Protease detection in the biosensor era: A review

Proteases have been proposed as potential biomarkers for several pathological conditions including cancers, multiple sclerosis and cardiovascular diseases, due to their ability to break down the components of extracellular matrix and basement membrane. The development of protease biosensors opened up the possibility to investigate the proteolytic activity of dysregulated proteases with higher efficiency over the traditional detection assays due to their quick detection capability, high sensitivity and selectivity, simple instrumentation and cost-effective fabrication processes. In contrast to the recently published review papers that primarily focused on one specific class of proteases or one specific detection method, this review article presents different optical and electrochemical detection methods that can be used to design biosensors for all major protease families. The benefits and drawbacks of various transducer techniques integrated into protease biosensing platforms are analyzed and compared. The main focus is on activity-based biosensors that use peptides as biorecognition elements. The effects of nanomaterials on biosensor performance are also discussed. This review should help readers to select the biosensor that best fits their needs, and contribute to the further development of this research field. Protease biosensors may allow better comprehension of protease overexperession and potentially enable novel devices for point-of-care testing.