doi:10.1016/j.bios.2006.10.024
Copyright © 2006 Elsevier B.V. All rights reserved.
Electrical detection of DNA hybridization: Three extraction techniques based on interdigitated Al/Al2O3 capacitors
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L. Moreno-Hagelsieba, b, 
, 
, B. Foultierd, G. Laurenta, c, R. Pampina, b, J. Remacled, J.-P. Raskina, c and D. Flandrea, b, ,
aResearch Center on Micro and Nanoscopic Materials and Electronic Devices, Belgium
bMicroelectroniques Laboratory, Université catholique de Louvain, Belgium
cMicrowave Laboratory, Université catholique de Louvain, Belgium
dLaboratoire de Biochimie et Biologie Cellulaire, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium
Received 24 April 2006;
revised 12 October 2006;
accepted 23 October 2006.
Available online 28 November 2006.
Abstract
Based on interdigitated aluminum electrodes covered with Al2O3 and silver precipitation via biotin-antibody coupled gold nano-labels as signal enhancement, three complementary electrical methods were used and compared to detect the hybridization of target DNA for concentrations down to the 50 pM of a PCR product from cytochrome P450 2b2 gene. Human hepatic cytochrome P450 (CYP) enzymes participate in detoxification metabolism of xenobiotics. Therefore, determination of mutational status of P450 gene in a patient could have a significant impact on the choice of a medical treatment. Our three electrical extraction procedures are performed on the same interdigitated capacitive sensor lying on a passivated silicon substrate and consist in the measurement of respectively the low-frequency inter-electrodes capacitance, the high-frequency self-resonance frequency, and the equivalent MOS capacitance between the short-circuited electrodes and the backside metallization of the silicon substrate. This study is the first of its kind as it opens the way for correlation studies and noise reduction techniques based on multiple electrical measurements of the same DNA hybridization event with a single sensor.
Keywords: Biosensors; Anodic aluminum oxide; Interdigitated electrodes; Hybridization; DNA; Electrical detection
Fig. 1. (a) Top view of completed interdigitated structure with access lines; (b) electrode fingers close-up; (c) interdigitated capacitors after silver precipitation (darker area corresponds to precipitated silver spot); (d) SEM picture 3000-fold magnified, showing the presence of silver grains for the 0.1 nM target DNA concentration.
Fig. 2. Electrical set-ups for measuring: (a) capacitance variation between electrodes; (c) MOS capacitance between the short-circuited electrodes and the metallic backside of the silicon substrate; (e) self-resonance frequency of the capacitive sensor. Small-signal equivalent circuits for measurements of: (b) Low-frequency capacitance between the interdigitated electrodes; (d) MOS-like capacitance to substrate; (f) self-resonance frequency of the structure over a wide frequency band.
Fig. 3. Silver coverage percentage area calculation method: (a) SEM picture of the sample with the silver particles after hybridization; (b) pixels classification by intensity level featuring two distributions, white and black; (c) silver coverage average values and standard deviations (error bars) over 20 samples, as a function of hybridized target DNA concentrations extracted in active (dark columns) and non active (pale columns) areas.
Fig. 4. Electrical measurement results for the capacitive sensor vs. all concentrations tested: (a) capacitance variation at low frequency (100 kHz), calculated as capacitance obtained at the target concentration minus capacitance for the 0 nM solution; (b) MOS-like capacitance vs. substrate voltage curves from −10 to 10 V; (c) capacitance curves extracted from the imaginary part of the complex impedance as a function of the frequency showing the self-resonance frequency of the sensor (i.e. where the capacitance curve crosses the frequency axis).
Fig. 5. Comparison between average values found, for the various target DNA concentrations, for: (a) silver coverage extracted from SEM images, (b) low-frequency capacitance variation (target concentration result minus the 0 nM), (c) C-MOS capacitance to substrate variations extracted from Fig. 4(b) at 0 V, and (d) self-resonance frequency shifts extracted from curve in Fig. 4(c).
Table 1.
Recent works comparison data from different approaches in DNA hybridization electrical detection on silicon technologies (values indicated with an ‘*’ were based on approximate conversion data, IDE = interdigitated electrodes)
Table 2.
Average and standard deviation of the differences measured, between the various target concentrations and the 0 nM reference case, for the three electrical methods: inter-electrode capacitance (CIDE), MOS capacitance to substrate (C-MOS) and resonance frequency
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