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Photodynamic therapy (PDT) provides a potential therapeutic approach for killing malignant cell/solid tumors, but currently approved photosensitizers (PSs) are generally excited by visible light, limiting the penetration depth in tissues. It is necessary to develop a near-infrared (NIR) responsive photodynamic platform, providing maximum tissue penetration. Here, we present a gold nanopeanut platform exhibiting dual functions of NIR PDT and two-photon luminescence imaging. The nanopeanut with a size less than 100 nm exhibits two distinct NIR surface plasmon absorption bands at approximately 1110 and 1300 nm. To perform PDT, we conjugated commercial toluidine blue O (TBO) PS on the surface of the nanopeanuts. With spectral overlap, the 1230-nm femtosecond Cr: forsterite laser can excite the surface plasmons of nanopeanuts, transfer energy to TBO, and generate singlet oxygen to kill cells. Moreover, the plasmon resonance-enhanced two-photon luminescence of nanopeanuts can be used to map their delivery in vivo. These results demonstrate that the PS-conjugated gold nanopeanut is an effective theranostic system for NIR PDT.

For deep imaging depth and least invasiveness, people commonly use 1100-1300 nm femtosecond laser sources to perform label-free in vivo microscopy. The modalities include reflectance confocal, two & three photon fluorescence, and second & third harmonic generation microscopy. However, most of the laser sources are typically based on bulky oscillators, which are sensitive to environment conditions and less stable for routine clinical use. In contrast, fiber-based lasers have simpler cavity design and potentially compact size for movable use. In this presentation, 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 achieved by a Bismuth Borate (BIBO) or Magnesium-doped periodically poled Lithium Niobate (MgO:PPLN) mediated frequency doubling of the 2300 nm solitons, generated from an excitation of 1550 nm Er:fiber femtosecond laser pulses on a large mode area photonic crystal fiber. Combined with a laser scanned microscope and a home-build data acquisition card, we achieve a pulse-per-pixel harmonic generation microscopy in vivo at a 30 Hz frame rate. In the future, this solution is potential to be used for label-free clinical virtual optical biopsy.

Photodynamic therapy (PDT) is a light-activated chemotherapeutic treatment that utilizes singlet oxygen and reactive oxygen species induced oxidative reactions to react with surrounding biological substrates, which either kills or irreversibly damages malignant cells. We used multiphoton nonlinear optical microscopy to observe the photo-dynamic effects of TBO-AuNR-in-shell NPs. Excited by femtosecond Cr:forsterite laser operating at 1230nm, singlet oxygen were generated through a plasmon-enhanced two-photon nonlinear optical process. For cells took up NPs, this photodynamic effect can kill the cell. From nonlinear optical microscopy images, we found they shrunk after 3 minutes of illumination.

We demonstrate a fiber-based, three-color femtosecond source for simultaneous imaging of three fluorescent proteins (FPs) using two-photon fluorescence microscopy (2PM). The three excitation wavelengths at 775 nm, 864 nm and 950 nm, are obtained through second harmonic generation (SHG) of the 1550-nm pump laser and the 1728-nm and 1900-nm solitons generated through soliton self-frequency shift (SSFS) in a large-mode-area (LMA) fiber. These energetic pulses are well matched to the two-photon excitation peaks of red, cyan and yellow fluorescent proteins (TagRFPs, TagCFPs, and TagYFPs) for efficient excitation. We demonstrate simultaneous 2PM of human melanoma cells expressing a “rainbow” combination of these three fluorescent proteins.

A 1.2- to 2.2-mum tunable femtosecond light source based on the soliton-self-frequency-shift effect of high-power Cr: forsterite laser pulses propagating inside a highly nonlinear photonic crystal fiber is reported. The demonstrated soliton self-frequency shift is higher than 42% of the pump laser frequency, corresponding to a record 910-nm wavelength tuning range. Due to the advantages of simplicity, easy tunability, high-temperature stability, and low cost of this new femtosecond light source, it accordingly, could be widely applicable for many applications.

