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We present a new platform for sensitive molecular detection and control spanning 1) multiplexed genetic and proteomic screening, 2) single-cellular bacterial identification and drug susceptibility testing, and 3) chiral molecular synthesis and separation, based on high-quality-factor phase gradient metasurfaces. The high-quality factor of our metasurfaces produces a large amplification of the electromagnetic field, increasing the response to targeted binding of biomarkers. Simultaneously, the optical signal is beam-steered for multiplexed detection. We develop these metasurfaces for a new respiratory panel of SARS-CoV-2, RSV, and influenza; Raman-based identification and antibiotic susceptibility testing of pathogens; and sensitive identification and purification of chiral molecules including amino acids and small-molecule pharmaceuticals and agrochemicals.
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Biomedical Applications for Ultrafast Laser Systems I
Picosecond pulsed lasers can provide significant advantages for high precision, minimally invasive surgery compared to conventional electrocautery tools or utilising continuous wave or long pulsed lasers which can induce high degrees of thermal damage. By combining a range of characterisation techniques such as high-speed imaging, surface profilometry and histopathological analysis of the laser ablated regions we have gained deeper understanding into the dynamics of the plasma-mediated ablation. For example, correlation of time-resolved images with histopathology reveals subtleties about the process such as cavitation effects which must be mitigated in order minimise collateral thermal damage. Additionally, by investigating these phenomena on clinically relevant tissue models we can move towards the realisation of new surgical procedures for more complete removal of disease (such as cancer) from delicate and vital structures within the human body. Such procedures require this high precision to minimise necrotic tissue margins, avoiding severe complications and preserving function. In addition to the fundamentals of laser tissue interactions, novel optical technologies such as beam shaping, micro-optics, imaging and novel fibre optic delivery have also been investigated in order to enable practical and deployable devices.
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This Conference Presentation, “Femtosecond laser microdissection (fs-LM) for single cell RNA sequencing,” was recorded at SPIE Photonics West held in San Francisco, California, United States.
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Biomedical Applications for Ultrafast Laser Systems II
Ultrashort laser pulses deliver broadband sources for excitation of multiple fluorophores at the same time, therefore providing to medical imaging systems an advance tool for imaging deeper into samples. Furthermore, due to their short pulse duration, and smaller average power they also allow to extend the life time of in vivo samples. Ultrashort laser pulses can also be used in surgery for removing damaged tissues in very difficult areas with reduced access, therefore being excellent tools in medical applications.
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We optimized the spectral coverage of self-phase-modulation-enabled femtosecond fiber sources by careful investigations into the influence of input pulse width, fiber length, and fiber damage, and we have demonstrated a widely tunable source ranging from 740-1250 nm for two-photon microscopy applications. In addition, tens of milliwatt tunable near-UV/visible spectrum is easily obtained by a frequency-doubled conversion, and the gap between the fundamental and frequency-doubled spectra can be filled with the nonlinear wave breaking around 650 nm. A multi-modality microscopy incorporating two-photon microscopy and confocal fluorescence microscopy was also demonstrated to prove the versatility of our development for biomedical imaging.
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We present our latest results into the freeform 3D nanoprinting of arrays of TiO2 nanorods. We demonstrate that the rate of photocatalysis of Methylene Blue increases significantly, due to increase in active surface area. Our results open the route to using 3D-printed TiO2 nanorods for other energy applications, such as hydrogen generation.
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Titanium based dental implant suffer sometimes from failure due to lack of osseointegration in the jaw bone. In this work, we study the generation of Laser Induced Periodic Structures (LIPSS) using three different femtosecond lasers with wavelengths of 1030,515 & 257nm. Fully covered Titanium alloy (Ti6AlV) samples with different LIPSS periodicities are produced and wettability tests are performed prior and post sterilization of the samples. Finally, a comparison between the effect of different LIPSS on the cell adhesion is performed using mesenchymal stem cells to identify the best pattern for enhanced cell adhesion.
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Femtosecond technologies will enable new fields of use and new methods of production thanks to the "agility" of high-power fs lasers associated with beam engineering. The relative slowness of the removal processes in femtosecond mode is no longer a limitation and the unique quality of ultra-short processes is therefore accessible to an increasingly important panel of industrial implementation. We report on the versatile use of femtosecond pulses at more than 300W average power at a wavelength of 1030 nm, 200W at 515nm, and 100W at 343 nm, free triggering of the laser output pulses, and burst generation.
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Neuronal dysfunction due to lack of functional copy of specific genes leads to several neurological disorders, and gene replacement or editing based therapies require efficient gene delivery. Further, activation of specific cells by optical, ultrasound and other methods requires insertion of gene-encoding actuators into cells. I will present use of near-infrared ultrafast laser microirradiation platform for efficient and spatially-targeted delivery of different therapeutic genes to neuronal tissue. Specifically, I will describe use of this platform for delivery of gene encoding for neuroprotective and anti-angiogenic PEDF molecule to retina that exhibited protection from different insults. Ultrafast laser based delivery of ambient-light activatable multi-characteristic opsin (MCO) to retinal cells led to functional improvement, measured by electrophysiology. Besides, targeted delivery, the ultrafast laser based non-viral gene delivery could circumvent the payload limitation of AAV-based delivery, and large genes such as ABCA4 (mutation of which leads to photoreceptor dysfunction) could be delivered to retina. In-vivo neuromodulation by ultrafast laser based perforation of cell membrane opens up new possibilities such as redosing in subjects requiring gene transfer without causing inflammatory or immune response.
