Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

Rapid single-photon color imaging of moving objects.

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

Miniaturized spectroscopy with tunable and sensitive plasmonic structures.

A broad linewidth and a lack of spectral analysis limit the applications of plasmonic sensors. In this Letter, a plasmonic sensor with a large sensitivity in the terahertz (THz) range is proposed based on high-quality factor (>1000) surface lattice resonance in subwavelength near-flat metallic gratings. Moreover, such a highly selective spectral manipulating scheme, plus the greatly localized plasmonic resonance, enables miniaturized spectroscopy based on a single detector by integrating an electro-optical material with the gratings. A spectral resolution of 0.1 GHz at a center frequency of 1.1 THz is predicted showing a four times improvement of measuring efficiency. This technique shows promising potential in on-site matter inspection and point-of-care testing.

Alignment-insensitive bilayer THz metasurface absorbers exceeding 100% bandwidth.

Metamaterial absorbers have been a topic of considerable interest in recent years, with a particular focus on Terahertz (THz) frequencies due to many natural materials having a weak interaction with THz light. Great efforts have aimed to expand such THz absorbers to cover a wide bandwidth whilst also being highly efficient. However, many of these require cascaded or stacked multilayer resonant elements, where even a small deviation in the alignment between layers is extremely detrimental to the performance. Here, we propose a bilayer metasurface absorber (thickness ∼ λ/6) that is immune to such layer misalignments capable of exceeding a fractional bandwidth (FWHM) of 100% of the central frequency. The design works due to a novel absorption mechanism based on Salisbury Screen and anti-reflection absorption mechanisms, using fractal cross absorbers to expand the bandwidth. Our work is of particular benefit to developing devices which require ultra-wide bandwidth, such as bolometric sensing and planar blackbody absorbers, with the extremely robust absorption responses being unaffected by any misalignments between layers - a limiting factor of previous absorbers.

Reoperation following lumbar spinal surgery: costs and outcomes in a UK population cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES).

PURPOSE: To assess the likelihood of persistent postoperative pain (PPP) following reoperation after lumbar surgery and to estimate associated healthcare costs. METHODS: This is a retrospective cohort study using two linked UK databases: Hospital Episode Statistics and UK Clinical Practice Research Datalink. Costs and outcomes associated with reoperation were evaluated over a 2-year postoperative period using multivariate logistic regression for cases who underwent reoperation and controls who did not, based on demographics, index surgery type, smoking status, and pre-index comorbidities using propensity score matching. RESULTS: Risk factors associated with reoperation included younger age and the presence of diabetes with complications or rheumatic disease. The rate of PPP after reoperation was much higher than after index surgery, with 79 of 200 (39.5%; 95% CI 32.5%, 46.5%) participants experiencing ongoing pain compared with 983 of 5022 (19.5%; 95% CI 18.5%, 20.7%) after index surgery. Mean costs in the 2 years following reoperation were £1889 higher (95% CI £2, £3809) than for patients with PPP who did not undergo repeat surgery over an equivalent follow-up period. With the cost of reoperation itself included, the mean cost difference for patients who underwent reoperation compared with matched controls rose to £7221 (95% CI £5273, £9206). CONCLUSIONS: High rates of PPP and associated healthcare costs suggest that returning to the operating room is a complex and challenging decision. Spinal surgeons should review whether the potential benefits of additional surgery are justified when other approaches to managing and relieving chronic pain have demonstrated superior outcomes. These slides can be retrieved under Electronic Supplementary Material.

Towards Portable Nanophotonic Sensors.

