225 results found
Greaves G, Kiryushko D, Auner H, et al., 2023, Label-free nanoscale mapping of intracellular organelle chemistry, Communications Biology, Vol: 6, Pages: 1-7, ISSN: 2399-3642
The ability to image cell chemistry at the nanoscale is key for understanding cell biology, but many optical microscopies are restricted by the ~(200–250)nm diffraction limit. Electron microscopy and super-resolution fluorescence techniques beat this limit, but rely on staining and specialised labelling to generate image contrast. It is challenging, therefore, to obtain information about the functional chemistry of intracellular components. Here we demonstrate a technique for intracellular label-free chemical mapping with nanoscale (~30 nm) resolution. We use a probe-based optical microscope illuminated with a mid-infrared laser whose wavelengths excite vibrational modes of functional groups occurring within biological molecules. As a demonstration, we chemically map intracellular structures in human multiple myeloma cells and compare the morphologies with electron micrographs of the same cell line. We also demonstrate label-free mapping at wavelengths chosen to target the chemical signatures of proteins and nucleic acids, in a way that can be used to identify biochemical markers in the study of disease and pharmacology.
Hughes KMM, Ito M, Vaquero-Stainer A, et al., 2023, Room Temperature Operation of a Quantum Ratchet Intermediate Band Solar Cell, SOLAR RRL, ISSN: 2367-198X
Yang J, Dichtl P, Florez J, et al., 2022, Stimulated emission tomography analysis of plasmonic nanoantennas, Conference on Active Photonic Platforms held Part of SPIE Nanoscience and Engineering Conference, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
Pearce E, Phillips CC, Oulton RF, et al., 2020, Heralded spectroscopy with a fiber photon-pair source, Applied Physics Letters, Vol: 117, Pages: 1-6, ISSN: 0003-6951
The correlations between photons generated by nonlinear optical processes offer advantages for many quantum technology applications, including spectroscopy, imaging, and metrology. Here, we use spontaneous four-wave mixing in a birefringent single-mode fiber pumped by a tunable pulsed laser as a broadly tunable source of phase-matched non-degenerate photon pairs for spectroscopy. The pairs are tunable such that the idler beam measures the transmittance spectrum of a sample in the near infrared, while the visible signal beam independently reports correlation information. By the time-resolved counting of both signal and idler photons, we use photon-number correlations to remove uncorrelated noise from the probe beam. Here, we have used heralded spectroscopy to measure the absorption spectrum of gallium arsenide near its band edge, despite the idler photon spectrum being dominated by a large background from spontaneous Raman scattering.
Hart WS, Amrania H, Beckley A, et al., 2020, Label-Free Chemical Nano-Imaging of Intracellular Drug Binding Sites
Optical microscopy has a diffraction limited resolution of about 250 nm.Fluorescence methods (e.g. PALM, STORM, STED) beat this, but they are stilllimited to 10 s of nm, and the images are an indirect pointillistrepresentation of only part of the original object. Here we describe a way ofcombining a sample preparation technique taken from histopathology, with aprobe-based nano-imaging technique, (s SNOM) from the world of Solid StatePhysics. This allows us to image subcellular structures optically, and at ananoscale resolution that is about 100 x better than normal microscopes. Byadding a tuneable laser source, we also demonstrate mid-infrared chemicalnano-imaging (MICHNI) in human myeloma cells and we use it to map the bindingsites of the anti cancer drug bortezomib to less than 10 zL sized intracellularcomponents. MICHNI is label free and can be used with any biological materialand drugs with specific functional chemistry. We believe that its combinationof speed, cheapness, simplicity, safety and chemical contrast promises atransformative impact across the life sciences.
