An Integrated Graphene-MXene Electrochemical Transistor Array Platform for Accurate Prostate Cancer Diagnosis Using Plasma sEV-Derived E2F5 Biomarker

Abstract

Exosomes have been investigated for the diagnosis of prostate cancer (PC) due to their capability of offering a real-time reflection of tumor burden. However, discriminating benign prostatic hyperplasia (BPH) from healthy controls (HC) and varying PC grades remains a challenge in clinical settings. Here, an ultrasensitive electrochemical field-effect transistor based on porous graphene-MXene composites has been constructed that circumvents the Debye screening limitations in detecting large biomolecular targets like exosomes. Additionally, the device leverages synergistic interfacial effects to enhance receptor binding density, which contributes to high sensitivity, leading to a detection limit of 200 exosomes/ml (approximately three orders of magnitude lower than the most sensitive antibody-based reports), with a wide range (similar to 108 exosomes/ml) and detection time within 30 min. Further, dielectrophoresis (DEP) enabled in situ exosome enrichment is integrated, enabling direct analysis of clinical samples without ultracentrifugation. Most importantly, the efficacy of E2F5 as an exosomal protein has been validated for accurate PC diagnosis in all patient cohorts. Multiple features have been extracted from the sensor response and analyzed using an ensemble classification method. Interestingly, the outcomes reveal that the sensor successfully distinguished BPH from HCs with appreciable accuracy of 91.11% and shows similar diagnostic performance with lower grade PC, higher grade PC, and healthy patients.