Publications
See a list of publications below or visit the Photonics academic staff page and click on a particular member of staff to access their personal web page, which includes a list of their own publications.
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Conference paperHong Y, Bottrill KRH, Taengnoi N, et al., 2021,
Amplified O-band direct-detection transmission using bismuth-doped fiber amplifiers
, 12th International Conference on Information Optics and Photonics (CIOP), Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X -
Journal articleJones B, McGlone ER, Fang Z, et al., 2021,
Genetic and biased agonist-mediated reductions in β-arrestin recruitment prolong cAMP signalling at glucagon family receptors
, Journal of Biological Chemistry, Vol: 296, Pages: 1-15, ISSN: 0021-9258Receptors for the peptide hormones glucagon-like peptide-1 (GLP-1R), glucose-dependent insulinotropic polypeptide (GIPR) and glucagon (GCGR) are important regulators of insulin secretion and energy metabolism. GLP-1R agonists have been successfully deployed for the treatment of type 2 diabetes, but it has been suggested that their efficacy is limited by target receptor desensitisation and downregulation due to recruitment of β-arrestins. Indeed, recently described GLP-1R agonists with reduced β-arrestin-2 recruitment have delivered promising results in preclinical and clinical studies. We therefore aimed to determine if the same phenomenon could apply to the closely related GIPR and GCGR. In HEK293 cells depleted of both β-arrestin isoforms the duration of G protein-dependent cAMP/PKA signalling was increased in response to the endogenous ligand for each receptor. Moreover, in wild-type cells, “biased” GLP-1, GCG and GIP analogues with selective reductions in β-arrestin-2 recruitment led to reduced receptor endocytosis and increased insulin secretion over a prolonged stimulation period, although the latter effect was only seen at high agonist concentrations. Biased GCG analogues increased the duration of cAMP signalling, but this did not lead to increased glucose output from hepatocytes. Our study provides a rationale for development of GLP-1R, GIPR and GCGR agonists with reduced β-arrestin recruitment, but further work is needed to maximally exploit this strategy for therapeutic purposes.
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Conference paperTawy G, Minassian A, Damzen MJ, 2021,
8.5W Linear and 3.6W Ring TEM<sub>00</sub> Diode-Pumped Alexandrite Lasers
, Conference on Lasers and Electro-Optics Europe / European Quantum Electronics Conference (CLEO/Europe-EQEC), Publisher: IEEE -
Journal articleAhmad H, Samion MZ, Kamely AA, et al., 2020,
Multiwavelength Brillouin Generation in Bismuth-Doped Fiber Laser With Single- and Double-Frequency Spacing
, JOURNAL OF LIGHTWAVE TECHNOLOGY, Vol: 38, Pages: 6886-6896, ISSN: 0733-8724 -
SoftwareGong H, Wenjun G, Neil M, 2020,
HexSimProcessor
This repository is for the publication: "GPU-accelerated real-time reconstruction in Python of three-dimensional datasets from structured illumination microscopy with hexagonal patterns". It includes: raw data from experiments and simulations, the code for generating the simulated data, and the code for post-processing the raw data.
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Conference paperTewari S, Agrawal U, Verma S, et al., 2020,
Ensemble model for COVID-19 detection from chest X-ray scans using image segmentation, fuzzy color and stacking approaches
Coronavirus is a virus of RNA-type that can infect both humans and animal and causes a wide variety of respiratory infections. In humans, it also causes pneumonia. Since coronavirus has been declared a pandemic, Reverse Transcription Polymerase Chain Reaction (RT-PCR) has been the standard method for detection but is a time consuming operation and due to sudden surge in demand it has a high cost. In this study, coronavirus was detected from X-ray scans of chest using a deep learning model consisting of fuzzy image enhancement, offline data augmentation, image segmentation and classification through Convolutional Neural Network. For training and classification, an ensembeled model consisting of the features of VGG-16, ResNet-50 and MobileNetV2 was built and optimized with bayesian optimization. The proposed model achieved an overall accuracy of 96.34%. The precision, recall and F1-Score for COVID-19 class was 100%, 96% and 98% respectively.
