Development of an integrated CMOS DNA detection biochip
Development of an integrated CMOS DNA detection biochip
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DOI：
10.1016/j.snb.2006.03.045
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发表时间：
2007-01-10
影响因子：
8.4
通讯作者：
Chen, Ping-Hei
中科院分区：
文献类型：
--
作者：
Cheng, Yi-Ting;Tsai, Chien-Ying;Chen, Ping-Hei
本文提出了一种采用自组装多层金纳米粒子（AuNPs）电检测方法的CMOS DNA检测生物芯片。该生物芯片的每个测点由三个主要部分组成；一对带有纳米间隙的电极，一个电流放大电路，和一个带有嵌入式温度传感器的加热器。该生物芯片首先由TSMC（台湾半导体制造有限公司）0.35 μ m 2P4M标准CMOS工艺制造。然后，采用后cmos微加工蚀刻工艺暴露纳米间隙表面，通过样品中的单链dna杂交来测试样品中多层AuNPs的建立。一对电极之间的间隙距离为350nm。在进行DNA检测测量之前，在两个微电极之间的纳米间隙表面建立自组装单层AuNPs。如果单链dna之间发生杂交，可以观察到多层aunp。多层aunp之间的电流比单层aunp之间的电流增加约1000倍，这表明测试样品中存在目标DNA。在将电极与嵌入式电流放大器集成后，多层aunp的电流被放大到mA数量级，可以很容易地通过商用伏安-欧姆-毫安表测量。采用加热元件和温度传感器的加热系统可以区分单碱基对失配杂交和互补杂交，从而建立多层aunp。该生物芯片上靶DNA的最低检测浓度为0.1 nM。(c) 2006 Elsevier B.V.版权所有
This paper presents a CMOS DNA detection biochip using an electrical detection method with self-assembly multilayer gold nanoparticles (AuNPs). Each measuring spot of this biochip consists of three major parts; a pair of electrodes with a nanogap, a current amplifier circuit, and a heater with an embedded temperature sensor. The biochip is first fabricated by a TSMC (Taiwan Semiconductor Manufacturing Company Ltd.) 0.35 mu m 2P4M standard CMOS process. Then, post-CMOS micromachining etch processes are used to expose the surface of the nanogap, to test samples for the establishment of multilayer AuNPs through hybridization between single strand DNAs in the samples. The gap distance between a pair of electrodes is 350 nm. Before taking DNA detection measurements, self-assembly monolayer AuNPs is established on the nanogap surface between two microelectrodes. Multilayer AuNPs can be observed if hybridization between single strand DNAs occurs. An approximately 1000-fold increase in electric current between the multilayer AuNPs over the monolayer AuNPs serves an indication of the presence of target DNA in test samples. After integrating the electrodes with an embedded current amplifier, the electric current of multilayer AuNPs is amplified to the order of mA that can be easily measured by a commercial Volt-Ohm-Milliammeter. The heating system with a heating element and a temperature sensor can be used to distinguish single base-pair mismatch hybridization from complementary hybridization for the establishment of multilayer AuNPs. The lowest detectable concentration of target DNA on this biochip is 0.1 nM. (c) 2006 Elsevier B.V. All rights reserved.