Electronic Detection of Nucleic Acid Molecules with a Field-Effect Transistor
Sven Ingebrandt, Yinhua Han, Malla-Reddy Sakkari, Regina Stockmann, Oleksandr Belinskyy
and Andreas Offenhäusser
Institute of Thin Films and Interfaces (ISG-2), Leo-Brandt Str., Forschungszentrum Jülich,
52428 Jülich, Germany
ABSTRACT
Currently, systems for the detection of nucleic acid sequences, known as DNA-chips, are
getting lots of attention. Such systems usually involve either an enzymatic or chemical labelling
reaction as part of the detection process. The next generation of DNA-chips aims at a labelfree,
fully electronic readout system. Several new approaches to signal generation that avoid a
labelling step have been developed in recent years. Besides other surface sensitive measurements
the possibility of electrochemical impedance and field-effect measurements for the detection of
biomolecules have been discussed. The fully electronic detection of charged biomolecules based
on the field-effect principle offers a labelfree method, which combines the unique sensitivity and
selectivity of biomolecular recognition reactions with an electronic chip-based readout. In this
approach one type of molecules is fixed at a surface and the biomolecular reaction with
complementary molecules is detected by change in the drain-source current of the transistor. This
change can occur by a change of the interface capacitance of the transistor gate or by change of
the surface potential during adsorption of the molecules. At the moment a complete theoretical
description of the detection principle is still under discussion. However, the fully electronic
readout of biomolecular reactions offers a unique principle for the construction of many different
sensors for bioassays. We are working on an approach to detect the hybridization of DNA
sequences using electrolyte-oxide-semiconductor field-effect transistor (EOSFET) arrays. This
method allows direct and in situ detection of specific DNA sequences without any labelling.
INTRODUCTION
The detection of Desoxyribo Nucleic Acid (DNA) molecules in biotechnology and in
medical diagnostics and precautions is an already commonly used method in medicine. For a
genetic testing at the ‘point of care’ - means in the doctor’s surgery - fast, cheap and miniaturized
analytical systems are required. Most of the classical methods are using the concept of DNA
hybridization, where known single-stranded DNA sequences are immobilized onto a surface and
the analyte is recognized by its strong binding affinity to the complementary strands. The
hybridization event can then be detected with many different principles like radioactive,
fluorescence, electrochemical, microgravimetric, enzymatic and electroluminicence methods
[e.g. 1, 2]. Commonly used, labelfree techniques are based on the direct detection of the intrinsic
electrical charge of DNA [3, 4, 5] or on capacitance [6] and impedance [7] changes at the
surface. Most of the sensors are using cyclic voltammetry, pulse voltammetry or
chronopotentiometry together with redox-active indicators as reviewed by [8]. Recently the
detection limit of field-effect sensors was enhanced such, that single base mismatches in 12-mer
oligonucleotides can be detected [4]. A miniaturized, integrated, addressable, multichannel
A6.9.1 Mater. Res. Soc. Symp. Proc. Vol. 828 © 2005 Materials Research Society