WO2019109254A1 - Procédé de préparation de nanopore et ses utilisations ainsi que réseau - Google Patents

Procédé de préparation de nanopore et ses utilisations ainsi que réseau Download PDF

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Publication number
WO2019109254A1
WO2019109254A1 PCT/CN2017/114643 CN2017114643W WO2019109254A1 WO 2019109254 A1 WO2019109254 A1 WO 2019109254A1 CN 2017114643 W CN2017114643 W CN 2017114643W WO 2019109254 A1 WO2019109254 A1 WO 2019109254A1
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Prior art keywords
nanopore
window
layer
cavity
substrate
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PCT/CN2017/114643
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English (en)
Chinese (zh)
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刘泽文
王一凡
陈琦
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清华大学
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Priority to PCT/CN2017/114643 priority Critical patent/WO2019109254A1/fr
Publication of WO2019109254A1 publication Critical patent/WO2019109254A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B1/00—Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures

Definitions

  • the invention relates to the field of silicon-based three-dimensional processing technology, in particular to a preparation method and application of a nanopore and an array, in particular to a controllable silicon-based nanopore suitable for a biomacromolecule detection platform, a near-field optical and an atomic lithography grating. Production and feedback methods.
  • Biomacromolecule sequencing is one of the core technologies of modern life science research technology.
  • the pore size of the solid nanopores can be flexibly controlled by humans, and has ideal biochemical pore stability, excellent physical and chemical properties.
  • FIB focused ion beam technology
  • researchers have successfully produced a variety of nanometer, sub-nanometer solid pores with controlled pore size.
  • the fabrication of solid-state nanopores also faces some problems. Firstly, the solid-state nanopore shape made by FIB has poor controllability and the channel is usually cylindrical. The effective length depends on the thickness of the film. The robustness and spatial resolution cannot be optimized at the same time.
  • all nanopore-based sequencing methods are used. There is currently no effective method for controlling the rate at which biomolecules pass through the nanopore, due to the too fast perforation rate and low temporal resolution.
  • the present invention aims to solve at least one of the technical problems in the related art to some extent. It is an object of the present invention to provide a method for preparing nanopores which can achieve sub-nanometer precision and precise precision controllability.
  • a method for preparing a nanopore comprising the steps of: (1) forming a first masking layer and a second masking layer on a front side and a back side of the substrate, respectively; (2) The first masking layer and the second masking layer are separately patterned to form a front nanopore window and a front reference window on the first masking layer, and a back window on the second masking layer; the back window Corresponding to the frontal nanopore window and the front reference window, the front reference window has a size larger than the front nanopore window by 200 nm to 2 ⁇ m; (3) the frontal nanopore window and the front reference The substrate corresponding to the window is subjected to a first etching to form a front reference cavity and a front nanopore cavity; (4) a tracer gas is disposed in the front nanopore cavity, and is closed; (5) corresponding to the back window Performing a second etching on the substrate while detecting whether the tracer gas is present in the working environment,
  • a square aspect ratio
  • a rectangle aspect ratio ⁇ 10:1
  • a slit length and width Ratio >10:1
  • polygons number of sides n>4
  • the front side nanopore window is indicated by the front reference window, and the height of the front side reference cavity and the front side nanopore cavity formed can be ensured after etching, and the formation of such a structure can ensure that the front nanopore cavity tip is not thinned. It is etched to ensure that it is less than 1.5 ⁇ m from the bottom surface after thinning, which reduces the etching time of the atomic layer etching stage and improves the preparation efficiency. Then, using atomic layer etching, etching a layer of silicon atoms in each cycle, precision control can be achieved, and high-precision tracer gas atom detection equipment can be used to perform high-precision monitoring of nanopore opening events, and nanometers can be realized. The pore size control of the pores is increased to the sub-nanometer precision level.
  • the method for preparing the nanopore may further include the following additional technical features:
  • the front reference window in step (2) is spaced apart from the front nanopore window.
  • the front reference window and the front nanopore window are spaced apart to facilitate the use of the front reference cavity formed by the front reference window to monitor the height of the front nanopore cavity formed by the front nanopore window, thereby facilitating the indication of the formation of the nanopore.
  • step (3) between step (3) and step (4), further comprising (6): thinning the substrate corresponding to the back window to form a thinned surface, to the front reference The aperture is closest to the thinned surface to form a front reference aperture opening through the substrate.
  • the color feedback method is used in step (6) to monitor that the thinned surface is closest to the front reference aperture cavity to form a front reference aperture opening through the substrate.
  • the distance between the thinned surface and the front surface nanopore cavity is less than 1.5 ⁇ m, preferably 140 nm. 1.4 ⁇ m.
  • the second etching is an atomic layer etching, and the trace gas in the working environment is once detected every time one layer of atoms is etched.
  • Atomic layer etching ensures that each cycle of etching removes an atomic layer of etched material. This further ensures the control of the preparation accuracy of the nanopore. Other etchings have no way to achieve this effect.
  • the etching process is a cyclic process, the environment between each cycle is more favorable for the capture and detection of the tracer gas.
