Tunable Pulses Research Articles

Characterization Challenges of Self-Assembled Polymer-SPIONs Nanoparticles: Benefits of Orthogonal Methods.

Size and zeta potential are critical physicochemical properties of nanoparticles (NPs), influencing their biological activity and safety profile. These are essential for further industrial upscale and clinical success. However, the characterization of polydisperse, non-spherical NPs is a challenge for traditional characterization techniques (ex., dynamic light scattering (DLS)). In this paper, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with polyvinyl alcohol (PVAL) exhibiting different terminal groups at their surface, either hydroxyl (OH), carboxyl (COOH) or amino (NH2) end groups. Size, zeta potential and concentration were characterized by orthogonal methods, namely, batch DLS, nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (TRPS), transmission electron microscopy (TEM), asymmetric flow field flow fractionation (AF4) coupled to multi-angle light scattering (MALS), UV-Visible and online DLS. Finally, coated SPIONs were incubated with albumin, and size changes were monitored by AF4-MALS-UV-DLS. NTA showed the biggest mean sizes, even though DLS PVAL-COOH SPION graphs presented aggregates in the micrometer range. TRPS detected more NPs in suspension than NTA. Finally, AF4-MALS-UV-DLS could successfully resolve the different sizes of the coated SPION suspensions. The results highlight the importance of combining techniques with different principles for NPs characterization. The advantages and limitations of each method are discussed here.

Proteomic profiling of exosomes derived from pancreatic beta-cells cultured under hyperglycemia

Abstract Introduction Cargo carried by extracellular vesicles (EVs) is considered a promising diagnostic marker, especially proteins. EVs can be divided according to their size and way of biogenesis into exosomes (diameter < 200 nm) and ectosomes (diameter > 200 nm). Exosomes are considered to be of endocytic origin, and ectosomes are produced by budding and shedding from the plasma membrane [1]. Methods The first step of this study was a characterization of the exosome sample. Using Tunable Resistive Pulse Sensing (qNano) size distribution and concentration were measured. The mean size of exosomes was 120±9.17 nm. In the present study, a nano liquid chromatography coupled with tandem mass spectrometry (nanoLCMS/MS) was used to compare protein profiles of exosomes secreted by pancreatic beta cells (1.1B4) grown under normal glucose (NG, 5 mM D-glucose) and high glucose (HG, 25 mM D-glucose) conditions. The EV samples were lysed, and proteins were denatured, digested, and analyzed using a Q-Exactive mass spectrometer coupled with the UltiMate 3000 RSLC nano system. The nanoLC-MS/MS data were searched against the SwissProt Homo sapiens database using MaxQuant software and protein quantitation was done by the MaxLFQ algorithm. Statistical analysis was carried out with Perseus software. Further bioinformatic analysis was performed using the FunRich 3.1.4 software with the UniProt protein database and String [2]. Results As a result of the nanoLC-MS/MS analysis more than 1,000 proteins were identified and quantified in each sample. The average number of identified proteins in exosomes was 1,397. Label-free quantitative analysis showed that exosome composition differed significantly between those isolated under NG and HG conditions. Many pathways were down-regulated in HG, particularly the ubiquitin-proteasome pathway. In addition, a significant up-regulation of the Ras-proteins pathway was observed in HG. Conclusion Our description of exosomes protein content and its related functions provides the first insight into the EV interactome and its role in glucose intolerance development and diabetic complications. The results also indicate the applicability of EV proteins for further investigation regarding their potential as circulating in vivo biomarkers.

Widely tunable XUV harmonics using double IR pulses.

