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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 $2.7 {\boldsymbol {\mu }}\text{M}$ , respectively. The LOD and resolution for aPSA were 0.5 and 2.0 ng $/$ 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. [ABSTRACT FROM AUTHOR]

We demonstrate a proof of concept highly miniaturised fluorescence imager and its application to detecting cancer in resected human colon cancer tissues. Fluorescence imaging modalities have already been successfully implemented in traditional endoscopy. However, the procedure still causes discomfort and requires sedation. Wireless fluorescence capsule endoscopy has the potential to improve diagnostic accuracy with less inconvenience for patients. In this paper we present a 5 mm $\times6$ mm $\times5$ mm optical block that is small enough to integrate into a capsule endoscope. The block integrates ultrathin filters for optical isolation and was successfully integrated with a sensitive CMOS SPAD array to detect green fluorescence from Flavin Adenine Dinucleotide (FAD), which is an endogenous fluorophore responsible for autofluorescence in human tissues, and fluorescence from the cancer selective molecular probe ProteoGREEN™-gGlu used to label colorectal cancer cells. In vitro studies were validated using a commercial Modulus™ Microplate reader. The potential use of the device in capsule endoscopy was further validated by imaging healthy and malignant resected human tissues from the colon to detect changes in autofluorescence signal that are crucial for cancer diagnosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We present the design and application of a $64\times 64$ pixel SPAD array to portable colorimetric sensing, and fluorescence and x-ray imaging. The device was fabricated on an unmodified 180 nm CMOS process and is based on a square p+/n active junction SPAD geometry suitable for detecting green fluorescence emission. The stand-alone SPAD shows a photodetection probability greater than 60% at 5 V excess bias, with a dark count rate of less than 4 cps/ $\mu \text{m}^{\mathbf {2}}$ and sub-ns timing jitter performance. It has a global shutter with an in-pixel 8-bit counter; four 5-bit decoders and two 64-to-1 multiplexer blocks allow the data to be read-out. The array of sensors was able to detect fluorescence from a fluorescein isothiocyanate (FITC) solution down to a concentration of 900 pM with an SNR of 9.8 dB. A colorimetric assay was performed on top of the sensor array with a limit of quantification of $3.1~\mu \text{m}$. X-rays images, using energies ranging from 10 kVp to 100 kVp, of a lead grating mask were acquired without using a scintillation crystal. [ABSTRACT FROM AUTHOR]

The measurement of nanophotonic sensors currently requires the use of external measuring equipment for their read-out such as an optical spectrum analyzer, spectrophotometer, or detectors. This requirement of external laboratory-based measuring equipment creates a “chip-in-a-lab” dilemma and hinders the use of nanophotonic sensors in practical applications. Making nanophotonic sensors usable in everyday life requires miniaturization of not only the sensor chip itself but also the equipment used for its measurement. In this paper, we have removed the need of external measuring equipment by monolithically integrating 1-D grating structures with a complementary metal-oxide-semiconductor (CMOS) integrated circuit having an array of photodiodes. By doing so, we get a direct electrical read-out of the refractive index changes induced when applying different analytes to grating structures. The gratings are made of CMOS compatible silicon nitride. Employing a nanophotonic sensor made of CMOS compatible material allows fabrication of the integrated sensor chip in a commercial CMOS foundry, enabling mass production for commercialization with low cost. Our results present a significant step toward transforming present laboratory-based nanophotonic sensors into practical portable devices to enable applications away from the analytical laboratory. We anticipate the work will have a major impact on technology for personalized medicine, environmental, and industrial sensing. [ABSTRACT FROM AUTHOR]

Metabolites are the ultimate readout of disease phenotype that plays a significant role in the study of human disease. Multiple metabolites sometimes serve as biomarkers for a single metabolic disease. Therefore, simultaneous detection and analysis of those metabolites facilitate early diagnostics of the disease. Conventional approaches to detect and quantify metabolites include mass spectrometry and nuclear magnetic resonance that require bulky and expensive equipment. Here, we present a disposable sensing platform that is based on complementary metal–oxide–semiconductor process. It contains two sensors: an ion sensitive field-effect transistor and photodiode that can work independently for detection of pH and color change produced during the metabolite-enzyme reaction. Serum glucose and cholesterol have been detected and quantified simultaneously with the new platform, which shows good sensitivity within the physiological range. Low cost and easy manipulation make our device a prime candidate for personal metabolome sensing diagnostics. [ABSTRACT FROM PUBLISHER]

Elevated cholesterol levels are associated with a greater risk of developing cardiovascular disease and other illnesses, making it a prime candidate for detection on a disposable biosensor for rapid point of care diagnostics. One of the methods to quantify cholesterol levels in human blood serum uses an optically mediated enzyme assay and a bench top spectrophotometer. The bulkiness and power hungry nature of the equipment limits its usage to laboratories. Here, we present a new disposable sensing platform that is based on a complementary metal oxide semiconductor process for total cholesterol quantification in pure blood serum. The platform that we implemented comprises readily mass-manufacturable components that exploit the colorimetric changes of cholesterol oxidase and cholesterol esterase reactions. We have shown that our quantification results are comparable to that obtained by a bench top spectrophotometer. Using the implemented device, we have measured cholesterol concentration in human blood serum as low as 29 \mu \textM with a limit of detection at 13 \mu \textM , which is approximately 400 times lower than average physiological range, implying that our device also has the potential to be used for applications that require greater sensitivity. [ABSTRACT FROM PUBLISHER]

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 45~\mu \textm 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. [ABSTRACT FROM AUTHOR]

We describe the development and optical characterization of a planar medium infrared (mid-IR) InSb photodetector on a GaAs substrate technology, capable of integrating MESFETs, to demonstrate a new active pixel device architecture. Our results pave the way for the development of integrated mid-IR focal plane array circuits on a single chip. Device structures with areas down to 0.0016 mm $^{{ {2}}}$ were investigated. By deploying a silicon nitride passivation layer, we were able to reduce leakage current in reverse bias by up to 27% to yield an improved rectifier. Extensive optical characterization was carried out in the near- and mid-IR wavelength range. Responsivities of up to 3.54 A/W and quantum efficiency values above unity were obtained in the near-IR range as a consequence of illumination above the bandgap causing impact ionization. In the mid-IR range, responsivities of up to 0.97 A/W were observed. The bandwidth of the devices proved compatible with video-rate standard sampling rates. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM PUBLISHER]

Medium wavelength infrared (MWIR) detectors are of increasing importance in defense, security, commercial, and environmental applications. Enhanced integration will lead to greater resolution and lower cost focal plane arrays (FPAs). We present the monolithic fabrication of an active photopixel made in InSb on a GaAs substrate that is suitable for large-scale integration into an FPA. Pixel addressing is provided by the cointegration of a GaAs MESFET with an InSb photodiode (PD). Pixel fabrication was achieved by developing novel materials and process steps, including isolation etches, a gate recess etch, and low temperature processes, to make Ohmic contacts to both the GaAs and InSb devices. Detailed electrical and optical measurements in an FTIR demonstrated that the PD was sensitive to radiation in the range of 3– 5~\mu \textm at room temperature, and that the device could be isolated from its contacts using the integrated MESFET. This heterogeneous technology creates great potential to realize a new type of monolithic FPA of addressable pixels for imaging in the MWIR range. [ABSTRACT FROM AUTHOR]