Oral Cells-On-Chip: Design, Modeling and Experimental Results.

Recent advances in periodontal studies have attracted the attention of researchers to the relation between oral cells and gum diseases, which is a real threat to overall human health. Among various microfabrication technologies, Complementary Metal Oxide Semiconductors (CMOSs) enable the development of low-cost integrated sensors and circuits for rapid and accurate assessment of living cells that can be employed for the early detection and control of periodontal diseases. This paper presents a CMOS capacitive sensing platform that can be considered as an alternative for the analysis of salivatory cells such as oral neutrophils. This platform consists of two sensing electrodes connected to a read-out capacitive circuitry designed and fabricated on the same chip using Austria Mikro Systeme (AMS) 0.35 µm CMOS process. A graphical user interface (GUI) was also developed to interact with the capacitive read-out system and the computer to monitor the capacitance changes due to the presence of saliva cells on top of the chip. Thanks to the wide input dynamic range (IDR) of more than 400 femto farad (fF) and high resolution of 416 atto farad (aF), the experimental and simulation results demonstrate the functionality and applicability of the proposed sensor for monitoring cells in a small volume of 1 µL saliva samples. As per these results, the hydrophilic adhesion of oral cells on the chip varies the capacitance of interdigitated electrodes (IDEs). These capacitance changes then give an assessment of the oral cells existing in the sample. In this paper, the simulation and experimental results set a new stage for emerging sensing platforms for testing oral samples.

Wide Input Dynamic Range Fully Integrated Capacitive Sensor for Life Science Applications.

This paper presents a new fully integrated CMOS capacitance sensor chip with a wider input dynamic range (IDR) compared to the state-of-the-art, suitable for a variety of life science applications. With the novel differential capacitance to current conversion topology, it achieves an IDR of about seven times higher compared to the previous charge based capacitive measurement (CBCM) circuits and about three times higher compared to the CBCM with cascode current mirrors. It also features a calibration circuitry consisting of an array of switched capacitors, interdigitated electrodes (IDEs) realized on the topmost metal layer, a current-controlled 300 MHz oscillator, and a counter-serializer to create digital output. The proposed sensor, fabricated in AMS 0.35 µm CMOS technology, enables a high-resolution measurement, equal to 416 aF, of physiochemical changes in the IDE with up to 1.27 pF input offset adjustment range (IOAR). With a measurement speed of 15 µs, this sensor is among the fast CMOS capacitive sensors in the literature. In this paper, we demonstrate its functionality and applicability and present the experimental results for monitoring 2 µL evaporating droplets of chemical solvents. By using samples of solvents with different conductivity and relative permittivity, a wide range of capacitance and resistance variations in the sample-IDE interface electric equivalent model can be created. In addition, the evaporating droplet test has inherently fast dynamic changes. Based on the results, our proposed device addresses the challenge of detecting small capacitance changes despite large parasitic elements caused by the ions in the solution or by remnants deposited on the electrode.

A New Whole Genome Culture-Independent Diagnostic Test (WG-CIDT) for Rapid Detection of Salmonella in Lettuce.

The rapid detection of foodborne microbial pathogens contaminating fresh fruits and vegetables during the intervening period between harvest and consumption could revolutionize microbial quality assurance of food usually consumed raw and those with a limited shelf life. We have developed a sensitive, shotgun whole genome sequencing protocol capable of detecting as few as 1 colony forming unit (cfu) of Salmonella enterica serovar Typhimurium spiked on 25 g of lettuce. The Ion Torrent sequencing platform was used to generate reads of globally amplified DNA from microbes recovered from the surface of lettuce followed by bioinformatic analyses of the nucleotide sequences to detect the presence of Salmonella. The test is rapid and sensitive, and appropriate for testing perishable foods, and those consumed raw, for Salmonella contamination. The test has the potential to be universally applicable to any microbial contaminant on lettuce as long as a suitable bioinformatics pipeline is available and validated. A universal test is expected to pave the way for preventive and precision food safety and the re-shaping of the entire spectrum of food safety investigations from the current disease-limiting, reactive procedure to a proactive, disease prevention process.

FPGA-Accelerated 3rd Generation DNA Sequencing.

