Found results matching for:
Author: Alberto Yúfera García
Year: Since 2002
Journal Papers
Bioimpedance Sensing of Implanted Stent Occlusions: Smart Stent
A. Rodriguez, P. Barroso, A. Olmo and A. Yufera
Journal Paper · Biosensors, vol. 12, no. 6, article 416, 2022
abstract
doi
Coronary artery disease is one of the most common diseases in developed countries and affects a large part of the population of developing countries. Preventing restenosis in patients with implanted stents is an important current medical problem. The purpose of this work is to analyse the viability of bioimpedance sensing to detect the formation of atheromatous plaque in an implantable stent. Simulations in COMSOL Multiphysics were performed to analyse the performance of the proposed bioimpedance sensing system, based on the Sheffield technique. Both non-pathological and pathological models (with atheromatous plaque), including the flow of blood were considered. Simulations with the non-pathological model showed a homogeneous distribution of the measured current intensity in the different electrodes, for every configuration. On the other hand, simulations with the pathological model showed a significant decrease of the measured current intensity in the electrodes close to the simulated atheromatous plaque. The presence of the atheromatous plaque can, therefore, be detected by the system with a simple algorithm, avoiding the full reconstruction of the image and the subsequent computational processing requirements.
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
abstract
doi
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
abstract
doi
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
abstract
doi
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
abstract
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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
abstract
doi pdf
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
abstract
doi
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
abstract
doi pdf
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.
Electrical pulse stimulation of skeletal myoblasts cell cultures with simulated action potentials
P. Villanueva, S. Pereira, A. Olmo, P. Pérez, Y. Yuste, A. Yúfera and F. de la Portilla
Journal Paper · Journal of Tissue Engineering and Regenerative Medicine, vol. 13, no. 7, pp 1265-1269, 2019
abstract
doi
Electrical pulse stimulation has an important effect on skeletal muscle development and maturation. However, the methodology for controlling these stimulation parameters to develop in vitro functional skeletal muscle tissues remains to be established. In this work, we have studied the effect of simulated action potentials on the growth and differentiation of skeletal myoblast cell cultures. A circuit simulating action potentials of 0.15 and 0.3 V/mm, at a frequency of 1 Hz and with a 4-ms pulse width, is proposed. Results show an important improvement of the growth rate and differentiation of myoblasts at a voltage of 0.15 V/mm. Parameters such as electrodes geometry or type of signals must be considered in the development of in vitro skeletal muscle.
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
abstract
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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
abstract
doi pdf
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
abstract
doi pdf
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
abstract
doi pdf
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).
Microcontroller-Based Sinusoidal Voltage Generation for Electrical Bio-Impedance Spectroscopy Applications
J.A. Castro, A. Olmo, P. Pérez and A. Yúfera
Journal Paper · Journal of Computer and Communications, vol. 4, no. 17, pp 51-58, 2016
abstract
doi pdf
A sinusoidal voltage wave generator is proposed based on the use of micro-processor digital signals with programmable duty-cycles, with application to real-time Electrical Cell-substrate Impedance Spectroscopy (ECIS) assays in cell cultures. The working principle relies on the time convolution of the programmed microcontroller (μC) digital signals. The expected frequency is easily tuned on the bio-impedance spectroscopy range [100 Hz, 1 MHz] thanks to the μC clock frequency selection. This system has been simulated and tested on the 8 bits μC ArduinoTM Uno with ATmega328 version. Results obtained prove that only three digital signals are required to fit the general specification in ECIS experiments, below 1% THD accuracy, and show the appropriateness of the system for the real-time monitoring of this type of biological experiments.
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
abstract
doi pdf
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.
Monolithic integration of Giant Magnetoresistance (GMR) devices onto standard processed CMOS dies
M.-D. Cubells-Beltrán, C. Reig, A. de Marcellis, E. Figueras, A. Yúfera, B. Zadov, E. Paperno, S. Cardoso and P.P. Freitas
Journal Paper · Microelectronics Journal, vol. 45, no. 6, pp 702-707, 2014
abstract
doi
Giant Magnetoresistance (GMR) based technology is nowadays the preferred option for low magnetic fields sensing in disciplines such as biotechnology or microelectronics. Their compatibility with standard CMOS processes is currently investigated as a key point for the development of novel applications, requiring compact electronic readout. In this paper, such compatibility has been experimentally studied with two particular non-dedicated CMOS standards: 0.35 μm from AMS (Austria MicroSystems) and 2.5 μm from CNM (Centre Nacional de Microelectrònica, Barcelona) as representative examples. GMR test devices have been designed and fabricated onto processed chips from both technologies. In order to evaluate so obtained devices, an extended characterization has been carried out including DC magnetic measurements and noise analysis. Moreover, a 2D-FEM (Finite Element Method) model, including the dependence of the GMR device resistance with the magnetic field, has been also developed and simulated. Its potential use as electric current sensors at the integrated circuit level has also been demonstrated.