Simultaneous imaging of cells expressing multiple fluorescent proteins (FPs) is of particular interest in applications such as mapping neural circuits, tracking multiple immune cell populations, etc. To visualize both in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissues, two-photon fluorescence microscopy (2PM) is a powerful tool that has found wide applications. However, simultaneous imaging of multiple FPs with 2PM is greatly hampered by the lack of proper ultrafast lasers offering multi-color femtosecond pulses, each targeting the two-photon absorption peak of a different FP. Here we demonstrate simultaneous two-photon fluorescence excitation of RFP, YFP, and CFP in human melanoma cells engineered to express a “rainbow” pallet of colors, using a novel fiber-based source with energetic, three-color femtosecond pulses. The three-color pulses, centered at 775 nm, 864 nm and 950 nm, are obtained through second harmonic generation of the 1550 nm pump laser and SHG of the solitons at 1728 nm and 1900 nm generated through soliton self-frequency shift (SSFS) of the pump laser in a large-mode-area (LMA) fiber. The resulting wavelengths are well matched to the two-photon absorption peaks of the three FPs for efficient excitation. Our results demonstrate that multi-color femtosecond pulse generation using SSFS and a turn-key, fiber-based femtosecond laser can fulfill the requirements for simultaneous imaging of multiple FPs in 2PM, opening new opportunities for a wide range of biological applications where non-invasive, high-resolution imaging of multiple fluorescent indicators is required.

We observed distinct bandwidth degradation behaviors in low-temperature-grown GaAs (LTG-GaAs)-based traveling-wave photodetectors (PDs) under /spl sim/1300-nm telecommunication wavelength operation. Compared with the bandwidth degradation behaviors of different excitation wavelengths (/spl sim/800 and /spl sim/1550 nm) in LTG-GaAs-based PDs, the saturation behaviors at the studied wavelength are more serious and can be attributed to "hot electron" effect of photogenerated carriers. The disclosed unique material properties of LTG-GaAs are important for its applications in ultrafast optoelectronics and understanding its carrier dynamics with the defect states.

With the development of nonlinear optics and new imaging methods, near-infrared (NIR) light can excite contrast agents to probe biological specimens both functionally and structurally with a deeper imaging depth and a higher spatial resolution than linear optical approaches. There is considerable and growing interest in how biological specimens respond to NIR light. Moreover, the visible absorption band of most functional nanomaterials becomes NIR-excitable through multiphoton processes, thus allowing multifunctional imaging and combined therapy with noble metal and magnetic nanoparticles both in vitro and in vivo. A groundbreaking example is the use of different laser techniques to excite single-type NIR-absorbing/emitting nanomaterials to produce multiphoton emission by femtosecond lasers using either a remote control system for photodynamic therapy or photo-induced chemical bond dissociation. These techniques provided superior anatomical resolution and detection sensitivity for in vivo tumor-targeted imaging than those offered by conventional methods. Here we summarize the most recent progress in the development of smart NIR-absorbing/emitting nanomaterials for in vivo bioapplications. Nanomaterials that absorb or emit near-infrared light are increasingly being used to probe the structures and functions of biosystems. In particular, they are valuable for in vivo monitoring of drug nanocarriers, which offer many advantages over conventional drug-delivery methods. Joao Conde of Massachusetts Institute of Technology in the USA and co-workers give a timely review of recent progress in this area. They consider the various types of near-infrared absorbing and emitting nanomaterials. The scientists assess nine kinds of nanoparticles that are useful for multiphoton microscopy. They then overview toxicity studies of these materials. Finally, the researchers provide a roadmap for future research by listing ten properties that ideal near-infrared bioprobes would possess. Specifically, they note that ideal bioprobes should be biocompatible, versatile and multifunctional. A huge interest shows that optical contrast agents to probe biological specimen both functionally and structurally with deeper action depth and better spatial resolution is closely related with the development of near-infrared (NIR) light excitation and nonlinear optics and new imaging methods. This review will go beyond the state-of-the-art by revisiting the up-to-date progress in developing smart NIR-to-NIR and upconverted nanomaterials for in vivo bioapplications. The latest advances in the development of novel NIR-to-NIR linear and nonlinear optical nanomaterials and their potential applications in cancer targeting, diagnosis and therapeutics and deep-tissue imaging are described.

