Encontrados resultados para:
Autor: Gloria Huertas Sánchez
Año: Desde 2002
Artículos de revistas
A Plethysmography Capacitive Sensor for Real-Time Monitoring of Volume Changes in Acute Heart Failure
E. Rando, P. Perez, S. Fernandez-Scagliusi, F.J. Medrano, G. Huertas and A. Yufera
Journal Paper · IEEE Transactions on Instrumentation and Measurement, vol. 70, article 4005912, 2021
resumen
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A small, wearable, low-weight, and low-power-consumption device for plethysmography capacitive sensing is proposed herein. The device allows carrying out real-time monitoring of leg volume changes in patients suffering from heart failure (HF) conditions. The dynamic of fluid overload in patients with acute HF serves as a prognosis marker for this type of severe disease and, consequently, these patients can benefit from a wearable monitoring system to measure their body volume evolution during and after hospitalization. Our approach is based on contactless capacitive wearable structures implemented by two different sensor realizations located in the ankle: 180°-parallel capacitor plates (two modes of operations are compared, with the patient’s body connected to ground and to the average voltage between plates) and planar-parallel capacitor plates whose overlapped surface varies with the volume of the patient’s leg. Both realizations exhibit good sensitivity to leg volume changes. The acquisition of capacitance values is performed via a simple circuit that achieves notable performance in simulated volume analysis. A preliminary pilot clinical prototype is described as well.
A computer-aided design tool for biomedical OBT sensor tuning in cell-culture assays
P. Pérez, J.A. Serrano, M.E. Martín, P. Daza, G. Huertas and A. Yúfera
Journal Paper · Computer Methods and Programs in Biomedicine, vol. 200, article 105840, 2021
resumen
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It is proposed a computer program for system design of biosensors applied to monitoring cell culture dynamics. The program allows obtaining confident system information by electrical stimulation. All system components (electrodes, cell culture and test circuits) are properly modelled. The employed procedure can be applied to any other 2D electrode layout or alternative circuit technique for ECIS test. Finally, deep insight information on cell size, number, and time-division can be extracted from the comparison with real cell culture assays in the future.
Alternative General Fitting Methods for Real-Time Cell-Count Experimental Data Processing
J.A. Serrano, P. Perez, G. Huertas and A. Yufera
Journal Paper · IEEE Sensors Journal, vol. 20, no. 24, pp 15177-15184, 2020
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This paper reports two general methods for extraction of cell-electrode electrical model parameters in cell culture (CC) assays. The presented approaches can be applied to CC assays based on electrical cell-substrate impedance spectroscopy (ECIS) technique for real-time supervision, providing the cell number per square centimeter, i.e., the cell density, as main result. Both of the proposed methods - minimization of system equations and data predictive model - search, during the experiment, the optimum values of the electrical model parameters employed for the electrode-cell model. The results of this search enable a fast and efficient calculation of the involved cell-electrode model parameters and supply real-time information on the cell number. For the sake of experimental validation, we applied the proposed methods to practical CCs in cell growth assays with a cell line of AA8 Chinese hamster ovarian fibroblasts and the Oscillation Based Test technique for bioimpedance measurements. These methods can be easily extrapolated to any general cell lines and/or other bioimpedance test methodologies.
Editorial: Design and Application of Biomedical Circuits and Systems
A. Yúfera, G. Huertas and B. Calvo
Journal Paper · Electronics, vol. 9, no. 11, article 1920, 2020
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Editorial of the Design and Application of Biomedical Circuits and Systems Special Issue.
Electrical modeling of the growth and differentiation of skeletal myoblasts cell cultures for tissue engineering
A. Olmo, Y. Yuste, J.A. Serrano, A. Maldonado-Jacobi, P. Pérez, G. Huertas, S, Pereira, A. Yufera and F. de la Portilla
Journal Paper · Sensors, vol. 20, no. 11, article 3152, 2020
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In tissue engineering, of utmost importance is the control of tissue formation, in order to form tissue constructs of clinical relevance. In this work, we present the use of an impedance spectroscopy technique for the real-time measurement of the dielectric properties of skeletal myoblast cell cultures. The processes involved in the growth and differentiation of these cell cultures in skeletal muscle are studied. A circuit based on the oscillation-based test technique was used, avoiding the use of high-performance circuitry or external input signals. The effect of electrical pulse stimulation applied to cell cultures was also studied. The technique proved useful for monitoring in real-time the processes of cell growth and estimating the fill factor of muscular stem cells. Impedance spectroscopy was also useful to study the real-time monitoring of cell differentiation, obtaining different oscillation amplitude levels for differentiated and undifferentiated cell cultures. Finally, an electrical model was implemented to better understand the physical properties of the cell culture and control the tissue formation process.
Evaluation of Implanted Stent Occlusion Status Based on Neointimal Tissue Bioimpedance Simulations
J.M. Portillo-Anaya, P. Perez, A. Olmo, G. Huertas and A. Yufera
Journal Paper · Journal of Sensors, vol. 2019, article 7167186, 2019
resumen
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This paper describes the characterization of the light hole, also known as the lumen, in implanted stents affected by restenosis processes using bioimpedance (BI) as a biomarker. The presented approach will enable real-time monitoring of lumens in implanted stents. The basis of the work hereby reported is the fact that neointimal tissues involved in restenosis can be detected and measured through their impedance properties, namely, conductivity and permittivity. To exploit these properties, a 4-electrode setup for BI measurement is proposed. This setup allows study of the influence of the various tissues involved in restenosis fat, muscle, fibre, and endothelium, together with the blood, on the BI value at several frequencies. In addition, BI simulation tests were performed using the electric physics module available in COMSOL Multiphysics®. Interestingly, fat constitutes the most influential layer on the value of impedance (measured in kΩ/μm-magnitude change per micrometre of lumen occlusion). A case study using a standard stent is also presented. In this study, where the involved tissues and blood were simultaneously considered, we conducted an analysis for stable and vulnerable plaques in restenosis test situations. In this regard, the proposed method is useful to test the stent obstruction and detect potential dangerous cases due to nonstable fat accumulation.
