Wideband Fully-Programmable Dual-Mode CMOS Analogue Front-End for Electrical Impedance Spectroscopy

This paper presents a multi-channel dual-mode CMOS analogue front-end (AFE) for electrochemical and bioimpedance analysis. Current-mode and voltage-mode readouts, integrated on the same chip, can provide an adaptable platform to correlate single-cell biosensor studies with large-scale tissue or organ analysis for real-time cancer detection, imaging and characterization. The chip, implemented in a 180-nm CMOS technology, combines two current-readout (CR) channels and four voltage-readout (VR) channels suitable for both bipolar and tetrapolar electrical impedance spectroscopy (EIS) analysis. Each VR channel occupies an area of 0.48 mm 2 , is capable of an operational bandwidth of 8 MHz and a linear gain in the range between -6 dB and 42 dB. The gain of the CR channel can be set to 10 kΩ, 50 kΩ or 100 kΩ and is capable of 80-dB dynamic range, with a very linear response for input currents between 10 nA and 100 μ A. Each CR channel occupies an area of 0.21 mm 2 . The chip consumes between 530 μ A and 690 μ A per channel and operates from a 1.8-V supply. The chip was used to measure the impedance of capacitive interdigitated electrodes in saline solution. Measurements show close matching with results obtained using a commercial impedance analyser. The chip will be part of a fully flexible and configurable fully-integrated dual-mode EIS system for impedance sensors and bioimpedance analysis

CMOS Design of Reconfigurable SoC Systems for Impedance Sensor Devices

La rápida evolución en el campo de los sensores inteligentes, junto con los avances en las tecnologías de la computación y la comunicación, está revolucionando la forma en que recopilamos y analizamos datos del mundo físico para tomar decisiones, facilitando nuevas soluciones que desempeñan tareas que antes eran inconcebibles de lograr.La inclusión en un mismo dado de silicio de todos los elementos necesarios para un proceso de monitorización y actuación ha sido posible gracias a los avances en micro (y nano) electrónica. Al mismo tiempo, la evolución de las tecnologías de procesamiento y micromecanizado de superficies de silicio y otros materiales complementarios ha dado lugar al desarrollo de sensores integrados compatibles con CMOS, lo que permite la implementación de matrices de sensores de alta densidad. Así, la combinación de un sistema de adquisición basado en sensores on-Chip, junto con un microprocesador como núcleo digital donde se puede ejecutar la digitalización de señales, el procesamiento y la comunicación de datos proporciona características adicionales como reducción del coste, compacidad, portabilidad, alimentación por batería, facilidad de uso e intercambio inteligente de datos, aumentando su potencial número de aplicaciones.Esta tesis pretende profundizar en el diseño de un sistema portátil de medición de espectroscopía de impedancia de baja potencia operado por batería, basado en tecnologías microelectrónicas CMOS, que pueda integrarse con el sensor, proporcionando una implementación paralelizable sin incrementar significativamente el tamaño o el consumo, pero manteniendo las principales características de fiabilidad y sensibilidad de un instrumento de laboratorio. Esto requiere el diseño tanto de la etapa de gestión de la energía como de las diferentes celdas que conforman la interfaz, que habrán de satisfacer los requisitos de un alto rendimiento a la par que las exigentes restricciones de tamaño mínimo y bajo consumo requeridas en la monitorización portátil, características que son aún más críticas al considerar la tendencia actual hacia matrices de sensores.A nivel de celdas, se proponen diferentes circuitos en un proceso CMOS de 180 nm: un regulador de baja caída de voltaje como unidad de gestión de energía, que proporciona una alimentación de 1.8 V estable, de bajo ruido, precisa e independiente de la carga para todo el sistema; amplificadores de instrumentación con una aproximación completamente diferencial, que incluyen una etapa de entrada de voltaje/corriente configurable, ganancia programable y ancho de banda ajustable, tanto en la frecuencia de corte baja como alta; un multiplicador para conformar la demodulación dual, que está embebido en el amplificador para optimizar consumo y área; y filtros pasa baja totalmente integrados, que actúan como extractores de magnitud de DC, con frecuencias de corte ajustables desde sub-Hz hasta cientos de Hz.<br /

Sensing Cell-Culture Assays with Low-Cost Circuitry

An alternative approach for cell-culture end-point protocols is proposed herein. This new technique is suitable for real-time remote sensing. It is based on Electrical Cell-substrate Impedance Spectroscopy (ECIS) and employs the Oscillation-Based Test (OBT) method. Simple and straightforward circuit blocks form the basis of the proposed measurement system. Oscillation parameters – frequency and amplitude – constitute the outcome, directly correlated with the culture status. A user can remotely track the evolution of cell cultures in real time over the complete experiment through a web tool continuously displaying the acquired data. Experiments carried out with commercial electrodes and a well-established cell line (AA8) are described, obtaining the cell number in real time from growth assays. The electrodes have been electrically characterized along the design flow in order to predict the system performance and the sensitivity curves. Curves for 1-week cell growth are reported. The obtained experimental results validate the proposed OBT for cell-culture characterization. Furthermore, the proposed electrode model provides a good approximation for the cell number and the time evolution of the studied cultures.España, Feder TEC2013-46242-C3-1-

