Cell constant studies of bipolar and tetrapolar electrode systems for impedance measurement

In comparison to the bipolar or two-electrode system, the tetrapolar or four-electrode arrangement is a well-known technique to reduce electrode polarisation just as effectively. However, recent studies have showed that phenomena such as negative sensitivity and multiple current paths can compromise the advantages of the tetrapolar electrode arrangement, thereby potentially limiting its applications. This paper reveals a novel method to evaluate the performance of the different electrode systems in which the concept of cell constant is extended to an impedance measurement system. We employ it as a standardised parameter to quantitatively analyse planar electrode systems in bipolar and tetrapolar measurement modes. Indeed, the cell constant is a key parameter in conductivity sensors to evaluate electrodes designs since it is independent of any readout electronics. A comparison of measurement modes using finite element methods (FEM) simulations and measurements for sodium chloride solutions is presented. While the cell constant of the bipolar electrode system is one order of magnitude greater than that of the tetrapolar arrangement, it shows large discrepancy over the measured frequency range. In contrast, despite the existence of measurement errors, the tetrapolar arrangement yields a uniform cell constant and good agreement with the simulations.This work is partially supported by the Isaac Newton Trust.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.snb.2015.07.08

Modeling and Characteristic Study of Thin Film Based Biosensor Based on COMSOL

The model of thin film based biosensor is built based on COMSOL in order to simulate and optimize the electronic characteristic of dipolar electrodes system and tetrapolar electrodes system. Zones of negative sensitivity exist between current carrying electrodes and voltage measuring electrodes while the polarization occurs at the edges of electrodes. By changing the parameters embracing distance between electrodes, thickness of electrodes, and the width of inner electrodes (for tetrapolar electrodes system only), the polarization and zones of negative sensitivity can be receded to some extent, which improves the system’s performance. Tetrapolar electrodes system has less polarization but more negative-sensitivity zones compared to dipolar electrodes system and different setups response differently to these changing parameters

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

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

Desenvolvimento de hardware para análise de bioimpedância em banda larga

The bioimpedance spectroscopy is a technique that allows the biological tissue research from its electrical properties. The applications include body composition, research in cancer cells, bioimpedance tomography and others. This paper realizes the development of a bioimpedance analyzer for frequencies between 1 kHz and 1 MHz and impedance range between 50 and 1 kΩ. The system perform the acquisition with a tetrapolar topology, which a current excitation used was ternary chirp signal. For device control and visualization of the results, a software was also developed in LabVIEW platform. As a result, the project requires a total time of 2.47 s to perform the bioimpedance measurement, however only 10 ms are used for tissue excitation, the resolution obtained was 2.44 Ω for the module and 0.29° for the phase, with errors of accuracy around 30 Ω (module) and 6 ° (phase).A espectroscopia de bioimpedância é uma técnica que permite a investigação do tecido biológico a partir de suas propriedades elétricas, cujas aplicações incluem composição corporal, investigações em células de câncer, tomografia por bioimpedância e outros. O presente trabalho apresenta o desenvolvimento de um analisador de bioimpedância para frequências entre 1 kHz e 1 MHz e faixa de impedâncias entre 50 Ω e 1 kΩ. O sistema realiza aquisição com uma topologia tetrapolar, a qual será utilizada uma excitação de corrente com chirp ternária. Para controle do dispositivo e visualização dos resultados foi desenvolvido também um software em plataforma LabVIEW. Como resultado, o projeto necessita de um tempo total de 2,47 s para realizar a medição de bioimpedância, onde apenas 10 ms são utilizados para excitação do tecido, a resolução obtida foi de 2,44 Ω para o módulo e 0,29° para a fase, com erros de exatidão da ordem de 30 Ω (módulo) e de 6° (fase)

