CN-121975925-A - DNA sequencing system based on in-plane heterojunction and surface enhanced Raman scattering

CN121975925ACN 121975925 ACN121975925 ACN 121975925ACN-121975925-A

Abstract

The invention relates to the field of biological detection, biotechnology and nanotechnology, in particular to a DNA sequencing system based on an in-plane heterojunction and surface-enhanced Raman scattering, which comprises an in-plane heterojunction with a middle strip, an excitation light source, a current loop mechanism and a spectrometer, wherein metal nanoparticles are arranged on two sides of the in-plane heterojunction, the excitation light source is used for exciting plasma resonance of the metal nanoparticles, the current loop mechanism is used for driving DNA sequencing molecules adsorbed on the heterojunction strip to move along the middle strip, and the spectrometer is used for detecting Raman spectra of the DNA sequencing molecules. The invention can efficiently capture and definitively transport the sequencing molecules to the metal surface plasma electric field enhancement region to finish sequencing based on Raman signals, and repeated detection of the same molecule can be realized by repeatedly passing the electric field enhancement region through the back and forth movement of the molecules only by changing the direction of the electric field in the current loop.

Inventors

MENG LIJUN
ZHOU RUHONG

Assignees

杭州市第一人民医院(西湖大学附属杭州市第一人民医院)

Dates

Publication Date: 20260505
Application Date: 20260402

Claims (10)

1. A DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering, comprising: The plane heterojunction is provided with a middle strip, and metal nano particles are arranged on two sides of the plane heterojunction; the excitation light source is used for exciting the plasmon resonance of the metal nano particles; A current loop mechanism for driving the DNA sequencing molecules adsorbed on the heterojunction strip to move along the middle strip, and The spectrometer is used for detecting the Raman spectrum of the DNA sequencing molecule.
2. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 1, wherein the middle band has a strong affinity for DNA sequencing molecules and the material on both sides of the middle band has a weak affinity for DNA sequencing molecules.
3. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 2, wherein the in-plane heterojunction is formed by splicing and connecting a plurality of two-dimensional materials in a plane, a middle strip is formed by two-dimensional materials with stronger affinity with DNA sequencing molecules, and two-dimensional materials with weaker affinity with DNA sequencing molecules are arranged outside the middle strip.
4. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 3, wherein the two-dimensional material comprises one or more of graphene, boron nitride.
5. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 1 or 2 or 3 or 4, wherein the electrodes of the heterojunction, metal nanoparticle, DNA sequencing molecule and current loop are all in aqueous solution.
6. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 1 or 2 or 3 or 4, wherein the current loop mechanism comprises a power source and two electrodes, one pair of electrodes located on each side of the middle strip.
7. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 6, wherein the current loop mechanism further comprises a voltage measurement device connected across the power supply and the electrode.
8. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 1 or 2 or 3 or 4, wherein the metal nanoparticles comprise one or more of silver and gold.
9. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 8, wherein the thickness of the metal nanoparticles is between 4nm and 6nm, or the metal nanoparticles are equilateral triangles with a distance from the apex to the base of the triangle between 36nm and 44nm.
10. The DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering of claim 1 or 2 or 3 or 4, wherein the width of the middle band is 1nm to 3nm.

Description

DNA sequencing system based on in-plane heterojunction and surface enhanced Raman scattering Technical Field The invention relates to the fields of biological detection, biotechnology and nanotechnology, in particular to a DNA sequencing system based on in-plane heterojunction and surface enhanced Raman scattering. Background As a key technology in modern biological research and medical precision diagnosis, DNA sequencing technology has undergone many innovations over the last decades, achieving rapid development. The latest generation sequencing technology targets single molecule, real-time detection, long-read long sequencing, low cost and high throughput, and commonly includes nanopore sequencing devices using ion current detection, as well as various solid state nanostructure sequencing devices using surface enhanced raman scattering. In the past, researchers have developed a number of theoretical and experimental exploration for raman scattering-based sequencing schemes. However, these works basically follow the thought of nanopore sequencing, namely, a nanopore allowing sequencing molecules to pass through is constructed through various forms of metal structures, and then the detection of each section of the molecule is completed by utilizing the enhancement effect of a metal surface plasmon resonance electric field on a Raman signal in the process of passing through the nanopore. Such a structure has the disadvantages that 1) charged molecules in a solution are generally driven by an electric field perpendicular to the nanopore to approach and pass through the nanopore, which is accompanied by intense thermal movement of the molecules, so that the nanopore is not efficient in collecting the molecules, and 2) conventional nanopores can only perform a single detection of the same molecule because the molecules are not returned once they pass through the nanopore from one side solution to the other. Disclosure of Invention The invention aims to overcome the defects that the collection efficiency of the conventional nanopore on molecules is low and the nanopore can only finish single detection on the same molecule in a sequencing scheme based on Raman scattering in the prior art. In order to achieve the above purpose, the present invention adopts the following technical scheme: a DNA sequencing system based on in-plane heterojunction and surface enhanced raman scattering, comprising: The plane heterojunction is provided with a middle strip, and metal nano particles are arranged on two sides of the plane heterojunction; the excitation light source is used for exciting the plasmon resonance of the metal nano particles; The device comprises a heterojunction strip, a current loop mechanism, a spectrometer and a control unit, wherein the current loop mechanism is used for driving DNA sequencing molecules adsorbed on the heterojunction strip to move along the middle strip, and the spectrometer is used for detecting Raman spectra of the DNA sequencing molecules. Alternatively, the middle band has a stronger affinity for DNA sequencing molecules and the material on both sides of the middle band has a weaker affinity for DNA sequencing molecules. More preferably, the in-plane heterojunction is formed by splicing and connecting a plurality of two-dimensional materials in a plane, a middle strip is formed by the two-dimensional materials with stronger affinity with DNA sequencing molecules, and the two-dimensional materials with weaker affinity with the DNA sequencing molecules are arranged on the outer side of the middle strip. Optionally, the two-dimensional material includes one or more of graphene and boron nitride. Optionally, the current loop mechanism includes a power source and two electrodes, one pair of electrodes being located on each side of the central strip. Optionally, the current loop mechanism further comprises a voltage measuring device, and two ends of the voltage measuring device are connected between the power supply and the electrode. Optionally, the metal nanoparticles comprise one or more of silver and gold. Optionally, the thickness of the metal nano-particles is 4nm-6nm, or the metal nano-particles are equilateral triangles, and the distance from the vertex to the bottom of the triangle is 36nm-44nm. Optionally, the width of the middle strip is 1nm-3nm. The beneficial effects of the invention at least comprise: 1) The invention adopts the in-plane heterojunction structure to efficiently capture and transport the sequencing molecules to the metal surface plasma electric field enhancement region deterministically to finish the sequencing based on Raman signals. On the other hand, as the molecules are always adsorbed on the middle strip of the heterojunction, repeated detection of the same molecule can be realized by repeatedly passing through the electric field enhancement region through the back and forth movement of the molecules only by changing the direction of the electric field in the