Enhanced laser-driven proton acceleration via improved fast electron heating in a controlled pre-plasma.

The interaction of ultraintense laser pulses with solids is largely affected by the plasma gradient at the vacuum-solid interface, which modifies the absorption and ultimately, controls the energy distribution function of heated electrons. A micrometer scale-length plasma has been predicted to yield a significant enhancement of the energy and weight of the fast electron population and to play a major role in laser-driven proton acceleration with thin foils. We report on recent experimental results on proton acceleration from laser interaction with foil targets at ultra-relativistic intensities. We show a threefold increase of the proton cut-off energy when a micrometer scale-length pre-plasma is introduced by irradiation with a low energy femtosecond pre-pulse. Our realistic numerical simulations agree with the observed gain of the proton cut-off energy and confirm the role of stochastic heating of fast electrons in the enhancement of the accelerating sheath field.

Toward an effective use of laser-driven very high energy electrons for radiotherapy: Feasibility assessment of multi-field and intensity modulation irradiation schemes.

Radiotherapy with very high energy electrons has been investigated for a couple of decades as an effective approach to improve dose distribution compared to conventional photon-based radiotherapy, with the recent intriguing potential of high dose-rate irradiation. Its practical application to treatment has been hindered by the lack of hospital-scale accelerators. High-gradient laser-plasma accelerators (LPA) have been proposed as a possible platform, but no experiments so far have explored the feasibility of a clinical use of this concept. We show the results of an experimental study aimed at assessing dose deposition for deep seated tumours using advanced irradiation schemes with an existing LPA source. Measurements show control of localized dose deposition and modulation, suitable to target a volume at depths in the range from 5 to 10 cm with mm resolution. The dose delivered to the target was up to 1.6 Gy, delivered with few hundreds of shots, limited by secondary components of the LPA accelerator. Measurements suggest that therapeutic doses within localized volumes can already be obtained with existing LPA technology, calling for dedicated pre-clinical studies.

Experimental study on the performances of second-harmonic dispersion interferometers at 10.6 µm and 1064 nm for plasma density measurements.

Two common-path interferometers based on CO2 and Nd:Y3Al5O12 (Nd:YAG) lasers are benchmarked with a two-arm microwave interferometer on a hydrogen plasma produced by an RF discharge and injected into a large magnetic-confinement vessel. The ∼1019m-2 line-integrated electron density is clearly measured in agreement by the interferometers. The frequency spectrum of the measured data is analyzed on the 20 kHz range for all interferometers and up to 600 kHz for the Nd:YAG laser-based interferometer. Mechanical vibration measurements performed on the components of the two common-path interferometers result in a peak-to-peak displacement up to about one and twenty wavelengths for the CO2 and Nd:YAG laser-based interferometers, respectively. Such results set for the first time, to the best of our knowledge, a quantitative limit for the displacement that the two second-harmonic dispersion interferometers can sustain while still providing a high sensitivity for accurate plasma density measurements.

Widefield quantitative phase imaging by second-harmonic dispersion interferometry.

Widefield optical characterization of transparent samples is of great importance for gas flow and plasma diagnostics, for example, as well as label-free imaging of biological samples. An optically transparent medium, however, cannot be imaged by techniques based on intensity contrast imaging. Very well-known qualitative phase-contrast imaging methodologies are routinely used to overcome this limitation, and quantitative phase-imaging approaches have also been developed. Here we report the demonstration of, to the best of our knowledge, a novel widefield quantitative phase-imaging technique, based on fully common-path second-harmonic dispersion interferometry that is combined with pixel-by-pixel homodyne dual-channel polarization-dependent phase detection. The device is tested in a harsh environment reaching sub-10 mrad harmonic phase dispersion sensitivity and a spatial resolution of several tens of microns with an optical configuration that is very stable and easy to implement. The time resolution of the demonstrated device is 600 ps, set by the laser-pulse time duration.

Functional Multichannel Poly(Propylene Fumarate)-Collagen Scaffold with Collagen-Binding Neurotrophic Factor 3 Promotes Neural Regeneration After Transected Spinal Cord Injury.