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Journal articleSparks H, Dent L, Bakal C, et al., 2020,
Dual-view oblique plane microscopy (dOPM)
, Biomedical Optics Express, Vol: 11, Pages: 7204-7220, ISSN: 2156-7085We present a new folded dual-view oblique plane microscopy (OPM) techniquetermed dOPM that enables two orthogonal views of the sample to be obtained by translating apair of tilted mirrors in refocussing space. Using a water immersion 40× 1.15 NA primaryobjective, deconvolved image volumes of 200 nm beads were measured to have full width athalf maxima (FWHM) of 0.35±0.04 μm and 0.39±0.02 μm laterally and 0.81±0.07 μm axially.The measured z-sectioning value was 1.33±0.45 μm using light-sheet FWHM in the frames ofthe two views of 4.99±0.58 μm and 4.89±0.63 μm. To qualitatively demonstrate that the systemcan reduce shadow artefacts while providing a more isotropic resolution, a multi-cellularspheroid approximately 100 μm in diameter was imaged.
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Journal articleWang S, Wang Y, Thipparapu NK, et al., 2020,
Tunable CW Bi-Doped Fiber Laser System From 1320 to 1370 nm Using a Fiber Bragg Grating
, IEEE PHOTONICS TECHNOLOGY LETTERS, Vol: 32, Pages: 1443-1446, ISSN: 1041-1135 -
Conference paperGouveia RM, Lepert G, Gupta S, et al., 2020,
Biomechanical Modulation Therapy: Stem Cell Therapy Without the Stem Cells for the Treatment of Severe Ocular Burns
, Trans-Agency Scientific Meeting on Developing Medical Countermeasures to Treat the Acute and Chronic Effects of Ocular Chemical Toxicity, Publisher: ELSEVIER IRELAND LTD, Pages: S8-S8, ISSN: 0378-4274 -
Conference paperKerridge-Johns WR, Jaillot J-B, Damzen MJ, 2020,
Shear plate Interferometer for complex angular momentum field generation
, Frontiers in Optics, Publisher: OSA, Pages: 1-1We show that a shear plate interferometer can generate high purity complex angular momentum states and is simple, cheap, compact, and could operate in wavelength regions where optics for conventional techniques are not available.
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Conference paperWysoczanski R, Baker JR, Fenwick P, et al., 2020,
Analysis of defective phagocytosis in COPD using super-resolution microscopy and automated bacterial quantification
, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936 -
Journal articleQuicke P, Howe CL, Song P, et al., 2020,
Subcellular resolution 3D light field imaging with genetically encoded voltage indicators
, Neurophotonics, Vol: 7, ISSN: 2329-4248Significance: Light-field microscopy (LFM) enables high signal-to-noise ratio (SNR) and light efficient volume imaging at fast frame rates. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from LFM’s volumetric imaging capability due to high required sampling rates and limited probe brightness and functional sensitivity.Aim: We demonstrate subcellular resolution GEVI light-field imaging in acute mouse brain slices resolving dendritic voltage signals in three spatial dimensions.Approach: We imaged action potential-induced fluorescence transients in mouse brain slices sparsely expressing the GEVI VSFP-Butterfly 1.2 in wide-field microscopy (WFM) and LFM modes. We compared functional signal SNR and localization between different LFM reconstruction approaches and between LFM and WFM.Results: LFM enabled three-dimensional (3-D) localization of action potential-induced fluorescence transients in neuronal somata and dendrites. Nonregularized deconvolution decreased SNR with increased iteration number compared to synthetic refocusing but increased axial and lateral signal localization. SNR was unaffected for LFM compared to WFM.Conclusions: LFM enables 3-D localization of fluorescence transients, therefore eliminating the need for structures to lie in a single focal plane. These results demonstrate LFM’s potential for studying dendritic integration and action potential propagation in three spatial dimensions.
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Journal articleQuicke P, Howe CL, Song P, et al., 2020,
Subcellular resolution three-dimensional light-field imaging with genetically encoded voltage indicators
, Neurophotonics, Vol: 7, ISSN: 2329-4248Significance: Light-field microscopy (LFM) enables high signal-to-noise ratio (SNR) and light efficient volume imaging at fast frame rates. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from LFM's volumetric imaging capability due to high required sampling rates and limited probe brightness and functional sensitivity. Aim: We demonstrate subcellular resolution GEVI light-field imaging in acute mouse brain slices resolving dendritic voltage signals in three spatial dimensions. Approach: We imaged action potential-induced fluorescence transients in mouse brain slices sparsely expressing the GEVI VSFP-Butterfly 1.2 in wide-field microscopy (WFM) and LFM modes. We compared functional signal SNR and localization between different LFM reconstruction approaches and between LFM and WFM. Results: LFM enabled three-dimensional (3-D) localization of action potential-induced fluorescence transients in neuronal somata and dendrites. Nonregularized deconvolution decreased SNR with increased iteration number compared to synthetic refocusing but increased axial and lateral signal localization. SNR was unaffected for LFM compared to WFM. Conclusions: LFM enables 3-D localization of fluorescence transients, therefore eliminating the need for structures to lie in a single focal plane. These results demonstrate LFM's potential for studying dendritic integration and action potential propagation in three spatial dimensions.