A CMOS low pass filter for soc lock-in-based measurement devices

This paper presents a fully integrated Gm–C low pass ¿lter (LPF) based on a current ¿steering Gm reduction-tuning technique, specifically designed to operate as the output stage of a SoC lock-in amplifier. To validate this proposal, a first-order and a second-order single-ended topology were integrated into a 1.8 V to 0.18 µm CMOS (Complementary Metal-Oxide-Semiconductor) process, showing experimentally a tuneable cutoff frequency that spanned five orders of magnitude, from tens of mHz to kHz, with a constant current consumption (below 3 µA/pole), compact size (&lt;0.0140 mm2 /pole), and a dynamic range better than 70 dB. Compared to state-of-the-art solutions, the proposed approach exhibited very competitive performances while simultaneously fully satisfying the demanding requirements of on-chip portable measurement systems in terms of highly efficient area and power. This is of special relevance, taking into account the current trend towards multichannel instruments to process sensor arrays, as the total area and power consumption will be proportional to the number of channels

1.0 v-0.18 µm CMOS tunable low pass filters with 73 db dr for on-chip sensing acquisition systems

This paper presents a new approach based on the use of a Current Steering (CS) technique for the design of fully integrated Gm–C Low Pass Filters (LPF) with sub-Hz to kHz tunable cut-off frequencies and an enhanced power-area-dynamic range trade-off. The proposed approach has been experimentally validated by two different first-order single-ended LPFs designed in a 0.18 µm CMOS technology powered by a 1.0 V single supply: a folded-OTA based LPF and a mirrored-OTA based LPF. The first one exhibits a constant power consumption of 180 nW at 100 nA bias current with an active area of 0.00135 mm2 and a tunable cutoff frequency that spans over 4 orders of magnitude (~100 mHz–152 Hz @ CL = 50 pF) preserving dynamic figures greater than 78 dB. The second one exhibits a power consumption of 1.75 µW at 500 nA with an active area of 0.0137 mm2 and a tunable cutoff frequency that spans over 5 orders of magnitude (~80 mHz–~1.2 kHz @ CL = 50 pF) preserving a dynamic range greater than 73 dB. Compared with previously reported filters, this proposal is a competitive solution while satisfying the low-voltage low-power on-chip constraints, becoming a preferable choice for general-purpose reconfigurable front-end sensor interfaces

Development of real-time cellular impedance analysis system

The cell impedance analysis technique is a label-free, non-invasive method, which simplifies sample preparation and allows applications requiring unmodified cell retrieval. However, traditional impedance measurement methods suffer from various problems (speed, bandwidth, accuracy) for extracting the cellular impedance information. This thesis proposes an improved system for extracting precise cellular impedance in real-time, with a wide bandwidth and satisfactory accuracy. The system hardware consists of five main parts: a microelectrode array (MEA), a stimulation circuit, a sensing circuit, a multi-function card and a computer. The development of system hardware is explored. Accordingly, a novel bioimpedance measurement method coined digital auto balancing bridge method, which is improved from the traditional analogue auto balancing bridge circuitry, is realized for real-time cellular impedance measurement. Two different digital bridge balancing algorithms are proposed and realized, which are based on least mean squares (LMS) algorithm and fast block LMS (FBLMS) algorithm for single- and multi-frequency measurements respectively. Details on their implementation in FPGA are discussed. The test results prove that the LMS-based algorithm is suitable for accelerating the measurement speed in single-frequency situation, whilst the FBLMS-based algorithm has advantages in stable convergence in multi-frequency applications. A novel algorithm, called the All Phase Fast Fourier Transform (APFFT), is applied for post-processing of bioimpedance measurement results. Compared with the classical FFT algorithm, the APFFT significantly reduces spectral leakage caused by truncation error. Compared to the traditional FFT and Digital Quadrature Demodulation (DQD) methods, the APFFT shows excellent performance for extracting accurate phase and amplitude in the frequency spectrum. Additionally, testing and evaluation of the realized system has been performed. The results show that our system achieved a satisfactory accuracy within a wide bandwidth, a fast measurement speed and a good repeatability. Furthermore, our system is compared with a commercial impedance analyzer (Agilent 4294A) in biological experiments. The results reveal that our system achieved a comparable accuracy to the commercial instrument in the biological experiments. Finally, conclusions are given and the future work is proposed

The Investigation and Implementation of electrical Impedance Tomography Hardware System