By optimizing the thermal properties of crystals, we report a femtosecond Cr:forsterite laser with a highest ever 1.4W output power, which is desired for many applications, including biomedical imaging, studies of fibers, and photonic devices.

The authors demonstrated an artificial material composed of ordered semiconductor quantum dots (QDs) with functional acoustic properties. The phononic bandgap of this three-dimensional (3D) artificial crystal was characterized by Raman and transient reflectivity spectroscopies. The Raman spectra exhibited interferometric patterns caused by the coherent interference of acoustic-phononrelated Raman signals, revealing the structural information of the crystal. In addition, the acoustic tunneling in the QD crystal was studied by the transient spectroscopy with the picosecond ultrasonic technique. The measured signals indicated that the QDs are responsible for the scatterings of the acoustic phonons at the bandgap frequency, while the QD crystal serves as a phononic meta material for low-frequency phonons.

The problem of weak harmonic generation signal intensity limited by photodamage probability in optical microscopy and spectroscopy could be resolved by increasing the repetition rate of the excitation light source. Here we demonstrate the first photomultiplier-based real-time second-harmonic-generation microscopy taking advantage of the strongly enhanced nonlinear signal from a high-repetition-rate Ti:sapphire laser. We also demonstrate that the photodamage possibility in common biological tissues can be efficiently reduced with this high repetition rate laser at a much higher average power level compared to the commonly used ~80- MHz repetition rate lasers.

With a 2D scanning MEMS mirror, we demonstrate a miniaturized epi-third-harmonic-generation microscope with a video rate and a 0.7µm transverse resolution. In vivo THG imaging of human skin is demonstrated.

We proved the existence of resonant-enhanced dipolar interaction between THz-photons and confined acoustic phonons in nanocrystals. By a specific core-shell charge separation, the dipolar (l=1) confined acoustic modes was activated to absorb THz waves.

With miniaturized tube lenses and two-dimensional asynchronous scanning of the microelectro-mechanical-system mirror, we demonstrated a 24 Hz frame-rate miniaturized two-photon fluorescence/second-harmonic-generation microscope system. Sub-micron transverse resolution of sectioning images can be achieved.

We report here the observation of piezoelectricity-induced terahertz photon absorption related to confined acoustic phonons in nanoparticles. Terahertz photon inactive $(l=0)$ breathing modes become terahertz photon active in wurtzite CdSe nanocrystals due to the piezoelectric coupling. Obvious absorption peaks related to $(l=0)$ modes appeared in the terahertz absorption spectra and the frequency of the peaks were inversely proportional to the size of the CdSe nanocrystals. This piezoelectrically coupled electric vibration provides a mechanism for low-dimensional systems to convert a terahertz photon into a phonon of the same frequency.

By using a frequency-controlled narrow band THz source, a Fourier Transform Infrared (FTIR) spectroscopy system, and a frequency-controlled terahertz (THz) emitter, for the first time, we studied the THz photon absorption related to the THz confined acoustic vibrations in semiconductor nanocrystals. Through a specific charge separation in the CdSe/CdTe type-II nanocrystals and a piezoelectric coupling in the wurtzite CdSe nanocrystals, the THz photons can be resonantly coupled with (l=1) dipolar modes and the (l=0) breathing modes, respectively. Our results provide new mechanisms for low dimensional systems to convert a THz photon into a phonon of the same frequency.

International audience; Taking advantage of the specific core-shell charge separation structure in the CdSe/CdTe core-shell Type-II quantum dots (QDs), we experimentally observed the resonant-enhanced dipolar interaction between millimeter-wave (MMW) photons and their corresponding (l = 1) confined acoustic phonons. With proper choice of size, the absorption band can be tuned to desired frequency of MMW imaging. Exploiting this characteristic absorption, in a fiber-scanned MMW imaging system, we demonstrated the feasibility of CdSe/CdTe QDs as the contrast agents of MMW imaging.

