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首页> 外文期刊>Sensors and Actuators >Label-free methylation specific sensor based on silicon microring resonators for detection and quantification of DNA methylation biomarkers in bladder cancer
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Label-free methylation specific sensor based on silicon microring resonators for detection and quantification of DNA methylation biomarkers in bladder cancer

机译：基于硅微环共振器的无标记甲基化特异性传感器，用于膀胱癌中DNA甲基化生物标志物的检测和定量

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摘要

Detection and quantification of DNA methylation is important to provide an opportunity to resolve clinical issues such as cancer early detection, progression, and drug treatments. In spite of myriad current technologies for DNA methylation detection that have been developed in last decade, they are still complicated and inadequate to be used as in vitro clinical diagnostic device. This work presents the first methylation specific sensor based on the silicon microring resonators which achieves fast, simple and specific label-free detection of DNA methylation after the bisulfite conversion. The methylated promoter regions of three genes (DAPK, E-cadherin and RARβ), which have been widely studied as biomarkers for human cancers including bladder cancer, are used as the target DNA sequences. We show that the methylated targets are strongly captured by methylated probe compared to unmethylated probe or vice versa. The discrimination between methylated and unmethylated DNA sequences is achieved within 5 min after hybridization between target and probe. Additionally, we have quantified DNA methylation density using various proportions (100,75,50,25, and 0% of methylation sites) of methylation sequences of DAPK gene. Finally, we confirmed that the sensor can clearly detect the methylation of RARβ gene by using amplified target from genomic DNA of cancer cells. Therefore, our technique can be used to detect and quantify the methylation density in cancer biomarkers.
机译：DNA甲基化的检测和定量对于提供解决诸如癌症早期检测，进展和药物治疗之类的临床问题的机会很重要。尽管近十年来开发了无数种用于DNA甲基化检测的当前技术，但它们仍然很复杂且不足以用作体外临床诊断设备。这项工作提出了第一个基于硅微环共振器的甲基化特异性传感器，该传感器可在亚硫酸氢盐转化后实现对DNA甲基化的快速，简单和特定的无标记检测。已广泛研究了三个基因（DAPK，E-cadherin和RARβ）的甲基化启动子区域作为人类癌症（包括膀胱癌）的生物标志物，并将其作为目标DNA序列。我们显示，与未甲基化的探针相比，甲基化的目标被甲基化的探针强烈捕获，反之亦然。靶标和探针杂交后5分钟内即可实现甲基化和未甲基化DNA序列的区分。此外，我们使用DAPK基因甲基化序列的各种比例（分别为100、75、50、25和0％的甲基化位点）来量化DNA甲基化密度。最后，我们证实了该传感器可以通过使用癌细胞基因组DNA中的扩增靶标来清楚地检测RARβ基因的甲基化。因此，我们的技术可用于检测和量化癌症生物标志物中的甲基化密度。

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  • 来源
    《Sensors and Actuators》 |2013年第2期|404-411|共8页
  • 作者

    Yong Shin; Agampodi Promoda Perera; Jack Sheng Kee; Junfeng Song; Qing Fang; Guo-Qiang Lo; Mi Kyoung Park;

  • 作者单位

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

    Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, Singapore 117685, Singapore;

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  • 正文语种 eng
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  • 关键词

    DNA methylation; silicon microring resonator; methylation specific sensor; label-free detection; bladder cancer; cancer biomarker;

    机译：DNA甲基化;硅微环谐振器;甲基化特异性传感器;无标签检测;膀胱癌;癌症生物标志物;

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