Chemical Current-Conveyor: a new approach in biochemical computation

Biochemical sensors that are low cost, small in size and compatible with integrated circuit technology play an essential part in the drive towards personalised healthcare and the research described in this thesis is concerned with this area of medical instrumentation. A new biochemical measurement system able to sense key properties of biochemical fluids is presented. This new integrated circuit biochemical sensor, called the Chemical Current-Conveyor, uses the ion sensitive field effect transistor as the input sensor combined with the current-conveyor, an analog building-block, to produce a range of measurement systems. The concept of the Chemical Current-Conveyor is presented together with the design and subsequent fabrication of a demonstrator integrated circuit built on conventional 0.35μm CMOS silicon technology. The silicon area of the Chemical Current-Conveyor is (92μm x 172μm) for the N-channel version and (99μm x 165μm) for the P-channel version. Power consumption for the N-channel version is 30μW and 43μW for the P-channel version with a full load of 1MΩ. The maximum sensitivity achieved for pH measurement was 46mV per pH. The potential of the Chemical Current Conveyor as a versatile biochemical integrated circuit, able to produce output information in an appropriate form for direct clinical use has been confirmed by applications including measurement of (i) pH, (ii) buffer index ( ), (iii) urea, (iv) creatinine and (v) urea:creatinine ratio. In all five cases the device has been demonstrated successfully, confirming the validity of the original aim of this research project, namely to produce a versatile and flexible analog circuit for many biochemical measurement applications. Finally, the thesis closes with discussion of another potential application area for the Chemical Current Conveyor and the main contributions can be summarised by the design and development of the first: ISFET based current-conveyor biochemical sensor, called 'Chemical Current Conveyor, CCCII+' has been designed and developed. It is a general purpose biochemical analog building-block for several biochemical measurements. Real-time buffer capacity measurement system, based on the CCCII+, which exploits the imbedded analog computation capability of the CCCII+. Real-time enzyme based CCCII+ namely, Creatinine-CCCII+ and Urea-CCCII+ for real-time monitoring system of renal system. The system can provide outputs of 3 important parameters of the renal system, namely (i) urea concentration, (ii) creatinine concentration, and (ii) urea to creatinine ratio

A Flexible, Highly Integrated, Low Power pH Readout

Medical devices are widely employed in everyday life as wearable and implantable technologies make more and more technological breakthroughs. Implantable biosensors can be implanted into the human body for monitoring of relevant physiological parameters, such as pH value, glucose, lactate, CO2 [carbon dioxide], etc. For these applications the implantable unit needs a whole functional set of blocks such as micro- or nano-sensors, sensor signal processing and data generation units, wireless data transmitters etc., which require a well-designed implantable unit.Microelectronics technology with biosensors has caused more and more interest from both academic and industrial areas. With the advancement of microelectronics and microfabrication, it makes possible to fabricate a complete solution on an integrated chip with miniaturized size and low power consumption.This work presents a monolithic pH measurement system with power conditioning system for supply power derived from harvested energy. The proposed system includes a low-power, high linearity pH readout circuits with wide pH values (0-14) and a power conditioning unit based on low drop-out (LDO) voltage regulator. The readout circuit provides square-wave output with frequency being highly linear corresponding to the input pH values. To overcome the process variations, a simple calibration method is employed in the design which makes the output frequency stay constant over process, supply voltage and temperature variations. The prototype circuit is designed and fabricated in a standard 0.13-μm [micro-meter] CMOS process and shows good linearity to cover the entire pH value range from 0-14 while the voltage regulator provides a stable supply voltage for the system

Hybrid dual mode sensor for simultaneous detection of two serum metabolites

Metabolites are the ultimate readout of disease phenotype that plays a significant role in the study of human disease. Multiple metabolites sometimes serve as biomarkers for a single metabolic disease. Therefore, simultaneous detection and analysis of those metabolites facilitate early diagnostics of the disease. Conventional approaches to detect and quantify metabolites include mass spectrometry and nuclear magnetic resonance that require bulky and expensive equipment. Here, we present a disposable sensing platform that is based on complementary metal–oxide–semiconductor process. It contains two sensors: an ion sensitive field-effect transistor and photodiode that can work independently for detection of pH and color change produced during the metabolite-enzyme reaction. Serum glucose and cholesterol have been detected and quantified simultaneously with the new platform, which shows good sensitivity within the physiological range. Low cost and easy manipulation make our device a prime candidate for personal metabolome sensing diagnostics