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Laser-induced shock waves have been gaining attention for biological and medical applications in which shock waves influence cell permeation. However, the mechanisms of permeation remain mostly unclear because of the difficulty of observing the transient and dynamic behaviors of the shock waves and the cells. Here we present an all-optical measurement method that can quantitatively capture the pressure distribution of the propagating shock wave and simultaneously monitor the dynamic behavior of cell membranes. Using this method, we find that a sharp pressure gradient causes cell membrane permeation. Our measurement will further advance biological and medical applications of shock waves.
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Micro processing applications using femtosecond lasers have developed thanks to the quality of the process. A challenge still to be addressed is the capability to deliver the beam through a fibre. One solution is the use of hollow-core inhibited coupling fibres, nevertheless its use requires a beam stabilization to insure a stable operation.
This study attempts to qualify two beam stabilisation systems: two piezo motors coupled with four quadrant detectors and Cailabs’ all-optical mode-cleaner system based Multi-Plane Light Conversion (MPLC) technology. To do such output fibre transmission efficiency and beam quality are investigated under controlled fluctuation of beam pointing.
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Displays are fundamentally light control devices and the better the light can be controlled the higher quality the display is. Today’s display technologies do not feature a high level of light control because they use incoherent light emitters, that means light is emitted in a wide cone, over a large wavelength spectrum and at low intensity. Here we present a new display architecture that is built around the highly controlled emission of laser light at every sub-pixel of the display, offering vast improvements in energy efficiency, image quality and ability to generate 3D images.
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We are addressing the need for better understanding of the mechanical effects involved in the femtosecond laser processing of transparent materials. By focusing infrared (1.03μm) laser pulses with a duration of 360fs and an energy of ~1μJ inside the bulk of a fused silica cube, we generate a plasma that absorbs laser energy. We then use a time-resolved microscope-polariscope based on a pump-and-probe scheme to measure optical transmission and stress-induced birefringence. Our methodology provides a link between initial ionization stages and the hydrodynamic response of the excited material thus allowing a full description of the interaction until the nanosecond timescale.
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In this study, we investigate the conversion of femtosecond laser energy deposition from plasma into a shockwave in ambient air. The experiments are carried out using a 380fs pulsed laser at 1.03μm, with laser intensities below the filamentation threshold. The measurements of this dynamic phenomenon are carried out with the help of a time-resolved transmission microscope, and the pressure and temperature space-time evolution are evaluated using a theoretical model. In our conditions we generate shockwaves with initial pressure loading in the range of GPa and maximum propagation velocity in the order of a few km/s.
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We present a way to exploit 3D resonant mechanical micro-structures, embedded in glass substrates, to achieve optical signals switching at MHz frequency. These structures are realised by means of femtosecond laser pulses: combining direct waveguide writing and laser-assisted etching in hydrofluoric acid of the 3D microstructure. The mechanical oscillation of the resonator induces periodical refractive index modifications, due to localised stress, across the waveguide region, thus modulating the phase of the propagating optical signal.
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Justinas Pupeikis, Benjamin Willenberg, Francois Bruno, Mike Hettich, Alexander Nussbaum-Lapping, Matthias Golling, Carolin P. Bauer, Sandro L. Camenzind, Benayad Abdelmjid, et al.
Proceedings Volume Frontiers in Ultrafast Optics: Biomedical, Scientific, and Industrial Applications XXII, PC119910I https://doi.org/10.1117/12.2609555
We present a free-running 80-MHz polarization-multiplexed solid-state dual-comb laser which delivers 1.8 Watts of average power with 110-fs pulse duration per comb. We apply this free-running dual-comb laser to picosecond ultrasonic measurements via a high-sensitivity pump-probe setup. We demonstrate ultrasonic measurements on thin-film samples, and compare our measurements to ones obtained with a pair of locked femtosecond lasers and x-ray diffraction measurements. Our data show that a free-running dual-comb laser is well-suited for picosecond ultrasonic measurements and thus it offers significant reduction in complexity and cost for this widely adopted non-destructive testing technique.
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In this study, we investigate multiple etchants and laser parameters. Interestingly, we show that there is an optimal energy dose one order of magnitude smaller than the currently used ones, and notably, at a regime where nanogratings are not yet formed. This energy dose yields higher process efficiency and lower processing time, and this, with unprecedented aspect ratio levels. We further demonstrate that for low dose exposure is the formation of laser-induced bond matrix defects in the glass matrix and not the presence of nanogratings that drives the etching selectivity.
