Towards functional miniaturized lasers

Rosacea is a common skin disease clinically characterized by skin flushing, persistent erythema, papules/pustules and telangiectasia. Laser therapy is an ideal option for the treatment of rosacea-associated telangiectasia and rhinophyma. The most commonly used lasers include 585-/595-nm pulsed dye lasers, long-pulsed 1 064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, carbon dioxide (CO2) laser, erbium:yttrium-aluminum-garnet (Er:YAG) laser, fractional laser, and so on. Intense pulsed light and pulsed dye laser have shown favorable therapeutic effects on rosacea-associated erythema and telangiectasia with high safety and short downtime. Long-pulsed Nd:YAG laser can only be used to target wide blood vessels and to treat resistant telangiectasia. CO2 laser, Er:YAG laser and fractional laser can be used to improve rhinophyma. In clinic, combined treatment using multiple lasers may result in better therapeutic outcomes. Key words: Rhinophyma; Lasers; Lasers, dye; Therapeutic uses; Intense pulsed light

Pulsed dye lasers have revolutionized the treatment of port wine stains (PWS). A dramatic improvement over previous therapies, pulsed dye laser

Objective To evaluate the clinical efficacy and safety of 595-nm pulsed dye laser with topical timolol maleate 0.5% solution for the treatment of superficial infantile hemangioma (IH) . Methods Complete clinical data were collected from 156 infants with superficial IH, who received treatment with 595-nm pulsed dye laser combined with topical timolol maleate 0.5% solution in the Department of Dermatology of the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University from July 2015 to July 2016, and analyzed retrospectively. Of the 156 patients, 44 were males, and 112 were females, with an average age of 3.8 ± 0.7 months (range, 24 days - 1 year) . These patients were treated with 595-nm pulsed dye laser every 5 weeks and topical application of timolol maleate solution twice a day. Each treatment with timolol maleate solution lasted 30 minutes. When the hemangioma regressed generally, the treatment with laser and timolol maleate solution was stopped. At weeks 5, 10, 15 and 30, the visual analogue scale (VAS) was used to evaluate the efficacy, and adverse reactions were recorded. These patients were followed up till 6 months after the end of treatment. The relationships of area and thickness of hemangioma with treatment duration, treatment sessions and VAS scores were analyzed. Results After 5 - 30 weeks of treatment, hemangiomas regressed to different extents, and the cure rate was 93.59% (146/156) . At weeks 5, 10, 15 and 30, the VAS scores were 3.12 ± 0.23, 4.45 ± 0.52, 5.45 ± 0.71 and 7.59 ± 1.64 respectively. Repeated-measures analysis of variance showed that the VAS scores all significantly increased over time (F = 189.35, P 3 mm) , and significantly differed among the above 3 groups at different time points (F = 215.56, P 3 mm (11.03 ± 0.72 months, P 9 cm2) , and significantly increased over time in these groups; Kruskal-Wallis H test showed that there was a significant difference in the treatment sessions among the above 3 groups (H = 10.45, P < 0.01) , and the group with the initial area of hemangiomas < 3 cm2 showed the least treatment session. The adverse reactions were mild, and no adverse cardiovascular or respiratory events were observed. Conclusion The 595-nm pulsed dye laser combined with topical timolol maleate 0.5% solution is effective and safe for the treatment of superficial IH. Key words: Hemangioma; Infant; Lasers, dye; Timolol; Treatment outcome; 595-nm Pulsed dye laser

The Time Dependent Schrödinger Equation In A Strong Laser Field

A experimental study on short pulse generation from praseodymium-doped fluoride mode-locked fibre lasers and gain-switched DFB semiconductor laser is presented[l]. The fiber lasers were modelocked either by using a phase modulator (PM) or cross phase modulation (XPM). In the first case, pulses of 33 ps and 75 mW (peak power) at 419 MHz were obtained. In the second case, we used a 1.55 µn gain-switched diode laser to modulate the phase of the 1.3 um laser field via intracavity XPM. This produced 50 ps, 13 mW pulses at 2.8 GHz. In this second laser we also observed stable dark pulses with 140 to 220 ps duration, making this laser attractive as a dark soliton generator. In the case of the gain-switched (GS) diode laser, we obtained (after spectral filtering) 5 ps, 20 mW at 1 GHz. Using this GS laser we propagated solitons in 50 km of standard fibre, thus demonstrating its potentials as a simple and inexpensive soliton quality laser source.

