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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.

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., (© 2023. The Author(s).)

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.

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., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Annese, Giagkoulovits, Barrett and Cumming.)

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.

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.

Background: To date, the process of adaptation in the setting of aesthetic medicine has not been investigated. The combination of complex advanced feedback in the current intense social media milieu, in conjunction with easily accessible and effective aesthetic treatments, has produced pockets of overtreated patients and over-zealous practitioners. We examine whether aesthetic assessments of attractiveness and what appears natural can be distorted by the cognitive process of adaptation., Methods: Forty-eight female participants were exposed to photographs of female faces in whom lip fullness had been strongly under- or over-exaggerated, while remaining within the bounds of natural appearing lips. Before and after evaluation of the exaggerated images, participants were asked to rate an alternative set of faces in terms of attractiveness (reflecting direct assessment of effective beauty impression) and naturalness (reflecting indirect assessment of beauty norms). The evaluation set consisted of six base faces that had been digitally altered to create a systematically varying 11 step set of lip sizes from extremely thin, to the original version, to very full., Results: Second-order polynomial fits indicated clear shifts of the subjects' facial aesthetic assessments towards the specific lip fullness of the adaptors. In contrast, such adaptions were not found for ratings of face naturalness. In contrast to research demonstrating mathematical foundations and unchanging rules governing perceptions of beauty, we show that simple viewing of exaggerated feature morphologies can rapidly result in recalibration of a person's assessment of attractiveness., Conclusion: This paper provides evidence that facial attractiveness is fluid, and that there are psychological mechanisms that cause an aesthetic bias. Over-exposure to exaggerated features can lead to significant changes to a person's ideas of attractiveness., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Goldie et al.)

Pixel scaling effects have been a major issue in the development of high-resolution color image sensors due to the reduced photoelectric signal and color crosstalk. Various structural color techniques have been proposed, and the large freedom in color manipulation by the structure design has been demonstrated. However, the optical efficiency and color distortion limit the practical applications due to their intrinsic filtering mechanism. Instead, the on-chip full-color routing is quite desirable for improving the signal-to-noise ratio. In this study, a single-layer quick response code-like nanorouter is proposed for the full-color light routing in a pixel level of image sensors. It shows much higher routing efficiency than various planar lens schemes for signal wavelength focusing. Moreover, over 60% signal enhancement with robust polarization insensitivity is obtained in all three primary color bands with the same nanorouter by a multi-objective optimization method. Negligible color distortion is observed from the reconstructed color image. Such a simple nanorouter scheme is promising for the development of image sensors, photovoltaics and displays.

We present the first realisation of simultaneous multi-spectral fluorescence imaging using a single-photon avalanche diode (SPAD) array, where the spectral unmixing is facilitated by a plasmonic metasurface mosaic colour filter array (CFA). A 64 × 64 pixel format silicon SPAD array is used to record widefield fluorescence and brightfield data from four biological samples. A plasmonic metasurface composed of an arrangement of circular and elliptical nanoholes etched into an aluminium thin film deposited on a glass substrate provides the high transmission efficiency CFA, enabling a bespoke spectral unmixing algorithm to reconstruct high fidelity, full colour images from as few as ∼3 photons per pixel. This approach points the way toward real-time, single-photon sensitive multi-spectral fluorescence imaging. Furthermore, this is possible without additional bulky components such as a filter wheel, prism or diffraction grating, nor the need for multiple sample exposures or multiple detectors., (© 2021 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using l-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Objective: Early stage diagnosis of sepsis without overburdening health services is essential to improving patient outcomes., Methods: A fast and simple-to-use platform that combines an integrated circuit with paper microfluidics for simultaneous detection of multiple-metabolites appropriate for diagnostics was presented. Paper based sensors are a primary candidate for widespread deployment of diagnostic or test devices. However, the majority of devices today use a simple paper strip to detect a single marker using the reflectance of light. However, for many diseases such as sepsis, one biomarker is not sufficient to make a unique diagnosis. In this work multiple measurements are made on patterned paper simultaneously. Using laser ablation to fabricate microfluidic channels on paper provides a flexible and direct approach for mass manufacture of disposable paper strips. A reusable photodiode array on a complementary metal oxide semiconductor chip is used as the transducer., Results: The system measures changes in optical absorbance in the paper to achieve a cost-effective and easily implemented system that is capable of multiple simultaneous assays. Potential sepsis metabolite biomarkers glucose and lactate have been studied and quantified with the platform, achieving sensitivity within the physiological range in human serum., Conclusion: We have detailed a disposable paper-based CMOS photodiode sensor platform for real-time simultaneous detection of metabolites for diseases such as sepsis., Significance: A combination of a low-cost paper strip with microfluidic channels and a sensitive CMOS photodiode sensor array makes our platform a robust portable and inexpensive biosensing device for multiple diagnostic tests in many different applications.