Monitoring living cell assays with bio-impedance sensors
P. Daza, A. Olmo, D. Cañete and A. Yúfera
Journal Paper · Sensors and Actuators, B: Chemical, vol. 176, pp 605-610, 2013
abstract
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This work proposes a cell¿microelectrode model to be used on cell culture assays as an alternative to end-point protocols employed in cell growth and cell biometry applications. The microelectrode model proposed is based on the area overlap between the microelectrode sensor and the living cells as main parameter. This model can be applied to cell size identification, cell count, and their extension to cell growth, motility and dosimetry protocols. A procedure to fit the proposed model to microelectrode electrical performance is presented, enabling the decoding of empirical measurements and its interpretation in terms of number of cells. This fitting procedure depends on three parameters: microelectrode geometry, gap resistance between substrate attached cells and microelectrode and, mainly, on microelectrode area covered by cells. The model has been implemented employing Analog Hardware Descriptions Language (AHDL) to be incorporated also to mixed-mode simulation processes during circuit design flow.
Cell-culture real time monitoring based on bio-impedance measurements
P. Daza, D. Cañete, A. Olmo, J.A. García and A. Yúfera
Journal Paper · Sensors & Transducers Journal, vol. 14-1, Special Issue, pp 266-275, 2012
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This paper proposes the application of a cell-microelectrode model in cell biometry experiments, using the cell-electrode area overlap as its main parameter. The model can be applied to cell size identification and cell count, and further extended to study cell growth and dosimetry protocols. Experiments have been conducted in AA8 cell line, obtaining promising results.
Generation of HDL models for bio-impedance sensor simulation based on microelectrodes
A. Yúfera and E. Gallego
Journal Paper · Sensors and Transducers, vol. 10, pp 160-170, 2011
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This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre and post system analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bio-impedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data decoding from measurements. The developed program allows cell culture image processing for geographic information extraction and sensor sizing, generating cell count and Analog Hardware Description Language (AHDL) equivalent circuits useful for whole system simulations. © 2011 IFSA.
Use of Electrical Impedance Spectroscopy (EIS) to Monitor Cryoprotectant Concentration in Cellular and Tissue Cryopreservation Protocols
A. Olmo, B. Buzon, A. Yufera and R. Risco
Journal Paper · Cryobiology, vol. 61, no. 3, pp 392, 2010
abstract
doi
In this paper we theoretically analyse the use of Electrical Impedance Spectroscopy (EIS) to efficiently monitor cryoprotectant concentration in cryopreservation protocols.
In order to correctly determine the perfusion of cryoprotectant inside tissues and organs, with its spatial distribution, it is necessary to previously study the influence that the frequency, temperature and electrode configuration have in bioimpedance measurements.
We have analysed with COMSOL Multiphysics software the frequency response of a 2-electrode system to different concentrations of Me2SO, perfused into 3T3 fibroblasts and monolayers of Mesenchymal Stem Cells (MSCs), fundamental for tissue-based therapeutics.
An electrical model based on a previous work was used (Olmo et al., 2010). This model constitutes a complete electrical description of the electrode-cell system, including the electrode-electrolyte double layer, electrode-cell gap, electrolyte-cell double layer and cellular membrane, besides taking into account electrical properties of intra and extra-cellular medium. The Quasi-statics module of COMSOL was used to perform the finite element simulations, for different frequencies.
Simulations show the system easily detects changes in cryoprotectant concentration, being necessary to optimize both frequency and electrode configuration to efficiently detect cryoprotectant perfusion inside the biological material. Temperature influence on conductivity and permittivity, as well as on electrode interfaces, has also been discussed in detail.
The model and finite element method simulation herewith reported has proved to be a good tool, which can be used to optimize the design of experimental setups. These models can also be extended in the future, to analyse the use of more complex three-dimensional EIS systems, which can monitor cryoprotectant perfusion in the cryopreservation of more complex tissues and organs.
Design of a CMOS closed-loop system with applications to bio-impedance measurements
A. Yúfera and A. Rueda
Journal Paper · Microelectronics Journal, vol. 41, no. 4, pp 231-239, 2010
abstract
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This paper proposes a method for impedance measurements based on a closed-loop implementation of CMOS circuits. The proposed system has been conceived for alternate current excited systems, performing simultaneously driving and measuring functions, thanks to feedback. The system delivers magnitude and phase signals independently, which can be optimized separately, and can be applied to any kind of load (resistive and capacitive). Design specifications for CMOS circuit blocks and trade-offs for system accuracy and loop stability have been derived. Electrical simulation results obtained for several loads agree with the theory, enabling the proposed method to any impedance measurement problem, in special, to bio-setups including electrodes. (C) 2010 Elsevier Ltd. All rights reserved.
