Equipo compacto de medida de impedancia eléctrica multifrecuencia basado en señales multiseno

A continuación se presenta el desarrollo e implementación de un sistema compacto de medida multifrecuencia de Espectroscopia de Impedancia Eléctrica (EIE). A diferencia de los equipos clásicos de medida de impedancia eléctrica basados en la técnica de barrido frecuencial, dicho sistema permite la caracterización instantánea del espectro de impedancia gracias a la realización simultánea de múltiples medidas espectrales mediante el uso de señales multiseno. Para disminuir el error en determinación de amplitud y fase en la medida se pretende aumentar la relación señal-ruido mediante la minimización del factor de cresta. Para ello, se ha implementado un algoritmo genético y una distribución bilateral cuasi logarítmica (BQL) de frecuencias que concentra un número mayor de puntos espectrales alrededor de la frecuencia de relajación de la impedancia del sistema biológico a medir. La aplicación final es la caracterización in-vitro del proceso de crecimiento y diferenciación celular de miocitos a partir de células madre, con la intención de regenerar tejido cardíaco en el campo de la ingeniería de tejidos.Postprint (published version

Modeling the non-stationary behaviour of time-varying electrical bioimpedance

The electrical bioimpedance (EBI) measurement of varying biological systems Z(¿,t) (e.g. the heart, the lungs,.) by means of electrical impedance spectroscopy (EIS) remains an open challenge today. Briefly stated, the bioimpedance is widely assumed to be time-invariant when it is measured with the frequency sweep EIS approach. Hence, time-varying changes are thus ignored or treated as a noise source. In this work, we attempt to model the time-variant effects and obtain a simple (periodically) time-varying [(P)TV)] electrical circuit model with (P)TV parameters from experimental in vivo EBI data using the model proposed by Fricke- Morse. The aim is then to illustrate that a limited number of harmonic components of the electrical circuit parameters, which corresponds to an integer number of the bio-system periodicity, can be used to have a realistic evolution of the bioimpedance over time as well as in frequency.Peer ReviewedPostprint (published version

On the calculation of the D-optimal multisine excitation power spectrum for broadband impedance spectroscopy measurements

The successful application of impedance spectroscopy in daily practice requires accurate measurements for modeling complex physiological or electrochemical phenomena in a single frequency or several frequencies at different (or simultaneous) time instants. Nowadays, two approaches are possible for frequency domain impedance spectroscopy measurements: (1) using the classical technique of frequency sweep and (2) using (non-)periodic broadband signals, i.e. multisine excitations. Both techniques share the common problem of how to design the experimental conditions, e.g. the excitation power spectrum, in order to achieve accuracy of maximum impedance model parameters from the impedance data modeling process. The original contribution of this paper is the calculation and design of the D-optimal multisine excitation power spectrum for measuring impedance systems modeled as 2R-1C equivalent electrical circuits. The extension of the results presented for more complex impedance models is also discussed. The influence of the multisine power spectrum on the accuracy of the impedance model parameters is analyzed based on the Fisher information matrix. Furthermore, the optimal measuring frequency range is given based on the properties of the covariance matrix. Finally, simulations and experimental results are provided to validate the theoretical aspects presented.Peer ReviewedPostprint (published version

Monitoring cell monolayers during electroporation: Electrical impedance spectroscopy measurements

Electroporation or electropermeabilization is a phenomenon observed when lipid bilayers, generally cell membranes, are exposed to high electric field pulses becoming transiently permeable to molecules that under regular conditions are not able to penetrate through them. This change in molecular permeability is believed to be produced by transient aqueous pores created in the lipidic structure and can be monitored by changes in the electrical conductivity of these membranes. The aim of this study is to use fast electrical impedance spectroscopy to measure the process of electroporation applied on cell monolayers growing attached to standard multiwell plates. The frequency response of the impedance can provide useful information about the extent of permeabilization in the cell membranes exposed to high electric fields and also the time dynamics of creation and resealing of these pores. For this study we used a microelectrode assembly specifically designed for in situ performance of both electroporation and impedance measurements. The design of the microelectrodes is based on a spiral geometry conceived to improve the uniformity of the electric field applied and to perform impedance measurements in a four-electrode configuration.Postprint (published version

Towards on line monitoring the evolution of the myocardium infarction scar with an implantable electrical impedance spectrum monitoring system.