Phillips CC, 2019, Thermal artefacts in two-photon solar cell experiments, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723
Hart WS, Panchal V, Melios C, et al., 2019, Highly resonant graphene plasmon hotspots in complex nanoresonator geometries, 2D Materials, Vol: 6, ISSN: 2053-1583
Van der Waals surface polariton nanostructures are promising candidates for miniaturisation of electromagnetic devices through the nanoscale confinement of infrared light. To fully exploit these nanoresonators, a computationally efficient model is necessary to predict polariton behaviour in complex geometries. Here, we develop a general wave model of surface polaritons in 2D geometries smaller than the polariton wavelength. Using geometric approximation widely tuneable infrared nanoimaging and local work function microscopy, we test this model against complex mono-/bi-layer graphene plasmon nanoresonators. Direct imaging of highly resonant graphene plasmon hotspots confirms that the model provides quantitatively accurate, analytical predictions of nanoresonator behaviour. The insights built with such models are crucial to the development of practical plasmonic nanodevices.
Amrania H, Woodley-Barker L, Goddard K, et al., 2018, Mid-infrared imaging in breast cancer tissue: an objective measure of grading breast cancer biopsies, Convergent Science Physicsl Oncology, Vol: 4, ISSN: 2057-1739
Introduction: -The majority of cancers are diagnosedusingexcised biopsy specimens. These are graded, using a gold-standard histopathology protocol based onhaemotoxylin and eosin (“H+E”)chemical staining. Howeverthe grading is done by eye and if the same biopsy is graded by differentpractitioners, they typically only agree ~70% of the time. The resultingovertreatment problem constitutes a massive unmet need worldwide.Objective:-Ournew ‘Digistain’technology, uses mid-infrared imaging to mapthe fractional concentration of nucleic acids, i.e. the nuclear-to-cytoplasmic chemical ratio (NCR) across an unstained biopsy section. It allows a quantitative “Digistain index” (DI) score, corresponding to the NCR, to be reproducibly extracted from an objective physical measurement of a cancer. Our objective here is to evaluate itspotential for aiding cancer diagnosis for the first time. We correlate the DI scores with H+E grades in a double-blind clinical pilot trial.Methods:-Two adjacent slices were taken from 75 breast cancer FFPE blocks; one was graded with the standard H+E protocol, and also used to define a “Region of Interest” (RoI). Digistain was then used to acquire a DI value averaged over the corresponding RoI on the other (unstained) sliceand theresults werestatistically analysed.Results:-We find the DI score correlates significantly (p=0.0007) with tumorgradein a way that promises to significantly reduce the inherent subjectivity and variability in biopsy grading.Discussion: The NCR is elevated by increased mitotic activity because cells divide when they are youngerand, on average, becomesmaller asthe disease progresses. Also, extra DNA and RNA is generated as thenuclear transcription machinery goes awry and nuclear pleomorphism occurs. Both effects make the NCR a recognized biomarker for a wide range of tumors
Vaquero-Stainer A, Yoshida M, Hylton NP, et al., 2018, Semiconductor nanostructure quantum ratchet for high efficiency solar cells, Communications Physics, Vol: 1, ISSN: 2399-3650
Conventional solar cell efficiencies are capped by the ~31% Shockley–Queisser limit because, even with an optimally chosen bandgap, some red photons will go unabsorbed and the excess energy of the blue photons is wasted as heat. Here we demonstrate a “quantum ratchet” device that avoids this limitation by inserting a pair of linked states that form a metastable photoelectron trap in the bandgap. It is designed both to reduce non-radiative recombination, and to break the Shockley–Queisser limit by introducing an additional “sequential two photon absorption” (STPA) excitation channel across the bandgap. We realise the quantum ratchet concept with a semiconductor nanostructure. It raises the electron lifetime in the metastable trap by ~104, and gives a STPA channel that increases the photocurrent by a factor of ~50%. This result illustrates a new paradigm for designing ultra-efficient photovoltaic devices.
