CN109680052A - The preparation method of nano-porous thin film, gene sequencing device and nano-porous thin film - Google Patents
The preparation method of nano-porous thin film, gene sequencing device and nano-porous thin film Download PDFInfo
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- CN109680052A CN109680052A CN201910032354.7A CN201910032354A CN109680052A CN 109680052 A CN109680052 A CN 109680052A CN 201910032354 A CN201910032354 A CN 201910032354A CN 109680052 A CN109680052 A CN 109680052A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
Abstract
Present disclose provides the preparation methods of a kind of nano-porous thin film, gene sequencing device and nano-porous thin film, the nano-porous thin film includes: substrate, the film bulk in the one side that the substrate is arranged in and the nano pore through the film bulk, wherein, there is through-hole corresponding with the nano pore, the nano pore, which has, to be passed through for accommodating single nucleic acid molecules and can change the moving direction of nucleic acid molecules to reduce the test section of nucleic acid molecules movement speed on the substrate.The nano-porous thin film of the disclosure, due to having the test section for being only capable of accommodating single nucleic acid molecules and passing through in nano pore, and the test section can reduce the movement speed of nucleic acid molecules by changing the moving direction of nucleic acid molecules, nucleic acid molecules are slower by the speed of test section, it can be improved the data volume of the detection signal got, and then can be improved the accuracy of gene sequencing.
Description
Technical field
This disclosure relates to gene sequencing technology field, in particular to a kind of nano-porous thin film, thin using the nano-pore
The gene sequencing device of film and the preparation method of nano-porous thin film.
Background technique
From 1970s, people have successively developed three generations's DNA sequencing technology.First generation DNA sequencing technology base
In Sanger method, time-consuming completes the Human Genome Project in 15 years, directly spends about 3,000,000,000 dollars.Second generation DNA sequencing technology
With the characteristics of high throughput, it is only necessary to the sequencing of human genome can be completed less than 1,000,000 dollars once week, cost.In recent years, it is based on
The DNA single-molecule detection analysis of solid nano hole device is considered as most being hopeful to realize third generation fast and low-cost human gene
One of technology path of sequencing becomes the hot spot of research and explorative research at present, and 1000 dollars of cost or less is real in 24 hours
The gene order-checking of existing single people.It may be implemented to be based on by the hole that electrophoresis in the solution drives molecule to pass through a nanoscale
The single-molecule detection and analysis ability of nano-pore device.It can be by various means to a large amount of points in the confined space of nano-pore
Son is quickly analyzed, and when the high-polymer molecule passes through nano-pore, the structural information of the high-polymer molecule and the signal of detection are special
Sign has one-to-one relationship.Directly single strand dna of many kilobases to length can be characterized using the characteristic, avoided
Amplification or labelling experiment prepare link, make it possible fast and low-cost DNA sequencing technology.
Current experimental result shows that the speed that DNA passes through nano-pore is about 102 to 105base/ms, such as outside 120mV
Under making alive effect, the DNA without outer addition of constraints by the speed of alpha hemolysin nanochannel is about 103base/ms, is much surpassed
The sample frequency (< 250kHz) of existing commercial patch-clamp detection system is crossed.It can be seen that existing nanopore sensor is real
The main problem of existing single base identification is: DNA molecular is too fast by nano-pore speed, leads to existing patch-clamp or other signals
The significant figure strong point that acquisition system obtains is very little, can not go out each base according to the signal resolution of blocking electric current.
Summary of the invention
In view of the above problem of the existing technology, the purpose of the present invention is to provide a kind of nano-porous thin film, using this
The gene sequencing device of nano-porous thin film and the preparation method of the nano-porous thin film, make nucleic acid molecules by passing through the nano-pore
The speed of the nano pore of film is slower, to improve the accuracy of gene sequencing.
According to the first scheme of the disclosure, a kind of nano-porous thin film is provided comprising: substrate is arranged in the substrate
One side on film bulk and nano pore through the film bulk, wherein have on the substrate and received with described
The corresponding through-hole in metre hole road, the nano pore, which has, to be passed through for accommodating single nucleic acid molecules and can change nucleic acid molecules
Moving direction to reduce the test section of nucleic acid molecules movement speed.
