Detection and Analysis of Extracellular Vesicles in Physiological Salt Environment Using AlGaN/GaN High Electron Mobility Transistor Biosensors

Abstract

In the present work, we have utilized antibody functionalized AlGaN/GaN high electron mobility transistor (HEMT) to capture EVs from high salt environment (1X PBS) and resulting change in electrical response of the sensor has been correlated with the concentration of EVs. The unique high field modulation applied to the sensor facilitates target detection overcoming Debye screening. Our sensor can achieve better sensitivity (detection limit of 107 EVs/mL) than the conventional technologies used for EV detection such as nanoparticle tracking analyzer. Furthermore, our sensor methodology can also be used to determine the surface markers present in the captured EVs. In our sensor, when EVs are captured by the immobilized anti-CD63, the solution capacitance varies as the applied potential drops across the solution, thereby modulating the HEMT drain current. When we employed a secondary antibody such as anti-CD9 to bind with CD9 which is abundantly present on the exosomal membrane, the impedance increases, resulting in more potential drop across the solution and therefore, a decrease in drain current. The results indicate that our sensor can perform EV enumeration and exosomal surface marker analysis to establish a comprehensive diagnostic model for EVs in physiological fluids.