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Conference paperSathian J, Abadi MM, Damzen MJ, et al., 2020,
Communication characteristics of high-brightness light sources based on luminescence concentration
Communication characteristics of high-brightness solid-state light sources based on luminescence concentration generated using blue emitting InGaN light emitting diode arrays are demonstrated here for the first time. The proposed device is used as a transmitter in visible light communications, and its performance is evaluated.
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Journal articleDamzen M, Sathian J, Tawy G, et al., 2020,
Non-astigmatic Alexandrite ring laser design with wavelength-tunable single-longitudinal-mode operation
, Journal of the Optical Society of America B: Optical Physics, Vol: 37, Pages: 2185-2192, ISSN: 0740-3224This work presents a study of a fully nonastigmatic design of a single-longitudinal-mode, wavelength-tunable, unidirectional alexandrite ring laser cavity and assessment of its performance compared to more complex laser design requiring astigmatism compensation. A “displaced mode” nonastigmatic laser cavity design eliminating astigmatic cavity elements is developed around an alexandrite crystal end-pumped by a low-brightness, high-power red diode laser pump system. Single-longitudinal-mode, continuous-wave operation is demonstrated with output power of 700 mW with an excellent TEM00 mode (M2<1.1) across a wide pump power range. Wavelength tuning from 748–773 nm is produced using a birefringent filter plate. The nonastigmatic alexandrite laser design achieves better spatial quality and resilience to maintain TEM00 operation across wide variation in pump-induced lensing compared to the astigmatic design. To the best of our knowledge, this is the first wavelength-tunable, single-longitudinal-mode operation of a unidirectional alexandrite ring system in a fully nonastigmatic cavity regime.
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Journal articleTawy G, Minassian A, Damzen M, 2020,
High-power 7.4W TEM00 and wavelength-tunable Alexandrite laser with novel cavity design and efficient fibre-coupled diode-pumping
, OSA Continuum, Vol: 3, Pages: 1638-1649, ISSN: 2578-7519We report significant improvement in the performance of TEM00 alexandrite laser operation by employing high power fibre-coupled red diode pumping, novel cavity design, and active direct Shack-Hartmann wavefront sensor measurement of pump-induced lensing. We demonstrate 12.7 W of laser power in low-order (𝑀2∼5) mode operation from a compact double-end-pumped cavity, and with novel cavity design, a record power of 7.4 W in TEM00 operation with excellent beam quality (𝑀2≤1.1). With single-end pumping, laser power of 4.7 W (𝑀2∼1.3) was achieved with slope efficiencies as high as 54.9 %; a record efficiency for red-diode-pumped alexandrite. Using a birefringent filter, continuous laser wavelength tuning from 725-808 nm is achieved in diffraction-limited TEM00 mode, with laser power of 4.7 W at 765 nm, and >1 W across 730-805 nm, which is a higher tunable power than any other directly diode-pumped vibronic laser, to the best of our knowledge.
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Journal articleSparks H, Dvinskikh L, Firth J, et al., 2020,
Development a flexible light-sheet fluorescence microscope for high-speed 3D imaging of calcium dynamics and 3D imaging of cellular microstructure
, Journal of Biophotonics, Vol: 13, ISSN: 1864-063XWe report a flexible light‐sheet fluorescence microscope (LSFM) designed for studying dynamic events in cardiac tissue at high speed in 3D and the correlation of these events to cell microstructure. The system employs two illumination‐detection modes: the first uses angle‐dithering of a Gaussian light sheet combined with remote refocusing of the detection plane for video‐rate volumetric imaging; the second combines digitally‐scanned light‐sheet illumination with an axially‐swept light‐sheet waist and stage‐scanned acquisition for improved axial resolution compared to the first mode. We present a characterisation of the spatial resolution of the system in both modes. The first illumination‐detection mode achieves dual spectral‐channel imaging at 25 volumes per second with 1024 × 200 × 50 voxel volumes and is demonstrated by time‐lapse imaging of calcium dynamics in a live cardiomyocyte. The second illumination‐detection mode is demonstrated through the acquisition of a higher spatial resolution structural map of the t‐tubule network in a fixed cardiomyocyte cell.