Tunable attosecond pulses are necessary for various attosecond resolved spectroscopic applications, which can potentially be obtained through the tuning of high harmonic generation. Here we show theoretically, using the time-dependent Schrödinger equation and strong field approximation, a continuously tunable spectral shift of high-order harmonics by exploiting the interaction of two delayed identical infrared (IR) pulses within the single-atom response. The tuning spans more than twice the driving frequency (∼2ω) range, for several near-cutoff harmonics, with respect to only one control parameter: the change in delay between the two IR pulses. We show that two distinct mechanisms contribute to the spectral shift of the harmonic spectra. The dominant part of the spectral shift of the harmonics is due to the modulation of the central frequency of the composite IR-IR pulse with respect to delay. The second contribution comes from the non-adiabatic phase-shift of the recolliding electron wavepacket due to the change in amplitude of the subcycle electric field within the double pulse envelope. For optical few-cycle pulses this scheme can produce tunable attosecond pulse trains (APT), and in the single-cycle regime the same can be used for tuning isolated attosecond pulses (IAP). We quantify the dependence of tuning range and tuning rate on the laser pulse duration. We envision that the proposed scheme can be easily implemented with compact in-line setups for generating frequency tunable APT/IAP.

Low spatial frequency laser-induced periodic surface structures in fused silica inscribed by widely tunable femtosecond laser pulses

The formation and evolution of laser-induced periodic surface structures in fused silica under irradiation of widely tunable (in the 1–3 upmum range) linearly polarized femtosecond (200 fs) pulses was studied experimentally. The structures were inscribed in high fluence regime (exceeding the surface ablation threshold for a single pulse) and characterized by using scanning electron microscopy and two dimensional Fourier transform. The results revealed rapid (after irradiation with a few successive pulses) formation of periodic laser-induced periodic surface structures aligned parallel to laser polarization, whose period increases with increasing the inscription wavelength, obeying the lambda /n law. With further increase of number of pulses, the generated structures gradually reorganize into laser polarization-independent low spatial frequency annular structures associated with formation of the damage crater, which fully established after irradiation with a few tens of successive laser pulses. This particular evolution scenario was observed over the entire wavelength tuning range of incident pulses.

Critical Role of Hodgkin Lymphoma Cells-Derived Large and Small Extracellular Vesicles in the Regulation of the Immune-Inflammatory Microenvironment

