Real-time MoS2-silicon photoelectrochemical biosensor for tracking mitochondrial metabolic dysfunction in metastatic cancers

• MoS₂ enhances PEC biosensor signal by improving charge separation • Biosensor discriminates metastatic from non-metastatic gastric cancer cells • Photocurrent output correlates with cell number for quantitative profiling • Real-time monitoring of mitochondrial redox shifts via ETC modulation • Label-free PEC platform enables metabolic stratification and drug response assessment Mitochondrial dysfunction and dysregulated redox signaling are critical drivers of cancer progression and therapeutic resistance, yet current methods lack sufficient temporal resolution to monitor mitochondrial function in living cells in real time. Here, we report a molybdenum disulfide (MoS₂)-enhanced photoelectrochemical (PEC) biosensor integrated with a silicon solar cell to dynamic tracking of mitochondrial redox activity. Incorporation of MoS₂ substantially improved photogenerated charge separation and interfacial electron transfer, yielding a 57.7% increase in PEC signal intensity compared with unmodified electrodes. The biosensor distinguished metastatic from non-metastatic gastric cancer phenotypes: MKN45 and NCI-N87 cells exhibited 2.42-fold and 1.41-fold higher photocurrents, respectively, relative to AGS cells. Photocurrent output correlated strongly with cell number (R² > 0.986), enabling quantitative metabolic profiling. Sequential treatment with mitochondrial modulators—oligomycin, FCCP, and rotenone/antimycin A—produced bidirectional photocurrent changes reflective of oxidative phosphorylation flux and electron transport chain inhibition, demonstrating real-time bioenergetic tracking. These results establish that PEC output as a sensitive surrogate for mitochondrial redox dynamics. The MoS₂-based PEC platform thus provides a rapid, label-free approach for functional mitochondrial analysis, with translational potential for cancer diagnostics, metabolic stratification, and therapeutic response evaluation.