Data-Analytics Modeling of Electrical Impedance Measurements for Cell Culture Monitoring
E. García, P. Pérez, A. Olmo, R. Díaz, G. Huertas and A. Yúfera
Journal Paper · Sensors, vol. 19, no. 21, art. 4639, 2019
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High-throughput data analysis challenges in laboratory automation and lab-on-a-chip devices´ applications are continuously increasing. In cell culture monitoring, specifically, the electrical cell-substrate impedance sensing technique (ECIS), has been extensively used for a wide variety of applications. One of the main drawbacks of ECIS is the need for implementing complex electrical models to decode the electrical performance of the full system composed by the electrodes, medium, and cells. In this work we present a new approach for the analysis of data and the prediction of a specific biological parameter, the fill-factor of a cell culture, based on a polynomial regression, data-analytic model. The method was successfully applied to a specific ECIS circuit and two different cell cultures, N2A (a mouse neuroblastoma cell line) and myoblasts. The data-analytic modeling approach can be used in the decoding of electrical impedance measurements of different cell lines, provided a representative volume of data from the cell culture growth is available, sorting out the difficulties traditionally found in the implementation of electrical models. This can be of particular importance for the design of control algorithms for cell cultures in tissue engineering protocols, and labs-on-a-chip and wearable devices applications.
Remote Cell Growth Sensing using Self-Sustained Bio-Oscillations
P. Pérez, G. Huertas, A. Olmo, A. Maldonado-Jacobi, J. Serrano, M. Martín, P. Daza and A. Yúfera
Journal Paper · Sensors, vol. 18, no. 8, art. 2550, 2018
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A smart sensor system for cell culture real-time supervision is proposed, allowing for a significant reduction in human effort applied to this type of assay. The approach converts the cell culture under test into a suitable "biological" oscillator. The system enables the remote acquisition and management of the "biological" oscillation signals through a secure web interface. The indirectly observed biological properties are cell growth and cell number, which are straightforwardly related to the measured bio-oscillation signal parameters, i.e., frequency and amplitude. The sensor extracts the information without complex circuitry for acquisition and measurement, taking advantage of the microcontroller features. A discrete prototype for sensing and remote monitoring is presented along with the experimental results obtained from the performed measurements, achieving the expected performance and outcomes.
An empirical-mathematical approach for calibration and fitting cell-electrode electrical models in bioimpedance tests
J.A. Serrano, G. Huertas, A. Maldonado-Jacobi, A. Olmo, P. Pérez, M.E. Martín, P. Daza and A. Yúfera
Journal Paper · Sensors, vol. 18, no. 7, article 2354, 2018
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This paper proposes a new yet efficient method allowing a significant improvement in the on-line analysis of biological cell growing and evolution. The procedure is based on an empirical-mathematical approach for calibration and fitting of any cell-electrode electrical model. It is valid and can be extrapolated for any type of cellular line used in electrical cell-substrate impedance spectroscopy (ECIS) tests. Parameters of the bioimpedance model, acquired from ECIS experiments, vary for each cell line, which makes obtaining results difficult and -to some extent-renders them inaccurate. We propose a fitting method based on the cell line initial characterization, and carry out subsequent experiments with the same line to approach the percentage of well filling and the cell density (or cell number in the well). To perform our calibration technique, the so-called oscillation-based test (OBT) approach is employed for each cell density. Calibration results are validated by performing other experiments with different concentrations on the same cell line with the same measurement technique. Accordingly, a bioimpedance electrical model of each cell line is determined, which is valid for any further experiment and leading to a more precise electrical model of the electrode-cell system. Furthermore, the model parameters calculated can be also used by any other measurement techniques. Promising experimental outcomes for three different cell-lines have been achieved, supporting the usefulness of this technique.
Sensing Cell-Culture Assays with Low-Cost Circuitry
P. Pérez, G. Huertas, A. Maldonado-Jacobi, M. Martín, J.A. Serrano, A. Olmo, P. Daza and A. Yúfera
Journal Paper · Scientific Reports, vol. 8, no. 1, article 8841, 2018
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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.
Real-time electrical bioimpedance characterization of neointimal tissue for stent applications
D. Rivas-Marchena, A. Olmo, J.A. Miguel, M. Martinez, G. Huertas and A. Yufera
Journal Paper · Sensors, vol. 17, no. 8, art. 1737, 2017
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To follow up the restenosis in arteries stented during an angioplasty is an important current clinical problem. A new approach to monitor the growth of neointimal tissue inside the stent is proposed on the basis of electrical impedance spectroscopy (EIS) sensors and the oscillation-based test (OBT) circuit technique. A mathematical model was developed to analytically describe the histological composition of the neointima, employing its conductivity and permittivity data. The bioimpedance model was validated against a finite element analysis (FEA) using COMSOL Multiphysics software. A satisfactory correlation between the analytical model and FEA simulation was achieved in most cases, detecting some deviations introduced by the thin “double layer” that separates the neointima and the blood. It is hereby shown how to apply conformal transformations to obtain bioimpedance electrical models for stack-layered tissues over coplanar electrodes. Particularly, this can be applied to characterize the neointima in real-time. This technique is either suitable as a main mechanism for restenosis follow-up or it can be combined with proposed intelligent stents for blood pressure measurements to auto-calibrate the sensibility loss caused by the adherence of the tissue on the micro-electro-mechanical sensors (MEMSs).
