231 results found
Coombes C, Angelou C, Al-Khalili Z, et al., 2024, Performance of a novel spectroscopy-based tool for adjuvant therapy decision-making in hormone receptor-positive breast cancer: a validation study., Breast Cancer Res Treat
PURPOSE: Digistain Index (DI), measured using an inexpensive mid-infrared spectrometer, reflects the level of aneuploidy in unstained tissue sections and correlates with tumor grade. We investigated whether incorporating DI with other clinicopathological variables could predict outcomes in patients with early breast cancer. METHODS: DI was calculated in 801 patients with hormone receptor-positive, HER2-negative primary breast cancer and ≤ 3 positive lymph nodes. All patients were treated with systemic endocrine therapy and no chemotherapy. Multivariable proportional hazards modeling was used to incorporate DI with clinicopathological variables to generate the Digistain Prognostic Score (DPS). DPS was assessed for prediction of 5- and 10-year outcomes (recurrence, recurrence-free survival [RFS] and overall survival [OS]) using receiver operating characteristics and Cox proportional hazards regression models. Kaplan-Meier analysis evaluated the ability of DPS to stratify risk. RESULTS: DPS was consistently highly accurate and had negative predictive values for all three outcomes, ranging from 0.96 to 0.99 at 5 years and 0.84 to 0.95 at 10 years. DPS demonstrated statistically significant prognostic ability with significant hazard ratios (95% CI) for low- versus high-risk classification for RFS, recurrence and OS (1.80 [CI 1.31-2.48], 1.83 [1.32-2.52] and 1.77 [1.28-2.43], respectively; all P < 0.001). CONCLUSION: DPS showed high accuracy and predictive performance, was able to stratify patients into low or high-risk, and considering its cost and rapidity, has the potential to offer clinical utility.
Hughes KM, Ito M, Vaquero-Stainer A, et al., 2024, Increasing the two-photon photocurrent saturation limit in a quantum ratchet intermediate band solar cell, Applied Physics Letters, Vol: 124, ISSN: 0003-6951
A quantum ratchet intermediate band solar cell based on a quantum well superlattice is investigated. The design is similar to that of a previously reported device, but it employs a stronger built-in electric field across the heterojunction; therefore, it works at higher illumination intensities before the photocurrent saturates due to photocarrier accumulation screening out the field and causing leveling of the bands. In this present device, saturation of the two-photon photocurrent occurred at a valence-to-intermediate band pulse energy of ∼4 nJ, approximately ten times greater than the previously reported device, making it more suitable for concentrator applications.
Ma Y, Gemmell N, Pearce E, et al., 2023, Eliminating thermal infrared background noise by imaging with undetected photons, Physical Review A: Atomic, Molecular and Optical Physics, Vol: 108, ISSN: 1050-2947
Spectroscopy and imaging in the mid-infrared (2.5µm∼λ∼25µm) is bedeviled by the presence of a strong 300-K thermal background at room temperature that makes infrared (IR) detectors decades noisier than can be readily achieved in the visible. The technique of imaging with undetected photons (IUP) exploits the quantum correlations between entangled photon pairs to transfer image information from one spectral region to another, and here we show that it does so in a way that is immune to the thermal background. This means that IUP can be used to perform high-speed photon-counting measurements across the mid-IR spectrum, using uncooled visible detectors that are many times cheaper, faster, and more sensitive than their IR counterparts.
Coombes C, Amrania H, Angelou C, et al., 2023, Validation of a novel and rapid reagent free assay to predict outcomes for adjuvant therapy decision making in hormone receptor-positive breast cancer., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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.
Gemmell NR, Florez J, Pearce E, et al., 2023, Loss-compensated and enhanced midinfrared interaction-free sensing with undetected photons, Physical Review Applied, Vol: 19, ISSN: 2331-7019
Sensing with undetected photons enables the measurement of absorption and phase shifts at wavelengths different from those detected. Here, we experimentally map the balance and loss parameter space in a nondegenerate nonlinear interferometer, showing the recovery of sensitivity despite internal losses at the detection wavelength. We further explore an interaction-free operation mode with a detector-to-sample incident optical power ratio of over 200. This allows changes in attowatt levels of power at 3.4μm wavelength to be detected at 1550 nm, immune to the level of thermal black-body background. This reveals an ultrasensitive infrared imaging methodology capable of probing samples effectively “in the dark.”
Hughes KMM, Ito M, Vaquero-Stainer A, et al., 2023, Room Temperature Operation of a Quantum Ratchet Intermediate Band Solar Cell, SOLAR RRL, Vol: 7, ISSN: 2367-198X
Pearce 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 . 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.
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, VIRCHOWS ARCHIV, Vol: 469, 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, Publisher: SPRINGER, 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.
Baker MJ, Goodacre R, Sammon C, et al., 2016, Single cell analysis/data handling: general discussion., Faraday Discuss, Vol: 187, Pages: 299-327
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.
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.
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