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

Abstract

In this work, a way to cell-culture real-time monitoring system by means of the Oscillation-Based Test (OBT) methodology [1]is proposed and implemented with Texas Instrument (TI) components. The idea is inspired in previous works from the authors [1] in the area of testing analogue integrated circuits and deals with solving some critical points in this kind of biological measurements. The use of the cell-microelectrode model proposed in [2]confirms the feasibility of the approach. A simple topology based on a non-linear element embedded 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, growth rhythm, etc. We use the Describing Function (DF) approach for the involved mathematical calculations required to analyse the “biological circuit”, thus 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. In order to establish the accuracy of these theoretical predictions, the oscillators have been previously implemented and validated by simulations and, finally, empirical results have been achieved from an experimental demonstrator employing TI modules and elements.