Enhancing Small Molecule Sensing With Aptameric Functionalized Nano Devices

ABSTRACT Small‐molecule biomarkers are critical to physiological and neurological function, yet their reliable quantification in biofluids remains technically challenging. Conventional optical and electrochemical sensors suffer from insufficient sensitivity at picomolar levels, signal instability in complex media, susceptibility to interference from chemically similar species, and reliance on labels or bulky instrumentation, limiting their suitability for rapid, portable biochemical sensing. Field‐effect transistor (FET) biosensors offer a compelling alternative through label‐free electrical detection of molecular interactions at the sensor surface. Here, we present a nanostructured silicon nanowire FET (SNF) functionalized with a serotonin‐specific DNA aptamer for sensitive and selective serotonin detection. Exploiting the high surface‐to‐volume ratio and tunable electronic properties of the nanostructured channel, the device achieves a limit of detection of 1 pM with a response spanning a tested concentration range from 1 pM to 1 µM. Measurements were performed in artificial sweat, a high‐ionic‐strength environment representative of challenging biofluid conditions, to evaluate device performance under strong ionic screening. Surface characterization via AFM, XPS, and water contact angle measurements confirms successful probe immobilization, while density functional theory (DFT) simulations provide qualitative insight into charge redistribution associated with aptamer conformational changes. This work establishes a proof‐of‐concept nano‐FET platform for small‐molecule detection in high‐ionic environments.