Panagiotis Kassanos

An Integrated Analog Readout for Multi-Frequency Bioimpedance Measurements

Bioimpedance spectroscopy is used in a wide range of biomedical applications. This paper presents an integrated analog readout, which employs synchronous detection to perform galvanostatic multi-channel, multi-frequency bioimpedance measurements. The circuit was fabricated in a 0.35-μm CMOS technology and occupies an area of 1.52 mm2. The effect of random dc offsets is investigated, along with the use of chopping to minimize them. Impedance measurements of a known RC load and skin (using commercially available electrodes) demonstrate the operation of the system over a frequency range up to 1 MHz. The circuit operates from a ±2.5 V power supply and has a power consumption of 3.4-mW per channel.

A novel front-end for impedance spectroscopy

A novel method for calculating unknown impedances is presented. In contrast to synchronous detection (SD), which provides the real and imaginary components, the magnitude and phase of the impedance are calculated. Non-accurate generation of the required in-phase and quadrature signals required in SD and mismatches between the channels generate large errors. The proposed method does not require such signals. The measured potential across the sensor is rectified and then low-pass filtered to obtain the magnitude. The phase is calculated by two comparators followed by an XOR gate. A prototype of the system was built using discrete components and proof of concept measurements were carried out using resistors and capacitors of known values.

Towards the development of an electrochemical biosensor for hCG? detection

The free beta subunit of human-chorionic-gonadotropin (hCGbeta) is critical for various aspects of human health. Detection and quantification of this protein are essential during pregnancy as it provides clinicians valuable information regarding the progress of a pregnancy and the health of a foetus. Furthermore, it can be used as a biomarker for gestational trophoblastic disease (GTD), germ cell tumours and some non-trophoblastic gynaecological cancers and common epithelial tumours. Monitoring hCGbeta levels is particularly important for patient treatment monitoring and relapse detection especially in GTD. This paper presents an investigation of the characteristics of the first two stages necessary for the development of a bio-impedance hCGbeta sensor, using impedance spectroscopy and commercially available microelectrodes. Additionally, electrical equivalent circuit models based on the experimental results of these stages are presented. The biosensor is based on the formation of stable antibody-antigen complexes on golden microband electrodes covered with a layer of a self-assembled monolayer (SAM) or with both SAM and protein G. The preliminary results and analysis relate the interfacial processes and physical structure of the sensor to its electrical behaviour. Finally, preliminary results obtained from the sensor without protein G, which strongly indicate hCGbeta detection, are also presented.

A tetrapolar bio-impedance sensing system for gastrointestinal tract monitoring

Surgical Site Infection (SSI) imposes a significant burden clinically and compromises patient recovery. Anastomosis in the gastrointestinal (GI) tract is a particularly challenging case where failure of the anastomosis can lead to leakage, resulting in an increase in mortality rates. However early diagnosis and intervention are hampered by a lack of continuous sensing and long diagnostic intervals of current clinical practices. Tissue ischemia in the vicinity of the anastomosis has been found to be an early surrogate marker for anastomotic leakage. Electrical bio-impedance is a promising non-invasive technique for identifying and monitoring tissue ischemia. In this paper the modelling, design and validation of a bio-impedance system including compact instrumentation and a novel bio-impedance sensor optimized for mucosal tissue measurements in the GI tract are presented. The preliminary system, including the impedance probe, is validated experimentally for GI implant applications to provide early detection of tissue ischemia following GI surgery.

Towards an optimized design for tetrapolar affinity-based impedimetric immunosensors for lab-on-a-chip applications

Electrochemical impedance detection of biomolecules relies on the electrode system used. The architecture of the metal electrodes, on top of which the biosensing materials and consequently the target molecules are immobilized, is of particular importance. A high and uniform sensitivity of the sensor to impedance changes in regions of interest is required. In this paper, the sensitivity of tetrapolar coplanar-electrode systems is investigated as a function of electrode position, with the use of FEM modeling. The results indicate, that bringing the inner two electrodes closer to the outer two, increases positive and reduces negative sensitivity regions with zero sensitivity to impedance changes always present on the electrode surface.