In some embodiments, the nano pore has the first hole section, close of the one side close to the film bulk
Second hole section of the another side of the film bulk and the third hole between first hole section and second hole section
Section, the third hole section form the test section.
In some embodiments, first hole section and second hole section dislocation arrangement, the third hole section are connected to
Between first hole section and second hole section, to form the test section.
In some embodiments, the film bulk includes the first film layer and the second film layer being stacked.
In some embodiments, first hole section is located in first film layer, and second hole section is located at described the
In two film layers, the third hole section is arranged along the contact surface direction of first film layer and second film layer.
In some embodiments, second film layer has close to the one side of first film layer and connects with second hole section
The third hole section is collectively formed in logical deep gouge, the deep gouge and first film layer.
In some embodiments, the third hole section is heavy between first film layer and second film layer by being deposited on
It is formed after laminated peel.
In some embodiments, the aperture of first hole section is 50nm to 100nm；The aperture of second hole section is
50nm to 100nm；The aperture of the third hole section is 0.5nm to 2nm；The length of the third hole section is 5nm to 10nm.
In some embodiments, first film layer with a thickness of 5nm to 20nm；Second film layer with a thickness of 5nm
To 20nm.
According to the alternative plan of the disclosure, provide a kind of gene sequencing device comprising: container, detection unit and
Nano-porous thin film as described above, wherein for containing the solution comprising nucleic acid molecules, the nano-porous thin film is set the container
It sets in the container the container is separated into two chambers, the detection unit is used for respectively and in two chambers
Solution is electrically connected, to generate the detection letter of the base sequence of characterization nucleic acid molecules when nucleic acid molecules are by the test section
Number.
According to the third program of the disclosure, a kind of preparation method of nano-porous thin film is provided comprising:
Film bulk is formed on substrate；
Substrate described in released part is to form through-hole；
The released part film bulk corresponding with the through-hole to form the nano pore with test section,
In, the test section is used to accommodate single nucleic acid molecules and passes through and can change the moving direction of nucleic acid molecules to reduce nucleic acid point
Sub- movement speed.
It is in some embodiments, described to form film bulk on the substrate, comprising:
The first film layer is formed on the substrate；
Sedimentary is formed by depositing operation in first film layer of part；
The second film layer is formed in first film layer and the sedimentary.
In some embodiments, the released part film bulk corresponding with the through-hole has inspection to be formed
The nano pore in survey portion, comprising:
Part second film layer corresponding with the sedimentary is removed to form the second hole section of the nano pore；
Sedimentary is removed to form the third hole section of the nano pore；
Part first film layer corresponding with the sedimentary is removed to form the second hole with the nano pore
First hole section of section sequence.
It is in some embodiments, described to form film bulk on the substrate, further includes:
First film layer described in released part is to form the first hole section of the nano pore；
The first hole section of the nano pore is filled to form the flat surface for depositing the sedimentary.
It should be appreciated that foregoing general description and it is described in detail below be merely exemplary with it is illustrative, rather than use
In the limitation disclosure.
This section provides the various realizations or exemplary general introduction of technology described in the disclosure, is not the complete of disclosed technology
The comprehensive disclosure of portion's range or all features.
Detailed description of the invention
In order to illustrate more clearly of the technical solution of the embodiment of the present disclosure, the attached drawing to embodiment is simply situated between below
It continues, it should be apparent that, the accompanying drawings in the following description merely relates to some embodiments of the present disclosure, rather than the limitation to the disclosure.
Fig. 1 be the present embodiments relate to nano-porous thin film structural schematic diagram；
Fig. 2 is the partial enlarged view of the part A of nano-porous thin film in Fig. 1；
Fig. 3 be the present embodiments relate to gene sequencing device structural schematic diagram；
Fig. 4 is the curent change schematic diagram that detection unit detects when nucleic acid molecules pass through nano pore；
Fig. 5 be the present embodiments relate to nano-porous thin film preparation method the first embodiment flow chart；
Fig. 6 be the present embodiments relate to nano-porous thin film preparation method second of embodiment flow chart.