Electrical impedance tomography (EIT) is a medical imaging technology that provides a tomographic representation of the distribution of electrical impedance within the body. As the electrical impedance varies for different body tissues, it is possible to characterize tissues from the images and to detect physiological events. EIT systems have been developed from applying a single signal frequency to a range of frequencies. Imaging at multiple frequencies significantly improves the ability to characterize and differentiate heterogeneity within the region of interest. Applications of EIT are limited by its poor resolution as a consequence of limited number of electrodes and lack of independently published measurements. In a practical EIT system design the parallel structure is normally adopted as it provides a real time monitoring structure. However, there is a difficulty in expanding to a 2-dimensitional or 3-dimensitional high resolution imaging system, as the number of electrodes increase. In this thesis, a serial structure spectrum EIT system has been investigated and developed. Modelling of the electrical circuit has shown that the system bandwidth is degraded primarily by the signal transmission in the coaxial cable and multiplexer. To remove the capacitive effect of these components, a distribute system concept has been developed. The concept uses active electrodes in which a current source and a front end amplifier are embedded in the electrode which makes direct contact with the tissue being measured. The active electrode is based on the Howland current source. The required high output impedance of Howland current source can be realised by matching the two resistor arms. However, from the electrical equivalent circuit analysis the actual output impedance of this circuit was found to be degraded by the op-amp' s limited open loop gain, especially at higher frequencies. To solve the problem, the author describes in detail a novel method of compensating for the above effects. Subsequent circuit tests showed significant improvement after the compensation. Further, to improve the small signal noise ratio a programmable gain amplifier to adapt the frame data measurement was developed. These developments have led to the feasibility of active electrodes. The thesis describes in detail the development, of the MK2 EIT system which is presented as the output of this research

A Novel Power-Efficient Wireless Multi-channel Recording System for the Telemonitoring of Electroencephalography (EEG)

This research introduces the development of a novel EEG recording system that is modular, batteryless, and wireless (untethered) with the supporting theoretical foundation in wireless communications and related design elements and circuitry. Its modular construct overcomes the EEG scaling problem and makes it easier for reconfiguring the hardware design in terms of the number and placement of electrodes and type of standard EEG system contemplated for use. In this development, portability, lightweight, and applicability to other clinical applications that rely on EEG data are sought. Due to printer tolerance, the 3D printed cap consists of 61 electrode placements. This recording capacity can however extend from 21 (as in the international 10-20 systems) up to 61 EEG channels at sample rates ranging from 250 to 1000 Hz and the transfer of the raw EEG signal using a standard allocated frequency as a data carrier. The main objectives of this dissertation are to (1) eliminate the need for heavy mounted batteries, (2) overcome the requirement for bulky power systems, and (3) avoid the use of data cables to untether the EEG system from the subject for a more practical and less restrictive setting. Unpredictability and temporal variations of the EEG input make developing a battery-free and cable-free EEG reading device challenging. Professional high-quality and high-resolution analog front ends are required to capture non-stationary EEG signals at microvolt levels. The primary components of the proposed setup are the wireless power transmission unit, which consists of a power amplifier, highly efficient resonant-inductive link, rectification, regulation, and power management units, as well as the analog front end, which consists of an analog to digital converter, pre-amplification unit, filtering unit, host microprocessor, and the wireless communication unit. These must all be compatible with the rest of the system and must use the least amount of power possible while minimizing the presence of noise and the attenuation of the recorded signal A highly efficient resonant-inductive coupling link is developed to decrease power transmission dissipation. Magnetized materials were utilized to steer electromagnetic flux and decrease route and medium loss while transmitting the required energy with low dissipation. Signal pre-amplification is handled by the front-end active electrodes. Standard bio-amplifier design approaches are combined to accomplish this purpose, and a thorough investigation of the optimum ADC, microcontroller, and transceiver units has been carried out. We can minimize overall system weight and power consumption by employing battery-less and cable-free EEG readout system designs, consequently giving patients more comfort and freedom of movement. Similarly, the solutions are designed to match the performance of medical-grade equipment. The captured electrical impulses using the proposed setup can be stored for various uses, including classification, prediction, 3D source localization, and for monitoring and diagnosing different brain disorders. All the proposed designs and supporting mathematical derivations were validated through empirical and software-simulated experiments. Many of the proposed designs, including the 3D head cap, the wireless power transmission unit, and the pre-amplification unit, are already fabricated, and the schematic circuits and simulation results were based on Spice, Altium, and high-frequency structure simulator (HFSS) software. The fully integrated head cap to be fabricated would require embedding the active electrodes into the 3D headset and applying current technological advances to miniaturize some of the design elements developed in this dissertation

Advances in Solid State Circuit Technologies

This book brings together contributions from experts in the fields to describe the current status of important topics in solid-state circuit technologies. It consists of 20 chapters which are grouped under the following categories: general information, circuits and devices, materials, and characterization techniques. These chapters have been written by renowned experts in the respective fields making this book valuable to the integrated circuits and materials science communities. It is intended for a diverse readership including electrical engineers and material scientists in the industry and academic institutions. Readers will be able to familiarize themselves with the latest technologies in the various fields

Electronics for Sensors

The aim of this Special Issue is to explore new advanced solutions in electronic systems and interfaces to be employed in sensors, describing best practices, implementations, and applications. The selected papers in particular concern photomultiplier tubes (PMTs) and silicon photomultipliers (SiPMs) interfaces and applications, techniques for monitoring radiation levels, electronics for biomedical applications, design and applications of time-to-digital converters, interfaces for image sensors, and general-purpose theory and topologies for electronic interfaces