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WO2019109253A1 - Procédé de réglage de la taille effective d'un nanopore à l'état solide dans un système à nanopores à l'état solide - Google Patents

Procédé de réglage de la taille effective d'un nanopore à l'état solide dans un système à nanopores à l'état solide Download PDF

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WO2019109253A1
WO2019109253A1 PCT/CN2017/114642 CN2017114642W WO2019109253A1 WO 2019109253 A1 WO2019109253 A1 WO 2019109253A1 CN 2017114642 W CN2017114642 W CN 2017114642W WO 2019109253 A1 WO2019109253 A1 WO 2019109253A1
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solid
nanopore
state
semiconductor substrate
voltage
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English (en)
Chinese (zh)
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刘泽文
陈琦
王一凡
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Tsinghua University
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Tsinghua University
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403—Cells and electrode assemblies
    • G01N27/413—Concentration cells using liquid electrolytes measuring currents or voltages in voltaic cells

Definitions

  • the present invention relates to the field of nanofabrication technology, and in particular to a method for regulating the effective size of solid nanopore in a solid state nanopore system.
  • nanopores can be roughly divided into: bio-nanopores, solid-state nanopores, and composite nanopores.
  • bio-nanopores solid-state nanopores
  • composite nanopores Compared with the early application of biological nanopores, solid nanopores, due to their superior robustness, better semiconductor and microfluid preparation compatibility, and more flexible preparation methods, are receiving more and more attention from the academic community. With emphasis. Solid-state nanopores have a wide range of applications and broad developments in many fields, such as DNA single-molecule sequencing, nanolithography, near-field optical modulation, ion logic circuits, microfluidics and natural simulation platforms, water purification and desalination, and organic Degradation of pollutants, etc.
  • the size of the nanopore is related to the thermal conductivity and conductance of the nanoporous membrane, the surface crystallization, the adsorption of the fluid on the nanopore wall surface, and the ion transport properties in the nanopore. Therefore, how to effectively control the size of the nanopore, has great significance.
  • FIB focused ion beam
  • FEB focused electron beam
  • the present invention aims to solve at least one of the technical problems in the related art to some extent. To this end, it is an object of the present invention to provide a method for regulating the effective size of solid-state nanopores that is reversible, efficient, low-cost, non-invasive or controllable.
  • the invention provides a method of regulating the effective size of solid nanopores in a solid state nanopore system.
  • the solid-state nanopore system includes: an electrolyte solution; a semiconductor substrate on which a solid-state nanopore is disposed and placed in the electrolyte solution, the solid-state nanopore wall surface One And absorbing a second charged ion to form an electric double layer on the wall surface of the nanopore, wherein the first electric charge and the second electric charge are opposite in polarity; a voltage component, the voltage component and the The semiconductor substrate is electrically connected; the method for regulating the effective size of the solid nanopore in the solid state nanopore system comprises: applying a predetermined voltage with a different voltage value to the semiconductor substrate through the voltage component to obtain a solid nanopore of different sizes size.
  • the inventors have found that the magnitude of the predetermined voltage applied to the semiconductor substrate affects the effective size of the solid-state nanopore, and by applying a voltage component to the semiconductor substrate to apply a predetermined voltage having a different voltage value, the effective size of the solid-state nanopore can be changed accordingly. Therefore, the effective size of the solid nanopore can be regulated in real time, and the method is reversible, high-efficiency, low-cost, no damage, does not introduce foreign materials and affects the surface characteristics of the solid nanopore, and does not adversely affect the length of the solid nanopore.
  • the influence, the shape retention is good, the operation steps are simple, the time and labor are saved, and the controllability is good, and the automation and real-time regulation can be realized.
  • the solid-state nanopore effective size d d 0 -2 ⁇ D , wherein d 0 is the physical size of the solid-state nanopore, ⁇ D is the thickness of the electric double layer and satisfies the following formula:
  • I a potential of a predetermined position in the solid-state nanopore, and has a predetermined correspondence relationship with the predetermined voltage, where x is a distance between the predetermined position and a center of a circumcircle of the cross-sectional shape of the solid-state nanohole, e
  • K B is the Boltzmann constant and T is the temperature.
  • the potential of the predetermined position in the solid-state nanopore satisfies the following relationship:
  • R is the distance between the solid nanopore wall surface of the solid nanopore cross-sectional pattern and the center of the circumcircle of the cross-sectional pattern
  • ⁇ * w is the charge density of the solid nanopore wall surface
  • ⁇ f is a dielectric constant of the electrolyte solution at a position corresponding to R
  • ⁇ w is a charge density of the solid nanopore wall surface when the predetermined voltage is zero
  • ⁇ g is a dielectric of the solid nanopore wall material
  • E g is the electric field strength produced by the predetermined voltage.
