Programmable low-voltage continuous-time filter for audio applications

The implementation of a continuous-time filter (CTF) useful for audio frequency applications is presented in this paper. The filter functions can be programmed and tuned with two independent control variables. The filter here proposed has been designed to work at 1.5 V of power supply and at a maximum of 0.5 /spl mu/A/OTA for the worst case current consumption. Electrical simulations of a Tow-Thomas biquad (TTB) show the possibility of obtaining low-pass and band-pass filter functions over the 10 Hz-40 kHz frequency range by changing a control current over four decades.Comisión Interministerial de Ciencia y Tecnología TIC-97-064

Design of a CMOS closed-loop system with applications to bio-impedance measurements

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.Ministerio de Ciencia e Innovación TEC2007-6807

A microscopy technique based on bio-impedance sensors

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.Junta de Andalucía P0-TIC-538

Automatic Generation of Analog Hardware Description Language (AHDL) Code from Cell Culture Images

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.Ministerio de Ciencia e Innovación TEC2007-6807

Herramienta para el aprendizaje de un sistema de adquisición de datos

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.Junta de Andalucía P09-TIC538

Generation of HDL models for bio-impedance sensor simulation based on microelectrodes

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

Data-Analytics Modeling of Electrical Impedance Measurements for Cell Culture Monitoring

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 applicationsEspaña, Ministerio de Ciencia e Innovación y Universidades project RTI2018-093512-B-C2

Using microelectrode models for real time cell-culture monitoring

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.Junta de Andalucía P0-TIC-538

A CMOS Bio-Impedance Measurement System

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.Ministerio de Ciencia e Innovación TEC2007-6807

Microcontroller-Based Sinusoidal Voltage Generation for Electrical Bio-Impedance Spectroscopy Applications

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 Arduino™ 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.Spanish founded Project: TEC 2013- 46242-C3-1-P: Integrated Microsystem for Cell Culture AssaysFEDE