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Journal articleBattle RA, Chandran AM, Runcorn TH, et al., 2023,
Mid-infrared difference-frequency generation directly pumped by a fiber four-wave mixing source
, Optics Letters, Vol: 48, Pages: 387-390, ISSN: 0146-9592We demonstrate a new, to the best of our knowledge, method of generating mid-infrared pulses by difference frequency mixing the Stokes pulse generated by four-wave mixing in a photonic crystal fiber with the remaining pump pulse. The Stokes pulses generated by four-wave mixing are inherently overlapped temporally and spatially with the pump pulse at the output of the fiber. Focusing this output into a nonlinear crystal phase matched for difference frequency generation between the pump and Stokes pulses results in a simple method of generating mid-infrared pulses. With a pump source at 1.064 µm, and a photonic crystal fiber engineered to generate Stokes pulses at approximately 1.65 µm, we generate 160 mW of mid-infrared light at approximately 3 µm through difference frequency generation.
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Conference paperTemel T, Murray RT, Wang L, et al., 2023,
Power Scaling of a Narrowband-Seeded PPLN Non-Resonant Optical Parametric Oscillator
A PPLN non-resonant optical parametric oscillator injection-seeded by narrowband sub-100-mW CW radiation at the signal wavelength produces > 3 W idler average power at 2376 nm for a 20-kHz repetition rate, with sub-2-nm spectral linewidth.
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Conference paperLiang M, Minassian A, Damzen M, 2023,
Acousto-optic Q-switched Alexandrite Laser with Wavelength Tuning and Second Harmonic Generation
Alexandrite is an excellent solid-state laser medium for high-power Q-switched operation due to its high thermal conductivity (23 Wm<sup>−1</sup>K<sup>−1</sup>) and long upper-state lifetime (262 µs). Whilst electro-optically Q-switched (EO-QS) Alexandrite lasers with red diode-pumping have been demonstrated [1], this work presents results of the first ever Acousto-Optic Q-switched (AO-QS) Alexandrite laser. In addition, we present results of the conversion of the output of the wavelength-tuned AO-QS laser to tunable ultraviolet by second harmonic generation.
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Conference paperXiao H, Jiang X, Damzen MJ, 2023,
Alexandrite Lasers Operating with High-power Blue-diode-pumping
Alexandrite is a solid-state laser with excellent thermal properties for power scaling and together with its broad wavelength tunability (~720-820 nm) provides potential for applications in remote sensing, biophotonics, and quantum technologies. Until recently, diode pumping has been predominantly performed by red semiconductor lasers near 638nm, however, blue diodes operating near 445nm have higher emitter power, higher-brightness and low-cost ($/W) making them attractive as alternative pump sources for Alexandrite lasers. This work focuses on the investigation of Alexandrite lasers pumped by a high-power fibre-delivered blue diode module achieving record blue-pumped powers and provides in-depth laser performance characterisation.
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Conference paperTawy G, Davidson NP, Mennea PL, et al., 2023,
375-400nm UV Generation via an Alexandrite laser and Zn-indiffused MgO-doped PPLN Waveguides
Laser sources in the UV-blue region at around 350-400 nm are of increasing importance for applications including quantum technologies and material processing. To operate in a wide range of environments, these laser sources need to be compact, robust and have low-power and minimal cooling requirements. The work presented here looks at combining rapid progress in two areas of laser development for addressing these applications. Diode-pumped Alexandrite lasers have become a low-cost and simple approach to achieving multi-watt powers in the near-infrared at around 720-800 nm [1]. Zn-indiffused MgO-doped PPLN waveguides have recently demonstrated impressive second harmonic generation (SHG) conversion efficiencies in the near-infrared [2] as well as conversion into the UV with doubling to 390 nm recently reported [3].
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Conference paperPearce E, Flórez J, Gemmell NR, et al., 2023,
Enhancing Nonlinear Interferometers for Imaging with Undetected Photons: Seeding and High-Gain
Infrared (IR) imaging and spectroscopy is invaluable to many disciplines for its ability to probe molecular responses, from material analysis to diagnostic medicine. However, these applications are often limited by inefficient, noisy detectors. Non-degenerate nonlinear interferometers (NLIs) offer an alternative route through a technique known as imaging with undetected photons [1]. For an NLI producing visible-IR photon pairs, a change in the IR due to an object can be observed as a change to the interference of the visible photons. The IR does not need to be detected, bypassing the need for IR detectors completely.
