A critical challenge to translating field effect transistors into biochemical sensor platforms is the requirement of a gate electrode, which imposes restrictions on sensor device architectures and results in added expense, poorer scalability, and electrical noise. Here we show that it is possible to eliminate the need of the physical gate electrode and dielectrics altogether using a synthetic tube-in-a-tube (Tube<^>2) semiconductor. Composed of a semiconducting single-walled carbon nanotube nested in a charged, impermeable covalent functional shell, Tube<^>2 allows the semiconducting conduction pathway to be modulated solely by surface functional groups in a chemically gated-all-around configuration. The removal of physical gates significantly simplifies the device architecture and enables photolithography-free, highly scalable fabrication of transistor sensors in nonconventional configurations that are otherwise impossible. We show that concomitant FET sensitivity and single-mismatch selectivity can be achieved with Tube<^>2 even in a two-terminal, thin film transistor device configuration that is as simple as a chemiresistor. Miniaturized two-terminal field effect point sensors can also be fabricated, using a straightforward dice-and-dip procedure, for the detection of tuberculosis biomarkers.