Wrinkled Graphene Field Effect Transistor in Heterodyne Mode for Ultrasensitive Detection of Exosomes toward Early Cancer Screening

Abstract

Exosomes are nanosized vesicles which have gathered significant importance as biomarkers for cancer diagnosis. Thus, there is a clear need to detect exosomes with sufficient accuracy and sensitivity. Recent reviews reveal that field effect transistors have the potential to reach lower detection limits without any labels or complex surface modification strategies. However, the major limitation is caused by screening of the charges of exosomes by the Debye layer due to their larger size in the range of 30 to 200 nm. To address this issue, here we develop a wrinkled graphene structure on a glass substrate following a scalable approach enabled by integrating the deposition of thermally reduced graphene oxide on silver nanoparticles decorated glass coupled with alternating current mode heterodyne operation for detection of exosomes extracted from lung cancer cells. Both of these phenomena result in the expansion of the electrical double layer at the graphene–electrolyte interface. Additionally, the exosomes act as dipoles at high frequency and the ac mode current modulation occurs as a function of polarizability resulting in a limit of detection (LOD) of around 1200 exosomes ml^–1 expanding a wide range of 12 × 10⁷ exosomes ml^–1 in buffer. Summarizing, this work exhibits a lowering of LOD by 2 orders of magnitude compared to state-of-the-art single-antibody-based exosome detection, thereby upgrading the potential clinical value for early cancer diagnosis.