Exosome Biosensor Based on Quantum Dots-Modified Field Effect Transistor

The escalating demand for high-throughput and miniaturized biosensors has spurred significant advancements in biosensor chips. However, challenges remain in achieving high sensitivity and specificity in miniaturized devices. Herein, we construct a sensitive exosome biosensor based on quantum dots (QDs)-modified field effect transistor. PbS QDs were drop-coated onto the gate of a high electron mobility transistor (HEMT), followed by surface modification with CD63 antibodies (anti-CD63) through a ligand exchange strategy, and subsequent bovine serum albumin (BSA) blocking treatment. Exosomes with CD63 proteins enriched in the surface were isolated from MCF-7 breast cancer cell lines to serve as target analytes. The specific binding events between CD63 antigen and antibody capture exosomes onto the gate of HEMT, affecting the output current (<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i><sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D</sub>). The synergy of the capacitance coupling effect of the modification layer and the intrinsic signal amplification capability of HEMT assists in significantly modulating the two-dimensional electron gas (2DEG), resulting in amplified <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i><sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D</sub>. With constant gate voltage applied, the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i><sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D</sub> of the biosensor sensitively increases with exosome concentration within a wide range of 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup>-10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">9</sup> particles/mL at <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i><sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D</sub> = 3.5 V, and the LOD is estimated to be 9 × 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> particles/mL. This exosome biosensor demonstrates its potential for clinical applicability and paves the way for the development of miniaturized exosome biosensor chips.