Method for carrying out deceleration and monomolecular capture on nucleic acid molecule based on solid-state nano hole

A nucleic acid molecule and nanopore technology, which is used in material analysis by electromagnetic means, chemical instruments and methods, biochemical equipment and methods, etc. Time resolution, effect of increased residence time, high current signal-to-noise ratio

Active Publication Date: 2012-08-01
美国哈佛大学 +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The signal noise obtained by this capture technology is very large, and the experimental device is complicated, which requires high technical requirements

Method used

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  • Method for carrying out deceleration and monomolecular capture on nucleic acid molecule based on solid-state nano hole
  • Method for carrying out deceleration and monomolecular capture on nucleic acid molecule based on solid-state nano hole
  • Method for carrying out deceleration and monomolecular capture on nucleic acid molecule based on solid-state nano hole

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Embodiment

[0040] 1) Preparation of chip devices

[0041] The purpose of this step is to prepare a solid-state nanoporous device that can be operated in a transmission electron microscope, so that the high-energy convergent electron beam in the transmission electron microscope can be used to punch holes in the suspended film of the device, thereby realizing a nanoporous device. This includes a series of micro-nano processing technology involved in traditional semiconductor processing technology, and also involves a series of modern cutting-edge nano-scale processing technology.

[0042] The specific method is as follows: First, a 4-inch silicon wafer with a (100) surface is grown with 2 microns of silicon oxide on both sides, and low-stress silicon nitride of about 150 to 200 nanometers is deposited by a low-pressure chemical vapor deposition method. Then make a photolithography mask, the purpose is to make a lot of 3mm×3mm small substrate periodic distribution on a 4-inch silicon wafer ...

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Abstract

The invention discloses a method for carrying out deceleration and monomolecular capture on a nucleic acid molecule based on a solid-state nano hole. The method comprises the following steps of: adding the nucleic acid molecule to be measured into a nano hole sequencing device filled with an electrolyte, wherein the nano hole sequencing device comprises an electrolytic bath provided with an anode and a cathode, and a solid-state nano hole thin film for separating the anode of the electrolytic bath from the cathode of the electrolytic bath; placing the nucleic acid molecule in a positive chamber of the electrolytic bath; during measurement, introducing a pressure external field into the positive chamber as a driving external field for the perforation of the nucleic acid molecule; applying a voltage between the anode and the cathode as an electric field external field reverse to the pressure external field; and in a measurement process, enabling the acting force of the pressure external field, from which the nucleic acid molecule is suffered in the nano hole to be more than or approximately equal to electric field force according to a deceleration purpose or a capture purpose to be realized by the method. By using the method, on the premise that the signal-to-noise ratio of a measurement signal is not decreased, the speed at which a DNA (deoxyribonucleic acid) molecule penetrates through a nano hole device can be effectively decreased, and a perforation speed can be slowed down for above one order of magnitude.

Description

technical field [0001] The invention relates to a method for decelerating nucleic acid molecules and capturing single molecules based on solid-state nanopores. Background technique [0002] DNA single-molecule detection and analysis based on solid-state nanopore devices is considered to be one of the most promising technical routes for realizing the third generation of rapid and low-cost human gene sequencing (realizing the genome sequencing of a single person within 24 hours at a cost of less than $1,000), and has become In addition to research groups such as Harvard University, Boston University, Brown University, Caltech, and Delft University of Technology in the Netherlands, IBM also announced in October 2009 to join the next generation of human genome sequencing- The $1,000 plan uses nanopore device-based sequencing technology as a realization method, enabling nanopore research to move from basic research to application (D.Branton, et al.Nature Biotechnology 26(10), 114...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N27/48
CPCC12Q1/68G01N33/48721C12Q1/6869B01L3/50273B01L3/502761B01L2200/0663B01L2300/0896B01L2400/0415B01L2400/0487B01L3/502707C12Q2523/303C12Q2527/109C12Q2563/116C12Q2565/631G01N27/44765G01N27/44791G01N27/453
Inventor 赵清鲁铂俞大鹏
Owner 美国哈佛大学
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