Purpose: To compare rates of persistent postoperative pain (PPP) after lumbar spine surgery-commonly known as Failed Back Surgery Syndrome-and healthcare costs for instrumented lumbar spinal fusion versus decompression/discectomy., Methods: The UK population-based healthcare data from the Hospital Episode Statistics (HES) database from NHS Digital and the Clinical Practice Research Datalink (CPRD) were queried to identify patients with PPP following lumbar spinal surgery. Rates of PPP were calculated by type of surgery (instrumented and non-instrumented). Total healthcare costs associated with the surgery and covering the 24-month period after index hospital discharge were estimated using standard methods for classifying health care encounters into major categories of health care resource utilization (i.e., inpatient hospital stays, outpatient clinic visits, accident and emergency attendances, primary care encounters, and medications prescribed in primary care) and applying the appropriate unit costs (expressed in 2013 GBP)., Results: Increasing the complexity of surgery with instrumentation was not associated with an increased rate of PPP. However, 2-year healthcare costs following discharge after surgery are significantly higher among patients who underwent instrumented surgery compared with decompression/discectomy., Conclusions: Although there is a not insubstantial risk of ongoing pain following spine surgery, with 1-in-5 patients experiencing PPP within 2 years of surgery, the underlying indications for surgical modality and related choice of surgical procedure do not, by itself, appear to be a driving factor.

Precision metabolomics and quantification for cost-effective rapid diagnosis of disease are the key goals in personalized medicine and point-of-care testing. At present, patients are subjected to multiple test procedures requiring large laboratory equipment. Microelectronics has already made modern computing and communications possible by integration of complex functions within a single chip. As More than Moore technology increases in importance, integrated circuits for densely patterned sensor chips have grown in significance. Here, we present a versatile single complementary metal-oxide-semiconductor chip forming a platform to address personalized needs through on-chip multimodal optical and electrochemical detection that will reduce the number of tests that patients must take. The chip integrates interleaved sensing subsystems for quadruple-mode colorimetric, chemiluminescent, surface plasmon resonance, and hydrogen ion measurements. These subsystems include a photodiode array and a single photon avalanche diode array with some elements functionalized to introduce a surface plasmon resonance mode. The chip also includes an array of ion sensitive field-effect transistors. The sensor arrays are distributed uniformly over an active area on the chip surface in a scalable and modular design. Bio-functionalization of the physical sensors yields a highly selective simultaneous multiple-assay platform in a disposable format. We demonstrate its versatile capabilities through quantified bio-assays performed on-chip for glucose, cholesterol, urea, and urate, each within their naturally occurring physiological range.

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.

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.

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.