DNA measurement machines are undergoing an orders-of-magnitude size and power reduction. As a result, the analysis of genetic molecules is increasingly appropriate for mobile platforms. However, sequencing these measurements (converting to the molecule's A-C-G-T text equivalent) requires intense computing resources, a problem for potential realizations as mobile devices. This paper proposes a step towards addressing this issue, the design and implementation of a low-power real-time FPGA hardware accelerator for the basecalling task of nanopore-based DNA measurements. Key basecalling computations are identified and ported to a custom FPGA which operates in tandem with a CPU across a high-speed serial link and a simple API. A measured speed-up over CPU-only basecalling in excess of 100X is realized with an energy efficiency improvement of three orders of magnitude.

A Novel Method for Detection and Progress Assessment of Visual Distortion Caused by Macular Disorder: A Central Serous Chorioretinopathy (CSR) Case Study.

This paper presents a new mathematical model along with a measurement platform for accurate detection and monitoring of various visual distortions (VD) caused by macular disorders such as central serous chorioretinopathy (CSR) and age-related macular degeneration (AMD). This platform projects a series of graphical patterns on the patient's retina and calculates the severity of VDs accordingly. The accuracy of this technique relies on the accurate detection of distorted lines by the patient. We also propose a simple mathematical model to evaluate the VD created by CSR. The model is used as a control for the test results achieved from the proposed platform. The proposed platform consists of the required hardware and software for the generation and projection of patterns along with the collection and processing of patients against their standard optical coherence tomography (OCT) images. Based on these results, the OCT images agree with the VD test results, and the proposed platform can be used as an alternative home monitoring method for various macular disorders.

Recent Advances of Computerized Graphical Methods for the Detection and Progress Assessment of Visual Distortion Caused by Macular Disorders.

Recent advances of computerized graphical methods have received significant attention for detection and home monitoring of various visual distortions caused by macular disorders such as macular edema, central serous chorioretinopathy, and age-related macular degeneration. After a brief review of macular disorders and their conventional diagnostic methods, this paper reviews such graphical interface methods including computerized Amsler Grid, Preferential Hyperacuity Perimeter, and Three-dimensional Computer-automated Threshold Amsler Grid. Thereafter, the challenges of these computerized methods for accurate and rapid detection of macular disorders are discussed. The early detection and progress assessment of macular disorders can significantly enhance the required clinical procedure for the diagnosis and treatment of macular disorders.

NGRID: A novel platform for detection and progress assessment of visual distortion caused by macular disorders.

This paper presents a new graphical macular interface system (GMIS) for accurate, rapid, and quantitative measurement of visual distortion (VD) in the central vision of patients suffering from macular disorders. In this system, a series of predefined graphical patterns or multiple grids (NGRID) are randomly selected from a library of patterns and visualized on the screen, then the VDs identified by the patient are recorded as binary codes using various control methods including speech recognition. Scalable Vector Graphics (SVG) is used to generate the patterns and save them into a central library. Based on the projected patterns and the patients' responses, a VD graph or so-called heatmap is generated for eye-care purposes. We demonstrate and discuss the functionality of the proposed system for the detection and progress assessment of a macular condition in patients suffering from Central Serous Chorioretinopathy (CSR). Also, we characterize the proposed technique to evaluate the systematic error and response time on healthy human subjects with normal vision. Based on these results, the voice recognition input method exhibits a lower error but a higher response time compared to other input devices. We run the proposed NGRID VD technique to evaluate the effect of CSR on the visual field of a CSR patient. The generated heatmaps are in agreement with standard Optical Coherence Tomography (OCT) images obtained at different times from both the left and right eyes. These results reveal the applicability of the proposed technique for the detection and assessment of macular disorders. Based on these results, the proposed NGRID platform shows great promise for use as an alternative solution for in-home monitoring of various macular disorders and as a means of forwarding responses to secured cloud facilities for future data analysis.

Microbiological Sensing Technologies: A Review.

Microorganisms have a significant influence on human activities and health, and consequently, there is high demand to develop automated, sensitive, and rapid methods for their detection. These methods might be applicable for clinical, industrial, and environmental applications. Although different techniques have been suggested and employed for the detection of microorganisms, and the majority of these methods are not cost effective and suffer from low sensitivity and low specificity, especially in mixed samples. This paper presents a comprehensive review of microbiological techniques and associated challenges for bioengineering researchers with an engineering background. Also, this paper reports on recent technological advances and their future prospects for a variety of microbiological applications.