Introduction: Classical Hodgkin Lymphoma (cHL) is characterized by a low number of CD30+ malignant cells and an extensive immune-inflammatory microenvironment. However, this unique histopathological picture and its pathogenesis are still partially understood. Extracellular vesicles (EVs) are submicron particles delimited by a lipid bilayer that promote (tumor) intercellular communication and carry bioactive molecules that can influence the immune system. Based on size and biogenesis mechanism, Small (S-) and Large (L-) EVs (30-200 nm and 0.2-10 µm, respectively) have been identified. Extracellular Adenosine Triphosphate (eATP), a key component of the tumor microenvironment, plays a role in biogenesis and dynamics of EVs. Here we aim to elucidate the role of cHL cell-derived EVs in the education of the immune microenvironment. Methods: cHL L-428 cell line was cultured in exosome-free medium for 48 hours at 37°C in the presence or absence of eATP (1 mM). L-428 cell blebbing has been detected by fluorescence microscopy (DAPI and FITC-Cholera Toxin B subunit (CTxB) labeling). L-EVs and S-EVs were isolated from the cell culture supernatant by differential ultracentrifugation (2.800g for 2.8K and 20.000g for 20K L-EVs, and 100.000g for 100K S-EVs) and purified by iodixanol density gradient. L- and S-EVs were then characterized by Tunable Resistive Pulse Sensing (TRPS), single EV-flow cytometry, and MACSPlex (bead-based antigen binding array). Functionally, normal peripheral blood mononuclear cells were in vitro cultured with titrated amount of isolated L- and S-EVs (from 1:5 to 1:20) for 24 hours. The intracytoplasmic interleukin-1β and interferon-γ production by CD14+ monocytes and CD3+/CD4+/CD8+ T cells was assessed by flow cytometry. Results: Our results showed that human cell line L-428 is able to produce L-EVs through membrane blebbing (Figure 1A). According to EV size distributions, both 2.8K and 20K L-EVs displayed a size range from 1 to 4 µm whereas S-EVs were enriched in particles of 150-200 nm diameter. Interestingly, the amounts of S-EVs shed by L-428 cells were significantly higher compared to the number of L-EVs. Considering the EV surface protein phenotype, S-EVs express all the EV-related tetraspanin proteins (CD9, CD63, and CD81). By contrast, L-EV express CD63 and CD81 only. Additionally, in L-EVs we observed an enrichment of cancer-related markers including SSEA-4, CD44, CD24, CD29 and CD133-1 in comparison with the S-EV counterpart. Of note, the expression of selected immune-related molecules such as CD86 and CD40 was higher in the 2.8K and 20K L-EVs as compared with that of the 100K S-EVs. The HLA-II molecules were expressed by all fractions, with the highest expression in 2.8K L-EVs. Along with PD-L1, the CD30 HL-associated marker was expressed by all EV fractions at the same extent. When we tested the effects of eATP on EVs produced by L-428 cells, we found a highly decline in the expression of EV-surface proteins from all EV sub-fractions, being most noticeable in L-EVs. Importantly, only PD-L1 expression was increased in the 20K L-EVs after eATP treatment. Functionally, at variance with S-EVs (Figure 1B), L-EVs highly stimulate the intracytoplasmic production of interleukin-1β by monocytes. Conversely, L-EVs derived from e-ATP treated L-428 cells fail to stimulate the intracytoplasmic production of interleukin-1β by CD14+ monocytes, which instead was promoted by the e-ATP treated S-EV counterparts. Of note, neither L-EVs nor S-EVs stimulated interferon-γ production by CD14+ monocytes. No intracytoplasmic production of the selected inflammatory cytokines has been observed when T-cells treated with EVs were analyzed. Conclusions: These results demonstrate that L-EVs from HL cells display a cancer- and immune-related phenotype and play a role in the modulation of the immune microenvironment by promoting the production of inflammatory cytokines by monocytes. This might be partially due to the high expression of CD44 on the surface of L-EVs, since it has been previously demonstrated that cancer-derived soluble CD44 may trigger monocyte/macrophage interleukin-1β production. Interestingly, eATP plays a role in shaping the immune modulatory ability of L- and S-EVs. These findings shed light on the role of HL-derived EVs in the establishment of the immune-inflammatory microenvironment and provide novel insight into clinically relevant EV driven mechanisms in HL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Plasma Extracellular Vesicle-Associated microRNAs for Early Response Prediction in Patients with High-Grade B-Cell Lymphoma

