Modular Functionalized Gates for Field-Effect Transistor Biosensors Enabling Reliable Detection of Trace miRNAs.

Carbon nanotube field-effect transistor (CNT-FET) biosensor, featured with high sensitivity, label-free operation and miniaturization, has emerged as a promising candidate platform to detect trace microRNAs (miRNAs), which are critical disease biomarkers whose aberrant expression is closely associated with cancer progression. However, the complex assembly process of probes on gates often damages the performance of CNT FETs, which makes sensitivity of the sensor unable to meet reliable detection of ultralow concentration biomarkers. Here, we report a detachable CNT FET biosensor with a modular gate chip for ultrasensitive and reproducible miRNA detection. Specifically, the sensitive gate array and the CNT FET are separately fabricated as two modules with reserved liquid metal connection ports. After biofunctionalized process, the sensitive gate modules are assembled to FET modules to form the complete biosensors. This design not only avoids damage to CNT FETs caused by harsh environments during the assembly process of biological probes, but also allows the CNT FETs to be reused repeatedly. Using miRNA-21 as a model target, the modular biosensors exhibit ultrahigh sensitivity (limit of detection of 0.36 aM) and exceptional reproducibility (a response variation below 5.1%). Clinical serum analysis of 48 samples reveals significantly elevated miRNA-21 levels in liver, lung, and breast cancer patients compared with healthy individuals, with results showing excellent agreement with qRT-PCR ( = 0.98). The CNT FET biosensor with a modular sensitive gate provides a robust paradigm for cost-effective, decentralized miRNA screening.