Detection of single-base mutation of DNA oligonucleotides with different lengths by terahertz attenuated total reflection microfluidic cell

Mingjie Tang; Mingkun Zhang; Liangping Xia; Zhongbo Yang; Shihan Yan; Huabin Wang; Dongshan Wei; Chunlei Du; Hong-Liang Cui

doi:10.1364/BOE.400487

Detection of single-base mutation of DNA oligonucleotides with different lengths by terahertz attenuated total reflection microfluidic cell

Biomed Opt Express. 2020 Aug 31;11(9):5362-5372. doi: 10.1364/BOE.400487. eCollection 2020 Sep 1.

Authors

Mingjie Tang^{1

2

3}, Mingkun Zhang^{1

3}, Liangping Xia^{1

4}, Zhongbo Yang¹, Shihan Yan¹, Huabin Wang¹, Dongshan Wei^{1

5}, Chunlei Du¹, Hong-Liang Cui¹

Affiliations

¹ Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ These authors contributed equally to this work.
⁴ Key Laboratory of Micro Nano Optoelectronic Devices and Intelligent Perception Systems, Yangtze Normal University, Chongqing, 408100, China.
⁵ School of Electronic Engineering, Dongguan University of Technology, Dongguan, Guangdong, 523808, China.

Abstract

Many human genetic diseases are caused by single-base mutation in the gene sequence. Since DNA molecules with single-base mutation are extremely difficult to differentiate, existing detection methods are invariably complex and time-consuming. We propose a new label-free and fast terahertz (THz) spectroscopic technique based on a home-made terahertz attenuated total reflection (ATR) microfluidic cell and a terahertz time-domain spectroscopy (THz-TDS) system to detect single-base-mutated DNA molecules. The detected object DNA molecules are normal hemoglobin gene, sickle cell anemia gene (15 nt), JAK2 gene wild type and JAK2 V617F gene mutation (39 nt) from sickle cell anemia and thrombocytopenia, respectively. Results show that the oligonucleotide fragments with single-base mutation can be identified by THz spectroscopy combined with the ATR microfluidic cell, and the recognition effect of short oligonucleotide fragments with single-base mutation is better than that of long oligonucleotide fragments. The terahertz biosensor is shown to have high sensitivity and can be used to detect DNA molecules directly in the solution environment.