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.

中文翻译：

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太赫兹衰减全反射微流细胞检测不同长度DNA寡核苷酸的单碱基突变

许多人类遗传病是由基因序列中的单碱基突变引起的。由于具有单碱基突变的DNA分子极难区分，因此现有的检测方法总是复杂且耗时。我们提出了一种新的无标记快速太赫兹（THz）光谱技术，该技术基于自制的太赫兹衰减全反射（ATR）微流控细胞和太赫兹时域光谱（THz-TDS）系统来检测单碱基突变DNA分子。检测到的目标DNA分子分别是正常血红蛋白基因，镰状细胞性贫血基因（15 nt），JAK2基因野生型和镰状细胞性贫血和血小板减少症的JAK2 V617F基因突变（39 nt）。结果表明，通过THz光谱结合ATR微流体细胞可以鉴定出具有单碱基突变的寡核苷酸片段，具有单碱基突变的短寡核苷酸片段的识别效果优于长的寡核苷酸片段。太赫兹生物传感器具有很高的灵敏度，可用于直接在溶液环境中检测DNA分子。