The bio-oscillator: A circuit for cell-culture assays
G. Huertas, A. Maldonado, A. Yufera, A. Rueda and J.L. Huertas
Journal Paper · IEEE Transactions on Circuits and Systems II: Express Briefs, vol. 62, no. 2, pp 164-168, 2015
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A system for cell-culture real-time monitoring using an oscillation-based approach is proposed. The system transforms a cell culture under test into a suitable 'biological' oscillator, without needing complex circuitry for excitation and measurement. The obtained oscillation parameters are directly related to biological test, owed to an empirically extracted cell-electrode electrical model. A discrete prototype is proposed and experimental results with living cell culture are presented, achieving the expected performances.
Sine-wave signal characterization using square-wave and Sigma Delta-modulation: Application to mixed-signal BIST
D. Vázquez, G. Huertas, A. Luque, M.J. Barragán, G. Léger, A. Rueda and J.L. Huertas
Journal Paper · Journal of Electronic Testing-Theory and Applications, vol. 21, no. 3, pp 221-232, 2005
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This paper presents a method for extracting, in the digital domain, the main characteristic parameters of an analog sine-wave signal. It is based on a double-modulation, square-wave and sigma-delta, together with a simple Digital Processing Algorithm. It leads to an efficient and robust approach very suitable for BIST applications. In this line, some considerations for on-chip implementation are addressed together with simulation results that validate the feasibility of the proposed approach.
Oscillation-based test in oversampled ΣΔ modulators modulators
G. Huertas, D. Vázquez, E. Peralías, A. Rueda and J.L. Huertas
Journal Paper · Microelectronics Journal, vol. 33, no. 10, pp 799-806, 2002
resumen
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This paper discusses a way of applying the oscillation-based test (OBT)/oscillation-based built-in-self test concept to oversampled ΣΔ modulators, exploiting previous experience coined through the implementation of OBT in SC integrated filters. Analytical and simulation results demonstrate that it is always feasible to find out an OBT configuration for a typical discrete-time second-order modulator structure without adding a substantial extra circuitry, but only resorting to local feedback loops. A feedback strategy can be chosen providing enough freedom to force oscillations, which can be worthwhile for testing purposes. The selected oscillation parameters allow us to establish criteria for a high fault coverage.
On-Chip Evaluation of Oscillation-Based-Test Output Signals for Switched-Capacitor Circuits
D. Vázquez, G. Huertas, G. Leger, E. Peralías, A. Rueda and J.L. Huertas
Journal Paper · Analog Integrated Circuits and Signal Processing, vol. 33, no. 2, pp 201-211, 2002
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This work presents a simple and low-cost method for on-chip evaluation of test signals coming from the application of the Oscillation-Based-Test (OBT) technique. This method extracts the main test signal features (amplitude, frequency and DC level) in the digital domain requiring just a very simple and robust circuitry. Experimental results obtained from an integrated chip demonstrate the feasibility of the approach.
Practical oscillation-based test of integrated filters
G. Huertas, D. Vázquez, E. Peralías, A. Rueda and J.L. Huertas
Journal Paper · IEEE Design & Test of Computers, vol. 19, no. 6, pp 64-72, 2002
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Oscillation-based test techniques show promise in detecting faults in mixed-signal circuits and require little modification to the circuit under test. Comparing both the oscillation's amplitude and frequency yields acceptable test quality.
Testing mixed-signal cores: A practical oscillation-based test in an analog macrocell
G. Huertas, D. Vázquez, E. Peralías, A. Rueda and J.L. Huertas
Journal Paper · IEEE Design & Test of Computers, vol. 19, no. 6, pp 73-82, 2002
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A formal set of design decisions can aid in using oscillation-based test for analog subsystems in SoCs. The goal is to offer designers testing options that don't have significant area overhead, performance degradation, or test time.
A simple and secure start-up circuitry for oscillation-based-test application
D. Vázquez, G. Huertas, A. Rueda and J.L. Huertas
Journal Paper · Analog Integrated Circuits and Signal Processing, vol 32, no. 2, pp 187-190, 2002
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doi
A simple start-up strategy specially suitable for the oscillation-based-test application of opamp-based circuits is presented. The proposed approach not only ensures that the oscillator will start to run (safe start-up) but also the steady-state (SS) can be reached very fast (short transient-time).
Congresos
Modeling Edema Evolution with Electrical Bioimpedance: Application to Heart Failure Patients
M. Puertas, L. Giménez, A. Pérez, S.F. Scagliusi, P. Pérez, A. Olmo, G. Huertas, J. Medrano and A. Yúfera
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2021
resumen
This work presents a procedure to calculate the edema time-evolution in HF patients from bioimpedance (BI) measurements performed in their corresponding legs. The data for diagnosis are picked-up using a wearable device specifically developed for the application in accuted heart failure patients in the context of HF-VOLUM project. The main objective of the project is the calculus of the edema or volume evaluation in legs as a consequence of liquid accumulation, basically, water, as a procedure to real time supervision of the patient health. For that, as an initial step, a calibration method is proposed to extract the extracellular volume component from bioimpedance measurements done in healthy subjects, and then, applied to unhealthy ones. In the method, intra and extra cellular resistances are calculated from fitted Cole-Cole model parameters derived from BI spectroscopy measurements, and employed for the calculus of the extracellular resistance. Results obtained in a small pilot assay, with four healthy subject and two heart failure subjects, show sensitivities in the ranges of -5.2 to -1.94 ml/Ω in leg volume for healthy people, and -122.4 to -41.47 ml/Ω in unhealthy people. Measurements taken at test point of 50 kHz frequency show comparable sensitivities. We expect to extend this pilot to a wider sample to further validation and confirmation of the proposed calibration method for wearable device here described.
