Nicolas Moser

ISFETs in CMOS and Emergent Trends in Instrumentation: A Review

Over the past decade, ion-sensitive field-effect transistors (ISFETs) have played a major role in enabling the fabrication of fully integrated CMOS-based chemical sensing systems. This has allowed several new application areas, with the most promising being the fields of ion imaging and full genome sequencing. This paper reviews the new trends in front-end topologies toward the design of ISFET sensing arrays in CMOS for these new applications. More than a decade after the review of the ISFET by Bergveld which summarized the state of the art in terms of device and early readout circuity, we describe the evolution in terms of device macromodel and identify the main sensor challenges for current designers. We analyze the techniques that have been reported for both ISFET instrumentation and compensation, and conclude that topologies are focusing on device adaptation for offset and drift cancellation, as opposed to system compensation which are often not as robust. Guidelines are provided to build a tailored CMOS ISFET array, emphasizing that the needs in terms of applications are the keys to selecting the right pixel architecture. Over the next few years, the race for the largest and densest array is likely to be put on hold to allow the research to focus on new pixel topologies, ultimately leading to the development of reliable and scalable arrays. A wide range of new applications are expected to motivate this paper for at least another decade.

A novel pH-to-time ISFET pixel architecture with offset compensation

A novel pixel architecture is presented to be part of a pH-based DNA microarray using ISFETs as chemical sensors. The design, based on APS architectures, performs pulse width modulation to encode the pH in time. It allows compensation for a major ISFET nonideality, offset in the threshold voltage, which is caused by trapped charge on the floating gate and the passivation layer of the ISFET. Also, the drop in sensitivity due to the passivation capacitance inherent to CMOS processes is attenuated. The system is implemented using a 0.35 fim standard CMOS technology. The pixel is shown to achieve a high and tunable accuracy of between 0.55 μs/dpH and 2.9 μs/dpH. Along with an estimation of the noise and the incidence of calibration, this leads to a resolution of approximately 20 mpH on a 1 pH-range. Trapped charge compensation proves to be effective up to an offset voltage of 1.25 V. The pixel is compact and reaches a total area of 16.5 μm × 16.25 μm.

Live demonstration: A CMOS-based ISFET array for rapid diagnosis of the Zika virus

We demonstrate a diagnostics platform which integrates an ISFET array and a temperature control loop for isothermal DNA detection. The controller maintains a temperature of 63°C to perform nucleic acid amplification which is detected by the on-chip sensors. The 32×32 ISFET array is first calibrated to cancel trapped charge and then measures the change in the pH of the reaction. The sensor data is sent to a microcontroller and the reaction is monitored in real-time using a MATLAB interface. Experiments confirm a change of 0.9 pH when tested for the presence of RNA associated with the Zika virus.

Bio-inspired pH sensing using ion sensitive field effect transistors

In this paper, we present a novel bio-inspired CMOS-based hexagonal ISFET sensor which, compared to traditional devices, exhibit a more compact arrangement as part of large arrays and provides benefits in terms of capacitive attenuation. We classify these novel sensors as Enclosed Gate Transistors (EGTs) and provide a layout in standard AMS 0.35 μm technology. Electrical characteristics are derived theoretically for the device, including an effective W/L, and simulations for both AMS 0.18 and 0.35 μm CMOS processes are provided. The results indicate a decrease in parasitic gate capacitance between 20 % and 40%, highlighting the advantages in attenuation of respectively 0.36 dB and 0.71 dB for the smallest lengths of devices. The noise performance is also improved, with the input referred noise reduced by 1 or 2 % for each process. The devices were fabricated in standard 0.35 μm CMOS technology for future characterisation.