Background: Early and accurate outcome prediction is essential in the clinical management of high-grade B-cell lymphoma (HGBL). An early switch to salvage treatments for those patients who are likely to develop refractory/relapsed disease may improve overall survival. Unfortunately, the positive predictive value of an interim PET-CT is not high enough to guide treatment decisions. Extracellular vesicle-associated microRNAs (EV-miRNAs) are considered promising liquid biopsy-based biomarkers for lymphomas. We performed small RNA sequencing of plasma samples collected during treatment and applied machine learning to build EV-miRNA signatures for early response prediction in patients with HGBL with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH). Methods: We analyzed PAXgene ccfDNA plasma samples, from 38 of the 97 patients included in the HOVON-152 trial (NCT03620578), a prospective, multicenter, non-randomized phase II trial. In this trial, patients with HGBL-DH/TH receive one cycle of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by five cycles of dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). Patients who achieve complete metabolic response (CMR) at the end-of-induction (EOI) receive one year of nivolumab consolidation. Response was assessed by an EOI PET-CT and classified as CMR (Deauville score 1-3) (responders) or no-CMR (non-responders). 20 responders and 18 non-responders (enrichment for non-responders), were selected for this analysis. We isolated plasma EVs with size exclusion chromatography as confirmed with transmission electron microscopy (TEM), tunable resistive pulse sensing (TRPS), and western blot (WB). Library preparation was done according to an unbiased, unique molecular identifier (UMI)-enhanced small RNA sequencing protocol (IsoSeek) (van Eijndhoven et al., 2021. bioRxiv) and sequenced on the NovaSeq 6000 (Illumina). We applied machine learning including the least absolute shrinkage and selection operator (LASSO), Elastic Net, and Ridge Regression to build models with EV-miRNAs for early EOI response prediction. We selected the most optimal model based on the lowest misclassification error. Then the model was internally validated and tested with bootstrapping (1000x) and over optimism estimate as well as the adjusted AUC was calculated. Results: TEM after one cycle of R-CHOP revealed abundant particles < 200 nm and TRPS measured significantly higher particle concentration in EV-enriched fractions. Plasma EVs were positive for CD63, CD81, flotillin-1, syntenin, HSP70, and negative for calnexin as determined by WB in accordance with the Minimal Information for Studies of EVs (MISEV) criteria 2018 for EV characterization. The most optimal model was an Elastic Net regression (a = 0.4) model consisting of 199 miRNAs with an area under the curve (AUC) of 0.95 (Confidence Interval (CI): 0.90 - 0.99) (Figure 1) [Sensitivity: 88%, Specificity: 90%; Positive Predictive Value (PPV): 90%, Negative Predictive Value (NPV): 87%]. We tested our model with bootstrapping (1,000x). After taking into account of over optimism estimate of 0.14, the adjusted AUC was 0.81 (CI: 0.64-0.96), which is higher than the performance of interim PET/CT [Sensitivity: 33-87%, Specificity: 49-94%; PPV: 20-74%, NPV: 64-95%] (Burggraaff 2019, PMID: 30141066). Conclusion: Machine learning models using plasma EV-miRNAs prepared with the IsoSeek small RNA sequencing protocol yielded a robust signature that can predict EOI response already after one cycle of R-CHOP with a NPV of 87% and a PPV of 90%. The next step is to validate this model in a large cohort of HGBL-DH/TH cases and explore its potential in all subtypes of diffuse large B-cell lymphoma. If validated in independent cohorts, this novel approach could potentially, in combination with other modalities such as cell-free DNA and interim PET-CT, guide early risk-adapted treatment strategies in aggressive high-grade B-cell lymphomas. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Gigahertz bursts with tunable pulse interval and pulse number based on sinusoidal saturable absorption

Optical pulse bursts are multiple pulses that arise from the balance between attractive and repulsive effects and are used for pulsed laser deposition, flow measurement, various micromachining, spectroscopic, and biomedicine. Different application fields have special requirements for the pulse burst, such as burst width, frequency, number of pulses per burst, and the pulse interval etc. Here, we propose and demonstrate the generation of GHz pulse bursts with both tunable pulse number and pulse interval in a nonlinear polarization rotation (NPR) mode-locked fiber laser for the first time. Taking advantage of the sinusoidal saturated absorption of the NPR, with the increase of pump power, only the number of pulses per burst increases one by one in a relatively low pump power range, while only the pulse interval increases gradually in a high pump power range. In addition, one pulse burst with a 22.8-GHz repetition rate is achieved, which is the highest intra-burst repetition rate directly obtained in all-fiber lasers to the best of our knowledge. The numerical results agree qualitatively well with the experiments. Our work gives an insight into the formation of pulse bursts in mode-locked fiber lasers.

