Detection and acquisition system for solid-state nano-pore nucleic acid sequencing electric signals

Abstract

The invention relates to the fields of genetics and molecular biology, and provides a detection and acquisition system for solid-state nano-pore nucleic acid sequencing electric signals. The system comprises a current-voltage conversion circuit, a conditioning circuit and a base characteristic signal data acquisition circuit which are successively connected to one another; the current-voltage conversion circuit is used for converting characteristic current signals into voltage signals, the characteristic current signals are generated by passing bases through solid-state nano-pores under the driving of an electric field, the conditioning circuit is used for amplifying and filtering the voltage signals, and the base characteristic signal data acquisition circuit is used for longtime continuously acquiring output signals of the conditioning circuit and outputting acquisition data to a computer for processing. The system overcomes the disadvantages of detection of electric signals in a solid-state nano-pore nucleic acid sequencing in a patch clamp system, employs detection channels which are mutually independent with one another and different gains aiming at four kinds of bases, realizes detection and acquisition of greatly changeable pA-nA grade current signals, improves the speed and the resolution of base characteristic current signal acquisition, and thereby increasing the identification precision.

Description

technical field [0001] The invention belongs to the fields of genetics and molecular biology, and more specifically relates to a detection and collection system for solid-state nanopore nucleic acid sequencing electrical signals. Background technique [0002] Nucleic acid sequencing technology is an important means of genetics and molecular biology research, and it is also an effective tool for clinical disease diagnosis and treatment. With the advancement of the Genome Project, nucleic acid sequencing technology is playing an increasingly important role. Solid-state nanopore nucleic acid sequencing (see invention patent 200610116294.X) is a low-cost, high-read-length, high-throughput third-generation sequencing method. Among the current methods, it is most likely to be realized within 24 hours at a cost of only US$1,000 The goal of personal whole-genome sequencing. Nanopore nucleic acid sequencing mostly adopts the method of electrophoresis. When bases pass through nanosc...

AI Technical Summary

Problems solved by technology

[0004] The traditional use of the patch clamp system is to detect the current of ion channels in cells, and there are some functional redundancy and insufficient performance in the application of solid-state nanopore nucleic acid sequencing

Existing patch clamp systems mostly use 12-bit or 16-bit analog-to-digital converters. Although the maximum sampling rate of a single channel can reach 200-500kHz, after multiplexing, each channel shares the sampling rate, which cannot meet the requirements of multiple channels at the same time. High-precision parallel high-speed acquisition requirements

In addition, when the existing patch clamp system performs nanopore nucleic acid sequencing, the characteristic currents induced by different bases are all amplified with the same magnification factor. There is a problem with insufficient resolution

For nanopore nucleic acid sequencing, the consequences of the above problems not only greatly compress the space for post-processing of collected data, but also affect the identification of characteristic current details

Although amplifiers made with integrated circuit technology can reduce noise and expand bandwidth, the cost is obviously too high in the case of nucleic acid sequencing (≤1000bp / s) using exonuclease to reduce the speed

Images