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Journal articleHong Y, Sakr H, Taengnoi N, et al., 2020,
Multi-Band Direct-Detection Transmission Over an Ultrawide Bandwidth Hollow-Core NANF
, JOURNAL OF LIGHTWAVE TECHNOLOGY, Vol: 38, Pages: 2848-2856, ISSN: 0733-8724 -
Conference paperWang S, Wang Y, Thipparapu NK, et al., 2020,
All-Fiber Wavelength-Tunable Bi-Doped Laser Employing a Fiber Bragg Grating Operating in the 1300nm Band
, ISSN: 1092-8081We present a Bi-doped fiber laser (BDFL) at 1340nm with >170mW output power and 35% slope efficiency. A wavelength-tunable version of the BDFL facilitated by an FBG is demonstrated from 1315-1340nm with >120mW output power.
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Conference paperHong Y, Bottrill KRH, Taengnoi N, et al., 2020,
First Investigation on Double-and Single-Sideband Formats in BDFA-Enabled O-Band Transmission
, ISSN: 1092-8081We experimentally compare 50-Gb/s single-and double-sideband formats in an O-band BDFA-amplified transmission system over different distances. The results show that single-sideband transmission is beneficial for distances beyond ∼50km at more dispersive O-band wavelengths.
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Conference paperTaengnoi N, Bottrill KRH, Hong Y, et al., 2020,
Experimental Characterization of Bismuth-Doped Fibre Amplifier: Electrical NF, PDG, and XGM
, ISSN: 1092-8081We present a detailed characterisation of the emergent bismuth-doped fibre amplifier, characterising performance in terms of electrical noise figure, polarisation dependent gain, and cross gain modulation. The results support its suitability for high capacity links.
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Journal articleJones B, McGlone ER, Fang Z, et al., 2020,
Signal bias at glucagon family receptors: rationale and downstream impacts
<jats:title>Abstract</jats:title><jats:p>Receptors for the peptide hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) are important regulators of insulin secretion and energy metabolism. Recently described GLP-1 receptor agonists showing signal bias in favour of cyclic AMP over β-arrestin-2 recruitment have delivered promising results in preclinical studies. Here we first sought to establish the role of β-arrestins in the control of intracellular signalling and trafficking responses at the closely related GLP-1, GIP and GCG receptors, through studies performed in cells depleted of both β-arrestin isoforms. We also generated analogues of GLP-1, GCG and GIP which in some cases showed selective reduction in β-arrestin-2 recruitment <jats:italic>versus</jats:italic> cAMP signalling compared to the parent peptide. Despite reduced acute signalling potency and/or efficacy, some biased GLP-1 and GIP analogues increased maximal sustained insulin secretion from INS-1 832/3 clonal beta cells, although only at high agonist concentrations. Biased GCG analogues did not affect maximal insulin release, or glucose output in hepatocytes.</jats:p>
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Journal articleGeorgiadou E, Haythorne E, Dickerson MT, et al., 2020,
The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice
, Diabetologia, Vol: 63, Pages: 1368-1381, ISSN: 0012-186XAims/hypothesisMitochondrial oxidative metabolism is central to glucose-stimulated insulin secretion (GSIS). Whether Ca2+ uptake into pancreatic beta cell mitochondria potentiates or antagonises this process is still a matter of debate. Although the mitochondrial Ca2+ importer (MCU) complex is thought to represent the main route for Ca2+ transport across the inner mitochondrial membrane, its role in beta cells has not previously been examined in vivo.MethodsHere, we inactivated the pore-forming subunit of the MCU, encoded by Mcu, selectively in mouse beta cells using Ins1Cre-mediated recombination. Whole or dissociated pancreatic islets were isolated and used for live beta cell fluorescence imaging of cytosolic or mitochondrial Ca2+ concentration and ATP production in response to increasing glucose concentrations. Electrophysiological recordings were also performed on whole islets. Serum and blood samples were collected to examine oral and i.p. glucose tolerance.ResultsGlucose-stimulated mitochondrial Ca2+ accumulation (p< 0.05), ATP production (p< 0.05) and insulin secretion (p< 0.01) were strongly