Metabolites, the small molecules that underpin life, can act as indicators of the physiological state of the body when their abundance varies, offering routes to diagnosis of many diseases. The ability to assay for multiple metabolites simultaneously will underpin a new generation of precision diagnostic tools. Here, we report the development of a handheld device based on complementary metal oxide semiconductor (CMOS) technology with multiple isolated micro-well reaction zones and integrated optical sensing allowing simultaneous enzyme-based assays of multiple metabolites (choline, xanthine, sarcosine and cholesterol) associated with multiple diseases. These metabolites were measured in clinically relevant concentration range with minimum concentrations measured: 25 μM for choline, 100 μM for xanthine, 1.25 μM for sarcosine and 50 μM for cholesterol. Linking the device to an Android-based user interface allows for quantification of metabolites in serum and urine within 2 min of applying samples to the device. The quantitative performance of the device was validated by comparison to accredited tests for cholesterol and glucose., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Scalable immunoassay multiplexing offers a route to creating rapid point-of-care (POC) diagnostics. We present a method for multiplexing immunoassays on the surface of a complementary metal oxide semiconductor (CMOS) sensor array integrated circuit (IC) without the use of physical separators such as wells or channels. Major advantages of using a CMOS sensor array include low mass-manufacturing costs, the possibility to multiplex multiple assays on a single IC, and improved signal when averaging multiple sensors, along with providing a platform where wash steps can be incorporated to maximize selectivity and sensitivity compared to paper based lateral flow immunoassay. The device was able to differentiate between samples containing either, neither, or both rabbit anti-mouse (RAM) antibodies and/or anti-HIV gp120 antibodies in serum using a gold-nanoparticle promoted silver enhancement immunoassay. HIV antibody concentrations down to 100 μg/mL were readily detected, which is three times lower than those typically found in infected humans (300-500 μg/mL), and the limit of detection was 10 μg/mL.

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.

We report on the design and fabrication of a hybrid sensor that integrates transmission-mode localized surface plasmonic resonance (LSPR) into a quartz crystal microbalance (QCM) for studying biochemical surface reactions. The coupling of LSPR nanostructures and a QCM allows optical spectra and QCM resonant frequency shifts to be recorded simultaneously and analyzed in real time for a given surface adsorption process. This integration simplifies the conventional combination of SPR and QCM and has the potential to be miniaturized for application in point-of-care (POC) diagnostics. The influence of antibody-antigen recognition effect on both the QCM and LSPR has been analyzed and discussed., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To characterise incidence and healthcare costs associated with persistent postoperative pain (PPP) following lumbar surgery., Design: Retrospective, population-based cohort study., Setting: Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases., Participants: Population-based cohort of 10 216 adults who underwent lumbar surgery in England from 1997/1998 through 2011/2012 and had at least 1 year of presurgery data and 2 years of postoperative follow-up data in the linked CPRD-HES., Primary and Secondary Outcomes Measures: Incidence and total healthcare costs over 2, 5 and 10 years attributable to persistent PPP following initial lumbar surgery., Results: The rate of individuals undergoing lumbar surgery in the CPRD-HES linked data doubled over the 15-year study period, fiscal years 1997/1998 to 2011/2012, from 2.5 to 4.9 per 10 000 adults. Over the most recent 5-year period (2007/2008 to 2011/2012), on average 20.8% (95% CI 19.7% to 21.9%) of lumbar surgery patients met criteria for PPP. Rates of healthcare usage were significantly higher for patients with PPP across all types of care. Over 2 years following initial spine surgery, the mean cost difference between patients with and without PPP was £5383 (95% CI £4872 to £5916). Over 5 and 10 years following initial spine surgery, the mean cost difference between patients with and without PPP increased to £10 195 (95% CI £8726 to £11 669) and £14 318 (95% CI £8386 to £19 771), respectively. Extrapolated to the UK population, we estimate that nearly 5000 adults experience PPP after spine surgery annually, with each new cohort costing the UK National Health Service in excess of £70 million over the first 10 years alone., Conclusions: Persistent pain affects more than one-in-five lumbar surgery patients and accounts for substantial long-term healthcare costs. There is a need for formal, evidence-based guidelines for a coherent, coordinated management strategy for patients with continuing pain after lumbar surgery., Competing Interests: Competing interests: At the time of the study, CNC was employed by PHMR, LLC, who received consulting fees from Medtronic. SW, MS and T-CK received consulting fees from PHMR, LLC. RT, AM, JB, DC and SE received consulting fees from Medtronic as advisors to the project., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., Competing Interests: The authors declare no conflict of interest.

