Review on electrochemical sensors for anticancer drug susceptibility testing

Anticancer drug susceptibility tests play an essential role in areas such as drug development, pharmacokinetic research, and precision oncology. Across these tests, the methods that are traditionally used for gauging the drug effect-by determining the cell viability of in vitro cell models after drug exposure-are commonly time-consuming and limited to end-point detection. In this regard, electrochemical sensors have emerged as a promising alternative to increase throughput and yield real-time pharmacokinetic monitoring. In this critical review, considerations on the operating principles, advantages, and disadvantages of the state-of-the-art electrochemical drug screening devices are critically discussed. Promising sensing devices have addressed drug susceptibility tests by monitoring (i) cellular, e.g., cell proliferation, adhesion, and detachment for 2D cells and the formation of ionic inter-cell gap junctions for 3D cells, or (ii) extracellular markers, e.g., O₂, pH, and metabolic intermediates such as glucose, lactate, and hydrogen peroxide. The advances in these devices are covered here in two parts relying on the aforesaid viability indicators, i.e., cellular and extracellular markers, of 2D and 3D cell models (i.e., spheroids and organ-on-a-chip systems). These advances have aimed at boosting the performance of sensors by utilizing nanomaterials and machine learning. Finally, an outlook on the field's bottlenecks to overcome is provided, seeking to draw new sensing paradigms in electrochemical drug susceptibility tests. Briefly, multisensor, microfluidic, and machine learning-aided sensing devices coupled with 3D cell models stand out as an attractive alternative to offer high-throughput, reproducible, real-time, accurate, and free-calibration predictions of in vivo drug effects. This type of platform can play a key role in steering electrochemical sensors to bridge the translational gap between research and end users in daily anticancer drug susceptibility testing applications.