inhibited in beta cell-specific Mcu-null (βMcu-KO) animals, in vitro, as compared with wild-type (WT) mice. Interestingly, cytosolic Ca2+ concentrations increased (p< 0.001), whereas mitochondrial membrane depolarisation improved in βMcu-KO animals. βMcu-KO mice displayed impaired in vivo insulin secretion at 5 min (p< 0.001) but not 15 min post-i.p. injection of glucose, whilst the opposite phenomenon was observed following an oral gavage at 5 min. Unexpectedly, glucose tolerance was improved (p< 0.05) in young βMcu-KO (<12 weeks), but not in older animals vs WT mice.Conclusions/interpretationMCU is crucial for mitochondrial Ca2+ uptake in pancreatic beta cells and is required for normal GSIS. The apparent compensatory mechanisms that maintain glucose tolerance in βMcu-KO mice remain
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Journal articleHong Y, Bottrill KRH, Taengnoi N, et al., 2020,
Experimental Demonstration of Dual O plus C-Band WDM Transmission Over 50-km SSMF With Direct Detection
, JOURNAL OF LIGHTWAVE TECHNOLOGY, Vol: 38, Pages: 2278-2284, ISSN: 0733-8724 -
Journal articleFang Z, Chen S, Pickford P, et al., 2020,
The influence of peptide context on signaling and trafficking of glucagon-like peptide-1 receptor biased agonists
, ACS Pharmacology & Translational Science, Vol: 3, Pages: 345-360, ISSN: 2575-9108Signal bias and membrane trafficking have recently emerged as important considerations in the therapeutic targeting of the glucagon-like peptide-1 receptor (GLP-1R) in type 2 diabetes and obesity. In the present study, we have evaluated a peptide series with varying sequence homology between native GLP-1 and exendin-4, the archetypal ligands on which approved GLP-1R agonists are based. We find notable differences in agonist-mediated cyclic AMP signaling, recruitment of β-arrestins, endocytosis, and recycling, dependent both on the introduction of a His → Phe switch at position 1 and the specific midpeptide helical regions and C-termini of the two agonists. These observations were linked to insulin secretion in a beta cell model and provide insights into how ligand factors influence GLP-1R function at the cellular level.
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Journal articleGratus J, McCall MW, Kinsler P, 2020,
Electromagnetism, axions, and topology: A first-order operator approach to constitutive responses provides greater freedom
, Physical Review A: Atomic, Molecular and Optical Physics, Vol: 101, Pages: 043804-1-043804-18, ISSN: 1050-2947We show how the standard constitutive assumptions for the macroscopic Maxwell equations can be relaxed. This is done by arguing that the Maxwellian excitation fields (D, H) should be dispensed with, on the grounds that they (a) cannot be measured, and (b) act solely as gauge potentials for the charge and current. In the resulting theory, it is only the links between the fields (E, B) and the charge and current (ρ, J) that matter; and so we introduce appropriate linear operator equations that combine the Gauss and Maxwell-Ampère equations with the constitutive relations, eliminating (D, H). The result is that we can admit more types of electromagnetic media, notably, these relations can allow coupling in the bulk to a homogeneous axionic material; in contrast to standard electromagnetism where any homogeneous axionlike field is completely decoupled in the bulk, and only accessible at boundaries. We also consider a wider context, including the role of topology, extended nonaxionic constitutive parameters, and treatment of Ohmic currents. A range of examples including an axionic response material is presented, including static electromagnetic scenarios, a possible metamaterial implementation, and how the transformation optics paradigm would be modified. Notably, these examples include one where topological considerations make it impossible to model using (D, H).
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Conference paperWang Y, Thipparapu NK, Richardson DJ, et al., 2020,
Broadband Bismuth-Doped Fiber Amplifier with a Record 115-nm Bandwidth in the O and e Bands
We report a bismuth-doped fiber amplifier providing >20dB gain from 1345nm-1460nm with 31dB maximum gain and 4.8dB NF at 1420nm for a -23dBm signal. The gain coefficient and temperature-dependent-gain coefficient are 0.042dB/mW and -0.015dB/°C, respectively.
