基于多模式信号检测的超灵敏传感器的基础理论与关键技术

The objective of this research program is to develop an ultra-sensitive sensor that can detect multi-mode signals targeting at single base identification. An atomic force microscope is integreted in the detecting system to control the translocation speed of a DNA strand through a nanopore. With the help of the speed control system and displacement measurment system in the AFM, the translocation speed of a DNA strand is expected to control below 1base/ms. A nano field effect transistor integreted on the sensor is designed on a single layer molybdenum disulfide. The change of the local potential induced by the translocation of DNA through the nanopore can be detected by the nano-FET. The factors that affect the change of the ionic currents and local potential will be investigated by a molecular dynamics simulation model. The model tries to simulate the whole translocation process of a DNA strand through a nanopore that inculdes the DNA thermal diffusion in bulk solution, captured process by the nanopore and the translocation through the nanopore. Electrical double strucuture in a solid liquid interface is also invetigated with the MD simulation and measured with a surface force appratus. Through understanding the physics behind the interaction between the DNA strands and nanopore, the sensor will be optimized in its geometrical size and its working eviroment conditions that includes solution parameters and the translocation speed. .The expected results from the proposal include further understanding the electrical double layer structure in a confined space, extension study of the nanofluid dynamics and of course the ability that can distinguish a single base. The delivery from this research program may provide a core technology for developing next generation of DNA sequencing machine..

课题以实现单碱基辨识为目标，设计、制造一种能检测多模式信号的超灵敏传感器，采用原子力显微镜的速度控制系统和位移测量系统，实现DNA过孔速度的主动控制；设计基于单层二硫化钼纳米带的场效应晶体管，实现DNA过孔信号的原位放大；通过测量通过纳米孔的离子电流、二硫化钼纳米带的电流信号辨识通过纳米孔的生物分子。在基础理论研究方面，开展分子动力学模型的建模，研究DNA在溶液池内的自由扩散运动中其空间姿态的变化规律、被纳米孔捕获的机理及通过纳米孔的动力学过程，通过全过程的分子动力学仿真，研究DNA的空间姿态、生物分子与纳米孔的作用过程及溶液内的离子空间分布对纳米孔离子电流信号、纳米孔口的局部电势的影响规律，在此基础上，建立描述生物分子在纳米孔内输运的纳流体动力学模型、受限环境下固液界面双电层模型。

课题以实现单碱基辨识为目标，设计、制造一种能检测多模式信号的超灵敏传感器：采用原子力显微镜操控DNA，以及电渗流驱动单碱基过孔等多种方法，实现了单分子过孔速度的主动控制；设计基于单层二硫化钼纳米带的场效应晶体管，通过纳米孔的离子电流、二硫化钼纳米带的源漏电流信号，结合原子力显微镜的力信号和制造出的纳米孔位移信号等，实现多模式信号的同步检测；采用介电击穿实现了法低成本、快速、大规模并行制孔，以亚纳米可控的尺寸精度，制造出一系列不同目标孔径的纳米孔，实现了不同链长DNA分子的筛选和单碱基的辨识。在基础理论研究方面，开展分子动力学模型的建模，发现了连续体输运理论在直径4.5 nm以下纳米孔内逐渐失效的临界点，揭示出水合层剥离和离子对形成是导致更小的纳米孔内离子迁移率剧烈下降的重要机理。在此基础上，完成生物大分子在纳米受限空间内的输运理论，包括生物分子在溶液中扩散运动、被纳米孔的捕获过程和进入纳米孔后堵塞离子电流的主要影响因素，建立了描述生物分子在纳米孔内输运的纳流体动力学模型、受限环境下固液界面双电层模型。