Development of laser fabrication methods for lab-on-a-chip microfluidic multisensing devices in the past decades

Objective To observe the efficacy of Er ∶ YAG laser and pulsed dye laser (PDL) in treating facial acne scars.Methods A total of 78 cases with facial acne scars were divided into two groups.The test group included 40 patients that were treated by Er ∶ YAG laser (total three treatments,once three months)and irradiated by PDL (total four times,once per month),while the control group included 38 patients treated by Er ∶ YAG laser only.After three months of the last treatment,the effective rate and side effects were recorded and compared.Results The efficacy of the test group reached 92.5％ (37/40) and 77.5％ (31/40) for acne scars and post-acne erythema,respectively.However,the effective rate of the control group was 73.7％ (28/38) and 47.4％ (18/38).There were statistically significant differences between two groups (P＜0.05).Regarding reported adverse effects,there were four cases in the test group and two cases in the control group that appeared mild pigmentation.After symptomatic treatment,the skin color recovered.There was no other side effect in both two groups.Conclusions The effectiveness of Er ∶ YAG laser and PDL is better than Er ∶ YAG laser only in treating facial acne scars,and thus it is worthwhile for popularization and application in acne scars. Key words: Laser; Acne; Scar

Laser treatment has become a popular method for resolving peri-implantitis, but the full range of its effects on implant surfaces is unknown. The purpose of the present investigation was to analyze the influence of different clinically applicable erbium:yttrium-aluminum-garnet (Er:YAG), carbon dioxide (CO2), and diode laser parameters on titanium surfaces that were either polished or sandblasted, large-grit, acid-etched (SLA). Six polished and six SLA titanium disks were irradiated at nine different power settings (n = 54 polished, 54 SLA) with Er:YAG, CO2, or diode lasers. The CO2 and diode lasers were used in continuous wave mode, and the Er:YAG laser was used in a pulsed manner. The surface of each disk was analyzed by scanning electron microscopy and confocal white light microscopy. Each disk was irradiated on six circular areas of 5 mm in diameter with the same specific laser setting for 10 seconds. Within the chosen parameters, the CO2 and diode laser did not cause any visible surface alterations on either the polished or SLA disks. In contrast, both polished and SLA disks showed surface alterations when irradiated with the pulsed Er:YAG laser. The SLA surfaces showed alteration after 10 seconds of irradiation with Er:YAG laser at 300 mJ/10 Hz. The surfaces of the polished disks did not show alteration with the Er:YAG laser until they were irradiated at the higher energy of 500 mJ/10 Hz for 10 seconds. The results of confocal white light microscopy were in agreement with scanning electron micrographs. In contrast to continuous-wave diode and CO2 laser irradiation, pulsed Er:YAG laser irradiation caused distinct alterations with power settings beyond 300 mJ/10 Hz on the SLA surface and 500 mJ/10 Hz on the polished surface. Thus, it is only safe to use the Er:YAG laser for implant surface irradiation with settings no higher than 300 or 500 mJ/10 Hz.

