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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]

This paper presents an approach for matching the transconductance characteristics of CMOS ISFET arrays by removing trapped charge. We describe how to design arrays of floating-gate ISFETs so that ultraviolet (UV) radiation and bulk-substrate biasing can be used to remove the random amount of trapped charge that accumulates on the gates during fabrication. The approach is applied directly to a prototype single-chip 2 x 2 array of ISFETs, which is designed and fabricated in a standard 0.35-µm CMOS process. By considering the transconductance characteristics of the 2 x 2 array before and after UV exposure, it is shown that the response can be matched after 10 h and that the ISFET threshold voltages converge to an equilibrium value of approximately -1 V. After matching, it is found that the ISFET array has a measured sensitivity of 46 mV/pH and can successfully image a change in the pH of a homogeneous electrolyte solution. [ABSTRACT FROM AUTHOR]

Metal interconnect has become a major limiting factor in the growth of VLSI technology. A passive VLSI interconnect layout is proposed in which the current density is constant along its length. The result is a tapered track that has lower capacitance, hence lower power consumption, and improved high frequency performance. Simulations indicate that tapered tracks give delay reductions that permit operating frequencies up to 33% higher, and power savings of 42%, compared with equivalent rectangular tracks. Such interconnects will be of value in high speed clock nets where low skew and long paths are necessary. [ABSTRACT FROM AUTHOR]

Abstract: We describe a complete lab-on-a-chip type ion-sensitive chemical sensor array system for imaging proton concentration and flow. The core of the imaging system relies on a 715.8μm×715.8μm large 64×64-pixel ISFET sensor array that is designed and fabricated in a conventional 4-metal 0.35μm CMOS process along with readout circuitry and additional electronics. The high-speed and real-time data acquisition of ∼100frame per second (fps), 40μs per pixel, results in a large amount of data that is streamed to the hard disk. Image reconstruction methods allow visualization of the dynamic behavior of chemical substances and ionic spreads over the sensor array at a resolution of the size of a pixel. The functionalities of the on-chip ion-camera device are demonstrated using appropriate acid and alkaline solutions. A pH sensitivity of 20mV/pH was achieved without modification to the foundry processed chip. [Copyright &y& Elsevier]

Abstract 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. Highlights • Multiplexed detection of four different metabolite biomarkers using an integrated-circuit-based handheld device with capability to detect and quantify in <2 min. • The metabolites (choline, xanthine, cholesterol and sarcosine), detected in bio-fluids,are implicated in ischaemia and prostate cancer. • The CMOS-chip, with isolated micro-wells, allows metabolite-assays without cross-contamination of assay reagents and signal cross-talk. • A handheld device, with an Android-based user-interface application for phones and tablets, is capable of being powered through a simple micro-USB. [ABSTRACT FROM AUTHOR]

• A sensor array performs better than a standalone sensor with the same area independently by the type of the sensor. • A defined signal standard deviation can be achieved by tuning the number of sensors embedded into a sensor array. • Optimization strategy for simultaneous multiple sensing on a sensor array. An important consideration when scaling semiconductor sensor devices is the effect it may have on noise performance. Overall signal to noise ratio can be improved both by increasing sensor size, or alternatively by averaging the signal from two or more smaller sensors. In the design of sensor systems it is not immediately clear which is the best strategy to pursue. In this paper, we present a detailed theoretical and experimental study based on three different sensor arrays that show that an array of small independent sensors is always less noisy than a large sensor of the same size. [ABSTRACT FROM AUTHOR]