Extracellularly Detectable Electrochemical Signals of Living Cells Originate from Metabolic Reactions

Abstract

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.

Recent Advances in Electrochemical Detection of Cell Energy Metabolism

“…In this section, we discuss the various applications of EC biosensors for monitoring metabolic reactions (Table 3). The first discovery made by Koo et al pertained to the identification of intracellular metabolic pathways as the primary sources of EC signals that may be detected extracellularly [115]. This finding was supported by Figure 7A in their study.…”

Progress in Nano-Biosensors for Non-Invasive Monitoring of Stem Cell Differentiation

“…Gold's conductivity is 4.11 × 10 7 S/m, which is highly favourable for electrochemical sensors [54]. Moreover, gold is colloidal in AuNPs, which has various advantageous features for electrochemical sensors [55][56][57][58][59][60][61][62][63]. For example, AuNPs are easy to synthesise and can be conjugated with multiple biomolecules, such as protein ligands, nucleic acids, and antibodies, which can enforce the intrinsic properties of the AuNPs [64][65][66].…”