Wide-Range Optical CMOS-Based Diagnostics

Colorimetric, chemiluminescence and refractive index based diagnostics are some of the most important sensing techniques in biomedical science and clinical medicine. Conventionally laboratories and medical clinics rely on bulky and dedicated equipment for each diagnostic technique independently. In this paper, we present CMOS sensor based solutions, comprising a single photon avalanche detector array and photodiode array. The CMOS platform offers low cost integration and wide range of light-based diagnostic techniques, leading to development of point-of-care devices

Monolithic Integration of a Plasmonic Sensor with CMOS Technology

Monolithic integration of nanophotonic sensors with CMOS detectors can transform the laboratory based nanophotonic sensors into practical devices with a range of applications in everyday life. In this work, by monolithically integrating an array of gold nanodiscs with the CMOS photodiode we have developed a compact and miniaturized nanophotonic sensor system having direct electrical read out. Doing so eliminates the need of expensive and bulky laboratory based optical spectrum analyzers used currently for measurements of nanophotonic sensor chips. The experimental optical sensitivity of the gold nanodiscs is measured to be 275 nm/RIU which translates to an electrical sensitivity of 5.4 V/RIU. This integration of nanophotonic sensors with the CMOS electronics has the potential to revolutionize personalized medical diagnostics similar to the way in which the CMOS technology has revolutionized the electronics industry

A 16 x 16 CMOS amperometric microelectrode array for simultaneous electrochemical measurements

There is a requirement for an electrochemical sensor technology capable of making multivariate measurements in environmental, healthcare, and manufacturing applications. Here, we present a new device that is highly parallelized with an excellent bandwidth. For the first time, electrochemical cross-talk for a chip-based sensor is defined and characterized. The new CMOS electrochemical sensor chip is capable of simultaneously taking multiple, independent electroanalytical measurements. The chip is structured as an electrochemical cell microarray, comprised of a microelectrode array connected to embedded self-contained potentiostats. Speed and sensitivity are essential in dynamic variable electrochemical systems. Owing to the parallel function of the system, rapid data collection is possible while maintaining an appropriately low-scan rate. By performing multiple, simultaneous cyclic voltammetry scans in each of the electrochemical cells on the chip surface, we are able to show (with a cell-to-cell pitch of 456 μm) that the signal cross-talk is only 12% between nearest neighbors in a ferrocene rich solution. The system opens up the possibility to use multiple independently controlled electrochemical sensors on a single chip for applications in DNA sensing, medical diagnostics, environmental sensing, the food industry, neuronal sensing, and drug discovery

Hybrid Amperometric and Potentiometric Sensing Based on a CMOS ISFET Array

Potentiometry and amperometry are some of the most important techniques for electroanalytical applications. Integrating these two techniques on a single chip using CMOS technology paves the way for more analysis and measurement of chemical solutions. In this paper, we describe the integration of electrode transducers (amperometry) on an ion imager based on an ISFET array (potentiometry). In particular, this integration enables the spatial representation of the potential distribution of active electrodes in a chemical solution under investigation

An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification

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 216 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

Antibiotic resistance of vibrio parahaemolyticus isolated from cockles and shrimp sea food marketed in Selangor, Malaysia

Introduction: The main aim of this study is to determine the antibiotic profile of V. parahaemolyticus gastroenteritis associated with the consumption of contaminated shrimp and cockles marketed in Selangor Malaysia. V. parahaemolyticus is the leading cause of seafood-associated gastroenteritis in Asian Countries typically is associated with the consumption of raw shellfish and oysters specially shrimp and cockles. Rapid, sensitive and specific detection methods are needed to control V. parahaemolyticus infections. We describe a recognized the pathogenic V. parahaemolyticus in shrimp and cockles that will be the risk of gastroenteritis associated with the consumption of seafood marketed in Malaysia. Methods: This study was carried out between July 2011 and August 2013 at the Center of Excellence for Food Safety Research, Faculty of Food Science and Technology, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, and Faculty of Biotechnology, Dep. of Cell and Molecular Biology, University Putra Malaysia and other centers as collaboration. The seafood samples were collected from different markets and more than 400 samples from shrimp and cockles were investigated for detection and isolation of V. parahaemolyticus. CHROMagar Vibrio and TCBS agar media were used for fast detection and isolation of V. parahaemolyticus isolates. PCR based methods targeted to toxR regulatory gene, tlh the species and family gene, tdh and trh the virulence genes were extensively used. The antibiotic susceptibility testing of 65 V. parahaemolyticus isolates recovered from retail shrimp and cockles seafood were determined with four types of E-test antibiotic strips. Results: All the 65 isolates were positive to toxR and tlh genes. Out of 65 isolates, only eight isolates (12.31%) were positive for tdh virulence gene isolated form cockles and shrimp (3 isolates from shrimp and 5 isolates from cockles), whereas twenty six (40%) isolates were positive for trh virulence gene isolated from shrimp and cockles (9 from shrimp and 17 from cockles). This result indicates high occurrence of tdh+ and trh+ isolates in shrimp and cockles marketed in Malaysia. None of the isolates tested possess both virulence genes. For the antibiotic E-test susceptibility test, overall, V. parahaemolyticus is remained susceptible to tetracycline (97%). A slight increase in the susceptibility of tetracycline is observed from 2011 to 2013. While reduced susceptibility was detected only in V. parahaemolyticus for ampicillin. The mean of MIC of the isolates toward ampicillin is increased from 64 μg/ml in 2011 to 128 μg/ml in year 2013. The current study demonstrates a high risk of pathogenic V. parahaemolyticus in the shrimp and cockles marketed in Selangor Malaysia. Conclusions: The potential risk of V. parahaemolyticus infection due to the consumption of contaminated seafood in Malaysia should not be neglected. The increased resistance of ampicilin from our studies in Malaysia since 2004 to 2013 could be in indication of antibiotic abuse in clinical and agricultural used of ampicilin in Malaysia

A colorimetric CMOS-based platform for rapid total serum cholesterol quantification

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 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 μM with a limit of detection at 13 μM, 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

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Researching corporate social responsibility in the Middle East - the current state and future directions

Corporate social responsibility (CSR) has the potential to yield economic and social value in the Middle East (ME), especially given the current high environmental flux in the region. Although much scholarly has been paid to CSR issues, a key question remains about how to operate responsibly in the ME, particularly since institutional environments and stakeholders’ needs vary across ME states. The purpose of this paper is to provide a systematic review of the current state of CSR in the ME. We identify thirty-eight articles that are most pertinent to CSR in the ME and examine the main theoretical frameworks, methodologies, trajectories for further conceptual development, gaps where new research pathways need to be created and also future research questions. From the systematic review, we reveal how attention on CSR in the ME is slowly gaining traction. A snapshot of the gaps identified include the collaboration between business and NGOs, the impact of stakeholders and institutions on CSR, the impact of political and economic crisis on CSR and the influence of individualistic characteristics shaping managers’ CSR behaviour. In addition to such gaps, we present an agenda for future research