Michael J. Schöning

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.

Epidermal tattoo potentiometric sodium sensors with wireless signal transduction for continuous non-invasive sweat monitoring

This article describes the fabrication, characterization and application of an epidermal temporary-transfer tattoo-based potentiometric sensor, coupled with a miniaturized wearable wireless transceiver, for real-time monitoring of sodium in the human perspiration. Sodium excreted during perspiration is an excellent marker for electrolyte imbalance and provides valuable information regarding an individuals physical and mental wellbeing. The realization of the new skin-worn non-invasive tattoo-like sensing device has been realized by amalgamating several state-of-the-art thick film, laser printing, solid-state potentiometry, fluidics and wireless technologies. The resulting tattoo-based potentiometric sodium sensor displays a rapid near-Nernstian response with negligible carryover effects, and good resiliency against various mechanical deformations experienced by the human epidermis. On-body testing of the tattoo sensor coupled to a wireless transceiver during exercise activity demonstrated its ability to continuously monitor sweat sodium dynamics. The real-time sweat sodium concentration was transmitted wirelessly via a body-worn transceiver from the sodium tattoo sensor to a notebook while the subjects perspired on a stationary cycle. The favorable analytical performance along with the wearable nature of the wireless transceiver makes the new epidermal potentiometric sensing system attractive for continuous monitoring the sodium dynamics in human perspiration during diverse activities relevant to the healthcare, fitness, military, healthcare and skin-care domains.

Porous silicon as a substrate material for potentiometric biosensors

For the first time porous silicon has been investigated for the purpose of application as a substrate material for potentiometric biosensors operating in aqueous solutions. Porous silicon was prepared from differently doped silicon substrates by a standard anodic etching process. After oxidation, penicillinase, an enzyme sensitive to penicillin, was bound to the porous structure by physical adsorption. To characterize the electrochemical properties of the so build up penicillin biosensor, capacitance - voltage (C - V) measurements were performed on these field-effect structures.

Wearable electrochemical sensors for in situ analysis in marine environments

The development of wearable screen-printed electrochemical sensors on underwater garments comprised of the synthetic rubber neoprene is reported. These wearable sensors are able to determine the presence of environmental pollutants and security threats in marine environments. Owing to its unique elastic and superhydrophobic morphology, neoprene is an attractive substrate for thick-film electrochemical sensors for aquatic environments and offers high-resolution printing with no apparent defects. The neoprene-based sensor was evaluated for the voltammetric detection of trace heavy metal contaminants and nitroaromatic explosives in seawater samples. We also describe the first example of enzyme (tyrosinase) immobilization on a wearable substrate towards the amperometric biosensing of phenolic contaminants in seawater. Furthermore, the integration of a miniaturized potentiostat directly on the underwater garment is demonstrated. The wearable sensor-potentiostat microsystem provides a visual indication and alert if the levels of harmful contaminants have exceeded a pre-defined threshold. The concept discussed here is well-suited for integration into dry- and wetsuits worn by divers and recreational surfers/swimmers, thereby providing them with the ability to continuously assess their surroundings for environmental contaminants and security hazards.

Penicillin detection by means of field-effect based sensors: EnFET, capacitive EIS sensor or LAPS?

Abstract Three types of semiconductor field-effect penicillin sensors, enzyme field-effect transistors (EnFETs), capacitive electrolyte–insulator–semiconductor (EIS) sensors and light-addressable potentiometric sensors (LAPS) have been developed and tested for the penicillin detection. For all sensor types the enzyme penicillinase was adsorptively immobilised directly onto a pH-sensitive Ta 2 O 5 surface. Some basic parameters of these sensors (e.g. sensitivity, linear range, detection limit, response time, hysteresis and life time) are investigated and their performances with regard to the respective measurement set-up as well as the sensor configuration are compared.

Development of multisensor systems based on chalcogenide thin film chemical sensors for the simultaneous multicomponent analysis of metal ions in complex solutions

Abstract A new type of thin film chemical microsensors based on chalcogenide glass-sensitive materials was developed by means of silicon planar technology and pulsed laser deposition technique. These miniaturised ion-selective electrodes (ISEs) exhibit Nernstian responses over five concentration decades with detection limits of 1×10 −7 mol/l towards the primary ions Cu and Pb, and 4×10 −7 and 3×10 −5 mol/l towards Cd and Tl, respectively. The thin film microsensors have been shown to be perspective instruments for the simultaneous multicomponent analysis of complex liquid media based on the principles of an ‘electronic tongue’ device. Incorporating the thin film sensors into a sensor array allowed the multicomponent analysis of heavy metal-ion species (Pb 2+ , Cd 2+ , Zn 2+ and Fe 3+ ). The concentrations of Pb 2+ -, Cd 2+ - and Zn 2+ -ions can be determined simultaneously by direct potentiometric measurements using a sensor array of seven all-solid-state thin film chemical microsensors with an accuracy of 15–30%. The sensor array allows overcoming the problem of an insufficient selectivity of single sensors. The suggested microsystem-compatible fabrication technique favours a further miniaturisation, aimed to a fully integrated electrochemical microsystem.

