Electrochemical Sensing in 3D Cell Culture Models: New Tools for Developing Better Cancer Diagnostics and Treatments

Abstract

Simple Summary Over the last few years, there has been a scientific revolution with the appearance of organ-on-a-chip models that overcome the limitations of conventional 2D systems, while reproducing more faithfully the in vivo features of tissues and organs. The integration of sensors in these systems allows the monitoring of a variety of parameters that could be relevant for the study of diseases. Electrochemical biosensors are ideal candidates for this integration, since they can be miniaturised and are very reliable in real-time continuous measurements of a large panoply of relevant biomarkers. In the context of cancer, these electrochemical cancer-on-a-chip models have the potential to become essential tools for the study of cancer development and drug efficacy. Abstract Currently, conventional pre-clinical in vitro studies are primarily based on two-dimensional (2D) cell culture models, which are usually limited in mimicking the real three-dimensional (3D) physiological conditions, cell heterogeneity, cell to cell interaction, and extracellular matrix (ECM) present in living tissues. Traditionally, animal models are used to mimic the 3D environment of tissues and organs, but they suffer from high costs, are time consuming, bring up ethical concerns, and still present many differences when compared to the human body. The applications of microfluidic-based 3D cell culture models are advantageous and useful as they include 3D multicellular model systems (MCMS). These models have demonstrated potential to simulate the in vivo 3D microenvironment with relatively low cost and high throughput. The incorporation of monitoring capabilities in the MCMS has also been explored to evaluate in real time biophysical and chemical parameters of the system, for example temperature, oxygen, pH, and metabolites. Electrochemical sensing is considered as one of the most sensitive and commercially adapted technologies for bio-sensing applications. Amalgamation of electrochemical biosensing with cell culture in microfluidic devices with improved sensitivity and performance are the future of 3D systems. Particularly in cancer, such models with integrated sensing capabilities can be crucial to assess the multiple parameters involved in tumour formation, proliferation, and invasion. In this review, we are focusing on existing 3D cell culture systems with integrated electrochemical sensing for potential applications in cancer models to advance diagnosis and treatment. We discuss their design, sensing principle, and application in the biomedical area to understand the potential relevance of miniaturized electrochemical hybrid systems for the next generation of diagnostic platforms for precision medicine.