Nanogap Capacitors for Label Free DNA Analysis
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Nanogap Capacitors for Label Free DNA Analysis Joon Sung Lee, Yang-Kyu Choi, Michael Pio, Jeonggi Seo and Luke P. Lee Berkeley Sensor and Actuator Center Department of Bioengineering, University of California at Berkeley, Berkeley, CA 94720 ABSTRACT Nanogap capacitors are fabricated for DNA hybridization detection. Without labeling, the nanogap capacitors on a chip can function as DNA microarray sensors. The difference in dielectric properties between single-stranded DNA and double-stranded DNA permits use of capacitance measurements to detect hybridization. To obtain high detection sensitivity, a 50 nm gap capacitor was fabricated using a Si- nanotechnology. To ensure proper measurement of DNA’s dielectrical properties, the probe ssDNA was first immobilized onto the electrode surface using self-assembly monolayers and allowed to hybridize with the target ssDNA. The capacitance changes were measured for 35- mer homonucleotides. The self-assembly monolayer and DNA immobilization events were verified independently by contact angle measurement and FTIR. Capacitance values are measured at frequencies ranging from 75 kHz to 5 MHz, using 0 VDC bias and 25 mVAC signals. Approximately 9% change in capacitance was observed after DNA hybridization at 75 kHz. INTRODUCTION Capacitance measurements can provide fast and sensitive in-situ monitoring of DNA hybridization without DNA labeling. This method provides an alternative to conventional DNA hybridization detection techniques such as radiochemical, enzymatic, fluorescent, and electrochemiluminescent methods, which can be cumbersome and time consuming processes because of the need for DNA labeling [1-3]. The investigation of dielectric properties of DNA was done even before the publication of Watson and Crick’s double helix work, but it is not easy to implement in a DNA microarray system. Previously several groups have tried to measure DNA hybridization with capacitance measurement; however, their methods were limited in reproducibility and sensitivity [4, 5]. Berney et al. used an electrolyte- insulator-semiconductor scheme and obtained a 3% capacitance change but had trouble with reproducibility of the measurements due to the crudeness of the device [4]. Other researchers used an electrochemical method and observed a 2% capacitance change but also reported low reproducibility due to poor insulating properties of the oligonucleotide layer [5]. There are two different capacitance measurement methods. In the first method, the capacitance is measured at the solution-electrode interface with a three-electrode system. Using an appropriate circuit model, the capacitance can be calculated with measured current. In this method, the sensitivity variation in the bulk solution can be solved using a reference cell. However, only 2-3% capacitance changes were measured after hybridization and reproducibility issues were also reported [4, 5]. In the second scheme, DNA is placed in between two opposing electrodes and the capacitance change is measured. Their device is limited by the difficul
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