Optical trapping allows manipulating very small objects – varying from Angstoms to micron size particles – without physical contact by taking advantage of laser light. This technique, relying on light momentum transfer, allows manipulating biological matter (such as cells, organelles, vesicles or chemically functionalized artificial particles, etc.) and offers promising potentialities for research in biotechnology and biochemistry. Individually confining a large number of microscopic objects opens new ways for the downscaling of analysis tools for drug screening, particles sorting and the assessment of statistical data. In particular, the combination of optical trapping with microfluidics greatly enlarges the possibilities offered by both techniques. This PhD work takes place in a research aiming at developing novel bio-analytical instrumentation relying on large arrays of optical traps compatible with microfluidic systems. The dissertation focuses on the use of micro-optics for generating extended matrices of three-dimensional optical traps capable of capturing a large number of particles within microfluidic environments. The stability of optical traps is first studied with special emphasis on the conditions present in microfluidic flows, both from a theoretical and an experimental point of view, and trapping forces achievable on biological cells are investigated. A multiple optical trapping system relying on microlens arrays, adapted to work on commercial microscopes, is shown to be capable of generating arrays of more than 500 three-dimensional traps. Simultaneously trapping in multiple planes is also evidenced using matrices of microlenses, thanks to a self-imaging effect of the array of traps. Furthermore, possibilities offered by multiple optical trapping within microfluidic environments are explored. Polystyrene spheres as well as biological particles, such as native vesicles, can be trapped in arrays, manipulated inside microfluidic devices and analyzed in parallel through fluorescence microscopy while extremely small quantities of chemical reagents are flown past the array. Finally, for the sake of system miniaturization and further extension of the number of traps, multiple three-dimensional optical trapping based on arrays of miniaturized high numerical aperture parabolic mirrors is proposed, allowing the optics necessary for optical trapping, fluorescence excitation and collection to be integrated at the level of a microfluidic chip. Such miniaturized mirror matrices did not even exist before this thesis; their fabrication and characterization are detailed in this dissertation.

We demonstrate the characteristics of 2 mm to 1 cm long vertical-cavity surface-emitting laser (VCSEL) amplifiers that emitted continuous wave (CW). VCSELs have various applications in different fields, including datacom, optical interconnects, printers, and sensors. However, VCSEL technology has not been applied in laser material processing that needs a light source with high power density. This is because single-mode (SM) VCSELs have fundamental difficulty in producing beams having an output power of more than several milliwatts. On the contrary, the application range of VCSEL amplifiers is expected to be extended into fields that simultaneously require lasers with high power and high beam quality because they have the potential to attain both characteristics. In this paper, we demonstrate the CW operation of high-power SM 2 mm to 1 cm long VCSEL amplifiers that had an output power of several watts at 20 °C. By optimizing the top-mirror reflectivity and seed-laser wavelength, the output power was linearly proportional to the amplifier length when the growth of amplified spontaneous emission (ASE) was suppressed. The I–L characteristics for different amplifier lengths were measured. All devices emitted narrow beams with divergence angles of approximately 0.1°. The maximum SM output power of the devices with lengths of 2 mm, 6 mm, and 1 cm were 0.62, 2.13, and 3.25 W, respectively. This result shows the possibility to achieve high power and high beam quality for direct semiconductor laser processing.