A CMOS optical PSD with submicrometer resolution
R. Doldán, E. Peralías, A. Yufera and A. Rueda
Journal Paper · Analog Integrated Circuits and Signal Processing, vol. 53, no. 2-3, pp 109-118, 2007
abstract
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This paper presents the design of an optical Position Sensing Detector (PSD) for application in biological material gene identification. The system is able to measure changes in the position of a light spot emitted by a Vertical Cavity Surface Emitting Laser (VCSEL). Changes in spot position are produced by the deflections of a microcantilever used to sense the hybridisation process of the biological material. Detection of these deflections requires submicrometer resolution. The photodetectors and the detection algorithm proposed in this paper have been designed and optimized for this resolution. A 0.35 mu m CMOS prototype consisting of an array of 22 PSDs has been implemented and experimentally characterized. The obtained results confirm that displacements of the light spot position as low as 0.15 mu m can be detected.
A highly sensitive microsystem based on nanomechanical biosensors for genomics applications
L.M. Lechuga,J. Tamayo, M. Álvarez, L.G. Carrascosa, A. Yufera, R. Doldán, E. Peralías, A. Rueda, J.A. Plaza, K. Zinoviev, C. Domínguez, A. Zaballos, M. Moreno, C. Martínez-A, D. Wenn, N. Harris, C. Bringer, V. Bardinal, T. Camps, C. Vergnenègre, C. Fontaine, V. Díaz and A. Bernad
Journal Paper · Sensors and Actuators, B: Chemical, vol. 118, no. 1-2, pp 2-10, 2006
abstract
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Microcantilever-based biosensors are a promising tool to detect biomolecular interactions in a direct way with high accuracy. We show the development of a portable biosensor microsystem able to detect nucleic acid hybridization with high sensitivity. The microsystem comprises an array of 20 micromechanical cantilevers produced in silicon technology, a polymer microfluidic system for delivery of the samples, an array of 20 vertical cavity surface emitting lasers (VCSELs) with collimated beams thanks to an integrated microlens array, an optical coupling element to provide the optical path required, and chips with the photodetectors and the CMOS circuitry for signal acquisition and conditioning, capable of measuring the cantilever deflection with sub-nanometer resolution. Robust immobilization and regeneration procedures have been implemented for the oligonucleotide receptor sequences. In a further innovation, an optical waveguide cantilever transducer has been also developed in order to improve the final performance of the device. This has a number of advantages in terms of a simple optical geometry and improved sensitivity.
A tissue impedance measurement chip for myocardial ischemia detection
A. Yufera, A. Rueda, J.M. Muñoz, R. Doldán, G. Léger and E.O. Rodríguez-Villegas
Journal Paper · IEEE Transactions on Circuits and Systems I-Regular Papers, vol. 52, no. 12, pp 2620-2628, 2005
abstract
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In this paper, the design of a specific integrated circuit for the measurement of tissue impedances is presented. The circuit will be part of a multi-micro-sensor system intended to be used in cardiac surgery for sensing biomedical parameters in living bodies. Myocardium tissue impedance is one of these parameters which allows ischemia detection. The designed chip will be used in a four-electrode based setup where the effect of electrode interfaces are cancelled by design. The chip includes a circuit to generate the stimulus signals (sinusoidal current) and the circuitry to measure the magnitude and phase of the tissue impedance. Several integrated circuits have been designed, fabricated and tested, in a 0.8-mu m CMOS process, working at 3 V of power supply. Some of them including building blocks, and other with the whole measurement system. Experimental tests have shown the circuit feasibility giving expected results for both in-vitro and in-vivo test conditions.
A 1.25-V micropower Gm-C filter based on FGMOS transistors operating in weak inversion
E. Rodríguez-Villegas, A. Yufera and A. Rueda
Journal Paper · IEEE Journal of Solid-State Circuits, vol. 39, no. 1, pp 100-111, 2004
abstract
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This paper presents a novel linearized transconductor architecture working at 1.25 V in a 0.8-mum CMOS technology with very low power consumption. The special features of the floating-gate MOS (FGMOS) transistor are combined in weak and strong inversion leading to a simplified topology with fewer stacked transistors and a very low noise floor. The design methodology is thoroughly explained, together with the advantages and disadvantages of working with the FGMOS transistor. Furthermore, second-order effects arising from nonideal behavior of the device, are analyzed and limits for the performance are established Experimental results from a second-order low-pass/bandpass filter that was implemented using the transconductor show a tunability of over one and a half decades in the audio range, a dynamic, range of over 62 dB, and a maximum power consumption of 2.5 muW. These results demonstrate the suitability of the FGMOS transistor for implementing analog continuous-time filters, while at, the same time pushing down, the voltage limits of process technologies and simplifying the circuit topologies to obtain significant power savings.
