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

Novel Current-Mode Sensor Interfacing and Radio Blocks for Cell Culture Monitoring

Since 2004 Imperial College has been developing the world’s first application-specific instrumentation aiming at the on-line, in-situ, physiochemical monitoring of adult stem cell cultures. That effort is internationally known as the ‘Intelligent Stem Cell Culture Systems’ (ISCCS) project. The ISCCS platform is formed by the functional integration of biosensors, interfacing electronics and bioreactors. Contrary to the PCB-level ISCCS platform the work presented in this thesis relates to the realization of a miniaturized cell culture monitoring platform. Specifically, this thesis details the synthesis and fabrication of pivotal VLSI circuit blocks suitable for the construction of a miniaturized microelectronic cell monitoring platform. The thesis is composed of two main parts. The first part details the design and operation of a two-stage current-input currentoutput topology suitable for three-electrode amperometric sensor measurements. The first stage is a CMOS-dual rail-class AB-current conveyor providing a low impedancevirtual ground node for a current input. The second stage is a novel hyperbolic-sinebased externally-linear internally-non-linear current amplification stage. This stage bases its operation upon the compressive sinh−1 conversion of the interfaced current to an intermediate auxiliary voltage and the subsequent sinh expansion of the same voltage. The proposed novel topology has been simulated for current-gain values ranging from 10 to 1000 using the parameters of the commercially available 0.8μm AMS CMOS process. Measured results from a chip fabricated in the same technology are also reported. The proposed interfacing/amplification architecture consumes 0.88-95μW. The second part describes the design and practical evaluation of a 13.56MHz frequency shift keying (FSK) short-range (5cm) telemetry link suitable for the monitoring of incubated cultures. Prior to the design of the full FSK radio system, a pair of 13.56MHz antennae are characterized experimentally. The experimental S-parameter-value determination of the 13.56MHz wireless link is incorporated into the Cadence Design Framework allowing a high fidelity simulation of the reported FSK radio. The transmitter of the proposed system is a novel multi-tapped seven-stage ring-oscillator-based VCO whereas the core of the receiver is an appropriately modified phase locked loop (PLL). Simulated and measured results from a 0.8μm CMOS technology chip are reported

Integrated circuit & system design for concurrent amperometric and potentiometric wireless electrochemical sensing

Complementary Metal-Oxide-Semiconductor (CMOS) biosensor platforms have steadily grown in healthcare and commerial applications. This technology has shown potential in the field of commercial wearable technology, where CMOS sensors aid the development of miniaturised sensors for an improved cost of production and response time. The possibility of utilising wireless power and data transmission techniques for CMOS also allows for the monolithic integration of the communication, power and sensing onto a single chip, which greatly simplifies the post-processing and improves the efficiency of data collection. The ability to concurrently utilise potentiometry and amperometry as an electrochemical technique is explored in this thesis. Potentiometry and amperometry are two of the most common transduction mechanisms for electrochemistry, with their own advantages and disadvantages. Concurrently applying both techniques will allow for real-time calibration of background pH and for improved accuracy of readings. To date, developing circuits for concurrently sensing potentiometry and amperometry has not been explored in the literature. This thesis investigates the possibility of utilising CMOS sensors for wireless potentiometric and amperometric electrochemical sensing. To start with, a review of potentiometry and amperometry is evaluated to understand the key factors behind their operation. A new configuration is proposed whereby the reference electrode for both electrochemistry techniques are shared. This configuration is then compared to both the original configurations to determine any differences in the sensing accuracy through a novel experiment that utilises hydrogen peroxide as a measurement analyte. The feasibility of the configuration with the shared reference electrode is proven and utilised as the basis of the electrochemical configuration for the front end circuits. A unique front-end circuit named DAPPER is developed for the shared reference electrode topology. A review of existing architectures for potentiometry and amperometry is evaluated, with a specific focus on low power consumption for wireless applications. In addition, both the electrochemical sensing outputs are mixed into a single output data channel for use with a near-field communication (NFC). This mixing technique is also further analysed in this thesis to understand the errors arising due to various factors. The system is fabricated on TSMC 180nm technology and consumes 28µW. It measures a linear input current range from 250pA - 0.1µW, and an input voltage range of 0.4V - 1V. This circuit is tested and verified for both electrical and electrochemical tests to showcase its feasibility for concurrent measurements. This thesis then provides the integration of wireless blocks into the system for wireless powering and data transmission. This is done through the design of a circuit named SPACEMAN that consists of the concurrent sensing front-end, wireless power blocks, data transmission, as well as a state machine that allows for the circuit to switch between modes: potentiometry only, amperometry only, concurrent sensing and none. The states are switched through re-booting the circuit. The core size of the electronics is 0.41mm² without the coil. The circuit’s wireless powering and data transmission is tested and verified through the use of an external transmitter and a connected printed circuit board (PCB) coil. Finally, the future direction for ongoing work to proceed towards a fully monolithic electrochemical technique is discussed through the next development of a fully integrated coil-on-CMOS system, on-chip electrodes with the electroplating and microfludics, the development of an external transmitter for powering the device and a test platform. The contributions of this thesis aim to formulate a use for wireless electrochemical sensors capable of concurrent measurements for use in wearable devices.Open Acces