Objective To preliminarily optimize the energy and density of laser radiation for the early treatment of hyperplastic scars in a rabbit ear model, and to explore possible therapeutic mechanisms. Methods Sixty-one hyperplastic scars were successfully established on the ears of 10 healthy New Zealand white rabbits with large ears, and randomly divided into 2 groups: 1-week group (30 scars) and 3-week group (31 scars) . These 2 groups were separately divided into 5 subgroups: group A treated with laser at a density of 100 PPA and an energy of 10 mJ, group B with laser at a density of 100 PPA and an energy of 50 mJ, group C with laser at a density of 169 PPA and an energy of 10 mJ, group D with laser at a density of 169 PPA and an energy of 50 mJ, and group E receiving no treatment. There were 6 scars in each group, except the group E in the 3-week group. Two healthy New Zealand white rabbits with large ears were not subjected to modeling, and served as group F (blank control group) . Immunohistochemical study was performed to determine the expression of matrix metalloproteinase (MMP) -13 in the skin tissues from the rabbit ears 1 week after the treatment. Three weeks after the treatment, the skin tissues from the rabbit ears were subjected to hematoxylin-eosin (HE) staining and Masson staining. Then, the structure of scars was observed, and scar elevation index was calculated. Statistical analysis was carried out by Kruskal-Wallis H test for the comparison of scar elevation index, and by one-way analysis of variance (ANOVA) for the comparison of the average absorbance value of MMP-13. Results As HE staining revealed, the groups A, B, C and D all showed thicker dermis and increased number of collagen fibers compared with the group F (normal skin tissues) , but showed thinner dermis, decreased number and more ordered arrangement of collagen fibers compared with the group E (untreated scar tissues) . No obvious difference was observed in the thickness of the dermis among the groups A, B, C and D. The scar elevation index significantly differed among the 6 groups (H= 22.757, P 0.05) . Conclusions Non-ablative fractional laser is effective for the treatment of early-stage hyperplastic scars. At the same laser density, 50-mJ laser was superior to 10-mJ laser for the treatment of hyperplastic scars, likely because high-energy laser can stimulate the recombi-nation of extracellular matrices and up-regulated MMP-13 expression to a greater extent. Key words: Cicatrix, hypertrophic; Lasers; Matrix metalloproteinase 13; Fractional laser; Energy

Selective Laser Sintering (SLS) and Selective Laser Melting (SLM) are parent Additive Manufacturing processes using a laser to solidify metallic, ceramic, polymer or composite powders. During the process, the object is built layer by layer. A laser source is responsible for the consolidation, by local heating. The light is deviated by a scanning head according to the instructions of an STL file. Then partial fusion of the particles takes place, followed by a solidification of the liquid created. Kinetics of these steps are very high and play an important role in the final microstructure (rearrangement of the particles, pore creation, residual stresses). In the case of polymers and composites the technique is now well understood and widely used, but for metals and ceramics it suffers from a lack of precision, surface roughness and poor mechanical properties. The goal of this Ph.D. work is to understand the effect of the thermal gradients on the consolidation process, using different laser parameters (power, pulse frequency, scan speed,…). In SLS, microscopic thermal gradients arise, due to the fact that the laser is pulsed and that only the exterior of the powder particles is molten. A thermal model to describe the interaction between a laser beam and a (spherical) grain is proposed. This model allows for the incorporation of the latent heat of fusion and for a realistic surrounding. The absorbed laser intensity is modeled by means of the Mie theory. Experiments where two particles of powder are isolated and illuminated by the laser are carried out in order to measure the interparticular necks and the volume of liquid formed for different repetition rates. The thermal model leads to good predictions of the particles final sintering state. Fluid flow models are investigated in order to determine the dynamic of the molten liquid. The main issue is to explain the capillary flow mechanisms leading from the molten material to the neck formation. Two models are derived to simulate the fluid flow between the particles. The first one simulates a capillary flow between two parallel plates. The second one deals with energetic considerations arising from Frenkel's principle. In both cases, the final output is the liquid life-time necessary to get the interparticular neck lengths experimentally observed. We point out that the two models predict the same liquid lifetime, although they are derived with different hypotheses. In SLM, continuous lasers are used and one has to deal with macroscopic thermal gradients, since the particles are completely molten. A very high laser power is used and the negative thermal effects (like thermal stresses or balling effects) are important. A solution to control them is to adjust the scanning strategy. Four scanning strategies are investigated for material with different thermal conductivities. The three-dimensional model used to describe the laser-matter interactions and the temperature evolution of the scanned powder bed allows for a finite latent heat (Stefan-problem) and for conductivity modifications due to the consolidation. We show that this finite element thermal model can be efficiently used to anticipate most of the problems (like cracks or balling) arising in practice. The benefit of avoiding thermal gradients is shown, in particular by EBSD analysis. Finally, applications of the SLS/SLM technique on different pieces built during this work are shown. A new way to build support structure is also proposed.