Appended drawing reference:
1- substrate；2- film bulk；The first film layer of 3-；The second film layer of 4-；5- sedimentary；6- nano pore；The first hole 7-
Section；The second hole section of 8-；9- third hole section；10- through-hole；11- filler；12- nano-porous thin film；13- container；14- detection unit；
15- chamber；16- nucleic acid molecules.
Specific embodiment
In order to enable the purposes, technical schemes and advantages of the embodiment of the present disclosure are clearer, below in conjunction with disclosure reality
The technical solution of the embodiment of the present disclosure is clearly and completely described in the attached drawing for applying example.Obviously, described embodiment is
A part of this disclosure embodiment, instead of all the embodiments.Based on described embodiment of the disclosure, this field is common
Technical staff's every other embodiment obtained under the premise of being not necessarily to creative work, belongs to the model of disclosure protection
It encloses.
Unless otherwise defined, the technical term or scientific term that the disclosure uses should be tool in disclosure fields
The ordinary meaning for thering is the personage of general technical ability to be understood." first ", " second " used in the disclosure and similar word are simultaneously
Any sequence, quantity or importance are not indicated, and are used only to distinguish different component parts." comprising " or "comprising" etc.
Similar word means that the element or object before the word occur covers the element or object for appearing in the word presented hereinafter
And its it is equivalent, and it is not excluded for other elements or object.
In order to keep the following explanation of the embodiment of the present disclosure to understand and concise, known function and known portion is omitted in the disclosure
The detailed description of part.
Shown in Figure 1, the embodiment of the invention provides a kind of nano-porous thin films comprising: substrate 1 is arranged in substrate 1
One side on film bulk 2 and nano pore 6 through film bulk 2, wherein substrate 1 is used for bearing film ontology 2,
There is through-hole 10 corresponding with nano pore 6 on substrate 1；Nano pore 6 have for accommodate single nucleic acid molecules pass through and
The moving direction of nucleic acid molecules can be changed to reduce the test section of nucleic acid molecules movement speed.The nucleic acid molecules can be DNA points
Son or RNA molecule.
Nano-porous thin film using the above structure passes through due to having to be only capable of accommodating single nucleic acid molecules in nano pore 6
Test section, and the test section can reduce the movement speeds of nucleic acid molecules, core by changing the moving direction of nucleic acid molecules
Acid molecule is slower by the speed of the test section, can be improved the data volume of the detection signal got, and then can be improved base
Because of the accuracy of sequencing.
Shown in Figure 2, in some embodiments, which can have the first hole section 7, the second hole section 8 and third
Hole section 9, wherein the first hole section 7 is arranged close to the one side of film bulk 2, and the second hole section 8 is set close to the another side of film bulk 2
It sets, for third hole section 9 between the first hole section 7 and the second hole section 8, third hole section 9 forms above-mentioned test section.In this way, nucleic acid
Molecule can pass through third hole section 9 under the guidance of the first hole section 7 or the second hole section 8, by again can be after the third hole section 9
The nano pore 6 is removed under the guidance of second hole section 8 or the first hole section 7, is conducive to going on smoothly for gene sequencing.Specifically,
The aperture of first hole section 7 and the second hole section 8 can be 50nm to 100nm, and the aperture of third hole section 9 can be 0.5nm to 2nm, the
The length of three hole sections 9 can be 5nm to 10nm.
In some embodiments, the first hole section 7 and the second hole section 8 dislocation arrangement, third hole section 9 are connected to the first hole section 7
And second between hole section 8, to form test section.Nucleic acid molecules need to change direction when through the first hole section 7 to third hole section 9,
It still needs to change direction through 9 to the second hole section 8 of third hole section, can be effectively reduced nucleic acid molecules in moving direction conversion process
Movement speed.5nm to 10nm namely the first hole section 7 and the second hole specifically, the first hole section 7 and the second hole section 8 can be staggered completely
The 5nm to 10nm that is most nearby staggered of section 8, by taking the first hole section 7 and the second hole section 8 are the round hole section of 50nm as an example, then the
The center line sequence 55nm to 60nm of the center line of one hole section 7 and the second hole section 8.
