Electrochemical sensors are considered an auspicious tool to detect biomolecules (e.g., DNA, proteins, and lipids), which are valuable sources for the early diagnosis of diseases and disorders. Advances in electrochemical sensing platforms have enabled the development of a new type of biosensor, enabling label-free, non-destructive detection of viability, function, and the genetic signature of whole cells. Numerous studies have attempted to enhance both the sensitivity and selectivity of electrochemical sensors, which are the most critical parameters for assessing sensor performance. Various nanomaterials, including metal nanoparticles, carbon nanotubes, graphene and its derivatives, and metal oxide nanoparticles, have been used to improve the electrical conductivity and electrocatalytic properties of working electrodes, increasing sensor sensitivity. Further modifications have been implemented to advance sensor platform selectivity and biocompatibility using biomaterials such as antibodies, aptamers, extracellular matrix (ECM) proteins, and peptide composites. This paper summarizes recent electrochemical sensors designed to detect target biomolecules and animal cells (cancer cells and stem cells). We hope that this review will inspire researchers to increase their efforts to accelerate biosensor progress—enabling a prosperous future in regenerative medicine and the biomedical industry.

Organoids that mimic the structural and cellular characteristics of kidneys in vitro have recently emerged as a promising source for biomedical research. However, uncontrollable cellular heterogeneity after differentiation often results in the generation of off-target cells, one of the most challenging issues in organoid research. This study proposes a new method that enables the real-time assessment of kidney organoids derived from stem cells. When placed on a conductive surface, these organoids generate unique electrochemical signals at ≈0.3 V with intensities proportional to the amount of kidney-specific cell types. Off-target cells (i.e., non-kidney cells) produce an electrical signature at 0 V that is distinguishable from other surrounding cell types, enabling non-destructive assessment of both the differentiation, and maturation levels of kidney organoids. The developed platform can be applied to other types of organoids and is thus highly promising as a tool for organoid-based drug screening, toxicity assessment, and therapeutics.

Redox reactions in live cells are generated by involving various redox biomolecules for maintaining cell viability and functions. These qualities have been exploited in the development of clinical monitoring, diagnostic approaches, and numerous types of biosensors. Particularly, electrochemical biosensor-based live-cell detection technologies, such as electric cell–substrate impedance (ECIS), field-effect transistors (FETs), and potentiometric-based biosensors, are used for the electrochemical-based sensing of extracellular changes, genetic alterations, and redox reactions. In addition to the electrochemical biosensors for live-cell detection, cancer and stem cells may be immobilized on an electrode surface and evaluated electrochemically. Various nanomaterials and cell-friendly ligands are used to enhance the sensitivity of electrochemical biosensors. Here, we discuss recent advances in the use of electrochemical sensors for determining cell viability and function, which are essential for the practical application of these sensors as tools for pharmaceutical analysis and toxicity testing. We believe that this review will motivate researchers to enhance their efforts devoted to accelerating the development of electrochemical biosensors for future applications in the pharmaceutical industry and stem cell therapeutics.

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Direct detection of cellular redox signals has shown immense potential as a novel living cell analysis tool. However, the origin of such signals remains unknown, which hinders the widespread use of electrochemical methods for cellular research. In this study, the authors found that intracellular metabolic pathways that generate adenosine triphosphate (ATP) are the main contributors to extracellularly detectable electrochemical signals. This is achieved through the detection of living cells (4,706 cells/chip, linearity: 0.985) at a linear range of 7,466–48,866. Based on this discovery, the authors demonstrated that the cellular signals detected by differential pulse voltammetry (DPV) can be rapidly amplified with a developed medium containing metabolic activator cocktails (MACs). The DPV approach combined with MAC treatment shows a remarkable performance to detect the effects of the anticancer drug CPI‐613 on cervical cancer both at a low drug concentration (2 µm) and an extremely short treatment time (1 hour). Furthermore, the senescence of mesenchymal stem cells could also be sensitively quantified using the DPV+MAC method even at a low passage number (P6). Collectively, their findings unveiled the origin of redox signals in living cells, which has important implications for the characterization of various cellular functions and behaviors using electrochemical approaches.