The aim of this PhD project is to investigate alternative sensing methodologies that can possibly improve the sensing performances of lab-on-chip (LOC) designed for biochemical applications. Suspended microchannel resonator (SMR) for bio-mechanical sensing applications have become very popular as detection of weigths of chemicals integrated in LOC. They exploit laser doppler vibrometry (LDV) for dynamic mode detection. In this thesis two different SMRs designs have been investigated, involving either technological challenges - the use of polymers as material and processing techniques based on laser micromachining - and different sensing phenomena - the use of the parametric resonance rather than the standard harmonic resonance response. The flexibility of two-photon direct laser writing is exploited to optimize a highly- versatile fabrication strategy based on a shell-writing procedure with the aim to reduce fabrication time of big inlet/outlet sections compatible with most microfluidic systems for LOCs. With respect to standard microfabrication techniques, requiring several technological steps to obtain suspended hollow structures, this method allows to fabricate complex SMR sensors in only one fabrication step, by virtue of its intrinsically three- dimensional nature. A SMR fixed-fixed beam has been fabricated and characterized by LDV. A different sensing mechanism based on the parametric resonance instead of the harmonic resonance has been investigated to develop a novel platform for the characterization of biomolecules in free-flow with unique specificity, sensitivity, and speed: to this purpose a PDMS based device was realized by laser machining, a rapid prototype fabrication technique; beside to it, a commercial fused silica capillary tubing was also employed in the realization of a prototype for this sensing mechanism, and both solutions were tested through LDV

Material and fabrication at low-cost used for lab-on-a-chip (LOC) system and the ease of operation without expensive and complicated instruments are crucial for wide application in our daily life. The current low-cost LOC material could be categorized as two types: paper-based LOC and polymer like polydimethylsiloxane (PDMS) based device. Paper-based devices enable the advantages of easy fabrication, disposable nature and least cost. Using an office laser printer to create a carbon powder pattern on the filter paper, we created a microwell pattern area of which the uncovered carbon powder enables a flow rate greater than that where covered with carbon powder along the filter; the flow can carry and localize single microalgae into the microwell separately. The separation process only takes 30 seconds and the separation performance of isolating single microalgae could be over 37% in average. The open-structure design of the paper device makes it operable with a common laboratory micropipette for sample retrieval and transfer. The paper-device can also function as an incubator for microalgae growth on simply rinsing the paper with a growth medium. In this research, we developed PDMS based filter LOC devices to separate microalgae and detect circulating tumor cells (CTCs). Clogging always becomes a main issue on filter based separation; cross-flow system was proven to reduce this drawback. We develop a centrifugally driven, multilayer, concentric filter device, a small bench-top centrifuge, which is commonly available in biochemical laboratories, was employed as part of our centrifugal microfluidic separation system. The cross-flow in our separation system was simply generated on altering the rate of rotation, as revolutions per minute (RPM), instantly through the relative motion of the device and the fluid. This strong cross-flow can wash away the particle and microalgae clogs at the filter pores, so increasing the filtration performance over 13.7 % without complicated control and expensive equipment. The use of the PDMS filter device enabled variously sized microparticles and environmentally collected microalgae samples to be readily separated in a few minutes. This device was also applied to detect CTCs. By using the anti–human EpCAM antibody coated polystyrene (PS) beads to capture CTCs which could enlarge the size of CTCs to create significant size different from normal cell like white blood cells (WBCs). With a concentric filter device and centrifugation, the unbound PS beads and WCBs would flow to the outer layer of the device; the targeted CTCs bound with PS beads would be retained in the inner filter layer. The inner filter layer is designed as a detection zone in which the bound cells are easily observed by microscope because of the small area of the inner channel and the enrichment effect. We successfully demonstrate that CTCs could be separated and detected in the concentration of one CTC per million of WBCs by this device and method.

