Cell-Culture Real-Time Monitoring System

Project 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. " Learn from yesterday, live for today, hope for tomorrow. The important thing is to not stop questioning " Albert Einstein 1. INTRODUCTION AND MOTIVATION Characterizing in detail the number of cells in a culture at a specific time as well as measuring the cell proliferation rate have deep implications in biomedicine, both at a technical and at a biological level. Indeed, the density of cells in the plate will affect the success of many different techniques, including transfection, infection, reaction to many chemicals, etc. Cells distributed too sparsely will have problems growing and will react strangely to all the aforementioned treatments. More important from a biological point of view, cell proliferation is a potent tool to define a cell. Excessive proliferation is the hallmark of cancer cells, and any physical or chemical treatments that slow down cell growth may lead to potential oncogenic therapies. Lack of proliferation normally represents excessive cell death, either due to extrinsic or intrinsic mechanisms, or the activation of cellular aging pathways (cellular senescence). Thus, understanding the processes that slow down or accelerate the proliferation of …