This paper presents a contactless, acoustic technique to manipulate and sort particles of varying size in both liquid and air media. An acoustic standing wave is generated by the superposition of counterpropagating waves emitted by two opposing emitters. The acoustic radiation force traps the smallest particles at the pressure nodes of the acoustic standing wave. The position of the particles can be manipulated by dynamically changing the phase difference between the two emitters. By applying a dynamic acoustic field (DAF), it is demonstrated that particles can be manipulated spatially and sorted according to size. The discrimination (sorting dynamic range) capability is initially demonstrated in liquid media by separating three different sets of polystyrene particles, ranging in size from 5 to 45μm in diameter. The separation between particles was performed up to a ratio of 5/6 in diameter (20% diameter difference). Finally, the scalability of the DAF method is demonstrated by sorting expanded polystyrene particles of 2 and 5 mm diameter in air.

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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 2(16) sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2-12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM-231 mM, encompassing glucose's physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine.

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.

Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.

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., (© 2015 John Wiley & Sons Ltd.)

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.

Wirelessly directed nerve regeneration: inductively powered electrical stimulation circuits on the biodegradable polymer polycaprolactone demonstrate directed regeneration of sensory neurons from a dorsal root ganglion. These circuits, produced using a unique transfer printing process, illustrate progress towards the use of electrical stimulation systems on biodegradable materials to improve peripheral nerve repair functional outcomes., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Balloon kyphoplasty provides symptomatic relief of vertebral compression fractures in elderly patients. Peri-operative complications are rare; however, they can potentially be devastating. To the best of our knowledge, complications during balloon kyphoplasty have not been described previously in published case reports., Case Presentation: A 66-year-old man who was a farmer of Caucasian origin presented with a 6-month history of back pain after a fall. We discovered a significant T12 wedge compression fracture, so we performed a T12 balloon kyphoplasty. Approximately 2 weeks after being discharged from our hospital, the patient presented with increasing back pain. He presented for a second time with excruciating pain on the left side of his thoracolumbar region, so he was admitted to our ward. X-rays did not show any further fractures or compromise, but magnetic resonance imaging showed extensive edema in the T11 and L1 vertebral bodies as well as fluid tracking from the T11-T12 disc into the vertebral body. Nine days after being discharged, the patient presented to the outpatient clinic with severe back pain. Magnetic resonance imaging at that visit showed edema at the levels above and below the T11/T12 disc. He was put into a brace and given 300mg of morphine, which did not provide any pain resolution. Posterior instrumentation from T9 to L2 (pedicle fixation of T9-T10 as well as L1-L2, rods in between and a crosslink above T11-T12) was performed as the final treatment, and the patient was discharged uneventfully., Conclusion: Patients presenting with residual pain over a previous balloon kyphoplasty level should raise high suspicion for a fracture or complication involving the levels above and/or below the balloon kyphoplasty. The best way to treat fractures that develop after a failed balloon kyphoplasty is to instrument and fuse posteriorly. Our present case report shows that a high level of suspicion for possible new fractures should be maintained for all similar cases.

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.

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.

We report on the design, fabrication, testing, and packaging of a miniaturized system capable of detecting autofluorescence (AF) from mammalian intestinal tissue. The system comprises an application-specific integrated circuit (ASIC), light-emitting diode, optical filters, control unit, and radio transmitter. The ASIC contains a high-voltage charge pump and single-photon avalanche diode detector (SPAD). The charge pump biases the SPAD above its breakdown voltage to operate in Geiger mode. The SPAD offers a photon detection efficiency of 37% at 520 nm, which corresponds to the AF emission peak of the principle human intestinal fluorophore, flavin adenine dinucleotide. The ASIC was fabricated using a commercial triple-well high-voltage CMOS process. The complete device operates at 3 V and draws an average of 7.1 mA, enabling up to 23 h of continuous operation from two 165-mAh SR44 batteries.

