Recent advances in biologically sensitive field-effect transistors (BioFETs).

Research in the field of biosensors has enormously increased over the recent years. Since the development of the first biosensor by Clark in 1962, where an amperometric oxygen electrode was immobilised with an enzyme (glucose oxidase),1 many efforts have been invested to create functional hybrid systems. These functional hybrid systems often benefit from the coupling of the unique recognition and signal-amplification abilities of biological systems, that have been developed and optimised during millions of years of evolution, with an artificial man-made signal detection and amplification system. Thus, the combination of knowledge in bioand electrochemistry, solid-state and surface physics, bioengineering, integrated circuit silicon technology and data processing offers the possibility of a new generation of highly specific, sensitive, selective and reliable micro (bio-)chemical sensors and sensor arrays. Moreover, the rapid development of silicon technology has stimulated the fabrication of miniaturised analytical systems such as mTAS (micro total analysis system), ‘lab on chip’ sensors, electronic tongue devices and electronic noses.2–17 Among the variety of proposed concepts and different types of biosensors, the integration of biologically active materials together with an ISFET (ion-selective field-effect transistor) is one of the most attractive approaches. The ISFET was invented by Bergveld18 in 1970 and has been introduced as the first miniaturised silicon-based chemical sensor. In spite of distinct difficulties with regard to practical applications, the great interest in ISFET-based biosensors, so-called biologically modified field-effect transistors (BioFETs), has generated a great number of publications, a flow that shows no sign of diminishing. The reason therefore is that silicon-based fieldeffect devices are currently being the basic structural element in a new generation of micro biosensors; they provide a lot of potential advantages such as small size and weight, fast response, high reliability, low output impedance, the possibility of automatic packaging at wafer level, on-chip integration of biosensor arrays and a signal processing scheme with the future prospect of low-cost mass production of portable microanalysis systems; moreover, their possible field of applications reaches from medicine, biotechnology and environmental monitoring through food and drug industries to defence and security. This paper gives a review of recent and significant advances in the research and development of BioFETs. In planing this review, we have chosen to focus mainly upon developments occurring during the last six years (from 1995 to the end of 2001). A computer search of the Science Citation Index has found that more than 400 publications concerning ISFETs and BioFETs have appeared from January 1995 to December 2001, indicating the intensity of research activities devoted to this important task. This review is in general limited to journal articles and usually does not include patents, conference proceedings, reports or PhD theses. Some references to important works reported prior to 1995 have also been added to provide additional source material. The review is organised as follows: The principles of the ISFET and BioFET are described in section 2. Recent advances in the development of various types of BioFETs are reviewed in section 3. Here, some examples of current applications of BioFETs are presented, too. Concluding points and future prospects of BioFETs are discussed in section 4. Michael J. Schöning was born in Bruchsal, Germany, in 1962. He received his diploma in 1989 and Ph.D. in 1993, both in electrical engineering, from the Technical University (TH) Karlsruhe. In 1989 he joined the Institute of Radiochemistry at the Research Centre Karlsruhe, Germany. Since 1993 he has been with the Institute of Thin Films and Interfaces at the Research Centre Jülich, and since 1999 he has been a Professor of applied physics at the University of the Applied Sciences Aachen, Germany. His research interests include silicon-based chemical and biological sensors, thin film techniques, solid-state physics, semiconductor devices and microsystem technology.