  • the substrate is a double throw silicon wafer, preferably a (100) crystal orientation silicon wafer, and the front side nanopore chamber and the front side reference aperture cavity are inverted quadrangular pyramid cavities.
  • the first masking layer and the second masking layer respectively comprise a silicon dioxide layer and a silicon nitride layer
  • the silicon dioxide layer is on the substrate
  • the silicon nitride A layer is on the silicon dioxide layer.
  • the first etching and the thinning treatment are performed by anisotropic wet etching.
  • an anisotropic wet etching is performed using an alkaline solution which is an alkali metal hydroxide or quaternary ammonium salt.
  • Anisotropic etching means that the etching rate of the etchant in a certain direction is much larger than other directions, and the silicon wafer is etched by using an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide or a quaternary ammonium salt. You can get the structure of different graphics.
  • the tracer gas is enclosed in the frontal nanopore chamber using a PDMS/glass cavity structure in step (4) and then fixed.
  • the fixation is carried out using a device that can withstand a gas pressure of at least 0.1 MPa, the device being selected from one of an oxygen plasma surface treatment device, a bonding device or a clamp aid.
  • the device used for fixing can guarantee a gas pressure of at least 0.1 MPa, which can ensure that the tracer gas atoms do not leak, so that precise monitoring can be achieved.
  • the clamping force on the chip is at least greater than 2 Kg, and the application force needs to be uniform to avoid damage to the chip due to uneven force.
  • fixing by other means such as an oxygen plasma surface treatment apparatus or other bonding means, it is sufficient that the tracer gas atoms are not leaked, so that precise monitoring can be performed.
  • the invention provides a nanopore array.
  • the nanopore arrays are arranged according to a certain rule; the nanopores are prepared by the preparation method described above.
  • the nanopores can be arranged in different ways to form different nanopore arrays, which can be applied in the fields of biomacromolecule detection, near-field optics and/or atomic lithography gratings.
  • a device comprising a nanopore comprising the following structure:
  • the front side and the back side of the substrate layer are a first masking layer and a second masking layer, respectively.
  • the first masking layer is provided with a front reference window and a front nanohole window, and the size of the front reference window is larger than the size of the front nanohole window by 200 nm to 2 ⁇ m;
  • the front reference window and the front nanopore window extend toward the substrate layer to form a front reference cavity and a front nanopore cavity;
  • the second masking layer is provided with a back window, and the back window is disposed corresponding to the front reference window and the front nanohole window, and the back window extends toward the substrate layer to form a back cavity;
  • the back cavity is corresponding to the front reference cavity, and forms a front reference cavity opening;
  • the back cavity corresponds to the front nanopore window as a nanopore.
  • the nanopore of the present invention may further include the following technical features:
  • the first masking layer and the second masking layer each comprise a silicon dioxide layer and a silicon nitride layer.
  • the silicon dioxide layer is on the substrate layer, and the silicon nitride layer is on the silicon dioxide layer.
  • the nanopore is prepared by the preparation method described above.
  • the invention provides the use of the nanopore array described above and the device described above in the field of biomacromolecule detection, near-field optics and/or atomic lithography gratings.
  • the invention has the beneficial effects that the invention utilizes a high-precision tracer gas atom detecting device to perform high-precision monitoring on the nanopore opening event, and can realize the aperture control of the nanopore to be improved to the sub-nanometer precision level, thereby Sub-nano-precision silicon-based nanopores are used in the field of biomacromolecular detection to improve the precision of detection.
  • the substrate is precisely etched by atomic layer etching (ALE), and a layer of silicon atoms is etched in each cycle, so that precision precision can be controlled.
  • ALE atomic layer etching
  • FIG. 1 is a flow diagram of the preparation of a nanopore in accordance with one embodiment of the present invention.
  • FIG. 2 is a schematic illustration of the height of the front side reference inverted quadrangular pyramid cavity and the front side nanopore inverted quadrangular pyramid cavity and the dimensions of the front side reference window and the front side nanopore window and the angle formed by the crystal face formed in accordance with one embodiment of the present invention.
  • FIG 3 is a cross-section of a clamping device that encapsulates a tracer gas structure in accordance with one embodiment of the present invention.
  • the invention provides a preparation method of nano pores, comprising the following steps:
  • the surface of the front reference window is 200 nm to 2 ⁇ m larger than the front nanopore window; (3) performing first etching on the substrate corresponding to the front nanopore window and the front reference window Forming a front reference hole cavity and a front surface nanopore cavity; (4) providing a tracer gas in the front surface nanopore cavity to be closed; and (5) performing a second etching on the substrate corresponding to the back surface window And simultaneously detecting whether the tracer gas exists in the working environment, and stopping the etching when detecting the presence of the tracer gas in the working environment to form the nanopore.
  • the tracer gas selected in the present invention may be helium, nitrogen, argon or the like, which is chemically stable and has atomic radii of 130, 160 and 192 pm.
  • the size of the front reference window and the size of the front nanopore mentioned in the present invention may be any corresponding shape, and may be square, circular, or rectangular.
  • the size of the present invention is the diameter or side length of the corresponding figure. As long as the size of the front reference window is larger than the size of the front nanopore window by 200 nm to 2 ⁇ m.