A 1-V micropower log-domain integrator based on FGMOS transistors operating in weak inversion
E. Rodríguez-Villegas, A. Yufera and A. Rueda
Journal Paper · IEEE Journal of Solid-State Circuits, vol. 39, no. 1, pp 256-259, 2004
abstract
doi
This paper describes the implementation of a low-power floating gate MOS-(FGMOS)-based log-domain integrator that reduces the minimum required voltage supply and the risk of instabilities. The performance of the block is illustrated with the experimental results of a second-order low-pass/bandpass filter working in the audio range with a 1-V voltage supply and a maximum power consumption of 2 muW. The experimental results show that the FGMOS transistor is a powerful device that enables the design of low-voltage-supply low-power-consumption filters which have very simple topologies.
Conferences
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
abstract
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
abstract
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
abstract
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.
Device circuit co-design of HyperFET transistors
J. Núñez, M. Jiménez and M.J. Avedillo
Conference · Conference on Design of Circuits and Integrated Systems DCIS 2019
abstract
In this paper, we describe device-circuit co-design experiments for Hybrid Phase Transition FETs (HyperFETs). HyperFET transistors, built by connecting a phase transition material (PTM) to the source terminal of a FET, are able to increase the ON current without triggering the OFF current. This enables reducing supply voltage and so power consumption. HyperFETs with different ON-OFF currents tradeoffs are analyzed. Inverter chains and ring oscillators built with them are evaluated in terms of power and compared to reference designs using FETs alone. Power reductions up to 50% are shown for a HyperFET with similar OFF current and higher ON current than its FET counterpart when nodes frequently switch. However, power penalties by a factor of 80 have been obtained for other simulation stimuli. Our results identify switching activity as critical for obtaining power advantages from the supply voltage reduction permitted by HyperFETs, and suggest guidance both at device and circuit level to take full advantage of these devices.
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
abstract
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
abstract
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
abstract
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
abstract
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
abstract
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
abstract
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
abstract
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.
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
abstract
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
abstract
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
abstract
Conference Paper
Oscillation-Based Test applied to cell culture monitoring
G. Huertas, A. Maldonado, A. Yufera and A. Rueda
Conference · IEEE SENSORS 2013
abstract
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
abstract
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
abstract
pdf
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.
GMR technology: a real candidate for monolithically integrated off-line IC current sensing
C. Reig, M.D. Cubells, A. Cano, J. Sanchís, D. Gilabert, J. Madrenas, A. Yúfera, E. Figueras, S. Cardoso and P.P. Freitas
Conference · International Conference on Analog VLSI Circuits, 2012
abstract
Abstract not available
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
abstract
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
abstract
pdf
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.
A Microelectrode-Cell Sensor Model for Real Time Monitoring
A. Yúfera, D. Cañete and P. Daza
Conference · International Conference on Sensor Device Technologies and Applications SENSORDEVICES 2011
abstract
pdf
In this paper the application of a cellmicroelectrode model to cell biometry experiments is proposed, using the cell-electrode area overlap as main parameter. The model can be applied to cell size identification, cell count, and their extension to cell growth and dosimetry protocols. Experimental results using AA8 cell line are presented, obtaining promising results.
Modeling Microelectrode Sensors for Cell-Culture Monitoring
A. Yúfera, D. Cañete and P. Daza
Conference · IEEE SENSORS 2011
abstract
It is proposed the use of a cell-microelectrode model for cell biometry applications. The model can be applied to cell size identification, cell count, and extended to cell growth and dosimetry protocols, by identifing the total area covered by cells. The work develops Analog Hardware Description Language (AHDL) codes for cell-microelectrode systems, considering the geometrical and technological parameters, enabling the possibility to simulate biological complex systems with convencional mixed-mode simulators as SpectreHDL. Experimental results are presented to calculate the cell number in growth and dosimetry experiments using AA8 cell line.