Objective: To observe the clinical effects of sequential treatments of pulsed dye laser (PDL) and ablative fractional carbon dioxide laser on early stage hypertrophic burn scars. Methods: From January 2016 to December 2017, 221 patients with 228 hypertrophic scars in all parts of body within 6 months post healing, conforming to the study criteria and treated in our department, were included in this prospective study. They were first treated by PDL, repeated at an interval of one month until the vascularity score of scar fell below 2 points, and then treated by ablative fractional carbon dioxide laser, repeated at an interval of 3 months. Their start time and numbers of treatment and follow-up time were recorded. Before the first treatment (hereinafter referred to as before treatment) and at the last follow-up (hereinafter referred to as after treatment), the vascularity, thickness, and pliability of scars were scored by a self-made scar rating scale. The scores of patients with the observation time between 6 to18 months post healing were compared among scars of patients grouped by age, body site of scar, starting time of treatment and numbers of treatment. The laser speckle contrast imaging technique was used to measure the blood flow value of scars. The itching symptom of the scars was evaluated by the Verbal Rating Scale. The satisfaction to the final effects of the doctors and patients was investigated and scored separately by Likert scale after treatment. The therapeutic or adverse reactions were recorded during the treatment. Data were processed with paired t test, Mann-Whitney U test, Wilcoxon signed rank sum test, Kruskal-Wallis H test, and Spearman rank correlation analysis. Results: (1) The patients were treated on (64±36) d post healing, by PDL for (2.5±1.3) times and by ablative fractional carbon dioxide laser for (2.2±1.2) times. The follow-up time was (331±189) d. (2) The vascularity, thickness, pliability scores and total scores of scars were (1.4±0.9), (2.0±0.8), (1.7±0.8), and (5.0±2.1) points respectively after treatment, which were significantly lower than those before treatment [(4.1±0.7), (3.1±0.8), (3.0±0.9), and (10.2±2.0) points respectively, t=43.332, 24.968, 28.063, 46.394, P<0.01]. (3) Among the 123 scars from 120 patients with observation time between 6 to 18 months post healing, there were no statistically significant differences in the vascularity, thickness, pliability scores and total scores of scars among patients with different ages after treatment (χ(2)=4.339, 1.826, 1.375, 2.879, P>0.05). There was only significant difference in the pliability scores of scars among different body sites (χ(2)=13.530, P<0.05). There were statistically significant differences in the vascularity, thickness, pliability scores and total scores of scars with different starting time of treatment (χ(2)=30.725, 25.233, 25.119, 35.798, P<0.01). There were significantly positive correlation between starting time of treatment and the vascularity, thickness, pliability scores and total scores of scars (r=0.492, 0.442, 0.446, 0.532, P<0.01). There were statistically significant differences in the vascularity, pliability scores and total scores of scars with different numbers of treatment (Z=4.883, 4.910, 5.049, P<0.05). There were significantly negative correlation between number of treatment and the vascularity, thickness, pliability scores and total scores of scars (r=-0.176, -0.131, -0.191, -0.201, P<0.05). (4) The blood flow values were determined in 18 scars of 18 patients. The results showed that the blood flow values of scars after treatment were significantly decreased compared with those before treatment (t=7.230, P<0.01). (5) The pruritus scores of scars of patients after treatment were significantly decreased compared with those before treatment (Z=12.818, P<0.01). (6) There were significant differences between the satisfaction scores of doctors and the scores of patients after treatment (t=12.130, P<0.01). (7) After PDL treatment, there were some edema and purpura reactions for all the patients, and 11 (5.0%) patients had blisters. After ablative fractional carbon dioxide laser treatment, 4 (1.8%) patients had blisters, 5 (2.3%) patients suffered inflammatory reaction and erosion, and 9 (4.1%) patients suffered pigmentation. Conclusions: The scores of hypertrophic burn scars can be obviously improved by sequential treatments of PDL and ablative fractional carbon dioxide laser. The effects can be more obvious with the earlier starting time and more numbers of treatment. The laser treatments can also decrease the blood flow values and alleviate the pruritus of scars, with high satisfaction of both patients and doctors.