The electric detection of trace amounts of biomolecule is a key challenge in the development of diagnostic tools, because it has several advantages, including compatibility with electronic products, the possibility of their being developed into portable devices, and their high sensitivity in comparison with other methods. Nanogap devices, which are one of the recent advances in the electric biosensing field, have several favorable key features, such as simple operation mechanism, ultrahigh sensitivity, and design flexibility of device structures.
In chapter 1 and 2, integrated nanogap electrodes with separations of several nanometers were fabricated to detect the biomoleucles by a simple and highly reproducible method of surface-catalyzed chemical deposition. By this method, multifingered nanogap electrodes of a few nanometers in separation were fabricated with a good yield (over 90%). The fabrication was achieved by immersing the initial gap electrodes obtained by conventional e-beam lithography into a stock solution containing Au ions and a mild reducing agent. After the surface-catalyzed chemical deposition, a rather wide initial gap distance of 18-52 nm was decreased to a few nanometers, showing a much narrower distribution.
In chapeter 3, DNA hybridization was electrically detected by monitoring the electric conductance change of a nanodevice comprised of two electrodes separated by a narrow gap whose width was comparable to the size of a nanoparticle. Specific hybridization of a target DNA to the capture DNA on the electrode and the probe DNA on the gold nanoparticle (AuNP) resulted in the immobilization of AuNPs between the electrodes, which in turn led to a conductance jump across the gap. After fabrication of the device, the whole area except the gap region was passivated by e-beam resist to reduce a possible loss of target DNA. Two types of thiol-modified single-strand DNAs, which would specifically hybridize with portions of the target DNA, were covalently attached onto the surfaces of the gold electrodes and nanoparticles. The conductance change upon immobilization of the nanoparticle was readily measurable at room temperature. The nanoparticles immobilized between the electrodes can be removed by a simple heat treatment.
In chapter 4, we reported a simple method for enhancing electric conductance in nanogap devices without any additional treatments, such as silver-enhancing process. In the nanogap device fabricated, the jump of electric conductance was derived primarily by the bio-selective immobilization of AuNPs of about 30 nm in diameter into the gap region between two electrodes spaced by 60-90 nm. The low electric conductance right after AuNP immobilization was greatly enhanced simply by repeated I-V scans at a relatively high voltage range of -5 to 5 V. A new conduction pathway was believed to be formed across the gap by the strong electric field established between the two electrodes. The higher conduction state of the nanogap device showed a very stable I-V curve, which was used as an excellent measure of the existence of prostate-specific antigen (PSA).
In chapter 5, we described the highly sensitive electrical detection of PSA using nanogap devices, In particular, PSA concentration was measured by calculating the probability of switch-on device which is defined as the percentage of low resistance device that are generated after immersion in AuNP probes solution. And the detection limit of the nanogap device was are improved by using optimized electric signal amplification factors such as the effects of the effective length of the electrodes, the blocking layers of the AuNP probes and Au electrodes, and the size ratio between the nanogap and the AuNP.
나노갭 생체검출소자는 (nanogap biosensor) 나노미터 크기의 갭을 가지는 금속 전극 사이에 생체물질의 유무에 따라서 전기적인 신호의 변화를 감지할 수 있는 소자를 말한다. 나노갭 소자는 신호의 증폭 효율이 매우 높아 고감도의 분자 검출이 가능하며, 소자의 구조와 동작원리가 단순하여 생체검출소자로의 개발이 매우 용이하다. 하지만 적은 양의 생체물질에 대해서도 민감하게 반응하기 위해서는 전극과 전극 사이의 갭 간격을 정밀하게 조절하는 기술과 절연체인 생체물질을 측정할 수 있는 기술이 필요하다. 본 논문에서는 나노갭 소자의 제작방법에서부터 실질적인 검출소자로 이용되기 위해서 필요한 소자의 전기적인 신호증폭과 신호처리에 대한 연구가 포함되어 있을 뿐만 아니라, 이를 이용하여 실질적인 생체표지제인 DNA (DeoxyriboNucleic Acid)와 PSA (Prostatic Specific Antigen)를 전기적으로 검출하였다.
Part 1에서는 나노갭 소자 제작에 대한 부분을 서술하였다. 표면촉진화학성장법은 (surface catalyzed chemical deposition) 환원제를 사용하여 금 전극표면에서만 선택적으로 금이 성장하는 것을 특징으로 하며 다수의 나노갭 소자를 쉽게 제작할 수 있는 것을 장점으로 한다. 우리는 다양한 실험조건을 (반응 시간, 반응 온도, 환원제의 농도) 변화하여 전극표면에서 이루어지는 금 이온의 환원량을 조절하였고 이것을 통해서 전극 사이 간격을 원하는 크기로 만들 수 있었다. 특히 다른 제작 방법에서 구현하기 어려운 수 나노미터 크기의 나노갭 소자를 쉽고 빠르게 대량으로 만드는 것이 가능하였다.
Part 2에서는 상기 방법으로 제작된 나노갭 소자를 이용하여 다양한 종류의 생체물질을 의미있는 농도에서 검출하였다. 전기적으로 부도체인 생체물질을 금 나노입자를 탐침으로 이용하여 검출하였고 나노갭의 간격, 금 나노입자의 크기, 측정전압의 세기를 조절하여 나노갭 소자의 측정감도를 크게 향상시켰다. 특히 생체물질의 농도가 진할수록 나노갭에 붙은 금 나노입자 수가 증가하고 이로 인하여 나노갭 소자의 전기적인 특성변화가 일어나는 소자의 비율이 증가된다는 사실을 통해서 정량분석이 어려운 나노갭 소자의 문제점을 집적화된 나노갭 소자를 사용하여 해결하였다.
