By combining information such as genomics, proteomics, and metabolomics data, multiomics methodologies have the potential to reveal the otherwise invisible processes of carcinogenesis. Using these ...data, a new-generation point-of-care (POC) device may support patient care through rapid diagnosis involving accurate and simultaneous multiomics measurements. In this work, we present a proof-of-concept portable system capable of measuring a metabolite (glutamate) and a protein proteolytically active prostate-specific antigen (aPSA) simultaneously on a single device in a 2-min interval using on-chip optical methods. The device has the potential to improve the current diagnostic pathways of prostate cancer (PCa) by reducing the high false-positive rate with the widely used total prostate-specific antigen (tPSA) test. We demonstrate a simultaneous assay of glutamate and aPSA in buffer and synthetic urine. For the glutamate assay, the limit of detection (LOD) and resolution were found to be 0.9 and <inline-formula> <tex-math notation="LaTeX">2.7 {\boldsymbol {\mu }}\text{M} </tex-math></inline-formula>, respectively. The LOD and resolution for aPSA were 0.5 and 2.0 ng<inline-formula> <tex-math notation="LaTeX">/ </tex-math></inline-formula>ml, respectively. The LOD and resolution achieved using this device are, therefore, in line with human physiological ranges. The platform is suitable for accommodating two independent optical assays, and, therefore, chemistry can be modified to measure different analytes regardless of their nature. This technological breakthrough has the potential to deliver an accurate multiomics portable device for PCa and may be extended to other diseases.
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.
Plasmonic metasurfaces provide unprecedented control of the properties of light. By designing symmetry-breaking nanoholes in a metal sheet and engineering the optical properties of the metal using ...geometry, highly selective transmission and polarization control of light is obtained. To date such plasmonic filters have exhibited broad (>200 nm) transmission line widths in the NIR and as such are unsuitable for applications requiring narrow passbands, e.g., multispectral imaging. Here we present a novel subwavelength elliptical and circular nanohole array in a metallic film that simultaneously exhibits high transmission efficiency, polarization insensitivity, and narrow line width. The experimentally obtained line width is 79 nm with a transmission efficiency of 44%. By examining the electric and magnetic field distributions for various incident polarizations at the transmission peak we show that the narrowband characteristics are due to a Fano resonance. Good agreement is obtained between the experimental data, simulations, and analytical calculations. Our design can be modified to operate in other regions of the electromagnetic spectrum, and these filters may be integrated with suitable detectors such as photodiodes and single-photon avalanche diode arrays.
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 Si 3 N 4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta 2 O 5 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.
Objective : The detection of metabolites such as choline in blood are important in clinical care for patients with cancer and cardiovascular disease. Choline is only present in human blood at low ...concentrations hence accurate measurement in an affordable point-of-care format is extremely challenging. Although complementary metal-oxide semiconductor (CMOS) and microfluidics are individually mature technologies, their integration has presented challenges that we overcome in a novel, cost-effective, single-step process. Methods: To demonstrate the process, we present the microfluidic integration of a metabolomics-on-CMOS point-of-care platform with four capillary microfluidic channels on top of a CMOS optical sensor array. Results: The fabricated device was characterised to verify the required structural profile, mechanical strength, optical spectra, and fluid flow. As a proof of concept, we used the device for the in-vitro quantification of choline in human blood plasma with a limit of detection of 3.2 μM and a resolution of 1.6 μM. Significance: Integration of microfluidics on to CMOS technology has the potential to enable advanced sensing technologies with extremely low limit of detection that are well suited to multiple clinical metabolite measurements.
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.
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.
Multi‐spectral materials, using hybridised plasmonic and metamaterial structures, can simultaneously exhibit unique resonant phenomena over several decades of wavelengths. A multi‐spectral material ...that combines a plasmonic colour filter array and a terahertz metamaterial absorber into a single material is a promising prospect for a coaxial multi‐spectral imager operating in the visible, near IR, and terahertz wavebands.
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.
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