A range of nanophotonic sensors composed of different materials and device configurations have been developed over the past two decades. These sensors have achieved high performance in terms of sensitivity and detection limit. The size of onchip nanophotonic sensors is also small and they are regarded as a strong candidate to provide the next generation sensors for a range of applications including chemical and biosensing for point-of-care diagnostics. However, the apparatus used to perform measurements of nanophotonic sensor chips is bulky, expensive and requires experts to operate them. Thus, although integrated nanophotonic sensors have shown high performance and are compact themselves their practical applications are limited by the lack of a compact readout system required for their measurements. To achieve the aim of using nanophotonic sensors in daily life it is important to develop nanophotonic sensors which are not only themselves small, but their readout system is also portable, compact and easy to operate. Recognizing the need to develop compact readout systems for onchip nanophotonic sensors, different groups around the globe have started to put efforts in this direction. This review article discusses different works carried out to develop integrated nanophotonic sensors with compact readout systems, which are divided into two categories; onchip nanophotonic sensors with monolithically integrated readout and onchip nanophotonic sensors with separate but compact readout systems.

CMOS compatible metamaterial absorbers for hyperspectral medium wave infrared imaging and sensing applications.

We experimentally demonstrate a CMOS compatible medium wave infrared metal-insulator-metal (MIM) metamaterial absorber structure where for a single dielectric spacer thickness at least 93% absorption is attained for 10 separate bands centred at 3.08, 3.30, 3.53, 3.78, 4.14, 4.40, 4.72, 4.94, 5.33, 5.60 µm. Previous hyperspectral MIM metamaterial absorber designs required that the thickness of the dielectric spacer layer be adjusted in order to attain selective unity absorption across the band of interest thereby increasing complexity and cost. We show that the absorption characteristics of the hyperspectral metamaterial structures are polarization insensitive and invariant for oblique incident angles up to 25° making them suitable for practical implementation in an imaging system. Finally, we also reveal that under TM illumination and at certain oblique incident angles there is an extremely narrowband Fano resonance (Q > 50) between the MIM absorber mode and the surface plasmon polariton mode that could have applications in hazardous/toxic gas identification and biosensing.

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy.

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work.

Nanophotonic Image Sensors.

The increasing miniaturization and resolution of image sensors bring challenges to conventional optical elements such as spectral filters and polarizers, the properties of which are determined mainly by the materials used, including dye polymers. Recent developments in spectral filtering and optical manipulating techniques based on nanophotonics have opened up the possibility of an alternative method to control light spectrally and spatially. By integrating these technologies into image sensors, it will become possible to achieve high compactness, improved process compatibility, robust stability and tunable functionality. In this Review, recent representative achievements on nanophotonic image sensors are presented and analyzed including image sensors with nanophotonic color filters and polarizers, metamaterial-based THz image sensors, filter-free nanowire image sensors and nanostructured-based multispectral image sensors. This novel combination of cutting edge photonics research and well-developed commercial products may not only lead to an important application of nanophotonics but also offer great potential for next generation image sensors beyond Moore's Law expectations.

Multi-spectral materials: hybridisation of optical plasmonic filters, a mid infrared metamaterial absorber and a terahertz metamaterial absorber.

Multi-spectral imaging systems typically require the cumbersome integration of disparate filtering materials and detectors in order to operate simultaneously in multiple spectral regions. Each distinct waveband must be detected at different spatial locations on a single chip or by separate chips optimised for each band. Here, we report on a single component that optically multiplexes visible, Mid Infrared (4.5 µm) and Terahertz (126 µm) radiation thereby maximising the spectral information density. We hybridise plasmonic and metamaterial structures to form a device capable of simultaneously filtering 15 visible wavelengths and absorbing Mid Infrared and Terahertz. Our synthetic multi-spectral component could be integrated with silicon complementary metal-oxide semiconductor technology where Si photodiodes are available to detect the visible radiation and micro-bolometers available to detect the Infrared/Terahertz and render an inexpensive, mass-producible camera capable of forming coaxial visible, Infrared and Terahertz images.

Uncooled CMOS terahertz imager using a metamaterial absorber and pn diode.

