Department of Electrical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.
Biosens Bioelectron. 2010 Nov 15;26(3):1093-7. doi: 10.1016/j.bios.2010.08.065. Epub 2010 Sep 19.
This work presents miniaturized CMOS (complementary metal oxide semiconductor) capacitive sensors for detection of the neurotransmitter dopamine (DA) down to the sub-fM range. Sensing resolution is significantly enhanced by monolithic sensor integration to reduce the parasitic effect and the use of sub-μm interdigitated microelectrodes as the sensing interface. The 5 × 5 sensor array contains five designs of different electrode sizes and each design has five sensors. The positive charges produced from protonation of boronate and amino group after immobilization of 4-carboxyphenylboronic acid (CPBA) result in an increase of the electrode-analyte capacitance. Then the negative charges produced after binding of CPBA and DA molecules decrease the electrode-analyte capacitance. Signal transduction is achieved through a CMOS readout circuit whose output frequency is inversely proportional to the capacitance. Experimental results showed the ratios of average percentage capacitance changes of the experiment groups over those of the control groups were all larger than one for the five designs at DA concentration of 0.1 fM. Selectivity against the non-analyte species, such as tyramine, has also been demonstrated.
本工作提出了用于检测神经递质多巴胺 (DA) 的小型化 CMOS (互补金属氧化物半导体) 电容式传感器,其检测下限可达亚飞摩尔级。通过将传感器进行单片集成以减小寄生效应,以及使用亚微米交错微电极作为传感界面,显著提高了传感分辨率。5×5 传感器阵列包含五种不同电极尺寸的设计,每种设计都有五个传感器。4-羧基苯硼酸 (CPBA) 固定化后,硼酸盐和氨基的质子化产生正电荷,导致电极-分析物电容增加。然后,CPBA 和 DA 分子结合后产生的负电荷会降低电极-分析物电容。通过 CMOS 读出电路实现信号转导,其输出频率与电容成反比。实验结果表明,在 DA 浓度为 0.1 fM 时,五种设计的实验组的平均电容变化百分比与对照组的比值均大于 1。此外,还证明了对非分析物物质(如酪胺)的选择性。