Effects of Electrical Fields on Neuroblastoma (N2A) Cell Differentiation: Preliminary Results
D. Martin-Fernández, P. Pérez-García, M.E. Martín, P. Daza, J.A. Serrano-Viseas, G. Huertas and A. Yúfera
Conference · International Conference on Biomedical Electronics and Devices BIODEVICES 2021
resumen
This work describes Electrical Stimulations (ES) assays on stem cells. The neuroblastoma (N2A) cell linage was submitted to several electrical fields to enable and enhance its differentiation toward neurons. Both Direct Current (DC) and Alternated Current (AC) time dependent electric field protocols were applied to N2A cell culture under differentiation conditions, obtaining different responses. Control and electrically excited samples’ number of differentiated cells and neurite lengths were measure after differentiation. Results showed that DC fields have a strong influence on N2A differentiation since the percentage of differentiated cells and the neurites lengths were the highest. In addition, a significant alignment of neurites measured with the applied electrical field has been detected, which demonstrates the high sensitivity of differentiation processes to electrical field polarity.
Designing bioimpedance based sensors for cell cultures test
P. Perez, A. Yúfera, J.A. Serrano and G. Huertas
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2020
resumen
This work presents a procedure to improve biomedical sensor design flow by including information taken from sensor technical specifications and data from its biomedical dynamics, in our case, the system described is sensing cell culture assays. The main structural components of a biosensor for cell culture with real-time monitoring are analyzed, modelled and incorporated into the system design flow in such a way that the resulting sensor designed by the procedure will engender analysis of the circuits' constraints and cell sensitivity, together with the dynamics imposed by the living cells. The time evolution for general cell cultures is reproduced, and an image processing approach is applied to transduce the cell increments to the cell-electrode parameters as previously defined. The proposed tool is applied to the Electrical Cell-Substrate Sensing (ECIS) technique for cell culture test using herein the Oscillation Based Test (OBT) as a bioimpedance testing method. Other bioimpedance test techniques could be directly implemented into the proposed tool to profit similar results. The aforementioned tool, that fully models a cell-culture assay, was experimentally tested using the AA8 cell line, and the results presented in this paper validating the tool predictions.
A plethysmographic sensor for monitoring volumen changes in cardiovascular pathologies
E. Rando, P. Pérez, G. Huertas and A. Yúfera
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2019
resumen
This paper presents a capacitive system capable of performing leg volume change monitorization in patients suffering from Heart Failure (HF) conditions. The body volume evolution serves as a prognosis marker for this kind of patients, such patients can benefit from a wearable monitorization system. The proposal is based on a contactless capacitive wearable structure implemented by a two-plate plane-parallel capacitor geometry. The system exhibits sensitivity to leg volume change and the sensor curves are provided. A 2.5x2.5cm capacitive electrode design will generate capacitive values within the range [1-2] pF. Acquisition of the capacitance value is performed via an electronic differentiator implemented using op-amps, illustrating good results in simulated volume analysis implemented using pspice.
Characterization of Implanted Stents through Neointimal Tissue Bioimpedance Simulations
J.M. Portillo-Anaya, P. Pérez, G. Huertas, A. Olmo, J.A. Serrano, A. Maldonado-Jacobi and A. Yúfera
Conference · International Conference of the IEEE Engineering in Medicine and Biology Society EMBC2019
resumen
This work describes how is possible the definition of the light hole or lumen in implanted stents affected by restenosis processes using the BioImpedance (BI) as biomarker. The main approach is based on the fact that neointimal tissues implied in restenosis can be detected and measured thanks to their respective conductivity and dielectric properties. For this goal, it is proposed a four-electrode setup for bioimpedance measurement. The influence of the several involved tissues in restenosis: fat, muscle, fiber, endothelium and blood, have been studied at several frequencies, validating the setup and illustrating the sensitivity of each one. Finally, a real example using a standard stent, has been analyzed for stable and vulnerable plaques in restenosis test cases, demonstrating that the proposed method is useful for the stent obstruction test. Bioimpedance simulation test has been performed using the electric physics module in COMSOL Multiphysics®.
Practical Characterization of Cell-Electrode Electrical Models in Bio-Impedance Assays
J.A. Serrano, P. Pérez, A. Maldonado, M. Martín, A. Olmo, P. Daza, G. Huertas and A. Yúfera
Conference · International Conference on Biomedical Electronics and Devices BIODEVICES 2018
resumen
This paper presents the fitting process followed to adjust the parameters of the electrical model associated to a cell-electrode system
in Electrical Cell-substrate Impedance Spectroscopy (ECIS) technique, to the experimental results from cell-culture assays. A new
parameter matching procedure is proposed, under the basis of both, mismatching between electrodes and time-evolution observed in
the system response, as consequence of electrode fabrication processes and electrochemical performance of electrode-solution
interface, respectively. The obtained results agree with experimental performance, and enable the evaluation of the cell number in a
culture, by using the electrical measurements observed at the oscillation parameters in the test circuits employed.
