFP)-expressing cells in whole blood was demonstrated. DiD-labeled untransfected and GFP-transfected cells were injected into live mice and the circulation dynamics of the externally injected cells were monitored. The detection efficiency of GFP-expressing cells in vivo was consistent with that observed in whole blood.

Cell flow analysis with a two-photon fluorescence fiber probe

We report the use of a sensitive double-clad fiber (DCF) probe for in situ cell flow velocity measurements and cell analysis by means of two-photon excited fluorescence correlation spectroscopy (FCS). We have demonstrated the feasibility to use this fiber probe for in vivo two-photon flow cytometry previously. However, because of the viscosity of blood and the non-uniform flow nature in vivo, it is problematic to use the detected cell numbers to estimate the sampled blood volume. To precisely calibrate the sampled blood volume, it is necessary to conduct real time flow velocity measurement. We propose to use FCS technique to measure the flow velocity. The ability to measure the flow velocities of labeled cells in whole blood has been demonstrated. Our two-photon fluorescence fiber probe has the ability to monitor multiple fluorescent biomarkers simultaneously. We demonstrate that we can distinguish differently labeled cells by their distinct features on the correlation curves. The ability to conduct in situ cell flow analysis using the fiber probe may be useful in disease diagnosis or further comprehension of the circulation system.

Fiber-optic multiphoton in vivo flow cytometry

We demonstrate the use of a double-clad fiber probe to conduct two-photon excited flow cytometry in a live mouse. High detection efficiency of GFP-expressing cells is demonstrated, and the initial dynamics of injected circulating cells is observed.

Fiber-optic two-photon fluorescence correlation spectroscopy for remote cell flow velocity measurements

We report the use of a sensitive double-clad fiber (DCF) probe for remote cell flow velocity measurement by the means of two-photon excited fluorescence correlation spectroscopy (FCS). The ability to measure the flow velocities of labeled cells in whole blood has been demonstrated. A flow velocity of as high as 40 cm/s has been measured. The theoretical lower limit is the self-diffusion of the cell, which is almost zero compared to typical body fluid flow. Owing to the unique feature of two-photon excitation, we can monitor multiple fluorescent markers simultaneously. Therefore, using high brightness nanoparticles to generate the reference signal, we can calibrate the real time flow velocity or even calculate the average size of the cells under measurement. The ability to conduct in vivo flow velocity measurement with single cell resolution using the fiber probe would provide a unique way for disease diagnosis or surveillance after treatment.

Two-photon fluorescence correlation spectroscopy through a dual-clad optical fiber

We report the use of a dual-clad optical fiber for two-photon excited fluorescence correlation spectroscopy. The ability to detect nanoparticles has been demonstrated. This technique shows the potential of conducing FCS measurements in vivo.