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Conference paperGeberbauer JWT, Kerridge-Johns WR, Damzen MJ, 2020,
Q-switched vortex laser using a Sagnac interferometer as an output coupler
, Solid State Lasers XXIX - Technology and Devices, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, Pages: 1-10, ISSN: 0277-786XVortex lasers are an attractive prospect for efficient generation of high-quality beams in compact, environmentally robust, and turnkey systems. We demonstrate conversion of a Q-switched, diode-pumped Nd:YVO4, TEM00 Gaussian laser into a vortex laser source by replacing the output coupling mirror by a vortex output coupler (VOC) based on an imbalanced Sagnac interferometer. The Q-switched VOC laser generated a vortex output with 5.1 W average power, slope efficiency of 46% at 150 kHz pulse repetition rate, only marginally lower than the 5.4 W and 49% slope efficiency of the plane mirror laser. Vortex handedness was switchable with a single VOC control without loss of vortex power. In both handedness cases the vortex mode quality was assessed to be excellent by detailed analysis of vortex phase profile and propagation characteristics and comparison to an ideal vortex. The power scaling potential of the VOC was demonstrated in a higher power cavity, achieving a vortex output power of 14.3 W and a slope efficiency of 55%. Further investigation verified the ability for the VOC laser to self-mode-filter the intracavity mode, showing maintenance of high TEM00 quality even after introducing deliberate mode to pump size mismatch, when the equivalent plane mirror laser becomes multimode. This work highlights the potential of the VOC as a simple route to high powered structured light sources using just standard high-power handling mirror components and its self-mode-filtering property to compensate intra-cavity spatial mode degradation when power-scaling.
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Journal articleGeberbauer J, Kerridge-Johns WR, Damzen MJ, 2020,
Q-switched laser with self-mode-filtering interferometric vortex output coupler
, OSA Continuum, Vol: 3, Pages: 204-213, ISSN: 2578-7519Vortex lasers are an attractive prospect for efficient generation of high-quality beams in compact, environmentally robust, and turnkey systems. We demonstrate conversion of a Q-switched, diode-pumped Nd:YVO4, TEM00 Gaussian laser into a vortex laser source by replacing the output coupling mirror by a vortex output coupler (VOC) based on an imbalanced Sagnac interferometer. The Q-switched VOC laser generated a vortex output with 5.1 W average power, slope efficiency of 46% at 150 kHz pulse repetition rate, only marginally lower than the 5.4W and 49% slope efficiency of the plane mirror laser. Vortex handedness was switchable with a single VOC control without loss of vortex power. In both handedness cases, the vortex mode quality was assessed to be excellent by detailed analysis of the vortex phase profile and propagation characteristics and comparison to an ideal vortex. Further investigation verified the ability for the VOC laser to self-mode-filter the intracavity mode, showing maintenance of high TEM00 quality even after introducing deliberate mode to pump size mismatch, when the equivalent plane mirror laser becomes multimode. This work highlights the potential of the VOC as a simple route to high powered structured light sources using just standard high-power handling mirror components and its self-mode-filtering property to compensate intra-cavity spatial mode degradation when power-scaling.
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Journal articleLagarto JL, Nickdel MB, Kelly DJ, et al., 2020,
Autofluorescence lifetime reports cartilage damage in osteoarthritis
, Scientific Reports, Vol: 10, ISSN: 2045-2322Osteoarthritis (OA) is the most common arthritis and its hallmark is degradation of articular cartilage by proteolytic enzymes leading to loss of joint function. It is challenging to monitor the status of cartilage in vivo and this study explores the use of autofluorescence lifetime (AFL) measurements to provide a label-free optical readout of cartilage degradation that could enable earlier detection and evaluation of potential therapies. We previously reported that treatment of ex vivo porcine cartilage with proteolytic enzymes resulted in decreased AFL. Here we report changes in AFL of ex vivo mouse knee joints, porcine metacarpophalangeal joints, normal human metatarsophalangeal articular tissue and human OA tibial plateau tissues measured with or without treatment using a compact single-point time resolved spectrofluorometer. Our data show that proteolytically damaged areas in porcine metacarpophalangeal joints present a reduced AFL and that inducing aggrecanases in mouse and human joints also significantly reduces AFL. Further, human cartilage from OA patients presents a significantly lower AFL compared to normal human cartilage. Our data suggest that AFL can detect areas of cartilage erosion and may potentially be utilised as a minimally-invasive diagnostic readout for early stage OA in combination with arthroscopy devices.
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