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We demonstrate the fabrication of double-network (DN) hydrogel microstructures inside a hydrogel by multi-photon cross-linking induced by focused femtosecond laser pulses. Two different poly(ethylene glycol) diacrylate (PEGDA, Mw=700 and 4000) solutions were prepared. A cross-linked PEGDA hydrogel molded into block-shape was immersed in PEGDA hydrogel prepolymer solutions of different molecular weight. Then the DN microstructures were fabricated by spatially-selective photo cross-linking of the polymer chains by femtosecond laser pulse irradiation. The mechanical strength of DN microstructures were enhanced which was confirmed by uniaxial compression test, suggesting the potential of our method for controlling spatial distribution of strength and stiffness.
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A point-by-point femtosecond laser fabrication technique was used to form filament arrays inside single-mode telecommunication fiber. The off-axis positioning of the grating from the neutral axis was key to enabling displacement optical sensing in single mode fiber. Optomechanical responses were enhanced with stress concentration in cantilevered optical fiber. The narrow geometry of the filament array facilitated sensing of a uniform strain field induced by the lateral displacement, or to null the response when filaments were orthogonally oriented. In this way, filament gratings could be overlaid for azimuthally resolved displacement sensing. The ability to measure transverse displacements paves the way toward developing more efficient optical accelerometers.
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We present novel techniques for tailoring the dispersive and spectral properties of fiber Bragg gratings (FBGs) using ultrashort pulsed phase mask inscription. Herein, we tune the spectral and dispersive properties of FBGs by a tailored modification of the effective refractive index of selected grating regions before, during, or after the FBG inscription. Furthermore, a comparison and application of these techniques in producing nonlinearly chirped FBGs with a linearly chirped phase mask as well as a uniform phase mask will be presented. This work paves the way for a flexible and cost-effective tailoring of the spectral and dispersive properties of femtosecond inscribed FBGs.
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We present a sub-2-cycle laser system combining high average power, pulse energy and repetition rate with CEP-stable operation. The laser system creates 300 fs pulses with 1.8 mJ pulse energy that are nonlinearly post-compressed down to few optical cycles in two subsequent multipass cells (MPC). A pulse duration of 5.8fs (sub-2-cycle) at a pulse energy of 1.1mJ in combination with 110W average power (100 kHz) is achieved. This corresponds to the shortest pulses and highest compressed average power for few-cycle MPCs. Furthermore, the carrier-to-envelope-phase stability amounts to 300 mrad for frequencies above 2 kHz as measured by stereo—above-threshold-ionization (ATI).
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We report on kW-level femtosecond lasers for flexible and high throughput industrial applications. Power scaling is achieved by a slab-based amplifier architecture. The laser concept is capable to generate high pulse energies in the multi-mJ range as well as high pulse repetition rates in the MHz or GHz ranges. Moreover, free triggering (FemtoTrig®) and burst options as well as frequency conversion to the green and UV spectral region will leverage these femtosecond lasers into future industrial applications.
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Ultrafast lasers are key tools for micromachining and medical applications, but also in a growing numbers of domains like telecoms, aerospace and microwave photonics, which are currently limited by the lack of reliability of the lasers and the achievable repetition rate. Menhir Photonics has now successfully demonstrated and deployed real-turnkey ultrafast laser oscillators at 1.5 um and GHz repetition rate with an unprecedent robustness. Reaching now up to 2.5 GHz of fundamental repetition rate and the lowest phase noise and timing jitter on the market, the MENHIR-1550 was already qualified for Space. The latest development of the MENHIR-1550 at 2.5 GHz will be presented (first commercial product of its kind) as well as the newest applications that it enabled worldwide, in the fields of green-house gases monitoring from Space, very fast dual-comb spectroscopy or photonics analog-to-digital converter.
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Femtosecond laser writing shows great potential for novel 3D photonic architectures and high quality NV- quantum emitters in the bulk of diamond. However, the direct writing method cannot achieve nanometric placement of NV- centers near the surface of diamond, which is required for certain quantum sensing tasks. We will demonstrate a hybrid approach where the advantages of 3D optical waveguides by femtosecond laser writing and precise and shallow placement of NV- centers by ion implantation will be combined to form an integrated quantum sensor with record high performance.
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Complex touch panel displays development is requiring high performance glass cutting techniques. Femtosecond lasers, combined to Bessel beam generation based on reflective axicons already showed quality and efficiency improvements, while being able to handle high peak and average power.
We described here recent developments for high quality Bessel beam generation using a fully reflective system. This complex Bessel beam presents an intensity plateau along its propagation axis, being twice more homogeneous and having a five times sharper tail compared to a classical Bessel beam. This development paves the way to complex and selective multi-layer glass cutting.
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We propose Type-II SHG-autocorrelation as a simple and robust tool for high-dynamic range pulse-contrast measurements of sub-μJ energy, high-repetition rate pulses. We demonstrate dynamic ranges of the autocorrelation of over 10^7 with input energies of 55 nJ at 1 MHz repetition rate. The device allows temporal resolutions of 25 fs over a wide scanning range of 1100 ps, supporting input wavelengths from 700-1200 nm. The technique provides the perfect tool for wide use pulse-contrast measurement and optimization, possibly enabling a more effective use of pulse energy in peak power driven material processing applications.
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