Study on Integrated Redox Image Sensor Employing Square Wave Voltammetry

豊橋技術科学大

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

An Approach to an Inhibition Electronic Tongue to Detect On-Line Organophosphorus Insecticides Using a Computer Controlled Multi-Commuted Flow System

An approach to an inhibition bioelectronic tongue is presented. The work is focused on development of an automated flow system to carry out experimental assays, a custom potentiostat to measure the response from an enzymatic biosensor, and an inhibition protocol which allows on-line detections. A Multi-commuted Flow Analysis system (MCFA) was selected and developed to carry out assays with an improved inhibition method to detect the insecticides chlorpyrifos oxon (CPO), chlorfenvinfos (CFV) and azinphos methyl-oxon (AZMO). The system manifold comprised a peristaltic pump, a set of seven electronic valves controlled by a personal computer electronic interface and software based on LabView® to control the sample dilutions into the cell. The inhibition method consists in the injection of the insecticide when the enzyme activity has reached the plateau of the current; with this method the incubation time is avoided. A potentiostat was developed to measure the response from the enzymatic biosensor. Low limits of detection of 10 nM for CPO, CFV, and AZMO were achieved

Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

Design of a Customized multipurpose nano-enabled implantable system for in-vivo theranostics

The first part of this paper reviews the current development and key issues on implantable multi-sensor devices for in vivo theranostics. Afterwards, the authors propose an innovative biomedical multisensory system for in vivo biomarker monitoring that could be suitable for customized theranostics applications. At this point, findings suggest that cross-cutting Key Enabling Technologies (KETs) could improve the overall performance of the system given that the convergence of technologies in nanotechnology, biotechnology, micro&nanoelectronics and advanced materials permit the development of new medical devices of small dimensions, using biocompatible materials, and embedding reliable and targeted biosensors, high speed data communication, and even energy autonomy. Therefore, this article deals with new research and market challenges of implantable sensor devices, from the point of view of the pervasive system, and time-to-market. The remote clinical monitoring approach introduced in this paper could be based on an array of biosensors to extract information from the patient. A key contribution of the authors is that the general architecture introduced in this paper would require minor modifications for the final customized bio-implantable medical device

Electrochemical Sensors and On-chip Optical Sensors

abstract: The microelectronics technology has seen a tremendous growth over the past sixty years. The advancements in microelectronics, which shows the capability of yielding highly reliable and reproducible structures, have made the mass production of integrated electronic components feasible. Miniaturized, low-cost, and accurate sensors became available due to the rise of the microelectronics industry. A variety of sensors are being used extensively in many portable applications. These sensors are promising not only in research area but also in daily routine applications. However, many sensing systems are relatively bulky, complicated, and expensive and main advantages of new sensors do not play an important role in practical applications. Many challenges arise due to intricacies for sensor packaging, especially operation in a solution environment. Additional problems emerge when interfacing sensors with external off-chip components. A large amount of research in the field of sensors has been focused on how to improve the system integration. This work presents new methods for the design, fabrication, and integration of sensor systems. This thesis addresses these challenges, for example, interfacing microelectronic system to a liquid environment and developing a new technique for impedimetric measurement. This work also shows a new design for on-chip optical sensor without any other extra components or post-processing.Dissertation/ThesisDoctoral Dissertation Electrical Engineering 201