KR101666725B1 - Nanopore device and method of manufacturing the same - Google Patents
Nanopore device and method of manufacturing the same Download PDFInfo
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- KR101666725B1 KR101666725B1 KR1020140183043A KR20140183043A KR101666725B1 KR 101666725 B1 KR101666725 B1 KR 101666725B1 KR 1020140183043 A KR1020140183043 A KR 1020140183043A KR 20140183043 A KR20140183043 A KR 20140183043A KR 101666725 B1 KR101666725 B1 KR 101666725B1
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Abstract
The nanopore element includes a nanopore structure having a nanopore having an inlet and an outlet, and an inlet and an outlet, the end being exposed to the inside of the nanopore, And a pair of first and second electrodes provided to measure a current flowing to the first electrode.
Description
The present invention relates to a nano-pore device and a method of manufacturing the same, and more particularly, to a nano-pore device capable of analyzing a nano-sized substance such as DNA and a method of manufacturing the nano-pore device.
The nanopore device has the characteristic of controlling very small amount of ion transport and analyzing the substances passing through the nanopore. Therefore, in recent years, the nanopore device has been actively studied.
For example, since a nanopore device has a structure similar to an ion channel of a living organism, a base such as A, G, T, or C included in DNA-like materials passing through a nanopore formed on the nanopore device Sequencing is underway. When a material such as the DNA passes through the nanopore, there is an energy barrier due to electrostatic interaction or geometric limitation. Therefore, the DNA can pass through the energy barrier. Thus, the DNA passing through the nanopore can block the flow of current due to the movement of ions flowing along the inside of the pore. As a result, a relatively low potential difference occurs when the DNA passes through compared to the potential at the time when only normal ions pass, so that the current is reduced. Research on the sequencing of the DNA using the size of the blocking current is under way, which is called a blocking current.
In addition, research is underway to analyze nanomaterials, such as microRNAs, nanowires, and nanoscale polymers, that are smaller than the size of nanopores, as well as DNA.
However, the pair of electrodes included in the nanopore device are generally located in a storage container in which an object such as DNA is stored. In this case, disturbances such as the movement of other materials or ions except the subject existing between the two electrodes occur. The accuracy of the inspection may deteriorate due to the influence of the disturbance.
Further, cloaking may occur at the entrance or exit of the nanopore, so that the entrance of the nanopore is closed and slowly opened again to cause the subject to move into the nanopore. As a result, it is difficult to precisely confirm the movement of the object, and it is difficult to detect a signal due to the flow of the object within the nanopore.
In addition, since the thickness of nanopore is too thick to analyze the nucleotide sequence of existing DNA, it is very difficult to precisely measure the change of blocking current according to the change of salt period interval.
SUMMARY OF THE INVENTION An object of the present invention is to provide a nanopore device capable of accurately measuring a blocking current generated between an inlet and an outlet of a nanopore.
An object of the present invention is to provide a method of manufacturing the nanopore device.
A nanopore element according to an embodiment of the present invention includes a nanopore structure having a nanopore having an inlet and an outlet to allow an object to be inspected to pass therethrough and the nanopore structure being spaced apart from each other between the inlet and the outlet, And a pair of first and second electrodes provided to measure a current flowing into the nanopore.
In one embodiment of the present invention, the nanopore has a size of 100 nm or less and a length of 10,000 nm or less.
In one embodiment of the present invention, the first and second electrodes each of gold, silver, metal, and yes, such as palladium, platinum, hafnium, copper pins, graphite, the reduced graphene, h-BN, WS 2, And MOS 2 , as shown in FIG.
In one embodiment of the present invention, each of the first and second electrodes may have a donut shape so as to penetrate the nanopore structure in a horizontal direction.
In an embodiment of the present invention, the first and second electrodes may be spaced apart from each other by an insulating layer formed in the vertical direction of the nanopore, and may be formed so as not to overlap each other when viewed in plan.
In an embodiment of the present invention, the first and second electrodes may be spaced apart from each other by an insulating layer formed in a vertical direction of the nanopore, and may be formed to face each other with respect to the nanopore.
Here, the insulating layer may have a gap of 5 nm or less between the first and second electrodes so that a tunneling current may be generated between the first and second electrodes.
The nanopore device according to an embodiment of the present invention may further include a third electrode disposed between the first and second electrodes and configured to control the flow of the inspected object flowing in the nanopore. Here, the third electrode may have an exposed portion exposed in the nanopore at one end thereof, and the exposed portion may be coated with a dielectric material.