In some embodiments, film bulk 2 may include the first film layer 3 and the second film layer 4 being stacked, the first film layer
3 and second film layer 4 thickness can be 5nm to 20nm, first film layer 3 and the second film layer 4 can pass through electro-deposition or chemistry
Depositing operation is formed.Wherein, the first hole section 7 is located in the first film layer 3, and the second hole section 8 is located in the second film layer 4.Third hole section 9
It is formed after being removed by the sedimentary 5 being deposited between the first film layer 3 and the second film layer 4.Specifically, forming first on substrate 1
After film layer 3, sedimentary 5 is formed using such as atomic layer deposition process in the part of the surface of the first film layer 3, then in the first film layer
3 and sedimentary 5 on deposit the second film layer 4, then using the first film layer of graphical treatment technique released part 3 formed the first hole section
7, the second film layer of released part 4 forms the second hole section 8, and removing sedimentary 5 forms third hole section 9.In this way, after sedimentary 5 is removed
A deep gouge is formed close to the one side of the first film layer 3 in the second film layer 4, the deep gouge and the first film layer 3 together form third hole section
9, which is arranged along the contact surface direction of the first film layer 3 and the second film layer 4.Atomic layer deposition process (ALD) can be fine
Control sedimentary 5 thickness, the aperture of third hole section 9 formed after further being removed by sedimentary 5 is also accurately controlled
System.The forming method of the third hole section 9 can be integrated in semiconductor technology, and operability is stronger, be suitable for quantization production.Specifically,
The material of the sedimentary 5 can be Al2O3Or Cu etc..With Al2O3For, deposition velocity can be set to every 12s and deposit an atom
Layer, every thickness degree is about 0.1nm, can accurately control the thickness of sedimentary 5 by controlling sedimentation time, and then by third hole
The aperture of section 9 is accurately controlled in 0.5nm to 2nm, make third hole section 9 and single stranded nucleic acid molecule diameter (single stranded nucleic acid molecule
Diameter is about 1nm) match, it can be effectively reduced the speed that nucleic acid molecules pass through nano pore 6, improve the accurate of gene sequencing
Degree.It should be noted that the nano pore 6 is not limited only to above structure, it is also not limited to above-mentioned technique, as long as its test section
Aperture, which is configured to can only to accommodate single nucleic acid molecules, to be passed through, and the structure of its test section is configured to change nucleic acid point
The moving direction of son is to reduce the movement speed of nucleic acid molecules.
Fig. 3 is the structural schematic diagram of the gene sequencing device of the embodiment of the present invention, shown in Figure 3, the embodiment of the present invention
Gene sequencing device include: container 13, detection unit 14 and nano-porous thin film 12 as described above, wherein container 13 is used
In containing the solution comprising nucleic acid molecules 16, nano-porous thin film 12 is arranged in container 13 so that container 13 is separated into two chambers
15, detection unit 14 with solution in two chambers 15 for being electrically connected respectively, with raw when nucleic acid molecules 16 pass through test section
At the detection signal of the base sequence of characterization nucleic acid molecules 16.
Sequencing approach using the gene sequencing device is as follows: nucleic acid molecules 16 are placed in the company, cathode institute of detection unit 14
The chamber 15 connect, applies driving voltage between the anode and cathode of detection unit 14, and driving nucleic acid molecules 16 are moved along nano pore 6
Dynamic, which can be 100~300mV, which can be Klorvess Liquid, and the molar concentration of the electrolyte can be 0.1-
3.2mol/L, the pH value of the electrolyte can be 8-10.Such as the nucleic acid molecules such as DNA molecular 16 pass through nano pore 6 when, due to resistance
Plug effect causes ion-flow rate to reduce, and current value changes, as shown in Figure 4.Different bases due to size direction and size not
Equally, by when current value change it is variant, pass through detection current variation value difference, it may be determined that base sequence.Since application is upper
The movement speed when nano-porous thin film 12 stated, nucleic acid molecules 16 pass through nano pore 6 is slower, being capable of collected detection letter
Number data volume it is larger, can be improved signal-to-noise ratio, and then improve the accuracy of genetic test.
