Alberto YUfera

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Papers by Alberto YUfera

Modeling Edema Evolution With Electrical Bioimpedance: Application to Heart Failure Patients

2021 XXXVI Conference on Design of Circuits and Integrated Systems (DCIS)

Alternative General Fitting Methods for Real-Time Cell-Count Experimental Data Processing

IEEE Sensors Journal, 2020

This paper reports two general methods for extraction of cell-electrode electrical model paramete... more 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 measuremen...

A first order incremental analog to digital converter based on continuous time circuits

In this paper, an incremental Analog-to- Digital Converter (ADC) designed as part of the signal- ... more 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 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 tracking algorithm for cell motility assays in CMOS systems

2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Jul 1, 2017

This work proposes a method for the study and real-time monitoring of a single cell on a 2D elect... more This work proposes a method for the study and real-time monitoring 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 the 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.

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An Empirical-Mathematical Approach for Calibration and Fitting Cell-Electrode Electrical Models in Bioimpedance Tests

Sensors (Basel, Switzerland), Jan 20, 2018

This paper proposes a new yet efficient method allowing a significant improvement in the on-line ... more 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 othe...

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Low-voltage analog filters using floating-gate MOSFETs

Proceedings of the 26th European Solid-State Circuits Conference, 2000

This paper proposes a new circuit implementation of low-voltage filters. The work exploits the in... more This paper proposes a new circuit implementation of low-voltage filters. The work exploits the instantaneous companding and threshold voltage control capabilities of multiple-input floating-gate MOSFETs to achieve wide input signal swings with low supply voltage. To demonstrate the viability of the approach, a 1.5V lowpass/band-pass second order filter for low frequency applications was designed. A working Si prototype has been obtained meeting specifications.

Cell-culture Real-Time Monitoring: an Oscillation-based Approach

Applying image processing to in-vitro human oocytes characterization

ABSTRACT This book chapter presents an image processing tool developed to in-vitro human oocytes ... more ABSTRACT 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.

Programmable Switched-Current Filters

ESSCIRC '93: Nineteenth European Solid-State Circuits Conference, 1993

This paper presents a programmable switched-current filter based on a universal wave filter struc... more This paper presents a programmable switched-current filter based on a universal wave filter structure which allows obtaining different filtering functions from a same low-pass reference filter, without altering the global circuit topology. A first circuit implementing a low-pass and a band-pass Chebyschev filter has been designed and fabricated in the ES2 1.5¿m CMOS process. The experimentally measured results are reported.

A Microelectrode-Cell Sensor Model for Real Time Monitoring

In this paper the application of a cell- microelectrode model to cell biometry experiments is pro... more In this paper the application of a cell- microelectrode 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.

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Cell-culture real time monitoring based on bio-impedance measurements

Part of this work was carried out thanks the financial help from the project: “Autocalibracion y ... more

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A Plethysmography Capacitive Sensor for Real-Time Monitoring of Volume Changes in Acute Heart Failure

IEEE Transactions on Instrumentation and Measurement

A small, wearable, low-weight, and low-power-consumption device for plethysmography capacitive se... more 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.

Design and Application of Biomedical Circuits and Systems

Electronics

The development of new sensing technologies, biomaterials, microelectronic devices, microfluidic ... more

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A CMOS Tracking System Approach for Cell Motility Assays

Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies, 2017

This work proposes a method for studying and monitoring in real-time a single cell on a 2D electr... more 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.

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Remote Cell Growth Sensing Using Self-Sustained Bio-Oscillations

Sensors (Basel, Switzerland), Jan 3, 2018

A smart sensor system for cell culture real-time supervision is proposed, allowing for a signific... more 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.

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From voltage oscillations to tissue-impedance measurements

2015 IEEE Biomedical Circuits and Systems Conference (BioCAS), 2015

A technique for real-time monitoring of bio-impedances using a Voltage Oscillation (VO) methodolo... more 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.

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Electrical Modeling of the Growth and Differentiation of Skeletal Myoblasts Cell Cultures for Tissue Engineering

Sensors

In tissue engineering, of utmost importance is the control of tissue formation, in order to form ... more 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 ...

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Real-Time Electrical Bioimpedance Characterization of Neointimal Tissue for Stent Applications

Sensors (Basel, Switzerland), Jan 28, 2017

To follow up the restenosis in arteries stented during an angioplasty is an important current cli... more 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...

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Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation

Stem Cells Translational Medicine, 2016

Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applic... more Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applications. However, a critical issue to be addressed before widespread hASC clinical translation is the dramatic variability in proliferative capacity and osteogenic potential among hASCs isolated from different donors. The goal of this study was to test our hypothesis that electrical cell-substrate impedance spectroscopy (ECIS) could track complex bioimpedance patterns of hASCs throughout proliferation and osteogenic differentiation to better understand and predict variability among hASC populations. Superlots composed of hASCs from young (aged 24-36 years), middle-aged (aged 48-55 years), and elderly (aged 60-81 years) donors were seeded on gold electrode arrays. Complex impedance measurements were taken throughout proliferation and osteogenic differentiation. During osteogenic differentiation, four impedance phases were identified: increase, primary stabilization, drop phase, and secondary stabilization. Matrix deposition was first observed 48-96 hours after the impedance maximum, indicating, for the first time, that ECIS can identify morphological changes that correspond to late-stage osteogenic differentiation. The impedance maximum was observed at day 10.0 in young, day 6.1 in middle-aged, and day 1.3 in elderly hASCs, suggesting that hASCs from younger donors require a longer time to differentiate than do hASCs from older donors, but young hASCs proliferated more and accreted more calcium long-term. This is the first study to use ECIS to predict osteogenic potential of multiple hASC populations and to show that donor age may temporally control onset of osteogenesis. These findings could be critical for development of patient-specific bone tissue engineering and regenerative medicine therapies. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1-10 SIGNIFICANCE Human adipose stem cells (hASCs) are an appealing cell source for bone tissue engineering and regenerative medicine applications because they can be obtained in high quantities via liposuction procedures and can differentiate down musculoskeletal lineages. However, a major barrier to clinical translation of hASCs is that cells from different donors have varying capacities to proliferate and differentiate. This study used electrical impedance spectroscopy to noninvasively track osteogenic differentiation of age-grouped donors in real time, showing that age-grouped hASCs have distinct complex impedance patterns. This method could be used to improve understanding of the biology that causes variability among hASC populations and to provide quantitative quality control standards for hASC populations in stem cell manufacturing and bone tissue engineering applications.

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