Lab-on-chip for integrated cell culture monitoring

Conductance spectroscopy, performed by measuring the electrical complex conductivity of the sample, can be a valid analytical method for cell cultures monitoring. The electromagnetic properties of inhomogeneous materials, and in particular of biological materials, are expressed in terms of complex conductivity, or permittivity, and are strictly related to shape, dimensions, volume fraction occupied by the particulate (cells) [1]. This technique allows, in a simple and non-invasive way, the real time determination of the cell volume fraction and the average size of the cells in the volume under measurement. Over the last years, Lab-on-Chip systems have increased their popularity in the field of biomolecular analysis due to their key features, such as reduced dimensions, capability to integrate and perform each step of the biomedical analysis in a single chip, quick response time, low reagents’ consumption and on-field use together with the opportunity to avoid bulk equipment and copious specialized personnel. All these advantages were made possible by the evolution of microelectronic technologies and their capability to adapt to different substrates and materials. This work presents the development of an integrated Lab-on-Chip system (see Fig. 1) with the aim to sort and estimate the biomass of living cancer cells suspended in culture medium via dielectric spectroscopy. The separation of sole medium and medium-cells mixture in two different areas of the chip is guaranteed by a polyimide-based membrane (see Fig. 2) [2] capable of performing cell filtering and placed between two microfluidic channels. Two couples of thin-film metal electrodes ensure a comparative dielectric investigation of the separated materials. Preliminary experiments have been performed in a bulk solution at three different cell concentrations. Results reported in Fig. 3 show a clear trend in the measured conductance and susceptance of the solution as a function of frequency. Further experiment will be performed in the lab-on-chip with and without the selective membrane and the achieved result will be compared to the theoretical model [1]. The proposed lab-on-chip represents a promising step for the development of novel valid solutions in the field of integrated cell sorting, cell monitoring and cell counting for a wide range of applications, from tissue engineering to biological analysis in space environment.