Comparison of tetrapolar injection-measurement techniques for coplanar affinity-based impedimetric immunosensors

This paper focuses on tetrapolar coplanar-electrode affinity-based sensors. In a tetrapolar electrode systems there are different ways with which signals can be injected and measured. These injection and measurement methods, namely the Wenner, Dipole-Dipole and Cross techniques, are investigated in this paper by analyzing their sensitivity distribution. This is conducted with the use of FEM modeling. The results indicate that the Dipole-Dipole technique provides only a small negative sensitivity region near the electrode surface plane. On the other hand, regions of positive sensitivity dominate in the Wenner while regions of negative sensitivity dominate in the Cross techniques.

Development of a Biosensor for hCGβ Detection

Detection and concentration monitoring of Human Chorionic Gonadotropin (hCG) and especially, its free beta-subunit, hCGβ, is critical for various aspects of the human health. From pregnancy tests to monitoring hCG and hCGβ blood levels, they provide physicians valuable information concerning the progress of a pregnancy and the health of a fetus. More importantly, they can also be used as markers of gestational trophoblastic disease (GTD), germ cell tumours and some non-trophoblastic tumours. Detection of hCGβ is also critical for patient treatment monitoring and for relapse detection. According to the literature, the use of hCGβ as a tumour marker is limited by the lack of high sensitivity and specificity sensors. In this paper we present the first two steps of the development of an impedance biosensor, based on the formation of a stable antibody-antigen complex on gold microband electrodes and the preliminary results and analysis of the interface processes, relating the physical structure of the sensor to its electrical behaviour using EIS.

A CMOS multi-sine signal generator for multi-frequency bioimpedance measurements

Multi-frequency signals are important for a variety of sensing and instrumentation applications. These include various impedimetric applications inhibiting a time-varying behavior, where a system has to be characterized rapidly across a specific bandwidth. In this paper a novel CMOS system is presented, which can generate a multi-sine signal with components of any desired frequency and amplitude, while generating at the same time the required 0° and 90° demodulation signals necessary at each frequency for a synchronous demodulation front-end. The proposed system performs summing of waveforms of different frequencies in the current domain, eliminating the need for an additional summing amplifier.

Optimization of bipolar and tetrapolar impedance biosensors

Impedance detection plays a crucial role in the development of Lab-on-a-Chip (LOAC) technologies. Various types of impedance biosensors have been developed over the years, with the main focus being centered on interdigital sensors. Optimization of impedance sensors has only recently attracted interest. In this paper we present a conformal mapping approach to the optimization of bipolar and tetrapolar impedance sensors. This technique enables an analytic equation for the sensitivity of the sensors to impedance changes to be obtained. Optimization of these sensors using this analytic equation was performed and a number of optimized sensor designs are presented in this paper.

Towards the development of an electrochemical biosensor for hCGβ detection

The free beta subunit of human-chorionic-gonadotropin (hCGbeta) is critical for various aspects of human health. Detection and quantification of this protein are essential during pregnancy as it provides clinicians valuable information regarding the progress of a pregnancy and the health of a foetus. Furthermore, it can be used as a biomarker for gestational trophoblastic disease (GTD), germ cell tumours and some non-trophoblastic gynaecological cancers and common epithelial tumours. Monitoring hCGbeta levels is particularly important for patient treatment monitoring and relapse detection especially in GTD. This paper presents an investigation of the characteristics of the first two stages necessary for the development of a bio-impedance hCGbeta sensor, using impedance spectroscopy and commercially available microelectrodes. Additionally, electrical equivalent circuit models based on the experimental results of these stages are presented. The biosensor is based on the formation of stable antibody-antigen complexes on golden microband electrodes covered with a layer of a self-assembled monolayer (SAM) or with both SAM and protein G. The preliminary results and analysis relate the interfacial processes and physical structure of the sensor to its electrical behaviour. Finally, preliminary results obtained from the sensor without protein G, which strongly indicate hCGbeta detection, are also presented.