[P2.2.007]
One-chip electronic detection of DNA hybridization using precision impedance-based
CMOS array sensor
1
1
2
1
1
1
K-H Lee* , J-O Lee , M-J Sohn , B Lee , J-B Yoon , G-H Cho
1
2
Korea Advanced Institute of Science and Technology, Korea, Republic of, Korea Research
Institute of Bioscience and Biotechnology, Korea, Republic of
This paper describes a label-free and fully electronic detection of DNA hybridization, which is
achieved by 16 x 8 CMOS-based sensor using a new impedance spectroscopy. The
impedance-based method is based on the changes of the reactive component, Csense, and the
charge-transfer resistance, Rsense, upon hybridization with complementary DNA targets. In the
previous label-free techniques, the measured Csense suffers from the Rsense that exists in
parallel and causes leakage. Thus they are hard to increase accuracy due to the variance
from sample to sample. In this paper, we present an impedance extraction driven by
triangular wave and an integral readout concept, which enables a reliable measurement of
both Csense and Rsense, a highly sensitive sensor and a stable operation independent of
external variables.
Description of the proposed impedance spectroscopy
The system was fabricated in an industrial 0.35-µm 4-metal 2-poly CMOS process, and
included gold working electrodes and readout electronics into one chip. The integrated
readout utilizing the parasitic insensitive integrator achieves an enlarged detection range and
improved noise performance.
The maximum changes of impedance components, Csense and Rsense, upon hybridization are
obtained with 1µM target DNA in only 2µl sample volume. The average relative variation of
Csense is 31.5 % while only 3.6 % is observed with 1µM non-complementary strand. Rsense
changes by 68.6 % with complementary DNA probes, and by only 8 % with noncomplementary strand.
The proposed sensor composed of the impedance extraction using triangular wave and the
integral architecture allows quantitatively evaluating the absorbed molecule densities, as well
as estimating DNA hybridization kinetics with a distinguishable variation of impedance. This
fully electronic microsystem shows great potential in applications for bioanalytical tools, pointof-care diagnosis, and PCR free detection system.
Chip micrograph and architecture
Measurements of PNA-DNA hybridization : capacitance (top), resistance (bottom)
Keywords : Label-free DNA, Hybridization, CMOS, Impedance
References:
[1] C. Stagni et al., “Fully Electronic CMOS DNA Detection Array Based on Capacitance
Measurement with On-Chip Analog-to-Digital Conversion,” ISSCC Dig. Tech. Papers, pp. 6978, Feb., 2006.
[2] L. Moreno-Hagelsieb et al, “Electrical detection of DNA hybridization: Three extraction
techniques based on interdigitated Al/Al2O3 capacitors,” Biosensors and Bioelectronics, Vol.
22, pp. 2199-2207, Apr., 2007.
[3] M. Yi et al., “Theoretical and experimental study towards a nanogap dielectric biosensor,”
Biosensors and Bioelectronics, Vol.20, pp. 1320-1326. Jan., 2005.
Keywords: Label-free DNA, Hybridization, CMOS, Impedance