We report the detection of biomolecular interactions using field effect devices such as metal-oxide-semiconductor (MOS) capacitor structures and polycrystalline silicon thin film transistors (Poly-Si TFTs). We have developed ion-sensitive field effect transistors with a silicon nitride sensing layer. Near ideal pH sensitivity has been achieved. A penicillin sensor has been fabricated by functionalizing the sensing area with the enzyme penicillinase. Label-free electrical detection of DNA hybridization has been achieved using both MOS capacitors and Poly-Si TFTs. DNA interactions occurring at the metal gate of the devices lead to an increase of negative charges attached to the gate. This change in electrical charges is reflected by significant shifts of the current-voltage or capacitance-voltage characteristics of the TFTs or MOS diodes, respectively. Single base pair DNA mismatches can be detected with the technique. The method can be extended to other chemical or biochemical systems such as proteins and cells. © 2005 Elsevier Ltd. All rights reserved.