Cell-Culture Real-Time Monitoring System

2011

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.

The cell concentration measurement on a culture assay using bioimpedance is a very useful tool, but it is complex to translate impedance to cell concentration values. The purpose of this work is to find a method to obtain in real time the cell concentration values for a given cell-culture assay using an oscillator as the measurement circuit. From a basic cell-electrode model, enhanced models of the cell culture immersed in a saline solution (culture medium) can be derived. These models can be used in a fitting routine to real time estimation of the cell concentration in a cell culture, using the oscillation frequency and amplitude delivered by measurement circuits proposed by the authors. Based on real experimental data (frequency and amplitude of oscillations) obtained by connecting the cell culture to an oscillator as a load, the fitting routine is simulated, and real time data of cell concentration is achieved. These results are compared with concentration data found by tradition...

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.

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 wellestablished 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.

Computer Methods and Programs in Biomedicine, 2021

Background and objectives: The biomedical engineering must frequently develop sensor designs by including information from performance of bio-samples (cell cultures or tissues), technical specifications of transducers, and constrains from electronic circuits. A computer program for realtime cell culture monitoring system design is developed; analyzing, modelling and integrating into the program design flow the electrodes, cell culture and test circuit's influences. Methods: The computer tool, first, generates an equivalent electric circuit model for the cellelectrode bio-systems based on the area covered by cells, which also considers the cell culture dynamics. Second, proposes an Oscillation Based Test (OBT) parameterized circuit, for Electrical Cell-Substrate Sensing (ECIS) measurements of the cell culture system bioimpedance. Third, simulates electrically the full system to define the best system parameter values for the sensor. Results: Reported experimental results are based on commercial gold electrodes and the AA8 cell line. Characteristics of the cell lines, as time-division or cell size, are incorporated into the program design flow, showing that for a given assay, the optimal OBT circuit parameters can be selected with the help of the computer tool. The electrical simulations of the full system demonstrate that the can be correctly predicted the output frequency and amplitude ranges of the voltage response, obtaining accurate results when cell culture approaches to confluence phase. Conclusion: 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.

Sensors and Actuators B: Chemical, 2013

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.

SENSORDEVICES 2011, The Second …, 2011

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.

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.