We demonstrate a low-cost uncooled terahertz (THz) imager fabricated in a standard 180 nm CMOS process. The imager is composed of a broadband THz metamaterial absorber coupled with a diode microbolometer sensor where the pn junction is used as a temperature sensitive device. The metamaterial absorber array is integrated in the top metallic layers of a six metal layer process allowing for complete monolithic integration of the metamaterial absorber and sensor. We demonstrate the capability of the detector for stand-off imaging applications by using it to form transmission and reflection images of a metallic object hidden in a manila envelope.

Optimizing the management of patients with spinal myeloma disease.

Myeloma is one of the most common malignancies that results in osteolytic lesions of the spine. Complications, including pathological fractures of the vertebrae and spinal cord compression, may cause severe pain, deformity and neurological sequelae. They may also have significant consequences for quality of life and prognosis for patients. For patients with known or newly diagnosed myeloma presenting with persistent back or radicular pain/weakness, early diagnosis of spinal myeloma disease is therefore essential to treat and prevent further deterioration. Magnetic resonance imaging is the initial imaging modality of choice for the evaluation of spinal disease. Treatment of the underlying malignancy with systemic chemotherapy together with supportive bisphosphonate treatment reduces further vertebral damage. Additional interventions such as cement augmentation, radiotherapy, or surgery are often necessary to prevent, treat and control spinal complications. However, optimal management is dependent on the individual nature of the spinal involvement and requires careful assessment and appropriate intervention throughout. This article reviews the treatment and management options for spinal myeloma disease and highlights the value of defined pathways to enable the proper management of patients affected by it.

Understanding protected area resilience: a multi-scale, social-ecological approach.

Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic.

A Nipkow disk integrated with Fresnel lenses for terahertz single pixel imaging.

We present a novel Nipkow disk design for terahertz (THz) single pixel imaging applications. A 100 mm high resistivity (ρ≈3k-10k Ω·cm) silicon wafer was used for the disk on which a spiral array of twelve 16-level binary Fresnel lenses were fabricated using photolithography and a dry-etch process. The implementation of Fresnel lenses on the Nipkow disk increases the THz signal transmission compared to the conventional pinhole-based Nipkow disk by more than 12 times thus a THz source with lower power or a THz detector with lower detectivity can be used. Due to the focusing capability of the lenses, a pixel resolution better than 0.5 mm is in principle achievable. To demonstrate the concept, a single pixel imaging system operating at 2.52 THz is described.

Hybridization of optical plasmonics with terahertz metamaterials to create multi-spectral filters.

Multi-spectral imaging systems typically require the cumbersome integration of disparate filtering materials in order to work simultaneously in multiple spectral regions. We show for the first time how a single nano-patterned metal film can be used to filter multi-spectral content from the visible, near infrared and terahertz bands by hybridizing plasmonics and metamaterials. Plasmonic structures are well-suited to the visible band owing to the resonant dielectric properties of metals, whereas metamaterials are preferable at terahertz frequencies where metal conductivity is high. We present the simulated and experimental characteristics of our new hybrid synthetic multi-spectral material filters and demonstrate the independence of the metamaterial and plasmonic responses with respect to each other.

On-chip ultrasensitive and rapid hydrogen sensing based on plasmon-induced hot electron-molecule interaction.

Hydrogen energy is a zero-carbon replacement for fossil fuels. However, hydrogen is highly flammable and explosive hence timely sensitive leak detection is crucial. Existing optical sensing techniques rely on complex instruments, while electrical sensing techniques usually operate at high temperatures and biasing condition. In this paper an on-chip plasmonic-catalytic hydrogen sensing concept with a concentration detection limit down to 1 ppm is presented that is based on a metal-insulator-semiconductor (MIS) nanojunction operating at room temperature and zero bias. The sensing signal of the device was enhanced by three orders of magnitude at a one-order of magnitude higher response speed compared to alternative non-plasmonic devices. The excellent performance is attributed to the hydrogen induced interfacial dipole charge layer and the associated plasmonic hot electron modulated photoelectric response. Excellent agreements were achieved between experiment and theoretical calculations based on a quantum tunneling model. Such an on-chip combination of plasmonic optics, photoelectric detection and photocatalysis offers promising strategies for next-generation optical gas sensors that require high sensitivity, low time delay, low cost, high portability and flexibility.