  • the wet etching forms nanopores. Due to the collapse structure and rectification characteristics, it is expected to fundamentally solve the problem of robustness and poor spatial and temporal resolution of nanopores.
  • the existing three-step all-wet etching combined with the dry-wet method for preparing nanopores is very difficult to realize for nanopores, especially single nanopores, and it is difficult to achieve precise control of sub-nanometer resolution of nanopores.
  • the inventors conducted in-depth research, and found that the precision of the nanopore preparation process can be achieved by setting a front reference window on the surface of the silicon substrate. Specifically, first, wet etching is used.
  • the front reference cavity and the front nanopore cavity are realized on the front surface of the double-throw (100) silicon wafer, and the single-sided rapid thinning is performed by wet etching on the back surface of the silicon wafer; when the back surface is thinned to form the front reference cavity
  • the polydimethylsiloxane (PDMS)/glass cavity structure is aligned with the front side of the silicon wafer in a tracer gas atmosphere, and reversible assembly is performed by oxygen plasma surface treatment, bonding or fixture assisting.
  • the gas is encapsulated into the cavity; the back side of the silicon wafer is precisely etched by atomic layer etching (ALE), and after the end of each etching cycle, the presence of the tracer gas atom is performed in a vacuum environment using an internal detection instrument of the etching apparatus. Detection, when the presence of tracer gas atoms is detected, indicates the formation of the desired nanopore.
  • ALE atomic layer etching
  • the present invention provides a method for preparing a silicon-based nanopore, comprising the following steps:
  • the front reference window formed in the step (2) is 200 nm to 2 ⁇ m larger than the front nanopore window, and the formed front reference inverted quadrangular pyramid cavity and the front surface nanopore inverted quadrangular pyramid can be ensured after etching.
  • the height of the cavity is different, and the formation of such a structure can ensure that the front nanopore quadrangular pyramid tip is not over-etched when thinning, and can be ensured to be less than 1.5 ⁇ m from the bottom surface after thinning, preferably 140 nm to 1.4 ⁇ m. Therefore, the etching time of the atomic layer etching stage is reduced, and the preparation efficiency is improved.
  • the step (6) uses an atomic layer etching to etch a layer of silicon atoms per cycle, thereby achieving precise precision control, and using high precision display Trace gas atom detection equipment, high-precision monitoring of nanopore opening events, can achieve nanopore aperture control to sub-nanometer accuracy level.
  • the nanopore can not directly observe the opening event of the nanopore, so it will affect the pore size of the nanopore.
  • the tracer gas detection combined with the atomic layer etching can ensure the opening of the nanopore during the etching process. Accurate monitoring of events.
  • the tracer gas atoms of different diameters are selected to meet the requirements of the pore size of different nanopores, and the nanopore aperture is accurately controlled.
  • FIG. 1 includes the following steps:
  • the silicon nitride layer 3 and the silicon dioxide layer 2 are patterned, and a front reference window 4 and a front nanopore window 5 are formed on the front side, respectively, and formed on the back surface.
  • a back window 8 wherein the front reference window 4 has a size larger than the front nanopore window 5 by 200 nm to 2 ⁇ m;
  • the back window by an anisotropic wet etching method using an alkaline etching solution, and placing phenolphthalein in the solution of the inverted quadrangular pyramid cavity, and thinning the back surface of the silicon to the back cavity 15
  • the thinning etching solution diffuses into the reference inverted quadrangular pyramid cavity to contact with the phenolphthalein, the solution turns red, and the etching is stopped.
  • the front nanopore inverted quadrangular pyramid cavity 7 is less than 1.5 ⁇ m from the thinned surface, preferably It is 140 nm to 1.4 ⁇ m;
  • the PDMS / glass cavity structure 9 and the frontal nanopore inverted quadrangular pyramid cavity are aligned and fixed, so that the front nanopore inverted quadrangular pyramid cavity is filled with atmospheric pressure tracer gas 10;
  • the difference between the internal and external pressure of the PDMS/glass cavity 9 causes the tracer gas atoms in the cavity to overflow from the nanopore, and the tracer gas atom detector can detect the presence of the tracer gas atoms;
  • the PDMS/glass cavity 9 is removed to obtain a silicon-based nanopore 11 having sub-nanometer precision controllability.
  • the double throwing silicon wafer in the above method for preparing a silicon-based nanopore, is a (100) double polished wafer, and the double throwing silicon wafer has a thickness of 300 to 700 ⁇ m.
  • the thickness of the silicon nitride layer is The thickness of the silicon dioxide layer is The silica can be grown by thermal oxidation, and the silicon nitride layer is deposited by low pressure ski vapor deposition (LPCVE) to form a silicon nitride layer having a thickness of
  • the thickness of the silicon nitride layer is The thickness of the silicon dioxide layer is The silicon oxide layer can be grown by thermal oxidation using a plasma enhanced chemical vapor deposition (PECVD) silicon nitride layer to form a silicon nitride layer having a thickness of PECVD PECVD PECVD PECVD PECVD PECVD PECVD PECVD PECVD silicon nitride layer to form a silicon nitride layer having a thickness of PECVD
  • the etching solution is a KOH solution
  • the etching temperature is 80° C.
  • the precision is controlled at ⁇ 1° C.
  • the IPA is isopropyl. alcohol.
  • reversible assembly may be performed using an apparatus such as oxygen plasma surface treatment, bonding or jig assist to fix the structure.
  • a Teflon holder 12 is used for attachment, wherein Figure 3 is a cross-sectional view of a clamping device enclosing a tracer gas structure, 13 being a screw and 14 being a nut .
  • the screw 13 is fixed to the nut 14 when it is fixed, and the screw 13 is removed from the nut 14 when it is removed.
  • the schematic diagram of the device containing the nanopore prepared by the above preparation method is shown in Fig. 1 (7).
  • the device can be used as a detection of biological macromolecules.