Many factors contribute to the poor axonal regrowth and ineffective functional recovery after spinal cord injury (SCI). Biomaterials have been used for SCI repair by promoting bridge formation and reconnecting the neural tissue at the lesion site. The mechanical properties of biomaterials are critical for successful design to ensure the stable support as soon as possible when compressed by the surrounding spine and musculature. Poly(propylene fumarate) (PPF) scaffolds with high mechanical strength have been shown to provide firm spatial maintenance and to promote repair of tissue defects. A multichannel PPF scaffold is combined with collagen biomaterial to build a novel biocompatible delivery system coated with neurotrophin-3 containing an engineered collagen-binding domain (CBD-NT3). The parallel-aligned multichannel structure of PPF scaffolds guide the direction of neural tissue regeneration across the lesion site and promote reestablishment of bridge connectivity. The combinatorial treatment consisting of PPF and collagen loaded with CBD-NT3 improves the inhibitory microenvironment, facilitates axonal and neuronal regeneration, survival of various types of functional neurons and remyelination and synapse formation of regenerated axons following SCI. This novel treatment strategy for SCI repair effectively promotes neural tissue regeneration after transected spinal injury by providing a regrowth-supportive microenvironment and eventually induces functional improvement.

Photoinitiator-free 3D scaffolds fabricated by excimer laser photocuring.

Photoinitiator-free fabrication of poly(ethylene glycol) diacrylate (PEGDA) scaffolds is achieved using a novel three-dimensional (3D) printing method called mask projected excimer laser stereolithography (MPExSL). The spatial resolution of photoinitiator-free curing is suitable for 3D layer-by-layer fabrication with a single layer thickness well controllable at tens to hundreds of microns using 248 nm wavelength for the irradiation. The photoinitiator-free scaffolds are superior compared to their counterparts fabricated by using photoinitiator molecules, showing a higher level of biocompatibility. A release of toxic chemicals from the photoinitiator containing scaffolds is proven by cell proliferation tests. In contrast, no toxic release is found from the photoinitiator-free scaffolds, resulting in the very same level of cell proliferation as the control sample. The demonstration of photoinitiator-free PEGDA scaffolds enables the fabrication of 3D scaffolds with the highest level of biocompatibility for both in vitro and in vivo applications.

Gold nanoparticle-filled biodegradable photopolymer scaffolds induced muscle remodeling: in vitro and in vivo findings.

Therapeutic stem cell transplantation bears the promise of new directions in organ and tissue replacement, but a number of its difficulties and perils are also well known. Our goal was to develop a method of transplantation by which the transplanted cells remain confined to the transplantation site and induce favorable processes. With the help of mask-projection excimer laser stereolithography, 3D hybrid nanoscaffolds were fabricated from biodegradable, photocurable PPF:DEF resin with incorporated gold nanoparticles (Au NPs). The scaffolds were tested in vitro and in vivo in order to find out about their biocompatibility and fitness for our purposes. In vitro, macrophages and mouse autologous adipose stem cells (ASCs) were seeded over the hybrid scaffolds and non-hybrid (with Au NPs) scaffolds for 4days. The hybrid nanocomposite greater stem cell dispension and stem cell adhesion than PPF scaffolds without Au NPs, but such a difference was not seen in the case of macrophages. In vivo, stem cells, scaffoldings and scaffoldings covered in stem cells were transplanted under the back skin of mice. After 14days, blood samples were taken and the affected skin area was excised. Cytokine and chemokine profiling did not indicate elevated immunomediators in the sera of experimental animals. Interestingly, the autologous-stem-cell-seeded hybrid nanocomposite scaffold induced muscle tissue regeneration after experimental wound generation in vivo. We could not observe such stem cell-induced tissue regeneration when no scaffolding was used. We conclude that PPF:DEF resin nanoscaffolds with incorporated gold nanoparticles offer a safe and efficient alternative for the enhancement of local tissue remodeling. The results also support the idea that adipose derived stem cells are an optimal cell type for the purposes of regenerative musculoskeletal tissue engineering.

Controlled antiseptic/eosin release from chitosan-based hydrogel modified fibrous substrates.

Fibers of cellulose networks were stably coated with N-methacrylate glycol chitosan (MGC) shells using subsequent steps of dip coating and photo-curing. The photo-crosslinked MGC-coated cellulose networks preserved their fibrous structure. A model hydrophilic antiseptic solution containing eosin, chloroxylenol and propylene glycol was incorporated into the shells to study the drug release dynamics. Detailed drug release mechanism into phosphate buffered saline (PBS) solutions from coated and pristine fibers loaded with the antiseptic was investigated. The results show that the MGC-coated cellulose fibers enable the controlled gradual release of the drug for four days, as opposed to fast, instantaneous release from eosin coated pristine fibers. This release behavior was found to affect the antibacterial efficiency of the fibrous cellulose sheets significantly against Staphylococcus aureus and Candida albicans. In the case of the MGC-eosin functionalized system the antibacterial efficiency was as high as 85% and 90%, respectively, while for the eosin coated pristine cellulose system the efficiency was negative, indicating bacterial proliferation. Furthermore, the MGC-eosin system was shown to be efficacious in a model of wound healing in mice, reducing the levels of various pro-inflammatory cytokines that modulate early inflammatory phase responses. The results demonstrate good potential of these coated fibers for wound dressing and healing applications. Due to its easy application on common passive commercial fibrous dressings such as gauzes and cotton fibers, the method can render them active dressings in a cost effective way.