Investigating the role of extracellular vesicles in peyronie's disease

A key effector cell in the pathophysiology of Peyronie's disease (PD) is the myofibroblast. Whilst the role of extracellular vesicles (EVs) and the secretome has been elucidated for other diseases, little is known about this in PD. This study aims to elucidate the role of EVs in myofibroblast transformation. Human primary fibroblasts were isolated from tunica albuginea (TA) of PD patients. Conditioned media was generated from cells treated with and without Transforming Growth Factor-ß1 (TGF-ß1). 10% Knockout Serum Replacement (KOSR) was used to avoid EV contamination from foetal calf serum (FCS). Conditioned media was concentrated after 72h and subjected to size-exclusion chromatography to isolate EVs and protein fractions. EVs were analysed via Tunable Resistive Pulse Sensing (TRPS) using the qNano Gold (Izon) to determine size, concentration, shape, and charge of the particles. Cells were treated with EVs in presence/absence of TGF-ß1 and myofibroblast transformation was quantified using In-Cell ELISA (ICE). TRPS analysis revealed that the TGF-ß1-treated cells produced more EVs (39.4 × 108 particles/mL) than untreated cells (7.24 × 108 particles/mL). Untreated cells showed a larger percentage population of particles >80nm compared to TGF-ß1-treated cells, which showed the highest concentration of particles at 70nm. Mean diameter was 92nm and 75nm for untreated and TGF-ß1-treated cells, respectively. There was no difference in charge of particles (zeta potential) between the groups. Slight differences in shape of particles could be detected, with the TGF-ß1-treated group showing more small but potentially elongated particles. No particles above 240nm were detected in either group. Preliminary ICE experiments revealed that isolated fractions impacted myofibroblast transformation. This is the first study to characterize the EV populations of fibroblasts and myofibroblasts in PD. Further work needs to be done to investigate the secretome and to identify the contents of these vesicles and their effect on fibroblast/myofibroblast biology in PD. Funded by ESSM (RG19-04)

Tunable S-band mode-locked thulium-doped fluoride fiber laser using nickel phosphorus trisulfide (NiPS3) saturable absorber

Nickel Phosphate Trisulfide (NiPS3) prepared using the LPE technique was used as a saturable absorber (SA) in a thulium-doped fluoride fiber laser for the generation of mode-locked pulses. The polishing method was used to prepare the arc-shaped fiber before the NiPS3 solution was drop-casted onto it to form the SA device. The SA exhibited nonlinear optical properties, with modulation depth and saturation intensity of 29.44 % and 0.547 kW/cm2 respectively. Insertion of the SA in the TDFF cavity produced mode-locked pulses with central wavelength and 3-dB bandwidth of 1505 nm and 0.68 nm respectively, with a pulse width of 3.56 ps. The mode-locking operation also has a repetition rate of 582 kHz and an SNR of about 58 dB at a pump power of 280 mW. The maximum average output power measured was 2.4 mW at maximum pump power, with maximum pulse energy and peak power at 4.12 nJ and 1.16 kW respectively. Due to the optical interaction between NiPS3 and the evanescent wave in this arrangement, a larger damage threshold can be achieved, enabling the laser performance to operate at higher output power. Tunability was achieved by simultaneous adjustment of extinction and wavelength knob on the tunable Mach-Zehnder Filter (TMZF). The shape of spectra remained unchanged and continued exhibiting Kelly’s sidebands throughout the tunability range of about 2 nm. These results provide the first demonstration of tunable mode-locked pulses in the S-band region.

Tunable Microwave Pulse Generation Based on an Actively Mode-Locked Optoelectronic Oscillator

A tunable microwave-pulse-generation scheme is proposed and demonstrated by employing an actively mode-locked optoelectronic oscillator (OEO) based on a microwave photonic filter (MPF). The MPF mainly consists of a phase-shifted fiber Bragg grating (PS-FBG) and a phase modulator. The microwave pulse trains with variable repetition rates are achieved by injecting an external signal, of which the frequencies are equal to an integer multiple of the free spectrum range (FSR) of the OEO. The multi-mode oscillation mechanism is discussed in detail theoretically and experimentally. A microwave pulse train with a central frequency of 9.25 GHz and repetition rate of 1.68 MHz is demonstrated by setting the injecting signal frequency to be the same with the FSR of the OEO. A tunable center frequency of the microwave pulses from 5.47 GHz to 18.91 GHz can be easily generated by tuning the laser frequency benefit from adopting the MPF. Furthermore, the microwave pulses with different pulse periods of 297.62 ns, 198.69 ns, and 148.81 ns are also realized by harmonic mode-locking. The proposed tunable microwave-pulse-generation method has potential applications in the pulse Doppler radar and communications.