An ion imaging ISFET array for Potassium and Sodium detection

In this paper, we present a novel approach to ISFET arrays which allows the conception of ion imaging Lab-on-CMOS platforms. K+ and Na+ selective polymer membranes are deposited on the surface of the array so that each pixel is selective to a particular ionic species. An initial calibration produces an accurate mapping of the array in terms of ion-selective regions and determines the sensitivity of the membrane. The system exhibits K+ and Na+ sensitivities of respectively 51.2 mV/dec and 46.8 mV/dec, and demonstrates good discrimination of Potassium and Sodium ions for a common solution exposed to the chip, with a reported error lower than 1%. This ISFET-based tri-ion imaging array constitutes the basis for a portable integrated multi-ion platform.

A robust ISFET array with in-pixel quantisation and automatic offset calibration

A pH-based microarray is presented using Ion-Sensitive Field-Effect Transistors (ISFETs) as chemical sensors for an ion imaging platform. The pH is quantised in time with a pixel architecture based on Active Pixel Sensors (APS), and decoded using a continuous time Pulse Width Modulation (PWM) decoder with a resolution which can be modulated through a multiplexer. The complete peripheral system sends the data obtained from the 8×8 array to a microcontroller through an SPI interface. A novel automatic ISFET calibration scheme provides feedback to compensate for trapped charge at device level, offering a trade-off between accuracy and speed of processing. The algorithm relies on a source voltage modulation, whereby the value for Vs in every pixel is identified and stored in an on-chip RAM. Intermediate calibrations may be run periodically for drift cancellation. The design is implemented in a 0.35 μm standard CMOS technology. The resolution of the PWM decoder is shown to lie between 9.55 ns and 29.1 ns. The system was simulated for various offset values, and shows a high resolution of 33 mpH. The initial calibration typically runs in 130 ms and the readout for the full array once calibrated is carried out in 832 μs, which offers a high time resolution for ion imaging.

Live demonstration: Real-time chemical imaging of ionic solutions using an ISFET array

We demonstrate a CMOS-based lab-on-chip platform which is capable of ion imaging to detect a variation in hydrogen, potassium and sodium ions. An ISFET array is used to detect a change in ion concentration with a calibration scheme to cancel the offset due to trapped charge. The SÍ3N4 passivation layer confers an inherent sensitivity to the sensors, and additional polymer membranes are pipetted containing a potassium and sodium ionophore. An initial algorithm identifies the sensitivity of each pixel towards the target ions. The user can inject a solution with a given concentration of ions and observe the real-time output change of the array on a MATLAB interface. The display then provides an estimate of the target ion concentration.

A CMOS ISFET array for wearable thermoelectrically powered perspiration analysis

Recent advances in micro-electronics and electro-chemical sensors has led to an emerging class of next generation wearables, detecting analytes in bio-fluids such as perspiration. Most of these devices utilise Ion Selective Electrodes (ISEs) as a detection method, however Ion Sensitive Field Effect Transistors (ISFETs) provide a solution with better integration and low-power consumption. This work presents a system consisting of an ISFET array designed to read the pH of perspiration as a current, average the signal to reduce noise and modulate the frequency of a transmittable pulse. The input referred noise of the array is shown to be reduced by a factor of 3, compared to a single sensor of the same overall power consumption. The sensing and processing system consumes less than 10μW making it feasible to be supplied by a thermoelectric generator.

Scaling ISFET instrumentation with in-pixel quantisation to deep submicron technologies

In this paper, we present an investigation of technology scaling applied to pixel architectures for chemical sensing using Ion-Sensitive Field-Effect Transistors (ISFETs). In particular, we focus our discussion on pixels which integrate mixed-signal circuitry, providing more computational power to perform in-pixel quantisation or sensor calibration. We present the case of our pixel topology and analyse its performance in five process nodes from 350nm to 65nm. Observations include a reduction of 95% in area, at the cost of increased noise and signal attenuation due to the passivation capacitance. In an attempt to characterise this trade-off, we derive a Figure of Merit and use this new performance parameter to demonstrate the interest of smaller feature sizes for ISFET pixel architectures, contrarily to the current trend in instrumentation. More considerations will be given to the implementation of ISFETs in deep submicron technologies.