Ultra-low-power chronopotentiometric peptide biosensor for real-time detection of MMP-9

Proteases are emerging biomarkers for diseases including cancer, cardiovascular disorders, and inflammation, making their detection valuable for early diagnosis and therapeutic monitoring. Translating biomarker monitoring from laboratories to personalized healthcare requires biosensors that are simple, selective, and compatible with point-of-care formats. To the best of our knowledge, we report the first peptide-based chronopotentiometric biosensor for protease detection. The sensor is fabricated on cost-effective disposable electrodes, has a straightforward design, and operates at ultra-low intrinsic sensing power (<1 nW), supporting future integration into compact sensing devices.

The sensor enables direct, label-free detection of matrix metalloproteinase-9 (MMP-9) with picomolar detection limit through potential shifts induced by peptide hydrolysis. Careful peptide design provides high selectivity against other MMP family members, and the device successfully detects proteases released from cells in moderately complex media. Inhibition studies confirm that the signal originates from proteolytic activity.

In parallel, the biosensing platform is validated using multi-parametric surface plasmon resonance (MP-SPR), providing an independent and robust optical method to confirm peptide–MMP-9 interactions. This work demonstrates peptide-based dual-platform sensing for highly sensitive, real-time protease detection and establishes a versatile foundation for future point-of-care and wearable biosensing applications.