  • the charge density is determined by a high precision charge meter.
  • the solid state nanoholes are in the shape of an inverted pyramid.
  • the electrolyte solution has a solubility of from 1 ⁇ mol/L to 1 mol/L and a pH of from 4.0 to 10.0.
  • the material forming the semiconductor substrate is silicon.
  • FIG. 1 shows a schematic structural view of a solid state nanopore system in accordance with an embodiment of the present invention.
  • Solid-state nanopores with superior robustness, semiconductor and microfluidic preparation compatibility, and more flexible preparation methods in DNA single-molecule sequencing, nanolithographic printing, near-field optical modulation, ion logic circuits, microfluidics, and natural
  • the simulation platform has good application prospects in the fields of water purification and desalination and degradation of organic pollutants. In actual use, different working conditions, different application requirements, different technical requirements, etc.
  • the reversible, high-efficiency, low-cost, non-invasive controllable method for measuring the effective size of nanopores is of great significance for realizing the application of solid-state nanopore sensors for molecular detection, separation, sequencing, etc., and improving sequencing accuracy.
  • the inventors found that when the solid nanopores are placed in an electrolyte solution, the wall surface will have a certain charge under certain conditions, so that it can adsorb the oppositely charged ions in the electrolyte solution to form an electric double layer on the surface. Structure, and the thickness of the electric double layer structure is related to the effective size of the solid nanopore.
  • the thickness of the electric double layer can be adjusted, the solid nanohole can be controlled reversibly, efficiently, at low cost, without damage and with good controllability.
  • the effective size the inventors further found that the thickness of the electric double layer is related to the potential of the solid nanopore, and the potential of the solid nanopore varies with the voltage of the substrate carrying the solid nanopore, thus The voltage of the substrate of the solid nanopore can easily realize the regulation of the effective size of the solid nanopore.
  • the present invention provides a method of regulating the effective size of solid nanopores in a solid state nanopore system.
  • the solid-state nanopore system includes: an electrolyte solution 4; a semiconductor substrate 3 on which a solid-state nanopore 1 is disposed and placed in the electrolyte solution 4.
  • the solid nanopore 1 wall has a first charge and adsorbs a second charged ion to form an electric double layer 2 on the nanopore wall surface, wherein the first charge and the second charge electrical property
  • the solid-state nanopore effective size d e d 0 -2 ⁇ D , wherein d 0 is the physical size of the solid-state nanopore 1 , ⁇ D is the thickness of the electric double layer 2 , and the voltage component 5,
  • the inventors have found that the magnitude of the predetermined voltage applied to the semiconductor substrate affects the effective size of the solid-state nanopore, and by applying a voltage component to the semiconductor substrate to apply a predetermined voltage having a different voltage value, the thickness of the electric double layer can be adjusted.
  • the effective size of the solid nanopore is changed accordingly, so that the effective size of the solid nanopore can be adjusted in real time, and the method is reversible, high-efficiency, low-cost, no damage, and does not introduce foreign materials to affect the surface characteristics of the solid nanopore, nor will it affect
  • the length of the solid nanopore has adverse effects, good shape retention, simple operation steps, time and labor saving, and good controllability, and can realize automation and real-time regulation.
  • the specific kind of the semiconductor substrate that can be employed according to the embodiment of the present invention is not particularly limited, and those skilled in the art can flexibly select according to actual use requirements and technical conditions.
  • the material from which the semiconductor substrate is formed is silicon. Thereby, it has good semiconductor characteristics and controllable processability, and has a wide range of use.
  • a specific method of forming solid nanoholes on a semiconductor substrate is not particularly limited, and those skilled in the art can flexibly select as needed.
  • solid state nanopores can be formed by a wet etch process.
  • a protective layer may be formed on the surface of the semiconductor substrate, and then the protective layer is patterned by a process such as photolithography, and then exposed by an etching solution such as an alkaline etching solution such as potassium hydroxide.
  • the semiconductor substrate is etched to form solid nanoholes.
  • the specific number of solid-state nanoholes is also not particularly limited, and may be one or plural, such as several, ten, tens, hundreds, or even tens of thousands.
  • the manner in which the solid-state nanopores are distributed on the semiconductor substrate is not particularly limited, may be distributed according to a predetermined rule, or may be randomly distributed.
  • a plurality of solid-states Nanopores can be distributed in an array. Therefore, it is easy to manufacture and convenient to use.
  • the specific shape of the above solid state nanopore is not particularly limited, and those skilled in the art can flexibly select according to needs.
  • the solid state nanopores may be in the shape of an inverted pyramid.
  • the effective length of the solid-state nanopore can be regarded as several atomic layer thicknesses, which solves the problem that the conventional solid-state nanopore channel is too long to cause the sequencing resolution to be difficult to reach a single Base problem.