Hart WS, Bak AO, Phillips CC, 2018, Ultra low-loss super-resolution with extremely anisotropic semiconductor metamaterials, AIP Advances, Vol: 8, ISSN: 2158-3226
We investigate the mechanisms for the reduction of losses in doped semiconductormultilayers used for the construction of uniaxial metamaterials and show that maxi-mizing the mean scattering time of the doped layers is key to spectrally isolating lossesand maximizing anisotropy. By adjusting the layer thickness ratio of the multilayer,we show that the spectral regions of extreme anisotropy can be separated from thoseof high loss. Using these insights and coupled with realistic semiconductor growthparameters, we demonstrate an InAs-based superlens with an excellent loss factorα≈52mm-1and maximum perpendicular permittivity,ε⊥>250. By tuning the dopingconcentration, we show that such a system can be designed to operate anywhere in theregionλ0≈5 to 25μm. We find that such a structure is capable of deep sub-wavelengthimaging (< λ0/15) at superlens thicknesses up to∼85μm (∼8λ0).
Pusch A, Yoshida M, Hylton NP, et al., 2017, The purpose of a photon ratchet in intermediate band solar cells, Pages: 2536-2537
The intermediate band solar cell (IBSC) concept aims to improve upon the Shockley-Queisser limit for single bandgap solar cells by also making use of below bandgap photons through sequential absorption processes via an intermediate band (IB). In order for this concept to be translated into more efficient solar cells there are still challenges to overcome; one of the most important is the increased recombination (radiative as well as non-radiative) associated with the additional states in the bandgap. A proposal to mitigate those recombination losses is the introduction of a photon ratchet into the IBSC, which effectively trades some of the energy of the excited electrons against these recombination losses. We show here that this can lead to substantial improvements even in the radiative limiting efficiency, where no non-radiative recombination is taken into account and that this advantage is especially prominent for IBSCs in which the transitions into and out of the IB are not very absorptive, a case commonly encountered for current IBSC proposals.
Amrania H, Phillips C, Shousha S, et al., 2016, Digistain: A novel biomarker imaging platform for grading breast DCIS using routinely processed paraffin sections, Publisher: SPRINGER, Pages: S64-S65, ISSN: 0945-6317
Amrania H, Phillips C, Shousha S, et al., 2016, Digistain: A novel biomarker imaging platform for grading breast DCIS using routinely processed paraffin sections, VIRCHOWS ARCHIV, Vol: 469, Pages: S64-S65, ISSN: 0945-6317
Goodacre R, Baker MJ, Graham D, et al., 2016, Biofluids and other techniques: general discussion., Faraday Discuss, Vol: 187, Pages: 575-601
Hylton N, Hinrichsen TF, Vaquero-Stainer AR, et al., 2016, Photoluminescence upconversion at GaAs/InGaP2 interfaces driven by a sequential two-photon absorption mechanism, Physical Review B, Vol: 93, ISSN: 2469-9950
This paper reports on the results of an investigation into the nature of photoluminescence upconversion at GaAs/InGaP2 interfaces. Using a dual-beam excitation experiment, we demonstrate that the upconversion in our sample proceeds via a sequential two-photon optical absorption mechanism. Measurements of photoluminescence and upconversion photoluminescence revealed evidence of the spatial localization of carriers in the InGaP2 material, arising from partial ordering of the InGaP2. We also observed the excitation of a two-dimensional electron gas at the GaAs/InGaP2 heterojunction that manifests as a high-energy shoulder in the GaAs photoluminescence spectrum. Furthermore, the results of upconversion photoluminescence excitation spectroscopy demonstrate that the photon energy onset of upconversion luminescence coincides with the energy of the two-dimensional electron gas at the GaAs/InGaP2 interface, suggesting that charge accumulation at the interface can play a crucial role in the upconversion process.
