MICROFLUIDIC DEVICE FOR REAL-TIME BIOPSY MONITORING

Currently, traditional 2D and 3D cancer models are the most used strategies for the study and the development of new drugs or pharmaceutical therapies. The lack of realistic modeling leads to low predictivity of effects and safety, and the high costs and time-consuming processes make them not always available and usable. Interest in microfluidic devices, in which it is possible to recreate perfusion and shear stresses, is driven by the need of a more physiological representation of the sample to be studied. Moreover, traditional sensors and characterization techniques provide information about cellular response, but often they are destructive for the tissue, incompatible with the device, expensive and give information only at the end of the process. The emergence of impedance-based measurements is due to its advantages, including, label-free, low cost, non-invasive, non-destructive, quantitative and real-time monitoring. In this work, a microfluidic device for real-time monitoring of liver cancer biopsies by impedance spectroscopy has been designed and fabricated. COMSOL simulation has been helpful to define the conical geometry of channels, proved to be optimal for perfusion of the tissue in the chamber. A prototype has been fabricated by a replica molding process and leakage tests at various flow rates (60 μl/h-3000 μl/h) have successfully validated the manufacturing protocol. Impedance measurements have been performed in static and non sterile conditions. Two vertical electrodes for each culture chamber have been used to measure the impedance of mouse liver biopsies immersed in William’s Medium, in a frequency range from 500 Hz to 10 MHz. Analysis of impedance-based curves reveal differences between untreated and fibrotic tissue. Furthermore, differences in impedance measurements have also been observed in a comparative study of others mouse tissues (kidney, spleen, pancreas and liver). Lastly, some fluid-dynamic measures have been evaluated. Data collected imposing different flow rates have confirmed that no noise is introduced with the flow of the culture medium. The obtained results confirm the feasibility of electrical impedance spectroscopy (EIS) in biopsy monitoring and show promises for time-dependent studies of anti-cancer drugs, based on impedance variation related to tissue changes. The presented device is a first step towards the development of a complete, high-throughput system for personalized medicine, using patient-specific biopsies.