Monitoring Muscle Stem Cell Cultures with Impedance Spectroscopy
Y. Yuste, J.A. Serrano, A. Olmo, A. Maldonado-Jacobi, P. Pérez, G. Huertas, S. Pereira, F. de la Portilla and A. Yúfera
Conference · International Conference on Biomedical Electronics and Devices BIODEVICES 2018
resumen
The aim of this work is to present a new circuit for the real-time monitoring the processes of cellular growth and differentiation of
skeletal myoblast cell cultures. An impedance spectroscopy Oscillation-Based technique is proposed for the test circuit, converting the
biological system into a voltage oscillator, and avoiding the use of very high performance circuitry or equipment. This technique proved
to be successful in the monitoring of cell cultures growth levels and could be useful for determining the degree of differentiation
achieved, of practical implications in tissue engineering.
Bioimpedance real-time characterization of neointimal tissue inside stents
D. Rivas-Marchena, A. Olmo, G. Huertas, A. Yúfera, J. A. Miguel and M. Martinez
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2017
resumen
It is hereby presented a new approach to monitor restenosis in arteries fitted with a stent during an angioplasty. The growth of neointimal tissue is followed up by measuring its bioimpedance with Electrical Impedance Spectroscopy (EIS). Besides, a mathematical model is derived to analytically describe the neointima´s histological composition from its bioimpedance. The model is validated by finite-element analysis (FEA) with COMSOL Multiphysics ®. Satisfactory correlation between the analytical model and the FEA simulation is achieved for most of the characterization range, detecting some deviations introduced by the thin "double layer" that separates the neointima and the blood. It is shown how to apply conformal transformations to obtain bioimpedance models for stack-layered tissues over coplanar electrodes. Particularly, this is applied to characterize the neointima in real-time. This technique is either suitable as a main mechanism of restenosis follow-up or it can be combined with proposed blood-pressure-measuring intelligent stents to auto-calibrate the sensibility loss caused by the adherence of the tissue on the micro-electro-mechanical sensors (MEMS).
A Tracking Algorithm For Cell Motility Assays in CMOS Systems
C. Martínez-Gómez, A. Olmo, G. Huertas, P. Pérez, A. Maldonado-Jacobi and A. Yúfera
Conference · International Conference of the IEEE Engineering in Medicine and Biology Society EMBC 2017
resumen
This work proposes a method for the study and real-time monitorization of a single cell on a 2D electrode matrix, of great interest in cell motility assays and in the characterization of cancer cell metastasis. A CMOS system proposal for cell location based on occupation maps data generated from Electrical Cell-substrate Impedance Spectroscopy (ECIS) has been developed. From experimental assays data, an algorithm based on analysis of the eight nearest neighbours has been implemented to find the cell center of mass. The path followed by a cell, proposing a Brownian route, has been simulated with the proposed algorithm. The presented results give an accuracy over 95% in the determination of the coordinates (x, y) from the expected cell center of mass.
A CMOS Tracking System Approach for Cell Motility Assays
C. Martínez-Gómez, A. Olmo, G. Huertas, P. Pérez, A. Maldonado-Jacobi and A. Yufera
Conference · International Conference on Biomedical Electronics and Devices BIODEVICES 2017
resumen
This work proposes a method for studying and monitoring in real-time a single cell on a 2D electrode matrix, of great interest in cell motility assays and in the characterization of cancer cell metastasis. A CMOS system proposal for cell location based on occupation maps data generated from Electrical Cell-substrate Impedance Spectroscopy (ECIS) has been developed. From this cell model, obtained from experimental assays data, an algorithm based on analysis of the 8 nearest neighbors has been implemented, allowing the evaluation of the cell center of mass. The path followed by a cell, proposing a Brownian route, has been simulated with the proposed algorithm. The presented results show the success of the approach, with accuracy over 95% in the determination of any coordinate (x, y) from the expected center of mass.
Monitoring Tissue Evolution on Electrodes with Bio-Impedance Test
A. Maldonado, P. Pérez, G. Huertas, A. Yúfera, A. Rueda, and J.L. Huertas
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2016
resumen
A technique for real-time monitoring of bio-impedances using a Voltage Oscillation (VO) methodology is proposed. The main idea relies on connecting the bio-system in such a way that a suitable electrical oscillator, which only uses a DC power source, is built. Thanks to the employed electrical models, the oscillation parameters can be directly related to the biological test. System simulations show that the impedance values of a tissue, called herein Zx, can be determined by measuring the actual frequency and amplitude of the proposed VO system, being possible to select the frequency range to optimize the system sensitivity.
Diseño de sistemas sensoriales basados en la plataforma Arduino
P. Brox, G. Huertas-Sanchez, A. Lopez-Angulo, M. Alvarez-Mora and I. Haya
Conference · Congreso de Tecnología, Aprendizaje y Enseñanza de la Electrónica TAEE 2016
resumen
Different sensory systems that are implemented using the open hardware platform Arduino are described in this paper. These projects are developed by students from the last course of Bachelor Physics Degree at the University of Seville. The educational purpose of the development of this kind of project is to apply their acquired knowledge in electronics to solve a specific problem.
Cell-Culture Measurements using Voltage Oscillations
A. Maldonado, P. Pérez, G. Huertas, A. Yúfera, A. Rueda and J.L. Huertas
Conference · IEEE Latin American Symposium on Circuits and Systems LASCAS 2016
resumen
A comprehensive system for real-time monitoring of a set of cell-cultures using a Voltage Oscillation (VO) methodology is proposed. The main idea is to connect the bioelectrical elements (electrodes&cell-culture) in such a way that sequentially a suitable electrical oscillator, which only uses a DC power source, is built. Using the employed electrical models given in [1, 2], the attained oscillation parameters (frequency and amplitude) can be directly related to the biological test. A digital circuitry is developed to pick-up the experimental measurements, which are gathered and shown in real-time in a web application.
