Ultrasensitive and label-free detection of pathogenic avian influenza DNA by using CMOS impedimetric sensors.

This work presents miniaturized CMOS (complementary metal oxide semiconductor) sensors for non-faradic impedimetric detection of AIV (avian influenza virus) oligonucleotides. The signal-to-noise ratio is significantly improved by monolithic sensor integration to reduce the effect of parasitic capacitances. The use of sub-μm interdigitated microelectrodes is also beneficial for promoting the signal coupling efficiency. Capacitance changes associated with surface modification, functionalization, and DNA hybridization were extracted from the measured frequency responses based on an equivalent-circuit model. Hybridization of the AIV H5 capture and target DNA probes produced a capacitance reduction of -13.2 ± 2.1% for target DNA concentrations from 1 fM to 10 fM, while a capacitance increase was observed when H5 target DNA was replaced with non-complementary H7 target DNA. With the demonstrated superior sensing capabilities, this miniaturized CMOS sensing platform shows great potential for label-free point-of-care biosensing applications.

[1]  Yasar Gurbuz,et al.  Label-free capacitive biosensor for sensitive detection of multiple biomarkers using gold interdigitated capacitor arrays. , 2010, Biosensors & bioelectronics.

[2]  V. Dravid,et al.  MOSFET-Embedded Microcantilevers for Measuring Deflection in Biomolecular Sensors , 2006, Science.

[3]  James A. Smagala,et al.  Experimental Evaluation of the FluChip Diagnostic Microarray for Influenza Virus Surveillance , 2006, Journal of Clinical Microbiology.

[4]  Po-Hung Yang,et al.  CMOS Open-Gate Ion-Sensitive Field-Effect Transistors for Ultrasensitive Dopamine Detection , 2010, IEEE Transactions on Electron Devices.

[5]  H. Eltoukhy,et al.  A 0.18-/spl mu/m CMOS bioluminescence detection lab-on-chip , 2006, IEEE Journal of Solid-State Circuits.

[6]  M. Chan,et al.  A high-density conduction-based micro-DNA identification array fabricated with a CMOS compatible process , 2003 .

[7]  Zhiqiang Gao,et al.  A DNA biosensor based on the detection of doxorubicin-conjugated Ag nanoparticle labels using solid-state voltammetry. , 2009, Biosensors & bioelectronics.

[8]  Byunghun Lee,et al.  One-chip electronic detection of DNA hybridization using precision impedance-based CMOS array sensor. , 2010, Biosensors & bioelectronics.

[9]  R. F. Dutra,et al.  Potential of a simplified measurement scheme and device structure for a low cost label-free point-of-care capacitive biosensor. , 2009, Biosensors & bioelectronics.

[10]  R. Thewes,et al.  A fully electronic DNA sensor with 128 positions and in-pixel A/D conversion , 2004, IEEE Journal of Solid-State Circuits.

[11]  Michael S.-C. Lu,et al.  5×5 CMOS capacitive sensor array for detection of the neurotransmitter dopamine. , 2010, Biosensors & bioelectronics.

[12]  Horng-Chih Lin,et al.  Poly-silicon nanowire field-effect transistor for ultrasensitive and label-free detection of pathogenic avian influenza DNA. , 2009, Biosensors & bioelectronics.

[13]  Booncharoen Wongkittisuksa,et al.  Label-free capacitive immunosensor for microcystin-LR using self-assembled thiourea monolayer incorporated with Ag nanoparticles on gold electrode. , 2008, Biosensors & bioelectronics.

[14]  Pedro Estrela,et al.  Label-free electrical detection of DNA hybridization for the example of influenza virus gene sequences. , 2008, Analytical biochemistry.

[15]  L. Benini,et al.  CMOS DNA Sensor Array With Integrated A/D Conversion Based on Label-Free Capacitance Measurement , 2006, IEEE Journal of Solid-State Circuits.

[16]  Bo Mattiasson,et al.  Continuous measurements of a binding reaction using a capacitive biosensor. , 2005, Biosensors & bioelectronics.

[17]  Nan Sun,et al.  CMOS RF Biosensor Utilizing Nuclear Magnetic Resonance , 2009, IEEE Journal of Solid-State Circuits.

[18]  Ching-Ho Wang,et al.  Simultaneous detection and differentiation of Newcastle disease and avian influenza viruses using oligonucleotide microarrays. , 2008, Veterinary microbiology.

[19]  Kevin W Plaxco,et al.  Microfluidic device architecture for electrochemical patterning and detection of multiple DNA sequences. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[20]  Bo Mattiasson,et al.  A comparative study of capacitive immunosensors based on self-assembled monolayers formed from thiourea, thioctic acid, and 3-mercaptopropionic acid. , 2006, Biosensors & bioelectronics.