In this work, we review our recent development on nanoultrasonics based on an optical piezoelectric transducer. By embedding strain patterns in piezoelectric nano-layers and by manipulating optical field intensity in temporal and spatial domains, THz nanoacoustic waves with an acoustic wavelength on the order of or shorter than 10 nm can be generated with a nanometer-scaled lateral spot size, much smaller than the excitation optical wavelength. Noninvasive subsurface ultrasonic imaging can thus be realized with a nanometer resolution.

In this talk, we will review our recent works about the GHz-repetition-rate (GRR) femtosecond lasers. These works make GRR femtosecond lasers more flexible in the manipulation of pulse repetition-rate and the operating wavelength. We first demonstrate a phase insensitive way to multiply the repetition-rate of a passive mode-locked laser in femtosecond regime. By inserting an intracavity flat surface with low reflectivity, we multiplied the repetition-rate of a femtosecond Cr:forsterite laser by ten times. It provides a simple and stable way to modify MHz-repetition-rate femtosecond lasers into GRR lasers. To achieve desired wavelength, which can't be directly generated by a gain medium, nonlinear conversion is required. But for GRR femtosecond lasers, the efficiency of single-pass conversion is low due to its low pulse energy. In order to increase the yield, we adopt the method of resonant-enhanced external cavity. With a resonant cavity matched to a 2-GHz repetition-rate Ti:sapphire laser, we demonstrated a high power femtosecond blue source at 2-GHz repetition-rate.

We demonstrate hollow-core and large-core photonic-crystal-fiber-based two-photon fluorescence microscopes at 0.8/spl mu/m and 1.3/spl mu/m. The two-photon excitation efficiencies and image performances are comparable to or better than those acquired by the conventional fiber-free system.

By inserting a low-reflectivity flat surface inside the oscillator cavity, we demonstrate a flexible and phase-insensitive method for multiplying the repetition rate of a femtosecond passive mode-locked solid-state laser. Without mode matching and feedback control, we successfully multiplied the repetition rate of a passively mode-locked Cr:forsterite laser from 124 MHz to 1.24 GHz. High-repetition-rate femtosecond optical pulses with average power of > 100 mW can be obtained with the demonstrated method.

Femtosecond carrier dynamics in InGaAsN single quantum well were studied for the first time. Pump-probe measurement shows the enhanced free carrier absorption due to highly excited carriers with a delayed carrier cooling time around 2/spl sim/3.7ps.

Multiple quantum well (MQW) structure piezoelectric semiconductor can be treated as a piezoelectric transducer to generate nanometer wavelength and THz frequency acoustic waves. The generation mechanism of nano acoustic wave (NAW) in quantum wells induced by femtosecond optical pulses can be modeled by a macroscopic elastic continuum theory. The absorption of the MQW's modulated by NAW's through quantum confined Franz-Keldysh (QCFK) effect allows another femtosecond optical probe pulses to monitor the propagating NAW. Many applications in typical ultrasonics can be achieved by NAWs. The simultaneous waveform synthesis is demonstrated by an optical coherent control technique. The phase of the totally reflected NAW is studied. Acoustic coherent control can be achieved by designing the thickness of the cap layer on the MQW. We also demonstrated the feasibility to apply THz NAWs to acoustically control an electronic device with higher operation speed and spatial accuracy. Seismology, which is the first step toward ultrasonic imaging, was also demonstrated. The arrival time of the echo is obtained by processing the transient transmission changes of the probe. Ultrafast technique and nano technology are ready for nano ultrasonics.

We observed distinct nonlinear behaviors of bandwidth degradation in low-temperature-grown-GaAs based traveling-wave-photodetectors under long wavelength (/spl sim/1300 nm) operation. The disclosed unique material properties of LTG-GaAs at different excitation wavelengths are important for its applications in ultrafast optoelectronic and understanding its carrier dynamics in the defect states.

