Signal amplification strategies in biosensing of extracellular vesicles (EVs)

Extracellular vesicles (EVs) are membrane-enclosed vesicles secreted from mammalian cells. EVs act as multicomponent delivery vehicles to carry a wide variety of biological molecular information and participate in intercellular communications. Since elevated levels of EVs are associated with some pathological states such as inflammatory diseases and cancers, probing circulating EVs holds a great potential for early diagnostics. To this end, several detection methods have been developed in which biosensors have attracted great attentions in identification of EVs due to their simple instrumentation, versatile design and portability for point-of-care applications. The concentrations of EVs in bodily fluids are extremely low (i.e. 1-100 per μl) at early stages of a disease, which necessitates the use of signal amplification strategies for EVs detection. In this way, this review presents and discusses various amplification strategies for EVs biosensors based on detection modalities including surface plasmon resonance (SPR), calorimetry, fluorescence, electrochemical and electrochemiluminescence (ECL). In addition, microfluidic systems employed for signal amplification are reviewed and discussed in terms of their design and integration with the detection methods.