Interface Cleaning Strategy of Carbon Nanotube Field-Effect Transistor Biosensors for Ultrasensitive Detection of Ophthalmic Biomarkers.

Carbon nanotube (CNT) field-effect transistor (FET) biosensors combine the molecular recognition capabilities of bioreceptors with the signal amplification and transduction functions of nano-FET devices, enabling highly specific and ultrasensitive biomolecule detection. However, interface degradation and contamination introduced in the micronanofabrication process of batch manufacturing led to inhomogeneity in biofunctionalization of device and sensing performance, thus limiting the reproducible preparation and large-scale application of CNT FET biosensors. In this study, we proposed a comprehensive interface cleaning strategy using inductively coupled plasma oxygen (ICP-O2) and ozone (O3) treatment to reduce process contamination, which led to a 20% increase in transconductance, a 18.75% increase in carrier mobility, and near-theoretical-limit subthreshold swing (68 mV/dec) of CNT FET biosensors. Notably, the cleaning strategy facilitates the introduction of additional aptamer probe binding sites, thereby improving the sensitivity about 6.6-fold. We studied inflammatory related factors of ophthalmic diseases in clinical testing and found that our biosensors could detect trace level IL-6/IgE proteins in a complex tear matrix, with the limit of detection (LOD) reaching 1.37 aM and good consistency with the results of the enzyme-linked immunosorbent assay (ELISA). This study provides insights into the interface engineering of carbon-based FET biosensors and is expected to promote the practical application of CNT FET biosensors in the on-site detection of ophthalmic disease biomarkers.