Development of a wireless parallel interdigitated electrode biosensing system for monitoring cancer cells treatment

Abstract

Chemotherapy is the most common cancer treatment in Malaysia due to its established methods for treating various types of cancers. Unfortunately, this treatment has low success rates of 30% to 70% with accompanying toxicity and side effects to the patients. To reduce the side effects, the choice of drugs and their dosage for chemotherapy must be optimized. Personalized chemotherapy is an evidence-based cancer treatment approach that customizes medication regimens according to an individual’s clinical characteristics. Biosensors play a crucial role in personalized medicine by providing real-time monitoring of an individual’s response to specific treatments. Electric Cell- Substrate Impedance Sensing (ECIS) is a technique that employs alternating current (AC) to assess cellular function under different physiological conditions, which is suitable for drug discovery applications. For this work, an ECIS biosensing device was developed to evaluate cancer cells’ response to chemotherapy drugs. The sensor design was optimized using COMSOL Multiphysics and MATLAB simulations. The sensor’s electrodes were fabricated using gold-coated copper-nickel on two different substrates, FR4 fiberglass and PET. These sensors were integrated with cell culture chambers and used to assess the toxicity and efficacy of chemotherapy drugs on primary cancer cells. The sensors were characterized physicochemically using SEM, EDX, and light microscope for electrochemical-migration behavior. For sensor validations, A549 lung cancer, SiHa ovarian cancer cell lines, and biopsy-derived lung cancer cells were cultured on the biosensors. Next, impedance measurements were taken at 12/24 hours intervals for 84/96 hours to observe the growth of the cells. The cells’ response towards the chemo-drugs (5-Fluororacil, Cisplatin, and Gemcitabine) using the biosensor were measured in terms of impedance changes and converted into cell index. These results were compared with experiments conducted using a commercial xCELLigence RTCA device. The optimum concentration of drugs was found to be 10 µg/ml for 5-Fluororacil and Gemcitabine and 5 µg/ml for Cisplatin. The results prove that the biosensor is biocompatible and can be used to monitor cell growth and perform cytotoxicity studies of both cell lines and primary cells. To facilitate sensor readout, a portable wireless system was developed using an Arduino microcontroller and AD5933-based PMODIA for data acquisition. The functionality of this system was verified by monitoring the growth of A375 skin cancer cells. This indicates that this biosensor system has the potential to be used as a personalized drug screening system for chemotherapy treatments of a particular cancer patient.