Amrania H, Drummond L, Coombes RC, et al., 2016, New IR imaging modalities for cancer detection and for intra-cell chemical mapping with a sub-diffraction mid-IR s-SNOM, Faraday Discussions, Vol: 187, Pages: 539-553, ISSN: 1364-5498
We present two new modalities for generating chemical maps. Both are mid-IR based and aimed at the biomedical community, but they differ substantially in their technological readiness. The first, so-called "Digistain", is a technologically mature "locked down" way of acquiring diffraction-limited chemical images of human cancer biopsy tissue. Although it is less flexible than conventional methods of acquiring IR images, this is an intentional, and key, design feature. It allows it to be used, on a routine basis, by clinical personnel themselves. It is in the process of a full clinical evaluation and the philosophy behind the approach is discussed. The second modality is a very new, probe-based "s-SNOM", which we are developing in conjunction with a new family of tunable "Quantum Cascade Laser" (QCL) diode lasers. Although in its infancy, this instrument can already deliver ultra-detailed chemical images whose spatial resolutions beat the normal diffraction limit by a factor of ∼1000. This is easily enough to generate chemical maps of the insides of single cells for the first time, and a range of new possible scientific applications are explored.
Baker MJ, Goodacre R, Sammon C, et al., 2016, Single cell analysis/data handling: general discussion., Faraday Discuss, Vol: 187, Pages: 299-327
Pusch A, Yoshida M, Hylton NP, et al., 2016, Limiting efficiencies for intermediate band solar cells with partial absorptivity: the case for a quantum ratchet, Progress in Photovoltaics, Vol: 24, Pages: 656-662, ISSN: 1099-159X
The intermediate band solar cell (IBSC) concept aims to improve upon the Shockley–Queisser limit for single bandgap solar cells by also making use of below bandgap photons through sequential absorption processes via an intermediate band (IB). Current proposals for IBSCs suffer from low absorptivity values for transitions into and out of the IB. We therefore devise and evaluate a general, implementation‐independent thermodynamic model for an absorptivity‐constrained limiting efficiency of an IBSC to study the impact of absorptivity limitations on IBSCs. We find that, due to radiative recombination via the IB, conventional IBSCs cannot surpass the Shockley–Queisser limit at an illumination of one Sun unless the absorptivity from the valence band to the IB and the IB to the conduction band exceeds ≈36%. In contrast, the introduction of a quantum ratchet into the IBSC to suppress radiative recombination can enhance the efficiency of an IBSC beyond the Shockley–Queisser limit for any value of the IB absorptivity. Thus, the quantum ratchet could be the vital next step to engineer IBSCs that are more efficient than conventional single‐gap solar cells.
Curtin OJ, Yoshida M, Pusch A, et al., 2016, Quantum cascade photon ratchets for intermediate band solar cells, IEEE Journal of Photovoltaics, Vol: 6, Pages: 673-678, ISSN: 2156-3381
We propose an antimonide-based quantum cascade design to demonstrate the ratchet mechanism for incorporation into the recently suggested photon ratchet intermediate-band solar cell. We realize the photon ratchet as a semiconductor heterostructure in which electrons are optically excited into an intermediate band and spatially decoupled from the valence band through a type-II quantum cascade. This process reduces both radiative and nonradiative recombination and can thereby increase the solar cell efficiency over intermediate-band solar cells. Our design method uses an adaptive simulated annealing genetic algorithm to determine the optimum thicknesses of semiconductor layers in the quantum cascade, allowing efficient transport (via phonon emission) of the electrons away from the interband active region.
