基于微纳制造的下一代基因测序系统研究现状与展望  

Research status and prospects of next generation sequencing system based on micro-nano manufacturing

作　　者：余静文[1,2] 陈云飞[1,2] 

机构地区：[1]东南大学机械工程学院,南京211189 [2]江苏省微纳生物医疗器械设计与制造重点实验室,南京211189

出　　处：《中国科学：技术科学》2017年第4期345-354,共10页Scientia Sinica(Technologica)

基　　金：国家重点基础研究发展计划(编号:2011CB707605);国家自然科学基金(批准号:51435003;51375092)资助项目

摘　　要：基因是遗传的基本单元,是DNA或RNA分子上具有遗传信息的特定核苷酸序列,它不仅与生物体的生、老、病、死等一切生命现象直接相关,也是决定生命健康的内在因素,下一代基因测序仪的研制目标是希望能够将基因测序的成本大幅度降低,测序速度快速提高,推进基因组技术的个性化医学走向现实,基于固体纳米孔的基因测序是最有可能实现高通量的物理测序技术,但目前面临生物分子电信号的信噪比低、生物分子过孔速度太快以及生物分子在纳米孔内的输运规律缺失等挑战,设计多模式纳米孔传感器,通过多模式信号交叉对比,同时降低纳米孔长度等方法,是提高检测灵敏度的有效方法,借鉴生物纳米孔对DNA过孔速度的控制,利用磁场、声叉等外力场可以为单碱基的辨识奠定基础,当纳米通道的几何尺寸小于双电层厚度时,基于连续理论的泊松-玻尔兹曼方程和纳维-斯托克斯方程将面临挑战,建立纳通道内生物分子输运规律将丰富流体力学的研究内容。Genes are the basic unit of heredity, which have specific nucleotide sequences of genetic information on DNA or RNA molecule. It is not only directly related to all life phenomena of the organism like birth, growth, sickness, and death, but also internal factors determine the life and health. The goal of next-generation sequencing machine is to significantly reduce the cost of DNA sequencing, increase sequencing speed rapidly and advance personalized medicine in genomic technologies to reality. It is believed DNA sequencing based on solid-state nanopores is physical sequencing technology most likely to achieve high-throughput sequencing, but now faces several challenges, such as low signal to noise ratio, biomolecules translocate too fast and the transport rules at nanoscale has not been established. Designing multi-mode nanopore sensors and cross-referencing multi-mode signal, while reducing the length of the nanopore is an effective method to improve the detection sensitivity. Learning from biological nanopores, using external force by means of magnetic tweezer or tuning fork to control DNA translocation speed can lay the foundation for the identification of single base. When the geometry of the nanochannel is less than the thickness of the electric double layer, Poisson-Boltzmann equation and Navier-Stokes equations based on the theory of continuous will be challenged, the transport rules of biological molecules established within nanochannel will tremendously enrich research contents of fluid mechanics.

关 键 词：基因测序 固态纳米孔 过孔速度 信噪比 输运规律 

分 类 号：Q78[生物学—分子生物学]