Different crystal growth and quality information can be obtained through the simultaneous acquisition of transmitted and reflected second-harmonic-generation images, which is combined with multiphoton, multimodal nonlinear microscopy to study the optical property in lateral-epitaxially-overgrown GaN

Low-temperature-grown GaAs (LTG-GaAs) based photodetectors (PDs) merit a lot of attentions due to their ultrahigh electrical bandwidth performances. We review the advantages and applications of LTG-GaAs based metal-semiconductor-metal traveling wave photodetectors (MSMTWPD) and discuss their ultra-high speed and record high power-bandwidth product performances in both short (/spl sim/800 nm) and long (/spl sim/1300 nm) wavelength regimes. The MSMTWPD has lower microwave loss and higher microwave velocity than the structure of p-i-n TWPD. The superior microwave guiding structure also implies that the electrical bandwidth is less sensitive to the photo-absorption volume. The measured impulse response and its corresponding frequency response of MSMTWPD are shown under high bias voltage (30 V) and high excitation optical pulse energy (/spl sim/71 pJ/pulse) at the wavelength of 800 nm. The obtained peak output voltage (V/sub p/ /spl sim/30 V) and electrical bandwidth (190 GHz) product (5.7 THz-V) is the highest among all reported ultrahigh speed PDs. The excellent power-bandwidth product performance is due to short carrier lifetime of LTG-GaAs and superior microwave guiding structure. By utilizing the mid-gap defect states in LTG-GaAs, the photo-absorption in long wavelength regimes (1.3 /spl mu/m-1.55 /spl mu/m) can also be achieved. The record high power-bandwidth product performance among all reported high speed PDs in long wavelength regime has also been demonstrated with LTG-GaAs based MSMTWPD. However, compared with the high power performances in short wavelength regime, the demonstrated device exhibits a serious bandwidth degradation effect under /spl sim/1.3 /spl mu/m wavelength excitation. The different nonlinear behaviors at 1.3 /spl mu/m wavelength possibly originate from that the photon energy (/spl sim/1 eV) is much higher than the subband-gap photon-absorption energy (/spl sim/0.7 eV), which will induce significant hot electron, inter-valley scatterings, and serious increasing in carrier lifetime. By contrast, the hot electron effect under short wavelength excitation (/spl sim/800 mn) is not evident as the photon energy of excitation wavelength is close to the band-to-band photo absorption energy.

The problem of weak signal intensity due to the low incident average intensity limited by photodamage probability in common nonlinear light microscopy and spectroscopy can be fundamentally solved by increasing the repetition rate of the excitation light source. Since the possibility of nonlinear photodamage is determined by the incident peak intensity (or pulse energy), increasing the repetition rate of the excitation light source while keeping its peak intensity (or pulse energy) well below than damage threshold will not provoke any optical damage but will augment the average nonlinear signals. We used a femtosecond Ti:sapphire laser with a 2-GHz repetition rate as the light source of a second-harmonic-generation (SHG) microscope and strongly enhanced SHG signal was observed while no photodamage could be identified. Compared with the common 80-MHz Ti:sapphire laser, the microscopic images taken with the 2-GHz laser require shorter acquisition time and exhibit higher contrast, resulting in real-time SHG imaging capability.

Summary form only given. Direct third-harmonic-generation (THG) implementation was first realized on a modelocked Cr:forsterite laser with the method of Third Order Autocorrelation for Direct optical pulse-shape measurement (TOAD). In this report, we demonstrate this technique on the commonly used Ti:sapphire modelocked laser for the first time. By using THG process in a single GaN thin film or a thin BBO crystal, the intensity profile of the optical pulses was directly obtained with the background free third-order autocorrelation trace. In addition, we employed the Gerchberg-Saxton algorithm to retrieve the corresponding phase by the obtained intensity and an additional spectral measurement.

Summary form only given. All-solid-state lasers shows advantages in compactness, stability, high output powers, and compatibility with newly developed mode locking mechanisms (like Kerr lens mode locking (KLM)). Even though the femtosecond solid state laser has already dominated the market for 10 years, there exists no femtosecond solid-state laser oscillator operating around 600-630 nm, which has already been widely applied for scientific studies during the dye-laser era. We demonstrate the first femtosecond mode-locked all-solid state laser oscillator covering the orange wavelength region of 600-630 nm. Femtosecond orange pulses with high average power was obtained directly from a laser oscillator by intracavity frequency doubling of a mode-locked Cr:forsterite laser using a BBO crystal. Intracavity frequency doubling shows advantages over external cavity frequency doubling due to simplicity and efficiency considerations that are key points of using solid-state instead of dye lasers.