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Conference paperKrawczyk B, Kudlinski A, Battle RA, et al., 2023,
Four-Wave Mixing Enhancement in a Yb-doped Photonic Crystal Fiber
Degenerate four-wave mixing (FWM) in photonic crystal fibers (PCFs) is an effective method for generating near-infrared coherent light across a wide range of wavelengths using compact, low-cost ytterbium or neodymium pump lasers [1]. For many applications, e.g. multiphoton microscopy, increasing the peak power of the short wavelength anti-Stokes sideband generated by FWM is advantageous. Several works have sought to scale the anti-Stokes peak power by optimizing the pump laser and PCF structure but the pump to anti-Stokes conversion efficiency remains limited by pump depletion [2]. By introducing Yb-doping into the core of a PCF designed for FWM, we propose to mitigate the effects of pump depletion by using stimulated emission to replenish the FWM pump energy that is transferred to the anti-Stokes (and Stokes) as it propagates down the fiber. Here we present a novel double-clad PCF with a Yb-doped core and demonstrate, for the first time to the best of our knowledge, that amplification of FWM pump pulses through stimulated emission increases the anti-Stokes power generated by FWM.
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Conference paperBattle RA, Simon D, Xiang Y, et al., 2023,
Cellular Level Resolution Ambient Mass Spectrometry Imaging using 3 µm Laser Ablation
Tissue can be rapidly ablated by lasers with wavelength around λ = 3 µm, which is strongly absorbed by water [1]. Mass spectrometry (MS) analysis of the ablated material can subsequently provide rich chemical data about the molecular content of the tissue. In mass spectrometry imaging (MSI), spatially resolved molecular data is obtained from a sample by collecting multiple mass spectra. From these individual spectra, the spatial distribution of molecules of interest can be mapped. In this work, we report a single-cell level resolution mass spectrometry imaging platform based on laser ablation using a parametric 3 µm laser source and Rapid Evaporative Ionization Mass Spectrometry (REIMS) [2]. The laser source is specifically developed to have high beam quality and sub-ns duration. This has allowed us to overcome previous ambient MSI spatial resolution limits, a key step to translating the benefits of MS analysis to clinical applications.
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Conference paperBattle RA, Simon D, Xiang Y, et al., 2023,
High resolution mass spectrometry imaging using 3 micron laser ablation
, ISSN: 1605-7422We report a single-cell level resolution (≤10 µm), laser desorption-based mass spectrometry imaging platform. An optical parametric amplifier is used to generate ∼100 ps, 200 nJ pulses at around 3 µm with a maximum repetition rate of 500 kHz. The pulses are tightly focussed on to fresh frozen animal tissue samples with a thickness of 10 µm. Small volumes of tissue are readily ablated by the laser and are subsequently chemically analyzed using a Rapid Evaporative Ionization Mass Spectrometry (REIMS) source installed on a time of flight mass analyzer. Raster scanning the samples through the laser focus enables the acquisition of mass spectrometry data which can be processed into images with pixel size 10 µm without oversampling, corresponding to cellular level resolution.
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Conference paperGeberbauer JWT, Murray RT, Runcorn TH, et al., 2023,
Yb fiber vortex laser using an interferometric mode converting output coupler
, ISSN: 0277-786XWe apply mode transformation to an Yb fiber laser for direct generation of a first order vortex mode (LG<inf>01</inf>), yielding LG<inf>01</inf> power of 5 W at 96 % purity (from modal decomposition) with 16 W pumping. The laser used standard single mode Yb doped fibers operating at 1064 nm. A free-space Sagnac interferometer formed one reflector of the cavity by feeding back the internal Gaussian mode of the fiber laser and output coupling a LG<inf>01</inf> via interferometric mode transformation. It was stable over hours of operation and days of inactivity, and was insensitive to polarisation. The maximum output power was only limited through heating of a optical element, which could be mitigated with thermal management. We also show that additional spiral phase plates (SPPs) are a route to higher purity, higher order vortex modes than with SPPs alone due to improved intensity matching between LG<inf>01</inf> and higher order states.