Four-order stiffness variation of laser-fabricated photopolymer biodegradable scaffolds by laser parameter modulation.

The effects of various fabrication parameters of our Mask Projection Excimer Laser StereoLithography (MPExSL) system were investigated. We demonstrate that laser parameters directly change the physical properties (stiffness, thermal degradation, and height/thickness) of the poly(propylene fumarate) (PFF) scaffold structures. The tested parameters were the number of pulses, fluence per pulse and laser repetition rate. We present a four-order tuning capability of MPExSL-fabricated structures' stiffness without altering the resin composition or using cumbersome post-treatment procedures. Thermogravimetric analysis and differential scanning calorimetry confirmed this tuning capability. Prototype-segmented scaffold designs are presented and analyzed to further expand the concept and exploit this in situ stiffness tuning capability of the scaffolds for tissue engineering and regenerative medicine applications.

Elastin-coated biodegradable photopolymer scaffolds for tissue engineering applications.

One of the main open issues in modern vascular surgery is the nonbiodegradability of implants used for stent interventions, which can lead to small caliber-related thrombosis and neointimal hyperplasia. Some new, resorbable polymeric materials have been proposed to substitute traditional stainless-steel stents, but so far they were affected by poor mechanical properties and low biocompatibility. In this respect, a new material, polypropylene fumarate (PPF), may be considered as a promising candidate to implement the development of next generation stents, due to its complete biodegradability, and excellent mechanical properties and the ease to be precisely patterned. Besides all these benefits, PPF has not been tested yet for vascular prosthesis, mainly because it proved to be almost inert, while the ability to elicit a specific biological function would be of paramount importance in such critical surgery applications. Here, we propose a biomimetic functionalization process, aimed at obtaining specific bioactivation and thus improved cell-polymer interaction. Porous PPF-based scaffolds produced by deep-UV photocuring were coated by elastin and the functionalized scaffolds were extensively characterized, revealing a stable bound between the protein and the polymer surface. Both 3T3 and HUVEC cell lines were used for in vitro tests displaying an enhancement of cells adhesion and proliferation on the functionalized scaffolds.

Study on the productivity of silicon nanoparticles by picosecond laser ablation in water: towards gram per hour yield.

An investigation on the productivity of silicon nanoparticles by picosecond laser ablation in water is presented. A systematic experimental study is performed as function of the laser wavelength, fluence and ablation time. In case of ablation at 1064 nm silicon nanoparticles with a mean diameter of 40 nm are produced. Instead, ablation at 355 nm results in nanoparticles with a mean diameter of 9 nm for short ablation time while the mean diameter decreases to 3 nm at longer ablation time. An original model based on the in-situ ablation/photo-fragmentation physical process is developed, and it very well explains the experimental productivity findings. The reported phenomenological model has a general validity, and it can be applied to analyze pulsed laser ablation in liquid in order to optimize the process parameters for higher productivity. Finally, an outlook is given towards gram per hour yield of ultra-small silicon nanoparticles.

Simple and effective graphene laser processing for neuron patterning application.

A straightforward fabrication technique to obtain patterned substrates promoting ordered neuron growth is presented. Chemical vapor deposition (CVD) single layer graphene (SLG) was machined by means of single pulse UV laser ablation technique at the lowest effective laser fluence in order to minimize laser damage effects. Patterned substrates were then coated with poly-D-lysine by means of a simple immersion in solution. Primary embryonic hippocampal neurons were cultured on our substrate, demonstrating an ordered interconnected neuron pattern mimicking the pattern design. Surprisingly, the functionalization is more effective on the SLG, resulting in notably higher alignment for neuron adhesion and growth. Therefore the proposed technique should be considered a valuable candidate to realize a new generation of highly specialized biosensors.

Fast, active droplet interaction: coalescence and reactive mixing controlled by electrowetting on a superhydrophobic surface.

