A CMOS Magnitude/Phase Measurement Chip for Impedance Spectroscopy

The measurement of electrical impedance is used in a plethora of biomedical applications. The most common technique used is synchronous demodulation, which provides the real and imaginary parts of the impedance. However, in practice, the method requires elaborate calibration and matching between the injection and monitoring stages. This paper presents the integrated realization of an alternative method that is less intricate to implement. The circuit was fabricated in a 0.35-μm CMOS technology, occupies an active area of 0.4 mm2 , and dissipates about 21 mW of power from ±2.5 V supplies. The chip was used to measure equivalent RC circuits of the electrode-tissue interface over the frequency range of 100 Hz to 100 kHz, showing good correlation with the theoretical results

Bioimpedance sensors: a tutorial

Electrical bioimpedance entails the measurement of the electrical properties of tissues as a function of frequency. It is thus a spectroscopic technique. It has been applied in a plethora of biomedical applications for diagnostic and monitoring purposes. In this tutorial, the basics of electrical bioimpedance sensor design will be discussed. The electrode/electrolyte interface is thoroughly described, as well as methods for its modelling with equivalent circuits and computational tools. The design optimization and modelling of bipolar and tetrapolar bioimpedance sensors is presented in detail, based on the sensitivity theorem. Analytical and numerical modelling approaches for electric field simulations based on conformal mapping, point electrode approximations and the finite element method (FEM) are also elaborated. Finally, current trends on bioimpedance sensors are discussed followed by an overview of instrumentation methods for bioimpedance measurements, covering aspects of voltage signal excitations, current sources, voltage measurement front-end topologies and methods for computing the electrical impedance

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

Multi-Parametric Rigid and Flexible, Low-Cost, Disposable Sensing Platforms for Biomedical Applications

The measurement of Na+, K+ and H+ is essential in medicine and plays an important role in the assessment of tissue ischemia. Microfabrication, inkjet- and screen-printing can be used for solid contact ion selective electrodes (ISE) realization; these, however, can be non-standardized, costly and time consuming processes. We present the realization of ISEs on post-processed electrodes fabricated via standardized printed circuit board (PCB) manufacturing techniques. In vitro results are presented from two rigid platforms (32 ISEs) for liquid sample dip-stick measurements and two flexible platforms (6 and 32 ISEs) for post-surgical intestinal tissue monitoring, each with a common reference electrode (RE). These are combined with optimized tetrapolar bioimpedance sensors for tissue ischemia detection. Both electroless and hard gold PCB finishes are examined. Apart from the electroless rigid platform, the rest demonstrated comparable and superior performance, with the pH sensors demonstrating the greatest deviation; the flexible hard gold platform achieved a sensitivity 4.6 mV/pH and 49.2 mV/pH greater than the electroless flexible and rigid platforms, respectively. The best overall performance was achieved with the hard gold flexible platform with sensitivities as large as 73.4 mV/pH, 56.3 mV/log [Na+], and 57.4 mV/log [K+] vs. custom REs on the same substrate. Simultaneous measurements of target analytes is demonstrated with test solutions and saliva samples. The results exhibit superior performance to other PCB-based pH sensors, demonstration of Na+ and K+ PCB-based sensors with comparable performance to potentiometric sensors fabricated with other techniques, paving the way towards mass-produced, low-cost, disposable, multi-parametric chemical sensing diagnostic platforms

Wearable Nano-Based Gas Sensors for Environmental Monitoring and Encountered Challenges in Optimization

With a rising emphasis on public safety and quality of life, there is an urgent need to ensure optimal air quality, both indoors and outdoors. Detecting toxic gaseous compounds plays a pivotal role in shaping our sustainable future. This review aims to elucidate the advancements in smart wearable (nano)sensors for monitoring harmful gaseous pollutants, such as ammonia (NH3), nitric oxide (NO), nitrous oxide (N2O), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), hydrogen sulfide (H2S), sulfur dioxide (SO2), ozone (O3), hydrocarbons (CxHy), and hydrogen fluoride (HF). Differentiating this review from its predecessors, we shed light on the challenges faced in enhancing sensor performance and offer a deep dive into the evolution of sensing materials, wearable substrates, electrodes, and types of sensors. Noteworthy materials for robust detection systems encompass 2D nanostructures, carbon nanomaterials, conducting polymers, nanohybrids, and metal oxide semiconductors. A dedicated section dissects the significance of circuit integration, miniaturization, real-time sensing, repeatability, reusability, power efficiency, gas-sensitive material deposition, selectivity, sensitivity, stability, and response/recovery time, pinpointing gaps in the current knowledge and offering avenues for further research. To conclude, we provide insights and suggestions for the prospective trajectory of smart wearable nanosensors in addressing the extant challenges

