This PDF file contains the front matter associated with SPIE Proceedings Volume 7203, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing

Two-photon imaging of human skin using ultra short laser pulses can be used to obtain information about the state of cells and tissues by means of their natural autofluorescence. Using this method, it is possible to determine whether the normal cell pattern is disturbed or the autofluorescence is influenced by internal or external stimuli. Two-photon fluorescence lifetime imaging (FLIM) can further enhance this providing information about physiological processes, fluorophores (like NAD(P)H, collagen, keratin, elastin, flavins, melanin,...) and external applied probes inside cells and tissue parts. For example the part of the cells metabolism and energy level can be determined by analyzing the NADH regarding its free / bound state and its oxidized / reduced state. The combination of two-photon imaging with FLIM may lead to a better understanding and diagnosis of skin reactions and disorders. We also present some results of in vivo simultaneous collagen and elastin measurements in skin dermis. Changes of dermal collagen and elastin content are characteristic for skin aging as well as for pathological skin conditions.

Fs-lasers are widely used for microsurgery and micromachining. Due to nonlinear interaction of ultrashort pulses with tissue or matter precisions of a few μm can be achieved. But particularly in the field of surgery this precision can not be obtained as the devices for diagnostics and treatment have to be changed due to separate systems. We show a combined system of a fs-laser and a Fourier-Domain optical coherence tomography (FD-OCT) enabling to cut and image the region of interest alternately. The FD-OCT offers non-invasive imaging at an axial resolution of 6, 2 μm and a transverse resolution of 3 μm in air which is comparable to the interaction zone of the fslaser-pulses. OCT-aided subsurface cutting is successfully demonstrated on biological ex-vito samples of porcine cornea and larynx. Furthermore it appeared that in situ OCT imaging enables to monitor cuts produced with pulse energies close to the energy threshold. In conclusion, this setup demonstrates the potential of a system combining cutting and OCT imaging within the same optical setup without the need of changing devices.

Pulsed light emitted from a near infrared (λ=800nm) femtosecond laser is capable of plasma induced photodisruption of various materials. We used femtosecond laser pulses to ablate human urinary calculi. Femtosecond pulsed laser interaction with urinary calculi was investigated with various stone compositions, different incident fluences and number of applied pulses. Spectral-domain optical coherence tomography was used to image cross sections of ablation craters on the surface of urinary calculi. Our results indicate that femtosecond laser pulses can ablate various calculi compositions. Crater diameter and depth varies from tens of microns to several hundred microns when up to 1000 pulses were applied. Future studies are required to determine if pulsed near infrared femtosecond laser pulses can be applied clinically for lithotripsy of urinary calculi.

Embryonic development strictly depends on fluid dynamics. As a consequence, understanding biological fluid dynamic is essential since it is unclear how flow affects development. For example, the specification of the left-right axis in vertebrates depends on fluid flow where beating cilia generate a directional flow necessary for breaking the embryonic symmetry in the so-called left-right organizer. To investigate flow dynamics in vivo proper labeling methods necessitate approaches that are compatible with both normal biology and in vivo imaging. In this study, we describe a strategy for labeling and analyzing microscopic fluid flows in vivo that meets this challenge. We developed an all-optical approach based on three steps. First we used sub-cellular femtosecond laser ablation to generate fluorescent micro-debris to label the flow. The non-linear effect used in this technique allows a high spatial confinement and a low invasiveness, thus permitting the targeting of sub-cellular regions deep inside the embryo. Then, we used fast confocal imaging and 3D-particle tracking were used to image and quantify the seeded flow. This approach was used to investigate the flow generated within zebrafish left-right organizer, a micrometer scale ciliated vesicle located deep inside the embryo and involved in breaking left-right embryonic symmetry. We mapped the velocity field within the vesicle and surrounding a single beating cilium, and showed that this method can address the dynamics of cilia-driven flows at multiple length scales. We could validate the flow features as predicted from previous simulations. Such detailed descriptions of fluid movements will be valuable in unraveling the relationships between cilia-driven flow and signal transduction. More generally, this all-optical approach opens new opportunities for investigating microscopic flow in living tissues.

Tandem mass spectrometry is a widely used tool for molecular structure determination of biomolecules. Advances in proteome analysis depend on the development of improved methods for ion activation that yield greater sequence information, with selective control over the fragmentation chemistry. A novel activation method, femtosecond laser-induced ionization/dissociation, is described here, and compared to collision induced dissociation through the analysis of three peptides.