Metamaterials (MM), artificial materials engineered to have properties that may not be found in nature, have been widely explored since the first theoretical(1) and experimental demonstration(2) of their unique properties. MMs can provide a highly controllable electromagnetic response, and to date have been demonstrated in every technologically relevant spectral range including the optical(3), near IR(4), mid IR(5) , THz(6) , mm-wave(7) , microwave(8) and radio(9) bands. Applications include perfect lenses(10), sensors(11), telecommunications(12), invisibility cloaks(13) and filters(14,15). We have recently developed single band(16), dual band(17) and broadband(18) THz metamaterial absorber devices capable of greater than 80% absorption at the resonance peak. The concept of a MM absorber is especially important at THz frequencies where it is difficult to find strong frequency selective THz absorbers(19). In our MM absorber the THz radiation is absorbed in a thickness of ~ λ/20, overcoming the thickness limitation of traditional quarter wavelength absorbers. MM absorbers naturally lend themselves to THz detection applications, such as thermal sensors, and if integrated with suitable THz sources (e.g. QCLs), could lead to compact, highly sensitive, low cost, real time THz imaging systems.

We present a device and method for performing vector transmission spectroscopy on biological specimens at terahertz (THz) frequencies. The device consists of artificial dielectric birefringence obtained from silicon microfluidic grating structures. The device can measure the complex dielectric function of a liquid, across a wide THz band of 2 to 5.5 THz, using a Fourier transform infrared spectrometer. Measurement data from a range of liquid specimens, including sucrose, salmon deoxyribonucleic acid (DNA), herring DNA, and bovine serum albumin protein solution in water are presented. The specimen handling is simple, using a microfluidic channel. The transmission through the device is improved significantly and thus the measurement accuracy and bandwidth are increased.

We show how an array of ion-sensitive-field-effect-transistors can be used to both spatially and temporally image the oscillating pH/ion waves produced by the Belousov-Zhabotinsky (BZ) reaction with high resolution., (This journal is © The Royal Society of Chemistry 2012)

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.

Real-time ion flux imaging: an ion-sensitive field-effect transistor (ISFET) array is coupled with optical microscopy to image the growth of, and ion flux through, micrometer-scale tubes and membranes built from polyoxometalate clusters. The correlation between the optical and ionic imaging data is excellent, showcasing the use of ISFET arrays for high-resolution spatial and temporal mapping of ionic movements., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: We report on the investigations of two gastroenteritis outbreaks, which were linked to a common source., Methods: Retrospective cohort studies were conducted for two gastroenteritis outbreaks which occurred in Auckland and in Waikato. Faecal samples and samples of oyster meat were analysed. Environmental surveys of implicated areas were conducted., Results: 10 out of 16 people who had eaten at a catered event in Auckland, and 3 out of 15 people who had eaten at a Waikato restaurant, experienced gastroenteritis. The symptoms, duration of illness and incubation periods were consistent with norovirus gastroenteritis in both outbreaks. The consumption of oysters was strongly associated with an increased risk of illness. Faecal samples were positive for norovirus. Oysters from both outbreaks were traced back to the same growing area. Samples of oyster meat from one of the restaurants and from the growing area were positive for norovirus. The growing area was closed for further investigation. A pipe from a waste water treatment plant was later found to be leaking partially treated effluent into a stream discharging near the implicated growing area., Conclusion: Investigation of these two outbreaks led to the discovery of a common source of norovirus at a commercial oyster growing area.

An acoustic particle manipulation system is presented, using a flexible printed circuit board formed into a regular heptagon. It is operated at 4 MHz and has a side dimension of 10 mm. The heptagonal geometry was selected for its asymmetry, which tends to reduce standing wave behavior. This leads to the possibility of having fine control over the acoustic field by varying the output phases of the transducer elements. Configurations with two and three active transducers are demonstrated experimentally. It is shown that with two transducers, the particles align along straight lines, the position of which can be moved by varying the relative excitation phases of the two transducers. With three active transducers, hexagonal-shaped patterns are obtained that can also be moved, again according to the phase of the excitation signals. Huygens' principle-based simulations were used to investigate the resultant pressure distributions. Good agreement was achieved between these simulations and both Schlieren imaging and particle manipulation observations.

