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

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.

Advances in Electrochemical Nano-Biosensors for Biomedical and Environmental Applications: From Current Work to Future Perspectives

“…Moreover, electrodeposited iridium oxide films were implemented for sensing cellular acidification using a potentiometric pH sensor. The designed biosensing setup enabled an initiative for pursuing 3D-cell biosensor-based cell cultures [ 117 ]. An aptasensor was designed for the impedimetric biosensong of Cyt-c using silver nanocluster conjugation [ 118 ].…”

Three-Dimensional Avian Hematopoietic Stem Cell Cultures as a Model for Studying Disease Pathogenesis

“…The evaluation of stability in cell culture can be measured by biosensors in the culture because they can be used for the evaluation of oxygen, nutrients, pH, and metabolites. The problems of the current approaches in electrochemical sensing in 3D cultures are reviewed by Oliveira et al (2021) . In a dynamic microfluidic system, channel volumes and dilution requirements must be determined to obtain reliable results by detection systems ( Castiaux et al, 2019 ).…”

Microelectromechanical Organs-on-Chip

“…Many metabolic cues consist of charged species, and they can be quantitatively detected by biochemical and electrochemical sensors [32] without recurring to microscopy techniques and terminal optical labelling, which considerably perturb the physiology of cells.…”