Active Field Effect Capacitive Sensors for High-Throughput, Label-free Nucleic Acid Analysis

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Active Field Effect Capacitive Sensors for High-Throughput, Label-free Nucleic Acid Analysis Manu Sebastian Mannoor12, Teena James12 Dentcho V. Ivanov12, Bill Braunlin3 and Les Beadling3 1 Microelectronics Research Center, New Jersey Institute of Technology, Newark, NJ, USA. 2 Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA 3 Rational Affinity Devices LLC. Newark, NJ-07103, USA ABSTRACT We report a highly selective technique for rapid and label-free analysis of nucleic acid sample using Metal Oxide Semiconductor (MOS) capacitive sensors. The binding of charged macromolecules such as DNA on the surface of these Field Effect Devices modifies the charge distribution in the Semiconductor (Si) region of the sensor. These changes are manifested as a significant shift in the Capacitance-Voltage (C-V) characteristics measured across the device. The speed and selectivity of the detection process is enhanced by the use of external electric field of controlled intensity. This simple and high-throughput sensing technique holds promises for future electronic DNA arrays and Lab-on-a Chip devices. INTRODUCTION The monitoring and detection of Deoxyribonucleic acid (DNA) re-association by base pairing (hybridization) at solid-liquid interfaces is of utmost importance for the development of high-throughput sequencing, genetic screening and biomolecular sensing with great potential application in future drug and diagnostic development. For instance, an increasingly large number of infectious diseases are diagnosable by molecular analysis of nucleic acids[1]. The hybridization event can be used as an analytical technique when the sequence of one of the members in the double stranded complex is known, as it infers the presence of a sequence complementary to the known sequence, in a sample of unknown nucleotide sequences. Several methods have been developed for the label-free electrical detection of oligonucleotide hybridization, among which Field-Effect devices utilizing the intrinsic molecular charge of the nucleotide sequences for the generation of the sensing signal, receives special attention. The compatibility of these devices with the standard micro and nano fabrication techniques makes them cost-effective. Most of the successful research work in this direction have made use of a Field Effect Transistor (FET) structure[2]. In this work, we demonstrate the potential of a simple and easy to fabricate Metal Oxide Semiconductor (MOS) capacitive structure in attaining selective detection of oligonucleotide hybridization. Our experiments show that there is almost no advantage in using a MOSFET (Metal Oxide Semiconductor Field Effect Transistor) structure to obtain the information equally accessible with a MOS capacitor, which is much easier to fabricate. In particular, the simultaneous shift in the C-V characteristics of a MOS capacitive sensor along both the capacitance and voltage axis makes the C-V method more informative than a static DC measurement on the transistor structure.