A computer-aided design tool for biomedical OBT sensor tuning in cell-culture assays

Abstract

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.

Oscillation-Based Spectroscopy for Cell-Culture Monitorization

“…OB Spectroscopy features an additional parameter, Q f , as the quality factor of the band pass filter (BPF) block. Influence of this parameter has been previously reported for single tuning of the OBT sensor (Pérez et al, 2020). However, exploration of different values of Q f may be of interest for acquiring additional information of the system under test.…”

“…The R gap factor serves as an example of the limitation existing in classic OBT cell culture sensor. Design procedures (Pérez et al, 2020) describe strategically tuned band pass filter blocks to maximize dynamic ranges and optimize information retrieval from sensor curves; this is performed by adjusting the filter central frequency of the BPF block to an operating point where the variation in both parameters is maximal across the biological process of a cell culture growing in a substrate. Cells adhered to the substrate (A c ) represent a portion of total substrate Area (A).…”

“…The Oscillation-Based Spectroscopy (OBS) is defined as a method for searching the optimum frequency range of OB systems and analyzing the sample under test for a wide range of frequencies, by programming its central frequency. Previous works manage to describe the design process for culture applications and a fine tuning of the OB parameters (Pérez et al, 2020).…”

Overview of the Application of Computer-Aided Tools in Information Systems Development

“…Therefore, both qualitative and quantitative costs must be considered in order to assess the expected value of a tool [1]. However, despite recent advances in the application of CAT in other sciences [22], [23] and advances in IS development with artificial intelligence [24], [25],…”