Label-Free and Ultrasensitive Detection of Cartilage Acidic Protein 1 in Osteoarthritis Using a Single-Walled Carbon Nanotube Field-Effect Transistor Biosensor.

Abstract

Osteoarthritis (OA), a prevalent degenerative joint disease, significantly affects the well-being of afflicted individuals and compromises the standard functionality of human joints. The emerging biomarker, Cartilage acidic protein 1 (CRTAC1), intricately associates with OA initiation and serves as a prognostic indicator for the trajectory toward joint replacement. However, existing diagnostic methods for CRTAC1 are hampered by the limited abundance, thus restricting the precision and specificity. Herein, a novel approach utilizing a single-walled carbon nanotube field-effect transistor (SWCNTs FET) biosensor is reported for the direct label-free detection of CRTAC1. High-purity semiconducting carbon nanotube films, functionalized with antibodies of CRTAC1, provide excellent electrical and sensing properties. The SWCNTs FET biosensor exhibits high sensitivity, notable reproducibility, and a wide linear detection range (1 fg/mL to 100 ng/mL) for CRTAC1 with a theoretical limit of detection (LOD) of 0.2 fg/mL. Moreover, the SWCNTs FET biosensor is capable of directly detecting human serum samples, showing excellent sensing performance in differentiating clinical samples from OA patients and healthy populations. Comparative analysis with traditional enzyme-linked immunosorbent assay (ELISA) reveals that the proposed biosensor demonstrates faster detection speeds, higher sensitivity/accuracy, and lower errors, indicating high potential for the early OA diagnosis. Furthermore, the SWCNTs FET biosensor has good scalability for the combined diagnosis and measurement of multiple disease markers, thereby significantly expanding the application of SWCNTs FETs in biosensing and clinical diagnostics.