Microscopic Detection of DNA Hybridization using Miniaturized Diamond DNA-FETs
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1039-P07-02
Microscopic Detection of DNA Hybridization using Miniaturized Diamond DNA-FETs Christoph E. Nebel, Hiroshi Uetsuka, Nianjun Yang, Takatoshi Yamada, and Hideyuki Watanabe AIST, Diamond Research Center, Tsukuba, 305-8568, Japan ABSTRACT Miniaturized DNA sensitive field-effect transistors (DNA-FET) have been realized using single crystalline diamond grown by plasma-enhanced chemical vapor deposition (CVD). To bond DNA to diamond, amine linker-molecules are covalently attached by photochemical means to Hterminated diamond surfaces. Using hetero-bifunctional cross-linker and thiol-modified singlestrand (ss) cancer marker DNA (CK20), the gate of diamond FETs is modified to sense hybridization of DNA, forming double-strand (ds) DNA molecules on the gate. The density of DNA bonded to diamond has been adjusted to about 1012 cm-2 and the experiments have been performed in phosphate buffer with different ionicity to control the Debye length of the Helmholtz layer. By hybridization, a gate-potential shift of 64 mV is detected in case of the 100 Å Debye lengths, while 46 mV is detected for 10 Å. This is discussed with respect to DNA related variations of charge and pH by hybridization. Time resolved experiments reveal exponential hybridization dynamics with a time constant of 600 s. The sensitivity limit of our experiment is about 1 nM.
1. INTRODUCTION The possibility of label-free electric detection of DNA-hybridization using semiconductor field effect transistors (FET) is an attractive alternative to electrochemical sensing. The integration of FETs into miniaturized multi-array sensor arrangements will allow performing label free, direct, fast, and in-expensive analysis of nucleic acid samples. The potential of miniaturization of such devices is a major advantage compared to amperometric techniques in electrochemistry. However, semiconductors for bio applications need to be chemical inert, bio-compatible and compatible with advanced micro-fabrication technology. Silicon, glass and gold can be biologically modified and are microelectronic-compatible, however, degradation of the interfaces has been a persistent problem, inhibiting the development of integrated biological sensors. Diamond is a promising candidate for such applications as it has all required characteristics like chemical inertness [1], biocompatibility [2, 3] and shows good electrical properties [4]. Diamond can be deposited by plasma enhance chemical vapor deposition (PECVD) on a variety of substrates, most prominent on silicon at moderate temperatures that are compatible with microelectronics processing. Over recent years, a variety of chemical surface modifications have been introduced to bond bio-organic molecules like DNA, enzymes and proteins covalently to diamond [5-11]. Hydrogen terminated insulating diamond shows surface conductivity, which is a unique feature and very attractive for sensing [12]. The nature of this conductivity has been discussed over several years and attracts still attention [13, 14]. A hole accumulation channel is genera
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