Summary form only given. Multi-wavelength generation of ultrashort and highly synchronized pulses directly from a single laser oscillator is of great interest in novel photonic networks utilizing combined optical wavelength-division multiplexed and time-division multiplexed data format. Many efforts were made already, but can achieve relative low output power on the order of several tens of /spl mu/W up to 1 mW. In this presentation, we will demonstrate a multiple-channel modelocked all-solid-state Cr:forsterite laser. By inserting an etalon into the cavity, 12 locked channels with total 280 mW average power were generated. Pulsewidth as short as 1.8 ps can be achieved for a single channel with reflectivity management.

Multi-photon fluorescence spectra of a number of commonly used biological probes were measured in this study. Significant spectral variation has been detected between single and multi- photon excitation. The result is important for the proper selection of spectral setting/dichroic beam splitter in the set- up of a multi-photon fluorescence microscope. The information can also be useful in the detection of multi-photon fluorescence in bio-chip technology. In addition, we have investigated a few highly fluorescent bio-molecules commonly found in plant cells.

The authors demonstrated that the piezoelectric superlattice, can serve as narrow-band detectors for propagating coherent longitudinal acoustic phonons at multiple frequencies corresponding to the spatial frequency of the superlattice and its higher harmonics, and its detection bandwidth is determined by the total structure width. By optically exciting a broadband propagating longitudinal acoustic pulse from a thin Ni film, the authors studied the acoustic spectral sensitivity function of a ten-period In0.12Ga0.88N∕GaN multiple quantum well. Because the barriers (19nm) and wells (3.6nm) are of different widths, the second detection band, corresponding to the second harmonic of the fundamental frequency, can be resolved.

We report a 2GHz repetition-rate, all-solid-state femtosecond blue source. Pumped by a 740mW femtosecond Ti:sapphire laser with the same repetition rate, 150mW femtosecond pulses at 409nm can be efficiently generated from the external resonant cavity with a lithium triborate crystal.

We demonstrate a compact and self-starting fiber-delivered femtosecond Cr:forsterite laser for nonlinear light microscopy. A semiconductor saturable absorber mirror provides the self-starting mechanism and maintains long-term stability in the laser cavity. Four double-chirped mirrors are employed to reduce the size of the cavity and to compensate for group velocity dispersion. Delivered by a large-mode-area photonic crystal fiber, the generated laser pulses can be compressed down to be with a nearly transform-limited pulse width with 2.2-nJ fiber-output pulse energy. Based on this fiber-delivered Cr:forsterite laser source, a compact and reliable two-photon fluorescence microscopy system can thus be realized.

We demonstrate a novel multimodal nonlinear spectral microscopy based on a femtosecond Cr:forsterite laser at 1230 nm. By acquiring the whole nonlinear spectrum in the visible and near-NIR region, this novel technique allows a combination of different imaging modalities, including second-harmonic generation, third-harmonic generation, and multiple-photon fluorescence. Combined with the selected excitation wavelength, which is located in the IR transparency window, this microscopic technique can provide high penetration depth with reduced damage and is ideal for studying living cells.

We demonstrate a multiple-channel, mode-locked, all-solid-state Cr:forsterite laser. By inserting an etalon into the laser cavity, we have generated 12 phase-locked channels with 9–19-ps pulse width near 1230 nm with 280-mW average output power from a single laser oscillator. By tuning the etalon bandwidth we can shorten the pulse width in a specific channel to 1.8 ps.

The generation of femtosecond optical pulses centered at ~620 nm directly from an all-solid-state laser oscillator is reported. Red pulses with pulse widths of the order of 170 fs were obtained with 24-mW average power at an 81-MHz repetition rate. They were achieved by intracavity frequency doubling of a mode-locked Cr(4+):forsterite laser with a 1-mm-thick beta-BaB(2)O(4) crystal. The process of laser mode locking was modified by surface coating the doubling crystal.