In the method of manufacturing a nanopore device according to an embodiment of the present invention, a nanopore structure having a nanopore formed through an inlet and an outlet may be formed so that an object can pass therethrough, The ends of the first and second electrodes are exposed to the inside of the nanopore, and a pair of first electrodes and second electrodes are formed to apply a voltage to the nanopore and measure a current.
In the method of manufacturing a nano-pore device according to an embodiment of the present invention, a pore layer is formed on a substrate, a first electrode layer made of a planar structure is formed on the pore layer, To form a first preliminary pore structure. An interlayer insulating layer is formed on the first electrode layer, and a second electrode layer made of a planar structure is formed on the interlayer insulating layer. Thereafter, an insulating film is formed on the second electrode layer, and the insulating film, the second electrode layer, the interlayer insulating film, the first electrode layer, and the pore layer are sequentially etched to have an inlet and an outlet A nanopore structure in which a nanopore is formed, a first electrode, and a second electrode are formed.
In one embodiment of the present invention, a step of partially etching the substrate to form a first opening at a position corresponding to the nanopore may be performed before forming an interlayer insulating film on the first electrode layer .
In the method of manufacturing a nanopore device according to an embodiment of the present invention, a storage container may be additionally attached so that the inlet is exposed on an insulating film pattern formed by the insulating film.
A method of fabricating a nanopore device according to an embodiment of the present invention includes the steps of: a) forming a first pore layer on a first substrate; b) forming a first electrode layer of a planar structure on the first pore layer Thereby forming a first preliminary pore structure including the first pore layer and the first electrode layer. c) forming an interlayer insulating film on the first electrode layer, and d) preparing a second preliminary pore structure in which the second substrate, the second pillar layer, and the second electrode layer are sequentially formed by using the steps a) to b) . e) placing the second preliminary pore structure on the interlayer insulating film so as to face the first preliminary pore structure, and f) attaching the interlayer insulating film and the second electrode layer. Thereafter, e) etching the second forayer layer, the second electrode layer, the interlayer insulating layer, the first electrode layer, and the first forayer layer sequentially to form a nano-pore structure having an nano-pore having an inlet port and an outlet port, A pore structure, a first electrode, and a second electrode are formed.
In the method of manufacturing a nanopore device according to an embodiment of the present invention, the step f) may include performing one of an anodic bonding process, a plasma bonding process, and a microwave bonding process.
In one embodiment of the present invention, the first substrate may be partially etched to form a first opening at a position corresponding to the nanopore before forming the interlayer insulating film on the first electrode layer, After forming the second electrode layer, the second substrate may be partially etched to form a second opening at a position corresponding to the nanopore.
According to the nano-pore device of the present invention, at least two electrodes formed to be spaced apart from each other between an inlet and an outlet of a nanopore. Therefore, it is possible to measure with improved resolution and reduced noise for ions or nanomaterials passing through the nanopore.
Furthermore, it is possible to analyze an object passing through various measurement signals more effectively. Therefore, the nanopore device can be utilized not only for sequencing DNA and microRNA, but also for analyzing various nanomaterials.
1 is a cross-sectional view illustrating a nanopore device according to an embodiment of the present invention.
2A and 2B are respectively a cross-sectional view and a plan view illustrating a nanopore device according to an embodiment of the present invention.
3 is a cross-sectional view illustrating a nanopore device according to an embodiment of the present invention.
4A to 4H are cross-sectional views illustrating a method of manufacturing a nanopore device according to the present invention.
5A to 5C are cross-sectional views illustrating a method of manufacturing a nanopore device according to the present invention.
Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. The present invention is capable of various modifications and various forms, and specific embodiments are illustrated in the drawings and described in detail in the text. It should be understood, however, that the invention is not intended to be limited to the particular forms disclosed, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. In the accompanying drawings, the sizes and the quantities of objects are shown enlarged or reduced from the actual size for the sake of clarity of the present invention.
The terms first, second, etc. may be used to describe various components, but the components should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component.
The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In the present application, the terms "comprise", "comprising", and the like are intended to specify that there is a feature, step, function, element, or combination of features disclosed in the specification, Quot; or " an " or < / RTI > combinations thereof.
Here, the interlayer distance corresponds to the channel and is defined as an interval therebetween that does not include the thickness of the single layer. However, for layered materials of atomic thicknesses that are difficult to accurately measure, the thickness of some single layers may be included in the interlayer spacing.
On the other hand, unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.
