Scalable Electrochemical FET Immunosensor with Crumpled Graphene for Sensitive Detection of Prostate Cancer Derived Exosomes

Abstract

Accurate exosome identification is necessary for distinguishing early-stage cancer patients from malignant conditions. In this work, a scalable field effect transistor (FET) immunosensor with crumpled graphene has been developed using silver nanoparticles formed via solid-state dewetting of thin silver films to pattern glass substrates, followed by conformal graphene deposition to enable early prostate cancer (PCa) diagnosis by sensitive exosome detection. This approach provides greater control over crumple geometry compared to conventional chemical vapor deposition. By optimizing the dewetting process and managing diffusion-driven particle distribution, crumple uniformity has been improved leading to reduced device-to-device variability which is an important requirement for clinical applications. Further refinement of graphene morphology allowed the wrinkle cavities to regulate ionic double-layer formation, enhancing the sensor’s ability to distinguish exosomes from benign prostatic hyperplasia (BPH) patients and healthy individuals. To boost performance, polyethylene glycol based co-immobilization of antibodies has been combined with electrokinetic enrichment of exosomes. This synergistic strategy reduced ionic screening, increased sensor response over fourfold, and achieved a detection limit as low as 100 exosomes/ml in plasma, with a dynamic range up to 10⁸ exosomes/ml within 30 minutes. The detection limit represents a more than three-order-of-magnitude improvement over previous single-antibody exosome detection methods and has successfully discriminated BPH and PCa patients with Gleason score 7 from healthy individuals. Collectively, these advancements demonstrate a novel sensing platform capable of accurate clinical cancer determination via liquid biopsy.