Using microelectrode models for real time cell-culture monitoring
A. Yúfera, P. Daza and D. Cañete
Conference · Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBS 2011
abstract
pdf
This paper proposes a cell-microelectrode model for cell biometry applications, based on the area overlap as main parameter. The model can be applied to cell size identification, cell count, and their extension to cell growth and dosimetry protocols. Experiments performed with comercial electrodes are presented, illustrating a procedure to obtain cell number in both growth and dosimetry processes. Results obtained for the AA8 cell line are promising.
Use of Electrical Impedance Spectroscopy (EIS) to Monitor Cryoprotectant Concentration in Cellular and Tissue Cryopreservation Protocols
A. Olmo, B. Buzon, A. Yufera and R. Risco
Conference · Annual Meeting on the Society for Cryobiology CRYO 2010
abstract
In this paper we theoretically analyse the use of Electrical Impedance Spectroscopy (EIS) to efficiently monitor cryoprotectant concentration in cryopreservation protocols.
In order to correctly determine the perfusion of cryoprotectant inside tissues and organs, with its spatial distribution, it is necessary to previously study the influence that the frequency, temperature and electrode configuration have in bioimpedance measurements.
We have analysed with COMSOL Multiphysics software the frequency response of a 2-electrode system to different concentrations of Me2SO, perfused into 3T3 fibroblasts and monolayers of Mesenchymal Stem Cells (MSCs), fundamental for tissue-based therapeutics.
An electrical model based on a previous work was used (Olmo et al., 2010). This model constitutes a complete electrical description of the electrode-cell system, including the electrode-electrolyte double layer, electrode-cell gap, electrolyte-cell double layer and cellular membrane, besides taking into account electrical properties of intra and extra-cellular medium. The Quasi-statics module of COMSOL was used to perform the finite element simulations, for different frequencies.
Simulations show the system easily detects changes in cryoprotectant concentration, being necessary to optimize both frequency and electrode configuration to efficiently detect cryoprotectant perfusion inside the biological material. Temperature influence on conductivity and permittivity, as well as on electrode interfaces, has also been discussed in detail.
The model and finite element method simulation herewith reported has proved to be a good tool, which can be used to optimize the design of experimental setups. These models can also be extended in the future, to analyse the use of more complex three-dimensional EIS systems, which can monitor cryoprotectant perfusion in the cryopreservation of more complex tissues and organs.
Bioimpedance monitoring for cryopreservation process control
A. Olmo, B. Buzón, A. Yúfera and R. Risco
Conference · International Conference of IEEE Engineering in Medicine and Biology Society EMBS 2010
abstract
pdf
This paper analyses the use of Electrical Impedance Spectroscopy (EIS) to efficiently monitor cryoprotectant concentrations in cryopreservation protocols. The proposed technique can improve methods such as Liquidus Tracking (LT), allowing vitrification without exposing tissues to damaging concentrations of cryoprotectant at relatively high temperatures, and avoiding rapid temperature changes. This work is focused to continuous monitoring of cryoprotectant concentrations by detecting changes in electrical impedance. These variations, derived from cryoprotectant perfusion inside cells and tissues, can be efficiently measure by using of EIS. Finite element simulation performed with COMSOL Multiphysics software was used to analyse the frequency response of a two-electrode system to several concentrations of Me2SO, perfused into 3T3 fibroblasts and monolayers of Mesenchymal Stem Cells (MSCs), fundamental in tissue-based therapeutics.
Herramienta para el aprendizaje de sistemas de adquisición de datos
M. Gamero and A. Yúfera
Conference · Congreso de Tecnología, Aprendizaje y Enseñanza de la Electrónica TAEE 2012
abstract
pdf
Se presenta un paquete de software didáctico que facilita el proceso de enseñanza/aprendizaje de la electrónica, orientado a un sistema de adquisición de datos elemental. Consta de una breve sección expositiva, en la que se describen los contenidos de la materia, más un conjunto de simulaciones que permiten al alumno conocer el funcionamiento interno de sus diversos componentes, la influencia de parámetros de interés, como el offset de los opamp, temperatura, etc. Para cada uno de los componentes, se aportan varias realizaciones que permiten al alumno interactuar con las simulaciones. Asímismo, el usuario puede elegir las especificaciones de cada componente funcional que mejor emulen el comportamiento real del sistema. Las simulaciones permiten conocer los valores intermedios y formas de onda de sus variables durante la ejecución.
El Entorno: Vision - E Laboratory
J. Molina and A. Yufera
Conference · Congreso de Tecnología, Aprendizaje y Enseñanza de la Electrónica TAEE 2012
abstract
pdf
Se presenta un entorno de programación para el estudio y desarrollo de algoritmos de tratamiento de imágenes y visión por computador. La herramienta permite la programación en cualquier lenguaje, con la única restricción de que se desarrolle bajo entornos windows. Se ha concebido como instrumento de ayuda a la realización de prácticas de laboratorio de alumnos en las asignaturas de tratamiento digital de imágenes de ingeniería informática.