Motion Artifact Reduction in Impedance Plethysmography Signal

The research related to designing portable monitoring devices for physiological signals has been at its peak in the last decade or two. One of the main obstacles in building such devices is the effect of the subject\u27s movements on the quality of the signal. There have been numerous studies addressing the problem of removing motion artifact from the electrocardiogram (ECG) and photoplethysmography (PPG) signals in the past few years. However, no such study exists for the Impedance Plethysmography (IP) signal. The IP signal can be used to monitor respiration in mobile devices. However, it is very susceptible to motion artifact. The main aim of this dissertation is to develop adaptive and non-adaptive filtering algorithms to address the problem of motion artifact reduction from the IP signal

Advances in Therapeutic Monitoring of Lithium in the Management of Bipolar Disorder

Since the mid-20th century, lithium continues to be prescribed as a first-line mood stabilizer for the management of bipolar disorder (BD). However, lithium has a very narrow therapeutic index, and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The quantification of lithium in clinical laboratories is performed by atomic absorption spectrometry, flame emission photometry, or conventional ion-selective electrodes. All these techniques are cumbersome and require frequent blood tests with consequent discomfort which results in patients evading treatment. Furthermore, the current techniques for lithium monitoring require highly qualified personnel and expensive equipment; hence, it is crucial to develop low-cost and easy-to-use devices for decentralized monitoring of lithium. The current paper seeks to review the pertinent literature rigorously and critically with a focus on different lithium-monitoring techniques which could lead towards the development of automatic and point-of-care analytical devices for lithium determination

