One-chip electronic detection of DNA hybridization using precision impedance-based CMOS array sensor.
This paper describes a label-free and fully electronic detection method of DNA hybridization, which is achieved through the use of a 16×8 microarray sensor in conjunction with a new type of impedance spectroscopy constructed with standard complementary metal-oxide-semiconductor (CMOS) technology. The impedance-based method is based on changes in the reactive capacitance and the charge-transfer resistance after hybridization with complementary DNA targets. In previously published label-free techniques, the measured capacitance presented unstable capacitive properties due to the parallel resistance that is not infinite and can cause a leakage by discharging the charge on the capacitor. This paper presents an impedance extraction method that uses excitation by triangular wave voltage, which enables a reliable measurement of both C and R producing a highly sensitive sensor with a stable operation independent of external variables. The system was fabricated in an industrial 0.35-μm 4-metal 2-poly CMOS process, integrating working electrodes and readout electronics into one chip. The integrated readout, which uses a parasitic insensitive integrator, achieves an enlarged detection range and improved noise performance. The maximum average relative variations of C and R are 31.5% and 68.6%, respectively, after hybridization with a 1 μM target DNA. The proposed sensor allows quantitative evaluation of the molecule densities on the chip with distinguishable variation in the impedance. This fully electronic microsystem has great potential for use with bioanalytical tools and point-of-care diagnosis.
Lee
Kang-Ho
KH
School of EECS, Korea Advanced Institute of Science and Technology, 335, Gwahakro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
Lee
Jeong-Oen
JO
Sohn
Mi-Jin
MJ
Lee
Byunghun
B
Choi
Suk-Hwan
SH
Kim
Sang Kyu
SK
Yoon
Jun-Bo
JB
Cho
Gyu-Hyeong
GH
D001483:Base Sequence; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D058266:Dielectric Spectroscopy; D004566:Electrodes; D004867:Equipment Design; D006046:Gold; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000737:chemistry; D012666:Semiconductors
D018076:DNA, Complementary; D020135:Peptide Nucleic Acids; D006046:Gold; D004247:DNA