Nanopore-CMOS Interfaces for DNA Sequencing.

DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces.

A Multidisciplinary Approach to High Throughput Nuclear Magnetic Resonance Spectroscopy.

Nuclear Magnetic Resonance (NMR) is a non-contact, powerful structure-elucidation technique for biochemical analysis. NMR spectroscopy is used extensively in a variety of life science applications including drug discovery. However, existing NMR technology is limited in that it cannot run a large number of experiments simultaneously in one unit. Recent advances in micro-fabrication technologies have attracted the attention of researchers to overcome these limitations and significantly accelerate the drug discovery process by developing the next generation of high-throughput NMR spectrometers using Complementary Metal Oxide Semiconductor (CMOS). In this paper, we examine this paradigm shift and explore new design strategies for the development of the next generation of high-throughput NMR spectrometers using CMOS technology. A CMOS NMR system consists of an array of high sensitivity micro-coils integrated with interfacing radio-frequency circuits on the same chip. Herein, we first discuss the key challenges and recent advances in the field of CMOS NMR technology, and then a new design strategy is put forward for the design and implementation of highly sensitive and high-throughput CMOS NMR spectrometers. We thereafter discuss the functionality and applicability of the proposed techniques by demonstrating the results. For microelectronic researchers starting to work in the field of CMOS NMR technology, this paper serves as a tutorial with comprehensive review of state-of-the-art technologies and their performance levels. Based on these levels, the CMOS NMR approach offers unique advantages for high resolution, time-sensitive and high-throughput bimolecular analysis required in a variety of life science applications including drug discovery.

Embedded CMOS basecalling for nanopore DNA sequencing.

DNA sequencing based on nanopore sensors is now entering the marketplace. The ability to interface this technology to established CMOS microelectronics promises significant improvements in functionality and miniaturization. Among the key functions to benefit from this interface will be basecalling, the conversion of raw electronic molecular signatures to nucleotide sequence predictions. This paper presents the design and performance potential of custom CMOS base-callers embedded alongside nanopore sensors. A basecalliing architecture implemented in 32-nm technology is discussed with the ability to process the equivalent of 20 human genomes per day in real-time at a power density of 5 W/cm2 assuming a 3-mer nanopore sensor.

High-speed event detector for embedded nanopore bio-systems.

Biological measurements of microscopic phenomena often deal with discrete-event signals. The ability to automatically carry out such measurements at high-speed in a miniature embedded system is desirable but compromised by high-frequency noise along with practical constraints on filter quality and sampler resolution. This paper presents a real-time event-detection method in the context of nanopore sensing that helps to mitigate these drawbacks and allows accurate signal processing in an embedded system. Simulations show at least a 10× improvement over existing on-line detection methods.

Dual-path NMR receiver using double transceiver microcoils.

We present a fully integrated CMOS dual path front-end receiver for NMR applications. Instead of conventional NMR systems which are using one transceiver coil, we propose a dual-path receiver in which it has two transceiver microcoils. This structure cancels the background signal and consequently improving the sensitivity. Spectral simulations of the dual-path receiver are used to verify cancellation of the background signal in this structure. The front-end receiver contains two differential low-noise amplifiers (LNA), two voltage buffers (for conventional mode), two phase shifters, two variable gain amplifiers (VGA), one differential LNA and voltage buffer at the end. This chain of dual-path receiver is designed for 21 MHz NMR settings. The front-end receiver achieves an input referred noise of 2.7 nV/√Hz and voltage gain of 80 dB. The chip is designed in a 0.13-µm CMOS technology and occupies an area of 1 mm × 2 mm.

CMOS-based high-speed nanopore recording: signals and systems.

This paper considers the potential of CMOS-based nanopore measurement systems for high-speed molecular recording and DNA sequencing in particular. As such it approximates the signal fidelity limitations of a CMOS-based nanopore readout channel and discusses the means by which throughput could be increased through the use of a parallel CMOS readout system.