Capacitive microsensors for biochemical sensing based on porous silicon technology

Abstract Porous EIS (electrolyte–insulator–semiconductor) structures of n-Si/SiO2/Si3N4 with a mean pore diameter of about 1 μm and a mean pore depth of about 2 μm have been realized for capacitive pH sensors. For the fabrication of the porous microsensors (down to “spot” sizes of 10 μm×10 μm), the n-doped silicon substrates have been photolithographically patterned by means of mask-matching technique using polyimide as a passivation material. The average pH sensitivity of the porous pH microsensor amounts about 56 mV/pH in the concentration range between pH 4 and pH 8. In order to prepare porous EIS biosensors the enzyme penicillinase has been adsorptively immobilized inside the porous structure. In the case of the porous biosensors an average penicillin sensitivity of about 90 mV/mM in the concentration range from 0.01 to 1 mM exists. Microreference electrodes, also prepared by the same porous silicon technology as for the pH- and biosensors, show a potential stability of more than 1 week in the long term.

Penicillin biosensor based on a capacitive field-effect structure functionalized with a dendrimer/carbon nanotube multilayer

Silicon-based sensors incorporating biomolecules are advantageous for processing and possible biological recognition in a small, reliable and rugged manufactured device. In this study, we report on the functionalization of field-effect (bio-)chemical sensors with layer-by-layer (LbL) films containing single-walled carbon nanotubes (SWNTs) and polyamidoamine (PAMAM) dendrimers. A capacitive electrolyte-insulator-semiconductor (EIS) structure modified with carbon nanotubes (EIS-NT) was built, which could be used as a penicillin biosensor. From atomic force microscopy (AFM) and field-emission scanning electron microscopy (FESEM) images, the LbL films were shown to be highly porous due to interpenetration of SWNTs into the dendrimer layers. Capacitance-voltage (C/V) measurements pointed to a high pH sensitivity of ca. 55 mV/pH for the EIS-NT structures. The biosensing ability towards penicillin of an EIS-NT-penicillinase biosensor was also observed as the flat-band voltage shifted to lower potentials at different penicillin concentrations. A dynamic response of penicillin concentrations, ranging from 5.0 microM to 25 mM, was evaluated for an EIS-NT with the penicillinase enzyme immobilized onto the surfaces, via constant-capacitance (ConCap) measurements, achieving a sensitivity of ca. 116 mV/decade. The presence of the nanostructured PAMAM/SWNT LbL film led to sensors with higher sensitivity and better performance.

Miniaturization of potentiometric sensors using porous silicon microtechnology

A new capacitive field-effect microsensor based on a porous EIS (electrolyte-insulator-semiconductor) structure is presented. The porous silicon sensor was prepared using standard techniques of semiconductor processing. A well-defined macroporous layer was formed on silicon by electrochemical etching and a SiO2Si3N4 sandwich was deposited as insulating and pH-sensitive layer. The porous sensor exhibits a high, near-Nernstian pH sensitivity of about 54 mV per decade in the concentration range from pH 4 to pH 8, similar to a planar non-porous EIS structure with the same layer sequence. The enlargement of the active sensor area (surface) due to the porous structure increases the measured capacitance and thus allows a scaling down of the sensor. The preparation of biosensors based on the same structure is demonstrated by immobilization of the enzyme penicillinase as biosensitive component.

A dual amperometric/potentiometric FIA-based biosensor for the distinctive detection of organophosphorus pesticides

Abstract Nerve agents, like pesticides on the basis of organophosphates (OPs) are among the most toxic chemical species that are known. To determine such pesticides with high sensitivity, selectivity and reliability, a novel dual amperometric/potentiometric biosensor chip with the immobilized enzyme organophosphorus hydrolase (OPH) has been developed and examined. The amperometric and potentiometric transducers of the biosensor chip have been prepared by means of thin-film techniques. In addition, the enzyme OPH was immobilized by using a cystamine/glutaraldehyde coupling technique on the amperometric gold electrode, and by means of a silane modification preparation on the potentiometric field-effect (EIS: electrolyte–insulator–semiconductor) sensor. Arranged in a serial set-up, the two biosensors have been integrated in a flow-injection analysis (FIA) system. Due to the two combined, but different electrochemical transducer principles, the developed dual amperometric/potentiometric biosensor chip enables selective information for injections of different groups of organophosphorus pesticides, like paraoxon, parathion, dichlorvos and diazinon down to the lower μM concentration range.