  • the term "physical size of solid state nanoholes” as used herein refers to the minimum distance between two opposing solid nanohole walls on a longitudinal section of a semiconductor substrate for solid shaped nanoholes of different shapes. "Effective size of solid state nanopores” refers to the minimum distance between two opposing electrical double layers on a longitudinal section of a semiconductor substrate.
  • the type of charge carried on the wall surface of the solid nanopore is not particularly limited, and may be a positive charge or a negative charge.
  • the solid nanopore wall surface is adsorbed and charged.
  • the oppositely charged ions form an electric double layer, that is, the positive charge on the wall surface of the solid nanopore adsorbs the anion to form an electric double layer, and the negative charge on the wall surface of the solid nanopore adsorbs the cation to form an electric double layer.
  • the solid nanopore wall has a certain degree of negative charge, and a small amount of cation is adsorbed in the electrolyte solution to form an electric double layer structure on the inner wall.
  • the effective size of the solid nanopore is related to the thickness of the electric double layer. After the solid nanohole having a certain physical size is formed on the semiconductor substrate, if the thickness of the electric double layer can be adjusted, the solid nanometer can be realized. Regulation of the effective size of the well. According to an embodiment of the invention, ⁇ D satisfies the following formula:
  • K B is the Boltzmann constant
  • T is the temperature. Therefore, based on the predetermined correspondence relationship and the above formula, the size of the ⁇ D can be controlled by controlling the magnitude of the predetermined voltage, thereby realizing the regulation of the effective size of the solid nanopore, and changing the effective size of the solid nanopore by using an electrical method,
  • the predetermined correspondence between the potential of the predetermined position in the solid-state nanopore and the predetermined voltage may be determined by applying a series of predetermined voltages having different voltage values to the semiconductor substrate through the voltage component, respectively detecting different voltage values The potential of the predetermined position in the corresponding solid state nanopore.
  • the correspondence between the potential of the predetermined position in the solid-state nanopore and the predetermined voltage within a certain range can be determined, thereby enabling regulation
  • the magnitude of the voltage of the predetermined voltage regulates the effective size of the solid nanopore.
  • the specific number of predetermined voltages having different voltage values is not particularly limited, and those skilled in the art can flexibly select according to actual needs.
  • the predetermined voltage and the potential of the predetermined position in the solid nanopore may be in a curved relationship or the like, and those skilled in the art may determine different potentials of the predetermined voltage according to the requirements of different correlations, and then prepare a comparison table or pass Algorithms such as simulation and fitting determine the correspondence between the two.
  • the potential of the predetermined position in the solid-state nanopore satisfies the following relationship:
  • R is the distance between the solid nanopore wall surface of the solid nanopore cross-sectional pattern and the center of the circumcircle of the cross-sectional pattern
  • ⁇ * w is the charge density of the solid nanopore wall surface
  • ⁇ f is the position corresponding to R (ie, in the solid-state nanopore cross-sectional pattern, at the solid nanopore wall surface at a distance R from the center of the circumcircle of the cross-sectional pattern)
  • the dielectric constant of the electrolyte solution ⁇ w is a charge density of the solid nanopore wall surface when the predetermined voltage is zero
  • ⁇ g is a dielectric constant of the solid nanopore wall material
  • E g is an electric field intensity generated by the predetermined voltage.
  • the specific method of determining the charge density in the above steps is not particularly limited, and those skilled in the art can flexibly select as long as it can be accurately measured.
  • the charge density of the solid nanopore wall surface can be determined by a high precision charge meter. Thereby, the device is simple, the operation is easy, the accuracy is high, and the cost is low.
  • the electrolyte solution that can be employed according to an embodiment of the present invention is not particularly limited. Those skilled in the art can flexibly choose according to needs.
  • the electrolyte solution has a solubility of from 1 ⁇ mol/L to 1 mol/L and a pH of from 4.0 to 10.0.
  • the electrolyte solution may be a KCl, NaCl or LiCl solution.
  • the raw materials are widely available, easy to obtain, low in cost, and safe.
  • the thickness of the electric double layer is not only affected by the potential of the solid nanopore, but also with the parameters of the electrolyte solution, such as various ion concentrations inside the electrolyte solution n i 0 (ion in unit volume) The number) is related to the valence Z i .
  • the above method of the present invention is applicable to the case of a specific electrolyte.
  • a correspondence between a predetermined voltage and a potential at a predetermined position in the solid nanopore can be determined in combination with a conventional test means or a calculation method, thereby determining between the predetermined voltage and the thickness of the electric double layer.
  • the relationship, so that the thickness of the electric double layer can be controlled by controlling the predetermined voltage, and the effective size of the solid nanopore can be controlled.