A device for performing vector transmission spectroscopy on aqueous and polar solvent specimens at terahertz frequencies is presented. The device enables the direct measurement of the complex dielectric function across the terahertz band using a Fourier transform IR spectrometer for lossy solutions. Using microfluidic sampling, specimen handling is straightforward and direct measurements on polar specimens are made possible. The method is scalable to longer or shorter wavelengths.

We present the simulation, implementation, and measurement of a polarization insensitive broadband resonant terahertz metamaterial absorber. By stacking metal-insulator layers with differing structural dimensions, three closely positioned resonant peaks are merged into one broadband absorption spectrum. Greater than 60% absorption is obtained across a frequency range of 1.86 THz where the central resonance frequency is 5 THz. The FWHM of the device is 48%, which is two and half times greater than the FWHM of a single layer structure. Such metamaterials are promising candidates as absorbing elements for bolometric terahertz imaging.

Metamaterial absorbers have attracted considerable attention for applications in the terahertz range. In this Letter, we report the design, fabrication, and characterization of a terahertz dual band metamaterial absorber that shows two distinct absorption peaks with high absorption. By manipulating the periodic patterned structures as well as the dielectric layer thickness of the metal-dielectric-metal structure, significantly high absorption can be obtained at specific resonance frequencies. Finite-difference time-domain modeling is used to design the structure of the absorber. The fabricated devices have been characterized using a Fourier transform IR spectrometer. The experimental results show two distinct absorption peaks at 2.7 and 5.2 THz, which are in good agreement with the simulation. The absorption magnitudes at 2.7 and 5.2 THz are 0.68 and 0.74, respectively.

We experimentally demonstrate plasmonic lenses working in the visible range with well controlled focal lengths using nano-slits in an aluminum film. The fabricated lenses were characterized using confocal scanning optical microscopy. Two lenses with a design focal length 3 microm and 6 microm at 633 nm were investigated in detail. The full-width half-maximum beam width at the focal point was found to be 470 nm and 490 nm, and the extension of the light spot was 1.3 mum and 2.3 mum respectively. Lens performance compared extremely well with the expected behaviour from finite-difference time-domain modeling. The focal length from experiment and simulation agreed to within 3.5%. The lens manufacture was found to be insensitive to deviations from the optimum process parameters indicating that lens components can be reliably designed and produced.

Three primary color (red, green and blue) filters consisting of subwavelength triangular-lattice hole arrays in an aluminum film on glass were simulated and fabricated. A silicon dioxide cap layer, deposited on the patterned aluminum film, was found to almost double the transmission efficiency for all the filters. The measured peak transmittance for each color filter was above 30%, exhibiting a wavelength spectrum with a full-width at half-maximum of approximately 100 nm. Simulation results of various structures with different cap layers revealed the enhanced coupling between surface plasmon resonances at both sides of the metal film in a symmetrical configuration. It was found that gratings with as few as three periods were sufficient to demonstrate filtering. The effect of metal thickness and hole size was investigated in detail.

We have developed low-loss polymer artificial dielectric quarter wave plates (QWP) operating at 2.6, 3.2 and 3.8 THz. The QWPs are imprinted on high density polyethylene (HDPE) using silicon masters. The grating period for the quarter wave plates is 60 microm. 330 microm, 280 microm and 230 microm deep gratings are used to obtain a pi/2 phase retardance between TE and TM polarization propagating through the QWPs. High frequency structure simulator (HFSS) was used to optimize the grating depth. Since the required grating depth is high, two plates, fixed in a back-to-back configuration were used for each QWP. A maximum aspect ratio (grating height/grating width) of 6.6 was used.