Terahertz single pixel imaging based on a Nipkow disk.

We describe a terahertz single pixel imaging system based on a Nipkow disk. Nipkow disks have been used for fast scanning imaging systems since the first experimental television was invented in 1926. In our work, a Nipkow disk with 24 scanning lines was used to provide an axial resolution of 2 mm/pixel. We also show that by implementing a microscanning technique the axial resolution can be further improved to 0.5 mm/pixel. Imaging of several objects was demonstrated to show that this simple scanning system is promising for fast or real time terahertz imaging applications.

Factor VIII companion diagnostic for haemophilia.

Haemophilia is predominantly an inherited disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. The condition of this disease is complex to manage, but many patients do so through home therapy and often only see their core multidisciplinary healthcare team annually. There is an increasing need for patients to be able to monitor their condition efficiently at home while staying connected with their healthcare team. As a consequence, a low-cost handheld self-monitoring solution for clotting factor is required. Here we have demonstrated a suitable one-step Factor VIII companion diagnostic sensing approach based on a chromogenic assay for haemophilia A. The results show comparable performance to the gold standard method. Our approach is able to deliver accurate cost-effective results in under 5 min from undiluted human plasma. It has the potential to be able to reduce the human and monetary costs of over- or under-medication for haemophiliacs.

Cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge versus iliac crest bone graft for lumbar degenerative disc disease in the United Kingdom.

AIMS: To develop a model to evaluate the cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge (ACS) versus iliac crest bone graft (ICBG) in patients with lumbar degenerative disc disease in the United Kingdom. MATERIALS & METHODS: A Markov decision-analytic model was constructed to calculate costs and quality-adjusted life-years over a 4-year time horizon in each treatment group, from a United Kingdom National Health Service perspective. An individual patient data meta-analysis was undertaken to synthesize data from four randomized controlled trials and two single-arm studies concerning health-related quality of life and procedural resource use. Current cost data from the United Kingdom were then applied to determine the overall mean cost per patient in each group. One-way and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty. RESULTS: The model predicted 4-year discounted cost savings of £192 per patient treated with dibotermin alfa/ACS, compared with ICBG, and a gain of 0.0114 QALYs per patient over the same time period. Sensitivity analyses indicated that the results were most sensitive to variability in the differences in health-related quality of life and secondary surgery rate, with dibotermin alfa/ACS having a 60% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained. LIMITATIONS: There is uncertainty in the difference in cost and QALYs between the two groups. However, comprehensive sensitivity analyses were undertaken to explore this and present the results in a transparent manner. CONCLUSIONS: Our results provide an economic case for the use of 4 mg dibotermin alfa/ACS versus iliac crest bone graft, with additional health benefits predicted at reduced overall cost.

An All-Dielectric Metasurface Polarimeter.

The polarization state of light is a key parameter in many imaging systems. For example, it can image mechanical stress and other physical properties that are not seen with conventional imaging and can also play a central role in quantum sensing. However, polarization is more difficult to image, and polarimetry typically involves several independent measurements with moving parts in the measurement device. Metasurfaces with interleaved designs have demonstrated sensitivity to either linear or circular/elliptical polarization states. Here, we present an all-dielectric meta-polarimeter for direct measurement of any arbitrary polarization state from a single-unit-cell design. By engineering a completely asymmetric design, we obtained a metasurface that can excite eigenmodes of the nanoresonators, thus displaying a unique diffraction pattern for not only any linear polarization state but all elliptical polarization states (and handedness) as well. The unique diffraction patterns are quantified into Stokes parameters with a resolution of 5° and with a polarization state fidelity of up to 99 ± 1%. This holds promise for applications in polarization imaging and quantum state tomography.