Fig. 5 is the flow chart of the first embodiment of the preparation method of the nano-porous thin film of the embodiment of the present invention, referring to Fig. 5
Shown, the preparation method of the nano-porous thin film of the embodiment of the present invention specifically comprises the following steps:
S101 forms film bulk 2 on substrate 1.Wherein, which is used as carrier, is used for bearing film ontology 2, can
Using silicon material substrate 1.Film bulk 2 can be used on such as chemical deposition, electro-deposition or the formation of other techniques and substrate 1.
S102, released part substrate 1 is to form through-hole 10.The through-hole 10 can be for example, by techniques such as laser engraving or etchings
It is formed.
S103, released part film bulk 2 corresponding with through-hole 10 have the nano pore 6 of test section to be formed,
In, test section is used to accommodate single nucleic acid molecules and passes through and can change the moving directions of nucleic acid molecules to be worn with reducing nucleic acid molecules
More speed.The nano pore 6 can be formed for example, by the graphical treatments technique such as photoetching or etching, can also by include photoetching and
Composite treatment process including the techniques such as etching is formed.It should be noted that can first be walked in step S102 and step S103
Rapid S102 can also first carry out step S103, can also alternately implement.
The nano-porous thin film prepared using the above method is passed through due to having to be only capable of accommodating single nucleic acid molecules in nano-pore
Test section, and the test section can reduce the movement speeds of nucleic acid molecules, core by changing the moving direction of nucleic acid molecules
Acid molecule is slower by the speed of the test section, can be improved the data volume of the detection signal got, and then can be improved base
Because of the accuracy of sequencing.In addition, the operability of the preparation method is stronger, it is suitable for quantization production.
Fig. 6 is the flow chart of second of embodiment of the preparation method of the nano-porous thin film of the embodiment of the present invention, referring to Fig. 6
Shown, the preparation method of the nano-porous thin film of the embodiment of the present invention is used to prepare nano-porous thin film as described above, specifically includes
Following steps:
S201 forms the first film layer 3 on substrate 1, and the first film layer of released part 3 is to form the first of nano pore 6
Hole section 7.The substrate 1 is used as carrier, is used for bearing film ontology 2, silicon material substrate 1 can be used.First film layer 3 can be used
Si3N4Material, the thickness of first film layer 3 can be 5nm to 20nm.Such as chemical deposition, electro-deposition can be used in first film layer 3
Or on the formation of other techniques and substrate 1.The graphical treatment technique such as deep ultraviolet light etching technics can be used in first hole section 7
It is formed, the diameter of first hole section 7 can be 50nm to 100nm.
S202 fills filler 11 in the first hole section 7 of nano pore 6 to form flat surface in the first film layer 3.
Specifically, the filler 11 in the first hole section 7 of nano pore 6 can be to use the Cu that for example atomic layer deposition process deposits, to fill out
The first hole section 7 of the nano pore 6 is filled, it then, can be for example, by planarization process techniques such as chemical mechanical grindings (CMP) to
The surface of one film layer 3 carries out planarization process, heavy for carrying out sedimentary 5 in the next steps to be formed in the first film layer 3
Long-pending flat surface.
S203 passes through depositing operation shape in the first film layer 3 on part corresponding with the first hole section 7 of nano pore 6
At sedimentary 5.The sedimentary 5 can be formed in the first film layer 3 for example, by atomic deposition (ALD) technique, the material of the sedimentary 5
Matter can be Al2O3Or Cu etc..With Al2O3For, deposition velocity can be set to every 12s and deposit an atomic layer, every thickness degree is about
For 0.1nm, the thickness of sedimentary 5 can be accurately controlled in 0.5nm to 2nm by controlling sedimentation time.