Automatic generation of Hardware Description Language (HDL) models for 2D bio-impedance microelectrode sensors useful in electrical simulations
A. Yúfera and E. Gallego
Conference · International Conference on Sensor Device Technologies and Applications SENSORDEVICES 2010
abstract
pdf
This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre and post system analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bio-impedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data decoding from measurements. The developed program allows cell culture image processing for geographic information extraction and sensor sizing, generating cell count and Analog Hardware Description Language (AHDL) equivalent circuits useful for whole system simulations. © 2010 IEEE.
Finite element simulation of microelectrodes for bio-impedance sensor applications
A. Olmo and A. Yúfera
Conference · International Conference on Sensor Device Technologies and Applications SENSORDEVICES 2010
abstract
pdf
Electrical models for microelectrode-cell interfaces are essential to match electrical simulations to real bio-systems performance and correctly to decode the results obtained experimentally. The accurate performance simulation of a microelectrode sensor to changes in the cell-electrode system, such as cell growth, enables the optimum microelectrode design process. We report the use of COMSOL quasi-static mode, contrary to other DC modes frequently used, including magnetic fields to calculate the bioimpedance of the system. A fully electrode-cell model has been built, and the effect of fibroblasts of different diameters on the simulated impedance of small microelectrodes (32-um square) has been studied, in order to validate the model and to characterize the microelectrode sensor response to changes in cell size and density. © 2010 IEEE.
Automatic generation of analog hardware description language (AHDL) code from cell culture images
A. Yúfera and E. Gallego
Conference · International Conference on Image Processing Theory, Tools and Applications IPTA 2010
abstract
This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre and post system analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bio-impedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data decoding from measurements. The developed program can be used in cell culture image processing for geographic information extraction and sensor sizing, generating cell count and Analog Hardware Description Language (AHDL) equivalent circuits useful for whole system electrical simulations. ©2010 IEEE.
Computer simulation of microelectrode based bio-impedance measurements with COMSOL
A. Olmo and A. Yúfera
Conference · International Conference on Biomedical Electronics and Devices BIODEVICES 2010
abstract
Electrical models for microelectrode-cell interfaces are essential to match electrical simulations to real bio-systems performance and correctly to decode the results obtained experimentally. The accurate response simulation of a microelectrode sensor to changes in the cell-electrode system, such as cell growth, enables the optimum microelectrode design process. We report the use of COMSOL quasi-static mode, contrary to other DC modes frequently used, including magnetic fields to calculate the bioimpedance of the system. A fully electrode-cell model has been built, and the effect of fibroblasts of different diameters on the simulated impedance of small microelectrodes (32-um square) has been studied, in order to validate the model and to characterize the microelectrode sensor response to changes in cell size and density.
A CMOS Bio-impedance Sensor System for Cell Culture Monitoring
A. Yúfera and A. Rueda
Conference · IEEE Circuits and Systems for Medical and Environmental Applications Workshop CASME 2009
abstract
Abstract not avaliable
A CMOS bio-impedance measurement system
A. Yufera and A. Rueda
Conference · IEEE Design and Diagnostics of Electronics Systems DDECS 2009
abstract
This paper proposes a new method for bio-impedance measurement useful to 2D processing of cell cultures. It allows to represent biological samples by using a new impedance sensing method, and exploiting the electrode-to-cell model for both electrical simulation and imaging reconstruction. Preliminary electrical simulations are reported to validate the proposal for Electrical Cell Impedance Spectroscopy (ECIS) applications. The results reported show that low concentration cell culture can be correctly sensed and displayed at several frequencies using the proposed CMOS system.
A method for bioimpedance measure with four- and two-electrode sensor systems
A. Yufera and A. Rueda
Conference · Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society EMBS 2008
abstract
This paper presents an alternative method to measure impedances based on constant amplitude voltage excitation. The method makes use of feedback principle to adapt the measure conditions to load under test, being easily applied to bioimpedance measure with electrode sensors. The method has been tested for several frequencies and loads, employing four and two electrode setups. Results from electrical simulations, using CMOS circuits, fulfil the expected performance. This technique can be extended to wide frequency and load ranges, being an excellent option for impedance spectroscopy and EIT applications.