Nanopore element
1 is a cross-sectional view illustrating a nanopore device according to an embodiment of the present invention.
Referring to FIG. 1, a
The
The
The
The
As compared with the case where the first and second electrodes are disposed in a reservoir that exists outside the
A pair of first and
In one embodiment of the present invention, each of the first and
In one embodiment of the present invention, each of the first and
Alternatively, a material having excellent electric conductivity such as silicon doped with a metal element is sufficient. Furthermore, a modified two-dimensional planar material doped with an element such as boron (B) or nitrogen may be used for the two-dimensional planar material, and the element that can be doped is not particularly limited. In addition, as a composite of nanomaterials, electrodes such as graphene coated with gold nanoparticles or electrodes composed of a double layer of Cr / Au can be used.
In one embodiment of the present invention, each of the first and
In an embodiment of the present invention, the ends of the first and
2A and 2B are respectively a cross-sectional view and a plan view illustrating a nanopore device according to an embodiment of the present invention.
2A, a
The
In this case, when the insulating film formed between the first and
Referring to FIG. 2A again, the first and
Referring to FIG. 2B, the first and
When the nanomaterial passes between the first and
At this time, the first and
3 is a cross-sectional view illustrating a nanopore device according to an embodiment of the present invention.
A nanopore device according to an embodiment of the present invention includes a
The voltage applied to the
The
In an embodiment of the present invention, each end of the
Manufacturing method of nanopore device
4A to 4H are cross-sectional views illustrating a method of manufacturing a nanopore device according to the present invention.
Referring to FIG. 4A, a
Referring to FIG. 4B, the
Referring to FIG. 4C, a
The first electrode layer may be formed of a metal such as gold, silver, copper, a metal compound such as AgCl or a carbon nanomaterial such as graphene or reduced graphene, and a composite thereof or a two-dimensional plane such as MoS 2 , WS 2 , Materials and complexes thereof. Meanwhile, the first electrode layer may include an electrochemically stable material in which an electrochemical reaction is inhibited with respect to an analyte ion.
For example, to form the
Referring to FIG. 4D, an
Referring to FIG. 4E, a
The
For example, in order to form the
In one embodiment of the present invention, each of the first and second electrode layers 115 and 125 may be patterned to have a predetermined shape (see FIGS. 2A and 2B). A photolithography process, an e-beam lithography process, a focused ion beam (FIB) process, or a nanoimprint process may be used to pattern the first and second electrode layers 115 and 125, respectively. . Thereby forming each of the first and second electrodes.
Referring to FIG. 4F, an insulating
Referring to FIG. 4G, the insulating
As compared with the case where the first and second electrodes are disposed in a reservoir existing outside the nanopore and accommodating the object, the
A pair of first and
In an embodiment of the present invention, the
5A to 5C are cross-sectional views illustrating a method of manufacturing a nanopore device according to the present invention.
5A, a
The second
Then, the second
Referring to FIG. 5B, the
5C, the
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. Will be clear to those who have knowledge of.
10: Nano-pore device 100: Nano-pore structure
101: inlet 103: outlet
105: Nano Pore 110: Substrate
113: forer layer 115: first electrode layer
117: first preliminary pore structure 120: interlayer insulating film
125: second electrode layer 140: insulating film
210: first electrode 220: second electrode
230: third electrode 310: first container
320: second container
Claims (18)
And a pair of first electrodes and a second electrode which are spaced apart from each other between the inlet and the outlet and whose ends are exposed to the interior of the nanopore and are capable of measuring a current flowing into the nanopore,
Wherein the first and second electrodes are formed so as not to overlap each other when viewed from a plan view.
Wherein the nanopore has a size of 100 nm or less and a length of 10,000 nm or less.
Forming a pair of first and second electrodes spaced apart from each other between the inlet and the outlet and having an end exposed to the inside of the nanopore and measuring a current flowing into the nanopore; Lt; / RTI >
Wherein the first and second electrodes are formed so as not to overlap each other when viewed in a plan view.