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Conference paperMurray RT, Wang L, Chen W, et al., 2023,
Narrowband seeding of a PPLN nonresonant optical parametric oscillator
, ISSN: 0277-786XWe present a nanosecond, non-resonant optical parametric oscillator (NRO) based on a 20 mm long periodically-poled LiNbO<inf>3</inf> (PPLN) crystal operating at 30-70 kHz. Pumping with a nanosecond Nd:YVO<inf>4</inf> laser at 1064 nm in a double-pass configuration, the signal plus idler average output power reached 1.2 W for a pump level of 4 W (at 35 kHz repetition rate). Narrowband seeding with a Tm-fiber laser is employed to narrow the linewidths of the signal to 0.8 nm and the idler to 2 nm. Continuous-wave seed levels as low as 2 mW were sufficient to produce the effect which means that this technique could be useful for single-frequency operation using DFB seed laser diodes. At higher pump power levels > 4 W, the linewidth narrowing effect produced by the seeding was insufficient to prevent broader linewidth operation of the NRO signal and idler outputs. Pumping the NRO at higher repetition rates to scale the average output power of the NRO whilst remaining in the narrow linewidth operation mode is discussed.
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Conference paperSparks H, Dent L, Ratcliffe CDH, et al., 2023,
Dual-view oblique plane microscopy for multi-well plate time-lapse 3D imaging assays in cancer research
This talk introduces the development of an image acquisition and processing pipeline based on a dual-view oblique plane microscopy (dOPM) system and which is suitable for multi-well plate imaging assays for cancer research.
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Conference paperRowe-Brown L, Curry N, Meyler S, et al., 2023,
Oblique plane microscopy for 3D, multi-color, 8-day time-lapse imaging of genetically heterogeneous breast cancer spheroids in 384-well plates with quantitative 3D analysis
, Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XXI, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 1605-7422 -
Journal articleKoufidis SF, McCall MW, 2022,
M?bius transformation and coupled-wave theory: Complete identification of the transfer matrix
, PHYSICAL REVIEW A, Vol: 106, ISSN: 2469-9926- Cite
- Citations: 8
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Journal articleRahman T, Baxan N, Murray R, et al., 2022,
An in vitro comparison of three nucleus pulposus removal techniques for partial intervertebral disc replacement: An ultra-high resolution MRI study
, JOR Spine, ISSN: 2572-1143 -
Journal articleDilliway C, Dyer O, Mandrou E, et al., 2022,
Working at the interface of physics and biology: An early career researcher perspective
, iScience, Vol: 25, Pages: 1-7, ISSN: 2589-0042 -
Journal articleMcCall M, Koufidis S, 2022,
Reverse circular Bragg phenomenon
, Physical Review Research, Vol: 4, ISSN: 2643-1564he problem of axial propagation of circularly polarized light in a circularly birefringent structurally chiral medium is exactly solved via full electromagnetic analysis. Underlying symmetries of the system's characteristic matrix reveal interesting insights, which are confirmed by coupled wave theory. For extreme values of chirality, a reverse circular Bragg resonance arises in the negative refraction regime where handedness reversal of counterpart modes occurs. A condition is identified under which circular birefringence precisely offsets structural chirality, rendering the medium simply linearly birefringent. Manufacturing such a medium is feasible via current metamedia and inorganic materials technology and has applications in optics, optoelectronics, and sensing.
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Journal articleHong W, Wright T, Sparks H, et al., 2022,
Adaptive light-sheet fluorescence microscopy with a deformable mirror for video-rate volumetric imaging
, Applied Physics Letters, Vol: 121, Pages: 1-7, ISSN: 0003-6951Light-sheet fluorescence microscopy (LSFM) achieves optically sectioned imaging with the relatively low photobleaching and phototoxic effect. To achieve high-speed volumetric LSFM imaging without perturbing the sample, it is necessary to use some form of remote refocusing in the detection beam path. Previous work used electrically tunable lenses, tunable acoustic gradient index of refraction lenses, or the remote-refocusing approach of Botcherby et al. [Opt. Lett. 32(14), 2007 (2007)] to achieve remote refocusing. However, these approaches generally only provide low-order defocus correction, which is not compatible with higher-NA objectives that require higher order defocus corrections or reduce the optical throughput. In order to simultaneously achieve high-speed remote refocusing and correct system aberrations, we employ a deformable mirror in the detection path that is capable of providing higher orders of defocus and aberration correction in an optical system with an NA of 0.72–0.75. We demonstrate high-speed volumetric imaging at 26.3 volumes per second and 35 frames per volume for a defocus range of −50 to 50 μm.