From voltage oscillations to tissue-impedance measurements
A. Maldonado, P. Perez, G. Huertas, A. Yufera, A. Rueda and J.L. Huertas
Conference · IEEE Biomedical Circuits and Systems Conference BioCAS 2015
resumen
A technique for real-time monitoring of bio-impedances using a Voltage Oscillation (VO) methodology is proposed. The main idea relies on connecting the bio-system in such a way that a suitable electrical oscillator, which only uses a DC power source, is built. Thanks to the employed electrical models, the oscillation parameters can be directly related to the biological test. System simulations show that the impedance values of a tissue, called herein Zx, can be determined by measuring the actual frequency and amplitude of the proposed VO system, being possible to select the frequency range to optimize the system sensitivity.
Towards Bio-Impedance Based Labs: A Review
P. Pérez, A. Maldonado, A. Yúfera, G. Huertas, A. Rueda and J.L. Huertas
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2015
resumen
Conference Paper
Oscillation-Based Test applied to cell culture monitoring
G. Huertas, A. Maldonado, A. Yufera and A. Rueda
Conference · IEEE SENSORS 2013
resumen
A method for cell-culture real-time monitoring by means of Oscillation-Based Test (OBT) technique is proposed. The idea is inspired in previous works from the authors in the area of testing analogue integrated circuits and deals with solving some critical points in this kind of biological measurements. A simple topology based on a non-linear element in a feedback loop is employed for converting the Cell-Culture Under Test (CCUT) into a suitable ¿biological¿ oscillator. Then, the oscillator parameters (frequency, amplitude, phase, etc...) are used as empirical markers to carry out an appropriate interpretation in terms of cell size identification, cell counting, cell growth, etc. The Describing Function (DF) approach employed, for the involved mathematical calculations in the analysis of the 'biological circuit', predicting the frequency and amplitude of the oscillations. The precise values of oscillation parameters are closely related to the cell-electrode area overlap in the cell-culture.
Electrical Cell-substrate Impedance Spectroscopy (ECIS) Measurements based on Oscillation-Based Test Techniques
G. Huertas, A. Maldonado, A. Yufera, A. Rueda and J.L. Huertas
Conference · International Workshop on Impedance Spectroscopy IWIS 2013
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A system for cell-culture real-time monitoring based on ECIS techniques, using the Oscillation-Based Test (OBT) meethodology is proposed. The system transforms a Cell-Culture under Test (CCUT) ¡nto a suitable 'bioIogical' oscillator, using only a DC power supply. Thanks to cell-electrode electrical models employed, the oscillation parameters obtained can be directly related with biological test. The system simulations solve with a 0.16 Hz/μm2 resolution on cell area detection for a proposed 50 x 50 μm2 microelectrode area.
Cell-culture Real-Time Monitoring: an Oscillation-based Approach
G. Huertas, A. Maldonado, J. Normando Olmo, A. Yúfera, A. Rueda and J.L. Huertas
Conference · Conference on the Design of Circuits and Integrated Systems DCIS 2013
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In this paper, a way to cell-culture real-time monitoring by means of Oscillation-Based Test (OBT) methodology is proposed. The proposed idea is inspired in previous works from the authors in the area of testing analogue integrated circuits and deals with solving some critical points of biological measurements. A simple topology based on a non-linear element in a feedback loop is employed for converting the Cell-Culture Under Test (CCUT) into a suitable 'biological' oscillator. Then, the oscillator parameters (frequency, amplitude, phase, etc...) are used as empirical markers to carry out an appropriate interpretation in terms of cell size identification, cell counting, cell growth, etc. The precise values of oscillation parameters are closely related to the cell-electrode area overlap in the cellculture. To establish the accuracy of these predictions, the oscillators have been implemented and validated in Simulink.
An Impedance-Based Microscopy for Cell-Culture Imaging Using Microelectrode Sensors
A. Olmo, G. Huertas and A. Yúfera
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2012
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Abstract not available
A Microscopy Technique based on Bio-impedance Sensors
A. Yúfera, G. Huertas and A. Olmo
Conference · European Conference on Solid-State Transducers EUROSENSOR 2012
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It is proposed a microscopy for cell culture applications based on impedance sensors. The imagined signals are measured with the Electrical Cell-Substrate Spectroscopy (ECIS) technique, by identifying the cell area. The proposed microscopy allows real-time monitoring inside the incubator, reducing the contamination risk by human manipulation. It requires specific circuits for impedance measurements, a two-dimensional sensor array (pixels), and employing electrical models to decode efficiently the measured signals. Analogue Hardware Description Language (AHDL) circuits for cell-microelectrode enables the use of geometrical and technological data into the system design flow. A study case with 8x8 sensor array is reported, illustrating the evolution and power of the proposed image acquisition.
(Some) Open Problems to Incorporate BIST in Complex Heterogeneous Integrated Systems
M.J. Barragán, G. Huertas, A. Rueda and J.L. Huertas
Conference · IEEE International Symposium on Electronic Design, Test and Applications DELTA 2010
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This paper presents an overview of test techniques that offer promising features when Built-In-Self-Test (BIST) must be applied to complex intgrated systems including analog, mixed-signal and RF parts. Emphasis is on techniques exhibiting a good trade-off between test requirements (basically in terms of signal accuracy and frequency) and test quality. © 2010 IEEE.
