Nanopore gene sequencing micro-current detection device and current stability compensation method

Abstract

The invention provides a nanopore gene sequencing micro-current detection device. The device comprises a detection circuit for current change when DNA molecules flow through a nanopore channel in a thin film, wherein the detection circuit comprises a first electrode, a second electrode, a third electrode and a constant potential circuit; and when a working electrode deviates, the constant potential circuit enables the ground potential of a counter electrode to change along with the ground potential of a reference electrode all the time, so that a stable voltage difference is kept between the first electrode and the second electrode. The invention further relates to a compensation method for nanopore gene sequencing micro-current stability. According to the invention, a current signal detected by the working electrode is changed into a voltage signal through an integral amplifier, the integral amplifier takes a capacitor as a feedback element, and two sampling and holding circuits are adopted to realize related double sampling, so that the noise performance is lower, and the bandwidth and the linearity of the signal are improved; meanwhile, the current signal is also subjected to filtering, denoising, compensation and other processing, so that the current detection accuracy is greatly improved.

Description

technical field [0001] The invention relates to the technical field of electronics, in particular to a nanopore gene sequencing microcurrent detection device. Background technique [0002] The third-generation nanopore gene sequencing technology, characterized by single-molecule, sequencing-by-synthesis, has significant advantages in read length, cost, and speed, and is one of the current research hotspots. The principle of nanopore sequencing is to determine the base sequence by detecting the weak characteristic current changes generated when the unwound DNA single strand passes through the nanopore. Therefore, accurate measurement of this characteristic current is one of the key technologies to achieve high-accuracy gene sequencing. At present, nanopore gene sequencing widely uses a two-electrode electrochemical system, and a certain voltage is applied between the two electrodes to drive DNA through the nanopore. However, due to the existence of the non-Faraday process, t...

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Problems solved by technology

Therefore, accurate measurement of this characteristic current is one of the key technologies to achieve high-accuracy gene sequencing. At present, nanopore gene sequencing widely uses a two-electrode electrochemical system, and a certain voltage is applied between the two electrodes to drive DNA through the nanopore. However, due to the existence of the non-Faraday process, the voltage difference between the two electrodes is very easy to fluctuate, resulting in a potential shift, and because the current is extremely weak, generally in the picoampere level, the change in the pressure difference will greatly affect the detection accuracy of the current , affecting the accuracy of the sequencing

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