Enhancing circulating tumor cell capture: Amin-functionalized bilayer graphene biosensing with integrated chip-level system for point-of-care testing

Abstract

Current research on the detection of circulating tumor cells (CTCs) as a diagnostic strategy is still in its early stages. Consequently, there is a need for an efficient platform to capture and accurately detect CTCs with high sensitivity. This study presents the development of a bio-sensing platform that employs a planar-gated graphene field-effect transistor (GFET). This platform is designed for the detection of CTCs associated with nasopharyngeal carcinoma (NPC). In this approach, bilayer graphene is functionalized through a low-damage nitrogen plasma treatment, and then further modified with specific antibodies to enable a label-free detection of CTCs. The real-time electrical signal changes of the sensor were analyzed, demonstrating advantages in terms of rapid sensing and cost-effective on chip fabrication and instrument investment. The results showed that the low-damage nitrogen plasma effectively aminated the graphene surface, with the C–NH2 bonds accounting for approximately 62.8 % of the nitrogen content. The linear detection range of the sensor from 1 cell/15 μl to 1 cell/1000 μl, with a limit of detection (LoD) of 1 cell/15 μl(∼66/ml). The sensitivity of the sensor was determined to be 0.040 V/decade with a linear regression of 0.93 and with high sensing specificity in mixture cells environments. The CTCs capture density on aminated graphene was calculated to be 238.6 ± 29.8 cells/mm2. We also integrated this sensor chip into a portable system, including the sensing and signal processing unit enabling fast detection and close to point-of-care diagnostic tests. This study provides a promising platform for the rapid and accurate detection of nasopharyngeal carcinoma CTCs for early detection and post-treatment monitoring.