Protein stretching sequencing platform with two-dimensional planar heterostructure and preparation method of protein stretching sequencing platform

Abstract

The invention relates to a protein stretching sequencing platform with a two-dimensional plane heterostructure and a control method and a manufacturing method of the platform. The protein stretching sequencing platform with the two-dimensional plane heterostructure is formed by seamless splicing of MoS2 and WS2, a channel track of the WS2 is designed in advance, different chemical potentials of the WS2 and the MoS2 are utilized, original bent and folded protein molecules to be detected are stretched, and the protein molecules can be adsorbed on the WS2 nanometer channel due to the WS2 adsorption effect, such that the thermal fluctuation of the amino acid is substantially reduced, and the helical conformation of the detected protein can be substantially reduced; the stretched protein molecule conformation adsorbed on the two-dimensional surface is beneficial to protein sequencing by using a high-resolution atomic force microscope or a scanning tunneling microscope, and the signal-to-noise ratio is remarkably improved. If a nanopore single-molecule detection technology is combined, low-cost and high-throughput protein sequencing is expected to be realized.

Description

technical field [0001] The invention belongs to the field of protein molecular electrophoresis drive, and in particular relates to a two-dimensional planar heterogeneous structure protein stretching sequencing platform and a preparation method thereof. Background technique [0002] Cellular protein information is often used as a source of biomarkers, which is very important for early detection of diseases. More than 150 amino acid mutations associated with Alzheimer's disease have been identified in Presenilin. Therefore, analyzing the three-dimensional structure of γ-secretase and understanding its normal work and pathogenic mechanism on this basis is not only of great scientific significance, but also plays an important guiding role in the development of drugs for Alzheimer's disease. [0003] The current protein sequencing method is to ionize the complete protein and enter it into a mass spectrometer to analyze and identify the protein from the polypeptide level. [000...

AI Technical Summary

Problems solved by technology

But there are also shortcomings. Optical tweezers have excellent time and space precision, but it will inevitably cause phototoxicity and heating of the sample, which will interfere with the results.

[0008] The disadvantage of magnetic tweezers is that the quality of microscope imaging is very high

[0009] In addition, protein molecules can also be stretched in high-speed fluids, but there is also a defect that the measured current in the pores is not accurate due to the fluctuation of protein molecules in the electrolyte

[0010] Most of the existing solid-state nanopores can promote the folding of proteins into their inherent structures, but there are also defects. For example, in nanopores with too small diameters, due to the non-specific interaction between solid-state nanopores and proteins, it is easy to cause clogging

[0011] Second, the development of fluorescence-based protein sequencing methods also has developmental problems.

The main limitations are the lack of organic fluorophores for the detection of 20+ different amino acids and the lack of suitable chemicals to specifically label all 20+ amino acids

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