A novel electrowetting-on-dielectrics (EWOD) device in open planar geometry allows probing of droplet mixing on a superhydrophobic substrate under quasi contact-free conditions. We demonstrate a droplet-based microreactor with integrated convective-flow mixing for the reactive-mixing of CaCl(2)/Na(2)CO(3) solutions. The device provides unique conditions for scattering, spectroscopy and imaging probes requiring an unobstructed droplet-access.

Influence of organic solvent on optical and structural properties of ultra-small silicon dots synthesized by UV laser ablation in liquid.

Ultra small silicon nanoparticles (Si-NPs) with narrow size distribution are prepared in a one step process by UV picosecond laser ablation of silicon bulk in liquid. Characterization by electron microscopy and absorption spectroscopy proves Si-NPs generation with an average size of 2 nm resulting from an in situ photofragmentation effect. In this context, the current work aims to explore the liquid medium (water and toluene) effect on the Si-NPs structure and on the optical properties of the colloidal solution. Si-NPs with high pressure structure (s.g. Fm3m) and diamond-like structure (s.g. Fd3m), in water, and SiC moissanite 3C phase (s.g. F4[combining macron]3m) in toluene are revealed by the means of High-Resolution TEM and HAADF-STEM measurements. Optical investigations show that water-synthesized Si-NPs have blue-green photoluminescence emission characterized by signal modulation at a frequency of 673 cm(-1) related to electron-phonon coupling. The synthesis in toluene leads to generation of Si-NPs embedded in the graphitic carbon-polymer composite which has intrinsic optical properties at the origin of the optical absorption and luminescence of the obtained colloidal solution.

Photopolymerization inhibition dynamics for sub-diffraction direct laser writing lithography.

Selective inhibition of the polymerization leads to sub-diffraction feature sizes in direct writing lithography-a principle based on the idea of stimulated emission depletion (STED) microscopy. However, the detailed understanding of the inhibition process is a key point to further enhance the resolution of the system. The authors present experiments focused on the time dynamics of the inhibition process, clarifying possible photophysical pathways.

Bioconjugated silicon quantum dots from one-step green synthesis.

Biofunctionalized silicon quantum dots were prepared through a one step strategy avoiding the use of chemical precursors. UV-Vis spectroscopy, Raman spectroscopy and HAADF-STEM prove oligonucleotide conjugation to the surface of silicon nanoparticle with an average size of 4 nm. The nanoparticle size results from the size-quenching effect during in situ conjugation. Photoemissive properties, conjugation efficiency and stability of these pure colloids were studied and demonstrate the bio-application potential, e.g. for nucleic acid vector delivery with semiconducting, biocompatible nanoparticles.

Very large spot size effect in nanosecond laser drilling efficiency of silicon.

The effect of the spot diameter in nanosecond excimer laser percussion drilling of through via in silicon wafer is presented. Experimental results show a ten fold increase of the ablation efficiency when decreasing the spot diameter from 220 µm to 9 µm at constant fluence in the range 7.5 J/cm(2) to 13.2 J/cm(2). Such effect is absent when using 60 ps deep-UV laser pulses. A model is developed that explain the findings in terms of plume shielding effect on the laser pulse. The model is successfully applied also on previously published data on deep-UV laser drilling of Polyamide and Alumina.

Harmonic interferometry in the visible and UV, based on second- and third-harmonic generation of a 25 ps mode-locked Nd:YAG laser.

A second-harmonic interferometer using 25 ps pluses is presented, achieving a sensitivity of 9x10(-10) m in measuring line-integrated dispersion between 1064 and 532 nm. Using the same laser source, a third-harmonic interferometer is demonstrated for the first time to our knowledge, achieving a sensitivity of 7x10(-9) m in measuring line-integrated dispersion between 1064 and 355 nm. The prospect for the development and use of high-harmonic interferometry is discussed.

Versatile second-harmonic interferometer with high temporal resolution and high sensitivity based on a continuous-wave Nd:YAG laser.

A second-harmonic interferometer based on a CW Nd:YAG laser is presented. The versatile device measures the line-integrated dispersion at the fundamental and second-harmonic wavelengths. A temporal resolution of 1.25 micros with sensitivity of 1.3 mrad and a temporal resolution of 10 micros with sensitivity of 0.3 mrad are demonstrated for a laser power of 0.6 W. For a laser power of only 150 mW a temporal resolution of 10 micros with sensitivity of 1 mrad is reported.