Forming a first electrode layer made of a planar structure on the forer layer to form a first pre-pore structure including the forer layer and the first electrode layer;
Forming an interlayer insulating film on the first electrode layer;
Forming a second electrode layer having a planar structure on the interlayer insulating film;
Forming an insulating film on the second electrode layer;
A nano-pore structure in which a nanopore having an inlet port and an outlet port is formed so that the insulating layer, the second electrode layer, the interlayer insulating layer, the first electrode layer, and the pore layer are processed, And forming a second electrode,
Wherein the first and second electrodes are formed so as not to overlap each other when viewed in a plan view.
b) forming a first electrode layer made of a planar structure on the first forer layer to form a first pre-pore structure including the first forer layer and the first electrode layer;
c) forming an interlayer insulating film on the first electrode layer;
d) preparing a second preliminary pore structure in which a second substrate, a second pore layer, and a second electrode layer are sequentially formed by using the steps a) to b);
e) positioning the second pre-pore structure on the interlayer dielectric to face the first pre-pore structure;
f) attaching the interlayer insulating layer and the second electrode layer; And
e) a process step is performed on the second pore layer, the second electrode layer, the interlayer insulating film, the first electrode layer, and the first pore layer to form a nano-pores having nano-pores having an inlet port and an outlet port, Forming a pore structure, a first electrode, and a second electrode on a substrate;
And forming a second opening at a position corresponding to the nanopore by partially etching the second substrate after forming the second electrode layer.
And patterning the first and second electrode layers, respectively. ≪ RTI ID = 0.0 > 11. < / RTI >
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KR1020140183043A KR101666725B1 (en) | 2014-12-18 | 2014-12-18 | Nanopore device and method of manufacturing the same |
PCT/KR2015/013705 WO2016099108A1 (en) | 2014-12-18 | 2015-12-15 | Nanopore element and method for manufacturing same |
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KR1020140183043A KR101666725B1 (en) | 2014-12-18 | 2014-12-18 | Nanopore device and method of manufacturing the same |
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KR102090587B1 (en) * | 2017-02-17 | 2020-04-28 | 우석대학교 산학협력단 | Method for manufacturing nitrogen doped graphene gas sensor and gas sensor made by the same |
CN108982615B (en) * | 2018-07-02 | 2020-08-11 | 浙江大学 | Integrated electrochemical electrode system based on nanochannel array surface gold/platinum spraying |
CN108982612B (en) * | 2018-07-02 | 2020-08-11 | 浙江大学 | Integrated electrochemical electrode system based on nanochannel array surface gold spraying |
KR102176130B1 (en) * | 2018-11-13 | 2020-11-10 | 고려대학교 산학협력단 | Detection device of biological molecule using a micropore |
US20220091093A1 (en) * | 2019-02-01 | 2022-03-24 | Northeastern University | MXene Nanopore Sequencer of Biopolymers |
KR102327635B1 (en) * | 2019-12-12 | 2021-11-17 | 광운대학교 산학협력단 | A method for preparing nano pore filter and the nano pore filter prepared thereby |
CN112114020A (en) * | 2020-09-14 | 2020-12-22 | 安徽师范大学 | Double-sensitive gold-modified DNA functionalized glass nanopore door control system, construction method and application |
IT202100015821A1 (en) * | 2021-06-17 | 2022-12-17 | Elements S R L | Device for detecting nano particles in a fluid. |
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US20040144658A1 (en) | 2003-01-27 | 2004-07-29 | Flory Curt A. | Apparatus and method for biopolymer indentification during translocation through a nanopore |
US20070138132A1 (en) | 2003-06-12 | 2007-06-21 | Barth Phillip W | Nanopore with resonant tunneling electrodes |
US20080187915A1 (en) | 2007-02-02 | 2008-08-07 | Stanislav Polonsky | Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore |
US20120193237A1 (en) | 2011-01-28 | 2012-08-02 | International Business Machines Corporation | Dna sequencing using multiple metal layer structure with different organic coatings forming different transient bondings to dna |
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KR101267789B1 (en) * | 2010-06-25 | 2013-06-04 | 서울대학교산학협력단 | DNA analyzing apparatus using nanopore structure, analyzing method and apparatus for quantitative detection of PCR products |
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US20040144658A1 (en) | 2003-01-27 | 2004-07-29 | Flory Curt A. | Apparatus and method for biopolymer indentification during translocation through a nanopore |
US20070138132A1 (en) | 2003-06-12 | 2007-06-21 | Barth Phillip W | Nanopore with resonant tunneling electrodes |
US20080187915A1 (en) | 2007-02-02 | 2008-08-07 | Stanislav Polonsky | Systems and Methods for Controlling the Position of a Charged Polymer Inside a Nanopore |
US20120193237A1 (en) | 2011-01-28 | 2012-08-02 | International Business Machines Corporation | Dna sequencing using multiple metal layer structure with different organic coatings forming different transient bondings to dna |
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