S204 forms the second film layer 4 in the first film layer 3 and sedimentary 5, and released part is corresponding with sedimentary 5
Second film layer 4 is to form the second hole section 8 with 7 sequence of the first hole section of nano-pore.Si can be used in second film layer 43N4Material
Matter, the thickness of second film layer 4 can be 5nm to 20nm.Second film layer 4 can be used such as chemical deposition, electro-deposition or other
In technique formation and substrate 1.The graphical treatment technique shape such as deep ultraviolet light etching technics can also be used in second hole section 8
At the diameter of second hole section 8 can be 50nm to 100nm.First hole section 7 and the second hole section 8 can be staggered 5nm to 10nm completely,
Namely first hole section 7 and the second hole section 8 the 5nm to 10nm that is most nearby staggered, be with the first hole section 7 and the second hole section 8
For the round hole section of 50nm, then the center line sequence 55nm to 60nm of the center line of the first hole section 7 and the second hole section 8.
S205 removes sedimentary 5 to form the third hole section 9 of nano-pore.Such as etching technics stripping can be used in the sedimentary 5
From.A deep gouge is formed close to the one side of the first film layer 3 in the second film layer 4 after the removing of sedimentary 5, the deep gouge and the first film layer 3 are total
It is same to form third hole section 9.Due to the 5nm to 10nm that is most nearby staggered of the first hole section 7 and the second hole section 8, so, formation
The length of third hole section 9 is about 5nm to 10nm.Since the thickness of sedimentary 5 is accurately controlled in 0.5nm to 2nm, sedimentary 5
The aperture of third hole section 9 can also be accurately controlled in 0.5nm to 2nm after removing, be passed through with only accommodating single nucleic acid molecules.
S206, released part substrate 1 corresponding with nano pore 6 have formed through-hole 10.The through-hole 10 can be for example, by
The techniques such as laser engraving or etching are formed, and the diameter of the through-hole 10 is much larger than the aperture of nano pore 6, to avoid nucleic acid point is influenced
Son passes through nano pore 6.
S207, the filler 11 in first hole section 7 in stripping nano duct 6, to form the nano pore 6 of perforation.This is filled out
Filling object 11 can be used such as etching technics removing.
The nano-porous thin film prepared using the above method, nano pore 6 are in piecewise dam axis, can change nucleic acid molecules
Moving direction, to reduce the movement speed of nucleic acid molecules, additionally it is possible to by accurately controlling the thickness of sedimentary 5 to realize to
The accurate control in the aperture of three hole sections 9 further decreases core so that third hole section 9 be made to be only capable of accommodating single nucleic acid molecules and pass through
The movement speed of acid molecule.In addition, this method can be integrated in semiconductor technology, operability is stronger, is suitable for quantization production.
Above embodiments are only exemplary embodiment of the present invention, are not used in the limitation present invention, protection scope of the present invention
It is defined by the claims.Those skilled in the art can within the spirit and scope of the present invention make respectively the present invention
Kind modification or equivalent replacement, this modification or equivalent replacement also should be regarded as being within the scope of the present invention.
Claims (14)
1. a kind of nano-porous thin film characterized by comprising substrate, the film bulk being arranged in the one side of the substrate with
And the nano pore through the film bulk, wherein there is through-hole corresponding with the nano pore, institute on the substrate
It states nano pore and has and pass through for accommodating single nucleic acid molecules and the moving direction of nucleic acid molecules can be changed to reduce nucleic acid
The test section of molecular motion velocity.
2. nano-porous thin film according to claim 1, which is characterized in that the nano pore has close to the film sheet
First hole section of the one side of body, close to the film bulk another side the second hole section and be located at first hole section and institute
The third hole section between the second hole section is stated, the third hole section forms the test section.
3. nano-porous thin film according to claim 2, which is characterized in that first hole section and second hole section dislocation
Arrangement, the third hole section is connected between first hole section and second hole section, to form the test section.
4. nano-porous thin film according to claim 3, which is characterized in that the film bulk includes first be stacked
Film layer and the second film layer.
5. nano-porous thin film according to claim 4, which is characterized in that first hole section is located at first film layer
Interior, second hole section is located in second film layer, and the third hole section is along first film layer and second film layer
The setting of contact surface direction.