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  • Engineering & Computer Science (AREA)
  • Nanotechnology (AREA)
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Abstract

L'invention concerne un procédé de préparation d'un nanopore et ses utilisations. Dans le nanopore, une structure de nanopore est mise en œuvre sur une surface d'un substrat au moyen d'une gravure, et l'autre surface du substrat est gravée pour réduire l'épaisseur. Lorsqu'un événement d'ouverture d'un pore de référence se produit en raison de la réduction d'épaisseur, un gaz traceur (10) est enfermé dans une cavité. Une gravure de couche atomique est appliquée à l'autre surface du substrat, et l'existence du gaz traceur (10) est détectée simultanément ; et lorsque des atomes du gaz traceur (10) sont détectés, cela indique que l'événement d'ouverture se produit, et la gravure est arrêtée de façon à obtenir un nanopore.
PCT/CN2017/114643 2017-12-05 2017-12-05 Procédé de préparation de nanopore et ses utilisations ainsi que réseau WO2019109254A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1807224A (zh) * 2005-12-27 2006-07-26 北京大学 Si基膜纳米孔道及其制备方法
CN102290332A (zh) * 2011-09-30 2011-12-21 复旦大学 一种制备高密度硅纳米孔阵列的方法
US8535544B2 (en) * 2010-07-26 2013-09-17 International Business Machines Corporation Structure and method to form nanopore
CN103449355A (zh) * 2012-05-31 2013-12-18 中国科学院微电子研究所 纳米孔阵列的制作方法
CN103820311A (zh) * 2014-02-26 2014-05-28 清华大学 用于单分子测序的纳米孔装置及其使用方法、制作方法
CN106916737A (zh) * 2017-03-28 2017-07-04 王哲 一种纳米孔单分子传感器以及制造纳米孔阵列的方法
WO2017184790A1 (fr) * 2016-04-19 2017-10-26 Takulapalli Bharath Capteur de nanopores, structure et dispositif comprenant le capteur, et procédés de formation et d'utilisation correspondants

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1807224A (zh) * 2005-12-27 2006-07-26 北京大学 Si基膜纳米孔道及其制备方法
US8535544B2 (en) * 2010-07-26 2013-09-17 International Business Machines Corporation Structure and method to form nanopore
CN102290332A (zh) * 2011-09-30 2011-12-21 复旦大学 一种制备高密度硅纳米孔阵列的方法
CN103449355A (zh) * 2012-05-31 2013-12-18 中国科学院微电子研究所 纳米孔阵列的制作方法
CN103820311A (zh) * 2014-02-26 2014-05-28 清华大学 用于单分子测序的纳米孔装置及其使用方法、制作方法
WO2017184790A1 (fr) * 2016-04-19 2017-10-26 Takulapalli Bharath Capteur de nanopores, structure et dispositif comprenant le capteur, et procédés de formation et d'utilisation correspondants
CN106916737A (zh) * 2017-03-28 2017-07-04 王哲 一种纳米孔单分子传感器以及制造纳米孔阵列的方法

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