An Integrated Platform for Differential Electrochemical and ISFET Sensing

A fully-integrated differential biosensing platform on CMOS is presented for miniaturized enzyme-based electrochemical sensing. It enables sensor background current elimination and consists of a differential sensor array and a differential readout IC (DiRIC). The sensor array includes a four-electrode sensor for amperometric electrochemical sensing, as well as a differential ISFET-based pH sensor to calibrate the biosensors. The ISFET is biased in weak inversion and co-designed with DiRIC to enable pH measurements from 1 to 14 with resolution of 0.1 pH. DiRIC enables differential current measurement in the range of ¿¿100 ¿¿A with more than 120dB dynamic range

An Extended CMOS ISFET Model Incorporating the Physical Design Geometry and the Effects on Performance and Offset Variation

This paper presents an extended model for the CMOS-based ion-sensitive field-effect transistor, incorporating design parameters associated with the physical geometry of the device. This can, for the first time, provide a good match between calculated and measured characteristics by taking into account the effects of nonidealities such as threshold voltage variation and sensor noise. The model is evaluated through a number of devices with varying design parameters (chemical sensing area and MOSFET dimensions) fabricated in a commercially available 0.35-µm CMOS technology. Threshold voltage, subthreshold slope, chemical sensitivity, drift, and noise were measured and compared with the simulated results. The first- and second-order effects are analyzed in detail, and it is shown that the sensors' performance was in agreement with the proposed model

An Auto-Offset-Removal circuit for chemical sensing based on the PG-ISFET

Published versio

Chemical Bionics - a novel design approach using ion sensitive field effect transistors

In the late 1980s Carver Mead introduced Neuromorphic engineering in which various aspects of the neural systems of the body were modelled using VLSI1 circuits. As a result most bio-inspired systems to date concentrate on modelling the electrical behaviour of neural systems such as the eyes, ears and brain. The reality is however that biological systems rely on chemical as well as electrical principles in order to function. This thesis introduces chemical bionics in which the chemically-dependent physiology of specific cells in the body is implemented for the development of novel bio-inspired therapeutic devices. The glucose dependent pancreatic beta cell is shown to be one such cell, that is designed and fabricated to form the first silicon metabolic cell. By replicating the bursting behaviour of biological beta cells, which respond to changes in blood glucose, a bio-inspired prosthetic for glucose homeostasis of Type I diabetes is demonstrated. To compliment this, research to further develop the Ion Sensitive Field Effect Transistor (ISFET) on unmodified CMOS is also presented for use as a monolithic sensor for chemical bionic systems. Problems arising by using the native passivation of CMOS as a sensing surface are described and methods of compensation are presented. A model for the operation of the device in weak inversion is also proposed for exploitation of its physical primitives to make novel monolithic solutions. Functional implementations in various technologies is also detailed to allow future implementations chemical bionic circuits. Finally the ISFET integrate and fire neuron, which is the first of its kind, is presented to be used as a chemical based building block for many existing neuromorphic circuits. As an example of this a chemical imager is described for spatio-temporal monitoring of chemical species and an acid base discriminator for monitoring changes in concentration around a fixed threshold is also proposed

A Novel Pseudo-PMOS Integrated ISFET Device for Water Quality Monitoring

The paper presents a performance analysis of novel CMOS Integrated pseudo-PMOS ISFET (PP-ISFET) having zero static power dissipation. The main focus is on simulation of power and performance analysis along with the comparison with existing devices, which is used for water quality monitoring. The conventional devices, generally used, consume high power and are not stable for long term monitoring. The conventional device has the drawbacks of low value of slew rate, high power consumption, and nonlinear characteristics, but in this novel design, due to zero static power, less load capacitance on input signals, faster switching, fewer transistors, and higher circuit density, the device exhibits a better slew rate and piecewise linear characteristics and is seen consuming low power of the order of 30 mW. The proposed circuit reduces total power consumption per cycle, increases the speed of operation, is fairly linear, and is simple to implement