Mixed-mode simulation of optical-based systems: PSD application
R. Doldán, E. Peralías, A. Yufera and A. Rueda
Conference · Conference on Bioengineered and Bioinspired Systems II, 2005
abstract
This paper reports a new model for electrical simulation of photodetector cells, that includes its complete dynamics, and enables full system characterization, both optical and electrical parts by using the same simulation environment (Spectre in our case). The modelling of the optical parts presented in this work allows the designer to change parameters such as incident spot position and optical power, speed in spot position, photodevices responsivity, pixel fill-factor, etc. The paper presents the design and the simulation-based verification of a Position Sensing Detection (PSD) system for applications with resolutions in the micrometer range and with spot movement tracking operation originated in a DNA sensing process.
Integrated Opto-Nanomechanical biosensor for functional genomic analysis (OPTONANOGEN)
F.J. Tamayo de Miguel, M. Álvarez, L.G. Carrascosa, L.M. Lechuga, J.A. Plaza, K. Zinoviev, C. Domínguez-Matas, A. Yúfera, A. Rueda, A. Zaballos, M. Moreno, C. Martínez-Alonso, C. Fontaine, V. Díaz and A. Bernad
Conference · Workshop on Nanomechanical Sensors 2004
abstract
pdf
Abstract not available
A first order incremental analog to digital converter based on continuous time circuits
R. Doldán, A. Yúfera and A. Rueda
Conference · International Measurements Conference XVII IMEKO 2003
abstract
pdf
In this paper, an incremental Analog-to-Digital Converter (ADC) designed as part of the signalconditioning circuitry for tissue impedance measurement system is presented. Continuous-time design techniques has been used and a modified implementation of the conversion algorithm, with respect to its discrete-time counterpart, has been developed. To reduce the influence of the no-idealities, analog and digital corrections have been also implemented. A prototype in 0.8μm CMOS technology has been fabricated and tested. Experimental results are reported.
A charge correction cell for FGMOS-based circuits
E.O. Rodríguez-Villegas, A. Yúfera and A. Rueda
Conference · Symposium on Integrated Circuits and Systems Design SBCCI 2003
abstract
This paper describes a novel cell used in circuits with Floating Gate MOS transistors (FGMOS) to compensate variations in the device effective threshold voltages caused by the trapped charge at the floating gate. The performance of the circuit is illustrated with experimental results showing a residual error below 1%. This coarse compensation makes possible to reduce charge effects to the same order of magnitude than the conventional mismatching in normal MOS transistors.
A micropower log domain FGMOS filter
E.O. Rodríguez-Villegas, A. Rueda and A. Yufera
Conference · IEEE International Symposium on Circuits and Systems ISCAS 2002
abstract
In this paper, a CMOS implementation of a low voltage micropower logarithmic biquad based on Floating Gate MOS transistors (FGMOS) is presented. The translinear principle applied to the floating gate MOS transistor leads to an easy implementation of the state-space equations without using the source terminal in the loop. The voltage supply can be reduced and also there is no need of separate wells. The technique is proven in this low/band pass filter working at 1V with a maximum power consumption of 2muW. The filter parameters can be adjusted in more than two decades, being the upper frequency around 150kHz.
An integrated circuit for tissue impedance measure
A. Yufera, G. Léger, E.O. Rodríguez-Villegas, J.M. Muñoz, A. Rueda, A. Ivorra, R. Gómez, N. Noguera and J. Aguilo
Conference · Conference on Microtechnologies in Medicine & Biology IEEE-EMB 2002
abstract
In this paper, the design of aa Integrated Circuit (IC) for the measurement of tissue impedance is presented. The chip is intended to be used in monitoring biomedical parameters in living bodies. Tissue impedance is one of these parameters which allows ischemia monitoring. The designed IC is used in a four-electrode based set-up in order to minimize the effect of electrode-electrolyte interface impedance. A needle shaped probe which contains the four electrodes for the impedance measurement and Integrated Circuits (ICs) required for excitation and measurement purpose have been designed, fabricated and tested in-vivo. The IC has been fabricated in a 0.8mum CMOS process, working at 3V of power supply. Test results have shown the circuit feasibility.
A continuous-time incremental analog to digital converter
R. Doldán, A. Yufera and A. Rueda
Conference · Symposium on Integrated Circuits and Systems Design SBCCI 2002
abstract
In this paper, an incremental Analog-to-Digital Converter (ADC) designed as part of the signal-conditioning circuitry for tissue impedance measurement system is presented. Continuous-time design techniques has been used for that which a modified implementation of the conversion algorithm, with respect to its discrete-time counterpart, has been developed. In order to reduce the influence of the no-idealities, analog and digital corrections has been also implemented. A first prototype in 0.8mum CMOS technology has been fabricated and tested. Simulation and experimental results are reported.
