Small-MoleculeFunctionalized Needle Transistor BiosensorEnables Direct and Selective Monitoring of SO2 In Vivo

Abstract In vivo electrochemical analysis with implantable microelectrodes enables real-time, high-resolution monitoring of chemical signals with exceptional sensitivity. However, directly detecting electrochemically inert molecules, such as SO2, remains challenging. To address this limitation, we designed and synthesized a small-molecule SO2 recognizer (SO2–SMR), which is capable of recognizing SO2 selectively. Then, we immobilized it onto the surface of a needle-based graphene field-effect transistor (FET), thereby achieving in vivo detection of SO2. Upon reacting with SO2, the SO2–SMR modulates the surface charge of the FET sensing channel, generating a quantifiable electronic signal. The constructed needle SO2–FET biosensor exhibits excellent affinity, selectivity, and sensitivity to the target SO2 molecules with a detection limit down to 31.39 fM in physiological solution. These properties make the SO2–FET biosensor an effective tool for monitoring of SO2 dynamics both at the cellular level and within living tumor tissue. Our findings indicate that tumor progression is closely associated with localized SO2 concentration, offering new insights into tumor development. By tracking SO2 fluctuations during tumor growth and in response to therapeutic intervention, the needle SO2–FET biosensor further demonstrates its potential as a powerful tool for evaluating the treatment efficacy. This approach provides a promising technological platform for monitoring the tumor progression and prognosis.