In recent years, the advantages of using small invertebrate animals as model systems for human disease have become increasingly apparent and have resulted in three Nobel Prizes in medicine or chemistry during the last six years for studies conducted on the nematode Caenorhabditis elegans (C. elegans). The availability of a wide array of species-specific genetic techniques, along with the transparency of the worm and its ability to grow in minute volumes make C. elegans an extremely powerful model organism. We present a suite of technologies for complex high-throughput whole-animal genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize C. elegans in a well-defined geometry, an integrated chip containing individually addressable screening chambers for incubation and exposure of individual animals to biochemical compounds, and a device for delivery of compound libraries in standard multiwell plates to microfluidic devices. The immobilization stability obtained by these devices is comparable to that of chemical anesthesia and the immobilization process does not affect lifespan, progeny production, or other aspects of animal health. The high-stability enables the use of a variety of key optical techniques. We use this to demonstrate femtosecond-laser nanosurgery and three-dimensional multiphoton microscopy. Used alone or in various combinations these devices facilitate a variety of high-throughput assays using whole animals, including mutagenesis and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as femtosecond-laser nanosurgery for large-scale in vivo neural degeneration and regeneration studies.

Femtosecond laser direct writing was applied to fabricate 3D diffractive optical elements in oxide glass. Here we report our initial results. We describe the consequences of fabricating Fresnel Zone Plates (FZPs) with various femtosecond laser parameters. Single or multiple layers of laser written FZPs were produced in borosilicate glasses. We are investigating the diffraction efficiencies as a function of laser and writing parameters such as pulse energy, writing speed and repetition rate.

We report the realization of an evanescently coupled laser-written type II array in χ-cut Lithium niobate. Certain processing parameters allow evanescent fields to extend beyond the regions of damage, while still increasing the index sufficiently to guide light. An array consisting of eleven coupled waveguides was fabricated. Coupling was evaluated by observing discrete diffraction patterns of single waveguide excitations at various array sites. Homogeneous coupling was verified within the array, while the outermost guides are slightly detuned due to being formed by just one damage structure.

The ability to integrate micro-channels for fluid transport with optical elements is attractive for the development of compact and portable chip-based sensors. Femtosecond Laser Direct Writing (FLDW) in transparent materials is a powerful tool for the fabrication of such integrated devices. We demonstrate the use of FLDW to fabricate coupled micro-fluidic channels and optical waveguides towards an integrated sensing device for molecular detection. Waveguides were directly written into the host material and channels were formed by modifying the molecular structure through FLDW followed by wet chemical etching. Multiple host materials including chalcogenide glasses for IR detection are discussed.

Self-imaging in integrated optical devices is interesting for many applications including image transmission, optical collimation and even reshaping of ultrashort laser pulses. However, in general this relies on boundary-free light propagation, since interaction with boundaries results in a considerable distortion of the self-imaging effect. This problem can be overcome in waveguide arrays by segmentation of particular lattice sites, yielding phase shifts which result in image reconstruction in one- as well as two-dimensional configurations. Here, we demonstrate the first experimental realization of this concept. For the fabrication of the segmented waveguide arrays we used the femtosecond laser direct-writing technique. The total length of the arrays is 50mm with a waveguide spacing of 16 μm and 20μm in the one- and two-dimensional case, respectively. The length of the segmented area was 2.6mm, while the segmentation period was chosen to be 16 μm. This results in a complete inversion of the global phase of the travelling field inside the array, so that the evolution dynamics are reversed and the input field is imaged onto the sample output facet. Accordingly, segmented integrated optical devices provide a new and attractive opportunity for image transmission in finite systems.

Flexures are mechanical elements used in micro- and precision-engineering to precisely guide the motion of micro-parts. They consist of slender bodies that deform elastically upon the application of a force. Although counter-intuitive at first, fused silica is an attractive material for flexure. Pending that the machining process does not introduce surface flaws that would lead to catastrophic failure, the material has a theoretically high ultimate tensile strength of several GPa. We report on high-aspect ratio fused silica flexures manufactured by femtosecond laser combined with chemical etching. Notch-hinges with thickness as small as twenty microns and aspect ratios comparable to aspect ratios obtained by Deep- Reactive-Ion-Etching (DRIE) were fabricated and tested under different loading conditions. Multiple fracture tests were performed for various loading conditions and the cracks morphologies were analyzed using Scanning Electron Microscopy. The manufactured elements show outstanding mechanical properties with flexural strengths largely exceeding those obtained with other technologies and materials. Fused silica flexures offer a mean to combine integrated optics with micro-mechanics in a single monolithic substrate. Waveguides and mechanical elements can be combined in a monolithic devices opening new opportunities for integrated opto-mechatronics devices.

Our study shows that a large variety of nano- and micro-scale structures can be controllably produced on metallic biomaterials such as titanium, platinum, and gold using direct femtosecond laser processing techniques. This process provides a way for controlling behaviors of both proteins and cells. Also, we find the laser treatment conditions for producing femtosecond laser-induced periodic structures that can be suitable for surface-plasmon-based biosensors.