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Journal articleRibenek VA, Korobko DA, Fotiadi AA, et al., 2022,
Supermode noise mitigation and repetition rate control in a harmonic mode-locked fiber laser implemented through the pulse train interaction with co-lased CW radiation: publisher's note
, OPTICS LETTERS, Vol: 47, Pages: 5582-5582, ISSN: 0146-9592 -
Journal articleKinsler P, McCall MW, Oulton RF, et al., 2022,
The surprising persistence of time-dependent quantum entanglement
, New Journal of Physics, Vol: 24, Pages: 1-14, ISSN: 1367-2630The mismatch between elegant theoretical models and the detailed experimental reality is particularly pronounced in quantum nonlinear interferometry (QNI). In stark contrast to theory, experiments contain pump beams that start in impure states and that are depleted, quantum noise that affects—and drives—any otherwise gradual build up of the signal and idler fields, and nonlinear materials that are far from ideal and have a complicated time-dependent dispersive response. Notably, we would normally expect group velocity mismatches to destroy any possibility of measurable or visible entanglement, even though it remains intact—the mismatches change the relative timings of induced signal–idler entanglements, thus generating 'which path' information. Using an approach based on the positive-P representation, which is ideally suited to such problems, we are able to keep detailed track of the time-domain entanglement crucial for QNI. This allows us to show that entanglement can be—and is—recoverable despite the obscuring effects of real-world complications; and that recovery is attributable to an implicit time-averaging present in the detection process.
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Journal articleTang M, 2022,
Super-resolution ultrasound localization microscopy of microvascular structure and flow for distinguishing metastatic lymph nodes – an initial human study
, Ultraschall in der Medizin, Vol: 43, Pages: 592-598, ISSN: 0172-4614Purpose Detecting and distinguishing metastatic lymph nodes (LNs) from those with benign lymphadenopathy are crucial for cancer diagnosis and prognosis but remain a clinical challenge. A recent advance in super-resolution ultrasound (SRUS) through localizing individual microbubbles has broken the diffraction limit and tracking enabled in vivo noninvasive imaging of vascular morphology and flow dynamics at a microscopic level. In this study we hypothesize that SRUS enables quantitative markers to distinguish metastatic LNs from benign ones in patients with lymphadenopathy.Materials and Methods Clinical contrast-enhanced ultrasound image sequences of LNs from 6 patients with lymph node metastasis and 4 with benign lymphadenopathy were acquired and motion-corrected. These were then used to generate super-resolution microvascular images and super-resolved velocity maps. From these SRUS images, morphological and functional measures were obtained including micro-vessel density, fractal dimension, mean flow speed, and Local Flow Direction Irregularity (LFDI) measuring the variance in local flow direction. These measures were compared between pathologically proven reactive and metastasis LNs.Results Our initial results indicate that the difference in the indicator of flow irregularity (LFDI) derived from the SRUS images is statistically significant between the two groups. The LFDI is 60% higher in metastatic LNs compared with reactive nodes.Conclusion This pilot study demonstrates the feasibility of super-resolution ultrasound for clinical imaging of lymph nodes and the potential of using the irregularity of local blood flow directions afforded by SRUS for the characterization of LNs.