Rapid joule heating improves vitrification based cryopreservation

Cryopreservation by vitrification has far-reaching implications. However, rewarming techniques that are rapid and scalable (both in throughput and biosystem size) for low concentrations of cryoprotective agent (CPA) for reduced toxicity are lacking, limiting the potential for translation. Here, we introduce a joule heating–based platform technology, whereby biosystems are rapidly rewarmed by contact with an electrical conductor that is fed a voltage pulse. We demonstrate successful cryopreservation of three model biosystems with thicknesses across three orders of magnitude, including adherent cells (~4 µm), Drosophila melanogaster embryos (~50 µm) and rat kidney slices (~1.2 mm) using low CPA concentrations (2–4 M). Using tunable voltage pulse widths from 10 µs to 100 ms, numerical simulation predicts that warming rates from 5 × 104 to 6 × 108 °C/min can be achieved. Altogether, our results present a general solution to the cryopreservation of a broad spectrum of cellular, organismal and tissue-based biosystems.

Observing Second Harmonic Generation and Enhancing Second-Order Nonlinearity from Germanium-on-Insulator

Second-order nonlinear χ2 processes hold the key to realizing various promising classical and quantum applications. Only conventional non-centrosymmetric materials like aluminium nitride (AlN) and lithium niobate (LN) exhibit a strong second-order nonlinearity. While germanium (Ge) has the advantage of mature foundry processing due to its complementary metal-oxide-semiconductor (CMOS) compatibility compared to conventional χ2 materials, it has a weak second-order nonlinearity owning to its inversion symmetry. It is predicted that exploiting micro-scale strain gradients induced by silicon nitride (SiN) stressors can break the inversion symmetry of Ge and enable more efficient second harmonic generation (SHG) in mid-infrared (MIR). We herein demonstrate SHG in visible and telecom S-band ranges by pumping our germanium-on-insulator (GOI) sample with a tunable femtosecond pulse laser. The signature quadratic power dependence curve of SHG has also been experimentally observed. In this report, we also propose a novel approach to breaking the inversion symmetry of Ge, which can amplify its weak second-order nonlinearity. We designed a Ge micro-bridge with a periodically changing nano-scale strain gradient that is orders of magnitude higher than the previously proposed structures utilizing SiN stressors. This results in a 3-orders of magnitude enhancement in χ2 according to both a classic anharmonic model and density potential theory. Our work paves the way toward a CMOS compatible and high χ2 nonlinear material for integrated photonic applications.

Electrodeposition of Functionally Graded Brazing Interlayers for Enhanced Joint Strength between Fusion Plasma-Facing Materials and Heat Sinks