A comparison of front-end amplifiers for tetrapolar bioimpedance measurements

Many commercial benchtop impedance analyzers are incapable of acquiring accurate tetrapolar measurements, when large electrode contact impedances are present, as in bioimpedance measurements using electrodes with micrometer-sized features. External front-end amplifiers can help overcome this issue and provide high common-mode rejection ratio (CMRR) and input impedance. Several discrete component-based topologies are proposed in the literature. In this article, these are compared with new alternatives with regard to their performance in measuring known loads in the presence of electrode contact impedance models, to emulate tetrapolar bioimpedance measurements. These models are derived from bipolar impedance measurements taken from the electrodes of a tetrapolar bioimpedance sensor. Comparison with other electrode models used in the literature established that this is a good and challenging model for bioimpedance front-end amplifier evaluation. Among the examined amplifiers, one of the best performances is achieved with one of the proposed topologies based on a custom front-end with no external resistors (AD8066/AD8130). Under the specific testing conditions, it achieved an uncalibrated worst-case absolute measurement deviation of 4.4% magnitude and 4° at 20 Hz, and 2.2% and 7° at 1 MHz accordingly with loads between 10 Ω and 10 kg. Finally, the practical use of the front-end with the impedance analyzer is demonstrated in the characterization of the bioimpedance sensor, in saline solutions of varying conductivities (2.5-20 mS/cm) to obtain its cell constant. This article serves as a guide for evaluating and choosing front-end amplifiers for tetrapolar bioimpedance measurements both with and without impedance analyzers for practical/clinical applications and material/sensor characterization

Nomograms of Iranian fetal middle cerebral artery Doppler waveforms and uniformity of their pattern with other populations' nomograms

<p>Abstract</p> <p>Background</p> <p>Doppler flow velocity waveform analysis of fetal vessels is one of the main methods for evaluating fetus health before labor. Doppler waves of middle cerebral artery (MCA) can predict most of the at risk fetuses in high risk pregnancies. In this study, we tried to obtain normal values and their nomograms during pregnancy for Doppler flow velocity indices of MCA in 20 – 40 weeks of normal pregnancies in Iranian population and compare their pattern with other countries' nomograms.</p> <p>Methods</p> <p>During present descriptive cross-sectional study, 1037 normal pregnant women with 20^th–40^thweek gestational age were underwent MCA Doppler study. All cases were studied by gray scale ultrasonography initially and Doppler of MCA afterward. Resistive Index (RI), Pulsative Index (PI), Systolic/Diastolic ratio (S/D ratio), and Peak Systolic Velocity (PSV) values of MCA were determined for all of the subjects.</p> <p>Results</p> <p>Results of present study showed that RI, PI, S/D ratio values of MCA decreased with parabolic pattern and PSV value increased with simple pattern, as gestational age progressed. These changes were statistically significant (P = 0.000 for all of indices) and more characteristic during late weeks of pregnancy.</p> <p>Conclusion</p> <p>Values of RI, PI and S/D ratio indices reduced toward the end of pregnancy, but PSV increased. Despite the trivial difference, nomograms of various Doppler indices in present study have similar pattern with other studies.</p

Modelling, design and validation of tetrapolar impedance biosensors for lab-on-a-chip applications

In the last decade the new scientific field of Lab-On-a-Chip (LOAC) systems arose. This field focuses on the miniaturization of standard and new laboratory techniques responsible for the manipulation and detection of biomolecules. This is a very diverse field with a vast number of different techniques being employed in order to develop such systems. The work carried out, focused on the detection of biomolecules. Electrochemical Impedance Spectroscopy (EIS), where the impedance is being measured as a function of frequency, has been used for the last 20 years in biosensor applications. However, it has failed to become widely available. The wider interest has been in the experimental procedure and not the instrumentation required or more importantly, the optimization of the electrode system used. Development of a customized system for the specific application and integration of such an instrument on a single microchip, would greatly aid towards the development, widespread deployment and standardization of EIS as a competitive, accurate, portable, simple to use, low cost, fast and label-free detection technique. This project, focused on the development of a tetrapolar impedance system, as tetrapolar electrode systems offer the advantage of reduced interfacial electrode polarization in contrast to bipolar and tripolar systems. For proof of principle, EIS was applied in the analysis of a biosensor developed for the detection of hCGb, a protein associated with various types of cancer. Commercially available coplanar-microband gold-electrode arrays were used in conjunction with a commercial impedance analyser in order to perform this analysis. Preliminary results indicated a clear differentiation between different biological and chemical layers and more importantly indicated hCGb detection. Thus, applicability of the tetrapolar technique for biomolecule detection was illustrated. The commercial electrode array, even though it did provide positive and promising results, was not optimized for the specific application. In order to do so, the Finite Element Method (FEM) modelling technique (Comsol Multiphysics) was employed in order to investigate the electric field properties of tetrapolar sensors. By utilizing the Geselowitz sensitivity theorem, the dependence of the sensitivity of the sensor to impedance changes on the sensor geometry was examined and understood. In order to optimize the sensor, a dedicated Matlab code employing the Conformal Mapping (CM) technique, was developed. This allowed the examination of the response of the sensitivity function over a specific region for millions of different geometries, reducing the computational and analytical time required with FEM. With 2D and 3D FEM models agreeing with the CM results and thus validating the CM analysis, a number of optimized tetrapolar sensors were generated. The optimization free parameters were the width (W) and the distance (D) between pairs of electrodes. The results also proved to be able to be scaled up and thus, a scaled-up (by 5x105) tank model of one of the optimized sensors was developed in order to experimentally prove the analysis. The first step towards a tetrapolar system is the bipolar and consequently bipolar (and thus interdigital) electrode systems were also briefly examined

Towards the development of an electrochemical biosensor for hCGβ detection

The free beta subunit of human-chorionic-gonadotropin (hCGβ) 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 hCGβ 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 hCGβ 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 hCGβ detection, are also presented