Thin film solar cells have shown a big potential to decrease cost of manufacturing for photovoltaic power generation. Despite of all research attempts to optimize materials and efficiency the mass production of thin film solar cells is still employing some mechanical steps of structuring, where thin films with a thickness of approximately 1 μm are selectively separated for the monolithic serial interconnection. Here we show the structuring of CIS (CuInSe₂) thin films solar cells by picosecond laser ablation. We used a new method, which we called "directly induced laser ablation" to increase process speed for the scribing of a Mo-film on glass (pattern 1, P1) to 4000 mm/s with an elliptically shaped beam. Directly induced laser ablation exhibits a non thermal behaviour. Standard laser ablation was used to create P2 and P3 lines at a process speed up to 200 mm/s. All processes showed their functionality for a complete interconnected solar module.

We have studied experimentally and numerically the pulse shaping dynamics of a diode-pumped thin-disk laser oscillator with active multipass cell and large output coupling rates. We demonstrate the generation of high energy subpicosecond pulses with energies of up to 25.9 μJ and durations of 928 fs directly from a thin-disk laser oscillator without further amplification. We have achieved these results by employing a selfimaging active multipass geometry in order to increase the output coupling rate for a suppression of nonlinear optical effects. With this system we have obtained stable single pulse operation in ambient atmosphere with average output powers above 76W at a repetition rate of 2.93 MHz. A semiconductor saturable absorber mirror was used to start and stabilize passive soliton mode locking. The experimentally studied laser pulses show good agreement with numerical simulations including the appearance of Kelly sidebands. We also present a modification to the soliton area theorem that is applicable for such a laser oscillator with active multiple pass cell and large output coupling rate. Furthermore, we demonstrate the laser's potential for micro machining applications by showing first examples of material processing, such as the determination of ablation thresholds and ablation rates for various materials.

We are developing directly diode-pumped femtosecond lasers for industrial applications. A mode-locked Yb:KYW laser with the pulse duration of 113 fs has been developed as a seed laser. An Yb:KGW crystal in the regenerative amplifier is pumped by a 75-W fiber-coupled laser diode. The seed pulse was amplified to 0.82 mJ at the repetition rate of 1 kHz. At the repetition rate of 100 kHz, the averaged output achieved more than 3 W after pulse compression. The power stability during four hours was 1.56 % (3σ). We confirmed that the amplified pulse was compressed to nearly Fourier transform limit. The calculated transform limited pulse width and the measured pulse width was 319 fs and 339 fs, respectively.

Pump-probe techniques are widely used to measure events on time scales much shorter than the resolution of electronic detectors, and are applied in such diverse fields as ultrafast spectroscopy, photo-acoustics, TeraHertz imaging, etc. In ultrafast photoacoustics measurements for instance, a pump beam launches in the sample acoustic waves, which are detected by a second, temporally shifted probe beam. Typical detection methods rely on very small changes in the reflection coefficient of the sample surface, requiring an averaging of the signal to improve the signal to noise ratio. Traditional pump-probe methods use a mechanical delay line to shift the two pulses in the time domain, where each measurement point corresponds to a single mechanical position of the delay line. Although very efficient for small measurement ranges, extending this method in the hundreds of picoseconds or nanosecond lead to a very long acquisition time, and unpractical length for the delay line. We present a new, compact detection system, using a compact dual-oscillator ultrafast laser system, specifically designed for pump-probe measurements over time scales as long 20 ns, with a sub-picosecond resolution. This system does not use any mechanical delay line, and allows for extremely fast acquisition time.

We demonstrate a femtosecond fiber laser system delivering >5-μJ, sub-400-fs pulses at a pulse repetition rate of 200 kHz. At constant average power the pulse repetition rate of this Watt-level femtosecond laser can be adjusted up to several MHz. The laser is monolithically integrated from the oscillator to the booster amplifier stage. The system was applied for structuring metallic as well as transparent media as e.g. biological tissues in ophthalmology.

We demonstrate a powerful and practical spectral interferometer with near-field scanning microscopy (NSOM) probes for measuring the spatiotemporal electric field of tightly focused ultrashort pulses with sub-micron spatial resolution and high spectral resolution. To make these measurements we use SEA TADPOLE which is a high spectral resolution, experimentally simplified version of spectral interferometry that uses fiber optics to introduce the pulse into the device. To measure the spatiotemporal field of focusing pulses, the entrance fiber is scanned around the focus and a measurement at each fiber position is made, so that E(ω) is found at many positions along the beam's cross section so that we can reconstruct E(x,y,z,ω). The make these measurements we require that the fiber's mode size be smaller than the focused spot size. In the past using optical fibers we were limited to measuring foci with NA's less than 0.1, and here by replacing the fiber with an NSOM fiber, we measure the spatiotemporal field of focused pulses with NAs as high as 0.44. To demonstrate this technique we measured pulses that were focused with two different microscope objectives to verify that we achieved the expected results. We also measured foci that had severe distortions, such as the Bessel-like X-shaped pulse caused by spherical aberrations and the "fore-runner pulse" due to chromatic aberrations and we verified these results with non-paraxial simulations. In our measurements we observed spatial features smaller than 1μm.