In response to the significant plasma science and engineering breakthroughs witnessed over the past decade, the fusion research community has developed an ambitious roadmap to achieve large-scale, energy-positive fusion reactors that will enable economically competitive fusion electricity. Critical to the success of commercial fusion energy is the development of materials able to serve as plasma facing components (PFCs) that can withstand the unprecedented high heat, particle, and neutron fluxes within the fusion reactor. Tungsten is a leading candidate for the plasma-facing portion of these PFCs because of its high melting point, high sputtering resistance, and low tritium retention. Copper or copper-based alloys (e.g., copper-chromium-zirconium alloy C18150) and reduced activation ferritic/martensitic (RAFM) steels have been proposed for the heat sink materials behind the tungsten armor due to their high thermal conductivity. Brazing is considered a promising method for joining the tungsten armor and heat sink layer. However, the extreme mismatch in the coefficient of thermal expansion (CTE) between tungsten and these potential heat sink materials makes directly joining these two layers challenging. This thermal stress can be reduced by incorporating a joining layer of functionally graded materials between the tungsten and heat sink that imparts gradual changes in CTE. Copper/tungsten or copper/tungsten carbide composites are leading candidates for these functionally graded materials. For these composites, gradual changes in the CTE are achieved by varying the volume fraction of tungsten/tungsten carbide in the composite, from tungsten-rich at the tungsten armor to tungsten-poor at the heat sink.This talk will discuss the development of a scalable, electrochemical approach for fabricating interlayers with functionally graded CTE that can decrease the thermal mismatch between tungsten PFCs and copper or RAFM-based heat sinks. In this approach, the copper/tungsten or copper/tungsten carbide composite are electrodeposited onto the tungsten PFC. This component is then bonded to the heat sink via brazing. A key objective of the work is to achieve compositional control during electrodeposition through the use of highly tunable pulse and pulse-reverse electric fields. Engineering of the electric field enables control of the mass transport and crystallization phenomena in the deposition process and thus enables control of composite properties such as composition, porosity, and surface roughness. Results from electrodeposition trials and mechanical testing of brazed joints under ambient conditions as an initial screen for interlayer performance will be discussed, in anticipation of high-heat flux testing of joint performance under fusion-relevant conditions.

Wavelength-switchable noise-like square pulsed fiber laser based on nonlinear effects

We report a fiber laser that can generate switchable wavelength noise-like square pulses (NLSPs) with a tunable pulse width based on nonlinear effects and nonlinear polarization rotation (NPR) mode-locking technology. In the single-wavelength NLSP, the 3 dB bandwidth is 1.68 nm and the central wavelength is 1558.61 nm. The widths of the spike and pulse duration are 1.47 ps and 5.14 μs. In the case of obtaining dual-wavelength noise-like squares, the pulse width is broadened from 84.4 to 875.8 ns by varying the pump power in the range of 60 to 450 mW. The dual-wavelength square pulse has a maximum energy of 27.26 nJ. The phenomena investigated in this work are conducive to a profound understanding of NLSPs formation in fiber laser and are of great significance for broadening the approach for achieving multi-wavelength square pulse.

Environmental noise reduction for tunable resistive pulse sensing of extracellular vesicles.

Extracellular vesicles (EVs) bearing biomolecules from parental cells can represent a novel source of disease biomarkers and are under intensive study for their clinical potential. Tunable resistive pulse sensing (TRPS) quantifies the magnitude of a small ionic resistive pulse current to determine the size, concentration, and zeta potential of EVs. Environmental noise is a common limiting factor that affects the precision of sensing devices. TRPS is particularly vulnerable to environmental noise, including both mechanical and electrical. The upper detection limit of the TRPS relies on the physical size of the elastomeric tunable nanopore. The lower limit relies on the electrical signal-to-noise ratio. Guided by simulation, we designed an external device to suppress environmental noise for TRPS measurement. Both mechanical and electrical environmental noise reductions were observed after using the shield. The study also validated the noise reduction function of the shield by quantifying EVs from different cell origins. Detection of EVs smaller than 200 nm was improved by using the shield; which was reported challenging for conventional quantification methods. The study highlighted a feasible approach to solve environmental noise challenges for TRPS based EV quantification.

250 fs, 130 mW Laser With Tunable Pulse Repetition Rate From 0.5 to 1.3 GHz

We report a compact ultrafast solid-state laser source with a pulse repetition rate continuously tunable in the range of 0.56–1.23 GHz. The optical cavity design allows a user to vary the repetition rate only by moving positions of two optical components inside the resonator, without a need to exchange components or realignment. The Yb:KYW crystal based cavity emits 250 femtosecond pulses at a central wavelength around 1040 nm, with a self-starting SESAM modelocking. In a robust modelocked operation mode, an average power up to 130 mW is achieved using a stabilized single mode pump diode at a wavelength of 981 nm, while the laser in continuous wave (CW) mode delivers up to 270 mW. Atmospheric air cooling was sufficient for both CW and modelocked laser operation. Quite low noise performance was observed, with carrier frequency SNR higher than 80 dB, although the measurements were taken with the open breadboard setup.