Bak AO, Yoxall EO, Sarriugarte P, et al., 2016, Harnessing a Quantum Design Approach for Making Low-Loss Superlenses, NANO LETTERS, Vol: 16, Pages: 1609-1613, ISSN: 1530-6984
Pusch A, Yoshida M, Hylton NP, et al., 2016, The Purpose of a Photon Ratchet in Intermediate Band Solar Cells, 43rd IEEE Photovoltaic Specialists Conference (PVSC), Publisher: IEEE, Pages: 9-12, ISSN: 0160-8371
Pusch A, Oh S, Wuestner S, et al., 2015, A highly efficient CMOS nanoplasmonic crystal enhanced slow-wave thermal emitter improves infrared gas-sensing devices, Scientific Reports, Vol: 5, ISSN: 2045-2322
The application of plasmonics to thermal emitters is generally assisted by absorptive losses in the metal because Kirchhoff’s law prescribes that only good absorbers make good thermal emitters. Based on a designed plasmonic crystal and exploiting a slow-wave lattice resonance and spontaneous thermal plasmon emission, we engineer a tungsten-based thermal emitter, fabricated in an industrial CMOS process, and demonstrate its markedly improved practical use in a prototype non-dispersive infrared (NDIR) gas-sensing device. We show that the emission intensity of the thermal emitter at the CO2 absorption wavelength is enhanced almost 4-fold compared to a standard non-plasmonic emitter, which enables a proportionate increase in the signal-to-noise ratio of the CO2 gas sensor.
Amrania H, Shousha S, Woodley L, et al., 2015, Digistain: A novel biomarker imaging platform for grading breast carcinoma using routinely processed paraffin sections, Publisher: SPRINGER, Pages: S13-S13, ISSN: 0945-6317
Amrania H, Shousha S, Woodley L, et al., 2015, Digistain: a novel biomarker imaging platform for grading breast carcinoma using routinely processed paraffin sections, 27th European Congress of Pathology (ECP 2015), Publisher: Springer Verlag, Pages: S13-S13, ISSN: 0945-6317
Objective: Digistain is a new technology platform that enables imagingand quantification of a newly conceived biomarker for grading breastcarcinoma in routinely processed, unstained paraffin sections withoutthe use of traditional stains or contrasting agents. By recording a uniqueoptical signature to analyze the chemical make-up of a biopsy quantitatively, the technique is unaffected by the subjectivity of traditional grading. Within minutes of loading a slide it yields a highly reproducible and user independent numerical score reflecting the cellularity of the tumour and its nuclear: cytoplasmic ratio. We report here our findings using an objective technique to grade breast tumours using quantitative criteria.Method: H&E stained sections from excision biopsies of 105 cases ofinvasive breast carcinoma were reviewed and graded using the ElstonEllisgrading system. Unstained sections from each case were loaded intothe Digistain platform to yield a numerical score - the Digistain Index(DI).Results: The cases were grouped according to histological grading. MeanDIs was calculated for each grade (1,2 and 3) to be 0.56, 0.61, and 0.68respectively with a maximum standard error of 0.02. The DI spread withineach grade was less than that across the three grades, thus validatingthis index as a viable grading indicator within the context of this study.Conclusion: We believe the new Digistain approach provides for the firsttime a cost effective and quantitative measure of tumour grade. This canbe developed to deliver an effective assessment of prognosis and recurrence risk beyond traditional qualitative measures based on H&E staining protocols.
Okada Y, Ekins-Daukes NJ, Kita T, et al., 2015, Intermediate band solar cells: Recent progress and future directions, Applied Physics Reviews, Vol: 2, ISSN: 1931-9401
Murphy FJ, Arbabzadah EA, Bak AO, et al., 2015, Optical chopper Q-switching for flashlamp-pumped Er,Cr:YSGG lasers, Laser Physics Letters, Vol: 12, ISSN: 1612-202X
Amrania H, Drummond L, Woodley L, et al., 2014, Digistain: A new objective method for grading breast carcinoma using routinely processed paraffin sections, VIRCHOWS ARCHIV, Vol: 465, Pages: S91-S92, ISSN: 0945-6317
Shammah N, Phillips CC, De Liberato S, 2014, Terahertz emission from asymmetric, doped quantum wells under resonant pumping, 6th International Conference on Optical, Optoelectronic and Photonic Materials and Applications (ICOOPMA), Publisher: IOP Publishing, ISSN: 1742-6588
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