Electronic Detection of Nucleic Acid Molecules with a Field-Effect Transistor
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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
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