Oscillation-based test in data converters: On-line monitoring
G. Huertas and J.L. Huertas
Conference · IEEE International Symposium on Electronic Design, Test and Applications DELTA 2008
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This paper discusses the test of data converters using the so-called Oscillation Based Test (OBT) approach [1]. Extension of the concept as applied to filters and sigma-delta converters are considered, paying attention to those applications where monitoring along the circuit lifetime can be worthwhile, as is the case for hostile environments. In this case, detection of threshold voltage shifting produced by Total Ionizing Dose (TID) is an example of what can be done by resorting to OBT.
Measuring SET effects in a CMOS operational amplifier using a built-in detector
J.M. Espinosa-Duran, J. Velasco-Medina, G. Huertas, R. Velasco and J.L. Huertas
Conference · IEEE AFRICON 2007
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This paper studies the effects produced by radiation Single Event Transient (SET) injected in the transistors of a custom operational amplifier, in order to evaluate their sensitivity to the radiation transient faults. A BID (Built-In Detector), was included in the circuit in order to amplify and detect the SETs effect. The circuit was designed using a non-rad-hard AMS-CMOS 0.8um process. In this case, simulation results allow the identification of the operational amplifier most sensitive transistors and the operating conditions during which the worst effects in the operational amplifier response were produced. ©2007 IEEE.
Total ionizing dose effects in switched-capacitor filters using oscillation-based test
J.M. Espinosa-Duran, J. Velasco-Medina, G. Huertas and J.L. Huertas
Conference · Symposium on Integrated Circuits and System Design SBCCI 2007
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This paper studies long-term effects produced by ionizing radiation in a switched-capacitor filter, using the Oscillation Based Test (OBT) approach [1]. In this case, threshold voltage shifting is considered as one of the major concerning effects produced by Total Ionizing Dose (TID). Simulation results show that the OBT approach is very well suited for detection of faulty filters. Copyright 2007 ACM.
Test of switched-capacitor ladder filters using OBT
E. Romero, G. Peretti, G. Huertas and D. Vázquez
Conference · International Mixed-Signals Testing Workshop IMSTW 2004
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In this paper, a way to test switched-capacitors ladder filters by means of Oscillation-Based Test (OBT) methodology is proposed. Third-order low-pass Butterworth and Elliptic filters are considered in order to prove the feasibility of the proposed approach. A topology with a non-linear element in an additional feedback loop is employed for converting the Circuit Under Test (CUT) into an oscillator. The idea is inspired in some author's previous works (G. Huertas, D. Vázquez, A. Rueda, J.L. Huertas, Oscillation-based Test Experiments in Filters: a DTMF example, in: Proceedings of the International Mixed-Signal Testing Workshop (IMSTW'99), British Columbia, Canada, 1999, pp. 249-254; G. Huertas, D. Vázquez, E. Peralías, A. Rueda, J.L. Huertas, Oscillation-based test in oversampling A/D converters, Microelectronic Journal 33(10) (2002) 799-806; G. Huertas, D. Vázquez, E. Peralías, A. Rueda. J.L. Huertas, Oscillation-based test in bandpass oversampled A/D converters, in: Proceedings of the International Mixed-Signal Test Workshop, June 2002, Montreaux (Switzerland), pp. 39-48; G. Huertas, D. Vázquez, A. Rueda, J.L. Huertas, Practical oscillation-based test of integrated filters, IEEE Design and Test of Computers 19(6) (2002) 64-72; G. Huertas, D. Vázquez, E. Peralías, A. Rueda, J.L. Huertas, Testing mixed-signal cores: practical oscillation-based test in an analog macrocell, IEEE Design and Test of Computers 19(6) (2002) 73-82). Two methods are used, the describing function approach for the treatment of the non linearity and the root-locus method for analysing the circuit and predicting the oscillation frequency and the oscillation amplitude. In order to establish the accuracy of these predictions, the oscillators have been implemented in SWITCAP (K. Suyama, S.C. Fang, Users' Manual for SWITCAP2 Version 1.1, Columbia University, New York, 1992). Results of a catastrophic fault injection in switches and capacitors of the filter structure are reported. A specification-driven fault list for capacitors is also defined based on the sensitivity analysis. The ability of OBT for detecting this kind of faults is presented. (c) 2005 Elsevier Ltd. All rights reserved.
Method for parameter extraction of analog sine-wave signals for mixed-signal built-in-self-test applications
D. Vázquez, G. Léger, G. Huertas, A. Rueda and J.L. Huertas
Conference · Design, Automation and Test in Europe Conference and Exhibition DATE 2004
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This paper presents a method for extracting, in the digital domain, the main characteristic parameters of an analog sine-wave signal. The required circuitry for on-chip implementation is very simple and robust, which makes the present approach very suitable for BIST applications. Solutions in this sense are addressed together with simulation results that validate the feasibility of the proposed approach.
A LP-LV high performance monolitic DTMF receiver with on-chip test facilities
D. Vázquez, G. Huertas, M.J. Avedillo, J.M. Quintana, A. Rueda and J.L. Huertas
Conference · Conference on VLSI Circuits and Systems 2003
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This paper presents a mixed-signal DTMF receiver implemented in a double-poly double-metal 0.6um technology able to operate in the range of 2.7V-5V of voltage supply with a low current consumption (<1mA). An smart digital detector and decoder algorithm provides a very good speech immunity. On-chip test facilities for the analog part have.. been incorporated into the chip. A modified opamp (called sw-opamp) has been used to provide external accessing to inputs and outputs of the main analog blocks for off-line testing purposes. The so-called Oscillation-Based-Test (OBT) has also been integrated to perform a structural testing of the analog part. The additional cost of such on-chip test facilities is very small: just one extra pin and an area overhead of around 7%. Experimental results demonstrate the good performance of the design and the feasibility of the testing approaches.
