Transistor sensing in salt solutions: Molecular binding to receptors on the surface of field-effect transistors (FETs) can be sensed through changes in transconductance. However, the saline solutions typically used with biomolecules create an electrical double layer that masks any events that occur within about 1 nanometer from the surface. Nakatsuka et al. overcame this limitation by using binding to large, negatively charged DNA stem loop structures that, upon ligand binding, cause conformational changes that can be sensed with an FET, even in solutions with high ionic strength. The authors demonstrate the sensing of charged molecules such as dopamine in artificial cerebrospinal fluid as well as neutral molecules such as glucose and zwitterion molecules like sphingosine-1-phosphate. Science , this issue p. 319