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Abstract

L'invention concerne un procédé de réglage d'une taille efficace d'un nanopore à l'état solide (1) dans un système à nanopores à l'état solide. Le système à nanopores à l'état solide comprend une solution électrolytique (4), un substrat semi-conducteur (3), et un ensemble à tension (5). Le substrat semi-conducteur (3) est pourvu des nanopores à l'état solide (1), et est disposé dans la solution électrolytique (4), des icônes sont adsorbées sur des surfaces de paroi des nanopores à l'état solide (1) pour former une double couche électrique (2), et l'ensemble à tension (5) est électriquement connecté au substrat semi-conducteur (3). Le procédé consiste à : appliquer des tensions préétablies de différentes valeurs de tension sur un substrat semi-conducteur (3) au moyen d'un ensemble à tension (5), de manière à obtenir des tailles efficaces de nanopores à l'état solide (1) de différentes tailles. Le procédé peut être réversible, a un rendement élevé et de faibles coûts, ne produit aucun dommage, n'affecte pas les caractéristiques de surface des nanopores à l'état solide (1) en raison de l'introduction d'un matériau étranger, et n'a pas d'effet négatif sur les longueurs des nanopores à l'état solide (1) et similaire, et la rétention de forme des nanopores à l'état solide (1) est bonne; et le procédé présente des étapes de fonctionnement simples, économise du temps et du travail et présente une bonne aptitude à la commande, et le réglage peut être mis en œuvre automatiquement en temps réel.
PCT/CN2017/114642 2017-12-05 2017-12-05 Procédé de réglage de la taille effective d'un nanopore à l'état solide dans un système à nanopores à l'état solide Ceased WO2019109253A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005105272A1 (fr) * 2004-04-20 2005-11-10 The Regents Of The University Of California Membranes intelligentes pour l'elimination des nitrates, l'epuration de l'eau et le transport ionique selectif
CN201917552U (zh) * 2010-12-22 2011-08-03 东南大学 一种基于玻璃微管的单纳米孔传感器
CN102687028A (zh) * 2009-10-28 2012-09-19 国际商业机器公司 用于脱盐的表面电荷激活的纳米多孔半渗透隔膜
CN104411386A (zh) * 2012-05-07 2015-03-11 渥太华大学 用于控制固态纳米孔的大小的方法
CN105573359A (zh) * 2015-12-10 2016-05-11 南京理工大学 施加压力控制纳米孔中离子传输选择度的方法
CN106570297A (zh) * 2016-11-15 2017-04-19 南京理工大学 一种带pH可调电解质层的锥形纳米孔离子整流研究方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005105272A1 (fr) * 2004-04-20 2005-11-10 The Regents Of The University Of California Membranes intelligentes pour l'elimination des nitrates, l'epuration de l'eau et le transport ionique selectif
CN102687028A (zh) * 2009-10-28 2012-09-19 国际商业机器公司 用于脱盐的表面电荷激活的纳米多孔半渗透隔膜
CN201917552U (zh) * 2010-12-22 2011-08-03 东南大学 一种基于玻璃微管的单纳米孔传感器
CN104411386A (zh) * 2012-05-07 2015-03-11 渥太华大学 用于控制固态纳米孔的大小的方法
CN105573359A (zh) * 2015-12-10 2016-05-11 南京理工大学 施加压力控制纳米孔中离子传输选择度的方法
CN106570297A (zh) * 2016-11-15 2017-04-19 南京理工大学 一种带pH可调电解质层的锥形纳米孔离子整流研究方法

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