6. nano-porous thin film according to claim 5, which is characterized in that second film layer is close to first film layer
There is the deep gouge being connected to second hole section on one side, the third hole section is collectively formed in the deep gouge and first film layer.
7. according to the described in any item nano-porous thin films of claim 4-6, which is characterized in that the third hole section is by being deposited on
It is formed after stating the sedimentary removing between the first film layer and second film layer.
8. according to the described in any item nano-porous thin films of claim 3-6, which is characterized in that the aperture of first hole section is
50nm to 100nm；The aperture of second hole section is 50nm to 100nm；The aperture of the third hole section is 0.5nm to 2nm；Institute
The length for stating third hole section is 5nm to 10nm.
9. according to the described in any item nano-porous thin films of claim 4-6, which is characterized in that first film layer with a thickness of
5nm to 20nm；Second film layer with a thickness of 5nm to 20nm.
10. a kind of gene sequencing device characterized by comprising container, detection unit and any one of such as claim 1-9
The nano-porous thin film, wherein the container exists for containing the solution comprising nucleic acid molecules, the nano-porous thin film setting
The container is separated into two chambers in the container, the detection unit for respectively with solution in two chambers
It is electrically connected, to generate the detection signal of the base sequence of characterization nucleic acid molecules when nucleic acid molecules are by the test section.
11. a kind of preparation method of nano-porous thin film characterized by comprising
Film bulk is formed on substrate；
Substrate described in released part is to form through-hole；
The released part film bulk corresponding with the through-hole is to form the nano pore with test section, wherein institute
It states test section and passes through and the moving directions of nucleic acid molecules can be changed for accommodating single nucleic acid molecules and worn with reducing nucleic acid molecules
More movement speed.
12. the preparation method of nano-porous thin film according to claim 11, which is characterized in that it is described formed on substrate it is thin
Membrane body, comprising:
The first film layer is formed on the substrate；
Sedimentary is formed by depositing operation in first film layer of part；
The second film layer is formed in first film layer and the sedimentary.
13. the preparation method of nano-porous thin film according to claim 12, which is characterized in that the released part with it is described
The corresponding film bulk of through-hole is to form the nano pore with test section, comprising:
Part second film layer corresponding with the sedimentary is removed to form the second hole section of the nano pore；
Sedimentary is removed to form the third hole section of the nano pore；
Part first film layer corresponding with the sedimentary is removed to form the second hole section phase with the nano pore
First hole section of dislocation.
14. the preparation method of nano-porous thin film according to claim 13, which is characterized in that the shape on the substrate
At film bulk, further includes:
First film layer described in released part is to form the first hole section of the nano pore；
The first hole section of the nano pore is filled to form the flat surface for depositing the sedimentary.
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| CN102621214A (en) * | 2012-03-13 | 2012-08-01 | 北京大学 | Method for carrying out deceleration and monomolecular capture on nucleic acid molecule based on solid-state nano hole |
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| CN104254771A (en) * | 2012-01-20 | 2014-12-31 | 吉尼亚科技公司 | Nanopore based molecular detection and sequencing |
| CN102621214A (en) * | 2012-03-13 | 2012-08-01 | 北京大学 | Method for carrying out deceleration and monomolecular capture on nucleic acid molecule based on solid-state nano hole |
| CN102899243A (en) * | 2012-09-21 | 2013-01-30 | 清华大学 | Graphene nanopore-microcavity-solid-state nanopore structure based DNA sequencing device and method |
| CN104407032A (en) * | 2014-11-05 | 2015-03-11 | 中国科学院物理研究所 | Ultrathin solid state nanopore with sub-2-nano aperture, sensor, and application of sensor |
| CN104694649A (en) * | 2015-03-10 | 2015-06-10 | 北京大学 | Nanopore sequencing method for nucleic acid molecules with low perforation rate and special nanopore device thereof |
| CN207318400U (en) * | 2017-10-25 | 2018-05-04 | 深圳宣泽生物医药有限公司 | A kind of double-layer nanometer aperture apparatus |
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