Micro-Nano-Bio Systems for on-line monitoring of in vitro biofilm responses

El treball presentat en aquesta tesi doctoral te com objectiu principal la contribució en el camp de la microbiologia per entendre el biofilms i el possible control de desenvolupament mitjançant l’ús de mètodes i enfoc multidisciplinari. Els biofilms estan definits com comunitats de microorganismes que creixen envoltats en una matriu exopolisacárida i s’adhereixen a una superfície inert o teixit viu. La formació dels biofilms bacterians tenen un gran interès en microbiologia clínica degut al desenvolupament d’infeccions que son causades pel contacte directe o per colonització de dispositius mèdics implantats i pròtesis. Actualment es consideren causa de més del 60 % de les infeccions bacterianes. El problema dels biofilms bacterians a nivell clínic es que mostren millor resistència a antibiòtics arribant inclús a ser de 500 a 5000 cops més resistents a agents antimicrobians comparant amb la mateixa bactèria planctònica (bactèria en suspensió). Hi ha hagut moltes temptatives d’adaptar mètodes a laboratoris clínics on es reprodueixen les condicions pel desenvolupament de biofilms, però encara no s’ha arribat a obtenir òptims protocols estàndard per a aquest propòsit de monitoritzar la formació i toxicitat a temps real. Ha crescut l’interès en disseny, desenvolupament i utilització de dispositius de microfluídica que poden emular els fenòmens biològics que ocorren amb diferents geometries, dinàmica de fluids i restriccions de transport de biomassa en microambients fisiològics. La recerca descrita en aquesta tesis s’ha dut a terme amb diferents mètodes “label-free” basats en la variació acústica y/o propietats elèctriques per a la monitorització de biofilms. El treball presentat en la monografia descriu un dispositiu “custom-made” per a la utilització d’Espectroscòpia de impedància electroquímica com a eina útil per a l’obtenció d’informació d’adherència i formació de biofilms. El fet d’afegir nanopartícules com a segon biosensor permet la correlació de biofilm amb la seva toxicitat a temps real per a la detecció del punt òptim de tractament de biofilms. Finalment el disseny d’aquesta tecnologia s’utilitza per l’assaig de la resposta de biofilms a antibiòtics com a model in vitro d’infeccions causades per biofilms.El trabajo presentado en esta tesis doctoral tiene como principal objetivo la contribución en el campo de la microbiología para entender los biofilms y el posible control de desarrollo mediante el uso de métodos y enfoque multidisciplinar. Los biofilms están definidos como comunidades de microorganismos que crecen embebidos en una matriz exopolisacárida y se adhieren a una superficie inerte o tejido vivo. La formación de los biofilms bacterianos tiene un gran interés en microbiología clínica debido al desarrollo de infecciones que son causadas por contacto directo o por colonización de dispositivos médicos implantados y prótesis. Actualmente se consideran la causa de más del 60 % de las infecciones bacterianas. El problema de los biofilms bacterianos a nivel clínico es que muestran mejor resistencia a antibióticos llegando incluso a ser de 500 a 5000 veces más resistentes a agentes antimicrobianos comparado a la misma bacteria planctónica (bacteria en suspensión). Ha habido muchas tentativas de adaptar métodos a laboratorios clínicos donde se reproducen las condiciones para el desarrollo de biofilms, pero aún no se ha llegado a obtener óptimos protocolos estándar para este propósito de monitorizar la formación y toxicidad en tiempo real. Ha crecido el interés en diseño, desarrollo y utilización de dispositivos de microfluídica que puedan emular los fenómenos biológicos que ocurren con diferentes geometrías, dinámica de fluidos y restricciones de transporte de biomasa en microambientes fisiológicos. La investigación descrita en esta tesis se lleva a cabo con diferentes métodos “label-free” basados en variación acústica y/o propiedades eléctricas para la monitorización de biofilms. El trabajo presentado en esta monografía describe un dispositivo “custom-made” para la utilización de Espectroscopia de impedancia electroquímica como herramienta útil para obtener información de adherencia y formación de biofilms. El hecho de añadir nanopartículas como segundo biosensor permite la correlación de biofilm con su toxicidad en tiempo real para la detección del punto óptimo del tratamiento de biofilms. Finalmente el diseño de esta tecnología es usada para el ensayo de la respuesta de biofilms a antibióticos como modelo in vitro de infecciones causadas por biofilms.The work presented in this thesis has the main aim to contribute in the field of clinical microbiology to understand the biofilms and the possible of development through the use of methods with multidisciplinary approach. Biofilms are defined as communities of microorganisms that grow embedded in a matrix of exopolysaccharides and adhering to an inert surface or living tissue. The formation of bacterial biofilms has an interest in clinical microbiology with the development of infections that usually arise from either direct contact or the colonization of implanted medical devices and prostheses. Currently they are considered the cause of over 60% of bacterial infections. The problem of bacterial biofilms at clinical level is showing great resistance to antibiotics, so that the biofilm bacteria are 500 to 5000 times more resistant to antimicrobial agents that the same bacteria grown in planktonic cultures (bacteria in suspension). There have been attempts to adapt methods to clinical laboratories where they reproduce the conditions of biofilms, but have not yet adopted an optimal standard protocol for this purpose to follow-up the formation and toxicity in real-time. There has been a growing interest in design, development and utilization of microfluidic devices that can emulate biological phenomena that occur in different geometries, fluid dynamics and mass transport restrictions in physiological microenvironments. The research described in this thesis deals with different label-free methods based on variation of acoustic and electric properties for biofilm monitoring. The work presented in this monograph describe a custom-made device for using electrochemical impedance spectroscopy (EIS) as useful tool to obtain information of adherence and formation of biofilms. The addition of nanoparticles as toxicity biomarker allows the correlation of biofilm formation with its toxicity in real-time for detention of the optimal point for biofilm treatment. Finally the design of this technology is used for testing the biofilm response to antibiotic as in vitro model of biofilm-related infection

Tissue classification from electric impedance spectroscopy for haptic feedback in minimally invasive surgery

Haptic feedback is missing in teleoperated surgical robots creating a sensory disconnect from the surgeon and their patient. This thesis proposes using the electric impedance of tissues, instead of the traditionally used mechanical impedance, to develop haptic feedback for surgical robots. Electric impedance spectroscopy (EIS) and a modified surgical needle were successfully able to measure the electric impedance for gel-based phantoms, ex-vivo tissue, and freshly excised organs. Processes for fitting the electric impedance of these tissues to the double-dispersion Cole model were developed including stochastic and deterministic approaches. The tissues were classified with least square error, k-Nearest Neighbour and Na??ve Bayes using the measured electric impedance and the extracted model parameter values. The thesis culminates in applications of using EIS as part of implementing vibrotactile and force feedback applications involving sets of user trials to validate its effectiveness in identifying the tissue through haptic feedback