Sensing Cell-Culture Assays with Low-Cost Circuitry

Abstract

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 well-established 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.

An Empirical-Mathematical Approach for Calibration and Fitting Cell-Electrode Electrical Models in Bioimpedance Tests

“…In this work, Matlab software has been used to simulate the calibration protocol, and for the testing and validation of the model in real time. The next step is to implement the Matlab script in the smart prototype of our OBT system approach [ 15 , 16 , 17 , 18 ]. The OBT prototype will then be able to autonomously follow the ff and the cell density in real time.…”

“…A mathematical description of the full system was required for cell-electrode electrical model estimation. The circuit system described in Figure 3 [ 15 , 16 , 17 , 18 ] has three main circuit blocks; a band-pass filter ( H BP ), a current source ( I Zc ), and a voltage comparator block ( K -gain amplifier, comparator filter – H CMP,F –, and the voltage discriminator).…”

“…In this work, the measurement method is the oscillation-based test (OBT), detailed in [ 15 , 16 , 17 , 18 ]. This technique is based on connecting the BioZ as an oscillator.…”

“…In summary, it is proposed to perform, first, a calibration procedure by employing the OBT technique [ 15 , 16 , 17 , 18 ], and second, to validate with this same technique, the results for other assays with different cells densities. Thus, different initial number of cells was seeded to validate the model obtained in the calibration step.…”

Remote Cell Growth Sensing Using Self-Sustained Bio-Oscillations

“…In the article, a system for performing this supervisory task is proposed using inexpensive discrete components. The global system is implemented using an oscillation-based test (OBT) sensor which is widely described in [ 3 , 4 , 5 ], based on an ARM Cortex-M7 microcontroller and an Intel Edison device as the external system-on-chip which communicates with the sensor using a wireless link based on Bluetooth technology. The peripheral blocks which provide the system with smart features are defined in detail herein.…”