Biomolecule sequencing method by Raman spectrum method

Abstract

The present invention provides a biomolecule sequencing method by a Raman spectroscopy method. The biomolecule sequencing method comprises the following steps: I, a nanopore device is provided and comprises a flexible substrate nanopore structure, and the flexible substrate nanopore structure comprises nanopores and a metal layer to reduce sizes of the nanopores to be 1-100 nm; II, biomolecules move towards the nanopores, a laser Raman microscope emits laser to the nanopores, and Raman spectrum signals are generated when the biomolecules pass through the nanopores; III, a spectrum measuring device measures Raman spectrum signals to obtain measurement data; and IV, a data acquisition and analysis device analyzes the measured data and outputs results. A detection strategy of using the surface-enhanced Raman spectrum has a technical effect of realizing detection of sub-nanometer spatial resolution and provides vibration spectrum of molecule specificity fingerprint information, the spectrum signals of all bases are not overlapped, and the biomolecule sequencing method has excellent discrimination and chemical sensitivity.

Description

technical field [0001] The invention belongs to the fields of gene sequencing and biomolecular sensing, and in particular relates to a system and a sequencing method for biomolecular sequencing using Raman spectroscopy. Background technique [0002] The measurement of genetic information has revolutionized the field of life sciences and medicine. In the future, precision medicine and personalized medicine will require new sequencing technologies with lower cost, faster speed, higher precision and longer read length. [0003] The new generation of single-molecule real-time sequencing technology addresses the need for longer read length and faster speed; the recent rapid development of biological nanopore sequencing technology further addresses the need for lower cost. Biological nanopore sequencing technology does not need to prepare a large number of samples, and the sample preparation process does not need to consume biological and chemical reagents, which greatly reduces ...

AI Technical Summary

Problems solved by technology

The current solid-state nanopore technology mainly realizes sequencing by measuring the ion blocking current, but it faces many challenges: first, the translocation behavior of the DNA chain in the nanopore is not easy to control, and the direction of the base is uncontrolled, which has great Randomness, DNA moves too fast (0.1-1μs / bp); DNA binds non-specifically to the surface of the nanopore to form a secondary or tertiary structure, blocks the nanopore, and restricts the normal translocation of the DNA chain; in traditional biological In solid-state nanopore detection technology, ion blocking current is generally used to distinguish different base sequences. However, current detection technology has an essential limitation: the electric field around the nanopore will extend to both sides, resulting in the extension of the effective length of the nanopore. , which limits the detection resolution

These problems have severely limited the successful implementation of solid-state nanopore sequencing technology.

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