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Journal articleRibenek VA, Korobko DA, Fotiadi AA, et al., 2022,
Supermode noise mitigation and repetition rate control in harmonic mode-locked fiber laser implemented through the pulse train interaction with co-lased CW radiation
, OPTICS LETTERS, Vol: 47, Pages: 5236-5239, ISSN: 0146-9592- Cite
- Citations: 4
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Journal articleCalvarese M, Paie P, Candeo A, et al., 2022,
Integrated optical device for Structured Illumination Microscopy
, OPTICS EXPRESS, Vol: 30, Pages: 30246-30259, ISSN: 1094-4087- Cite
- Citations: 2
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Journal articleConey AT, Beecher S, Damzen MJ, et al., 2022,
High-energy Q-switched Nd:YAG oscillator and amplifier development for large-mode, low-alignment sensitivity applications
, LASER PHYSICS LETTERS, Vol: 19, ISSN: 1612-2011- Cite
- Citations: 3
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Conference paperMunj A-H, Kerridge-Johns WR, 2022,
Ring Cavity Vortex Laser Using a Wedge-Plate Shearing Interferometer
, 2022 Conference on Lasers and Electro-Optics Pacific Rim (CLEO-PR), Publisher: IEEE, Pages: 1-2 -
Journal articleLightley J, Kumar S, Garcia E, et al., 2022,
Robust, single-shot, optical autofocus system utilizing cylindrical lenses to provide high precision and long range of operation
<jats:title>ABSTRACT</jats:title> <jats:p>We present a robust, “real-time” optical autofocus system for microscopy that provides high accuracy (<230 nm) and long range (∼130 µm) with a 1.4 numerical aperture oil immersion objective lens. This autofocus can operate in a closed loop, single-shot functionality over a range of ±37.5 µm and can also operate as a 2-step process up to ±68 µm. A real-time autofocus capability is useful for experiments with long image data acquisition times, including single molecule localization microscopy, that may be impacted by defocusing resulting from drift of components, e.g., due to changes in temperature or mechanical drift. It is also vital for automated slide scanning or multiwell plate imaging where the sample may not be in the same horizontal plane for every field of view during the image data acquisition. To realise high precision and long range, we implement orthogonal optical readouts using cylindrical lenses. We demonstrate the performance of this new optical autofocus system with automated multiwell plate imaging and single molecule localisation microscopy and illustrate the benefit of using a superluminescent diode as the autofocus light source.</jats:p>
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Journal articleChung CH, Li J, Steuer CE, et al., 2022,
Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.
, Clin Cancer Res, Vol: 28, Pages: 2329-2338PURPOSE: A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with a combination of cetuximab and nivolumab. PATIENTS AND METHODS: Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m2 i.v. and nivolumab 240 mg i.v. on day 1 and day 15 of each 28-day cycle. Expression of p16 and programmed cell death-ligand 1 (PD-L1) in archived tumors were determined. Tumor-tissue-modified human papillomavirus (TTMV) DNA was quantified in plasma. RESULTS: Ninety-five patients were enrolled, and 88 patients were evaluable for OS with a median follow-up of 15.9 months. Median OS in the 45 patients who had prior therapy for R/M HNSCC (cohort A) was 11.4 months, with a 1 year OS 50% [90% confidence interval (CI), 0.43-0.57]. Median OS in the 43 patients who had no prior therapy (cohort B) was 20.2 months, with a 1-year OS 66% (90% CI, 0.59-0.71). In the combined cohorts, the p16-negative immunostaining was associated with higher response rate (RR; P = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (P = 0.03) and longer OS (log-rank P = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (P = 0.01) and longer OS compared with higher median (log-rank P = 0.05). CONCLUSIONS: The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.
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Conference paperFu X, Bhargava A, Bailey S, et al., 2022,
Intra-epithelia cell dynamics shape evolutionary dynamics and selection of therapy resistant clones in lung cancer
, AACR Special Conference - Evolutionary Dynamics in Carcinogenesis and Response to Therapy, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472 -
Journal articleVan de Pette M, Dimond A, Galvao AM, et al., 2022,
Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice
, Nature Communications, Vol: 13, ISSN: 2041-1723Transmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, modified histones and DNA methylation. Similar processes in mammals can also affect phenotype through intergenerational or trans-generational mechanisms. Here we generate a luciferase knock-in reporter mouse for the imprinted Dlk1 locus to visualise and track epigenetic fidelity across generations. Exposure to high-fat diet in pregnancy provokes sustained re-expression of the normally silent maternal Dlk1 in offspring (loss of imprinting) and increased DNA methylation at the somatic differentially methylated region (sDMR). In the next generation heterogeneous Dlk1 mis-expression is seen exclusively among animals born to F1-exposed females. Oocytes from these females show altered gene and microRNA expression without changes in DNA methylation, and correct imprinting is restored in subsequent generations. Our results illustrate how diet impacts the foetal epigenome, disturbing canonical and non-canonical imprinting mechanisms to modulate the properties of successive generations of offspring.
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Conference paperWysoczanski R, Baker JR, Fenwick P, et al., 2022,
Defective Phagocytosis in COPD Macrophages Is Improved by Mitochondrial Antioxidants Without Alteration in Mitochondrial Function
, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X- Author Web Link
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- Citations: 1
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