Oscillation-based test in bandpass oversampled A/D converters
G. Huertas, D. Vázquez, A. Rueda and J.L. Huertas
Conference · IEEE International Mixed-Signal Testing Workshop IMSTW 2003
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This paper extends a study performed by the authors in Previous papers dealing with the OBT approach applied to low-pass modulators 'Microelectron. J. 33/10 (2002) 799', showing herein the specific features associated to the bandpass case. A practical feedback strategy will be proposed in order to built an effective oscillator, which can be valuable for testing purposes. Critical points of the proposed OBT solution will be considered in order to establish useful guidelines to apply this test approach to generic bandpass SigmaDelta modulators. (C) 2003 Elsevier Ltd. All rights reserved.
Practical solutions for the application of the oscillation-based-test in analog integrated circuits
D. Vázquez, G. Huertas, G. Léger, A. Rueda and J.L. Huertas
Conference · IEEE International Symposium on Circuits and Systems ISCAS 2002
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This paper presents practical solutions for solving the problems arising when applying Oscillation-Based-Test. It is devoted to discuss a practical on-chip evaluation of the generated test signals. The required circuitry is very simple and robust. Moreover, preliminary results obtained from an integrated prototype are also included.
Practical oscillation-based test in analog integrated filters: Experimental results
G. Huertas, D. Vázquez, A. Rueda and J.L. Huertas
Conference · IEEE International Workshop on Electronic Design, Test and Applications DELTA 2002
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This paper presents experimental results corresponding to the use of Oscillation-based Test (OBT) when applied to a switched-capacitor integrated filter. A universal biquad is used as an example to demonstrate the feasibility of the OBT technique.
Practical solutions for the application of the oscillation-based-test: Start-up and on-chip evaluation
D. Vázquez, G. Huertas, G. Léger, A. Rueda and J.L. Huertas
Conference · IEEE VLSI Test Symposium VTS 2002
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This paper presents practical solutions for two of the main topics arising when applying Oscillation-Based-Test: the start-up of the configured oscillator and the on-chip evaluation of the generated test signals. The required circuitry is very simple and robust. Moreover, preliminary results obtained from an integrated prototype are also included.
Libros
Del electrón al chip
G. Huertas, L. Huertas and J.L. Huertas
Book · 142 p, 2015
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¿Qué hay detrás de la revolución tecnológica a la que estamos expuestos? La televisión, los ordenadores. Los teléfonos móviles o los GPS son dispositivos con numerosas aplicaciones informáticas que usamos cada día. Hablamos con familiaridad de Facebook, WhatsApp, Twitter, Instagram y un sinfín de programas que han cambiado modos y hábitos sociales; pero ¿tenemos una idea de lo que hay detrás de esos programas y qué les permite cumplir su función? En realidad, todas esas herramientas dependen para su funcionamiento de procesos de conducción eléctrica; resumiendo mucho, del movimiento de una partícula que ahora nos parece familiar: el electrón. Pero el electrón no es una realidad visible para nosotros; solo lo son los equipos electrónicos y, en ellos, como máximo, sus componentes básicos: los chips. Este libro pretende hacer llegar al lector la relación de esos dos conceptos para entender el camino que nos ha conducido hasta estos instrumentos tecnológicos que tanto utilizamos.
Oscillation-Based-Test in Mixed-Signal Circuits
G. Huertas, D. Vázquez, A. Rueda and J.L. Huertas
Book · FRET, vol. 36, 452 p, 2006
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Oscillation-Based Test in Mixed-Signal Circuits presents the development and experimental validation of the structural test strategy called Oscillation-Based Test - OBT in short. The results here presented allow to assert, not only from a theoretical point of view, but also based on a wide experimental support, that OBT is an efficient defect-oriented test solution, complementing the existing functional test techniques for mixed-signal circuits.
Capítulos de libros
Remote Sensing of Cell-Culture Assays
P. Pérez, A. Maldonado-Jacobi, A.J. López, C. Martínez, A. Olmo, G. Huertas and A. Yufera
Book Chapter · New Insights into Cell Culture Technology, pp 135-155, 2017
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This chapter describes a full system developed to perform the remote sensing of cell-culture experiments from any access point with internet connection. The proposed system allows the real-time monitoring of cell assays thanks to bioimpedance measurement circuits developed to count the number of cell present in a culture. Cell-culture characterization is performed through the measurement of the increasing bioimpedance parameter over time. The circuit implementation is based on the oscillation-based test (OBT) methodology. Bioimpedance of cell cultures is measured in terms of the oscillation parameters (frequency, amplitude, phase, etc.) and used as empirical markers to carry out an appropriate interpretation in terms of cell size identification, cell counting, cell growth, growth rhythm, etc. The device is capable of managing the whole sensing task and performs wireless communication through a Bluetooth module. Data are interpreted and displayed on a computer or a mobile phone through a web application. The system has its practical application in drug development processes, offering a label-free, high-throughput, and high-content screening method for cellular research, avoiding the classical end-point techniques and a significant workload and cost material reduction.
Oscillation-based test strategies
G. Huertas-Sánchez, G. Leger, D. Vázquez, A. Rueda and J.L. Huertas
Book Chapter · Test and Design-For-Testability in Mixed-Signal Integrated Circuits, pp 259-298, 2004
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doi
This chapter aims to present a structural test methodology using the so-called OBT technique. The conceptual bases of the OBT approach are presented as well as many practical details on its application to practical integrated circuits.
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