The human heart tissue has a limited capacity for regeneration. Tissue and cellular therapies based on the use of stem cells may be useful alternatives to limit the size of myocardial infarction. In this paper, the preliminary results from an experimental campaign for on-line monitoring of myocardium scar infarction are presented. This study has been carried out under a research project that has as main objective the development and application of a bioactive patch implant for regeneration of myocardial infarction. Electrical Impedance Spectroscopy (EIS) has been chosen as a tissue state monitoring technique. What is presented in this communication is the first results of an implantable EIS measurement system which has been implanted in a subset of the animals corresponding to the control group, along one month. In all the animals, the myocardial infarction was induced by the ligation of the first circumflex marginal artery. In the animal group presented,the bioactive patch scaffold and the electrodes were implanted without the stem cells load. The scaffold is a piece of decellularized human pericardium, lyophilized and rehydrated with hydrogel RAD16-I. Nanogold particles were also placed near the electrodes to improve the electrode area conductivity. The results presented correspond to the subset of animals (n = 5), which had implanted the bioimpedance system monitoring the electrical impedance spectrum in vivo during 1 month. Two electrodes were connected to the bioactive patch implant. A total of 14 logarithmically spaced frequencies were measured every 5 minutes, from 100 Hz to 200 kHz. Results show a convergence of low-frequency and high frequency impedance magnitudes along the measurement period, which is coherent with the scar formation.Postprint (published version

Broadband electrical impedance spectroscopy for dynamic electrical bio-impedance characterization

The electrical impedance of biological samples is known in the literature as Electrical Bioimpedance (EBI). The Electrical Bioimpedance enables to characterize physiological conditions and events that are interesting for physiological research and medical diagnosis. Although the Electrical Bioimpedance weakness is that it depends on many physiological parameters, on the other hand, it is suitable for many medical applications where minimally invasive and real-time measurements with simple and practical implementations are needed. The Electrical Impedance Spectroscopy (EIS) techniques based on broadband excitations are expected to help to understand various unsolved problems in biomedical applications. Broadband EIS opens up the possibility to reduce drastically the measuring time for acquiring EBI time-variations but, at the same time, measuring in a short time compromises the EBI accuracy. The way to overcome this intrinsic loss of accuracy relies on the design of the appropriate time/frequency input excitation properties and the use of the suitable spectral analysis processing techniques. The presented thesis covers the topics related to study of broadband excitations for Impedance Spectroscopy in biomedical applications and, more specific, the influence of the multisine excitation time/frequency properties on the impedance spectrum accuracy and its optimization. Furthermore, an advanced fast signal processing method has been implemented to process in real-time EBI data corrupted by transients, a common situation when measuring in a short measuring time. Despite being the goal to apply all this knowledge for myocardial tissue regeneration monitoring, at the moment of drafting the thesis, any of the research projects that have supported this thesis have issued functional beating tissue. For that reason, the theory presented has been validated by a set of experimental measurements over animals and patients where the impedance spectrum time-varying properties were pretended to be characterized. The thesis presents novel findings of relevance of a successful application of broadband EIS in two different measurement campaigns where it has been put in practice: (1) within the collaboration of the pneumology and cardiology service from Hospital Santa Creu i Sant Pau for in-vivo human lung tissue characterization, and (2), within the measurement of animal healthy myocardium tissue electrical impedance including its dynamic behavior during the cardiac cycle

Multifrequency simultaneous bioimpedance measurements using multitone burst signals for dynamic tissue characterization

In this paper we present the keypoints to perform multifrequency simultaneous bioimpedance measurements using multitone signals. Concerning the frequency distribution, tones are spread over 1kHz to 1MHz range using a custom frequency distribution which we called Bilateral Quasi Logarithmic (BQL). BQL concentrates a higher number of tones around the impedance relaxation and contains a frequency plan algorithm. It minimizes the intermodulation effects due to non-linearities behaviours of the DUT and electrodes by slightly shifting the original tones in order to guarantee a guard bandwith. Regarding the multitone phase distribution, a Genetic Algorithm (GA) has been developed to minimize multitone Crest Factor (CF). This allow us to maximize the resultant Signal to Noise Ratio (SNR) of the acquisition system. This paper also presents the relation between parameters such as sampling frequency and ADC bits with the SNR and the effect in the overall amplitude and phase error when using multitone signals as excitation waveforms. Finally, we present characterization results from a measurement system based on a modular PXI architecture