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

Design of a single-chip pH sensor using a conventional 0.6-μm CMOS process

A pH sensor fabricated on a single chip by an unmodified, commercial 0.6-/spl μm CMOS process is presented. The sensor comprises a circuit for making differential measurements between an ion-sensitive field-effect transistor (ISFET) and a reference FET (REFET). The ISFET has a floating-gate structure and uses the silicon nitride passivation layer as a pH-sensitive insulator. As fabricated, it has a large threshold voltage that is postulated to be caused by a trapped charge on the floating gate. Ultraviolet radiation and bulk-substrate biasing is used to permanently modify the threshold voltage so that the ISFET can be used in a battery-operated circuit. A novel post-processing method using a single layer of photoresist is used to define the sensing areas and to provide robust encapsulation for the chip. The complete circuit, operating from a single 3-V supply, provides an output voltage proportional to pH and can be powered down when not required

Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

A 64-channel, 1.1-pA-accurate on-chip potentiostat for parallel electrochemical monitoring

Electrochemical monitoring is crucial for both industrial applications, such as microbial electrolysis and corrosion monitoring as well as consumer applications such as personal health monitoring. Yet, state-of-the-art integrated potentiostat monitoring devices have few parallel channels with limited flexibility due to their channel architecture. This work presents a novel, widely scalable channel architecture using a switch capacitor based Howland current pump and a digital potential controller. An integrated, 64-channel CMOS potentiostat array has been fabricated. Each individual channel has a dynamic current range of 120dB with 1.1pA precision with up to 100kHz bandwidth. The on-chip working electrodes are post-processed with gold to ensure (bio)electrochemical compatibility

Prototype MEMS Capacitive Pressure Sensor Design and Manufacturing.

This paper is intended to describe the design and manufacturing aspects of a simple micromachined capacitive pressure sensor working in the pressure range of 0-1000 mbar. 500 µm thick Borofloat® 33 glass and silicon wafers were used as substrates. The basic transducer structure consists of a rectangular silicon membrane as deformable electrode and a fix aluminum electrode formed on the glass surface. In order to determine the exact geometry of the silicon electrode structure numerical models and simulations were applied. The thin silicon membrane was fabricated by Si bulk micromachining, i.e. anisotropic alkaline etching with electrochemical etch-stop. The two wafers were bonded together at low temperature by anodic bonding. After bonding and dicing the wafers the pressure sensors were characterized mechanically and functionally also. Our results demonstrate the functional behavior of the manufactured sensor structures and provide excellent verification of the preliminary expectations based on theoretical calculations and electro-mechanical simulations