The high peak intensity of ultrafast lasers has allowed a wide variety of applications such as material processing, multiphoton imaging, and several spectroscopic technologies. Because ultrafast lasers are sensitive to the environment and the pulses are broadened by optics, commercial applications seldom use sub-100 fs pulses. This talk will explain how the theoretical concept of coherent control allowed our research group to revolutionize how femtosecond laser pulses are characterized and compressed. With MIIPS (multiphoton intrapulse interference phase scan) we are now able to deliver to the target transform limited pulses with pulse durations as short as 4.6 fs. The performance parameters of more than 16 different commercial lasers systems using MIIPS will be presented. Micromachining, two-photon microscopy, and standoff detection measurements from our group will be used to illustrate advantages realized by consistent delivery of ultrafast pulses through complex focusing optics.

We introduce a simple, compact, and automatically distortion-free single-grism pulse compressor that can compensate for large amounts of material dispersion in ultrashort pulses, which increases the pulse duration and decreases the peak intensity. Diffraction-grating pulse compressors can compensate for high dispersion, but they do not compensate for higher-order dispersion (important when GDD is large). Worse, all previous general-purpose grating designs have involved multiple gratings and so are also difficult to align and prone to distortions: small misalignments cause unwanted spatio-temporal pulse distortions. A compressor based on grisms solves the higher-order-dispersion problem because grisms allow the ratio of third-order to second-order dispersion to be tuned to match that of the material that introduced the GDD. A grism can also compensate for large amounts of dispersion. Unfortunately, previous grism compressors used multiple grisms and so are difficult to align and prone to spatio-temporal distortions. To overcome this problem, we introduce a single-grism compressor. It comprises only three elements: a reflection grism, a corner cube, and a roof mirror. SEA TADPOLE measured the compressor GDD and third-order dispersion, verifying its operation. This convenient device should be a valuable general tool.

We present an experimental study of the drilling of metal targets with ultrashort laser pulses with pulse durations from 800 fs to 19 ps at repetition rates up to 1 MHz, average powers up to 70 Watts, using an Ytterbium-doped fiber CPA system. Particle shielding and heat accumulation have been found to influence the drilling efficiency at high repetition rates. Particle shielding causes an increase in the number of pulses for breakthrough. It occurs at a few hundred kHz, depending on the pulse energy and duration. The heat accumulation effect is noticed at higher repetition rates. Although it overbalances the particle shielding thus making the drilling process faster, heat accumulation is responsible for the formation of a large amount of molten material that limits the hole quality. The variations of the pulse duration reveal that heat accumulation starts at higher repetition rates for shorter pulse lengths. This is in agreement with the observed higher ablation efficiency with shorter pulse duration. Thus, the shorter pulses might be advantageous if highest precision and processing speed is required.

We demonstrate a small device with a microfluidic channel and an integrated waveguide that functions a compact rudimentary tool for the detection, real-time monitoring, and potentially classification of algae. In order to reduce parasitic noise the micro-device used a curved subsurface optical waveguide to illuminate particles transiting through a microfluidic channel. The changes in the transmitted signal are monitored using a quadrant-cell photo-detector. The signals wavelets from the different quadrants are used to qualitatively distinguish different families of algae. Additional information, such as flow direction, is also provided. The channel and waveguide are fabricated out of a monolithic fused-silica substrate using a femtosecond laser-writing process combined with chemical etching. This proof-of-concept device paves the way for more elaborate femtosecond laser-based optofluidic micro-instruments incorporating waveguide network designed for the real-time analysis of cells and microorganisms in the field.

We report on the use of femtosecond laser pulses to fabricate photonic devices (waveguides and interferometers) inside commercial CE chips without affecting the manufacturing procedure of the microfluidic part of the device. The fabrication of single waveguides intersecting the channels allows one to perform absorption or Laser Induced Fluorescence (LIF) sensing of the molecules separated inside the microchannels. Microfluidic channels, with access holes, are fabricated using femtosecond laser irradiation followed by chemical etching. Mach-Zehnder interferometers are used for label-free sensing of the samples flowing in the microfluidic channels by means of refractive index changes detection.

Optical coherence microscopy (OCM) is used to image femtosecond laser direct written buried structures created within transparent media. Volumetric structures of optical damage and laser-induced refractive index change were produced in fused silica and borosilicate glass, respectively. Noninvasive 3D imaging of the structures was successfully demonstrated by a custom built OCM. High signal to noise ratio was obtained since the optical glasses have high transparency at the probe wavelength centered at 800 nm.