Femtosecond tunable solitons up to 4.8 µm using soliton self-frequency shift in an InF3 fiber

A tunable ultrashort soliton pulse source reaching up to 4.8 µm is demonstrated based on a 2.8 µm femtosecond fiber laser coupled to a zirconium fluoride fiber amplifier followed by a small core indium fluoride fiber. This demonstration is extending by 300 nm the long wavelength limit previously reported with soliton self-frequency shift (SSFS) sources based on fluoride fibers. Our experimental and numerical investigation highlighted the spectral dynamics associated with the generation of highly redshifted pulses in the mid-infrared using SSFS enhanced by soliton fission. This study is intended at providing a better understanding of the potential and limitations of SSFS based tunable femtosecond fiber sources in the 3–5 µm spectral range.

Multi-soliton pulse generation in a fiber laser by using a long-period fiber grating

In this paper, multi-soliton pulse generation is realized by incorporating a long period fiber grating into an Er-doped mode-locked fiber ring laser cavity. By using nonlinear polarization rotation mode-locking technique and a long period fiber grating that plays the role of spectral filter in the laser cavity, discretely tunable multi-soliton pulses can be produced at low lasing threshold of 80 mW. The number of solitons can be controlled by simply adjusting the polarization controller in the laser cavity. It is found that Kelly sideband of the traditional mode-locked solitons become weak as a result of introducing the long period fiber grating in the laser cavity, due to the fact that the nonlinearity and dispersion in the cavity are balanced, and hence stabilizing the soliton pulses. The use of long-period fiber grating has the advantages of effectively reducing the pumping threshold for the multi-soliton pulse generation, and supporting stable laser operation.

Ultrafast formation of quantized interlayer vibrations in Bi2Se3 by photoinduced strain waves.

This study comprehensively investigated the coherent lattice dynamics in Bi2Se3 by ultrafast optical pump-probe spectroscopy with tunable near-infrared probe pulses. Sample-thickness- and probe-wavelength-dependent experiments revealed the key role of Bi2Se3 optical property in the generation and detection of photoinduced strain waves, whose confinement initiated coherent interlayer vibrations. Furthermore, the frequency and lifetime of the interlayer vibrations could be quantitatively explained with a modified linear chain and an acoustic mismatch model considering elastic coupling at sample-substrate interfaces. The results of this work provide insights for analyzing and interpreting, through ultrafast optical spectroscopy, nanomechanical interactions in layered materials.

Crystal growth, spectra properties, and 2-μm laser performance of a novel “mixed” Tm3+-doped CaY0.65Gd0.35AlO4 crystal

A novel Tm3+: CaY0.65Gd0.35AlO4 (Tm3+: CYGA) disordered crystal was successfully grown for the first time, to the best of our knowledge, using the Czochralski method. The optical properties and laser performance were investigated in details. Owing to the addition of Gd3+ ions to the Tm3+: CYA crystal, the Tm3+: CYGA crystal possesses a wider Tm3+ absorption and emission spectra compared with those of the Tm3+: CYA and Tm3+: CGA crystals. In particular, the full width at half-maximum (FWHM) of the emission spectra at approximately 2 µm for the Tm3+: CYGA crystal was 221.3 nm, which is larger than those of the Tm3+: CYA (200 nm) and Tm3+: CGA (151 nm) crystals. Furthermore, an efficient laser operation of the Tm3+: CYGA crystal at 1974 nm was achieved for the first time, with a slope efficiency of up to 31.5 %, corresponding to a maximum output power of 810 mW. The results show that Tm3+: CYGA disordered crystals have the potential to be applied in ∼ 2-μm broadband tunable lasers and ultra-short pulse lasers.