A CMOS label-free DNA sensor using electrostatic induction of molecular charges

This paper reports a label-free biosensor for the detection of DNA hybridization. The proposed biosensor measures the surface potential on oligonucleotide modified electrodes using a direct charge accumulation method. The sensor directly and repeatedly measures the charges induced in the working electrode, which correspond to intrinsic negative charges in immobilized molecules. The sensor achieves an improved signal-to-noise ratio (SNR), through the oversampling effect of accumulation for charges and the differential architecture. The sensor also shows stable, robust, and reproducible measurement independent of slight changes in the reference voltage, unlike previous ion-sensitive field effect transistors (ISFETs), providing the benefits of choosing a wide variety of reference electrode materials. The proposed device is integrated with working electrodes, a reference electrode and readout circuits into one package via a 0.35 mu m complementary metal-oxide-semiconductor (CMOS) process. The sensor achieves a detectable range of 88.3 dB and a detection limit of 36 mu V for surface potential. It is demonstrated that the sensor successfully achieves specific detection of oligonucleotide sequences derived from the H5N1 avian influenza virus. The experiments show a limit of detection of 100 pM and include a single-base mismatch test in 18-mer oligonucleotides. (C) 2011 Elsevier B.V. All rights reserved.