Three-channel parallel DNA (deoxyribonucleic acid) sequencing sensor based on nanopore and AFM (atomic force microscopy) and detection method

Abstract

The invention discloses a three-channel parallel DNA (deoxyribonucleic acid) sequencing sensor based on a nanopore and an AFM (atomic force microscopy) and a detection method. The three-channel parallel DNA sequencing sensor comprises a blocked ionic current signal detection system, an AFM detection system, a tunneling current signal detection system and a nanopore single-molecular sensor. According to the invention, a chemical modification method is adopted to bond a to-be-detected single-strand DNA to a probe of the AFM, through control of the probe of the AFM, the motion direction and speed of the DNA in the nanopore can be controlled effectively, meanwhile, blocked ionic current and tunneling current which are generated during DNA translocation as well as traction change of the probe of the AFM can be detected simultaneously, three-channel parallel detection and signal parallel analysis are achieved, compared with the conventional nanopore single-molecular sensor, the capacity for recognizing a DNA basic group is improved greatly, and loss of effective signals is avoided. The three-channel parallel DNA sequencing sensor and the detection method can be accurately used for detection of an electrical signal and a force signal during DNA base sequence translocation in the nanopore, and great significance is provided for achievement of low-cost and high-throughput DNA sequencing.

Description

technical field [0001] The invention relates to a three-channel parallel DNA sequencing sensor and a sequencing detection method based on a nanopore and an atomic force microscope. Background technique [0002] Nanopore single-molecule sensors, whose working principle is based on the Coote counter, are unanimously believed by scientific researchers that they will be widely used in the fields of biomedicine, life science and technical science in the near future because of their simple principle and preparation process. However, the development of precise sequencing of DNA base sequences has been restricted by the scanning frequency of the patch clamp amplifier. At present, the sampling frequency of the patch clamp has not yet exceeded 4 MHz, and the existing sampling frequency is far from meeting the requirements of precise sequencing. . Therefore, researchers have adopted a series of methods to reduce the passing speed of DNA, (Meller A, Nivon L, Brandin E, et al. Rapid nan...

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