Books
Problemas de Electrónica Básica
A. Yúfera-García, J. Barbancho-Concejero, A. Estrada-Pérez, F. Sivianes-Castillo and A. Carrasco-Muñoz
Book · 200 p, 2009
abstract
Abstract not available
Tecnología de Computadores: Asignaturas en Red. Plan de Renovación de Metodologias Docentes. I Plan Propio de Docencia de la Universidad de Sevilla
A. Yúfera-García, J. Barbancho-Concejero, E. Ostua and A. Estrada Pérez
Book · 2008
abstract
Abstract not available
Book Chapters
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
abstract
doi
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.
Applying Image Processing to In-Vitro Human Ovocytes Characterization
J. Aragón, A. González and A. Yúfera
Book Chapter · Image Processing: Methods, Applications and Challenges, pp 87-103, 2012
abstract
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This book chapter presents an image processing tool developed to in-vitro
human oocytes analysis required in fertilization processes to biological
material classification. The application of the proposed tool allows a
non-invasive method to define the quality of human oocytes before to be
inseminated, enabling the possibility of selection the optimum one.
Specific segmentation algorithms have been developed to specific
biomedical images for identifying the cytoplasm area. The oocyte status
(normal, medium and highly stressed state) has been defined in terms of a
set of parameters extracted from the cytoplasm image. This status
quantification allows advising the biomedical staff during oocyte
selection, involving by the first time a useful metrics. Experimental
results proof that 83% of cases analyzed match with the expert evaluation.
ImagCell: A Computer Tool for Cell Culture Image Processing Applications in Bioimpedance Measurements
A. Yúfera, E. Gallego and J. Molina
Book Chapter · Software Tools and Algorithms for Biological Systems, Advances in Experimental Medicine and Biology, AEMB, vol. 696, pp 733-740, 2011
abstract
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This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre- and postsystem analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bioimpedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data decoding from measurements. The developed program allows cell culture image processing for geographic information extraction and generates cell count and equivalent circuit descriptions useful for system simulations.
Cell biometrics based on bio-impedance measurements
A. Yúfera, A. Olmo, P. Daza, P and D. Cañete
Book Chapter · Advanced Biometric Technologies, pp 343-366, 2011
abstract
doi pdf
Many biological parameters and processes can be sensed and monitored using their impedance as marker (Grimmes, 2008), (Beach. 2005), (Yúfera, 2005), (Radke, 2004), with the advantage that it is a non-invasive, relatively cheap technique. Cell growth, cell activity, changes in cell composition, shapes or cell location are only some examples of processes which can be detected by microelectrode-cell impedance sensors (Huang, 2004) (Borkholder, 1998). The electrical impedance of a biological sample reflects actual physical properties of the tissue. In frequency dependent analyses, the β-dispersion ranging from kilohertzs to hundreds of megahertzs (Schwan, 1957) is mainly affected by the shape of the cells, the structure of the cell membranes, and the amount of intra and extra cellular solution. Electrical bio-impedance can be used to assess the properties of biological materials (Ackmann, 1993) involved in processes such as cancer development (Giaever, 1991), (Blady, 1996), (Aberg, 2004); because the cells of healthy tissues and cancer are different in shape, size and orientation, abnormal cells can be detected using their impedance as a marker.
Among Impedance Spectroscopy (IS) techniques, Electrical Cell-substrate Impedance Spectroscopy (ECIS) (Giaever, 1986), based on two-electrode setups, allows the measurement of cell-culture impedances and makes it possible to determine the biological condition (material, internal activity, motility and size) of a cell type and its relationship with the environment; for example, the transfer flow through the cell membrane (Wang, 2010). One of the main drawbacks of the ECIS technique is the need to use efficient models to decode the electrical results obtained. To efficiently manage bio-impedance data, reliable electrical models of the full system comprising electrodes, medium and cells are required. Several studies have been carried out in this field (Giaever, 1991), (Huang, 2004), (Borkholder, 1998), (Joye, 2008), (Olmo, 2010), some of them employing Finite Element simulation (FEM) for impedance model extraction. These models are the key for matching electrical simulations to real system performances and hence for correctly decoding the results obtained in experiments.
A close-loop method for bio-impedance measurement with application to four and two-electrode sensor systems
A. Yúfera and A. Rueda
Book Chapter · New Developments In Biomedical Engineering, pp 263-286, 2010
abstract
doi pdf
Biomedical Engineering is a highly interdisciplinary and well established discipline spanning across engineering, medicine and biology. A single definition of Biomedical Engineering is hardly unanimously accepted but it is often easier to identify what activities are included in it. This volume collects works on recent advances in Biomedical Engineering and provides a bird-view on a very broad field, ranging from purely theoretical frameworks to clinical applications and from diagnosis to treatment.
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